Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

General acid and general base catalysis of the enolization of acetone : an extensive study Shelly, Kevin Paul 1988

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1988_A1 S54.pdf [ 10.98MB ]
Metadata
JSON: 831-1.0060243.json
JSON-LD: 831-1.0060243-ld.json
RDF/XML (Pretty): 831-1.0060243-rdf.xml
RDF/JSON: 831-1.0060243-rdf.json
Turtle: 831-1.0060243-turtle.txt
N-Triples: 831-1.0060243-rdf-ntriples.txt
Original Record: 831-1.0060243-source.json
Full Text
831-1.0060243-fulltext.txt
Citation
831-1.0060243.ris

Full Text

GENERAL ACID AND GENERAL BASE CATALYSIS OF THE ENOLIZATION OF ACETONE. AN EXTENSIVE STUDY. By KEVIN PAUL SHELLY B.Sc., Un i v e r s i t y College Galway, 1981 M.Sc, U n i v e r s i t y of B r i t i s h Columbia, 1984 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n THE FACULTY OF GRADUATE STUDIES DEPARTMENT OF CHEMISTRY We accept t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA May 1988 © Kevin Paul Shelly, 1988 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of C H E M I S T R Y The University of British Columbia Vancouver, Canada Date J u n e 1, 1988  DE-6 (2/88) i i ABSTRACT The e n o l i z a t i o n of acetone i s subject to both general a c i d and general base c a t a l y s i s , eqs. [1.10] and [1.78]. The Bronsted equation r e l a t e s the c a t a l y z i n g power of the acid or base to the equilibrium a c i d or base strength of the species involved, eqs. [1.14] and [1.13]. [1.10a] [1.10b] [1.78] log = a log + Constant [1.14] log k A- = -8 log + Constant [1.13] This work involved measuring e n o l i z a t i o n rate constants f o r over 130 a c i d and base c a t a l y s t s . These include monoprotic and d i p r o t i c carboxylic acids, phosphonic acids, carboxylate monoanions and dianions and phosphonate dianions. A number of the conjugate bases of the d i p r o t i c acids, i . e . b i f u n c t i o n a l monoanions, were also examined. A i i i number of e f f e c t s were probed by an examination of the r e s u l t i n g Bronsted p l o t s . In the case of general acid c a t a l y s i s , a number of s t e r i c a l l y crowded c a t a l y s t s displayed enhanced c a t a l y t i c a c t i v i t y . That i s to say, they are more e f f e c t i v e i n the e n o l i z a t i o n process than t h e i r e q u i l i b r i u m a c i d strengths would suggest. This r e s u l t was evident i n both carboxylic a c i d and phosphonic a c i d c a t a l y s i s , but not i n general base c a t a l y s i s . The ro l e of s t e r i c factors i n these processes i s unclear. A group of b i f u n c t i o n a l monoanions are shown to act as general acids i n the e n o l i z a t i o n process. A comparison of 5- and 2 - substituted isophthalate monoanions reveals a s t e r i c a c c e l e r a t i n g e f f e c t f o r the 2-substituted species, a r e s u l t consistent with e a r l i e r observations. Species with p o l a r i z a b l e substituents are better c a t a l y s t s , i n both a c i d and base c a t a l y s i s , and t h i s r e s u l t i s explained. A set of carboxylate dianions, whose conjugate monoanions possess no hydrogen-bonding, form a reasonable Bronsted l i n e . A p a i r of dian-ions deviate below t h i s l i n e , and the degree of deviation i s shown to be r e l a t e d to the degree of hydrogen-bonding present i n the conjugate monoanions. The group of phosphonate dianions gives a curved Bronsted p l o t suggesting a changing t r a n s i t i o n state as the base strength of the cata-l y s t i s var i e d . In terms of the Hammond postulate, a more favourable proton t r a n s f e r ( i n v o l v i n g a stronger base) i s leading to an e a r l i e r , more r e a c t a n t - l i k e t r a n s i t i o n state i . e . the proton trans f e r i s occur-r i n g e a r l i e r along the reaction coordinate. The curvature i s analyzed i v i n terms of Marcus Theory and gives experimental support to the concepts of t r a n s i t i o n state energetics that are encompassed i n the Hammond and Marcus models. A c o r r e l a t i o n of primary isotope e f f e c t s with the curved Bronsted l i n e i s presented and t h i s further maps out the varying degrees of proton t r a n s f e r i n the t r a n s i t i o n state. A number of other examples of experimental evidence for the Hammond postulate are presented. Carboxylic monoprotic acids, free from both p o l a r i z a b i l i t y and s t e r i c f a c t o r s , appear to form a curved Bronsted l i n e . While the curva-ture i s i n the d i r e c t i o n predicted by Marcus Theory, primary isotope e f f e c t s suggest that a changing t r a n s i i t o n state i s not a cause of the curvature. As well as the topics mentioned here, a number of other facets of the r e a c t i o n are discussed, including e l e c t r o s t a t i c f a c t o r s . I t i s shown, f or example, that including c a t a l y s t s of varying charge i n a si n g l e Bronsted c o r r e l a t i o n must be done with caution. V TABLE OF CONTENTS Page ABSTRACT i i TABLE OF CONTENTS v LIST OF TABLES v i i i LIST OF FIGURES x i i LIST OF ABBREVIATIONS xvii ACKNOWLEDGEMENTS xix 1. INTRODUCTION 1. Physical Organic Chemistry 1 2. Enolization 2 3. Bronsted Relationship 4 4. Statistical Factors 9 5. Meaning of the Bronsted Exponent 11 6. Curvature in Bronsted Plots I 14 7. Marcus Theory Derivation and Application 15 Limitations to Marcus Theory 25 8. Primary Isotope Effects 28 9. Curvature in Bronsted Plots II 34 10 Catalysis of Enolization 38 Base Catalyzed Enolization . 44 Acid Catalyzed Enolization 48 Third Order Term 52 vi 11. Bifunctional Catalysis 54 12. Steric Effects General Base Catalysis 58 General Acid Catalysis 63 2. SCOPE OF THE INVESTIGATION 65 3. RESULTS 66 1. Carboxylic Acids and Carboxylate Bases Monoprotic Acids and Monoanionic Bases 68 Diprotic Acids, Bifunctional Monoanions and Dianionic Bases 97 2. Arylphosphonic Acids pK Determinations 116 Phosphonate Dianions 116 Phosphonic Diacids 123 Phosphonate Monoanions 129 4. DISCUSSION 1. Carboxylate Base Catalysis Monoanions 131 Dianions 134 2. Carboxylic Acid Catalysis Monoprotic Acids 150 Diprotic Acids 173 3. Bifunctional Catalysts (Dicarboxylic Acid Monoanions) 175 4. Arylphosphonic Acids. Substituent Effects on their First and Second Dissociation Constants 184 Meta and Para Substituents 185 Ortho Substituents 193 5. Arylphosphonate Dianion Catalysis 198 6. Arylphosphonic Acid Catalysis 204 7. Arylphosphonate Monoanion Catalysis 208 v i i 8. General Discussion Curvature in General Acid Catalyzed Bronsted Plots 214 Curvature in General Base Catalyzed Bronsted Plots 226 9. Conclusions 233 10. Suggestions for Further Work 238 5. EXPERIMENTAL 1. General Kinetic Measurements 240 2. Carboxylic Acids 244 3. Phosphonic Acids 247 4. Isotope Measurements 247 5. Statistics 248 6. APPENDIX I Rate-Acidity Profile 249 II Solvent Isotope Effects in Base Catalysis 250 7. BIBLIOGRAPHY 252 v i i i LIST OF TABLES Table Page 1 Data of B e l l and Lidwell for acetone e n o l i z a t i o n catalyzed by acids and bases at 25°C. Data from r e f . (BL40) 41 2 Calculated rate constants for I^ O"1" and "OH from eqs. [1.71] and [1.72] and r a t i o s k Calc/kexpt . . . . 43 3 Data of Lienhard and Anderson for acetone e n o l i z a t i o n catalyzed by monoanions and c a l c u l a t e d values. Data from r e f . (LA67) 57 4 (a) Data for the c r o s s - s o l v i n g of simultaneous equations for acetic acid/acetate ion (b) r e s u l t s of the cross - solving of the equations 70 5 k j ^ a n d k A- values for acetone e n o l i z a t i o n catalyzed by carboxylic acids and carboxylate bases at 25°C and 0.1 M i o n i c strength, deter-mined by the simultaneous equation method 73 6 Results of p l o t t i n g k O D S vs. [A"] for a c e t i c acid/acetate ion buffers at 4 n values at 25°C and 0.1 M i o n i c strength 77 7 k j ^ a n d k^- values for acetone e n o l i z a t i o n catalyzed by carboxylic acids and carboxylate bases at 25°C and 0.1 M i o n i c strength, deter-mined by the buffer r a t i o method 81 8 pH, k Q D S and [HA] measurements for d i f l u o r o -a c e t i c a c i d solutions 85 9 k j ^ values for acetone e n o l i z a t i o n at 25°C, determined by plots of ( k o b s - k H+[H 30 +]) vs. [HA] . . 88 10 Results of p l o t t i n g k O D S vs. [HA] f o r 3-methyl-benzoic acid/3-methylbenzoate ion buffers at 3 n values at 25°C and 0.1 M i o n i c strength 91 11 and k^- values for acetone e n o l i z a t i o n catalyzed by benzoic acids and benzoates at 25°C and 0.1 M i o n i c strength 94 i x 12 Results of the k i n e t i c runs for 2,6-dinitro-benzoic a c i d giving a value of k ^ 97 13 Results of the k i n e t i c runs for o x a l i c a c i d giving values of k j ^ ^ using eqs. [3.25] and [3.26] . . 102 14 kjj fr, k j ^ - and k 2- values f o r acetone enoliza-t i o n at 25°C f or a group of a l i p h a t i c carboxylic acids and phthalic acid. Ionic strength 0.1 M unless otherwise stated 109 15 D i s s o c i a t i o n constants of iso p h t h a l i c acids i n water at 25°C, corrected to zero i o n i c strength I l l 16 ^HA" a n c * ( s o m e ) k 2- values for acetone enoliza-t i o n at 25°C and 0.05 M i o n i c strength f o r a group of i s o p h t h a l i c acids. Rate constants determined by ignoring the overlapping d i s s o c i a t i o n s . . . . . 114 17 ^HA" a n < ^ (some) k 2- values for acetone enoliza-t i o n at 25°C and 0.05 M i o n i c strength f o r a group of i s o p h t h a l i c acids. Rate constants determined by considering the overlapping d i s s o c i a t i o n s . . . . 115 18 D i s s o c i a t i o n constants of arylphosphonic acids i n water at 25°C, corrected to zero i o n i c strength 117 19 Results of p l o t t i n g k o b s vs. [HA"] for phenyl-phosphonate monoanion/dianion buffers at 3 m values at 25°C and 0.05 M i o n i c strength 119 20 Results of p l o t t i n g k o b s vs. [HA"] for 3,4-di-methylphenylphosphonate monoanion/dianion buffers at 4 m values at 25°C and 0.05 M i o n i c strength . . . 120 21 k 2- values f o r acetone e n o l i z a t i o n catalyzed by arylphosphonates at 25°C and 0.05 M i o n i c strength, determined by p l o t s of k o b s vs. [A^"] . . . 124 22 Results of the k i n e t i c runs f o r 2-fluorophenyl-phosphonic a c i d giving values of k j ^ A . . . . . . . 126 23 kjj values f o r acetone e n o l i z a t i o n catalyzed by arylphosphonic acids at 25°C and 0.1 M i o n i c strength, determined by d i v i d i n g ( k o b s -k^+[H30 +]) by [H2A] for a number of k i n e t i c runs . . . 128 X 24 ^HA" values f o r acetone e n o l i z a t i o n catalyzed by arylphosphonate monoanions at 25°C and 0.1 M i o n i c strength 130 25 k 2- values for acetone e n o l i z a t i o n catalyzed by carboxylate dianions at 25°C and 0.05 M io n i c strength unless otherwise stated. L i t e r a t u r e values are included where a v a i l a b l e . . . 137 26 K 1 / 2 K E and k 2 c a l c A 2 ° b S v a l u e s f o r e i S h t carboxylic d i p r o t i c acids 142 obs c a l c 27 kjj^ /k^A values f o r the group of a l i p h a t i c carboxylic acids possessing l i t t l e or no s t e r i c bulk 162 obs c a l c 28 ^-RA /^HA values for a l i p h a t i c carboxylic acids, meta and ortho benzoic acids 163 obs cal c 29 ^-EA /^HA values f o r a l i p h a t i c carboxylic acids possessing p o l a r i z a b l e substituents 166 T obs calc 30 pK 1 and k j ^ / k ^ values for a l i p h a t i c carboxylic acids possessing p o s i t i v e l y charged substituents 171 31 Substituent constant values (a and an) for meta and para substituents. Data from r e f s . (PD81, HW73) 188 32 a n (=a n para), oj° and E s ° values f o r ortho substituents. Data from r e f s . (HW73, BR84) 196 33 k 2- v a l u e s a n d k ^ - values (where measurable) for acetone e n o l i z a t i o n catalyzed by a l k y l -phosphonates at 25°C and 0.05 M i o n i c strength . . . 210 34 k n A values f o r acetone e n o l i z a t i o n at 25°C, measured i n D2O and r e s u l t i n g k^A(H20)/kjj^(D20) . . . 216 35 Caclulated k'^- values for acetone enoliza-t i o n catalyzed by carboxylate bases using eq. [1.77] with K Z H+ = 800 or 10 6 M 219 36 Results of Marcus Theory analysis of carboxy-l a t e anion data (Table 35) for protonated acetone e n o l i z a t i o n ; Units of kcal.mol"-'- pK Z H+ = -2.9 . . . . 221 x i 37 ^HA v a l u e s f ° r acetone-dg e n o l i z a t i o n at 25°C measured i n and the r e s u l t i n g k H / k D values 225 38 k 2- values for acetone-dg e n o l i z a t i o n at 25°C i n water, and the r e s u l t i n g k^/kp values; B values ca l c u l a t e d from eq. [4.46] on the basis of log K 2q/p, q = 3, p - 1 229 39 k^- values for acetone-dg e n o l i z a t i o n at 25°C i n water, and the r e s u l t i n g k^/kp values . . . . 233 40 Bronsted c o e f f i c i e n t s for proton abstraction from acetone (Z) and from protonated acetone (ZH +) 234 41 k^- values for acetone e n o l i z a t i o n at 25°C, measured i n D2O and r e s u l t i n g k^-(H^O)/^-(D2O) values 251 x i i LIST OF FIGURES Figure Page 1 Bronsted p l o t s r e s u l t i n g from both general a c i d c a t a l y s i s and general base c a t a l y s i s 8 2 Energy p r o f i l e for eq. [1.17], HA being a much weaker a c i d than BH + 12 3 Energy p r o f i l e f o r eq. [1.17], HA being a much stronger acid than BH + 12 4 Parabolas representing eqs. [1.22], F i g . 4(a) and [1.23} F i g . 4(b) 16 5 Intersecting parabolas at AG = 1/2 ( A G e q []_ 22] + A G e q 23]) r e P r e s e n t i n g the i n t r i n s i c b a r r i e r of the proton transfer process represented by eq. [1.17] , A G * 17 6 Displaced parabolas from F i g . 5 so as to give an o v e r a l l free energy change AG° < 0 (a) or AG° > 0 (b) 18 7 Energy p r o f i l e diagram describing eqs. [1.33]-[1.37] for an endothermic proton trans f e r (AG° > 0) . . 21 8 Bronsted p l o t for acetone e n o l i z a t i o n catalyzed by acids and bases. Data from Table 1, ref. (BL40) 41 9 Bronsted pl o t s for acetone e n o l i z a t i o n catalyzed by carboxylic acids and carboxylate bases. Rate constants determined by simultaneous equation method. B e l l and Lidwell's data added for comparison (BL40) 74 10 (a) Plots of k Q b s vs. [A"] for a c e t i c a c i d / acetate buffers, (b) Plots of (slope of k o b s vs. [A"]) vs. n for a c e t i c acid/acetate buffers . . . . 78 11 (a) Plots of k 0 b s vs. [HA] for methoxyacetic acid/methoxyacetate buffers, (b) Plots of (slope of k 0 b s vs. [HA]) vs. 1/n for methoxyacetic acid/methoxyacetate ion 79 x i i i 12 (a) Plots of (slope of k o b s vs. [HA]) vs. 1/n for chloroacetic acid/chloroacetate ion. (b) Plots of k o b s vs. [HA] for chloroacetic acid/chloroacetate buffers 80 13 Plot of k o b s vs. [H3O"1"] (stoichiometric concentration) for hydrochloric a c i d 83 14 Plots of ( k o b s - k H + [ H 3 0 + ] vs. [HA] for d i f l u o r o -a c e t i c a c i d and d i c h l o r o a c e t i c a c i d 86 15 Plots of ( k o b s - k H+[H 30 +] - k H 0[H 20] vs. [HA] for protonated glycine 89 16 (a) Plots of k o b s vs. [HA] for 3-methylbenzoic acid/3-methylbenzoate bu f f e r s . (b) Plot of (slope of k o b s vs. [HA]) vs. 1/n for 3-methyl-benzoic acid/3-methylbenzoate ion 90 17 Plots of (slope of k o b s vs. [A"]) vs. n for ( i ) 3-nitrobenzoic a c i d and ( i i ) 2-fluoro-benzoic a c i d 93 18 Plot of ( k o b s - k H+[H 30 +]) vs. [HA] for 2,6-dinitrobenzoic acid. Corresponding p l o t for t r i c h l o r o a c e t i c a c i d added for comparison 96 19 (a) Plots of k o b s vs. [A^"] for oxalate mono-anion/dianion buffers; (b) Plot of (slope of k o b s vs. [A^"]) vs. m for oxalate monoanion/ dianion 100 20 Plots of (slope of k o b s vs. [HA"]) vs. 1/m for 3-methylglutarate monoanion/dianion; (a) ignoring the overlapping K values and (b) considering the overlapping K values 105 21 (a) Plot of (slope of k o b s vs. [HA"]) vs. n for s u c c i n i c acid/monoanion bu f f e r s . (b) Plot of (slope of k o b s vs. [A^"]) vs. m for succinate monoanion/dianion buffers 107 22 Plot of pK^ and pK 2 for 5-substituted i s o p h t h a l i c acids i n water at 25°C against the Hammett meta-substituent constants 112 23 Plots of (slope of k o b s vs. [A^"]) vs. m for (a) i s o p h t h a l i c acid, (b) 5 - n i t r o i s o p h t h a l i c a c i d and (c) 2-bromoisophthalic a c i d 113 x i v 24 Plot of (slope of k o b s vs. [HA"] vs. 1/m for phenylphosphonate buffer 119 25 Plot of (slope of k o b s vs. [HA"]) vs. 1/m for 3,4-dimethylphenylphosphonate buffer 120 26 Plots of k O D S vs. [A^~] for phenylphosphonate buffers 122 27 Plots of k o b s vs. [A 2"] f o r 3,4-dimethyl-phenylphosphonate buffers 122 28 Plot of ( k o b s - k H+[H 30 +]) vs. [H 2A] for 2-fluorophenylphosphonic a c i d 127 29 Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by carboxylate monoanions; a l i p h a t i c bases, meta benzoate bases, ortho benzoate bases and three bases with large standard deviations; l i n e drawn with respect to the a l i p h a t i c bases 132 30(a) Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by carboxylate dianions; Bronsted l i n e f o r carboxylate monoanions added f o r comparison 135 30(b) Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by s i x carboxylate dianions with two deviating dianions; Bronsted l i n e f o r carboxylate monoanions added for comparison . . . . 139 31 Plot of K 2 c a l c / K 2 o b s against K L/2K E for a set of di c a r b o x y l i c acids 145 32 Bronsted p l o t for c a t a l y s i s of acetone enoliza-t i o n by carboxylic monoprotic acids; 22 a l i p h a t i c acids, 4 metabenzoic acids, 5 orthobenzoic acids and 3 ammoniocarboxylic acids. Line drawn f or a l i p h a t i c carboxylic acids 151 33 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by carboxylic acids 152 34 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by 19 carboxylic acids; curved l i n e hand-drawn f o r 16 of the acids; dichloro-, t r i c h l o r o -and tribromoacetic acids also present 154 35 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by 13 a l i p h a t i c carboxylic acids 159 X V 36 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by a l i p h a t i c carboxylic acids possessing no s t e r i c bulk 160 37 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by carboxylic acids; second degree curve drawn for 8 a l i p h a t i c acids; also shown are 7 a l i p h a t i c acids possessing s t e r i c bulk; 4 meta-benzoic acids and 5 orthobenzoic acids. 164 38 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by a l i p h a t i c carboxylic acids; 8 uncharged acids and 5 p o s i t i v e l y charged acids. Curve i s for uncharged acids 170 39 Bronsted p l o t f o r c a t a l y s i s of acetone enoliza-t i o n by a l i p h a t i c carboxylic acids; monoprotic and d i p r o t i c acids 174 40 Bronsted p l o t for c a t a l y s i s of acetone enoliza-t i o n by the monoanions of d i c a r b o x y l i c acids; monoanions acting as acids, involving pK 2, p =• 1, q = 4; Bronsted l i n e f o r carboxylic monoprotic acids added for comparison 177 41 Bronsted p l o t for c a t a l y s i s of acetone enoliza-t i o n by the monoanions of di c a r b o x y l i c acids; monoanions acting as bases, inv o l v i n g pK^, p = 2, q = 2; Bronsted l i n e for carboxylate bases added for comparison 177 42 Bronsted p l o t for c a t a l y s i s of acetone enoliza-t i o n by the monoanions of di c a r b o x y l i c acids; a l i p h a t i c monoanions, phthalate monoanion, 5-substi-tuted isophthalate monoanions and 2 - substituted isophthalate monoanions 179 43 Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by isophthalate monoanion 180 44 Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by isophthalate monoanions determined by consider-ing the overlapping d i s s o c i a t i o n s of the d i a c i d . . . 185 45 Plot of pK 2 for arylphosphonic acids against the substituent constants a n 187 46 Plot of pK 2 for arylphosphonic acids against the substituent constant a 187 xv i 47 Plot of pK^ for arylphosphonic acids against the substituent constant an 190 48 Plot of pK^ for arylphosphonic acids against the substituent constant a 190 49 Plot of pK^ against pK 2 for arylphosphonic acids; meta and para compounds and ortho compounds. Line drawn for meta and para compounds 199 50 Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by arylphosphonate dianions; meta and para compounds, ortho compounds and 3- and 4- CO2" compounds; l i n e drawn with respect to the meta and para compounds 200 51 Bronsted p l o t f o r c a t a l y s i s of acetone e n o l i z a t i o n by arylphosphonic acid; meta and para compounds and ortho compounds; l i n e drawn with respect to the meta and para compounds 205 52 Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by phosphonate dianions; meta and para a r y l compounds; ortho a r y l compounds and a l k y l compounds 212 53 Curved Bronsted p l o t for c a t a l y s i s of 'protonated acetone' e n o l i z a t i o n by carboxy-l a t e bases 222 54 Bronsted p l o t for acetone e n o l i z a t i o n catalyzed by phosphonate dianions, monocarboxylate anions and dianions 232 55 Rate-acidity p r o f i l e f o r the e n o l i z a t i o n of acetone 249 x v i i LIST OF ABBREVIATIONS a The Bronsted exponent when the c a t a y l s t s are proton donors 6 The Bronsted exponent when the c a t a l y s t s are proton acceptors p Number of equivalent a c i d i c protons q Number of equivalent s i t e s for proton attachment ^HA Rate constant for a monoprotic a c i d kji^A Rate constant f o r a d i p r o t i c a c i d k^- Rate constant f o r a monoanionic base k^2- Rate constant f o r a dianionic base IcRA" Rate constant for a b i f u n c t i o n a l monoanion of a d i p r o t i c a c i d ^A"-HA Rate constant for the simultaneous involvement of a c i d and base with the substrate (Third order term) k^+ Rate constant f o r hydronium ion k-QH Rate constant f o r hydroxide ion kj^Q Rate constant f o r water k^/kn Primary k i n e t i c isotope e f f e c t , i . e . r a t i o of rate constants for a p a r t i c u l a r c a t a l y s t with the substrate (k H) and the 2H substrate (kn) ^HA Equilibrium a c i d constant f o r a monoprotic a c i d K^- Equilibrium base constant f o r a monoanionic base Ky Autocatalysis constant f or water x v i i i n Buffer ratio of neutral acid to monoanion m Buffer ratio of monoanion to dianion £' ' Buffer ratio of dianion to trianion o Gr Free energy of reactants o s Free energy of products G* Free energy of transition state AG° Free energy of reaction AG* Free energy of activation Intrinsic barrier wr Work term for encounter of reactants WP Work term for separation of products (AG°) o b s Observed free energy of reaction (AG*)0-|-)S Observed free energy of activation p Hammett reaction constant a Hammett substituent constant a n Modified substituent constant oj° Inductive substituent constant for an ortho group Pj Coefficient for the ortho inductive parameter E s° Steric substituent constant for an ortho group 5 Coefficient for the ortho steric parameter xix ACKNOWLEDGEMENTS While only my name appears on the front of t h i s t h e s i s , I would l i k e to give c r e d i t to a few people, for without t h e i r help, there would be no th e s i s . I would l i k e to thank Dr. Ross Stewart for the opportunity to work with him, and for many h e l p f u l suggestions throughout the course of the research and the w r i t i n g of the thes i s . I also want to acknowledge the members of the research group, past and present, whose r e s u l t s I have used i n my work. In t h i s regard, the synthetic work of Dr. Kasinathan Nagarajan and Dr. Sampath Venimadhavan deserve s p e c i a l mention. These colleagues, along with a few summer students, namely L i s a Wong, Alex Lee, Lackbir Rai and Ol i v e r Lee, were also responsible for many pK determinations. The assistance of the elemental analyses, nmr, mass spectroscopy, s e c r e t a r i a l and workshop s t a f f i n the department, i s appreciated. Thanks are also due to my guidance committee, e s p e c i a l l y Dr. Pincock f o r h e l p f u l comments i n the preparation of t h i s t h e s i s . A b i g thank you to Rani Theeparajah for her e f f i c i e n t typing of same. Dr. Sampath Venimadhavan deserves s p e c i a l mention for h i s help and advice i n the w r i t i n g of the manuscript. Regards to a l l the friends that I met at the Chemistry Department and at International House. You a l l helped to make UBC and Vancouver such a great place to be. F i n a l l y , thanks to my family, j u s t f o r 'being there'. X X F O R R I T A - 1 -INTRODUCTION 1.1 PHYSICAL ORGANIC CHEMISTRY The subject of ph y s i c a l organic chemistry i s the study of organic chemistry by "quantitative and mathematical methods." This d e f i n i t i o n and the naming of the subject date back to Hammett's landmark book i n 1940 (H40). The organic chemist who claims that p h y s i c a l organic chemistry i s a branch of phys i c a l chemistry i s r e f l e c t i n g the opinion of the p h y s i c a l chemist who suggests the topic i s a branch of organic chemistry. Such opinions prompt the questions: Is chemistry a branch of physics? Is biochemistry a branch of chemistry? While p h y s i c a l organic chemistry i s on the borders of our defined areas of s p e c i a l i z e d chemistry f i e l d s , i n essence, chemistry, l i k e science, knows no bound-a r i e s . Each area merges with many around i t , eventually comprising the whole. By i t s very nature, p h y s i c a l organic chemistry i s a meeting of concepts and methods of several areas of chemistry. In conducting my research and preparing t h i s thesis, I had to consult various texts and jou r n a l s . These included Faraday Transactions I, The Journal of Organic Chemistry, The Journal of Physical Chemistry and Advances i n Chemical Physics. The scope of these journals i s a comment on the scope of ph y s i c a l organic chemistry, a scope that i s only l i m i t e d by the minds of those researching the topic. A main aim of ph y s i c a l organic chemists i s to a t t a i n a thorough understanding of reaction mechanism energetics and t r a n s i t i o n state - 2 -s t r u c t u r e s . In approaching such problems we need experimental r e s u l t s as a basis f o r further refinement and development of our concepts. Much progress has been made i n t h i s regard and much more has s t i l l to be achieved. This thesis contributes one very small part to that progress. 1.2 ENOLIZATION In 1904, Lapworth suggested that enol formation was the rate-l i m i t i n g step i n the halogenation of ketones, eq. [1.1] (L04). SLOW I ^ L CH{ \ C H 3 ^ ~ CH( \ H 2 F A S T C < \ C H 2 X Since then many s c i e n t i s t s have turned t h e i r a t t e n t i o n to the process of e n o l i z a t i o n of keto compounds. There are two main reasons f o r t h i s . F i r s t , i s the relevance of e n o l i z a t i o n to many rea c t i o n pathways. Secondly, e n o l i z a t i o n i s an example of a proton tran s f e r reaction, "a fundamental reaction i n Chemistry", as Koch recently described i t (K84). The subject of the e n o l i z a t i o n of simple carbonyl compounds was reviewed i n 1982 by Toullec (T82). Reactions of these compounds are of two general types; a d d i t i o n of a nucleophile to a carbonyl compound, eq. [1.2], and removal of a proton from the a-carbon, eq. [1.3]. Co-ordinating a Lewis acid, e.g. a proton, to the carbonyl oxygen w i l l help these two processes. Lowry and - 3 -[1.3] -1- BH + Richardson describe c a t a l y s i s by acids and bases as a " c e n t r a l theme of carbonyl reactions" (LR.87a). In p a r t i c u l a r the process of e n o l i z a t i o n i s of great importance i n organic and bio-organic chemistry, being involved i n condensation, oxidation, halogenation, racemization and isotope exchange reactions. The keto-enol equilibrium i n most carbonyl compounds i s well over to the keto side, and so the tautomer cannot be studied d i r e c t l y . Rather, k i n e t i c studies are frequently used to follow the conversion of ketone to enol or enolate anion. The enols of simple ketones have recently been detected i n aqueous s o l u t i o n allowing the k i n e t i c s of the enol-keto conversion to be measured (CH87). The enols of a carboxylic a c i d and an ester have also been reported (NH87). E n o l i z a t i o n i s catalyzed by acids and bases. A r e l a t i o n s h i p e x i s t s between the equilibrium strength (pK) of the a c i d or base and i t s e f f e c t i v e n e s s i n c a t a l y z i n g the e n o l i z a t i o n (rate constant). The r e l a t i o n s h i p , named a f t e r i t s co-discoverer, i s described i n the following section. - 4 -1.3 BRONSTED RELATIONSHIP In 1913, Dawson and Powis published a study of the e n o l i z a t i o n of acetone catalyzed by a number of acids ranging i n strength from acetic to hydrochloric a c i d (DP13). This was ten years before Bronsted defined acids as species that give up protons and bases as species that accept protons (B23). In 1913, the Arrhenius d e f i n i t i o n of acids was popular; i t defines acids as substances which give r i s e to hydrogen ions i n aqueous s o l u t i o n . An i n t e r e s t i n g account of the early h i s t o r y of acid and base d e f i n i t i o n s has been compiled by B e l l , going from the lat e eighteenth century to Bronsted's d e f i n t i o n (B73a). Dawson and Powis stated i n t h e i r paper that "evidence has been obtained i n support of the view that the ca t a l y z i n g power of an a c i d i s not e n t i r e l y due to the hydrogen ion, but that the undissociated a c i d also contributes to the observed e f f e c t . " They measured the rate constant f o r the e n o l i z a t i o n catalyzed by hydrogen ion and the undissociated acids. Of course, c a t a l y s i s by undissociated hydrochloric a c i d was subsequently disproven (B73b) . The authors drew attention to the fac t that the "catalyzing power of the undissociated a c i d diminishes r a p i d l y as the i o n i z a t i o n tendency decreases, a r e l a t i o n which has already been pointed out by Snethlage." However they could not f i n d any quantitative r e l a t i o n s h i p between these two fa c t o r s . Within the decade, Bronsted and Pederson were studying the decomposition of nitramide i n aqueous solu t i o n , eq. [1.4], (BP 24). NH 2N0 2 > H 20 + N 20 [1.4] Like many s c i e n t i s t s , before and a f t e r , t h e i r i n i t i a l aim i n studying t h i s r e a c t i o n proved f r u i t l e s s while a far more i n t e r e s t i n g r e s u l t became evident: a simple r e l a t i o n s h i p was seen to e x i s t between the rate constants f o r the base catalyzed decomposition of nitramide, kg, and the b a s i c i t y constants of the c a t a l y s t s , Kg, eq. [1.5]. A d e t a i l e d d i s c u s s i o n of t h i s reaction and i t s mechanism i s ava i l a b l e (B73c) . kg = (6.2 x 1 0 - 5 ) ( K B ) 0 - 8 3 [1.5] This r e l a t i o n s h i p has become known as the Bronsted r e l a t i o n s h i p . One wonders how close Dawson was to uncovering the c o r r e l a t i o n , and i f perhaps we might now be discussing the Dawson r e l a t i o n s h i p . Before di s c u s s i n g the r e l a t i o n s h i p further i t i s worth o u t l i n i n g some concepts of c a t a l y s i s . A c a t a l y s t i s a substance that increase the rate of rea c t i o n without i t s e l f being consumed. In the a c i d h y d r o l y s i s of most acetals the mechanism given i n eq. [1.6] operates (S85a). OCH 3 HOCH3 C H 3 — C OCH3 + H + C H ~ ^ 0 C h 3 [ L 6 a ] H H H f C H 3 CH3OH + ^ [ l - 6 b ] SLOW + CHg—C OCH 3 > C H j — C = O C H 3 > C H j — C OCKj + H H20 - 6 -The rate of t h i s r eaction depends only on the equilibrium a c t i v i t y of the proton, i . e . i n d i l u t e aqueous so l u t i o n , on the pH. Reactions of t h i s type can be represented by eq. [1.7]. There i s no proton transfer i n the rate c o n t r o l l i n g step of t h i s r e a c t i o n . Such c a t a l y s i s i s c a l l e d s p e c i f i c a c i d c a t a l y s i s . In speci-f i c base c a t a l y s i s the rate depends only on the equilibrium a c t i v i t y of hydroxide ion. On the other hand when the rate c o n t r o l l i n g step of a r e a c t i o n involves proton transfer, general acid and/or general base c a t a l y s i s w i l l be evident. The base catalyzed decomposition of n i t r a -mide i s an example of general base c a t a l y s i s . The rate depends on the nature and concentration of a l l the bases present i n the system, hydroxide and acetate i n an acetate b u f f e r , for example. The two routes by which general a c i d catalyzed reactions proceed are shown i n eqs. [1.8] and [1.9]. A-2 mechanism Z + H + [1.7a] Z H+ rate c o n t r o l l i n g step > p r o d u c t s [1.7b] Z + HA ZH + + A" [1.8a] ZH + + A" slow •> products [1.8b] A-S E -2 mechanism Z + HA slow •> products [1.9] 7 The a c i d catalyzed e n o l i z a t i o n of ketones i s an example of an A-2 mechanism, eq. [1.10]. I t can be shown that the A-2 and A-Sg-2 mechanisms are k i n e t i c a l l y equivalent (S85b). [1.10a] [1.10b] Reactions subject to general acid and/or general base c a t a l y s i s can be treated by eqs. [1.11a] and [1.12a] where HA i s the general acid and k j ^ the rate constant f or that acid; and A" i s the general base and k A- the rate constant f or that base. Since ^ - . K ^ = K W , eq. [1.11a] can be rewritten as eq. [1.11b]. Base C a t a l y s i s k A- = (const) ( K A - ) ^ [ l . H a ] k A- = ( c o n s t ) ( K H A ) " ^ [1.11b] Acid C a t a l y s i s k j ^ = ( c o n s t ) ( K H A ) " [1.12a] These equations are expressed as l i n e a r r e l a t i o n s h i p s i n eqs. [1.13] and [1.14]. Since -log = pK, eqs. [1.15a] and [1.16a] r e s u l t . - 8 -log k A- - -B log + C l o S kHA ~ a l o S KHA + c log k A- - 6 pK + C log k ^ -= —a pK + C [1.13] [1.14] [1.15a] [1.16a] In a s i t u a t i o n where both general a c i d and general base catalyses operate, two Bronsted l i n e s would r e s u l t as shown i n F i g . 1. 7-CD F i g . 1: Bronsted plots resulting from both general acid catalysis (open c irc les) and general base catalysis (closed c irc les) The Bronsted equation which began as an empirical observation, has over many years proven i t s relevance to the study of proton transfer r e a c t i o n s . As stated by B e l l i n 1978, "In conjunction with isotope e f f e c t s , a study of Bronsted r e l a t i o n s constitutes the most powerful method f o r e l u c i d a t i n g the d e t a i l e d structure of proton transfer r e a c t i o n s , one of the most important classes of reactions i n chemistry and biology" (B78). - 9 -1.4 STATISTICAL FACTORS In a comparison of p o l y p r o t i c acids or bases with monoacids or bases, rate and equilibrium constants must be corrected s t a t i s t i c a l l y (B73d, BL65). Thus Bronsted and Pedersen proposed the form of the Bronsted equation, eqs. [1.11c] and [1.12b], where p and q are s t a t i s t i -c a l f a c t o r s (BP24). Base C a t a l y s i s k A-/q - (const) (qK^/p) ~@ [1.11c] A c i d C a t a l y s i s kHA/P " (const) (qKm/p)a [1.12b] The number of equivalent a c i d i c protons i s represented by p, while q i s the number of equivalent s i t e s f o r proton attachment. These eqs. can be expressed as eqs. [1.15b] and [1.16b]. Base C a t a l y s i s log k / q = £(PK + log P / q ) + C [1.15b] Ac i d C a t a l y s i s log k / p = -e»(pK + log P/ q) + C [1.16b] Thus, i n comparing o x a l i c acid, (COOH)2, with a c e t i c acid, CH3COOH, p = 2 and 1 r e s p e c t i v e l y . While the former a c i d has two - 10 protons a v a i l a b l e , the l a t t e r has only one. The value of q i n both cases i s 2, as a carboxylate has two s i t e s for proton attachment. For phenol, C5H5OH, p = 1 and q = 1. With respect to the base c a t a l y s t s oxalate dianion, acetate and phenoxide, p = 1, q = 4 for (C00")2> p = 1, q = 2 for CH3COO", and p = 1 and q = 1 for C 6H 50". The values of p and q chosen for a homogeneous set of acids or bases i s immaterial, as i t only moves the Bronsted l i n e v e r t i c a l l y or h o r i z o n t a l l y while keeping the slope the same. These s t a t i s t i c a l c o r r e c t i o n s become important, however, when comparing the c a t a l y t i c e f f e c t s of acids or bases that have d i f f e r i n g values of p and q. A d e v i a t i o n from a Bronsted l i n e which i s s o l e l y dependent on the choice of values for p and q would have to be treated with caution. Generally deviations are s u f f i c i e n t l y large that they cannot be a t t r i b u t e d to an i n c o r r e c t choice of values for p and q. The hydronium ion, l^O"1" i s such an example. I t frequently deviates markedly from acid catalyzed Bronsted c o r r e l a t i o n s . Values of p = 3 and q = 1 are commonly used for l^O"1", the value of q being derived from the number of equivalent s i t e s f o r proton attachment i n the conju-gate base of the hydronium ion, H2O. Gold and Waterman have suggested that q = 2 as the oxygen atom has two lone p a i r s i n H2O (GW68). Regardless of whether a value of q = 2 or 1 i s used, the hydronium ion e x h i b i t s a marked negative deviation from most Bronsted l i n e s , ( i . e . decreased c a t a l y t i c a c t i v i t y ) . - 11 -1.5 MEANING OF THE BRONSTED EXPONENT The Bronsted exponent, a or 6, i s a measure of the s e n s i t i v i t y of the r e a c t i o n to change i n structure of the c a t a l y z i n g a c i d or base. These exponents l i e between the value of 0 and 1 for most reactions. The use of a or B depends on whether the c a t a l y s t s are proton donors (a) or acceptors (8). What i s the t h e o r e t i c a l meaning of the exponent? The r e l a t i o n s h i p can be considered a q u a n t i f i c a t i o n of the Hammond postulate, which states that i n an exothermic reaction the t r a n s i t i o n state should resemble the reactants, whereas i n an endothermic r e a c t i o n the t r a n s i -t i o n state should resemble the products (LR87b). Consider eq. [1.17]. When HA i s a much weaker a c i d than BH+, the re a c t i o n p r o f i l e shown i n F i g . 2 r e s u l t s . The t r a n s i t i o n state resembles products. Small s t r u c t u r a l changes that change the free o energy of the products Gp, cause s i m i l a r changes i n the free energy of . o a c t i v a t i o n G . Conversely changes i n the free energy of reactants G r have very l i t t l e e f f e c t on G5"4. In such an example a = 1 and the reverse r e a c t i o n (base c a t a l y s i s by A") w i l l be d i f f u s i o n c o n t r o l l e d , r e s u l t i n g i n a B value of 0. B + HA > BH + + A" [1.17] Consider the opposite extreme, when HA i s a much stronger acid than BH +, as shown i n F i g . 3. The t r a n s i t i o n state resembles reactants o o and so G w i l l be dependent on G r, not G p. The acid catalyzed forward - 12 -ENERGY B + HA weak weak base a c i d B- -H S t . BH + .A" s trong a c i d s t rong base REACTION COORDINATE F i g . 2: Energy p r o f i l e f or eq. [1 .17] , HA being a much weaker a c i d than B H + B + HA ptrong s trong base a c i d ENERGY weak a c i d REACTION COORDINATE F i g . 3: Energy p r o f i l e f o r eq. [1 .17] , HA being a much stronger a c i d than B H + 13 -rea c t i o n w i l l be d i f f u s i o n c o n t r o l l e d (a = 0) and the reverse -reaction w i l l have 8 = 1. In the region where BH + and HA are s i m i l a r i n ac i d strength, a and B values between 0 and 1 w i l l be observed. L e f f l e r and Grunwald have q u a n t i f i e d the Hammond postulate using eq. [1.18] where S denotes the e f f e c t of substituent changes on the quantity i t precedes (LG63). , , o o • o Since B = 1-a, AG = G —G r, and AG° = G p-G r eqs. [1.19], [1.20] and [1.21] r e s u l t . SG* = Q SG° + B SG° [1.18] SG* = a 5G° + SG° - a SG° [1.19] SG* - SG° = a (SG° - 6G°) [1.20] a = 6 AG*/5 AG° [1.21] Thus a can be defined as a " r a t i o of substituent e f f e c t s , namely, the substituent e f f e c t on the free energy of a c t i v a t i o n divided by the substituent e f f e c t upon the standard free energy change of the reaction" (K75). We can also i n t e r p r e t a as a measure of the p o s i t i o n of the t r a n s i t i o n state. A small value of a implies a t r a n s i t i o n state resembling reactants with l i t t l e t r a n s f e r of the proton. A large value of a implies a t r a n s i t i o n state resembling products, with a su b s t a n t i a l degree of proton transfer i n the t r a n s i t i o n state. Many good discus-sions of the Bronsted exponent and i t s meaning are av a i l a b l e (B73e,B78,K73,K75 and S85c). 14 -1.6 CURVATURE IN BRONSTED PLOTS I The Bronsted r e l a t i o n s h i p was the f i r s t l i n e a r free energy r e l a t i o n s h i p to be discovered, predating the Hammett equation by ten years. I t r e l a t e s the free energy of a c t i v a t i o n AG*, a k i n e t i c parameter, to the free energy of rea c t i o n AG°, a thermodynamic parameter. R e c a l l that a can be considered as 5AG*/5AG°, which i n the l i m i t i s dAG*/dAG°. This c o r r e l a t i o n between rate and e q u i l i b r i a i s a purely empirical observation and bears no r e l a t i o n s h i p to the laws of equ i l i b r i u m thermodynamics. An inherent assumption i n our discussion of the Bronsted exponent and the Hammond postulate i s the following; the p o s i t i o n of the t r a n s i -t i o n state along the reaction co-ordinate ( i . e . the extent of proton tr a n s f e r ) w i l l not change as the strength of the a c i d HA or the base B changes. This w i l l be true over a small range of a c i d or base strength, but over an extensive range of pK, changes i n the Bronsted c o e f f i c i e n t may r e s u l t . Bronsted predicted i n h i s o r i g i n a l paper that log k would be a curved rather than a l i n e a r function of log K (BP24). This curvature can be understood further and i n f a c t used (with care) to determine free energies of a c t i v a t i o n with the a i d of Marcus theory (CM68). 15 1.7 MARCUS THEORY 1.7.1 Derivation and A p p l i c a t i o n Marcus developed an equation r e l a t i n g the rate of electron trans-f e r processes to c e r t a i n parameters, and i t has since been applied with success to both proton tran s f e r and atom transfer reactions. Only a b r i e f relevant discussion of the theory w i l l be given here, as a number of review a r t i c l e s and recent papers address the issue (B78, K73, F75, LS81, JB82, K83, KL84, SA84, HP84, SK85, ES87 and LR87C). The approach to Marcus theory used here owes a great deal to r e f s . K73 and LR87c, with some modification introduced by t h i s author. Marcus theory a l l o c a t e s two contributions to an a c t i v a t i o n b a r r i e r ; (1) a thermodynamic part r e s u l t i n g from the o v e r a l l free energy change of the r e a c t i o n ; (2) an i n t r i n s i c k i n e t i c part which i s the reaction b a r r i e r that would e x i s t i f the reactants and products had the same free energy. Consider, for example, the proton transfer reaction, eq. [1.17], where AH could be acetone and B any base. B + HA > BH + + A - [1.17] Marcus theory envisages the r e a c t i o n coordinate as two i n t e r s e c t -ing parabolas, one representing the p o t e n t i a l energy surface for s t r e t c h i n g the A—H bond i n the reactants and the other representing the s t r e t c h i n g of the B—H bond i n the products. The locations of these parabolas are determined by the o v e r a l l free energy change and the 16 -i n t r i n s i c b a r r i e r . The i n t r i n s i c b a r r i e r i s obtained by considering symmetrical reactions, such as those shown i n eqs. [1.22] and [1.23], represented by the two parabolas i n F i g . 4. AH + A - + HA [1.22] HB BH [1.23] The parabolas are drawn so as to i n t e r s e c t at the a c t i v a t i o n ener-gies of eq. [1.22], AG e q_ [1.22] (Fig.4(a)) and eq. [1.23], AG e q [1.23] (Fi g . 4(b)). Fig . 4: Parabolas representing eqs. [1.22], F i g . 4(a) and [1.23], F i g . 4(b). - 17 -A new p a i r of parabolas i s drawn so as to i n t e r s e c t at the average of the a c t i v a t i o n energies of the two processes represented by eqs. [1.22] and [1 .23] . This average i s the i n t r i n s i c b a r r i e r , A G D , of the proton t r a n s f e r process represented by eq. [1.17] ( F i g . 5) . FREE ENERGY REACTION COORDINATE F i g . 5: I n t e r s e c t i n g parabolas at AG = 1/2 ( A G e q . [ 1 . 2 2 ] + A G e q [1 23]) , represent ing the i n t r i n s i c b a r r i e r of the proton t r a n s f e r process represented by eq. [1 .17] , A G D ^ The parabolas represent ing the ac tua l r e a c t i o n are shown i n F i g . 6(a) and (b) . They are generated by d i s p l a c i n g the parabolas of F i g . 5 v e r t i c a l l y r e l a t i v e to one another by the observed free energy change, AG°. The r e a c t i o n might be exergonic , AG° < 0, F i g . 6(a) or endergonic AG° > 0, F i g . 6(b) . The new po int of i n t e r s e c t i o n of the two parabolas i s the a c t i v a t i o n free energy b a r r i e r , AG**, f or the r e a c t i o n . I t can be - 18 -expressed in terms of AGQ, the in tr ins ic barrier and A G ° , the observed free energy change by deriving the mathematical expression for the point of intersection of the two parabolas in F ig . 6(a) or (b). 0 05 1 0 o.5 J i I 1 i REACTION COORDINATE REACTION COORDINATE F i g . 6: Displaced parabolas from F i g . 5 so as to give an overall free energy change AG° < 0 (a) or AG° > 0 (b). The general expression for the parabolas in F ig . 5 are X 2 = C^AG for parabola AH and ( X - l ) 2 = C2AG for parabola B,^ . where X is the reaction coordinate and and C 2 are parabola constants. For both parabolas at a X value of 0.5, AG - AG Q , the in tr ins ic barrier . Thus the constants and C 2 can be determined, = 1/4AGQ and C 2 = 1/4AGQ We can now write the equations for the parabolas as follows. 19 Parabola AH X 2 = (1/4AG D) AG [1.24] F i g . 5 Parabola B ( X - l ) 2 = (1/4AGQ) AG [1.25] F i g . 5 In F i g . 6(a) or (b) parabola B has been moved v e r t i c a l l y by a fa c t o r AG 0, and hence t h i s parabola i s now expressed by eq. [1.26]. Parabola AH i s F i g . 6(a) or (b) i s the same as i n F i g . 5, represented by eq. [1.24]. Parabola B ( X - l ) 2 = 1/4AG 0 (AG - AG°) [1.26] F i g . 6 The point of i n t e r s e c t i o n of parabolas AH and B i n F i g . 6(a) or (b) i s at AG = AG* and can be determined by s u b s t i t u t i n g the value for X at the point of i n t e r s e c t i o n from eq. [1.24], (AG*/4AG 0)1/ 2, into eq. [1.26] to give eq. [1.27]. [ ( A G ^ A G Q ) 1 / 2 - l ] 2 = 1/4AG Q (AG* — AG 0) [1.27] Eq. [1.27] i s rearranged to give an expression f o r AG*, as shown. AG*/4AGQ + 1 - 2 ( A G ^ A G Q ) 1 / 2 = AG*/4AGQ - AG°/4AGQ [1.28] ( A G ^ A G Q ) 1 / 2 - (1 + AG°/4AGQ) [1-29] AG* - (1 + AG°/4AGQ) 2 AGQ [1.30] 20 The p o s i t i o n of the t r a n s i t i o n state along the r e a c t i o n coordinate X can be determined by s u b s t i t u t i n g f or AG, which i s equivalent to AG*, from eq. [1.30"] into eq. [1.24]. The r e s u l t i s given i n eq. [1.31] and i s equivalent to a (or B), the Bronsted exponent determined by taking the d e r i v a t i v e of eq. [1.30] with respect to AG°. X = 1/2 (1 + AG°/4AGQ) - dAG*/dAG° = a [1.31] In F i g . 6(a), where AG° < 0, an a value of less than 0.5 would be observed. For F i g . 6(b), where AG 0 > 0, an a value greater than 0.5 would r e s u l t . The degree of curvature present i n a Bronsted p l o t w i l l be represented by eq. [1.32]. When the i n t r i n s i c b a r r i e r i s small a large degree of curvature w i l l r e s u l t . Conversely, with large values of i n t r i n s i c b a r r i e r s , Bronsted p l o t s w i l l show l i t t l e or no curvature. da/dAG° = 1/8AGQ [1.32] Our d i s c u s s i o n thus far has not considered the work expended i n b r i n g i n g the reactants from an i n f i n i t e distance apart to the p o s i t i o n where the proton tran s f e r can occur and then separating the products to i n f i n i t e distance. We should tr e a t the encounter of reactants, involv-ing a work term Wr, and the separation of products, i n v o l v i n g a work term Wp, as d i s t i n c t steps separate from the actual proton transfer i t s e l f and i n v o l v i n g a free energy change. A three step process representing the mechanism of proton transfer i s shown below. 21 AH + B A - H B ENCOUNTER 1.331 A - H — A H - B PROTON TRANSFER fl.34 -W H - B % P 'A' + HB+ SEPARATION [ 1 - 3 5 ; The observed free energy of reac t i o n ( A G ° ) O D S w i l l then be represented by eq. [1.36]. The observed free energy of a c t i v a t i o n ( A G ^ ) o b s w i l l be represented by eq. [1.37]. An energy p r o f i l e diagram fo r an endothermic reaction i s shown i n F i g . 7. <AG°) o b i (A G*)ob £ AG + VL. - VL AG + Wv [1.36] [1.37] E N C O U N T E R obs R E A C T I O N C O O R D I N A T E F i g . 7: Energy prof i le diagram describing eqs. endothermic proton transfer (AG° > 0) [1.33]-[1.37] for an - 22 -Subs t i t u t i n g AG^ from eq. [1.30] into eq. [1.37] gives eq. [1.38]. We can now substitute AG° from eq. [1.36] into eq. [1.38] gi v i n g eq. [1.39]. < A G ? % b s ~ C 1 + AG°/4AGo) 2 AGQ + Wr [1.38] ( A G * ) O B S - [1 + ( ( A G ° ) O B S - Wr + W p ) / 4 A G Q ] 2 AGQ + Wr [1.39] The work terms Wr and Wp and the i n t r i n s i c b a r r i e r A G Q are assumed to be constants along a reac t i o n s e r i e s . These assumptions together with l i m i t a t i o n s to t h i s approach, w i l l be discussed l a t e r . The parabolas shown i n F i g . 6(a) are a q u a n t i f i c a t i o n of the Hammond postulate showing an early t r a n s i t i o n state f o r a re a c t i o n with AG° < 0 and the Bronsted c o e f f i c i e n t ( i . e . the reaction coordinate) less than 0.5. A q u a n t i f i c a t i o n of the Hammond postulate showing a l a t e r t r a n s i t i o n state with AG° > 0 and the Bronsted c o e f f i c i e n t ( i . e . the rea c t i o n coordinate) greater than 0.5 i s shown i n Fi g . 6(b). The expression r e l a t i n g the observed free energy of a c t i v a t i o n , ( A G ^ ) O B S to the observed free energy of reaction, ( A G ° ) O B S , eq. [1.39] can be stated as a quadratic expression eq. [1.40], where the c o e f f i -cients a, b and c are defined by eqs. [1.41], [1.42] and [1.43] respec-t i v e l y . - 23 -( A G ? % b s = a + b ( A G ° ) O B S + c ( A G ° ) O B S [1.40] a = AG* + (Wp + WR)/2 + 1/16AG 0 (Wp — W r) 2 [1.41] b - 1/2 + 1/8AG* (Wp - Wr) [1.42] c - 1/16AGQ [1.43] Expressions for AG*, Wr and Wp can be determined using eqs. [1.41]-[1.43] g i v i n g eqs. [1.44]-[1.46]. A G Q » l/16c [1-44; Wr = a - b 2/4c [1.45] Wp = Wr + l/4c (2b - 1) [1.46] The observed free energy of a c t i v a t i o n , ( A G * ) o b s i s r e l a t e d to the observed rate constant k c a t for the c a t a l y s t (be i t HA or B) by eq. [1.47] where h, k and T are Planck's constant, Boltzmann's constant and K e l v i n temperature r e s p e c t i v e l y . The observed free energy of the reac-t i o n , ( A G ° ) o b s , i s r e l a t e d to the equilibrium constants of HA and BH + by eq. [ 1 . 4 8 ] . ( A G * ) o b s = - RT l n ( k c a t h / k T ) [1.47] - 24 ( A G ° ) o b s = - RT l n [A"][BH +]/[AH][B] - - RT l n 1^/1^+ [1.48] The quadratic expression, eq. [1.40] can be expanded i n terms of log k c a t , log k^A and log kg^+ to give a complex equation. Generally i n a Bronsted p l o t , one species w i l l be kept constant (the substrate) while the other i s v a r i e d (the c a t a l y s t ) . In eq. [1.17], HA could be the acid c a t a l y s t with B being the substrate. Since B remains unchanged, log ^BH + w i l i be a constant and the expansion of eq. [1.40] reduces to eq. [1.49]. The parameters AG Q, Wr and Wp are defined i n eqs. [1. 50]-[1.52]. log k ^ " A + B ( l o S KHA> + C < loS K H A ) 2 [1-49] AG Q = - 2.3 RT/16C [1.50] Wr = 2.3 RT (log kT/h - A + B 2/4C) [1.51] Wp = Wr + 2.3 RT (1/4C - B/2C - log K B H+) [1.52] The work term Wr and the i n t r i n s i c b a r r i e r can be determined from the c o e f f i c i e n t s of the Bronsted p l o t that shows curvature, without knowing the pK of the protonated substrate, BH +. This l a t t e r quantity i s needed i n order to determine the work term Wp. The other p o s s i b i l i t y involves HA i n eq. [1.17] being the sub-s t r a t e and B being a serie s of base c a t a l y s t s . Now log K^A w i l l be a constant and eq. [1.53] r e s u l t s , with the parameters AG D, Wr and Wp being defined by eqs. [1.54]-[1.56]. - 25 -log k B - D + E (log K B H+) + F (log K B H + ) 2 - [1.53] A G Q = - 2.3RT/16F [1.54] Wr = 2.3RT (log kT/h - D + E 2/4F) [1.55] Wp = Wr + 2.3RT (1/4F + E/2F + log K^) [1-56] Both a c i d and base c a t a l y s i s give the same r e s u l t i n r e l a t i n g the quadratic c o e f f i c i e n t s to the energy parameters, except for changes of sign i n the d e f i n i t i o n of Wp. Kreevoy and Oh have compiled a number of reactions and determined t h e i r i n t r i n s i c b a r r i e r s , A G D and work terms Wr (K073). Albery and co-workers have applied the same treatment to several other reactions (AC72). A l l these data have been c o l l e c t e d and discussed by Kresge (K73). The r e s u l t i n g i n t r i n s i c b a r r i e r s , AG Q, are small (averaging 4 k c a l mol'l) while the work terms Wr are generally much larger (averaging 12 k c a l mol"-'-) i n proton transfer reactions. 1.7.2 Limitations to Marcus Theory One of the assumptions i n the treatment j u s t described i s that AG 0, Wr and Wp are constant along a reaction s e r i e s . This assumption i s v a l i d where, f o r example, HA i s acetone and the bases are a series of oxygen anions. The bulk of AG 0 can be a t t r i b u t e d to AG* for the - 26 symmetrical reactions in v o l v i n g HA represented by eq. [1.22]. The free energy of a c t i v a t i o n f or the symmetrical reaction represented by eq. [1.23] w i l l be small for an oxygen anion, B. AH + A" > A" + HA [1-22] B + HB + > BH + + B [1.23] A di s c u s s i o n of s i t u a t i o n s where the i n t r i n s i c b a r r i e r i s not a constant i s a v a i l a b l e (K73). Other assumptions i n 'simple' Marcus theory involve the use of the parabolas i n F i g . 6; the distance moved by the hydrogen atom, d H, i s assumed to be constant as either AH or B i s varied; and the force constants of the A H bond, k^, and that of the H—B bond, k 2, are assumed equal. Kresge and Koeppl determined an expression for the free energy of a c t i v a t i o n involving these parameters, (an equation which reduces to eq. [1.30] i f k^ = k 2 and d H i s constant) (KK73). The authors determine that i n considering v a r i a t i o n s i n k^, k 2 and d^, a sigmoid dependence of a upon AG r e s u l t s . In the range of a = 0.2 - 0.8, the dependence i s almost l i n e a r , as predicted by Marcus theory. But the slopes of these l i n e s are greater than those predicted by Marcus theory, by about a f a c t o r of two. Other approaches to the proton transfer process give the same r e s u l t , i . e . i n t r i n s i c b a r r i e r s r e s u l t i n g from simple Marcus theory may be underestimated by as much as a factor of two (K73, LS81). For example a treatment by Lewis and co-workers invoked a hyperbolic modification of the Bronsted r e l a t i o n s h i p and determined that Marcus theory "provides a lower l i m i t for and indeed must underestimate - 27 -the ( i n t r i n s i c ) b a r r i e r " (LS81). The equation r e l a t i n g A G * and AG° used by these authors i s shown below, eq. [1.57], and d i f f e r s from Marcus theory, eq. [1.30] i n the magnitude of the c o e f f i c i e n t of the squared 7* term. This approach therefore leads to AG Q values twice that of Marcus theory. AG* = AG Q + AG°/2 + (AG°)V8AG 0 [1-57] AG* = AG* + AG°/2 + ( A G 0 ) 2 / 1 6 A G Q [1.30] While simple Marcus theory may underestimate AG Q, the r e l a t i v e values of AG Q and work terms obtained from the r e a d i l y applicable equa-tions are v a l i d . Despite the l i m i t a t i o n s of Marcus theory, i t gives r e s u l t s which have support from other t h e o r e t i c a l approaches to proton tr a n s f e r . As Kresge emphasizes i n h i s review, a number of t h e o r e t i c a l studies, as well as Marcus theory, p r e d i c t that the degree of curvature i n a Bronsted p l o t w i l l depend on the magnitude of A G Q (K73). There e x i s t s an experimental l i m i t a t i o n to a treatment involving Marcus theory. A curved Bronsted p l o t , free from a r t i f a c t s r e s u l t i n g from the use of c a t a l y s t s of d i f f e r e n t types, i s needed. The presence of curvature i n some of the l i t e r a t u r e examples treated with Marcus theory i s questionable i n t h i s regard (see p. 45 for example). The most serious c r i t i c i s m of Marcus theory i s whether i t i s v a l i d to separate the 'setting-up' of the reagents in v o l v i n g reagent p o s i t i o n -ing and solvent reorganization from the actual proton tran s f e r i t s e l f , an aspect which w i l l be discussed l a t e r . - 28 -1 . 8 PRIMARY ISOTOPE EFFECTS The use of the Bronsted r e l a t i o n s h i p i s often coupled with studies of primary isotope e f f e c t s as probes of proton t r a n s f e r reaction pathways and energetics, and reviews of the subject are a v a i l a b l e (M75, L76, and K76). The Westheimer p r i n c i p l e suggests how isotope e f f e c t s can be re l a t e d to the extent of proton transfer i n the t r a n s i t i o n state for those reactions i n which a bond to protium (deuterium, t r i t i u m ) i s broken. The p r i n c i p l e states that a maximum isotope e f f e c t should be found f o r a t r a n s i t i o n state i n which the hydrogen i s h a l f transferred between the donor and acceptor atoms (W61). I f there i s no breaking of a bond to the i s o t o p i c atom i n the t r a n s i t i o n state, only a small secondary isotope e f f e c t w i l l be expected. I f a t r a n s i t i o n state changes from being r e a c t a n t - l i k e (a close to zero) to being product-like (a close to unity) the isotope e f f e c t should r i s e and f a l l , being a maximum when the proton i s h a l f transferred. A c o r r e l a t i o n of a and isotope e f f e c t s can be obtained by using a q u a d r a t i c - f i t t e d Bronsted p l o t , eq. [1.49]. l o g k ^ = A + B (log Km) + C (log K ^ ) 2 [1.49] d log km/d log = B + 2C log K H A [1.58] For any a c i d of known pK, a value of a i s defined from the de r i v a t i v e of eq. [1.49], i . e . eq. [1.58]. When the proton i s h a l f - 29 -transferred, a maximum isotope e f f e c t should r e s u l t , a should be 0.5 and from eq. [1.31], AG° = 0 ( i . e . ApK = 0). Experimental evidence for these predictions i s d i f f i c u l t to obtain, r e q u i r i n g p r e c i s i o n of ky/kn values, a curved Bronsted p l o t and ApK values close to zero. Kreevoy and Oh obtained an expected c o r r e l a -t i o n of kn/kp and pK for the hydrolysis of diazoacetate anion catalyzed by trialkylammonium ions, eq. [1.59], (K073). + + R1R2R3NH + N2CHC00" > R XR 2R 3N + N2CH2COO" [1.59] V Products Kemp and Casey did not f i n d any s i g n i f i c a n t trends i n the isotope e f f e c t s f o r the proton abstraction from benzoisoxazoles by t e r t i a r y amines, eq. [1.60], (KC73a). Despite a t o t a l v a r i a t i o n i n rate by a fac t o r of 10^, no s i g n i f i c a n t v a r i a t i o n i n l i n e a r i t y of the Bronsted p l o t was observed. J R 1B 2R 3N ;i.60] Dixon and Bruice i n t h e i r study of the primary amine catalyzed i o n i z a t i o n of nitroethane found l i n e a r Bronsted pl o t s f or both the and 2 H substrates with B values of 0.57 ± 0.02 (DB70). Surpr i s i n g l y , t h e i r p l o t of k^/kn vs. pK showed a b e l l shaped curve, a l b e i t a poor one, with a maximum close to the pK of nitroethane, 8.5. A change of - 30 -solvent from H 20 to 50% dioxane-water (v/v) changes the pK of n i t r o -ethane to 10.7. Now, the p l o t of k^/kj) vs. pK r i s e s towards a pK value of 10.7. They could not determine i f the curve drops at pK values greater than 10.7, owing to experimental d i f f i c u l t i e s . Considering that l i n e a r Bronsted pl o t s were found for t h i s data, the authors conclude that "primary k i n e t i c isotope e f f e c t s are a more s e n s i t i v e probe of t r a n s i t i o n state than are Bronsted p l o t s . " Bordwell and Boyle i n 1971 b r i e f l y reviewed the topic of k i n e t i c isotope e f f e c t s as guides to t r a n s i t i o n state structures i n deprotona-t i o n reactions (BB71). The authors question the evidence of the maxima i n k^/kj) vs. ApK c o r r e l a t i o n s that have been reported. Instead they consider the p o s s i b i l i t y that many of the reactions have an inherent experimental inaccuracy, that s t e r i c and t u n n e l l i n g e f f e c t s may e x i s t and that low k^/kj) values i n cases of p o s i t i v e ApK values may be due to p r e - r a t e - l i m i t i n g e q u i l i b r i a . They conclude that there i s no simple c o r r e l a t i o n of Bronsted c o e f f i c i e n t s and isotope e f f e c t s with the extent of proton trans f e r i n the t r a n s i t i o n state. Bruniche-Olsen and Ulstrup have used a fundamentally d i f f e r e n t approach to isotope e f f e c t s i n proton transfer reactions from those discussed so f a r (BU79). They used the quantum theory of elementary processes i n condensed media to predict the k i n e t i c isotope e f f e c t of proton t r a n s f e r reactions i n homogeneous s o l u t i o n . Changes i n AG Q and ApK were assumed to be i n s i g n i f i c a n t when the isotope i s substituted. The authors have treated several sets of experimental data with t h e i r a n a l y s i s , i . e . the best t h e o r e t i c a l f i t of a parabola to the kj^/kj) vs. ApK p l o t using a set of equations derived from t h e i r approach. Their 31 -r e s u l t s support the view that a maximum isotope e f f e c t w i l l be observed a t ApK ~ 0. Unlike the Marcus approach which requires curvature i n Bronsted p l o t s to determine values of AG Q, t h i s approach can be used with l i n e a r Bronsted p l o t s as long as the p l o t of k^/krj vs. ApK i s experimentally a c c e s s i b l e . The magnitude of AG Q i s d i r e c t l y r e l a t e d to the width of the parabolic p l o t of k^/kp vs. ApK. Large values of AG Q imply broad curves, while small values involve sharp curves. This r e l a t i o n s h i p between the rate of decrease of k^/kj) with ApK and AG Q i s also predicted by Marcus theory (CM68, F75). Bunriche-Olsen and Ulstrup use the parameter E s, which i s the same as the A parameter used by Cohen and Marcus (CM68) and Kreevoy and Oh (K073). I t i s equal to 4AG Q and i s expressed i n units of eV which can be converted to k c a l mol"-'- by means of the r e l a t i o n s h i p 1 eV = 23.1 k c a l mol . The authors give an equation to determine AG Q from the co-e f f i c i e n t of the squared term from the quadratic expression of a p l o t of l o g k vs. ApK using t h e i r treatment, eqs. [1.61] and [1.62]. log k = A + B(ApK) + C(ApK) 2 [1-61] AG Q = E s / 4 = 2.3/16RTC [1.62 ] Curiously, eq. [1.62] and eq. [1.50], which r e s u l t s from simple Marcus theory, d i f f e r only i n sign and i n the p o s i t i o n of RT being i n the denominator i n eq. [1.62] and i n the numerator i n eq. [1.50]. As 32 -the units on e i t h e r side of eq. [1.62] do not balance there i s obviously something amiss. One wonders i f the two equations are equivalent. AG Q = - 2.3RT/16C [1.50] The r e s u l t s of B e l l and Grainger from the e n o l i z a t i o n of 3-nitro-(+)-camphor are analyzed by Bunriche-Olsen and Ulstrup (BG76). The r e s u l t of the best t h e o r e t i c a l f i t to the kpj/kn vs. ApK p l o t gives a AG 0 value of 1.5 k c a l mol"-'-. We have treated the quadratic expression from a p l o t of log k vs. ApK by the Marcus formalism, determining a AG Q value of 3.4 k c a l mol'^. The data of Bordwell and Boyle for the i o n i z a t i o n of a group of nitroalkanes give a value of AG 0 = 6.7 kcal mol"-'- (BB75, F75) . Bunriche-Olsen and Ulstrup determine a value of 4 k c a l mol"-'- for the same compounds. The agreement between the two d i s t i n c t l y d i f f e r e n t treatments i s not always t h i s close, however. For example i n the i o n i z a t i o n of e t h y l n i t r o a c e t a t e , Cohen and Marcus determined a AG Q value of 13 kcal mol" 1 from the Bronsted p l o t of B e l l and Spencer (CM68, BS59). Bunriche-Olsen and Ulstrup derive a value of e i t h e r 2.7 or 3.0 k c a l mol'-'- r e s p e c t i v e l y depending on whether two pyridine bases are included or not. Isotope e f f e c t maxima have also been observed when the proton t r a n s f e r occurs between a normal acid and a normal base. This process, (proton tran s f e r between oxygen or nitrogen) i s generally very f a s t while that in v o l v i n g a pseudo a c i d e.g. CH3COCHHCOCF3 (proton transfer - 33 -from carbon), i s generally much slower (E64). For example, the rate of protonation of the anions of acetic a c i d and the ac i d j u s t mentioned d i f f e r by a fac t o r of 7 x 10^ as shown below (C75), even though the pKj^ values of both acids are p r a c t i c a l l y the same. c , n10 M - l -1 CH 3C0 2 + H + 5 x 1 0 E — § £ £ > CH 3C0 2H pK - 4.76 [1.63] 2 -1 -1 CH3COCHCOCF3 + H + 7 - 5 x 1 0 — - — ^ e c — > CH3COCH2COCF3 pK = 4.70 [1.64] Kresge and co-workers have reported an isotope e f f e c t maximum for such a reaction, as shown below (BC7.8). 0~ OH I + I + A r C H N H 2 O C H 3 + HA s l o w > A r C H N H g O C H - + A " [1.65] The maximum isotope e f f e c t occurs at ApK ~ 0 and the Bronsted p l o t shows a sharp change i n slope from a = 0 to a = 1 i n the same region, as expected f o r a normal acid/base proton transfer (E64). The small si z e of the k^/k n maximum observed (~ 3) suggests that the proton transfer never becomes f u l l y rate determining. C l e a r l y , isotope e f f e c t s are important i n the study of proton t r a n s f e r processes. While some experimental r e s u l t s give support to our concepts of the process, other r e s u l t s i l l u s t r a t e possible flaws t h e r e i n . Tunnel e f f e c t s which were b r i e f l y mentioned e a r l i e r play a - 34 -d e f i n i t e r o l e i n isotope e f f e c t s , though the magnitude of t h e i r con-t r i b u t i o n i s a debatable subject . The term ' tunnel e f f e c t ' i s used "to descr ibe the motion of p a r t i c l e s across energy b a r r i e r s which would be imposs ible according to c l a s s i c a l mechanics but which i s p r e d i c t e d by quantum theory" (B80). The p r o b a b i l i t y of such n o n - c l a s s i c a l penetra-t i o n of the energy b a r r i e r increases with decreasing mass of the isotope i n v o l v e d ; thus the proton i s more prone to t u n n e l l i n g than the deuteron thereby r e s u l t i n g i n anomalously large kj^/kn va lues . I t has been suggested that tunnel e f f ec t s undermine any expected c o r r e l a t i o n of Bronsted c o e f f i c i e n t s and isotope e f fec t s (BB71, L76) . However, as tunnel e f f e c t s over lay the ' c l a s s i c a l ' e f f ec t of i s o t o p i c s u b s t i t u t i o n , c o r r e l a t i o n s between primary isotope e f fec t s with both t r a n s i t i o n state s t r u c t u r e and Bronsted c o e f f i c i e n t s do have a r o l e i n our understanding of the process invo lved . D e t a i l e d analyses of the tunnel e f f e c t are documented i n l i t e r a t u r e (L75, KW85, S87). 1.9 CURVATURE IN BRONSTED PLOTS II In 1977, Hupe and Wu studied the base ca ta lyzed e n o l i z a t i o n of a ketone wi th 30 oxyanions eq. [1.66] , (HW77). The authors used bases o [1.66 ] 35 -that vary i n pKj^ from 4.76 (CH3COO") to 16.0 (CH3CH2O"), including hydroxide ion (pK = 15.75). A d i s t i n c t l y curved Bronsted p l o t r e s u l t s . For bases of pK = 4.8 to 10.6, a B value of 0.75 i s found, while above a pK of 10.6 B f a l l s r a p i d l y to a value of 0.3. The hydroxide ion f i t s onto the curve for oxygen bases of high pK. The a p p l i c a t i o n of Marcus theory gives a value * 1 1 of AG Q = 2.5 k c a l mol and Wr = 15.1 k c a l mol . The small i n t r i n s i c b a r r i e r and the large degree of curvature imply a r a p i d l y changing t r a n s i t i o n state with changing c a t a l y s t pK, while the very large work term indicates the amount of energy needed to b r i n g the reactants together. I t may be r e c a l l e d that s i m i l a r r e s u l t s were obtained for other proton tran s f e r reactions (Section 1.7.1). The authors question such a small i n t r i n s i c b a r r i e r and conclude that "perturbation due to s o l v a t i o n of the bases" causes the Bronsted p l o t curvature. This e f f e c t , which i s dependent only on the pK of the c a t a l y s t , causes a decrease i n B for c a t a l y s t s with high b a s i c i t y . In 1984 Hupe and Pohl reported no s i g n i f i c a n t c o r r e l a t i o n of k^/kn and pK i n the same region where considerable curvature was present i n the Bronsted p l o t (HP84). The authors suggest that the decreasing B value, while p a r t l y due to a large i n t r i n s i c b a r r i e r (10 k c a l mol"-'-), i s mainly due to d i f f i c u l t y i n desolvating the i n c r e a s i n g l y basic anions. The work term Wr, assumed to be a constant i n Marcus theory, w i l l increase as the s o l v a t i o n of the base increases. Another example which i l l u s t r a t e s the care needed i n i n t e r p r e t i n g curved Bronsted p l o t s comes from the work of Bernasconi and Bunnell (BB85). They studied the i o n i z a t i o n of acetylacetone i n various - 36 -DMSO-H2O mixtures. Using j u s t s i x carboxylate anions, the authors observed downward curvature i n the Bronsted p l o t using DMSO-containing solvents. The degree of curvature increased as the content of DMSO present i n the solvent mixture was increased. The curvature was a t t r i b u t e d to the desolvation of the more basic/more solvated anions, and i s therefore independent of the substrate studied. Bernasconi and Paschalis confirmed the e f f e c t by examining the i o n i z a t i o n of another carbon a c i d , 1,3-indanone, and observing s i m i l a r r e s u l t s (BP86). Some chemists have questioned the v a l i d i t y of the Hammond postu-l a t e . Bordwell and Hughes drew attention to the d i f f i c u l t y of deter-mining whether curvature, i f present at a l l , i s due to changes i n AG° or to f a c t o r s such as sol v a t i o n or s t e r i c and e l e c t r o n i c e f f e c t s (BH84). They conclude that "there i s no compelling experimental evidence" that changing B values r e f l e c t changing AG° values. Hence, they question the experimental evidence for the a p p l i c a t i o n of the Hammond postulate and the Leffler-Grunwald approach. Other chemists have attempted to improve upon present concepts or to design new approaches. The use of energy surface diagrams based on two progress v a r i a b l e s (e.g. degree of proton transfer and solvation) has been advanced by More O ' F e r r a l l (M70, 3311). This q u a l i t a t i v e approach has been q u a n t i f i e d by Grunwald (G85). Murdoch has i l l u s t r a t e d the r e l a t i o n s h i p between More O ' F e r r a l l diagrams and Marcus rate theory (M83). Kurz has explained "anti-Hammond" behaviour, (reaction series i n which the f a s t e r reactions have more product l i k e t r a n s i t i o n s t a t e s ) , i n the context of Marcus rate theory (K83). Bernasconi has also d i r e c t e d h i s atte n t i o n to t h i s problem and developed the p r i n c i p l e of - 37 -nonperfect synchronization (B87). Bernasconi defines an i n t r i n s i c rate constant, k Q, for the general reaction shown below so that k Q — k^ = k.j_ when AG° = 0. Like the i n t r i n s i c b a r r i e r , k Q i s representative of a whole rea c t i o n set and i s independent of the thermodynamics of that set. HA + B „ A" + HB [1.17] k - l U s ually more than one concurrent process i s involved i n a reaction pathway. These processes may include bond formation/breakage, solva-tion/desolvation, resonance/loss of resonance, etc. and each may have made unequal progress at the t r a n s i t i o n state. In proton trans f e r reactions the concept of a " l a t e " or "early" t r a n s i t i o n state i s defined by the degree of bond formation or cleavage. The p r i n c i p l e of nonper-f e c t synchronization states that a product s t a b i l i z i n g f a c t o r that develops l a t e or a reactant s t a b i l i z i n g f actor that i s l o s t early always lowers k Q. Conversely a product d e s t a b i l i z i n g f a c t o r that develops l a t e or a reactant d e s t a b i l i z i n g factor that i s l o s t e arly increases k 0. Thus i n the two examples j u s t discussed, s o l v a t i o n of the oxyanion bases, a reactant s t a b i l i z i n g factor, which i s l o s t e a r l y ( i . e . before proton t r a n s f e r ) , decreases k Q causing negative deviations from the Bronsted p l o t , which i s 'seen' as curvature. Bernasconi has developed t h i s p r i n c i p l e i n a mathematical form (B87). C l e a r l y the Bronsted r e l a t i o n i s important i n helping us under-stand the proton t r a n s f e r process. More recent developments, such as Marcus theory, are also important, although they require experimental 38 v e r i f i c a t i o n . This has been forthcoming over the past two decades, as have r e s u l t s that i l l u s t r a t e the weaknesses i n our present concepts. This i s progress, a l i t t l e at a time. Jencks and co-workers expressed the r e a l i t y of the s i t u a t i o n i n 1982; " s t r u c t u r e - r e a c t i v i t y c o r r e l a t i o n s provide one of the most powerful tools f or probing the structure of t r a n s i t i o n states." Bronsted p l o t curvature "may represent a manifesta-t i o n of an a d d i t i o n a l v a r i a b l e that a f f e c t s the rate, rather than a change i n t r a n s i t i o n state structure. I t i s important, therefore, to examine c r i t i c a l l y the reasons for nonlinear s t r u c t u r e - r e a c t i v i t y c o r r e l a t i o n s " (JB82). 1.10 CATALYSIS OF ENOLIZATION Though Dawson and h i s co-workers and others had been studying the c a t a l y s i s of acetone e n o l i z a t i o n since the early 1900/s, much of the work was performed i n a le s s than rigorous manner. One of the f i r s t d e f i n i t i v e works on ketone e n o l i z a t i o n was published by B e l l and Lidwell i n 1940 (BL40). Certain aspects of t h i s study w i l l be discussed i n d e t a i l . The authors used a number of ketones and a number of c a t a l y s t s . The e n o l i z a t i o n of the ketones was followed by measuring rates of i o d i n a t i o n . The halogenation of the ketones i n aqueous s o l u t i o n i s f i r s t order i n ketone and zero-order i n halogen. The rate c o n t r o l l i n g step f o r the halogenation of the ketones i s the conversion of the ketone to i t s enol form, which then reacts r a p i d l y with halogen (L04, ZH39). 39 -B e l l and Lidw e l l measured the rates of decrease of iodine concentration, equivalent to the rate of e n o l i z a t i o n , by t i t r a t i n g r e a c t i o n samples with thiosulphate as the reaction proceeded. The rate of rea c t i o n i s given by eq. [1.67], where k o b s i s the sum of the c a t a l y t i c terms, eq. [1.68]. RATE = - d [ I 3 ' ] / d t = -d[ketone]/dt = k o b s [ k e t o n e ] [1.67] kobs " k H 2 o[H 20] + k H+[H 30 +] + k- O H["OH] + k^tHA] + k A-[A"] [1.68] The c a t a l y t i c terms include c a t a l y s i s by the solvent, water, kj ^ g and by the carboxylic acid, HA and conjugate base, A". At a constant b u f f e r r a t i o of the carboxylic a c i d and base, n = [ H A ] / [ A - ] > t h e p H should be constant, i . e . [H +] and ["OH] are constant, f o r a serie s of varying b u f f e r concentrations. A p l o t of k o b s vs. [A"] w i l l be l i n e a r with slope {k A- + nk^} and intercept (k^ 0 l H 2 ° ] + k H+[H 30 +] + k - 0 H [ ~ 0 H ] ) eq. [1.69]. The combination of a number of such series at d i f f e r e n t n values leads to the determination of k ^ and k A-, eq. [1.70], by p l o t t i n g the slope from eq. [1.69] vs. n, the buffer r a t i o . The slope of t h i s l i n e , eq. [1.70], i s k ^ and the intercept i s k A-. kobs - < kH 20[ H2°] + k H + [ H 3 0 + l + k-0Ht"0H]} + [A"] {k A- + nk^} [1.69] Slope from eq. [1.69] = k A- + n k ^ [1.70] - 40 -I n t h e i r s t u d y o f a c e t o n e e n o l i z a t i o n , B e l l and L i d w e l l u s e d an a c e t o n e c o n c e n t r a t i o n o f 0 . 2 7 M and an i n i t i a l i o d i n e c o n c e n t r a t i o n o f b e t w e e n 1 x 1 0 " ^ M and 2 x 1 0 " ^ M. Under t h e s e c o n d i t i o n s , t h e r e a c t i o n i s p s e u d o - z e r o - o r d e r i n a c e t o n e . The i o n i c s t r e n g t h o f e a c h s o l u t i o n was a d j u s t e d t o 0 . 1 1 M b y t h e a d d i t i o n o f s o d i u m c h l o r i d e , e x c e p t i n t h e c a s e o f m o n o c h l o r o a c e t a t e b u f f e r s , w h i c h w i l l be d i s c u s s e d l a t e r . I o n i c s t r e n g t h i s d e f i n e d by e q . [ 1 . 7 1 ] , where C^ i s t h e i o n c o n c e n t r a t i o n and t h e c h a r g e o f t h e i o n ( R 8 1 a ) . O n l y c h a r g e d s p e c i e s e . g . N a + , CH3COO" w i l l c o n t r i b u t e t o t h e i o n i c s t r e n g t h . I o n i c S t r e n g t h I = 1 / 2 1 C± Z±2 [ 1 - 7 1 ] The r e s u l t s o f B e l l and L i d w e l l f o r a c e t o n e e n o l i z a t i o n a r e g i v e n i n T a b l e 1 . I t c a n be s e e n t h a t t h e s t r o n g e s t a c i d (CICH2CO2H) i s t h e b e s t c a t a l y s t f o r a c e t o n e e n o l i z a t i o n , w h i l e i t s c o n j u g a t e b a s e (CICH2COO") i s t h e w o r s t c a t a l y s t . The s t a t i s t i c a l l y c o r r e c t e d B r o n s t e d p l o t s o f t h e a c i d and b a s e c a t a l y s i s a r e shown i n F i g . 8. A l e a s t -s q u a r e l i n e a r c o r r e l a t i o n o f t h e d a t a f o r t h e a c i d s and b a s e s g i v e s e q . [ 1 . 7 1 ] and [ 1 . 7 2 ] r e s p e c t i v e l y , where r i s t h e c o r r e l a t i o n c o e f f i c i e n t , and p and q h a v e v a l u e s o f 1 and 2 r e s p e c t i v e l y . A c i d C a t a l y s i s l o g ( k ^ / p ) = - 4 . 4 6 - 0 . 5 7 (pK + l o g p / q ) [ 1 . 7 1 ] r = 0.9995 Base C a t a l y s i s l o g ( k A - / q ) = - 1 0 . 9 + 0 . 8 8 (pK + l o g p / q ) [ 1 . 7 2 ] r = 0 . 9 9 9 7 41 -Table 1: Data of B e l l and L i d w e l l f or acetone e n o l i z a t i o n cata lyzed by acids (HA) and bases (A") at 2 5 ° C . Data from Ref. (BL40). A c i d 107 k m M ' 1 sec" 1 Base 107 k A - M - 1 s e c - 1 p K ^ C1CH 2C0 2H HOCH 2C0 2H CH 3C0 2H ( C H 3 ) 3 C C 0 2 H 12.7 3.25 1.02 0.73 C1CH 2C0 2" HOCH 2C0 2" C H 3 C 0 2 _ ( C H 3 ) 3 C C 0 2 ' 0.050 0.383 2.43 4.08 2.86 3.83 4.76 5.03 cn o o CD - 5 . 8 F i g . 8: 3 4 5 pK + log p/q Bronsted p l o t for acetone e n o l i z a t i o n cata lyzed by ac ids (open c i r c l e s , s o l i d l i n e ) and bases (c losed c i r c l e s , dashed l i n e ) . Data from Table 1, r e f . (BL40). - 42 The c o e f f i c i e n t s for the a c i d and base c a t a l y s i s are 0.57 (a) and 0.88 (B), r e s p e c t i v e l y . The authors report an a value of 0.55 using pK values of 2.86, 3.81, 4.76 and 5.04 for the four acids. The pK values used i n Table 1 and Fi g . 9 and indeed throughout t h i s t h e s i s , unless otherwise stated, are from the tabulations of Kortum and co-workers (KV61) and Serjeant and Dempsey (SD79). A least-squares l i n e a r regres-sion using the authors' pK values gives an a value of 0.57, not 0.55 as reported. In the case of chloroacetate buffers, B e l l and Lidwell had to overcome two problems. F i r s t l y , since i s approximately 250 times greater than k A-, the anion w i l l only make a meaningful con t r i b u t i o n to the observed rate i f the buffer r a t i o s h e a v i l y favour the anion. Secondly, at the pH of such buffer solutions the cont r i b u t i o n to the t o t a l rate from the hydronium ion was rather large and so large concen-t r a t i o n s of b u f f e r were needed, leading to an i o n i c strength of 0.2 M. The authors also determined rate constants of hydroxide (0.25 M ' ^ sec"-*-) and water (8.33 • 10"^ 2 M ' ^ sec"-'-) f o r acetone e n o l i z a t i o n . The rate constant of the hydronium ion (2.73-10"^ M"l sec"'-) i s given by the measurements of Dawson and Powis (DP13). The conventional pK values for hydroxide and hydronium ion are 15.74 and —1.74 r e s p e c t i v e l y derived from a value of 55.5 M for [H2O] (B73e). S u b s t i t u t i o n of the value for pK of H30 + and "OH into eq. [1.71] and [1.72], r e s p e c t i v e l y , affords us c a l c u l a t e d values of k^^Q+ and k-Qjj. As was mentioned e a r l i e r , while p = 3 f o r ^O"1" there i s some disagreement about whether to use q = 2 or q = 1 f o r H30 +. For "OH p = 2 but q could be 1 or 3 depending on how one counts the number of basic s i t e s i n the ion. The c a l c u l a t e d values f o r - 43 -H 30 + and "OH are given i n Table 2 along with the r a t i o of c a l c u l a t e d rate constants ( k c a i c ) to observed rate constants ( k e X p t ) . Table 2: C a l c u l a t e d ra te constants for H 3 0 + and "OH from and [1.72] and r a t i o s k c a l c / k e x p t eqs. [1.71] Catalyst P q k c a l c M " 1 s e c " 1 k c a l c / k e x p t "OH 2 1 1.80-103 7 x 10 3 3 3 2.06-103 8 x 10 3 H 30 + 3 1 5.71-10"4 21 3 2 8.48-10"4 31 The choice of p and q values does not a f f e c t the conclusion that hydroxide ion and hydronium ion are much less e f f e c t i v e as ca t a l y s t s than i s expected on the basis of the Bronsted r e l a t i o n s h i p for the other four c a t a l y s t s . In most cases, a c i d and base c a t a l y s i s of ketone e n o l i z a t i o n occurs at the same time. The two types of catalyses w i l l be discussed separately. 44 -1.10.1. Base Catalyzed Enolization (a) Curvature B e l l and Lidwe l l determined B values f o r carboxylate ion catalyzed e n o l i z a t i o n of a number of acetone d e r i v a t i v e s , as well as acetone. The Bronsted c o r r e l a t i o n f o r each der i v a t i v e was l i n e a r and the 8 values obtained (acetone, 0.88; chloroacetone, 0.82; dichloroacetone, 0.82) suggest that the proton i s more than h a l f transferred i n the t r a n s i t i o n state. In terms of the Hammond postulate, the t r a n s i t i o n state resembles products. A trend which was obvious to B e l l and Lidwe l l , and which further research supported, l i n k e d decreasing 8 values with increasing substrate r e a c t i v i t y (B73f). B e l l compiled a mass of data f o r the reac t i o n shown i n eq. [1.17] where HA i s a ketone, an ester or a ketoester and B i s any base, including carboxylate ions, phenolate ions and pyridines (B73f). HA + B > A - + BH + [1.17] A p l o t of log k vs. log (KHA/KBH"0 with appropriate s t a t i s t i c a l c o r r e l a t i o n s gave a curve, representing the decrease that occurs i n the 8 value with increasing reaction rate and increasing exothermicity. This trend i s predicted by the Hammond, Leffler-Grunwald and Marcus treatments. Many authors have quoted t h i s example i n i l l u s t r a t i n g the r e l a t i o n s h i p between the free energy of a c t i v a t i o n AG* and the free energy of re a c t i o n AG°. Others have suggested a d i f f e r e n t explanation - 45 i . e . separating the data for the monocarbonyls from that of the dicar-bonyls leads to two d i s t i n c t l i n e a r c o r r e l a t i o n s , the slope of the dicarbonyl set being less than that of the monocarbonyl set (KC73, BH85). Hupe and Wu have f i t t e d a l i n e f or the curved p l o t with AG 0 = 10 k c a l mol"''" and Wr = 4 k c a l mol" 1 by using the Marcus treatment, eq. [1.30] (HW77). This large i n t r i n s i c b a r r i e r implies a very gradually changing t r a n s i t i o n state structure. This analysis of B e l l ' s data by using eq. [1.30] reveals a weakness; the carbon acid substrate HA has been varied, negating the assumption used i n the equation's d e r i v a t i o n that AG 0 i s a constant. These same authors i l l u s t r a t e elegantly how s o l v a t i o n causes downward curvature i n a base catalyzed e n o l i z a t i o n , as discussed previously (Section 1.9). The base catalyzed e n o l i z a t i o n of acetylacetone was studied by Ahrens and co-workers (AE70). The data was f i t t e d to eq. [1.30] by Kreevoy and Oh with the i n c l u s i o n of hydroxide ion and water giving a low i n t r i n s i c b a r r i e r (3.3 kcal mol" 1) and a large work term (10.5 kcal mol" 1) (K073). The i n c l u s i o n of hydroxide and water, (ca t a l y s t s which deviate markedly from Bronsted p l o t s , Section 1.10), i s the cause of a sharply curving l i n e g i ving r i s e to a small i n t r i n s i c b a r r i e r . Of course such a treatment i s p o i n t l e s s , and without the two "curve-causing" c a t a l y t i c constants and two b i f u n c t i o n a l monoanions, a reason-ably l i n e a r Bronsted p l o t i s evident, with a B value of 0.58 (obtained by i n c l u d i n g f i v e carboxylate bases and four phenoxide bases). The study by B e l l and Grainger of the e n o l i z a t i o n of 3-nitro-(+)-camphor catalyzed by s i x carboxylate bases (including one dianion) and - 46 -monohydrogen phosphate dianion i s of s p e c i a l i n t e r e s t as i t combines the Bronsted p l o t with primary isotope e f f e c t s (see also Section 1.8). The isotope e f f e c t i s at a maximum at ApK ~ 0, while the Bronsted p l o t shows concave curvature, curvature which r e l i e s predominantly on the presence of the two dianions. As was mentioned previously, the k^/kn vs ApK p l o t has been used to determine an i n t r i n s i c b a r r i e r of 1.5 kca l mol" 1 (BU79, see p. 32). The use of the Marcus equation involves f i t t i n g the log (k/q) vs. ApK p l o t to a quadratic expression i n ApK and t h i s gives the r e s u l t shown. log (k/q) - 0.67 - 0.39 ApK - 0.025 (ApK) 2 [1.73] The c o r r e l a t i o n c o e f f i c i e n t (0.9955) i s better than that obtained from a l i n e a r c o r r e l a t i o n of log (k/q) to ApK (0.9844). The c o e f f i c i e n t of the squared term (0.025 ± 0.008) can be used to give an i n t r i n s i c b a r r i e r of 3.4 ± 1.1 kcal mol'l. The i n c l u s i o n of bases of d i f f e r e n t types i s a weakness, and as the f i v e carboxylate monoanions give a good l i n e a r Bronsted l i n e (B = 0.45, r - 0.9970), we could consider the two dianions to be deviating from t h i s l i n e . This example i l l u s t r a t e s the care necessary i n i n t e r p r e t i n g curvature i n Bronsted p l o t s , and the caution that should be exercised i n comparing d i f f e r e n t types of c a t a l y s t . Having s a i d that, the curvature present i n the Bronsted p l o t for 3-nitro-(+)-camphor e n o l i z a t i o n could be due i n whole or i n part to a change i n AG* with respect to AG°. Some i n d i c a t i o n of the v a l i d i t y of in c l u d i n g dianions with monoanions i n Bronsted c o r r e l a t i o n s i s needed before a more d e f i n i t i v e conclusion i s evident. - 47 -The r e s u l t s of Hupe and co-workers and those of Bernasconi and co-workers (Section 1.9) show the relevance of s o l v a t i o n i n e n o l i z a t i o n and other proton t r a n s f e r reactions, another factor which must be considered i n any e n o l i z a t i o n study. (b) Isotope E f f e c t s Primary k i n e t i c isotope e f f e c t s corresponding to k^/krj r a t i o s for base-catalyzed e n o l i z a t i o n of acetone and acetone-dg were f i r s t reported i n 1939, only seven years a f t e r the discovery of deuterium (RK39). The base studied was acetate ion and a kjj/kpj r a t i o of 7 resulted. The use of hydroxide ion as base provided values of 10.2 (B59), 7.5 (P59) and 9.2 (J65) . These values are a l l close to or above the t h e o r e t i c a l l y expected maximum k^/kjj of 6.9 (which comes from considering the zero-point energies of C-H and C-D bonds) and shows that the carbon hydrogen bond i s broken i n the rate c o n t r o l l i n g step. Jones obtained values of the isotope e f f e c t of hydroxide ion as the base at several temperatures; a decrease i n ky/kp with increasing temperature was observed (J65). The decrease res u l t e d from v i b r a t i o n a l energy di f f e r e n c e s between C-H and C-D decreasing as the temperature r i s e s , the k H / k D values being 13.5 at 1°C, 9.8 at 25°C and 7.9 at 43°C. In 1967, Jones v a r i e d the structure of the ketone using hydroxide ion as the base and examined k^/kj isotope e f f e c t s (JM67). The ketones studied were a l l substituted acetophenones and the isotope e f f e c t s v a r i e d from 12.1 (4-nitroacetophenone) to 18.2 (4-methoxyacetophenone). - 48 -A study i n v o l v i n g v a r i a t i o n of the base with one ketone substrate was reported i n 1976 (BG76). B e l l and Grainger examined the bromination of 3-nitro-(+)-camphor and 3-deuterio-3-nitro-(+)-camphor as was mentioned previously (Section 1.8). A maximum isotope e f f e c t , k^/k^ = 7.5, was observed at ApK ~ 0. A s i m i l a r r e s u l t was reported e a r l i e r i n the hydroxide ion catalyzed e n o l i z a t i o n of (-)-menthone (BC70). B e l l and Cox used water-dimethyl sulfoxide (DMSO) solvent mixtures and found that k^/k^ reached a maximum value (6.5), i n the solvent mixtures containing 30-40 mole % DMSO. A c i d i t y f unction values for hydroxide ion i n aqueous DMSO suggest that pK^o becomes roughly equal to the pK of the substrate, (-)-menthone, i n 30-40 mole % DMSO. The r e s u l t s are i n agreement with the concepts discussed previously (Section 1.8). 1.10.2 Acid Catalyzed Enolization (a) Mechanism The general a c i d catalyzed mechanism of ketone e n o l i z a t i o n i s shown i n eq. [1.10] f o r acetone, and i s credi t e d to Pedersen (P34). C H 3 ' X C H 3 CH3/ \ C H 3 [1.10a] O H * OH || SL0K I [1.10b] C H 3 C H 3 C H 3 ^ C H 0 - 49 -The observed rate f o r the reaction i s given by eq. [1.74]. -.Substi-t u t i n g f o r [ZH +] with ([ Z] [H +]/K Z H+) , and for [A -] with (Kj^HA] / [H +]) leads to eq. [1.75]. kobs " k'A" [ZH +][A-] [1.74] kobs " ( K V K H A/K Z H+)[Z][HA] = kHAtZJtHA] [1.75] Linear Bronsted r e l a t i o n s h i p s were found f o r acetone and cyclohexa-none, gi v i n g a values of 0.57 and 0.74, r e s p e c t i v e l y (BL40, LW69). These values are r e l a t e d to the 8 values for proton a b s t r a c t i o n by eq. [1.10b], 8 = 1 - a. Thus /3 i s 0.43 for protonated acetone and 0.26 for protonated cyclohexanone), suggesting t r a n s i t i o n states i n which the proton i s less than h a l f - t r a n s f e r r e d . Evidence supporting the mechanism described was accumulated by many workers over the years. The magnitude of primary isotope e f f e c t s measured f o r the general a c i d catalyzed e n o l i z a t i o n showed that the rate determining step involved breaking of the C-H bond (RK39, SS58). The absence of any solvent isotope e f f e c t s (using H 20 and D 20) for c a t a l y s i s by the general a c i d suggests that proton abstraction by the solvent does not occur (SD58). Lienhard and Wang compared the mechanism f or the hydro l y s i s of enol ethers, which involves rate determining proton trans f e r to the /3-carbon of the enol ether eq. [1.76], with the reverse of eq. [1.10b], ketoni-z a t i o n (LW69). - 50 -r R C = C R 2 4 HA + OB II R C CHR2 + A" [1.76] CH •f HA [1.10b] CH-, S i m i l a r rates and a values are found for the two processes. The agreement between solvent isotope e f f e c t s f o r enol ketonization and enol ether h y d r o l y s i s further supports the accepted mechanism (TD74). The value of k^/kp for hydronium ion catalyzed e n o l i z a t i o n of acetone reported by Reitz i n 1939, 5.0, was determined by using aceto-ne-d 6 of only 92% i s o t o p i c p u r i t y (RK39). Values of 6.5 (HK72) and 6.7 (TD74) have since been reported, values that are close to the t h e o r e t i -c a l maximum value and thus correspond to h a l f t r a n s f e r of the proton. For hydronium ion catalyzed e n o l i z a t i o n evidence has accumulated that suggests that the t r a n s i t i o n state contains molecules of water (T82). The decrease i n e n o l i z a t i o n rates at very strong a c i d concen-t r a t i o n s (CS79), the large negative entropy of a c t i v a t i o n (-16.5 c a l mol"'- K " l for acetone, DT73) , and the large negative volume of a c t i v a t i o n (-2.1 cm 3 mol"^ for acetone, BW64) are a l l consistent with such a t r a n s i t i o n state. 51 -(b) Proton A c t i v a t i n g Factor We can determine the rate constant for proton a b s t r a c t i o n from the protonated ketone by a general base, k ' A - , knowing k ^ , KzH + and K^, eq. [1 .77] . k'A" " <kHA K Z H + / K R A ) t 1 - 7 7 ] This rate constant can be compared with the rate constant for proton a b s t r a c t i o n from the unprotonated ketone by a general base, k A - , eq. [1 .78] . + A " C H 3 X C H 3 I HA [1.78] OH + [1.10b] C H 3 ' X C H , / V 4 HA The r a t i o of rate constants ( k ' A - / k A - ) has been c a l l e d the proton a c t i v a t i n g f a c t o r (paf) and was introduced by Stewart and S r i n i v a s a n (SS78). Us ing a pK£H + ° f -2.9 for acetone, paf values of 3 x 10 7 and 2 x 10 7 for water and acetate bases r e s p e c t i v e l y were c a l c u l a t e d (S85d). With carboxylates as bases, 0 •» 0.43 ( i . e . 1 - 0.57) for eq. [1 .10b], and 0.88 for eq. [1 .78] . The small B value i n the case of eq. [1.10b] r e f l e c t s the e a r l i e r t r a n s i t i o n state r e s u l t i n g from protonat ion 52 -of the acetone. This increase i n r e a c t i v i t y of the substrate i s measured by the paf and i s quite large f or the deprotonation of ketones. 1.10.3 Third Order Term The observed rate law used by B e l l and Lidwell (BL40) f o r the general a c i d and base catalyzed e n o l i z a t i o n of acetone with acetate b u f f e r s , f or example, i s represented by eq. [1.79] where k s u m includes the solvent, hydronium ion and hydroxide ion contributions (kjj Q E ^ O ] + k H+[H 30 +] + k- 0 H["0H]. kobs = kCH 3COOH[ C H3 C O O H] + kCH 3COO - r C H3 C 0 0"] + ksum t1-7 9] As the re a c t i o n i s subject to both a c i d and base c a t a l y s i s , there e x i s t s the p o s s i b i l i t y for simultaneous involvement of acid and base with the substrate. The p o s s i b i l i t y of such c a t a l y s i s was f i r s t sugested i n 1925 (LF25) and i n 1930 a third-order term in v o l v i n g both CH3COOH and CH3COO" was detected i n acetate buffers (DS30). The presence of t h i s term has been confirmed no fewer than three times since then (BJ53, HJ75a, AG82). The mechanism of such a process i s shown below (S85e). The amount that such a concerted process contributes to the observed rate i s small and indeed large concentra-tions of bu f f e r are necessary (0.4 M) i n order to observe the t h i r d order term i n the rate expression. - 53 -Hegarty and Jencks examined the t h i r d order term i n acetone enoliza-t i o n at an i o n i c strength of 2 M; they used seven carboxylate buffers and determined a 0 value of 0.15 (HJ75a). The smallness of the slope r e f l e c t s the c a n c e l l i n g of e f f e c t s i n going from strong acids/weak conjugate bases (e.g. CICH2COOH, CICH2COO") to weaker acids/stronger conjugate bases (e.g. CH3COOH, CH3COO") . Using acetone and acetone-dg, the authors determined a value of 5.8 for a primary isotope e f f e c t using acetate b u f f e r s . This suggests a considerable degree of C — H bond breaking i n the t r a n s i t i o n state. A rather large solvent isotope e f f e c t (H2O/D2O) of 2.0 indicates the involvement of the carboxylic acid proton i n the t r a n s i t i o n state. The authors suggest that the two proton transfers i n the reaction are simultaneous. Recent work with H2O-D2O mixtures supports such a push-pull mechanism (AG82). The presence or absence of the third-order term, k A- ^ [ A ' H H A ] , w i l l be obvious from the k i n e t i c r e s u l t s at d i f f e r e n t b u f f e r r a t i o s . At a given b u f f e r r a t i o n ([HA]/[A"]) a p l o t of k O D S vs [HA] or [A"] w i l l be l i n e a r i f the third-order term i s i n s i g n i f i c a n t (Section 1.10). Upward curvature i n such a p l o t , on the other hand, could be an indica-t i o n of the presence of the third-order term i n the rate law ( H J 7 5 b ) . I f t h i s i s the case eq. [1.81] can be transformed to eq. [1.82]. 5 4 -kobs " kHAtHA] + k A - ( A " ] + kA-.HAtA'ltHA] + ksum t 1 - 8 1 ] kobs " ksum - k H A n t A " ] + kA - tA"] + k A - _ ^ n f A" ] 2 [1.82] Rewriting eq. [1.82] as eq. [1.83] gives a l i n e a r r e l a t i o n s h i p between the left-hand side of eq. [1.83] and [A"], with slope k A- j^n and intercept (kj^n + k A - ) . VIA"] ( k o b s - k s u m ) = k ^ n + k A- + k A-_ H An[A"] [1.83] Thus, k A- fifr can be determined; when a number of such intercepts for d i f f e r e n t b u f f e r r a t i o s are p l o t t e d against n, k ^ (slope) and k A-(intercept) are obtained (BW66). 1.11 BIFUNCTIONAL CATALYSIS The third-order term i n acetone e n o l i z a t i o n involves simultaneous proton donation by one c a t a l y s t (HA) and proton acceptance by another c a t a l y s t (A"). I t has been c a l l e d b i f u n c t i o n a l c a t a l y s i s ( H J 7 5 a ) but i t i s important to d i s t i n g u i s h i t from simultaneous proton donation and proton acceptance by a b i f u n c t i o n a l c a t a l y s t containing both a c i d i c and basic groups. I t i s preferable to r e s t r i c t the use of the term 'bifunc-t i o n a l c a t a l y s i s ' to the l a t t e r d e f i n i t i o n and use the more s e l f -explanatory 'third-order term' f or acetone e n o l i z a t i o n that involves acid, base and acetone reacting simultaneously. - 55 -One of the e a r l i e s t reported examples of b i f u n c t i o n a l c a t a l y s i s i s the ep imer iza t ion of tetramethylglucose i n benzene ca ta lyzed by 2-pyridinone (SB52, EB83). The simultaneous t r a n s f e r of two protons i n a proton t r a n s f e r r e a c t i o n holds a s p e c i a l i n t e r e s t for chemists, e s p e c i a l l y as i t r e l a t e s to enzyme c a t a l y s i s (J69) . Cox and Jencks have reported b i f u n c t i o n a l c a t a l y s i s i n the general a c i d and general base ca ta lyzed r e a c t i o n of methoxyamine with phenyl-acetate (CJ81a, CJ81b). H* I  CH,CNHOCH, "*" ' CRH.OH [1-84] C H , C O C R H ^ + N H 2 O C H 3 ? CH3CNHOCH3 CgH • o b D or A" For the strong acids (pK < 2) the rate l i m i t i n g step involves n u c l e o p h i l i c a t tack by the amine on the carbonyl group a s s i s t e d by a molecule of general a c i d , HA. As the a c i d becomes weaker, the rate l i m i t i n g step becomes the protonat ion of the oxygen anion by the a c i d , eq. [ 1 . 8 5 ] . A curved Bronsted p l o t r e s u l t s from t h i s change i n rate determining step. c 6 " 6 o ^ N A 2 + " C 6 H 6 O ^ ^ - » P R O D U C T S <>CH3 0CH3 With the monoanions of c e r t a i n d i a c i d s (e .g . C I 3 C P O 3 H " , 0 P ( 0 H ) 2 0 " and 0 2 C ( 0 H ) 0 " ) , rate acce lera t ions up to 1 0 ^ times that expected were observed. Thi s rate a c c e l e r a t i o n was c r e d i t e d to concerted protonat ion of the oxygen anion and deprotonation of the n i t rogen c a t i o n eq. [1.86] . - 56 -> C . X —> / C \ • \ / [1.86] I O C H 3 O C H 3 The a b i l i t y to form eight membered rings in the transit ion state is a common feature of bifunctional catalysis (S85f). Lienhard and Andersen examined three reactions, including the enolization of acetone, in searching for bifunctional catalysis by the monoanions of dicarboxylic acids (LA67). Such concerted general acid general base catalysis would operate as shown below. [1.87] The authors used various buffer ratios and by an analogous treat-ment to that discussed previously (Section 1.10) they measured the rate constants for the monoanion k^A," and the dianion k A 2- . In the absence of bifunctional catalysis the authors expected to find rate constants that were close to the sum of the rate constants for the acid and base portions of the monoanions. These two contributions were calculated on the basis of the Bronsted plots for monocarboxylic acids and bases (BL40). The contribution of the monoanion as an acid, k a c i d ' can be calculated from eq. [1.88] knowing the second equilibrium constant of the diacid, K 2 . The contribution of the monoanion as a base k D a s e can - 57 be c a l c u l a t e d from eq. [1.89], knowing the f i r s t e quilibrium constant of the d i a c i d , K]_. l o g k a c i d - ° - 5 5 l o g < 2 K2) - 4 - 4 0 U-88] l o S kbase = " ° - 8 8 l o S ( K l / 2 ) " 1 0 - 8 2 I 1- 8 9! In t h i s regard i t may be noted that footnote C of table III i n r e f . (LA67) has an error, 'k A =' and 'kg =' should read 'log k A =' and 'log kg =' r e s p e c t i v e l y . The r e s u l t s of t h e i r c a l c u l a t i o n s are shown i n Table 3. Table 3: Data of Lienhard and Anderson f o r acetone e n o l i z a t i o n catalyzed by monoanions, k^-Cobs) and c a l c u l a t e d values k ^ - ( c a l c d ) (see t e x t ) . Data from r e f . (LA67). Catalyst 10 8 k^-Cobs) M"1 s e c - 1 10 8 k ^ - ( c a l c d ) M'1 s e c ' 1 Oxalate 7.83 28.8 monoanion Succinate 12.5 5.83 monoanion 1,1-cyclobutane-dicarboxylate monoanion 23.3 29.3 58 -The authors concluded from these r e s u l t s that the monoanions studied are not "unusually e f f e c t i v e c a t a l y s t s " for the e n o l i z a t i o n of acetone. They found the same r e s u l t for the mutarotation of glucose and the hydration of acetaldehyde. A study by Spaulding and co-workers of other p o t e n t i a l b i f u n c t i o n a l c a t a l y s t s of acetone e n o l i z a t i o n gave the same r e s u l t (SS77) . These authors examined the effectiveness of the phosphate dianion, OP(OH)02 2" and the arsenate dianion, OAs(OH)022", and found no noticeable rate a c c e l e r a t i o n a t t r i b u t a b l e to b i f u n c t i o n a l c a t a l y s i s . These r e s u l t s lead to a question l e f t unanswered by both groups of authors. I f these c a t a l y s t s containing both a c i d i c and basic function-a l i t i e s are not acting as b i f u n c t i o n a l c a t a l y s t s , are they acting then as general acids or as general bases? 1.12 STERIC EFFECTS 1.12.1 General Base Ca t a l y s i s An extensive study of general base catalyzed e n o l i z a t i o n of several ketones was reported by Feather and Gold i n 1965 (FG65). They studied the e f f e c t i v e n e s s s of a number of a l k y l pyridines as c a t a l y s t s , observ-ing no a c i d c a t a l y s i s by pyridinium ions. While a l i n e a r Bronsted p l o t was determined for acetone with 3-,4- and 5-substituted pyridines (B = 0.7), 2-substituted pyridines deviated from t h i s l i n e . The 2,6-substi-tuted pyridines produced s t i l l l a r g er deviations. This retardation of - 59 rate constants was also evident i n the e n o l i z a t i o n of other ketones. The magnitude of the deviations increased along the ketone seri e s from acetone ( C H 3 R , R = C O C H 3 ) to isopropylmethyl ketone ((Ct^^CHR) to pinacolone ((CH 3) 3CR). The use of pyridine bases i n the dedeuteration of 2-deuterio-iso-butyraldehyde gave the same r e s u l t (HH65). Unhindered pyridine bases produced a good Bronsted l i n e (B = 0.5), while the 2- and 6-alkyl pyridines deviated from that l i n e . Once again the deviation i s greater for the 2,6-substituted pyridines than for the 2-substituted pyridines. The use of meta and para phenolate anions produced a Bronsted l i n e p r a c t i c a l l y c o i n c i d i n g with that f or the pyridines and having the same slope. The two ortho-phenolates studied (chloro and methyl) f i t on the l i n e . The absence of s t e r i c e f f e c t s i n the phenoxides was a t t r i b u t e d to the e f f e c t of moving the basic atom one atom away from the r i n g . Other examples of such rate retardation i n general base c a t a l y s i s due to a l k y l pyridines include the mutarotation of glucose (CW63) as well as the i o n i z a t i o n of glyceraldehyde, dihydroxyacetone (GR67) and 2-nitropropane (BG66). Recent examples are the hyd r o l y s i s of phenylace-tates (N87) and the deprotonation of 1,2,3-trimethylpyrazinium ions (NL86). The use of 2-alkyl a n i l i n e s i n the l a t t e r example also leads to s t e r i c d e a c t i v a t i n g e f f e c t s r e l a t i v e to the Bronsted l i n e f o r the unhindered a n i l i n e s . The degree of deviation i s le s s than that observed f o r the hindered pyridines, probably r e f l e c t i n g the e f f e c t of moving the basic atom away from the r i n g . In the base catalyzed i o n i z a t i o n of 2-nitropropane, 2,6-dimethyl-- 60 py r i d i n e gave a primary k i n e t i c isotope e f f e c t of 19 (BG66). Studies i n aqueous alcohol y i e l d e d values of k^/kj) = 10 for pyridine, while for 2 ,4-dimethyl, 2, 6-dimethyl and 2 ,4, 6-trimethylpyridine k H/krj values of 15, 24 and 24 r e s p e c t i v e l y were observed (LF67). The r e l a t i o n between s t e r i c hindrance and increased k i n e t i c isotope e f f e c t s has been d i s -cussed by Caiman and co-workers (CC69) and by Lewis (L75). The e f f e c t i s a t t r i b u t e d to t u n n e l l i n g i n the case of protium compounds. A recent example of s t e r i c hindrance and t u n n e l l i n g involves proton transfer from a phenylnitromethane to substituted phenylguanidines (P87). S t e r i c e f f e c t s i n the opposite d i r e c t i o n i . e . rate accelerations were reported by B e l l and co-workers for base catalyzed halogenations of ketones and esters (BG49). Using a v a r i e t y of carbonyl compounds (bromoacetylacetone, benzoylacetone, acetylacetone, ethyl acetoacetate, et h y l a-bromoacetoacetate and d i e t h y l bromomalonate) and a range of base c a t a l y s t s (twelve or more, ranging i n pK from 2.86 to 5.03), a seri e s of Bronsted l i n e s were determined. Catalysts containing large groups e.g. CH3CH(CgH5)C02~ are more e f f e c t i v e than i s expected on the basis of a Bronsted l i n e defined by CH 3C0 2~, H0CH2C02" and C1CH 2C0 2". This rate a c c e l e r a t i o n i s more pronounced for the substrate ketones containing large groups e.g. bromoacetylacetone. The authors a t t r i b u t e such deviations to "the proximity of a large group i n the c a t a l y s t to a s i m i l a r group i n the substrate, which w i l l a f f e c t the t r a n s i t i o n state of the reaction, but not contribute anything to the d i s s o c i a t i o n constant" of the c a t a l y s t . Another proton trans f e r r e a c t i o n e x h i b i t i n g such s t e r i c rate a c c e l e r a t i o n i s the base catalyzed exchange of the methylene protons i n 61 -1,3-dimethyl-2-iminoimidazolin-4-one hydroiodide, eq. [1.90] (SS76a). A Bronsted l i n e was determined for 47 bases which included a l i p h a t i c monocarboxylates, meta- and para-substituted benzoates and pyridines (0 - 0.79). Enhanced c a t a l y t i c a c t i v i t y was exhibited by 12 ortho-sub s t i t u t e d benzoates, the deviation showing some c o r r e l a t i o n with substituent s i z e . [1.90] 4 BH* The authors consider f i r s t the e f f e c t on the equilibrium b a s i c i t y of benzoates of ortho substituents i . e . ortho benzoates being weaker bases than t h e i r meta and para counterparts. This e f f e c t had been a t t r i b u t e d to s t e r i c hindrance to resonance between the carbonyl group and the benzene r i n g i n the neutral acid molecule (E69). Another explanation for the e f f e c t involves hindrance to s o l v a t i o n of the neutral molecule (SS67). Thus, i n the proton loss from the substrate, catalyzed by ortho-benzoates, the " i n c i p i e n t a c i d molecule p a r t l y formed i n the t r a n s i t i o n state must be subject to s t e r i c hindrance to resonance (or solvation) to a considerably smaller extent than the f u l l y formed acid molecule." S t e r i c compression i n t r a n s i t i o n states (e.g. base c a t a l y s i s by 2-a l k y l pyridines) has been l i n k e d to increased isotope e f f e c t s caused by proton-tune1ling (p. 60). The absence of s t e r i c compression i n t h i s t r a n s i t i o n state i s r e f l e c t e d i n the isotope e f f e c t s f o r the ortho-- 62 -benzoates. These e f f e c t s are lower than those observed f o r monocarboxy-l a t e and meta- and para-benzoates of s i m i l a r b a s i c i t y (SS76b). Si m i l a r rate accelerations f o r ortho-benzoates were observed i n the deprotonation rates of 1,2,3-trimethylpyrazinium ion, eq. [1.91] (NL85). As was discussed previously, pyridines (and to a l e s s e r extent a n i l i n e s ) show conventional s t e r i c e f f e c t s i n t h i s r e a c t i o n i . e . rate decelera-t i o n s . [1.91] The e f f e c t of varying the l o c a t i o n of the a l k y l groups i n the substrate i n eq. [1.91] has also been studied (LS86). Using a sin g l e base ("OD), the authors discover that adjacent a l k y l groups activate the methyl group towards proton transfer. This example of s t e r i c rate a c c e l e r a t i o n i s indeed remarkable when one considers the deactivating polar e f f e c t of the adjacent a l k y l groups. Another example of a s t e r i c a l l y hindered substrate showing s t e r i c a c c e l e r a t i o n i s that of the e n o l i z a t i o n of 2,4,6-trimethylacetophenone, which reacts f a s t e r than acetophenone under comparable conditions by a f a c t o r of 10 3 (PG84). - 63 1.12.2 General Acid C a t a l y s i s A report of s t e r i c hindrance i n acid c a t a l y s i s involves the inver-sion of menthone (CW63). The use of 2-methyl or 2,6-dimethylpyridinium ion leads to rate decelerations by factors of 2 and 30 r e s p e c t i v e l y from the Bronsted r e l a t i o n s h i p f o r pyridinium ion and i t s 3- and 4-methyl d e r i v a t i v e s . Pyridinium ion c a t a l y s i s i s often undetectable i n the presence of pyridine base (kg » > kg^+) for those reactions subject to both general a c i d and general base c a t a l y s i s . As i n general base c a t a l y s i s , there are examples of s t e r i c accelera-t i o n i n general a c i d c a t a l y s i s . One of the cases discussed i n base c a t a l y s i s involved pyrazine derivatives and the exchange of t h e i r a c t i v a t e d methyl protons (LS86). This exchange i s also catalyzed by D30 + and C F 3 C O 2 D and a c t i v a t i o n by adjacent methyl groups i s observed here also. The h y d r o l y s i s of cyanoketenedimethylacetal i s subject to general a c i d c a t a l y s i s , a =0.62, eq. [1.92] (GW68). The effectiveness of NC H > / O C H 3  x O C H , NCH 2 C- [1.92] OCH, p i v a l i c a c i d (trimethylacetic acid) i s greater than expected on the basis of the Bronsted l i n e defined by a l l nine carboxylic acids by a 64 -f a c t o r of 1.2. Formic a c i d on the other hand, deviates negatively from the Bronsted l i n e by a factor of 1.6. Deviations of t h i s type, though small, were c o n s i s t e n t l y observed i n a study i n v o l v i n g f i v e ketene acetals (KS83). While formic and cyano-a c e t i c a c i d were below the Bronsted l i n e i n each case, chloroacetic and methoxyacetic a c i d were co n s i s t e n t l y above the l i n e s . These authors suggest that the i n t e r a c t i o n of bulky c a t a l y s t s and substrate must lower the free energy of the hydrolysis t r a n s i t i o n state. The e f f e c t of introducing bulk into the substrate i s shown by the a c i d catalyzed e n o l i z a t i o n of cyclohexanone as compared to acetone (LW69). In the a c i d catalyzed e n o l i z a t i o n of acetone, p i v a l i c a c i d showed no s t e r i c e f f e c t s when compared to a c e t i c , g l y c o l i c and chloroac-e t i c a c i d (BLAO). With cyclohexanone as the substrate, p i v a l i c a c i d i s more e f f e c t i v e as a c a t a l y s t by a factor of 3 than i s predicted from the Bronsted p l o t f o r the other carboxylic acids. This e f f e c t i s also present i n the hydrolysis of 1-methoxycyclohexanone. The authors a t t r i b u t e the e f f e c t to s t a b i l i z a t i o n of the t r a n s i t i o n state by hydrophobic bonding. Obviously the r o l e of s t e r i c e f f e c t s i n proton trans f e r reactions i s not straightforward, as both rate a c c e l e r a t i o n and re t a r d a t i o n have been observed i n d i f f e r e n t s i t u a t i o n s . - 65 -2. SCOPE OF THE INVESTIGATION The aim of this investigation is to examine a number of effects in general acid and general base catalysis. The reaction that has been chosen for study is the enolization of ketones, in particular, acetone, a substance that has come to be regarded as the prototypical carbonyl compound. We were specifically interested in the following matters. 1. The effect of changing the acid catalyst from a monoprotic acid to a diprotic acid and conversely the effect of changing the base from a monoanion to a dianion. By using a variety of monocarboxylic acids RCOOH and dicarboxylic acids R(C00H)2 as well as a group of phosphonic acids RPO3H2, these effects could be evaluated. 2. Whether or not monoanions of diacids act as bifunctional catalysts, and i f they do not, whether they act as general acids or general bases. 3. The effect of steric bulk in the catalyst; i.e. does i t cause rate acceleration, deceleration or no change from that expected on the basis of the Bronsted line for sterically unhindered catalysts. Previously quoted literature examples have shown a l l three effects. 4. Whether curvature in the acid and base Bronsted plots for acetone enolization can be observed over a wide span of catalyst pK values. - 66 -3. RESULTS The r e s u l t s presented here cover a range of c a t a l y s t s divided into two broad types; carboxylic acids and carboxylate bases, and phenylphos-phonic acids and phenylphosphonate bases. These r e s u l t s are discussed i n Chapter 4, which also includes r e s u l t s of further experimentation, r e s u l t s that were needed to help answer some of the questions a r i s i n g from analysis and discussion of these data. F u l l experimental d e t a i l s of a l l the work included i n t h i s thesis are i n Chapter 5. The method of choice for measuring the rates of e n o l i z a t i o n of acetone i s to measure the rates of i o d i n a t i o n of the enol or enolate anion with a spectrophotometric technique, eq. [3.1]. I A" JC i ^ I y ° \ x3 / C v [ 3 . r A I HA r Using pseudo f i r s t - o r d e r k i n e t i c s (as had been done by previous workers i n t h i s area, BL40, LW69, SS77, WM78) the decrease i n the absorbance of the t r i i o d i d e ion (I3") at a p a r t i c u l a r wavelength can be r e l a t e d to the rate of e n o l i z a t i o n as follows: the rate of disappearance of I3" can be determined from the l i n e a r p l o t of absorbance against time. Of course t h i s p l o t i s l i n e a r since the reaction i s zero-order i n 67 -t r i i o d i d e ion, because the concentration of acetone used (0.1 to 0.5 M) greatly exceeds that of t r i i o d i d e (4 x IO"-* to 5 x 10" 4 M). For example, suppose the re a c t i o n was set up so that the i n i t i a l concentra-tions of acetone and t r i i o d i d e were 0.1 M and 5 x 10" 4 M r e s p e c t i v e l y . Following the r e a c t i o n t i l l the concentration of t r i i o d i d e has decreased to 1 x 10" 4 M w i l l decrease the acetone concentration from 0.1 M to 0.0996 M, or 0.4%. Experimentally, the reaction w i l l show f i r s t - o r d e r k i n e t i c s ( i n acetone) with a rate constant k o b s (units of s e c " 1 ) . The system i s s a i d to follow pseudo f i r s t - o r d e r k i n e t i c s to c a l l a t tention to the f a c t that the behaviour i s f i r s t - o r d e r only under c e r t a i n conditions. The l i n e a r p l o t of absorbance against time ( i n seconds) i s r e l a t e d to the rate of reaction by eq. [3.2] where S i s the slope of such a p l o t and e i s the e x t i n c t i o n c o e f f i c i e n t (molar a b s o r p t i v i t y ) of t r i i o d i d e ion at the chosen wavelength (units of M"1 cm" 1). RATE =• - d [ I 3 " ] / d t = - d [acetone]/dt = k O D S [acetone] = - S/ej^- (units of M sec" 1) [3.2] This r e l a t i o n s h i p follows from Beer's law (the Bougeur-Lambert-Beer law, R81b), i . e . absorbance = e j ^ - [ I 3 " ] • i where I i s the c e l l path length (1 cm). The slope of absorbance, A vs. time, t, i s r e l a t e d to ej_ - by eq. [3.3] . S = d[A]/dt = ej - d [ I 3 " ] / d t [3.3] 68 -Hence k o b s can be determined and r e l a t e d to the sum of the c a t a l y t i c terms present i n the system under i n v e s t i g a t i o n eq. [3.4]. kobs " s/(«i 3- [acetone]) = U c a t [cat] [3.4] This work was done at low concentrations of c a t a l y s t that preclude the involvement of third-order terms i n eq. [3.4]. Thus, second-order rate constants for a v a r i e t y of c a t a l y s t types were measured. The r e s u l t s of these measurements are described i n d e t a i l i n the following sections. 3 . 1 CARBOXYLIC ACIDS AND CARBOXYLATE BASES 3 . 1 . 1 Monoprotic Acids and Monoanionic Bases Though B e l l and Lidwell had measured the rate constants for acetone e n o l i z a t i o n catalyzed by four carboxylic acids and t h e i r conjugate bases (Table 1, p. 41), we decided to extend the series to include a number of s t e r i c a l l y crowded c a t a l y s t s . There are two ways of determining the rate constants for reactions which follow rate laws such as eq. [1.68]. kobs - k H 2 0 [ H 2 ° ] + k H + t H 3 0 + ] + k-0H[" 0 H] + + k A " [ A " ] t 1 - 6 8 ! The f i r s t method, which was discussed previously (p. 39), involves - 69 -measuring the rates of rea c t i o n at a constant buffer r a t i o (n -- = [ H A ] / [ A " ] ) while varying the concentration of a c i d and base i n a number of such runs. The data obtained using d i f f e r e n t buffer r a t i o s can be combined to give values of k^A and k A- by using eq. [1.70]. This approach, which we c a l l the b u f f e r - r a t i o method, i s thorough but time-consuming, r e q u i r i n g at l e a s t nine k i n e t i c runs (preferably more) for each p a i r of acid/base c a t a l y s t s . Slope of k 0 D S vs. [A"] = k A- + nk^A [1-70] A second method makes use of the known values f o r the c a t a l y t i c rate constants of hydronium ion, hydroxide ion and water. Subtracting the sum of these three c o n t r i b i t o n s , k s u m , from the observed rate at a p a r t i c u l a r pH leads to an equation with two unknowns, k^A a n d k A-, eq. [3.5]. Measuring the rate at another pH w i l l give a second equation, which can be combined with the f i r s t equation to give both k^A a n d kA~ values. The r e s u l t s of t h i s method are b r i e f l y described here and i t i s shown that the method i s the l e a s t preferred approach to the determina-t i o n of the rate constants. The buffer r a t i o method (p. 75) i s the method of choice. kobs " ksum = kHA [HA] + kA" t A " ] [3-5] Cross-solving a number of simultaneous equations can lead to a number of values of the a c i d and base rate constants. For instance four k i n e t i c runs produce s i x values each of k^A a n £ i kA-. - 70 -This second approach, which we c a l l the simultaneous equation method, gave the r e s u l t s shown i n Table 4 for a c e t i c acid. Values used f o r the c a t a l y t i c constants of fc^O"1" and "OH were those l i s t e d by Hine and co-workers (HK72): The values of k H+ and k- 0H being 2.84 x 10" 5 M"1 s e c ' l and 0.166 sec"-'- r e s p e c t i v e l y , values which d i f f e r from those determined by B e l l and Lidwell (p. 43), these rate constants being the average of a number of r e s u l t s compiled from the l i t e r a t u r e . The rate constant used f o r water catalyzed e n o l i z a t i o n i s the value of B e l l and -I o 1 1 L i d w e l l , 8.33 x 1 0 ~ M ~ x sec'1- which when m u l t i p l i e d by the concentra-t i o n of H 20 ( i . e . 55.5 M, B73e) gives a value of 4.62 x 1 0 " 1 0 M"1 s e c " 1 for kjj g f ^ O ] . The concentrations of a c e t i c acid, [HA], and acetate ion, [A"], were determined from eq. [3.6] knowing the sum of [HA] and [A"]. log ([HA]/[A-]) - pK 1 - pH [3.6] This equation r e s u l t s from pK 1 = — log ([A" ] [H +] /[HA]) where pK-1- i s the pK of the acid HA at the i o n i c strength at which the pH was measured. This concentration dependent pK i s r e l a t e d to the thermo-dynamic pK (concentration independent, value at zero i o n i c strength), denoted by pK T, by eq. [3.7] where I i s the i o n i c strength (AS84a). pK 1 = pK T - (0.5115 7 l/(l + 1.5 7l)) [3.7] An i o n i c strength of 0.1 M was used i n the determination of k o b s , r e s u l t i n g i n pK^ being 0.11 units less than pK*\ The e f f e c t of the / ± -Table 4: (a) Data for the c r o s s - s o l v i n g of simultaneous equations k obs " k sum = ^HAf^A] + k A " [ A ~ l ^ o r a c e t i c ac id /ace ta te ion with p K 1 = 4.76 - 0.11 = 4.65, 0.1 M i o n i c s trength , 2 5 ° C . (b) Results of the c r o s s - s o l v i n g of the equations I - V. (a) 10° k o b s pH 10° k s u m 1 0 ° ( k o b s - k s u m ) [HA],M [A"],M Equation sec" 1 sec" 1 sec" 1 1. .431 3. .83 0. .467 0. ,964 0. ,08375 0. .01268 I 1. .364 4. .11 0. ,267 1. .10 0. ,07766 0. ,02240 II 1. .486 4. .42 0. .159 1. ,33 0. ,06655 0. .03919 III 1 .744 4. .925 0. .094 1. ,65 0. .03416 0. .06435 IV 2. .105 5, .44 0. .102 2. ,00 0. ,01430 0. .08816 V (b) i o « k H A 10 7 k A - I II III IV V I - 8.61 8.58 8.29 8.27 II 1.91 - 8.54 7.95 7.94 III 1.93 1.94 - 7.04 7.25 IV 2.12 2.14 2.19 - 7.92 V 2.14 2.14 2.15 2.14 k H A = 8 - 0 4 ± ° - 5 4 1 0 " 8 M " 1 sec" 1 k A - = 2.08 ± 0 . 1 1 10" 7 M " 1 sec" 1 - 72 -acetone on the pK was assumed to be n e g l i g i b l e , as i t comprised a maximum of only 3.7% by volume of the solvent (0.5 M). The cross-s o l v i n g of the: f i v e simultaneous equations for a c e t i c acid/acetate ion gave ten values of each rate constant; the average values and the standard deviations are shown i n Table 5 along with the r e s u l t s for ten other acids. The pH values were chosen so as to favour the species that had the smaller rate constant, but t h i s had a l i m i t a t i o n i n that pH values more than 1.5 units from pK 1 r e s u l t e d i n a disappearance of t r i i o d i d e that was not zero-order. Presumably t h i s was due to poor b u f f e r capacity. Generally the smaller rate constant of the acid/conjugate base p a i r shows the larger standard deviation, chloroacetate being the worst with a d e v i a t i o n of ±60%. In the case of the smaller rate constants of each p a i r , even those with acceptable standard deviations ( i . e . reasonable p r e c i s i o n ) , the accuracy of the values i s i n doubt; these values are generally larger than that expected on the basis of B e l l and Lidwell's Bronsted l i n e s and as further i n v e s t i g a t i o n i l l u s t r a t e d , the values are i n f a c t l arger than the presumably more accurate values obtained by the b u f f e r - r a t i o method. The Bronsted pl o t s using the r e s u l t s of the simultaneous equation method i s shown i n F i g . 9, with the values of B e l l and L i d w e l l f or comparison. The Bronsted equations are shown below. Acid catalysis log k j ^ = - 4.63 - 0.52 (pK + log 1/2) [3.8] r = 0.9808 Base catalysis log (log k A - /2 ) = r = 0.9225 - 8.88 + 0.45 (pK + log 1/2) [3.9] - 73 Table 5: a n d k A- values f o r acetone e n o l i z a t i o n catalyzed by carboxylic acids and carboxylate bases at 25° and 0.1 M i o n i c strength, determined by the simultaneous equations method, pK = pK T - 0.11, 2 Is the number of values of each rate constant determined. A c i d 107 kHA M" 1 s e c " 1 10? kA" M* •1 s e c " 1 pK T 2 C1CH 2C0 2H IC 1.4 + 1. 2 a 0. 613 + 0. 370 2.86 6 C 6H 5CH(0H)C0 2H 6. 72 + 0. 81 0. 761 + 0. 449 3.41 15 CH 3OCH 2C0 2H 4. 97 + 0. 61 0. ,524 + 0. 199 3.57 10 H0CH 2C0 2H 3. 31 + 0. 38 0. ,492 + 0. 215 3.83 10 C 6H 5CH 2C0 2H 1. 78 + 0. ,13 1. .68 + 0. .30 4.31 8 CH 3C0 2H 0. 804 + 0, .054 2. .08 + 0. .11 4.76 10 (CH 3) 2CHC0 2H 1. 16 + 0. .02 2, .82 + 0. .35 4. 86 10 CH 3CH 2C0 2H 0. 849 + 0 .249 3 .10 + 0, .22 4. 87 15 C 6H 1 1C0 2H 0. ,898 + 0 .180 3 .53 + 0 .10 4.91 10 (CH 3) 3CCH 2C0 2H 1. .21 + 0 .08 4 .26 + 0 .18 5.01 b 6 (CH 3) 3CC0 2H 0. ,887 + 0 .037 3 .94 + 0 .03 5.03 6 standard deviation pK^ determined i n t h i s work, see experimental. The poor degree of f i t of the data ( e s p e c i a l l y i n the case of the bases) necessitated a thorough redetermination of these rate constants by the b u f f e r - r a t i o method before any conclusions could be reached. - 74 -- 8 .8 I I I 2 3 4 6 pK + log p/q F i g . 9: Bronsted p l o t s for acetone e n o l i z a t i o n cata lyzed by (a) c a r b o x y l i c ac ids (open c i r c l e s ) data from Table 5 (b) carboxylate bases (open c i r c l e s ) data from Table 5. Rate constants determined by simultaneous equation method. B e l l and L i d w e l l ' s data (c losed squares, broken l i n e s ) added for comparison i n both (a) and (b) (BL40). 75 -The following points should be noted concerning the buf f e r r a t i o method. 1. The rate constants can be determined by a p l o t of the slope of k o b s vs. [A"] against n, the buffer r a t i o as previously described. Such a p l o t gives a s the slope and k A- as the intercept, eq. [1.70]. This was done for acid/conjugate base p a i r s where k ^ < k A-. The c o r r e l a t i o n c o e f f i c i e n t gives a measure of the degree of p r e c i s i o n of the k ^ measurement, p r e c i s i o n which was generally l e s s than that obtained f o r the (larger) k A- rate constants. In cases where Ic-HA > k A-, the slope of k Q D S vs. [HA] was p l o t t e d against 1/n, gi v i n g k A- as the slope and k ^ a s the intercept, eq. [3.10]. Slope of k O D S vs. [A"] = k A- + n k^A. [1-70] Slope of k o b s vs. [HA] - k ^ + (1/n) k A- [3.10] The standard deviation of the smaller rate constant i s a minimum when that rate constant i s the slope, rather than the intercept, of such p l o t s . 2. In any given set of buffer solutions at the same buffer r a t i o , n, the pH should be constant throughout the set. Generally the average pH of each set of carboxylate solutions had an average deviation no greater than 0.02 pH u n i t s . 3. I t follows from eq. [3.6] that at a n value of 1, the pH of the solu t i o n s equals pK 1. Likewise, at n = 2, pH = pK 1 — 0.3 and at n = 0.5, pH = pK 1 + 0.3. 4. Experimental r e s u l t s showed, not s u r p r i s i n g l y , that there i s a l i m i t to the range of buf f e r r a t i o s possible. That i s to say, outside the - 76 -range of 5 > n > 0.2, the buffer capacity diminished to the point where there were s i g n i f i c a n t changes i n pH within the buf f e r set which, i n turn, produced non zero-order decreases of t r i i o d i d e ion absorbance ( i . e . non-linear decreases were observed). 5. For c e r t a i n acid/conjugate base pai r s the much greater magnitude of the a c i d rate constant made a meaningful determination of the conjugate base rate constant impossible. This despite the f a c t that the choice of buf f e r r a t i o s i s always such that i t favours the smaller contributor (within the experimental l i m i t a t i o n of 5 > n > 0.2). In cases where k A- i s n e g l i g i b l e , the value of can be determined from a p l o t of k o b s vs. [HA], as eq. [3.5] reduces to eq. [3.11]. kobs ° ksum + kHA ["A] I3-11] The r e s u l t s for a c e t i c acid/acetate buffers at four b u f f e r r a t i o s are shown i n Table 6 and p l o t t e d i n F i g . 10(a). Generally each buffer r a t i o involved four concentrations, though three concentrations were used on a few occasions. The plo t s of k O D S vs. [HA] or [A"] had r ( c o r r e l a t i o n c o e f f i c i e n t ) > 0.9990 i n a l l cases. The average pH value of each i n d i v i d u a l b u f f e r - r a t i o set agrees with that expected on the basis of pK 1 =4.65. At n = 1, p H c a i c = 4.65, PHexpt = 4.63 and at n = 2.3 and 4 the values are p H c a i c = 4.34, 4.17 and 4.05, re s p e c t i v e l y , with p H e X p t = 4.345, 4.16 and 4.04, respec-t i v e l y . The agreement was not always t h i s good, the p H e X p t generally having an average deviation of ± 0.03 from the p H c a i c value. 77 Table 6: Resul ts of p l o t t i n g k o b s v s . [A"] for a c e t i c a c i d / a c e t a t e ion buffers at 4 n values (n = [HA]/[A~]) at 25°C and 0.1 M i o n i c s trength . n PH [A"],M 1 0 8 k o b s s e c ' l 10 8 Intercept 107 Slope sec M" i s e c -1 4.62 4.64 4.63 0.05046 0.03154 0.01892 1.800 1.211 0.774 0.9996 1.72 3.240 4.345 4.35 4.34 4.345 0.03362 0.02522 0.01681 0.00841 1.605 1.260 0.916 0.567 1.0000 2.22 4.115 4.16 4.15 4.16 4.16 0.02582 0.01936 0.01291 0.00645 1.570 1.262 0.944 0.608 0.9998 2.95 4.962 4.04 4.03 4.05 4.04 0.02029 0.01522 0.01015 0.00507 1.499 1.204 0.917 0.631 1.0000 3.39 5.704 - 78 -The slopes of the p l o t s of k Q D S vs. [A"] ( f i n a l column, Table 6) are p l o t t e d vs. n to provide the rate constants k ^ (slope) and k A-( i n t e r c e p t ) , F i g . 10(b). IA') n F i g . 10: (a) Plots of k o b s vs. [A"] for ac e t i c acid/acetate buffers. (b) Plot of (slope of k o b s vs. [A -]) vs. n f o r a c e t i c a c i d / acetate ion giving r = 0.9993, kHA = 8 2 4 ± ° - 2 2 1 0 " 8 M _ 1 s e c " 1 (slope) and k A- = 2.45 ± 0.06 IO" 7 M"1 s e c " 1 ( i n t e r c e p t ) . The r e s u l t s f o r methoxyacetic a c i d are shown i n F i g . 11. The large standard deviation of k A- r e f l e c t s the f a c t that the r a t i o of k ^ to k A - i s large (=20). The r e s u l t s f o r both chloroacetic a c i d and iodoacetic a c i d buffers show n e g l i g i b l e c a t a l y s i s by the carboxylate base. This can be seen from F i g . 12(a), where f o r chloroacetic a c i d b u f f e r s , the slope of k O D S 79 -F i g . 11: (a) Plots of k o b s vs. [HA] f o r methoxyacetic acid/methoxy-acetate buffers. (b) Plot of (slope of k o b s vs. [HA]) vs. 1/n f o r methoxyacetic acid/methoxyacetate ion g i v i n g r = 0.9752, k ^ = 4.80 ± 0.11 10"7 M"1 s e c " 1 (intercept) and k A - = 2.43 ± 0.39 IO" 8 M"1 sec" 1. vs. [HA] i s p l o t t e d against 1/n. The poor c o r r e l a t i o n c o e f f i c i e n t and the very large standard deviation of the slope i l l u s t r a t e the n e g l i g i b l e c o n t r i b u t i o n of the chloroacetate ion. Plots of k o b s vs. [HA] are shown i n F i g . 12(b); the slopes of these l i n e s are k ^ values (eq. [3.11], t h e i r average value agreeing with that obtained from the intercept of Fi g . 12(a). The r e s u l t s of fourteen carboxylic acid/conjugate base p a i r s sub-j e c t e d to the b u f f e r - r a t i o method are given i n Table 7. The r e s u l t s generally show much lower standard deviations than the r e s u l t s of the simultaneous-equations method, Table 5. The r e s u l t s f o r the larger rate - 80 -F i g . 12: (a) Plot of (slope of k ^ s v s • [HA]) vs. 1/n f o r c h l o r o a c e t i c acid/chloroacetate ion giving r = 0.4610, k j ^ = 11.0 ± 1.0 10" 7 M"1 s e c " 1 (intercept) and k A- = 1.75 ± 3.81 10" 9 M"1 s e c " 1 (slope). (b) Plots of k o b s vs. [HA] f o r chloroacetic acid/chloroacetate buffers, average of three slopes , k ^ = 11.5 ± 0.6 10" 7 M"1 sec" 1. constants of the acid/base pairs from both methods agree well, while there is a greater discrepancy between the smaller rate constants from both methods. Presumably the simultaneous-equation method leads to oversized values of the smaller rate constant of the acid/base pair . The more accurate results from the buffer-ratio method (Table 7) are discussed later . It is not possible to determine the rate constants for carboxylic acids stronger than chloroacetic acid using the buffer-ratio method. Unlike' the case of chloroacetic acid and weaker acids, we found that - 81 -Table 7: k ^ and k A- values f o r acetone e n o l i z a t i o n catalyzed by carboxylic acids and carboxylate bases at 25°C and 0.1 M i o n i c strength, determined by the buffer r a t i o method, br i s the number of buffer r a t i o s used. A c i d 10 7 k ^ 10 7 k A- pK T br Method 3 M"1 s e c " 1 M"1 s e c " 1 C1CH 2C0 2H 11 11 .0 .5 +1 +1 1. 0. 0 ,6 0. 017 + 0. 038 2. 86 3 I III ICH 2C0 2H 9. 9. 50 77 + + 0. 0. ,16 ,23 0. ,098 + 0. ,051 3. 18 3 I III C 6H 5CH(0H)C0 2H 7. 61 + 0. ,19 0. ,143 + 0. .058 3. ,41 3 I CH 30CH 2C0 2H 4. 80 + 0. ,11 0. .243 ± 0. .039 3. ,57 4 I H0CH 2C0 2H 3. 09 + 0, .10 0, .339 + 0, .031 3. .83 3 I C 6H 5CH 2C0 2H 1. 92 + 0 .12 1, .19 + 0 .09 4, .31 4 I CH 3C0 2H 0. 824 + 0 .022 2 .45 + 0 .06 4, .76 4 II CD 3C0 2H 0. 837 + 0 .047 2 .31 + 0 .13 4 ,77 b 3 II CH 3CH 2CH 2C0 2H 0. 881 + 0 .018 2 .79 + 0 .05 4. .82 3 II (CH 3) 2CHC0 2H 0. 670 + 0 .155 3 .03 + 0 .41 4 .86 3 II CH 3CH 2C0 2H 0. 654 + 0. .083 3, .22 + 0 .02 4, .87 3 II C 6H 1 1C0 2H 0. 774 + 0, .153 3, .19 + 0, .41 4, .91 3 II (CH 3) 3CCH 2C0 2H 0. 879 + 0. .020 4, .24 + 0. .05 5. ,01 c 3 II (CH 3) 3CC0 2H 0. 717 + 0. .027 4. .02 + 0. .09 5. ,03 3 II Slope Intercept Methods I (Slope of k o b s vs. [HA]) vs. 1/n k A- k j ^ II (Slope of k o b s vs. [A"]) vs. n k ^ k A-III Plot of k o b s vs. [HA] k ^ k s u m pK values from r e f . (SK63). pK determined i n t h i s work, see experimental. - 82 with the stronger carboxylic a c i d buffers, the pH v a r i e d considerably with concentration. At any b u f f e r - r a t i o , the lower the buffer concen-t r a t i o n , the higher i s the pH. A d i f f e r e n t k i n e t i c treatment was there-fore used f o r these carboxylic acids. For each carboxylic a c i d s o l u t i o n at a p a r t i c u l a r pH, the contribu-t i o n to the observed rate constant, k Q D S , i s given by eq. [3.12]. This expression r e s u l t s from eq. [1.68] since both the hydroxide ion and the carboxylate monoanion w i l l have n e g l i g i b l e contributions to k ^ g . I t may be r e c a l l e d that for chloroacetic acid, the conjugate monoanion showed n e g l i g i b l e c a t a l y s i s (p. 68). kobs " k H 2 0 [ H 2 0 ] + k H+[H 30 +] + k- O H["OH] + kHAfHA] + k A-[A"] [1.68] kobs = k H 2 0 l H 2 ° ] + k H + t H 3 0 + ] + ^HAlHA] t 3 - 1 2 ! For carboxylic a c i d solutions below pH 2.5 or so, the involvement of the water term (4.62 x IO"1*-* sec" 1) i n eq. [3.12] can be s a f e l y ignored, as i t w i l l comprise less than 0.5% of k Q D S . For example, at a pH of 2.5, the c o n t r i b u t i o n of the hydronium ion w i l l be (3.16 x 10" 3 M x 2.84 x 10" 5 M"1 s e c " 1 ) , i . e . 8.97 x 10" 8 s e c " 1 , or 99.5% of the t o t a l c o n t r i b u t i o n of hydronium ion and water. Involvement of the carboxylic a c i d i n the rate expression w i l l further reduce the s i g n i f i c a n c e of the water term. Hine and coworkers have reported a value for ky+ (2.84 x 10"-* M"1 sec" 1) which i s the average of 18 l i t e r a t u r e rate constants for the acid-catalyzed halogenation of acetone (HK72). We measured the value, - 83 under our experimental cond i t ions , us ing h y d r o c h l o r i c a c i d . The rate express ion for t h i s system i s shown below. k obs = k H + [ H 3 0 + ] [3-13] A number of h y d r o c h l o r i c a c i d so lut ions v a r y i n g i n concentrat ion from 1.9 x 10" 3 to 1.9 x 1 0 _ 1 M were used. The p l o t of k o b s against the s t o i c h i o m e t r i c concentrat ion of hydronium ion provides the value of as the slope (with n e g l i g i b l e in tercept ) and i s shown i n F i g . 13. Eight of the t h i r t y two k i n e t i c runs involved a d d i t i o n of between 1/3 and 4/5 equivalents of sodium hydroxide, with appropriate c o r r e c t i o n s for the 0.00 0.06 0.10 0.15 0.20 [ H + ] F i g . 13: Plot of k o b s vs. [R^O*] (stoichiometric concentration) for hydrochloric acid giving r = 0.9995, kH+ = 2.51 ± 0.02 x 10" M" 1 s e c - 1 (slope), and intercept 1.9 ± 1.5 x 10"8 sec" 1. Ionic strength was varied from 0.01 to 0.2 M. - 84 -concentration of hydronium ion. These r e s u l t s alone give a value of 2.43 ± 0.03 x 10" 5 M"1 s e c " 1 for k H+ compared with the value of 2.51 ± 0. 02 x 10"^ M"1 s e c " 1 for a l l t h i r t y two k i n e t i c runs. There i s a small but consistent difference between the stoichiomet-r i c concentration of hydronium ion and the concentration determined from the measured pH of each sol u t i o n . This l a t t e r 'pH' concentration i s always found to be s l i g h t l y smaller than the stoichiometric concentra-t i o n , determined by t i t r a t i o n with sodium hydroxide. Thus a k^+ value determined by using the i^O"1" 'pH' concentrations w i l l be s l i g h t l y larger than the value obtained using the stoichiometric HjO"*" concentrations. The p l o t of k o b s vs. [i^O"1"] determined from the pH for the same t h i r t y two k i n e t i c runs which were used to determine the stoichiometric k^+ value, gives the following r e s u l t ; r = 0.9960, slope = 2.95 ± 0.05 x 10" 5 M"1 s e c " 1 (k H+) and intercept = - 2.0 ± 3.9 x 10" 8 M " 1 s e c " 1 . While the ' s t o i c h i o m e t r i c a l l y ' derived rate constant for hydronium i on 1. e. kn+Cstoich.) can be considered the correct value, i t may be more appropriate to use the pH-derived value i . e . k^+(pH), i n a k i n e t i c treatment where measurements of pH are used to determine hydronium i on concentrations. The k i n e t i c treatment i s described using d i f l u o r o a c e t i c a c i d as an example; a number of carboxylic a c i d solutions are prepared by the add i t i o n of between 1/3 and 4/5 equivalents of sodium hydroxide to the free acid. For each p a r t i c u l a r s o l u t i o n at a p a r t i c u l a r pH, the concentration of the d i f l u o r o a c e t i c a c i d was determined from eq. [3.14], where [HA] 0 i s the i n i t i a l concentration of d i f l u o r o a c e t i c acid, [B"] i s the concentration of base added and [H +] i s c a l c u l a t e d from the pH - 85 -measurement (AS84b). The concentration of d i f l u o r o a c e t i c a c i d i n each s o l u t i o n i s r e l a t e d to k o b s by eq. [3.15]. [HA] = [HA] Q - [B-] - [H +] [3.14] kobs " k H + [ H 3 0 + ] = ^HAtHA] [3.15] The r e s u l t s f o r d i f l u o r o a c e t i c a c i d are shown i n Table 8, and F i g . 14 shows the p l o t of ( k o b s - k H+[H 30 +]) vs. [HA]. The slope of t h i s l i n e i s the value of k j ^ f ° r d i f l u o r o a c e t i c acid, 6.37 ± 0.12 x 10"^ M"1 Table 8: pH, k o b s and [HA] measurements f o r d i f l u o r o a c e t i c a c i d solutions pH 10 6 k o b s , s e c " 1 [HA], M 10 6 ( k o b s - k H + [ H 3 0 + ] ) a s e c " 1 1. .23 2. 563 0. 1321 0. 826 1. ,255 2. 400 0. 1163 0. 760 1. ,34 1. ,948 0. 0918 0. ,600 1. ,485 1. ,359 0. ,0628 0. ,393 1. .505 1. .242 0. ,0499 0. ,320 1 .745 0, .711 0, .0298 0, .180 1. .875 0 .511 0. .0189 0, .118 2, .05 0 .376 0, .0150 0, .113 k H+ = 2.95 x 10" 5 M " 1 s e c " l , [H 30 +] determined from pH. - 86 -s e c " 1 . The n e g l i g i b l e intercept i l l u s t r a t e s the n e g l i g i b l e c a t a l y s i s ..by d i f l u o r o a c e t a t e anion. The r e s u l t s f o r d i c h l o r o a c e t i c a c i d are p l o t t e d i n F i g . 14 also. 1 B l n i 1 1 1 0 . 0 0 0 . 0 4 0 .08 0.12 0.16 [HA] F i g . 14: Plots of ( k o b s - k H+[H 30 +]) vs. [HA] f o r d i f l u o r o a c e t i c a c i d (closed c i r c l e s ) g i ving r = 0.9990, slope, kuA. = 6 - 3 7 ± 0-12 x 10" 5 M"1 s e c " 1 and intercept 2.1 ± 9.3 x 10"^ s e c " 1 and d i c h l o r o a c e t i c a c i d (open c i r c l e s ) g i v i n g r = 0.9985, slope, kHA = 9 2 6 ± ° - 1 5 x 1 0 ~ 5 M _ 1 s e c and intercept 2.5 ± 9.2 x 10" 9 s e c " 1 The major part of k o b s i s the cont r i b u t i o n from hydronium ion, which i n the case of d i f l u o r o a c e t i c a c i d v a r i e s from 68% to 77% of k o b s . No attempt was made to keep the i o n i c strength of the d i f l u o r o a c e t i c a c i d 87 -solutions constant and from the r e s u l t s , with i o n i c strength varying from 0.1 M to 0.15 M, io n i c strength e f f e c t s on must be n e g l i g i b l e i n t h i s range. I t may be r e c a l l e d that both chloroacetic a c i d and iodoacetic a c i d showed n e g l i g i b l e c a t a l y s i s by the conjugate anion. The k ^ values f o r these two acids can be determined using t h i s approach and compared with the r e s u l t s from the b u f f e r - r a t i o method. As the pH of the solutions of these carboxylic acids are i n the range 2.46 to 3.66, the water term should be included i n the rate expression, eq. [3.12]. k o b s - k H+[H 30 +] - kH 2 o[H 20] = k^tHA] [3.12] Plots of ( k o b s - k H+[H 30 +] - k H 2 o [ H 2 0 ] ) vs. [HA] for both ch l o r o a c e t i c and iodoacetic a c i d are l i n e a r with n e g l i g i b l e intercepts. The value of kHA' i - e - the slope of the l i n e s , i s 10.9 ± 10" 7 M " 1 s e c " 1 for chl o r o a c e t i c a c i d and 9.47 ± 0.20 x 10" 7 M " 1 s e c " 1 for iodoacetic acid. These r e s u l t s compare favourably with the values determined using the b u f f e r - r a t i o method (Table 7); 11.0 ± 1.0 x 10" 7 M " 1 s e c " 1 for chl o r o a c e t i c a c i d and 9.50 ± 0.16 x 10" 7 M " 1 s e c " 1 for iodoacetic acid. A number of carboxylic acids were treated i n t h i s way and the k j ^ values determined are l i s t e d i n Table 9. No r e s u l t s were excluded f o r any a c i d i n the p l o t of ( k o b s - k H+[H 30 +]) vs. [HA] i n order to improve upon the degree of f i t (as measured by the c o r r e l a t i o n c o e f f i c i e n t , r ) . Rather, i n cases where the p l o t was s l i g h t l y scattered , a large number of k i n e t i c runs were used to define the l i n e . The r e s u l t s f o r proto-nated glycine, H 3NCH 2C0 2H, show the poorest c o r r e l a t i o n c o e f f i c i e n t - 88 -Table 9 : k ^ values for acetone enolization at 25°C, determined by plots of ( k o b s - k H +[H 3 0 + ] ) a vs. [HA], nk is the number of kinetic runs. Acid 1 0 ? k H A M " 1 sec" 1 P K T N K ICH 2C0 2H 9.47 ± 0.20 3.18 4 C1CH 2C0 2H 1 0 . 9 + 1 . 1 2.86 4 C1'H 3N +CH 2C0 2H 12.8 ± 0.9 2.36 b 16 C l " (CH 3) 2NHCH 2C0 2H 19.8 ± 0 . 3 1.94b 8 Cl"(CH 3) 3NCH 2C0 2H 28.5 ± 0.8 1.83 b 20 C1 2CHC0 2H 92.6 ± 1.5 1.36°, 1.36 d 14 F 2CHC0 2H 63.7 ± 1.2 1.34c, 1.30 d 8 Br 3CC0 2H 280 ± 15 0.73 d 16 C1 3CC0 2H 273 ± 6 0.52c, 0.69 d 8 F 3CC0 2H 205 ± 9 0.50 c, 0.54 d 8 kH+ - 2.95 x 10" 5 M ' 1 sec" 1, water term (4.62 x 1 0 " 1 0 sec"1) included where necessary. pK values from ref. (EF79). pK values from ref. (KF69). pK values determined in this laboratory (NV87). b c d 89 -(0.9685) and are shown i n F i g . 15. For a l l these acids the good degree of f i t of the experimental r e s u l t s to eq. [3.15] i s r e f l e c t e d by the small standard deviations of the values. In appropriate cases a c o r r e c t i o n f or the water term i s included i n the rate expression ( i . e . f o r the weaker acids and pH values greater than 2.5). Measuring k ^ and k A- values for benzoic acids i s extremely d i f f i c u l t owing to the low s o l u b i l i t y of these acids i n water. The b u f f e r - r a t i o method i s used, generally at b u f f e r - r a t i o s that favour the anion, thereby having acceptable concentrations of b u f f e r accessible. By t r i a l and error the maximum s o l u b i l i t y of each a c i d was determined 90 -under the experimental conditions. The acids studied are the more soluble, or rather the less insoluble, benzoic acids, which excludes 4-substituted and di s u b s t i t u t e d benzoic acids. In any p a r t i c u l a r b u f f e r - r a t i o set, comprising four solutions, only a small span of concentration i s used (generally a factor of three). The weakest benzoic a c i d studied, i s 3-methylbenzoic acid having a pK T of 4.27. An i o n i c strength of 0.1 M i s used, as i n the case of the a l i p h a t i c carboxylic acids. The k i n e t i c r e s u l t s at three buffer r a t i o s are shown i n Table 10 and Fig. 16(a). The slope of k O D S vs. [HA] i s pl o t t e d against 1/n i n F i g . 16(b) providing k ^ as the intercept and k A-as the slope. As i n the a l i p h a t i c carboxylic a c i d b u f f e r - r a t i o sets, 1E3 [HA] 1/n F i g . 16: (a) Plots of k o b s vs. [HA] for 3-methylbenzoic acid/3-methyl-benzoate buffers; (b) Plot of (slope of k o b s vs. [HA]) vs. 1/n for 3-methylbenzoic acid/3-methylbenzoate ion giving r = 0.9995, k ^ = 1.61 ± 0.08 x I O ' 7 M" 1 s e c - 1 (intercept) and k A - 8.81 ± 0.31 x I O - 8 M _ 1 s e c - 1 (slope). - 91 -Table 10: Results of p l o t t i n g k o b s v s . [HA] for 3-methylbenzoic a c i d / 3-methylbenzoate ion buffers at 3 n values (n = [HA]/[A~]) at 25°C and 0.1 M i o n i c s trength . n pH 103 [HA], 109 k o b s r 109 Intercept 107 Slope M sec" 1 sec" 1 M"1 sec"1 4.23 5.193 3.584 1 4.21 4.039 3.309 0.9992 2.28 2.525 4.205 2.885 3.030 4.215 1.731 2.706 4.54 5.093 3.200 0.5 4.525 3.961 2.842 0.9998 1.52 3.318 4.52 2.830 2.469 4.52 1.698 2.073 4.815 5.013 4.106 0.25 4.845 3.899 3.437 0.9987 1.27 5.151 4.84 2.785 2.852 4.81 1.671 2.319 - 92 -the average pH i s close to that expected on the basis of pK 1 _and the value of n, the b u f f e r r a t i o , eq. [3.6], pH = pK 1 - log n [3.6] The r a t i o of k j ^ to k A- i s approximately two for 3-methylbenzoic a c i d . As the benzoic a c i d chosen for study becomes stronger, t h i s r a t i o w i l l increase, making accurate determinations of k A- values more and more d i f f i c u l t . U n t i l , f o r the stronger benzoic acids, c a t a l y s i s by the conjugate benzoate anion becomes n e g l i g i b l e . I t i s possible to measure k A- values for three other benzoate anions using the same method as that used f o r 3-methylbenzoate anion ( i . e . p l o t of the slope of k o b s vs. [HA] against 1/n), a l b e i t with standard deviations topping 20% i n two of those cases. The corresponding k j ^ values for the conjugate acids of these benzoate anions have much smaller standard deviations. The three benzoic acids which gave these r e s u l t s are 2-methyl, 2-ethoxy and the unsubstituted compound. The values of k j ^ - and k A- for these c a t a l y s t s are given i n Table 11. Benzoic acids that are stronger than the group j u s t mentioned give p l o t s of the slope of k o b s vs. [HA] against 1/n with c o r r e l a t i o n c o e f f i c i e n t s l e s s than 0.900 (the poor c o r r e l a t i o n c o e f f i c i e n t r e f l e c -t i n g the almost n e g l i g i b l e c o n t r i b u t i o n of the anion to the rate expression). For these compounds (3-fluoro, 3-nitro and 2-fluoro benzoic a c i d s ) , the slopes of k o b s vs. [A"] are p l o t t e d against n to provide k j ^ as the slope and k A- as the intercept. In t h i s way, good c o r r e l a t i o n c o e f f i c i e n t s r e s u l t (>0.993, r e f l e c t i n g the good p r e c i s i o n 93 -of the slope, k ^ ) with almost n e g l i g i b l e intercepts. The r e s u l t s f o r 3-nitro and 2-fluorobenzoic a c i d are shown i n F i g . 17 and are l i s t e d i n Table 11, along with the r e s u l t s f o r 3-fluoro-benzoic acid. 8-1 ——7 1 F i g . 17: Plots of (slope of k o b s vs. [A"]) vs. n f o r ( i ) 3-nitrobenzoic a c i d (closed c i r c l e s ) g i v ing r = 0.9990, k ^ = 5.40 ± 0.19 x 10" 7 M"1 s e c - 1 (slope) and k A- = 6.87 ± 11.2 x I O - 9 M"1 s e c - 1 (intercept) and for ( i i ) 2-fluorobenzoic a c i d (open c i r c l e s ) g i v i n g r = 0.9940, k H A = 8.14 ± 0.69 x 10" 7 M"1 s e c " 1 (slope) and k A- = -6.26 ± 4.14 x 10" 8 M"1 s e c " 1 ( i n t e r c e p t ) . In a d d i t i o n to the seven benzoic acids discussed so f a r , two other benzoic acids were studied; 2-nitro and 2,6-dinitrobenzoic acid. These acids are stronger than chloroacetic a c i d and thus we can expect a large c o n t r i b u t i o n to k o b s from the hydronium ion, n e c e s s i t a t i n g a high concentration of HA to allow a measurement of the a c i d rate constants to - 94 -Table 11: a n ( i k A - values for acetone enolization catalyzed by benzoic acids and benzoates ions at 25°C and 0.1 M ionic strength Substituent 10' k ^ 10' k A- pK 1 b r a nk b Method 0 3-CH3 1.61 ± 0.08 0.881 ± 0.031 4.27 3 - I H 2.46 ± 0.17 0.638 ± 0.069 4.20 5 - I 2-C 2H 50 3.05 ± 0.34 0.689 ± 0.149 4.16 d 4 - I 2 - CH3 4.16 ± 0.20 0.364 ± 0.071 3.91 4 - I 3- F 3.39 ± 0.15 0.300 ± 0.087 3.86 4 - II 3-N02 5.40 ± 0.19 0.069 ± 0.112 3.49 4 - II 2-F 8.14 ± 0.69 -0.626 ± 0.414 3.27 4 - II 2-N02 39.5 ± 2.4 - 2.21 - 11 IV 2,6-(N0 2) 2 166 ± 12 - 1.14 - 7 IV a Number of buff e r r a t i o s used f o r methods I and I I . D Number of k i n e t i c runs used for method IV. Slope Intercept c Methods I (Slope of k o b s vs. [HA]) vs. 1/n k A- k ^ II (Slope of k o b s vs. [A"]) vs. n k j ^ k A-IV ( k o b s - k H+[H 30 +])/[HA] ^ pK determined i n t h i s laboratory (NV87). - 95 -be made. The r e l a t i v e l y high s o l u b i l i t y of these two benzoic acids makes t h i s p o s s i b l e . The b u f f e r - r a t i o method i s of no use for these two r e l a t i v e l y strong acids. Rather, as was the case with the d i - and t r i - h a l o a l i p h a t i c carboxylic acids (p. 83), a group of solutions at varying pH values and benzoic a c i d concentrations are prepared and k o b s measurements are made. The contr i b u t i o n from hydronium ion at each pH i s subtracted from the corresponding k o b s , to provide the value of kj^fHA] f o r the appropriate benzoic a c i d concentration, eq. [3 .15] . kobs - k H + t H 3 0 + ] = I W H A ] [3-15] The r e s u l t s f o r 2 , 6-dinitrobenoic a c i d are shown i n Table 12. Unlike the case of the d i - and t r i - h a l o a c i d s , which pose no s o l u b i l i t y problems whatsoever, the range of accessible concentrations of 2 , 6-di-nitrobenzoic a c i d i s li m i t e d . For d i f l u o r o a c e t i c a c i d (Table 8) the concentrations used spanned a factor of nine (1.3 x 10"! M to 1.5 x 10~ 2 M), whereas for the benzoic acid, a concentration range of only two i s possible (1.6 x 10~ 2 M to 7.6 x 10" 3 M); the upper l i m i t being imposed by the s o l u b i l i t y of the a c i d and the lower l i m i t being the minimum a c i d concentration needed f or the acid to make a meaningful co n t r i b u t i o n to k o b s . The p l o t of ( k o b s - k H+[H 3 0 + ] ) against [HA] for 2 , 6 - d i n i t r o -benzoic a c i d gives a poor l i n e (r = 0.9716) due to the small range of [HA] values used; F i g . 18 shows the r e s u l t , with t r i c h l o r o a c e t i c a c i d also shown f o r comparison. A more appropriate means of determining k j ^ fo r the p a i r of ortho-nitrobenzoic acids i s the following; f o r each 96 -20-i 16-+ • O f SB + a .* 10 « o r» 6 W 0.00 0.02 0.04 [HA] 0.06 0.08 F i g . 1 8 : P l o t o f ( k o b s - k H + [ H 3 0 + ] ) v s . [HA] f o r 2 , 6 - d i n i t r o b e n z o i c a c i d (open c i r c l e s ) g i v i n g r = 0 . 9 7 1 6 , s l o p e =^1.35 ± 0 . 1 5 x 1 0 " 5 M " 1 s e c " 1 and i n t e r c e p t 3 . 3 1 + 1 .73 x 1 0 ' " 8 s e c - 1 C o r r e s p o n d i n g p l o t f o r t r i c h l o r o a c e t i c a c i d added f o r c o m p a r i -s o n ( c l o s e d c i r c l e s ) . v a l u e o f ( k O D S — k j j + [ H 3 0 + ] ) , d i v i s i o n b y [HA] p r o v i d e s t h e r a t e c o n s t a n t , k ^ - The r e s u l t i n g k^A f o r 2 , 6 - d i n i t r o b e n z o i c a c i d ( a v e r a g e v a l u e f r o m s e v e n k i n e t i c r u n s ) i s 1.66 ± 0.12 x I O " 5 , T a b l e 12. T h i s r e s u l t and t h a t o b t a i n e d f o r 2 - n i t r o b e n z o i c a c i d a r e a t 0.1 M i o n i c s t r e n g t h and a r e l i s t e d i n T a b l e 11, a l o n g w i t h t h e r a t e c o n s t a n t s o b t a i n e d f o r t h e s e v e n o t h e r b e n z o i c a c i d s . - 97 Table 12: Results of the kinetic runs for 2,6-dinitrobenzoic acid giving a value of k ^ = 1.66 ± 0.12 x 10"5 M" 1 sec" 1 (obtained by dividing ( k o b s - kH+[H 30 +]) by [HA]). pH 10 7 k o b s 107 ( k o b s - kH+[H30+]) 10 2 [HA] ,M 10 5 sec" 1 sec" 1 M - l s e c - l 1. .73 8, .043 2. .550 1. .576 1. .62 1. ,63 8, .967 2. .052 1. .379 1, .49 1. ,675 8. .294 2. ,059 1. ,195 1. .72 1. ,80 6, .571 1. .896 1. ,166 1, .63 1. ,90 5. .408 1. ,694 1. ,083 1. .56 1. ,965 4. .697 1. ,499 ,835 1, .80 1. ,89 5. .174 1. ,374 ,763 1. ,80 3. ,1.2 Diprotic Acids, Bifunctional Monoanions and Dianionic Bases Carboxylic diprotic acids provide three catalyt ic entities for study, the neutral acid (H 2A), and monoanion (HA"), and the dianion (A 2 "). In the case of dicarboxylic acids with K i / K 2 values greater than 10 3 , the two carboxylic acid ionizations are separate processes and such systems can be treated as two dist inct dissociations', f i r s t l y the - 98 -d i p r o t i c a c i d to the conjugate monoanion; and then the m o n o a n i o n „ t o the conjugate d ian ion . In these s i t u a t i o n s , the appropriate k i n e t i c treatment can be chosen from those descr ibed thus f a r for each ac id /conjugate base p a i r , H 2 A/HA" and H A " / A 2 " . The appropriate k i n e t i c treatment w i l l depend on the r e l a t i v e magnitude of the two rate con-stants invo lved , k ^ A / H l A " o r k H A " / k A 2 " -However, i f the two pK values of the d i p r o t i c ac ids are separated by l e s s than 2.7 u n i t s of pK, the two i o n i z a t i o n s are s a i d to overlap (AS84C). In such s i t u a t i o n s , the f i r s t d i s s o c i a t i o n (H2A/HA") i s not 100% complete before the next one begins (HA"/A 2 ~) and a l l three species H2A, HA" and A^' are s imultaneously present to some degree. The concentrat ions of the three species can be determined us ing eqs. [3.16]-[3 .19] , knowing [ H + ] , K ^ 1 . and K 2 ^ ( e q u i l i b r i u m constants at the appropriate i o n i c strength) and C^Q^, the t o t a l concentrat ion of d i a c i d , monoanion and d ian ion present (R81c). D = [ H + ] 2 + K 1 I [ H + ] + K 1 I K 2 [3.16] [ H 2 A ] / C X 0 T = [ H + ] 2 / D [3.17] [ H A - ] / C T 0 T = K 1 I [ H + ] / D [3.18] [ A 2 - ] / C T 0 T = K 1 I K 2 I / D [3.19] F ive a l i p h a t i c d i c a r b o x y l i c acids were s tudied; two of these d iac ids have pK-L and pK2 values separated by more than 2.7 pK u n i t s , i . e . o x a l i c 99 -a c i d and diethylmalonic acid; the other three d i a c i d s have 'overlapping' pK values, i . e . s u c c i n i c acid, 3-methyl and 3,3-dimethylglutaric acid. For oxalate monoanion and dianion (pK 2 = 4.29), the rate law shown i n eq. [3.20] i s applicable. At b u f f e r - r a t i o s of m = [HA"]/[A 2"], eq. [3.20] can be rewritten as eqs. [3.21] or [3.22]. kobs - ksum + kHA"[HA"] + k A2-[A 2"] [3.20] kobs = ksum + [HA" ] {k^- + (l/m)k A2-) [3.21] kobs " k s u m + [ A 2 " ] < k A 2 - + m k H a " > [3.22] For each b u f f e r - r a t i o , m, a p l o t of k O D S vs. [HA"] w i l l have a slope ^kHA" + (l/m)k A2-). P l o t t i n g t h i s slope against 1/m provides k ^ - as the i n t e r c e p t and k A2- as the slope (eq. [3.21]). Conversely the slopes of the l i n e s r e s u l t i n g from p l o t s of k O D S vs. [A 2"] can be p l o t t e d against m g i v i n g k A2- as the intercept and k ^ - as the slope (eq. [3.22]) . Three b u f f e r - r a t i o s provided the r e s u l t s shown i n F i g . 19 for oxalate monoanion and dianion at 0.1 M i o n i c strength. The larger standard d e v i a t i o n of the dianion rate constant compared to the mono-anion rate constant r e f l e c t s the f a c t that k ^ - i s approximately 13 times k A2". The b u f f e r - r a t i o s used were 0.8, 0.5 and 0.25 and the pH value of these b u f f e r - r a t i o sets are close to that expected on the basis of eq. 100 -F i g . 19: (a) P lo t s of k o b s v s . [A z _] f or oxalate monoanion/dianion b u f f e r s ; (b) P lo t of (slope of k O D S v s • [A . 2 - ] ) v s . m for oxalate monoanion/dianion g i v i n g r = 0.9965, k ^ - = 6.32 ± 0.53 x IO" 7 M " 1 s e c - 1 (slope) and k A 2 - = 5.05 ± 2.98 x 10"' M " 1 s e c - 1 ( i n t e r c e p t ) . [3 .23] , p K 1 be ing equal to pK 1 - 0.33 at 0.1 M i o n i c s trength from eq. [3.24] (AS84d). pH = PK2 1 - l og m [3.23] PK2 1 - p K T - {1 .53457D/1 + 1.571) [3.24] As p K 2 = 4.29, pK2 = 3 . 9 6 therefore the p H c a l c values are 4.06, 4.26 and 4.56, at m values of 0.8, 0.5 and 0.25. The experimental pH values for the buf fer s o l u t i o n are 4.08 (m = 0.8) 4.29 (m = 0.5) and - 101 -4.57 (m = 0.25) , each value being the average ± 0 . 0 1 , of the four members of that p a r t i c u l a r b u f f e r - r a t i o set . For o x a l i c a c i d and oxalate monoanion (pK^ = 1.25), the rate law shown i n eq. [3.25] i s a p p l i c a b l e . As i n the case of the d i - and t r i - h a l o a l i p h a t i c c a r b o x y l i c a c i d s , the b u f f e r - r a t i o method cannot be used for the d i a c i d and monoanion species s ince the pK^ value i s so low. k obs " kH+[H 30+] + k H 2 A [ H 2 A ] + k ^ - t H A - ] [3.25] Un l ike the case of the halo a l i p h a t i c c a r b o x y l i c a c i d s , the conju-gate base of the d i a c i d , HA", does contr ibute to the observed r a t e . I t may be r e c a l l e d that the anion, A", does not contr ibute to the rate for the halo a c i d s . The presence of the monoanion term, k^A-fHA"] , i s evident from the k i n e t i c r e s u l t s shown i n Table 13, where the r e s u l t s of e ight i n d i v i d u a l k i n e t i c runs are shown. Use of eq. [3.26] gives 8 values of k H ^ A , obtained by d i v i d i n g ( k 0 D S - k H +[H 3 0 + ] ) by [ H 2 A ] , that show a large degree of s c a t t e r . k obs " k H + t H 3 ° + ] " k H 2 A t H 2 A ] t 3 - 2 6 ] k obs - k H +[H 3 0 + ] - kHA-IHA-] = k ^ I ^ A ] ( 3 - 2 5 l On the other hand use of eq. [3.25] , which inc ludes the monoanion term gives more cons i s tent values of k ^ A > Table 13. The rate constant used for HA" i s that determined from the k i n e t i c s at var ious m b u f f e r - r a t i o s values ( [ H A " ] / [ A 2 " ] ) , as described 102 -Table 13: Resul ts of the k i n e t i c runs for o x a l i c a c i d g i v i n g a value of k H A = 13.6 ± 2.5 x 10" 6 M " 1 sec" 1 us ing eq. [3.26] and k H 2 A = 11.6 ± 1.5 x I O " 6 M " 1 sec" 1 us ing eq. [3.25] pH 10 6 k o b s [ H 2 A ] , M [HA'] , M 10 6 k H A a 10 6 k H A b -i i i i i s e c " 1 M_J- sec"-1- M"-1- s e c " 1 1. .21 3. .367 0. ,1411 0. ,1631 11. ,0 10. .2 1. .235 3. ,041 0, .1243 0. .1495 10. .7 9. .89 1. .31 2. .503 0, .0970 0. .1463 10. .9 9. .95 1. .37 2. ,190 0. .0587 0. .1440 15. .9 14, .3 1. .51 1. .554 0, .0502 0. .1120 12, .8 11 .4 1. .75 0. ,968 0. .0295 0. .1124 15. .0 12, .6 1. .93 0. ,636 0. .0187 0. ,1030 15. .5 12, .0 2. .04 0. .526 0. .0152 0. .1065 16. .8 12, .4 Using eq. [3 .26] , exc luding monoanion term. Using eq. [3 .25] , i n c l u d i n g monoanion term. - 103 -previously, i . e . 6.32 x 10" 7 M"1 sec" 1. The concentrations of H 2A and HA" are given by eqs. [3.27] and [3.28], where [H2A] Q i s the i n i t i a l concentration of o x a l i c acid, [B"] i s the concentration of base added and [H +] i s c a l c u l a t e d from the pH measurement (AS84b). [H2A] = [H 2A] Q - [B-] - [H +] [3.27] [HA"] = [B"] + [H +] [3.28] The mean value of k H ^ A i s 11.6 ± 1.5 x 10" 6 M"1 sec" 1; the p l o t of ( k o b s — k^+[H30 +] — k^ A-[HA"]) vs. [H 2A] gives a reasonable l i n e with r = 0.9852, k H A = 9.51 ± 0.68 x 10" 6 M"1 s e c " 1 (slope) and a n e g l i g i b l e i n t e r c e p t of 9.39 ± 5.46 x 10" 8 M"1 sec" 1. The i o n i c strength of the solu t i o n s was not kept constant and v a r i e d from 0.2 to 0.1 M, the v a r i a t i o n showing no dramatic e f f e c t s on r e s u l t i n g k ^ A values. The second d i c a r b o x y l i c a c i d studied was diethylmalonic acid. At m b u f f e r - r a t i o s of 2 and 1, the k i n e t i c r e s u l t s showed n e g l i g i b l e cataly-s i s by the monoanion and so eq. [3.20] s i m p l i f i e s to eq. [3.29] kobs = ksum + kHA"[^A"] + k A2-[A 2"] [3.20] kobs " ksum + k A 2 " [ A 2 " ] [3-29] Use of eq. [3.21] which provides k ^ - as the intercept and k A2- as the slope, showed a n e g l i g i b l e value f o r the intercept. Accordingly eq. [3.29] was used f o r each buffer r a t i o (plot of k o b s vs. [A 2"]) giving a - 104 -' value of k A 2 - f o r the slope and k s u m for the i n t e r c e p t . The r e s u l t s of two b u f f e r - r a t i o s gave an average value of k A 2 - = 1.59 ± 0.15 x 10 "^ M " 1 sec" 1 , at 0.05 M i o n i c s trength . At an i o n i c s trength of 0.15 M (m = 0 .5 ) , a k A 2-va lue of 1.63 x 10"^ M " 1 sec"1- r e s u l t e d , a value very c lose to that at 0.05 M i o n i c s trength, i l l u s t r a t i n g the very small e f f ec t of i o n i c s trength on the k A 2 - va lue . The value of k ^ A for d ie thylmalonic a c i d i s determined us ing eq. [3.26] i n a s i m i l a r treatment to that used for o x a l i c a c i d . (Note that the monoanion i s not involved i n the rate law.) A p l o t of (k 0]-, s - k H + [ H 3 0 + ] ) against [H 2A] gives a s t r a i g h t l i n e , r = 0.9988, with k H ^ A = 1.32 ± 0.04 x 10" 6 M " 1 sec" 1 (slope) and a n e g l i g i b l e i n t e r c e p t 1.30 ± 0. 28 x 10" 8 M ' 1 sec" 1 . Thus for d ie thylmalonic a c i d , the monoanion makes no s i g n i f i c a n t c o n t r i b u t i o n to k o b s at pH values c lose to e i t h e r pK^ or p K 2 . Of the three a l i p h a t i c d i c a r b o x y l i c acids s tudied that have over lap-p ing pK^ and p K 2 values ( i . e . p K 2 — pK^ < 2 .7) , 3 -methy lg lutar ic a c i d (pK^ = 4.35, p K 2 = 5.44) has the smal lest d i f f erence between pK]^  and pK 2 1. e. the greatest degree of overlap of the two d i s s o c i a t i o n s . Ignoring t h i s over lap and t r e a t i n g t h i s d i a c i d i n the same manner as o x a l i c a c i d gives the r e s u l t shown i n F i g . 20; the p l o t of the slope of ( k o b s v s . [HA"]) against 1/m g i v i n g k A 2 - as the slope and k j ^ - as the i n t e r c e p t . The b u f f e r - r a t i o s are chosen to minimize the extent of the overlap of both i o n i z a t i o n s ; m values favouring the d ian ion i . e . m = 0.8, 0.5 and 0.25 w i l l r e s u l t i n small concentrat ions of the d i a c i d being present . I t i s p o s s i b l e to use t h i s experimental data, taking account of the over lapping i o n i z a t i o n constants , to determine the concentrat ions of a l l 105 -three species us ing eqs. [3 .16] - [3 .19] . When t h i s i s done, we f i n d that the concentrat ion of the d i a c i d , H 2 A , i s only between 0.3-2.2% of the t o t a l concentrat ion and i s assumed to make a n e g l i g i b l e c o n t r i b u t i o n to k O D S . P lo t s of k o b s v s . [HA"] thus c a l c u l a t e d are l i n e a r . A subsequent p l o t of the slope of these l i n e s against the c a l c u l a t e d 1/m values i s shown i n F i g . 20 along with the r e s u l t obtained by ignor ing the over-lapp ing d i s s o c i a t i o n constants . The end r e s u l t s of the two approaches are very s i m i l a r ; ignor ing the over lapping K values gives k j ^ - = 3.17 x 10" 7 M " 1 sec" 1 and k A 2 - = 4.10 x 10" 7 M " 1 sec" 1 ; cons ider ing the over-lapping K values (and ignor ing the k^ A [ H 2 A ] term) gives k ^ - = 3.33 x x 10" 7 M * 1 sec" 1 and k A 2 - = 4.02 x 10" 7 M " 1 sec" 1 . 0 - | 1 1 1 1 1 1 0 1 2 3 4 6 6 7 1/m F i g . 20: P lo t s of (slope of k o b s v s . [HA"]) vs . 1/m for 3-methylglu-tarate monoanion/dianion; (a) ignor ing the over lapping K values (open c i r c l e s , s o l i d l i n e ) g i v i n g r = 0.9952, k ^ - = 3.17 ± 1.07 x 10" 7 M " 1 sec" 1 ( in tercept ) and k A 2 - = 4.10 ± 0.40 x 10" 7 M " 1 sec" 1 ( s lope) . (b) cons ider ing the over lapping K values (c losed c i r c l e s , dashed l i n e ) g i v i n g r = 0.9966, k ^ 3.33 ± 1.33 x 10" 7 M " 1 sec" 1 ( in tercept ) and k A 2 - = 4.02 ± 0.33 x 10" 7 M " 1 sec" 1 ( s lope) . - 106 I t i s p o s s i b l e to inc lude a c o r r e c t i o n for k j ^ A i n the l a t t e r t rea t -ment. Since the pK^ of the d i a c i d (4.35) i s c lose to that of phenyl-a c e t i c a c i d (4 .31) , the value for the monoacid (Table 7, p. 80) cou ld be used as an approximate value for k ^ ^ - Using t h i s value (1.92 x 10" 7 M " 1 sec" 1 ) and the concentrat ions determined p r e v i o u s l y , appro-p r i a t e k ^ ^ R ^ A ] terms are subtracted from k ^ g p r i o r to the p l o t t i n g of k obs v s • [HA"]. The net r e s u l t i s l i t t l e change i n the monoanion and d i a n i o n rate constants from that obtained by ignor ing any involvement of the d i a c i d ; k ^ - = 3.18 ± 1.35 x 10" 7 M " 1 sec" 1 and k A 2-= 4.04 ± 0.34 x 10" 7 M " 1 s ec" 1 . From these c a l c u l a t i o n s and s i m i l a r treatment of the data for 3 , 3 - d i m e t h y l g l u t a r i c a c i d and s u c c i n i c a c i d , i t i s obvious that ignor ing the over lapping d i s s o c i a t i o n s and assuming two d i s t i n c t i o n i z a t i o n s has only a l i t t l e e f f e c t on the values of rate constants obtained. For the sake of s i m p l i c i t y , the r e s u l t s quoted are those obtained by t r e a t i n g the two d i s s o c i a t i o n s (H2A/HA" and HA"/A ) as separate steps. For the second d i s s o c i a t i o n b u f f e r - r a t i o s ( [HA"] / [A 2 "]) l e ss than 1 are genera l l y chosen to help negate the small errors r e s u l t i n g from t h i s approach, i . e . b u f f e r r a t i o s with the d ian ion as the major of the three species and n e g l i g i b l e d i a c i d concentrat ions . For the f i r s t d i s s o c i a -t i o n ( k H ^ / k ^ - measurments) , buf fer r a t i o s ([H2A]/[HA" ]) greater than 1 are chosen i . e . buf fer r a t i o s with the d i a c i d as the major of the three species and n e g l i g i b l e d ian ion concentrat ions . The r e s u l t s for s u c c i n i c a c i d from both the n([H2A] / [HA"]) and m ( [HA"] / [A 2 "] b u f f e r - r a t i o s are shown i n F i g . 21; the two values of k ^ -r e s u l t i n g from each treatment agree reasonably w e l l . The r e s u l t from n - 107 2 3 n 0.2 0.4 0.6 m I o.e F i g . 21: (a) P lo t of (slope of k o b s vs . [HA - ] ) v s . n for s u c c i n i c acid/monoanion buffers g i v i n g r = 0.9998, k^ A = 2.44 ± 0.04 x I O - 7 M " 1 s e c - 1 (slope) and k ^ - = 2.45 ± 0.11" x 10" 7 M " 1 s e c ' 1 ( i n t e r c e p t ) . (b) P lo t of (slope of k o b s v s . [ A 2 - ] ) v s . m f o r succinate monoanion/dianion buffers g i v i n g r = 0.9793, SHA" 2.75 ± 0.57 x 10"7 M " 1 s e c ' 1 (slope) and k A 2 - = 4.96 ± 0.32 x 10" 7 M " 1 sec" 1 ( in tercept ) b u f f e r - r a t i o s gives a value of k ^ - = 2.45 ± 0.11 x 10" 7 M " 1 sec" 1 , while a value of 2.75 ± 0.57 x 10" 7 M " 1 sec" 1 i s obtained from the m b u f f e r r a t i o s . For 3 , 3 - d i m e t h y l g l u t a r i c a c i d , i t was impossible to determine a value of at the second d i s s o c i a t i o n buf fer values as i t was swamped by the l a r g e r d ian ion rate constant. The p l o t of k o b s v s . [A 2 "] at M values of 0.5 and 1 gives an average value of k A 2 - = 7.74 ± 0.02 x 10" 7 M " 1 sec" 1 ( s l ope ) . At buf fer r a t i o s c lose to the f i r s t d i s s o c i a t i o n , both kjjA- and kjj^A can be determined by p l o t t i n g the slope of ( k Q D S v s . [H 2 A]) against 1/n, g i v i n g r = 0.9976, k H A = 2.44 ± 0.07 x 10" 7 M " 1 sec" 1 ( in t ercept ) and k ^ - = 7.95 ± 0.55 x 10" 8 M " 1 sec" 1 ( s lope) . For the f i v e d i a c i d s j u s t d iscussed, s o l u b i l i t y i s no problem and the only l i m i t a t i o n s to obta in ing a p a r t i c u l a r rate constant are e i t h e r - 108 -( i ) a r e a c t i o n of the species present wth t r i i o d i d e ion or ( i i ) the fac t that the ra te constant makes a n e g l i g i b l e c o n t r i b u t i o n to the rate express ion In the case of aromatic d i c a r b o x y l i c a c i d s , s o l u b i l i t y i s a problem and measurements of k ^ A values are imposs ible . However, by working at b u f f e r r a t i o s favouring the d ian ion ( i . e . m < 1), the s o l u b i l i t y f a c t o r can be mi t iga ted somewhat, and measurements of k ^ -and k A 2 - can be made. For p h t h a l i c a c i d , a p l o t of (slope of k ^ g vs . [ A 2 - ] ) against m at four b u f f e r r a t i o s gave the fo l lowing r e s u l t s (0.05 M i o n i c s trength) ; r - 0.9876, k A 2 - = 2.78 ± 0.11 x 10" 7 M " 1 s e c - 1 ( in tercept ) k ^ - = 1.59 ± 0.18 x 10" 7 M " 1 sec" 1 ( s lope) . These r e s u l t s , and the r e s u l t s of the f i v e a l i p h a t i c c a r b o x y l i c acids are shown i n Table 14. In order to fur ther evaluate the s t e r i c e f f e c t of ortho subst i tuents i n aromatic c a r b o x y l i c a c i d s , we decided to study a group of i s o p h t h a l i c a c i d s . Measurements of the kjj A values are impossible due to the poor s o l u b i l i t y of the d i a c i d i n water. However, values of both k ^ - and k A 2 - should be a c c e s s i b l e . We needed a set of s e l f - c o n s i s t e n t pK values (measured i n water) for a group of both 5 - subs t i tu ted (meta) and 2 - subs t i tu ted (ortho) i soph-t h a l i c a c i d s . While data e x i s t for an extensive set of 5 - subs t i tu ted d e r i v a t i v e s i n 50 wt % aqueous methanol (GS84); pK values i n water have not been repor ted , except for the unsubst i tuted i s o p h t h a l i c a c i d ; pK^ = 3.62, p K 2 = 4.60 (KV61). A c c o r d i n g l y , we measured the f i r s t and second d i s s o c i a t i o n constants of seven 2 - s u b s t i t u t e d i s o p h t h a l i c acids and correc ted them to the standard s t a t e . These acids are so luble enough to al low accurate - 109 -Table 14: kHoA> kHA" a n d k A 2 - v a l u e s f ° r acetone e n o l i z a t i o n at 25°C for a group of a l i p h a t i c c a r b o x y l i c ac ids and p h t h a l i c a c i d . Ionic s trength 0.10 M unless otherwise s ta ted . A c i d i o 7 k H 2 A 10 7 km- 10 7 k A 2-M " 1 sec" 1 M " 1 s e c - 1 M " 1 sec" 1 P K 1 P K 2 Oxa l i c 95.1 ± 6 . 8 a 6.32 ± 0.53 0.505 ± 0.298 1.25 4.29 Die thy lmalonic 13.2 ± 0.4 - 15.9 ± 1 .5 b 2.21 7.29 3 - M e t h y l g l u t a r i c - 3.17 ± 1 .07 b 4.10 ± 0 .40 b 4.35 5 .44 c 3 ,3-Dimethyl - 2.44 ± 0.07 0.795 ± 0.055 7.74 ± 0 .02 b 3.85 6.45 c g l u t a r i c S u c c i n i c 2.44 ± 0.04 2.45 ± 0.11 4.96 ± 0.32 4.20 5 .63 d P h t h a l i c - 1.59 ± 0 .18 b 2.78 ± 0 .11 b 2.91 5 .41 e a Ion ic s trength v a r i e d from 0.1 to 0.2 M. b Ion ic s trength 0.05 M. c pK values from r e f . (BB65). d pK values from r e f . (AS84d). e pK values determined i n t h i s laboratory (NV87) 110 -determinations of the pK^ va lues . A group of seven 5 - subs t i tu ted i s o p h t h a l i c ac ids was a lso examined with the l i m i t a t i o n of decreased s o l u b i l i t y as compared to the 2 - subs t i tu ted ac ids . Accord ing ly the pK^ values determined for these seven acids have a r e l a t i v e l y large average d e v i a t i o n of ± 0.05; the r e s u l t s are l i s t e d i n Table 15 along with those of the 2 - s u b s t i t u t e d acids and the unsubst i tuted compound. The average d e v i a t i o n for a l l the pK values quoted, exc luding the pK]^  values of the 5 - s u b s t i t u t e d a c i d s , i s ± 0.02. For 5-bromoisophthal ic a c i d , quest ion-able r e s u l t s were obtained for p K 2 . The value of 4.57 i s too h igh on the bas i s of the values of the other 5-halo acids (5-F, 4.39; 5-1, 4.41) and so i t was d i scarded . Instead, both pK^ and p K 2 for t h i s bromo a c i d were determined from the Hammett p l o t for s i x 5 - subs t i tu ted i s o p h t h a l i c a c i d s . In the case of 5 -methyl i sophthal ic a c i d , where s o l u b i l i t y i s a major problem, pK values were a lso c a l c u l a t e d from the Hammett p l o t s . The Hammett p l o t s are shown i n F i g . 22 us ing a values recommended by P e r r i n , Demsey and Serjeant for meta subst i tuents (PD81), values that are l i s t e d i n Table 15. The r e s u l t i n g Hammett equations for pK^ and p K 2 are shown i n eqs. [3.30] and [3 .31] . The poorer c o r r e l a t i o n c o e f f i c i e n t for the pK^ l i n e r e f l e c t s the poorer degree of accuracy of the pK^ measurements due to poor s o l u b i l i t y . From these l i n e s , pK^ and p K 2 values for 5-bromo and 5 -methy l i sophtha l i c a c i d are determined, and these are l i s t e d i n Table 15. - I l l -Table 15: Dissociation constants of isophthalic acids in water at 25°C, corrected to zero ionic strength 3 Subst i tuent pK]^  p K 2 cr, H 3. .61 4, .75 0, .00 5-OH 3. .56 4, .62 0. .13 5-OCH 3 3. .46 4. .67 0. .12 5-1 3, .28 4. .41 0. .35 5-F 3. .24 4. .39 0. .34 5-N02 2, .88 4. ,04 0. .71 5-Br 3, ,21 b 4. ,36 b 0. ,39 5-CH3 3. .68 b 4. ,82 b -0. ,06 2-CH3 2. .92 4. .25 2-OCH3 2. .91 4. .32 2-NHCOCH3 3. .10 4. ,52 2 - C l 2. .12 3. .38 2-Br 1. .91 3. ,28 2-1 1. .94 3. ,32 2-N02 1. .85 3. ,01 pK values determined i n t h i s laboratory (NV87). pK values c a l c u l a t e d from the Hammett p l o t s , see t ext . - 112 -6 * . o - | 1 1 1 1 1 - 0 . 2 0.0 0.2 0.4 0.6 0.8 F i g . 22: P lo t of pK^ (lower l i n e ) and p K 2 (upper l i n e ) f or 5 - subs t i tu ted i s o p h t h a l i c ac ids i n water at 25°C against the Hammett meta-subst i tuent constant; the p values are 1.05 (pK^) and 1.02 ( p K 2 ) . r = 0.9893 p K x = - 1.05 a + 3.62 [3.30] r = 0.9973 p K 2 = - 1.02 a + 4.76 [3.31] The k i n e t i c treatment used to determine k ^ " a n d k A 2 - values i s the same as that used for p h t h a l i c a c i d . Using at l ea s t three buf fer r a t i o s favour ing the d ian ion (m = 0.8, 0 .5, 0.33, and 0.25) , and ignor ing the over lapping d i s s o c i a t i o n s , p l o t s of the slope of ( k O D S vs . [A 2 "]) against m a f f o r d k A 2 - as the in tercept and k ^ - as the s lope . For most of the i s o p h t h a l i c acids s tudied , c a t a l y s i s by the d ian ion was n e g l i -g i b l e . The r e s u l t s for i s o p h t h a l i c , 5 - n i t r o i s o p h t h a l i c and 2-bromo-i s o p h t h a l i c acids are shown i n F i g . 23. - 113 -0 0.6 1 m F i g . 23: P l o t s of (slope of k o b s v s . [A^" ]) v s . m for (a) i s o p h t h a l i c a c i d (open c i r c l e s ) g i v i n g r = 0.9996, k ^ - = 3.45 ± 0.07 x I O " 7 M " 1 sec" 1 (s lope) and k A 2 - = 8.49 ± 0.37 x 10" 8 M " 1 s e c 4 ( i n t e r c e p t ) . (b) 5 - N i t r o i s o p h t h a l i c a c i d (c losed c i r c l e s ) g i v i n g r = 0.9924, k ^ - 5.59 ± 0.69 x 10" 7 M " 1 sec" 1 and and k A 2 - = -6.23 ± 3.90 x IO" 8 M " 1 sec" 1 . (c) 2-Bromoisophthal ic a c i d (open squares) g i v i n g r = 0.9992, k H A - = 3.12 ± 0.09 x I O " 6 M " 1 sec" 1 and k A 2 - = -5.86 ± 4.54 x 10" 8 M " 1 sec" 1 . The r e s u l t s for eleven i s o p h t h a l i c ac ids ( i n c l u d i n g s i x 2 - subs t i -tuted) are l i s t e d i n Table 16; only two meaningful values of k A 2 - were obta ined, i . e . values for 5-methyl and the unsubst i tuted a c i d . The experimental r e s u l t s can be used to determine k ^ ' / k ^ - values tak ing account of the over lapping d i s s o c i a t i o n s of the two c a r b o x y l i c a c i d m o i e t i e s , as was i l l u s t r a t e d prev ious ly for 3 -methy lg lutar ic a c i d (p. 105) us ing eqs. [3 .16] - [3 .19] . The r e s u l t s d i f f e r s l i g h t l y from those obta ined by t r e a t i n g the two d i s s o c i a t i o n s as d i s t i n c t processes; - 114 -Table 1 6 : kHA.- a n a " ( s o m e ) k A 2 - values for acetone e n o l i z a t i o n at 25° C and 0.05 M i o n i c s trength for a group of i s o p h t h a l i c a c i d s . Rate constants are determined by ignor ing the over lapping d i s s o c i a t i o n s . Subst i tuent 10' k ^ - 10' k A 2 - b r a M ' 1 sec" 1 M " 1 sec" 1 5 - C H 3 2.86 ± 0.33 0.917 ± 0.123 3 H 3.45 ± 0.07 0.849 ± 0.037 4 5-Br 3.88 ± 0.23 -0.184 ± 0.085 3 5-1 3.97 ± 0.29 0.047 ± 0.110 3 5-N0 2 5.59 ± 0.69 0.623 ± 0.390 3 2-OCH3 6.56 ± 0.26 -0.195 ± 0.098 3 2-CH3 7.95 ± 0.61 -0.084 ± 0.230 3 2 - C l 25.2 ± 0.4 -0.521 ± 0.231 4 2-Br 31.2 ± 0.9 -0.586 ± 0.454 4 2-1 34.7 ± 1.5 1.44 ± 0.56 3 2-N0 2 34.6 ± 0.6 -0.600 ± 0.237 3 Number of buf fer r a t i o s used. 115 -the values of k j ^ - are a l l increased by a fac tor of approximately 1.2. The r e s u l t s us ing t h i s method are l i s t e d i n Table 17. A l l the r e s u l t s for the d i c a r b o x y l i c ac ids w i l l be discussed i n d e t a i l l a t e r . Table 17: k ^ - and (some) k A2- values for acetone enolization at 25°C and 0.05 M ionic strength for a group of Isophthalic acids. Rate constants are determined by considering the overlapping dissociations. Subst i tuent 10 1 k ^ - 10' k A 2 - b r a M " 1 sec" 1 M " 1 sec" 1 5 - C H 3 3.28 ± 0.27 1.09 ± 0.05 3 H 4.09 ± 0.06 0.985 ± 0.020 4 5-Br 4.77 ± 0.03 0.383 ± 0.004 3 5-1 4.88 ± 0.16 0.512 ± 0.039 3 5-N0 2 6.88 ± 0.47 0.157 ± 0.132 3 2-OCH3 7.23 ± 0.23 0.319 ± 0.057 3 2-CH3 8.09 ± 0.95 0.460 ± 0.266 3 2-C1 32.6 ± 0.9 0.289 ± 0.288 4 2-Br 43.3 ± 1.1 0.147 ± 0.331 4 2-1 47.2 ± 2.1 0.422 ± 0.586 3 2-N0 2 44.3 ± 3.9 1.08 ± 0.88 3 - 116 -3.2 Arylphosphonic ac ids 3 .2 .1 pK determinations There are a number of reports i n the l i t e r a t u r e of the e f f e c t of subs t i tuents on the pK^ and p K 2 values of arylphosphonic a c i d s , most notably those of J a f f e and co-workers (JF53, JF54) and of N u a l l a i n (N74). The data of J a f f e and co-workers inc lude ortho , meta and para d e r i v a t i v e s but the pK values are not thermodynamic values; the data of N u a l l a i n , which are much less extensive , have been correc ted for i o n i c s trength e f f ec t s but include only two ortho compounds. Since we needed a set of s e l f - c o n s i s t e n t pK values for our c a t a l y t i c work we have measured the f i r s t and second d i s s o c i a t i o n constants of 36 arylphos-phonic ac ids and correc ted them to the standard s ta te , and these are l i s t e d i n Table 18. As i n the case of carboxylate buf fers the rates of e n o l i z a t i o n of acetone were determined i o d o m e t r i c a l l y by fo l lowing the decrease i n the absorbance of the t r i i o d i d e i o n . Since K;L/K 2 ~ 10^, the two i o n i z a t i o n s of the d i a c i d are d i s t i n c t processes; the c a t a l y t i c a c t i v i t y of the d i a c i d and d ian ion can therefore be t rea ted separate ly , while the monoanion w i l l be invo lved with both of these spec ies . 3 .2 .2 Phosphonate dianions The dependence of k O D S upon the composit ion of the buf fers i s given - 117 Table 18: Dissociation constants of arylphosphonic acids in water at 25°C, corrected to zero ionic strength a Subst i tuent pK^ p K 2 H 1.86 7. 51 3 - C H 3 1.95 7. 64 4-CH3 2 .00 7. 68 4 - C 2 H 5 1.99 7. ,65 3-CH3O 1.74 7. 42 4-CH3O 2 .00 7. 68 4 - C 2 H 5 0 2 .00 7. 65 3 - F 1.53 7. .16 3-C1 1.53 7. ,10 4-C1 1.58 7. .23 4 - B r 1.54 7. ,18 4-CN 1.27 6. ,79 3 - N 0 2 1.20 6. .69 4 - N 0 2 1 .19 6. .67 4 - N H 2 1 7. .84 /3-naphthyl b 7. .42 3-carboxy 1.55 7. , 78 c > d 4-carboxy 1 .51 7. . 6 4 c ' e 3 , 4 - ( C H 3 ) 2 2 .04 7. .76 3 , 5 - ( C H 3 ) 2 2.01 7. .73 2-CH3 2 .08 7. ,92 2 - C 2 H 5 2.11 8. .09 2 - ( C H 3 ) 2 C H 2 .13 8. .18 2-CH3O 2 .21 8, .21 2 - C 2 H 5 0 2.32 8. .42 2 - F 1.49 7 .19 2-C1 1 .56 7 .39 2 -Br 1.53 7 .37 2-1 1.56 7 .46 2 - N 0 2 1.28 7 .05 a-naphthyl b 7 .64 2 , 3 - ( C H 3 ) 2 2 .17 8 .07 2 , 4 - ( C H 3 ) 2 2 .17 8 .07 2 , 5 - ( C H 3 ) 2 2 .10 8 .00 2 , 6 - ( C H 3 ) 2 2 .39 8 .62 2 , 4 , 6 - ( C H 3 ) 3 2 .53 8 .82 a pK values determined i n t h i s laboratory (NS87). D E r r a t i c values obtained, l i k e l y because of low s o l u b i l i t y . d p K 2 = 4.37 e p K 2 - 4.27 - 118 by eq. [3.20] which can be rewr i t t en as eqs. [3.21] or [3.22] , where m i s the buf fer r a t i o of monoanion to d ian ion ( [ H A " ] / [ A 2 " ] ) . k obs " k sum + kHA"[HA"] + k A 2 " [ A 2 " ] [3.20] k obs " k sum + [HA"] (kHA- + ( l /m)k A 2 "} [3.21] k obs = k sum + I a 2 " ] < kA 2~ + n>-kHA") .22] So a p l o t of k o b s v s . [HA"] should give a l i n e with slope {k^- + ( l / m ) k A 2 " ) , which can be p l o t t e d vs . 1/m to give k ^ - ( in tercept ) and kA " ( s lope) . The r e s u l t s for phenylphosphonate buffers are shown i n Table 19, and p l o t t e d i n F i g . 24, showing n e g l i g i b l e c a t a l y s i s by the monoanion. Likewise , the r e s u l t s for 3,4-dimethylphenylphosphonate are l i s t e d i n Table 20, and shown i n F i g . 25. I n d i v i d u a l sets of buf fer r a t i o s showed more i n t e r n a l s ca t t er i n pH values (± 0.05) than was the case with monocarboxylic ac ids (± 0.02), the var iance being more pronounced i n the higher pH va lues . This was a t t r i b u t e d to the low concentrat ions of buf fer used (0.002-0.02 M) and the wide span of concentrat ions used at each b u f f e r - r a t i o (general ly a f a c t o r of 8) . A l l the measurements for phosphonate dianions were made at 0.05 i o n i c s trength , which r e s u l t e d i n a pK^ 1 value = p K 2 ^ - 0.26, as c a l c u l a t e d from eq. [3.24] (AS84d). Ionic s trength e f fec t s are greater for monoanion/dianion e q u i l i b r i a (eq. [3.24]) than for a c i d / monoanion e q u i l i b r i a (eq. [3 .7]) ; for example us ing t h i s l a t t e r equation 6 - 119 -4 -LU O-O _ J CO IO 2-F i g . 24: P l o t of (slope of k o b s v s . [HA - ] ) vs . *-HA" 0.08 x 1/m f o r phenylphospho-x nate buf fer g i v i n g r = 0.9997, k H A - = -8.0 ± 10.2 10" 7 ( i n t e r c e p t ) and k A 2 " = 3.03 ± 10" 5 (s lope) Table 19: Resul ts of p l o t t i n g k o b s v s . [HA - ] f or phenylphosphonate monoanion/dianion buffers at 3 m values (m = [ H A ~ ] / [ A 2 - ] ) at 2 5 ° C and 0.05 M i o n i c s trength . 1/m pH 10 2 [HA"] 10 7 k o b s r 10 8 i n t e r c e p t 10 5 Slope M sec" 1 sec" 1 M " 1 sec" 1 6.98 1.367 2.12 0.481 6.97 0.820 1.35 1.0000 1.99 1.41 6.93 0.273 0.58 7.40 0.460 2.07 1.20 7.38 0.276 1.48 0.9987 4.74 3.50 7.34 0.092 0.78 7.47 0.355 2.64 1.85 7.45 0.213 1.82 0.9999 6.52 5.57 7.38 0.071 1.05 - 120 -Fig. 25: Table 20: Results of plotting k o b s vs. [HA"] for 3,4-dimethylphenyl-phosphonate monoanion/dianion buffers at 4 m values (m = [HA"]/[A2-]) at 25°C and 0.05 M ionic strength 1/m pH 102 [HA"] 107 k o b s r 108 intercept 105 Slope M sec" 1 sec" 1 M"1 sec 7 14 0 708 1. 70 0 472 7 09 0 425 1. 15 1 0000 3. 13 1.96 7 09 0 014 0. 589 7 23 0 454 1. 62 0 667 7 24 0 182 0. 889 0 9983 3. 72 2.77 7 21 0 091 0. 654 7 18 0 045 0. 461 7 47 0 379 2 32 1 00 7 44 0 227 1 74 0 9977 7. 01 4.33 7 38 0 076 1. 00 7 72 0 378 4 33 2 00 7 67 0 270 3 45 0 9993 11. 7 8.43 7 67 0 162 2 60 7 64 0 054 1 58 121 w i th an i o n i c s trength monoanion d i s s o c i a t i o n . H A V A 2 " p K 1 = p K T - ( 1 . 53457 l ) / ( l + l.bjl) [3.24] HA/A" pK 1 = P K T - (0 .5115 , / l ) / ( l + 1 . 5 7 1 ) [3.7] The average pH value of each buf fer r a t i o set genera l ly agreed with the c a l c u l a t e d p K 1 value us ing eq. [3.24]. As c a t a l y s i s by the monoanion i s n e g l i g i b l e , eq. [3.20] reduces to eq . [3.29] and k A 2 - w i l l simply be the slope of the l i n e obtained from a p l o t of k o b s v s . [ A 2 " ] . k obs = k sum + k A 2 " [A 2"] t 3 - 2 9 ! The r e s u l t s of phenylphosphonate and 3,4-dimethylphenylphosphonate b u f f e r s us ing eq. [3.29] give values for k A 2 - which agree w e l l with those obtained from F i g s . 24 and 25: for phosphonate the r e s u l t s are 3.03 ± 0.08 x 1 0 - 5 ( F i g . 24) and 2.95 ± 0.05 x I O " 5 (average of 3 v a l u e s , eq. [3 .29] , F i g . 26); for 3,4-dimethylphenylphosphonate the r e s u l t s are 4.24 ± 0.07 x 10" 5 ( F i g . 25) and 4.21 ± 0.08 x 10" 5 (average o f 4 va lues , eq. [3 .29] , F i g . 27). A c c o r d i n g l y for the other buf fer systems, k^2- was simply determined from the slopes of the l i n e s us ing eq. [3.29] . Two buf fer r a t i o s were s t u d i e d (m = 2, 1 or 0 .5); the values of k A 2 - from these determinations g e n e r a l l y agreed w i t h i n ± 3% of the average va lue . General ly four of 0.05 gives pK 1 = pK 1 - 0.09 for a monoacid/ 122 -oH 1 1 1 — i 0.0 2.0 4 . 0 6.0 8.0 1E3 [A2"] F i g . 26: P lo t s of k o b s v s . [ A / _ ] for phenylphosphonate b u f f e r s , m = 2.08 (open c i r c l e s ) , slope = 2.93 x 10" 5 ; m = 0.833 (open t r i a n g l e s ) , slope = 2.91 x 10" 5 ; m = 0.540 (open squares) , slope = 3.01 x 10" 5 ; average slope = k A 2 - = 2.95 ± 0.05 x 10" M " 1 S B f . ' 1 . 0 | i i 0.0 2.0 4 .0 e.o 1E3 [A1] F i g . 27: P lo t s of k o b s v s . [ A 2 - ] f or 3,4-dimethylphenylphosphonate, m = 2.00 (open c i r c l e s ) , slope = 4.22 x 10" 5 ; m = 1.00 (open t r i a n g l e s ) , s lope 4.33 x 10"^; m = 0.667 (open squares) , slope = 4.15 x 10" 5 ; m = 0.472 (open diamonds), slope = 4.16 x 10"^; average slope = k A 2 - = 4.21 ± 0.08 x 10"^ M " 1 sec" 1 . 123 -d i f f e r e n t concentrat ions at each buf fer r a t i o were examined. The r e s u l t s for twenty seven arylphosphonate dianions are shown i n Table 21, along with the r e s u l t s of two phosphonate-carboxylate t r i a n i o n s . In the case of these l a t t e r c a t a l y s t s , the dependence of k o b s upon the buf fer composit ion i s g iven by eq. [3.32] where £ i s the buf fer r a t i o of d i a n i o n to t r i a n i o n ( [ H A 2 - ] / [ A 3 " ] ) . k obs " ksum + [ A 3 ' ) < kA 3" + * k H A 2 " ' t 3 - 7 6 ] In these cases, K2 /K3 > 10 3 and involvement of H2A" i n the rate express ion i s n e g l i g i b l e . The t r i a n i o n c a t a l y t i c constants are deter-mined from the slopes of the l i n e s obtained from p l o t s of k o b s v s . [ A J ~ ] . The consis tency of r e s u l t s obtained i n t h i s way at d i f f e r e n t buf fer r a t i o s , X., ind ica tes the absence of any s i g n i f i c a n t c a t a l y s i s by the d i a n i o n , H A 2 " . The buf fer r a t i o s used were 0.8 and 0.5 and while the average d e v i a t i o n for 4 -CO2" phosphonate t r i a n i o n i s a r e l a t i v e l y large 7%, the use of eq. [3.32] leads to a s i m i l a r value of k A 3 - but a negative value of k^jA2-. This ind ica tes that the 7% average d e v i a t i o n i s a mani fes ta t ion of experimental e r r o r rather than the presence of a c o n t r i b u t i o n from HA 2 " to the k 0 D S va lue . 3.2.3 Phosphonic diacids U n l i k e the case of [HA"]/[A 2 "] b u f f e r s , with [H 2 A]/[HA"] b u f f e r s , the pH v a r i e d with concentrat ion , as i n the case of the [HA]/[A"] - 124 -Table 21: values for acetone enolization catalyzed by arylphos-phonates at 25°C and 0.05 M ionic strength, determined by plots of k o b s vs. [A 2 -] (eq. [3.29]), br is the number of buffer ratios used. Substituent 105 kA2-• M"1 sec - 1 br 4-N02 0. ,670 + 0. 040a 2 3-N02 0. ,732 + 0. 002 2 4-CN 0. ,788 + 0. 024 2 3-C1 1. .48 + 0. ,00 2 3-F 1. .42 + 0. ,01 2 4-Br 1. .77 + 0. ,02 2 4-C1 1. .67 + 0. ,02 2 2-Naph 2, .24 + 0. .07 2 H 2. .95 + 0. ,05 3 3-CH3 3. .22 + 0. ,13 2 4-CH3 3, .48 + 0. ,07 2 4-C2H5 3 .48 + 0. .03 2 3,5-(CH3)2 3. .88 + 0. .23 2 3,4-(CH3)2 4, .21 + 0. .08 4 3-C00" 2. ,36b + 0. .02 2 4-C00" 2, . 34b + 0. .16 2 2-N02 1, .09 + 0. ,01 2 2-F 1. .42 + 0. ,00 2 2-C1 1. .96 + 0. ,02 2 2-Br 2. .35 + 0. .05 2 2-1 3. .12 + 0. ,12 4 1-Naph 3. .44 + 0. .10 2 2-CH3 4. .99 + 0. ,05 2 2,5-(CH3)2 5. ,72 + 0. ,06 2 2,3-(CH3)2 6. ,20 + 0. 12 2 2,4-(CH3)2 6. ,51 + 0. 07 2 2-C2H5 6. ,52 + 0. 20 2 2-CH(CH3)2 7. .85 + 0. ,16 2 2,6-(CH3)2 15. .9 + 0. ,3 2 a Deviations quoted are average deviations in the case of 2 buffer-ratios and standard deviations in the case of 3 or more buffer ratios. b kA3-. - 125 -buf fer s for d i - and t r i - h a l o a l i p h a t i c c a r b o x y l i c a c i d s . A r e l a t i v e l y concentrated s o l u t i o n of buf fer i s needed for the n e u t r a l a c i d to make a s i g n i f i c a n t c o n t r i b u t i o n to the observed r a t e . For severa l of these compounds low s o l u b i l i t y prevents values of k ^ A be ing obtained. The magnitude of the k{^ A values determined i s such that c a t a l y s i s by the monoanion i s n e g l i g i b l e , a fac t that i s evident from the k i n e t i c r e s u l t s and so eq. [3.26] i s a p p l i c a b l e . k obs = kH+[H30 +] + k H 2 A [ H 2 A ] [3.26] Some of the phenylphosphonic acids that were examined are so luble i n water to such an extent as to al low a range of a c i d concentrat ions to be examined (0.01 — 0.1 M). For example, for 2-f luorophenylphosphonic a c i d , the data i n Table 22 can be used to provide the k^ A value by p l o t t i n g ( k Q D S — k^+[H30+]) against [H2A] , as was done for the d i - and t r i - h a l o a c e t i c ac ids us ing the p r e v i o u s l y determined kjj+ value (p. 83, I O " 5 M " 1 sec ) . The r e s u l t i n g p l o t i s shown i n F i g . 28 with a s lope , k j j ^ , of 2.67 ± 0.03 x 10" 5 M " 1 sec" 1 . On the other hand, a value of kj^A can be c a l c u l a t e d for each k i n e t i c run by d i v i d i n g ( k O D S —ky+[H30 +]) by [ H 2 A ] , as was done for 2 - n i t r o and 2 , 6 - d i n i t r o -benzoic a c i d , to give a value of 2.54 ± 0.12 x 10"-* M " 1 sec" 1 for k H ^ A ( i n d i v i d u a l values for each k i n e t i c run are given i n Table 22). For most of the phosphonic acids s tudied only a l i m i t e d range of a c i d concentra t ion was a c c e s s i b l e , undermining the a p p l i c a b i l i t y of determin-ing kjj^ A as the slope of ( k O D S - k^-K^O"1"]) against [ H 2 A ] . Rather the second method descr ibed above i s used to c a l c u l a t e k H ^A va lues . The 126 -Table 22: Results of the k i n e t i c runs for 2-f luorophenylphosphonic a c i d g i v i n g a value of k H 2 A = 2.54 ± 0.12 x 10" 5 M " 1 s ec" 1 , obtained by d i v i d i n g < k o b s - k H +[H 3 0 + ] ) by [ H 2 A ] , or k H 2 A = 2.67 ± 0.03 x 10" 5 M " 1 s ec" 1 , slope of ( k o b s - k H + [ H 3 0 + ] ) against [ H 2 A ] . pH 107 k o b s 107 ( k o b s - k H+[H 30 +]) 10 2 [H 2 A], M 105 k H A 1 1 1 sec" 1 sec" 1 M " 1 sec" 2.21 3.347 1.528 0.641 2.38 2.11 4.903 2.613 1.110 2.35 2.12 5.142 2.904 1.173 2.48 2.07 6.806 4.295 1.632 2.63 2.04 8.438 5.748 2.231 2.58 1.80 12.42 7.745 3.047 2.54 1.99 13.74 10.72 4.006 2.68 1.74 18.52 13.15 5.122 2.57 1.685 28.23 22.14 8.339 2.66 - 127 0.00 0.02 0.04 0.06 [H2A] 0.08 0.10 F i g . 28: P lo t of ( k o b s - k H +[H 3 0 + ] ) vs . [H 2A] for 2 - f luoropheny l -phosphonic a c i d g i v i n g r = 0.9997, k R A = 2.67 ± 0.03 x 10" 5 M " 1 sec" 1 (slope) and in tercept -273 ± 1.0 x 10" 8 " » _ 1 sec T h e . r e s u l t s for 20 arylphosphonic acids are given i n Table 23 us ing th i s method. The cons is tency of the k H ^ A values obtained for d i f f e r e n t k i n e t i c runs at v a r y i n g concentrat ions of the monoanion, HA", i l l u s t r a t e s the n e g l i g i b l e involvement of that species i n the rate law. This i s not s u r p r i s i n g when one considers that the order of magnitude of the k H A values i s comparable to the k A 2 - va lues , which were shown p r e v i o u s l y to completely swamp the monoanion rate constant . The k H ^ A values l i s t e d i n Table 23 d i f f e r s l i g h t l y from those reported i n r e f . (NS87), i n which we used the f igure of 2.84 x 10" 5 M " 1 sec" 1 (HK72) for k H +, rather than our own value of 2.95 x 10" 5 M " 1 128 -Table 23: k ^ A values for acetone e n o l i z a t i o n cata lyzed by ary lphos-phonic ac ids at 25°C and 0.1 M i o n i c s trength , determined by d i v i d i n g ( k o b s - k H +[H30 + ]) by [H 2A] for a number of k i n e t i c runs (nk) . Subst i tuent 10 3 k H A - M " 1 sec" 1 nk 4 - N 0 2 3. 09 + 0. 21 4 3 - N 0 2 3. 15 + 0. 05 3 4-CN 2. 89 + 0. 10 3 3-C1 2. 23 + 0. 08 4 3 - F 2. ,46 + 0. ,04 4 H 1. ,83 + 0. ,13 14 3 - C H 3 1. .69 + 0, .04 4 3 , 4 - ( C H 3 ) 2 1 .43 + 0 .03 4 3-COOH 2 .39 + 0 .08 3 3-CH3O 1 .87 + 0 .05 4 2 - N 0 2 3 .18 + 0 .14 4 2 - F 2 .54 + 0 .12 9 2 - C l 2 .40 + 0 .10 4 2 - B r 2 .82 + 0 .15 6 2-1 2 .65 + 0, .10 4 2-CH3 1 .62 + 0 .07 4 2 - C 2 H 5 1 .43 + 0, .05 4 2 - C H ( C H 3 ) 2 1. .29 + 0. .07 4 2 , 6 - ( C H 3 ) 2 1. .03 + 0. .02 4 2-CH3O 1. .36 + 0. .03 4 - 129 -3.2 .4 Phosphonate Monoanions At pH values between pK^ and p K 2 for phenylphosphonic a c i d s , the observed rate law i s given by eq. [3.33] and the concentrat ion r a t i o of monoanion to both d i a c i d and monoanion i s approximately one hundred, i . e . [HA"]/[H2A] * [HA"] / [A 2 - ] « 10 2 . k obs = k sum + k H 2 A [ » 2 A ] + kHA-tHA"] + k A 2 " [ A 2 " ] t 3 - 3 3 ] Knowing k s u m and the concentrat ion of the c a t a l y t i c species H 2 A and A 2 " (from the pH), as w e l l as k H ^ A and k A 2 - (Tables 23 and 24), i t should be poss ib le to determine the c o n t r i b u t i o n from the monoanion to kobs> a n d hence determine k j ^ - . Attempts were made with 3 -n i t ropheny l -phosphonic a c i d , phenylphosphonic a c i d and 3,4-dimethylphenylphosphonic a c i d to determine k j ^ - • Inconsis tent r e s u l t s were obtained despite the f a c t that (a) [HA"] genera l ly c o n s t i t u t e d between 95% and 99% of C^QJ and (b) kjr A-[HA"] c o n s t i t u t e d between 9% and 60% of k Q D S • The r e s u l t s are given i n Table 24 with 3-nitrophenylphosphonate monoanion showing a r e l a t i v e l y small 25% standard d e v i a t i o n , while the other two monoanions have much l a r g e r dev ia t i ons . - 130 -Table 24: k HA- v a l u e s f ° r acetone enolization catalyzed by arylphos-phonate monoanions at 25°C and 0.1 M ionic strength Substituent 10' kj^- M* sec" 1 nk a 3-N02 1.09 ± 0.26 3 H 1.43 ± 1.24 4 3 ,4- (CH 3 ) 2 1.97 ± 1.16 4 Number of kinetic runs. - 131 4. DISCUSSION 4.1 CARBOXYLATE BASE CATALYSIS 4.1 .1 Monoanions The data i n Table 7, p . 81 inc lude rate constants for fourteen a l i p h a t i c carboxylate bases which can be used to define a Bronsted l i n e . We f e e l , however, that the data for both chloroacetate and iodoacetate should be excluded from the l i n e a r regress ion as the standard dev iat ions for those p a r t i c u l a r rate constants are so h i g h , (as a r e s u l t of the greater magnitude of the carboxy l i c a c i d rate constant ) . Data for seven benzoate anions are given i n Table 11, p. 94. F ive of these k A - values can be used i n a Bronsted p l o t , while the n e g l i g i b l e value for 2-f luorobenzoate anion (a negative value) and the large standard d e v i a t i o n for 3-nitrobenzoate anion leads us to omit those two anions from any l i n e a r regress ion . The Bronsted p l o t for the twelve a l i p h a t i c carboxylate anions i s shown i n F i g . 29 and leads to eq. [4 .1] . Values of p and q are 1 and 2, r e s p e c t i v e l y , and the pK values at zero i o n i c s trength have been used i n the c o r r e l a t i o n . The agreement between eq. [4.1] and the c o r r e l a t i o n us ing the data of B e l l and L i d w e l l eq. [1.72] i s very good (BL40, p. 40) . - 132 pK + log p/q F i g . 29: Bronsted plot for catalysis of acetone enolization by carboxylate monoanions; al iphatic bases (open c i rc l e s ) , meta benzoate bases (open squares), ortho benzoate bases (closed squares) and three bases with large standard deviations (open diamonds); l ine drawn with respect to the al iphatic bases. - 133 12 bases log ( k A - / q ) = - 10.9 + 0.885 (pK + log p/q) [4.1] r = 0.9974 ± ± 0.1 0.020 4 bases l o g (k A -/q) = - 10-9 + 0.879 (pK + log p/q) [1.72] r = 0.9997 The k A - values for ch loroacetate , iodoacetate and 3-nitrobenzoate anion are shown i n F i g . 29, but have not been inc luded i n the c o r r e l a -t i o n , f or the reason discussed p r e v i o u s l y . The r e s u l t s for f i v e benzoates (two meta, two ortho and the unsubst i tuted anion) are also shown i n F i g . 29 and w i l l be discussed presen t ly . The fo l lowing points should be noted: 1. These r e s u l t s confirm the work of B e l l and L i d w e l l (BL40), us ing a much l a r g e r data set (twelve k A - values as opposed to f o u r ) . The 0 value obtained, 0.89 ± 0.02, ind icates a la te ( i . e . a p r o d u c t - l i k e ) t r a n s i t i o n s tate i n v o l v i n g almost complete t rans fer of the proton from acetone to the carboxylate anion. This i s i l l u s t r a t e d i n eq. [1.78] , where A" i s a carboxylate anion. [1.78 ] •f HA 2. The f i v e benzoate anion k A - values inc luded i n F i g . 29 f i t reasonably w e l l on the l i n e def ined by the twelve a l i p h a t i c carboxylate anions . The i n c l u s i o n of the three meta benzoates i n the c o r r e l a t i o n of the twelve a l i p h a t i c bases gives eq. [4.2] (B = 0 .91) , which d i f f e r s 134 s l i g h t l y from the o r i g i n a l c o r r e l a t i o n , eq. [4 .1]; the a d d i t i o n of the two ortho benzoates (eq. [4.3]) has no e f f e c t on the s t a t i s t i c s of eq. [4 .2 ] . 15 bases l og ( k A - / q ) = - H - 0 + 0.906 (pK + log p/q) [4.2] r = 0.9955 ± ± 0.1 0.024 17 bases l og ( k A - / q ) = - 11.0 + 0.911 (pK + log p/q) [4.3] r = 0.9955 ± ± 0.1 0.022 In the case of the two ortho benzoates ne i ther a s t e r i c a c c e l e r a t i n g e f f e c t nor a s t e r i c dece l era t ing e f f e c t i s evident . 3. I t can be suggested that the small number of benzoates s tudied and the inherent s c a t t e r i n the Bronsted p l o t i s masking any small s t e r i c e f f e c t . However, the s t e r i c a l l y crowded a l i p h a t i c carboxylate bases ( e .g . p i v a l a t e and cyclohexane carboxylate anion) f i t very w e l l on the def ined l i n e i n F i g . 29. This fac t corroborates the absence of any s t e r i c e f f ec t s i n the carboxylate base ca ta lyzed e n o l i z a t i o n of acetone. 4.1.2 Dianions Combining the d ian ion data of Table 14, p. 109 and Table 16, p . 114 gives us e ight k A 2 - values for acetone e n o l i z a t i o n ca ta lyzed by carboxylate d ian ions . The Bronsted p l o t for these e ight dianions i s - 135 -shown i n F i g . 30(a) ( i n v o l v i n g pK 2 of course) eq. [4 .4] . The a l i p h a t i c monoanion Bronsted l i n e i s inc luded i n F i g . 30(a) for a comparison with the d ian ions . While the value of p for both types of base i s 1, the value o f q (number of equivalent s i t e s for proton attachment) i s 2 for the carboxylate monoanions and 4 for the carboxylate d ian ions . 8 bases l og (k A 2- /q ) = - 9.71 + 0.516 (pK 2 + l og p/q) r = 0.9610 ± ± 0.30 0.061 [4.4] - 6 . 6 -CO o -7 . 6 --8 . 6 / • / • * * / * * 0/ / • / * / / / s / / O 2.6 6.6 pK + log p/q F i g . 30(a): Bronsted plot for catalysis of acetone enolization by carboxylate dianions (open squares, dashed l ine) ; Bronsted l ine for carboxylate monoanions added for comparison (open diamonds, sol id l ine ) . 136 -These r e s u l t s requ ire d e t a i l e d d i s c u s s i o n . 1. A l l the dianions i n F i g . 30(a) are less e f f e c t i v e as c a t a l y s t s than i s expected on the bas i s of the Bronsted l i n e for the carboxylate monoanions. S i m i l a r dev iat ions have been observed p r e v i o u s l y ; Spaulding and co-workers i n t h e i r study of acetone e n o l i z a t i o n drew a t t e n t i o n to the negative d e v i a t i o n of diethylmalonate d ian ion from the Bronsted l i n e for monoanions def ined by B e l l and L i d w e l l ' s data (SS77); S r i n i v a s a n and Stewart d i scovered that the presence of an a d d i t i o n a l u n i t of negative charge i n the c a t a l y s t reduced the e f fec t iveness of the carboxylate base i n removing a proton from the methylene carbon of a c a t i o n i c crea t ine d e r i v a t i v e , eq. [1.90] p. 61 (SS76a). 2. The values of k A 2 - used i n F i g . 30(a) are l i s t e d i n Table 25, which a l so contains the values for three of those dianions that were pre-v i o u s l y reported by other workers, values that agree reasonably with our data . The negative d e v i a t i o n of the d ian ion rate constants from the monoanion Bronsted l i n e cannot be a t t r i b u t e d to an i o n i c s trength e f f e c t . As was i l l u s t r a t e d p r e v i o u s l y i n our measurements of k A 2 - for diethylmalonate (p. 104), i o n i c s trength e f fec t s on the d ian ion rate constant are minimal; while the use of p K 2 * values (pK at the i o n i c s trength at which k A 2 - or k A - i s measured) may be more appropriate i n F i g . 30, such an adjustment s t i l l leads to negative dev ia t ions for the dianions with respect to the monoanions' Bronsted l i n e , a l b e i t a s l i g h t l y smal ler d e v i a t i o n ( for k A - at 0.1 M I , p K 1 = p K T - 0.11; for k A 2 - at 0.1 M I , p K 2 J = p K 2 T - 0.33 and at 0.05 M I , p K ^ 1 = p K 2 T -- 137 0.26) . I t i s a lso worth not ing that the use of the s t a t i s t i c a l f a c t o r s , p and q, has no bear ing on the magnitude of the d e v i a t i o n . Table 25: k A2- values for acetone enolization catalyzed by carboxylate dianions at 25°C and 0.05 M ionic strength unless otherwise stated. Literature values are included where available Dianion p K 2 10' k A 2 - L i t e r a t u r e M " 1 sec" 1 value Oxalate 4. .29 0. 505 a 0. ,617 b Isophthalate 4. .75 0. .849 -5-Methyl i sophthalate 4. .82 0. ,917 -Phthalate 5. .43 2. .78 -3-Methylg lutarate 5. .44 4. .10 -Succinate 5, .63 4. .96 a 5. ,17 b 3 ,3-Dimethylg lutarate 6 .45 7, .74 -Diethylmalonate 7. .29 15. .9 21. , 0 C Ionic s trength 0.1 M Data from r e f . (LA67), 0.2 M i o n i c s trength Data from r e f . (SS77) , 0.1 M i o n i c s trength - 138 3. Another s t r i k i n g feature of the k A 2 - values i n F i g . 30(a) (af ter the d e v i a t i o n i s observed), i s the r e l a t i v e l y poor c o r r e l a t i o n of the data to a l i n e a r regres s ion , r = 0.9610. The $ value for the e ight d ian ions , 0.52 ( ± 0 . 0 6 ) , i s very d i f f e r e n t from the value of 0.89 (± 0.02) obtained for the twelve a l i p h a t i c monoanions, suggesting a much e a r l i e r t r a n s i t i o n s t a t e . Perhaps the d ian ion data i s b e t t e r represented by a curve (concave to the pK axis) than a l i n e a r regress ion; or maybe the s c a t t e r i n the p l o t i s a mani fes tat ion of the var iance i n the s t r u c t u r a l type of c a t a l y s t used or a randomness a t t r i b u t a b l e to experimental e r r o r . 4. A n a l y s i s of the dianions on an i n d i v i d u a l bas i s has l e d us to the f o l l o w i n g conc lus ion: two of the dianions are d e v i a t i n g negat ive ly from a Bronsted l i n e def ined by the other s i x d ian ions , F i g . 30(b). The e x c l u s i o n of diethylmalonate and 3 ,3 -d imethy lg lutarate from the Bronsted c o r r e l a t i o n leads to eq. [4 .5] , an equation that i s a s t a t i s t i c a l improvement upon eq. [4 .4] , The /S value of 0.78 ( ± 0 . 0 7 ) resembles the value obtained for the monoanions. 6 bases log (k A 2- /q ) - - 10.8 + 0.776 (pK 2 + log p/q) [4.5] r = 0.9831 ± ± 0.3 0.072 The evidence support ing th i s conc lus ion w i l l now be presented. For most d i c a r b o x y l i c ac ids a s t a t i s t i c a l fac tor of 4 and an e l e c t r o s t a t i c e f f e c t account for the value of the K^/K^ r a t i o (S85g). The s t a t i s t i c a l f a c t o r fol lows from the fac t that w i l l be twice as large as i t would - 139 pK + log p/q Fig . 30(b): Bronsted plot for catalysis of acetone enolization by six carboxylate dianions (open squares, so l id l ine) with two deviating dianions (closed c i rc le s ) ; Bronsted l ine for carboxylate monoanions added for comparison (open diamonds, dashed l ine ) . 140 -otherwise be and K 2 i s h a l f as large as i t would otherwise -be. The e l e c t r o s t a t i c e f f e c t deals with the d i s s o c i a t i o n of the second carboxyl group i n the molecule a lready possessing one u n i t of negative change; t h i s e f f e c t depends on the distance between the two carboxyl groups (HW82). For some d i c a r b o x y l i c ac ids a t h i r d f a c t o r i s re l evant to the K i / K 2 r a t i o . In the monoanion of the d i a c i d , hydrogen-bonding may occur between the carboxyl hydrogen and the carboxylate group; t h i s w i l l r e s u l t i n a l a r g e r and a smal ler K 2 than would otherwise be the case. The departure of K ^ / 4 K 2 from u n i t y i s a measure of both the e l e c t r o -s t a t i c e f f e c t and the hydrogen-bonding e f f e c t . In 1956, Westheimer and Benfey formulated a method for the q u a n t i t a t i v e eva luat ion of the hydrogen-bonding i n the monoanion (WB56). They suggested a comparision of K-L , the d i s s o c i a t i o n constant of the d i c a r b o x y l i c a c i d , with Kg the d i s s o c i a t i o n constant of the monomethyl ester of that a c i d . Without any hydrogen-bonding, K^ should be twice as great as Kg, due to the s t a t i s t i c a l f a c t o r , assuming that the e l e c t r o n i c e f fec t s of carboxyl and carbomethoxyl are equiva lent . However, i n the presence of hydrogen-bonding, K^ should be more than 2Kg; how much more r e f l e c t s the degree of hydrogen-bonding i n the monoanion of the d i a c i d . Thus the departure of K"L/2Kg from u n i t y i s a measure of the hydrogen-bonding e f f e c t . The f i r s t d i s s o c i a t i o n constant of p h t h a l i c a c i d i s 1.2 x 10" 3 (K^) while the d i s s o c i a t i o n constant of mono-methyl phthalate i s 0.6 x 10" 3 (Kg); thus for these compounds K^/2K£ ~ 1, i l l u s t r a t i n g the absence of any hydrogen-bonding e f f e c t . On the other hand, for d ie thy lmalonic a c i d K^/2Kg ~ 16, i l l u s t r a t i n g the presence of a hydrogen-bonding e f fec t - 141 -(WB56). In the case of ( ± ) - 2 , 3 - d i - t e r t - b u t y l s u c c i n i c a c i d , a value of 10^ i s obtained for K i / 2 K g whereas the value for s u c c i n i c a c i d i s 1 (S85 g) . The former i s a t y p i c a l case of the Thorpe-Ingold e f f e c t , where the hydrogen-bonded monoanion r e l i e v e s some of the s t e r i c s t r a i n r e s u l t i n g from the presence of the two t e r t - b u t y l groups (JG84). We have inves t iga ted the r e l a t i o n s h i p between the degree of devia-t i o n of a l l the dianions from the monocarboxylate Bronsted l i n e ( F i g . 30(a)) and the degree of hydrogen-bonding i n the monoanion. The l a t t e r quant i ty i s measured by the value of K^/2Kg. The former quant i ty i s measured by the r a t i o of the c a l c u l a t e d second d i s s o c i a t i o n constant of the d i a c i d , K 2 c a l c , to the measured second d i s s o c i a t i o n constant of the d i a c i d K 2 o b s . The value of K 2 c a l c i s a v a i l a b l e from eq. [4.1] by s u b s t i t u t i n g the measured value for k A 2 - in to eq. [4 .1] , the Bronsted l i n e def ined by the twelve a l i p h a t i c monobasic carboxylates . Thus K 2 c a l c i s the d i s s o c i a t i o n constant of the monoanion, HA", expected on the bas i s of the monobasic (A") Bronsted l i n e . log (k A 2- /4 ) - - 10.9 + 0.885 (pK 2 + log 1/4) [4.1] The r e s u l t s of both K;[/2K E and K 2 c a l c / K 2 o b s for the e ight dianions c a t a l y s t s are given i n Table 26. While the K i / 2 K E values for three of the c a t a l y s t s s tud ied are a v a i l a b l e (S85g, WB56), we needed the Kg values for f i v e mono-methyl e s t ers . For the two mono-methyl i sophtha l -ates (meta-methyl and unsubst i tu ted) , pKg values can be c a l c u l a t e d on the b a s i s of the Hammett equation for subs t i tu ted benzoic a c i d s , (eq. [4 .6 ] ) , us ing subst i tuent constant (a) values of 0.32 for meta-C0 2CH3 - 142 -Table 2 6 : K J ^ K J , and K 2 C A L C / K 2 O B S values for e ight c a r b o x y l i c d i p r o t i c ac ids A c i d K ] / 2 K E K 2 c a i c / K 2 O x a l i c 1. .0 2. .0 I s o p h t h a l i c 0. .93 3. .2 5 -Methy l i sophtha l i c 0, .91 3, .5 P h t h a l i c 1. .1 4, .0 3 - M e t h y l g l u t a r i c 1. .0 2, .6 S u c c i n i c 1. .1 3. .3 3 , 3 - D i m e t h y l g l u t a r i c 5, .0 13 Die thy lmalonic 16 41 and -0.06 for meta-CH 3 (PD81). Thus p K E of 3.88 (H) and 3.94 (meta-CH 3) are obtained for the mono-methyl i sophthalates pK = 4.20 - 2 a [4.6] The f i n a l three mono-methyl esters (oxalate , 3-methylglutarate and 3 ,3 -d imethy lg lu tarate ) were synthesized i n our laboratory and the pK E values determined (NV87). - 143 -The data i n Table 26 show a c o r r e l a t i o n between the degree of hydrogen-bonding i n the monoanion (as measured by K-^/2K^) and the degree of h o r i z o n t a l d e v i a t i o n (along the pK axis ) of the d ian ion from the monocarboxylate Bronsted l i n e (as measured by K 2 c a l c / K 2 o b s ) . For the s i x d i a c i d s with K^/2Kg values c lose to 1.0 (± 0 .1 ) , suggesting the absence of a hydrogen-bonding e f f e c t , the values of K 2 c a l c / K 2 o b s are c lose to 3 (± 1) , r e f l e c t i n g a small but cons i s tent negative d e v i a t i o n from the monocarboxylate Bronsted l i n e . Thus these s i x dianions should be grouped together, to give a Bronsted l i n e , almost p a r a l l e l to but d i s p l a c e d below the monocarboxylate Bronsted l i n e , eq. [4.5] F i g . 30(b). On the other hand, d ie thylmalonic and 3 , 3 - d i m e t h y l g l u t a r i c a c i d have K^/2K£ values w e l l above u n i t y (16 and 5.0 r e s p e c t i v e l y ) , i l l u s t r a t i n g the presence of a hydrogen-bonding e f f e c t i n the monoanion, the e f f e c t be ing greater for the diethylmalonate monoanion. The values for K 2 c a l c / K 2 o b s c o r r e l a t e with the K 1 / 2 K £ values for these substrates , the l a r g e r K 2 c a l c / K 2 o b s value ( i . e . greater d e v i a t i o n from the monocarboxylate Bronsted l i n e ) occurr ing for diethylmalonate d ian ion . I t can now be seen that a more appropriate view of the s i t u a t i o n i s to consider the two dianions whose conjugate ac ids HA" possess i n t e r n a l hydrogen-bonding as dev ia t ing from the Bronsted l i n e for the other s i x d ian ions , eq. [4 .5 ] . This d e v i a t i o n i s a h o r i z o n t a l displacement along the pK axis and can be explained as fo l lows . The K 2 values of d ie thy lmalonic a c i d and 3 , 3 - d i m e t h y l g l u t a r i c a c i d are l a r g e r than would otherwise be expected, owing to the presence of hydrogen-bonding i n the monoanion. I f the proton t r a n s f e r from acetone to the i on A 2 " i s normal i n the sense that the e f f ec t of nearby subst i tuents on the t r a n s i t i o n 144 -s tate and on the products i s s i m i l a r , we would expect no dev iat ions from the Bronsted l i n e . The fac t that dev iat ions are observed ind ica te s that there i s a d i f f erence i n the e f f ec t of hydrogen-bonding on the d i a n i o n / monoanion e q u i l i b r i u m and the e f f e c t i n the t r a n s i t i o n s ta te . I f the hydrogen-bonding i n the monoanion i s ne i ther a hindrance nor a help to the proton a b s t r a c t i o n from acetone by the d ian ion , the k A 2 ~ values for the two dianions w i l l r e f l e c t the K 2 value expected on the bas i s of no hydrogen-bonding. We can c a l c u l a t e the K 2 values of the ' d e v i a t i n g ' dianions expected on the bas i s of no hydrogen-bonding i n the monoanion with eq. [4 .5 ] , the Bronsted l i n e for s i x d ian ions . The r e s u l t s can be compared with the observed values of K 2 , the r a t i o i n d i c a t i n g the a c i d weakening e f f e c t of hydrogen-bonding i n the monoanion, i . e . K 2 c a l c / K 2 o b s . Of course, for the s i x dianions used to define the d ian ion Bronsted l i n e , values of K 2 c a l c / K 2 o b s are c lose to u n i t y (± 0 .4 ) . (The r a t i o K 2 c a l c / K 2 o b s used here d i f f e r s from that used i n Table 26, where the monocarboxylate Bronsted l i n e (eq. [4.4]) was used as the bas i s for d e f i n i n g K 2 c a l c ) . This cou ld be the f i r s t q u a n t i t a t i v e measure of the hydrogen-bonding e f f e c t on K 2 values of d i p r o t i c carboxy l i c a c i d s . I t comes over t h i r t y years s ince Westheimer and Benfey q u a n t i f i e d the e f f e c t of hydrogen-bonding on values of such acids (WB56). Thus, f or 3 ,3 -d imethyl -g l u t a r i c a c i d , the a c i d strengthening e f f e c t on due to hydrogen-bonding i n the monoanion i s 5.0 ( K ^ / 2 K £ ) ; the a c i d weakening e f f e c t on K 2 due to hydrogen-bonding i n the monoanion i s 3.8 ( K 2 c a l c / K 2 o b s ) . In the case of d ie thy lmalonic a c i d , the a c i d strengthening e f f ec t on i s 16 while the a c i d weakening e f f ec t on K 2 i s 10. A p l o t of K 2 c a l c / K 2 o b s 145 against K^/2K£ i s shown i n F i g . 31, i l l u s t r a t i n g the l i n e a r r e l a t i o n s h i p between the two q u a n t i t i e s . The slope of the l i n e i s 0.6 (obtained by e i t h e r i n c l u d i n g a l l e ight points i n the c o r r e l a t i o n or j u s t i n c l u d i n g the two 'hydrogen-bonded' p o i n t s ) ; thus the a c i d strengthening e f f ec t on K 2 of hydrogen-bonding i n the monoanion i s approximately 60% of the r e l a t e d a c i d weakening e f fec t on . I t must be s a i d , though, that more data are needed ( i . e . k A 2-va lues and hence K 2 c a l c values) before a thorough, c r i t i c a l assessment of the r e l a t i o n s h i p between K 2 c a - ' - c / K 2 0 k s and K i / 2 K g can be made; while more k A 2- values that co inc ide with eq. [4.5] would help towards a refinement of that Bronsted l i n e (and thus a refinement of the degree of d e v i a t i o n of c e r t a i n k A 2 - va lues ) , severa l 12 0 4 8 12 16 * l / 2 K E F i g . 31: P l o t of K 2 c a l c / K 2 o b s against K^/2K£ f o r a set of d i c a r b o x y l i c a c i d s ; K 2 values c a l c u l a t e d from eq. [4 .5 ] ; l i n e drawn f o r a l l po in ts g i v i n g r = 0.9968, slope = 0.59 ± 0.02, in te rcep t = 0.57 ± 0.12. 146 -more d e v i a t i n g k A 2 - values are needed to probe the aforementioned r e l a t i o n s h i p . The choice of d i a c i d s to study i n order to observe dev ia t ions from the d ian ion Bronsted l i n e i s obvious from the large compi la t ion of K ^ / 2 K g values a v a i l a b l e (S85g). T h i s d i s c u s s i o n presupposed the absence of an e f f e c t i n the t r a n s i -t i o n s tate a t t r i b u t a b l e to hydrogen-bonding i n the monoanion. However, as shown below, the system could be operat ing such that an e f f e c t i s f e l t by the t r a n s i t i o n state i . e . the second carboxylate could be c o o r d i n a t i n g the proton that i s being abstracted by the f i r s t carboxy-l a t e u n i t . • . : H - C The slope of 0.6 that was der ived from our c o r r e l a t i o n of K 2 ° a / K 2 ° D S and K ^ / 2 K g , could be r e l a t e d to the magnitude of the hydrogen-bonding e f f e c t i n the t r a n s i t i o n s ta te , i . e . t h i s l a t t e r fac tor may be only 40%, (100-60%), of the r o l e played by hydrogen-bonding i n the e q u i l i b r i u m a c i d s trength of the monoanion. I f t h i s i s the case, the d e v i a t i o n for these dianions could be dependent on the c a t a l y s t , the substrate and the r e a c t i o n . On the other hand, i f the f i r s t explanat ion i s the c o r r e c t one, ( K 2 c a l c / K 2 ° b s measuring the hydrogen-bonding e f f ec t on K2) changing e i t h e r the substrate or the r e a c t i o n w i l l have no e f f ec t on the magnitude of the e f f e c t . A study could be undertaken to decipher the c o r r e c t i n t e r p r e t a t i o n . - 147 -5. The large d e v i a t i o n of diethylmalonate d ian ion from that expected on the b a s i s of the monocarboxylate Bronsted l i n e for acetone e n o l i z a t i o n has been reported p r e v i o u s l y (SS77). The d e v i a t i o n ( c i r c a 1 log un i t ) has a l so been observed i n the h y d r a t i o n of a number of a l i p h a t i c aldehydes and the mutarotat ion of glucose, react ions subject to both general a c i d and general base cata lyses (PD69). U n t i l now, no adequate exp lanat ion has been o f fered for the abnormally low c a t a l y t i c a c t i v i t y of t h i s d i a n i o n . (Unfortunately the data for a l l these react ions i s very sparse , making an a n a l y s i s , as descr ibed i n p. 146, i n c o n c l u s i v e . ) 6. I t may be r e c a l l e d that a study of the e n o l i z a t i o n of 3 -n i t ro - (+ ) -camphor ca ta lyzed by f i v e monocarboxylate bases, one d icarboxy la te base (malonate dianion) and mono-hydrogen phosphate d ian ion , af fords a curved Bronsted p l o t (BG76, p. 46). The curvature i s dependent on the i n c l u -s i o n of the two dianions i n the Bronsted p l o t and i s therefore quest ion-able i n the l i g h t of our r e s u l t s for a wide s t r u c t u r a l range of d i c a r -boxylate d ian ions . A be t t er i n t e r p r e t a t i o n of the data i s to consider a l i n e a r Bronsted l i n e def ined by the f i v e monoanions, with the two dianions d e v i a t i n g negat ive ly from t h i s l i n e , an i n t e r p r e t a t i o n sup-ported by our r e s u l t s . 7. A c r i t i c a l quest ion has been purposely l e f t unanswered i n our d i s c u s s i o n thus f a r . Why are d icarboxyla te bases less e f f e c t i v e as c a t a l y s t s than monocarboxylate bases i n the e n o l i z a t i o n of acetone? One o f the p r e r e q u i s i t e s to obta in ing a l i n e a r Bronsted p l o t i s that the c a t a l y s t s used i n the c o r r e l a t i o n must be s t r u c t u r a l l y s i m i l a r ; th i s - 148 -i s p a r t l y an e m p i r i c a l observat ion suggested by c o n s i d e r a t i o n of the vas t number of documented Bronsted c o r r e l a t i o n s . Deviat ions from Bronsted l i n e s , when c a t a l y s t s of d i f f e r e n t s t r u c t u r a l type are inc luded , are c r e d i t e d to an e f fec t due to the d i f f erence i n the types of c a t a l y s t s tud ied . Information can a lso be gleaned from Bronsted p l o t s where c a t a l y s t s of d i f f e r e n t s t r u c t u r a l type c o l l e c t i v e l y give a l i n e a r c o r r e l a t i o n . I t has long been observed that c a t a l y s t s of d i f f e r e n t charge type can often l ead to dev ia t ions , both p o s i t i v e and negative (K73). A study by Kresge and co-workers i n v o l v i n g the h y d r o l y s i s of v i n y l ethers i l l u s t r a t e s such a s i t u a t i o n (KC73b, CE77). This r e a c t i o n involves rate determining proton t rans fer from a general a c i d to the substrate (A—Sg2, eq. [1 .9] , p. 6) and leads to a good Bronsted c o r r e l a t i o n for a set of n e u t r a l carboxy l i c a c i d s . A group of amino ac ids forms a d i s t i n c t l i n e , p a r a l l e l to but d i sp laced downward from the c a r b o x y l i c a c i d l i n e , genera l ly by a fac tor of two i n k j ^ . On the other hand, a number of a l k y l monohydrogen phosphonate anions define a l i n e of l a r g e r s lope , above, the carboxy l i c a c i d l i n e . The rate a c c e l e r a t i o n f a c t o r v a r i e s , depending on the substrate s tudied , but i s greater than the d e c e l e r a t i o n f a c t o r for the amino a c i d s . The authors a t t r i b u t e such e f f ec t s to a charge i n t e r a c t i o n i n the t r a n s i t i o n s ta te , where the substrate i s tak ing on p o s i t i v e charge. An i n t e r a c t i o n between t h i s charge and the p o s i t i v e charge i n the amino acids w i l l be r e p u l s i v e , r a i s i n g the energy of the t r a n s i t i o n state and l eading to negative dev ia t ions from the Bronsted l i n e for n e u t r a l c a r b o x y l i c a c i d s . In the case of phosphonate monoanions, which are acids possess ing a negative - 149 -subs t i tuent , the i n t e r a c t i o n w i l l be a t t r a c t i v e and have the opposite e f f e c t to that for the amino ac ids . These i n t e r a c t i o n s are a f f e c t i n g AG 5*, not AG°, and thus lead to deviat ions from the r a t e - e q u i l i b r i u m c o r r e l a t i o n . The greater magnitude of the p o s i t i v e d e v i a t i o n as compared to the negative d e v i a t i o n r e f l e c t s ( i ) the c lose l o c a t i o n of the negative charge to the a c i d i c proton i n the phosphonate monoanions and ( i i ) the i n t r i n s i c aim of both systems to minimize the t r a n s i t i o n s ta te energy ( i . e . maximum rate a c c e l e r a t i o n and minimum rate dece ler-at ion) . Our r e s u l t s for base ca ta lyzed e n o l i z a t i o n of acetone could be e l e c t r o s t a t i c i n nature . The negative d e v i a t i o n of the dianions from the monoanion l i n e would then be c r e d i t e d to an i n t e r a c t i o n that r a i s e s the t r a n s i t i o n state energy. The r o l e of an a d d i t i o n a l u n i t of negative charge i n the c a t a l y s t causing a r e p u l s i v e , e n e r g y - r a i s i n g i n t e r a c t i o n i s unc l ear . Such an i n t e r a c t i o n should be r e l a t e d to the distance separat ing the two carboxylates; increas ing t h i s dis tance should decrease the e f f e c t and therefore minimize, i f not o b l i t e r a t e , the d e v i a t i o n for the d ian ions . This i s not the case; the set of dicarboxy-l a t e s which form the Bronsted l i n e i n F i g . 30(b) cover a wide s t r u c t u r a l type but d i s p l a y no r e l a t e d perce ivable trend i n t h e i r degree of d e v i a t i o n from the monocarboxylate l i n e . Thus an e l e c t r o s t a t i c i n t e r a c -t i o n that i s lowering the t r a n s i t i o n state energy seems implaus ib le . We w i l l d iscuss other poss ib le explanations for t h i s e f f e c t at a l a t e r stage. - 150 -4.2 C A R B O X Y L I C A C I D C A T A L Y S I S 4 .2 .1 Monoprotic acids The data i n Table 7, p. 81 and Table 9, p. 88 inc lude rate constants f o r twenty two a l i p h a t i c c a r b o x y l i c ac ids ; Table 11, p. 94 contains va lues for nine benzoic ac ids . The Bronsted p l o t for a l l of t h i s data i s presented i n F i g . 32. C a r e f u l ana lys i s of the informat ion a v a i l a b l e from F i g . 32 w i l l now be presented. Cons ider ing the fourteen a l i p h a t i c c a r b o x y l i c ac ids i n c l u s i v e of c h l o r o a c e t i c a c i d and weaker a c i d s , we can compare our r e s u l t s with those of B e l l and L i d w e l l cover ing the same pK range. The values of k j ^ that are used for iodoacet ic and c h l o r o a c e t i c are those from Table 7 (method I ) , p. 80. The Bronsted l i n e for t h i s group of ac ids i s shown i n F i g . 33, and i s defined by eq. [4 .7] . The agreement between t h i s l i n e and the r e s u l t s of B e l l and L i d w e l l i s reasonable (eq. [1 .71] , BL40). 14 acids r = 0.9900 log ( k ^ / p ) = - 4.33 0.605 (pK + log p/q) + [4.7] 0.025 4 acids r = 0.9995 log (kj^/p) = - 4.46 0.569 (pK + log p/q) [1.71] - 151 -pK + log p/q Fig . 32: Bronsted plot for catalysis of acetone enolization by carboxylic monoprotic acids; 22 al iphatic acids (open c i r c l e s ) , 4 meta benzoic acids (open squares), 5 ortho benzoic acids (closed c ircles) and 3 ammonio carboxylic acids (open triangles) . Line drawn for al iphatic carboxylic acids. - 152 -6.6 -7.6 I i 1 1 1 2.4 2.0 3.4 3.9 4 .4 4.0 pK + log p/q F i g . 33: Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by c a r b o x y l i c ac ids The fo l l owing points should be noted: 1. These a l i p h a t i c c a r b o x y l i c acids give an a value of 0.605 ± 0.025, s l i g h t l y l a r g e r than that obtained by B e l l and L i d w e l l who used a much smal ler data set . This a value ind ica tes a /9 value of 0.395 for the base ca ta lyzed proton a b s t r a c t i o n from protonated acetone. I t may be r e c a l l e d that the general a c i d ca ta lyzed e n o l i z a t i o n of acetone involves two steps; the f i r s t involves e q u i l i b r i u m protonat ion of the carbonyl - 153 -oxygen; the second involves the a b s t r a c t i o n of a hydrogen from proto-nated acetone by the conjugate base of the general a c i d (eq. [1.10] , p. 48). A 8 value of 0.395 for the second step ind ica te s a t r a n s i t i o n s tate i n which the proton i s l e ss than h a l f - t r a n s f e r r e d , that i s , a t r a n s i t i o n s tate that resembles reactants as shown i n eq. [1.10b], HA being a c a r b o x y l i c a c i d . The same process i n v o l v i n g unprotonated acetone has a B value of 0.89; the much smal ler 8 value obtained with protonated acetone r e f l e c t s the degree of a c t i v a t i o n conferred on acetone on being protonated, l ead ing to an e a r l i e r , more r e a c t a n t - l i k e t r a n s i t i o n s ta te . One of the aims of t h i s study i s to inves t iga te s t e r i c e f f ec t s on acetone e n o l i z a t i o n . With data now a v a i l a b l e for f i v e ortho benzoic ac ids and four meta benzoic a c i d s , as w e l l as a number of s t e r i c a l l y crowded a l i p h a t i c a c i d s , we can evaluate t h i s e f f e c t . However two other e f f ec t s r e l a t e d to the d i - and t r i - h a l o a l i p h a t i c c a r b o x y l i c ac ids w i l l be addressed f i r s t . 2. The Bronsted l i n e shown i n F i g . 32 i s drawn for a l l the nineteen a l i p h a t i c a c i d s , eq. [4 .8 ] . The s t a t i s t i c s of the l i n e a r regres s ion are an improvement upon eq. [4 .7 ] , a Bronsted l i n e obtained by exc luding the f i v e ' s t r o n g ' h a l o - a c i d s . C H 2 •f HA [1.10b ] - 154 19 a c i d s r = 0.9961 log (k^/p) - - 4.42 - 0.583 (pK + log p/q) + + 0.04 0.013 [4.8] The a values of both lines are similar, eq. [4.8] having the smaller a and the smaller standard deviation, 0.583 ± 0.013. However, we believe that this group of al iphatic acids is more properly repre-sented by a gentle curve, concave to the pK axis; a curve that includes the dif luoro- and trif luoroacetic acids, but has the dichloro- , t r i -chloro- and tribromoacetic acids as positive deviations, F ig . 34. - 4 .a CB O / CBr 3C0 2H C C I 3 C O 2 H CCI2HC02H CF 3C0 2H CF2HC02H CICH2C02H , ICH2C02H X). CP-3ft 2.5 pK + log p/q F i g . 34: Brons ted p l o t f o r c a t a l y s i s o f acetone e n o l i z a t i o n by n ine t een c a r b o x y l i c a c i d s ; curved l i n e hand-drawn f o r s i x t e e n o f the a c i d s (open c i r c l e s ) ; d i c h l o r o - , t r i c h l o r o - and t r i b r o m o a c e t i c a c i d s a l s o present (open squares ) . - 155 -The reasons for the conc lus ion are the fo l l owing . The values for the ' s t r o n g ' h a l o - a c i d s are very p r e c i s e , the standard deviat ions of between 2% and 5% being adequately represented by the span of the c i r c l e s and squares i n F i g . 34. The pK values of these ac ids have been measured i n t h i s l abora tory . The l i t e r a t u r e r e s u l t s , where a v a i l a b l e , agree reasonably w e l l with our r e s u l t s (Table 9, p. 88, NV87). In a comparison of the d i - and t r i - h a l o a c e t i c a c i d s , f l u o r i n e and c h l o r i n e be ing the halogens, we f i n d that the c h l o r o - a c i d s are more e f f e c t i v e as c a t a l y s t s than the f l u o r o - a c i d s (a f a c t o r of 1.3 for the t r i - h a l o acids and 1.5 for the d i - h a l o a c i d s ) . This fac t i s c l e a r l y evident from F i g . 14, p . 86, where the p l o t s of ( k Q D S - k H +[H30 + ]) against [HA] for d i f l u o r o - and d i c h l o r o a c e t i c acids are compared. The greater c a t a l y t i c e f f ec t iveness of the c h l o r o - a c i d s i s cur ious , cons ider ing that the pK measurements p lace the f l u o r o - a c i d s as the s l i g h t l y stronger a c i d s . The data i n F i g . 34 can be i n t e r p r e t e d i n one of two ways. A l i n e a r r e g r e s s i o n i n c l u d i n g a l l nineteen c a r b o x y l i c ac ids (as shown i n F i g . 32) has both d i f l u o r o - and t r i f l u o r o a c e t i c a c i d as negative dev iat ions from the Bronsted l i n e . Such a reading of the data requires an explanat ion for these two dev ia t i ons . A second i n t e r p r e t a t i o n involves the gentle curve, i n c o r p o r a t i n g the two ' s t rong ' f l u o r o - a c i d s while exc luding the other three ' s t r o n g ' h a l o - a c i d s , as shown i n F i g . 34. We favour the l a t t e r conc lus ion s ince the p o s i t i v e deviat ions of the d i c h l o r o - , t r i c h l o r o - and tr ibromoacet ic acids from t h i s curve can be explained on the bas i s of p o l a r i z a b i l i t y . A h i g h l y p o l a r i z a b l e atom i s one whose e l e c t r o n c loud can be e a s i l y deformed by an e l e c t r i c f i e l d , such as w i l l be produced by ions i n 156 -s o l u t i o n (RS71). P o l a r i z a t i o n of the e l e c t r o n c loud would a lso occur i n the t r a n s i t i o n s tate of the general a c i d ca ta lyzed e n o l i z a t i o n of acetone, which involves hydrogen a b s t r a c t i o n from protonated acetone by the conjugate base of the a c i d . Such a p o l a r i z a t i o n w i l l f a c i l i t a t e t h i s process , and therefore lead to enhanced c a t a l y t i c a c t i v i t y for c a r b o x y l i c ac ids possess ing p o l a r i z a b l e subs t i tuents . Th i s i n f e r s , of course, that p o l a r i z a b i l i t y exerts a l a r g e r inf luence on the t r a n s i t i o n s tate than on the e q u i l i b r i u m a c i d i t i e s . E f f e c t s of t h i s k i n d have been reported p r e v i o u s l y (NL86). P o l a r i z a b i l i t y increases as one goes down a group i n the P e r i o d i c Table and so a p l a c i n g for the halogens i n order of i n c r e a s i n g p o l a r i z a -b i l i t y has F < C i < Br < I . On th i s bas i s the greater c a t a l y t i c a c t i v i t y of tr ibromo- and t r i c h l o r o - a c e t i c ac ids over t r i f l u o r o a c e t i c a c i d can be a t t r i b u t e d to a p o l a r i z a b i l i t y rate-enhancement for the bromo- and c h l o r o - a c i d s ; l ikewise i n the case of d i f l u o r o a c e t i c a c i d and d i c h l o r o a c e t i c a c i d . The most p o l a r i z a b l e halogen i . e . i od ine , should show a ra te constant above that expected on the bas i s of the Bronsted l i n e for the other c a r b o x y l i c ac ids . Inspect ion of F i g . 34 shows that iodoace t i c a c i d i s s l i g h t l y on the p o s i t i v e s ide of the Bronsted l i n e ; the value for k ^ i s almost comparable to the value for c h l o r o a c e t i c a c i d , an a c i d whose d i s s o c i a t i o n constant i s twice that of iodoacet ic a c i d . We had hoped to fur ther i l l u s t r a t e the r o l e of p o l a r i z a b i l i t y i n these systems by measuring k ^ value for methy l th ioace t i c a c i d , the s u l f u r analogue of methoxyacetic a c i d . The p o l a r i z a b i l i t y of s u l f u r i s greater than that of oxygen and so, one would expect enhanced c a t a l y t i c 157 -a c t i v i t y for the s u l f u r - c o n t a i n i n g compound. Unfortunate ly , the compound reacts r a p i d l y with t r i i o d i d e i o n . Further ana lys i s of the p o l a r i z a b i l i t y e f f e c t , on a q u a n t i t a t i v e b a s i s , w i l l be presented s h o r t l y . 3. The ana lys i s of the values as j u s t descr ibed begs the quest ion: why i s the Bronsted p l o t curved? The curvature i s i n the d i r e c t i o n p r e d i c t e d by the Hammond postulate and Marcus theory; the use of the twelve weaker a l i p h a t i c carboxy l i c acids (mandelic a c i d and weaker) to def ine one Bronsted l i n e gives an a value of 0.621 (± 0.035); the three s tronger ac ids ( ch loroace t i c and stronger) gives an a value of 0.546 ± 0.051. Having s a i d that , the l i n e a r regress ion of a l l f i f t e e n acids gives a much b e t t e r s t a t i s t i c a l r e s u l t than e i t h e r of the two c o r r e l a -t ions j u s t mentioned; a c o r r e l a t i o n c o e f f i c i e n t of 0.9957 and an a value of 0.555 ± 0.014 r e s u l t . Thus the data are quite adequately descr ibed by a l i n e a r c o r r e l a t i o n . This issue w i l l be d iscussed l a t e r , a f t er c o n s i d e r a t i o n of some fac tors that are re levant as to whether a curved or a l i n e a r c o r r e l a t i o n of t h i s data i s more appropr ia te . 4. We w i l l now discuss the ro l e of s t e r i c e f fec t s i n the a c i d ca ta lyzed r e a c t i o n . I t i s evident from F i g . 32, p. 151, that while the meta benzoic ac ids e s s e n t i a l l y f a l l on the l i n e def ined by the twenty two a l i p h a t i c c a r b o x y l i c a c i d s , the f i v e ortho benzoic ac ids f a l l s l i g h t l y above such a l i n e . The p o s i t i v e deviat ions from the def ined Bronsted l i n e are small but they are cons i s tent . Consider ing that the Bronsted l i n e (or curve) should more proper ly i n t e r s e c t the two points for the - 158 -f l u o r o - a c e t i c acids i n Fi g . 34, the p o s i t i v e deviations of the two ortho-nitro benzoic acids i s enhanced. The s i z e of the deviation f o r the f i v e ortho benzoic acids bears some r e l a t i o n s h i p to the s i z e of the ortho substituent; 2-fluorobenzoic a c i d f a l l s j u s t above the Bronsted l i n e , while 2,6-dinitrobenzoic a c i d shows a p o s i t i v e deviation of greater magnitude. The s t e r i c a c c e l e r a t i o n present i n the ortho benzoic acids l e d us to c r i t i c a l l y examine the a l i p h a t i c acids. Using several of the a l i p h a t i c acids, acids of a s t r u c t u r a l type where l i t t l e or no s t e r i c a c t i v a t i o n i s expected, a Bronsted l i n e i s defined, F i g . 35. The acids used to define t h i s l i n e are C1CH2C02H, CH3OCH2C02H, HOCH2C02H, CH 3C0 2H, CD 3C0 2H and CH 3CH 2C0 2H; the r e s u l t i s given i n eq. [4.9]. 6 acids l og (k^/p) = - 4.37 - 0.607 (pK + log p/q) [4.9] r = 0.9985 ± ± 0.06 0.016 The other a l i p h a t i c acids are included i n F i g . 35; these acids, a l l possessing s t e r i c bulk, are C 6H 5CH(0H)C0 2H, C 6H 5CH 2C0 2H, CH 3CH 2CH 2C0 2H, (CH 3) 2CHC0 2H, C 6H i : LC0 2H, (CH 3) 3CCH 2C0 2H and (CH 3) 3CC0 2H. The f a c t that the 'sterically-crowded' c a t a l y s t s appear on or above the Bronsted l i n e i n F i g . 35 leads us to conclude that a small s t e r i c a c c e l e r a t i n g e f f e c t i s present i n most of those c a t a l y s t s . An estimation of the s t e r i c a c c e l e r a t i n g f a c t o r on k ^ can be made by comparing the measured k ^ value with the k j ^ value c a l c u l a t e d on the basis of the Bronsted l i n e f o r those acids possessing l i t t l e or no s t e r i c bulk. We can include d i f l u o r o - and t r i f l u o r o - a c e t i c a c i d i n t h i s category (along with the s i x - 159 3.4 3.9 pK + log p/q 4.9 g. 35: Bronsted plot for catalysis of acetone enolization by thirteen al iphatic carboxylic acids; l ine drawn for six acids (open c i r c l e s ) , as l i s ted in the text; seven other acids (open diamonds), as l i s ted in the text. 160 -a l i p h a t i c ac ids l i s t e d p r e v i o u s l y ) . The i n t e r p r e t a t i o n of the Bronsted p l o t as a curved or a l i n e a r c o r r e l a t i o n must now be s e t t l e d ; the d i v i s i o n of the a l i p h a t i c c a r b o x y l i c acids into two groups, i . e . those possess ing s t e r i c bulk (seven ac ids) and those not possess ing s t e r i c bu lk (e ight a c i d s ) , makes the d e c i s i o n as to the choice of c o r r e l a t i o n for the Bronsted l i n e s impler . The choice of a l i n e a r or a curved c o r r e l a t i o n can be made based upon an eva luat ion of the r e s u l t s of both c o r r e l a t i o n s for the group of ac ids possess ing l i t t l e or no s t e r i c bulk; the r e s u l t s (using a qua-d r a t i c express ion to define the curve) are presented i n eqs. [4.10] and [4 .11] , and shown i n F i g . 36. The degree of f i t i s s l i g h t l y b e t t e r for .4.0 -, . pK + log p/q F i g . 36: Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by a l i p h a t i c c a r b o x y l i c ac ids possessing no s t e r i c bulk; dotted s t r a i g h t l i n e , l i n e a r c o r r e l a t i o n , eq. [4.10]; s o l i d curve l i n e , quadrat ic c o r r e l a t i o n , eq. [4 .11] . - 161 -the quadrat ic express ion, and an inspec t ion of F i g . 36 suggests that the second degree curve i s a more appropriate c o r r e l a t i o n of the data . 8 acids; r = 0.9985 log ( W P ) = - 4.56 - 0.562 (pK + log p/q) [4.10] + + 0.04 0.013 8 acids; r = 0.9990 log ( I C - H A / P ) = - 4.60 - 0.497 (pK + log p/q) - 0.013 (pK + log p / q ) 2 ± ± ± [4.11] 0.06 0.054 0.01 A c o n s i d e r a t i o n of the r a t i o of the observed k^A values to the k^A values c a l c u l a t e d us ing e i t h e r eq. [4.10] or [4 .11] , i l l u s t r a t e s that the quadrat ic express ion i s more appropr ia te . The r e s u l t s are given i n Table 27; i n the case of eq. [4.10] , the l i n e a r c o r r e l a t i o n , the r a t i o k ^ A ° b s / k ^ A C a l c shows a pa t t ern with the values at the extremit ies of the l i n e e q u a l l i n g one or l e s s , while the values i n the centre of the l i n e are greater than one; on the other hand, the values of k ^ A ° b s / k ^ A C a l c for eq. [4 .11] , the quadrat ic c o r r e l a t i o n , show a random sca t t er above and below u n i t y . This fac t favours eq. [4.11] as the c o r r e l a t i o n of choice; a choice that i s a lso supported by the genera l ly smaller dev ia t ions from u n i t y for the k j j A ° k s / k j j A C a l c values found with eq. [4.11] than with eq. [4.10] . We can now use eq. [4.11] to evaluate the magnitude of the s t e r i c a c c e l e r a t i o n e f f e c t on kjjA f ° r the other seven a l i p h a t i c a c i d s , as w e l l as f o r the meta and ortho benzoic a c i d s . The r e s u l t s of these c a l c u l a -t ions are given i n Table 28; F i g . 37 i l l u s t r a t e s the magnitude of the 162 -Table 27: kHA / kHA C ° v a l u e s f o r the group of a l i p h a t i c carboxylic acids possessing l i t t l e or no s t e r i c bulk. Values of k ^ A 0 3 1 0 c a l c u l a t e d from a s u b s t i t u t i o n of the appropriate pK value into eq. [4.10] ( l i n e a r c o r r e l a t i o n ) or eq. [4.11] (quadratic c o r r e l a t i o n ) . A c i d k H A ° b S A H A C a l C k H A 0 b S A H A C a l C (eq. [4.10]) (eq. [4.11]) F 3 C C 0 2 H 1.00 1.07 F 2 CHC0 2 H 0.837 0.821 C1CH 2 C0 2 H 1.09 1.00 CH 3 0CH 2 C0 2 H 1.19 1.11 H0CH 2 C0 2 H 1.07 1.01 C H 3 C 0 2 H 0.955 0.980 C D 3 C 0 2 H 0.982 1.01 C H 3 C H 2 C 0 2 H 0.873 0.908 - 163 -Table 28: k H A S / k H A ° ° values for a l i p h a t i c c a r b o x y l i c a c i d s , meta and ortho benzoic a c i d s . Values of k ^ 0 3 ^ c a l c u l a t e d from a s u b s t i t u t i o n of the appropriate pK value in to eq. [4 .11] . A c i d v obs n. c a l c k H A / k H A A l i p h a t i c c a r b o x y l i c ac ids : C 6 H 5 CH(OH)C0 2 H 1.42 C 5H 5CH2C0 2H 1.22 CH3CH2CH2CO2H 1.14 (CH 3) 2CHC0 2 H 0.918 C 6 H 1 1C0 2 H 1.14 (CH3)3CCH2C02H 1.49 (CH 3) 3CC0 2 H 1.25 Benzoic a c i d s : H 1.34 3 - C H 3 0.964 3-F 1.16 3-N02 1.12 2 - C 2 H 50 1.57 2 - C H 3 1.52 2-F 1.26 2-N02 1.56 2,6-(N0 2) 2 1.77 - 164 -F i g . 37: Bronsted plot for catalysis of acetone enolization by carboxylic acids; second degree curve drawn for eight al iph-at ic acids (open c irc le s ) ; also shown are seven al iphatic acids possessing steric bulk (open diamonds); four meta benzoic acids (open squares) and five ortho benzoic acids (closed c i rc l e s ) . - 165 -deviations for these acids. The largest deviations (as measured._by k ^ A ^ S / k j j A 0 3 1 0 ) are for the ortho benzoic acids, with the larger substituent generally having the greater deviation. Thus 2,6-dinitro-benzoic acid is a factor of 1.8 times more effective as a catalyst than is expected on the basis of the equilibrium acid strength. Benzoic acid and i t s meta derivatives have values of k j r A ° b s / k j j A c a - ' - c that are generally lower than those found for the ortho-substituted acids. The al iphat ic carboxylic acids show varying effects; the bulky mandelic and t-butylacetic acids showing the larger deviations (k^ A o l : > s /k j j A c a ' ' - c = 1.4), while dimethylacetic and butanoic acid have values of k H A ° b s / k H A C a l C c l o s e t o unity. Incidentally the use of the linear correlation eq. [4.10] gives values of k ^ ^ k s / k ^ 0 3 1 0 comparable to, and showing the same trend, as the data in Table 28. Possible explanations for such steric accelera-tion w i l l be discussed after analysis of the results for a l l the catalyt ic species under investigation. We can also use eq. [4.11] to quantify the po lar izabi l i ty accelerat-ing effect discussed previously. The results are given in Table 29 and show the expected trend. The largest acceleration is for tribromoacetic acid, with trichloroacetic acid showing a comparable deviation. It is interesting that the accelerating effect of dichloroacetic and iodo-acetic acid are also comparable; this indicates that the po lar izabi l i ty effect of two chlorine atoms is roughly the same as the po lar izabi l i ty of one iodine atom. A consideration of Fig . 36 from the viewpoint of a l inear correla-tion re l ies heavily on the point for trif luoroacetic acid; on the other 166 -Table 29: k H A ° b S A H A C a l C values for al iphatic carboxylic acids possessing polarizable substituents. Values of k ^ 1 obtained using eq. [4.11] A c i d k H A ° b S A H A C a l C C 1 3 C C 0 2 H 1.71 B r 3 C C 0 2 H 1.83 C1 2 CHC0 2 H 1.28 I C H 2 C 0 2 H 1.31 hand the e x c l u s i o n of t h i s a c i d lends fur ther support to a curved c o r r e l a t i o n of the c a r b o x y l i c a c i d set . I t i s p o s s i b l e that the p o l a r i z a b i l i t y e f f e c t i s y i e l d i n g a s l i g h t l y overs ized value of k j ^ for t r i f l u o r o a c e t i c a c i d ; a quadrat ic c o r r e l a t i o n of the other seven acids gives a much b e t t e r r e s u l t (r = 1.00) than a l i n e a r c o r r e l a t i o n of the same data (eqs. [4.12] and [4.13] r e s p e c t i v e l y ) . log ( k ^ / p ) = - 4.58 - 0.556(pK + log p/q) [4.12] + + 0.07 0.018 7 acids, r = 1.0000 log (kj^/p) - - 4.82 - 0.351(pK + log p/q) - 0.0355(pK + log p / q ) 2 ± ± ± 0.04 0.032 0.0054 [4.13] 167 The d e v i a t i o n of the t r i f l u o r o a c e t i c a c i d from the curve def ined by eq. [4.13] as measured by k j ^ ° b s / k j } A c a - ' - c i s a fac tor of 1.65; the values for the four ac ids l i s t e d i n Table 27 ( t r i c h l o r o a c e t i c a c i d e t c . ) increases with the use of eq. [4 .13] . The acids now have k ^ A o b s / k H A c a - ' - c values of 2.50, C 1 3 C C 0 2 H ; 2.67, B r 3 C C 0 2 H ; 1.58, C1 2 CHC0 2 H; 1.47, I C H 2 C 0 2 H . (The r e l a t i v e magnitude of these values i s unchanged from those l i s t e d p r e v i o u s l y . ) I t i s i n t e r e s t i n g that the p o l a r i z a b i l i t y e f f e c t of three f l u o r i n e atoms i s only s l i g h t l y higher than e i t h e r two c h l o r i n e atoms or one iodine atom. This treatment presumes that the e f f e c t of p o l a r i z a b i l i t y on d i f l u o r o a c e t i c and c h l o r o a c e t i c a c i d i s n e g l i g i b l e . As s t e r i c a l l y bulky c a t a l y s t s have been shown to deviate p o s i t i v e l y from the Bronsted l i n e , the p o l a r i z a b i l i t y e f f ec t could w e l l be super-imposed on the s t e r i c e f f e c t , e s p e c i a l l y i n the case of the t r i - h a l o ac ids and, i n p a r t i c u l a r the ac ids possess ing the l a r g e r halo atoms. An attempt to inc lude more c a r b o x y l i c acids (with pK values l e ss than c h l o r o a c e t i c ac id) i n the Bronsted p l o t i n order to fur ther evaluate the curved c o r r e l a t i o n proved f u t i l e . Unfor tunate ly , cyanoac-e t i c a c i d (pK value of 2.47) reacts r a p i d l y with t r i i o d i d e i o n . While we d i d measure the k j ^ values for protonated g lyc ine and two of i t s d e r i v a t i v e s (pK values between 1.83 and 2.36), these ac ids i l l u s t r a t e d an e f f e c t of t h e i r own. 5. I t i s evident from F i g . 32 that the ammonio c a r b o x y l i c ac ids are l e ss e f f e c t i v e c a t a l y s t s than i s expected on the bas i s of the Bronsted l i n e for the uncharged c a r b o x y l i c ac ids ; thus protonated g lyc ine and i t s - 168 dimethyl and t r i m e t h y l d e r i v a t i v e s show negative dev iat ions from that l i n e . The magnitude of the d e v i a t i o n can be estimated from the value of k H A o b s / k H A c a - ' - c , ; k ^ 0 3 1 0 values a v a i l a b l e from eq. [4.11]; the average r e s u l t f or the three ac ids i s 0.62 ± 0.08 i l l u s t r a t i n g c a t a l y t i c r e t a r d a t i o n by a f a c t o r of 1.6. T h i s e f f e c t could be r e l a t e d to the e f f e c t d iscussed p r e v i o u s l y i n the case of carboxylate monoanions and d ian ions . I t may be r e c a l l e d that the dianions formed a d i s t i n c t Bronsted l i n e d i s p l a c e d downward from the monocarboxylate l i n e by about a fac tor of three i n the rate constants . In t h i s case the d e v i a t i o n i s a l so i n the negative d i r e c -t i o n , but involves c a r b o x y l i c acids bear ing p o s i t i v e l y charged s u b s t i -tuents . The three acids examined are a l l s t r u c t u r a l l y s i m i l a r and prompted us to quest ion the e f f ec t of increas ing the dis tance between the p o s i t i v e charge and the c a r b o x y l i c a c i d p o r t i o n of the c a t a l y s t . We chose to evaluate t h i s e f f ec t by obta in ing the t r i m e t h y l ammonio d e r i v a t i v e s of butanoic and hexanoic a c i d and measuring the k ^ va lues . The reported pK values for these two acids (3 .98, 4.26) l e d us to expect a measureable k A - value for the conjugate monoanion of the c a r b o x y l i c a c i d . Measurements for both of these ac ids were made at four b u f f e r - r a t i o s at 0.1 M i o n i c s trength (I) and gave exce l l en t k i n e t i c r e s u l t s . The r e s u l t s for 4-trimethylammoniobutanoic a c i d ((CH3)3N+(CH2)3CO2H) are k ^ = 1.59 ± 0.06 x 10" 7 M " 1 s e c - 1 and k A - = 8.05 ± 0.28 x 1 0 - 8 M ' 1 s e c - 1 (n va lues of 0.25, 0 .5 , 1 and 4 ) . The r e s u l t s for 6-trimethylammoniohexa-n o i c a c i d ( ( C ^ ^ N ^ C ^ s C T ^ H ) k ^ = 1.18 ± 0.04 x 10" 7 M " 1 sec" 1 and k A - = 1.77 ± 0.09 x 10" 7 M " 1 sec" 1 (n values of 0 .5 , 1, 2 and 4) . There - 169 -i s a large discrepancy, for both of these a c i d s , between the pR^ values reported i n the l i t e r a t u r e (EF79) and the p K 1 values (I •= 0.1 M) a v a i l a b l e from the average pH values at each n value (pK 1 = pH + log n ) . The p K 1 values are 4.13 ± 0.04 for the b u t y r i c a c i d d e r i v a t i v e and 4.51 ± 0.02 for the hexanoic a c i d d e r i v a t i v e (at 0.1 M i o n i c s trength) . These values have been confirmed i n t h i s laboratory by potent iometr ic t i t r a t i o n of the ac ids (NV87). To avoid any quest ion of i o n i c s trength e f f ec t s on pK^ causing apparent deviat ions for the p o s i t i v e l y charged a c i d s , we w i l l use pK 1 values i n the Bronsted p l o t . In the case of the two acids j u s t mentioned and the n e u t r a l carbox-y l i c a c i d s , rate constants have been measured at an i o n i c s trength of 0.1 M. The p K 1 values for the uncharged acids agree with that expected on the bas i s of eq. [3.7] (p. 71), i . e . pK1- - 0.11 at 0.1 M i o n i c s trength . However measurements of f ° r protonated g lyc ine and i t s N-methyl d e r i v a t i v e s have been obtained over a span of i o n i c s trength (0.1 to 0.4 M), a var iance that seemingly has no e f f e c t on k j ^ . Values of p K 1 are a v a i l a b l e from experimental data and these a lso show no v a r i a t i o n with i o n i c s trength . The r e s u l t s are l i s t e d i n Table 30. The Bronsted curve def ined by e ight uncharged acids (using p K 1 ) i s given by eq. [4.14] (same acids as i n F i g . 36). The corresponding Bronsted p l o t contains the r e s u l t s for the charged a c i d s , F i g . 38. A measure of the degree of d e v i a t i o n for these ac ids i s g iven by k ^ 0 ^ / k ^ 0 3 - 1 0 , where k ^ 0 3 1 0 i s the value expected on the bas i s of eq. [4.14] . Some dev ia t ions are obvious i n F i g . 38 and the values of k ^ c ^ c / k ^ 0 1 3 5 i n Table 30 quant i fy these r e s u l t s . While acids possess ing p o s i t i v e charges near the c a r b o x y l i c a c i d centre genera l ly deviate from the 170 --4.0 F i g . 38: Bronsted p l o t f or c a t a l y s i s of acetone e n o l i z a t i o n by a l i p h a t i c carboxy l i c a c i d ; 8 uncharged acids (open c i r c l e s ) , 5 p o s i t i v e l y charged acids (c losed c i r c l e s ) . Curve i s f or uncharged acids (eq. [A.14]) Bronsted l i n e , the e f f e c t i s removed by increas ing the distance between the two moie t i e s . ( l og k ^ / p ) 4.66 - 0.500 (pK 1 + log p/q) - 0.131 (pK 1 + log p / q ) 2 ± ± ± 0.05 0.051 0.010 [4.14] - 171 -Table 30: p K 1 and ^HA S A H A ° C values for a l i p h a t i c c a r b o x y l i c acids possess ing p o s i t i v e l y charged subs t i tuents . Values of k j j A 0 3 1 0 obtained us ing eq. [4.14] A c i d p K 1 kjjA° D S / k H A C 3 1 C (CH3) 3 N + CH 2 C02H 1. .95 + 0. ,02 0. ,944 (CH 3 )2N + HCH2C0 2 H 2. .05 + 0. ,05 0. ,749 H 3 N + C H 2 C 0 2 H 2, .40 + 0. .03 0, ,744 ( C H 3 ) 3 N + ( C H 2 ) 3 C 0 2 H 4, .13 + 0. ,04 0. .930 ( C H 3 ) 3 N + ( C H 2 ) 5 C 0 2 H 4 .51 + 0, .02 1, .17 In the case of tr imethy1glyc ine , i t seems that a p o s i t i v e charge c lose to the c a r b o x y l i c a c i d has no e f f ec t on k ^ . However, we can a t t r i b u t e a rate a c c e l e r a t i n g s t e r i c e f f e c t to k ^ for t h i s a c i d , on the bas i s of our e a r l i e r d i s c u s s i o n . The two fac tors work i n oppos i t i on to one another g i v i n g the r e s u l t shown. I t may be r e c a l l e d that t - b u t y l -a c e t i c a c i d , the carbon analogue of t h i s a c i d , shows a r e l a t i v e l y large p o s i t i v e d e v i a t i o n from the Bronsted l i n e . The t r a n s i t i o n s tate for the process involves hydrogen a b s t r a c t i o n from protonated acetone by the carboxylate base. I t seems that when the base possesses a u n i t of p o s i t i v e charge c lose to the carboxylate , a r e p u l s i v e i n t e r a c t i o n occurs which r a i s e s the energy of the t r a n s i t i o n - 172 s ta te . This e f f e c t i s small (a rate r e t a r d a t i o n by a f a c t o r of 1.3 for protonated g lyc ine) and may r e f l e c t an e l e c t r o s t a t i c r epu l s ive i n t e r a c -t i o n between the substrate and the c a t a l y s t . The system w i l l t r y to minimize t h i s e f f e c t and th i s may, i n p a r t , exp la in the r e l a t i v e l y small s i z e of the e f f e c t . I f the c a t a l y s t has a s tructure which can minimize the i n t e r a c t i o n , i t w i l l do so and thus the degree of d e v i a t i o n i s almost n e g l i g i b l e for the four-carbon ammonion compound. The s ix -carbon ammonio compound i s a c t u a l l y above the l i n e to a very small extent. The r o l e of a s t e r i c a c c e l e r a t i n g fac tor for these two acids should be minimal , cons ider ing the e a r l i e r r e s u l t for butanoic a c i d . The values of k A - determined for the conjugate anions of the two acids j u s t mentioned can be compared with the values expected on the bas i s of the Bronsted l i n e for monobasic carboxylates (using p K 1 values i n the c o r r e l a t i o n ) . For 4-trimethylammoniobutanoate anion, the k A " ° b S / k A " C a ' ' ' C value i s 0.946 and for 6-trimethylammoniohexanoate anion the k A - o b s / k A - c a l c value i s 0.957. These r e s u l t s i l l u s t r a t e a n e g l i g i b l e e f f e c t for base a b s t r a c t i o n of a proton from acetone when the base possesses a u n i t of p o s i t i v e charge that i s some distance from the carboxylate p o r t i o n of the base. We are unable to measure k A - values for bases possess ing a p o s i t i v e charge c lo ser to the carboxylate group, e .g . g l y c i n e . A study by Cox and co-workers invo lved the base ca ta lyzed e n o l i z a -t i o n of two ketones that possess p o s i t i v e l y charged ammonio groups i n the substrate i t s e l f (CM81). They found rates 10^ times l a r g e r than those of the corresponding base ca ta lyzed react ions for e i t h e r the n e u t r a l aminoketone or acetophenone. The e f f e c t diminished with an 173 -increase i n the length of the a l k y l cha in separat ing the carbonyl and the ammonio moiety. The authors suggest that in tramolecu lar e l e c t r o s -t a t i c s t a b i l i z a t i o n of the negative charge developing on the carbonyl oxygen i n the t r a n s i t i o n state causes the rate a c c e l e r a t i o n . In our case, which i s an intermolecular s i t u a t i o n , no e f f e c t i s observed, perhaps r e f l e c t i n g the d i f f i c u l t y i n having the ammonio subst i tuent i n the c o r r e c t p o s i t i o n i n space to s t a b i l i z e the developing negative charge on the carbonyl oxygen. Another i n t e r e s t i n g study i n v o l v i n g e l e c t r o s t a t i c e f f ec t s has been reported by Dahlberg and co-workers (DK83). 4.2.2 D i p r o t i c Acids Table 14, p . 109 contains four k^^A va lues . This small group of d i -c a r b o x y l i c a c i d rate constants should provide some i n s i g h t into the e f f e c t of changing the c a t a l y s t from a monoprotic a c i d to a d i p r o t i c a c i d . These k ^ A values are shown i n F i g . 39, which a lso include the Bronsted l i n e for monoprotic c a r b o x y l i c a c i d s . I t seems, from F i g . 39, that two of the four d i a c i d s are e s s e n t i a l l y on the l i n e f o r the monoacids, i . e . o x a l i c and s u c c i n i c a c i d . On the other hand d ie thy lmalonic and 3 , 3 - d i m e t h y l g l u t a r i c a c i d f a l l below the monoacid l i n e . I t may be r e c a l l e d that the dianions of these two acids dev ia ted n e g a t i v e l y from the Bronsted l i n e for the other d ian ions , an e f f e c t which i s r e l a t e d to the degree of hydrogen bonding i n the mono-anion . The same e f f e c t would q u a l i t a t i v e l y e x p l a i n the r e s u l t s i n th i s case. 174 -. a . a> o 2.6 pK + log p/q F i g . 39: Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by a l i p h a t i c c a r b o x y l i c ac ids ; monoprotic ac ids (open c i r c l e s , s o l i d l i n e ) and d i p r o t i c ac ids (c losed c i r c l e s , dotted l i n e ) While the d e v i a t i o n for d ie thy lmalonic a c i d ( K 1 o b s / K i c a l c = 4 . 7 ) i s greater than that of 3 , 3 - d i m e t h y l g l u t a r i c a c i d ( K i ° b s / K i c a l c = 2 .1) , the magnitude of the e f f e c t i s much smal ler than the e f f e c t on as measured by K i / 2 K g (16 and 5.0 r e s p e c t i v e l y ) . These r e s u l t s suggest that the e f f e c t of hydrogen-bonding i n the t r a n s i t i o n s tate i s only s l i g h t l y l e s s than the e f f e c t on the e q u i l i b r i u m a c i d s trength of the d i a c i d . The process i s represented by eq. [1.10b] below, where A" i s the monoanion of the d i a c i d . 175 -[1.10b] •f H A 4.3 BIFUNCTIONAL CATALYSTS (DICARBOXYLIC ACID MONOANIONS) A c o l l e c t i o n of data from Table 14, p. 109, and Table 16, p. 114, provides s ix teen rate constants for the monoanions of d i c a r b o x y l i c a c i d s . One of the aims of t h i s work i s to evaluate the r o l e played by such monoanions i n the e n o l i z a t i o n of acetone. Are these b i f u n c t i o n a l monoanions ( i . e . those conta in ing both -CO2H and -CO2" groups) a c t i n g as b i f u n c t i o n a l c a t a l y s t s (eq. [1.87] p. 56)? A study by other workers i n v o l v i n g three monoanions suggests the absence of b i f u n c t i o n a l c a t a l y -s i s (p. 54, LA67). I f t h i s i s the s i t u a t i o n , another quest ion has to be answered; are these c a t a l y s t s conta in ing both a c i d i c and bas i c funct ion-a l i t i e s a c t i n g as general acids or general bases? 1. Our approach to answering these questions involved dual ana lys i s of the s ix teen kjj^- values; ( i ) i f the monoanions are a c t i n g as general ac ids ( i . e . protonat ion of acetone, fol lowed by hydrogen a b s t r a c t i o n from acetone by the conjugate d i a n i o n ) , the Bronsted p l o t involves a c o r r e l a t i o n of k ^ - with pK2, and should have a negative slope (s ince the weaker a c i d w i l l be the poorer c a t a l y s t ) . ( i i ) I f the monoanions are a c t i n g as general bases ( i . e . hydrogen a b s t r a c t i o n from acetone by the carboxylate f u n c t i o n a l i t y of the monoanion), the Bronsted p l o t 176 -involves a c o r r e l a t i o n of k H A - with pK^, and should have a p o s i t i v e slope (s ince the stronger base w i l l be the be t t er c a t a l y s t ) . The r e s u l t s of both Bronsted p l o t s could very w e l l ind ica te whether general a c i d or general base c a t a l y s i s i s operat ive . The i n c l u s i o n of the Bronsted l i n e s for c a r b o x y l i c monoprotic acids ( F i g . 34, p. 154) and for t h e i r conjugate bases ( F i g . 29, p. 132) i n the appropriate Bronsted p l o t for the monoanions could answer the quest ion of whether b i f u n c -t i o n a l c a t a l y s i s i s operat ive; i f the monoanions are a c t i n g as b i f u n c -t i o n a l c a t a l y s t s , we should expect cons iderable e x a l t a t i o n of the c a t a l y t i c constants over values expected on the bas i s of the Bronsted l i n e s for the monoprotic acids and t h e i r conjugate bases. The two r e s u l t i n g Bronsted p l o t s are shown i n F i g s . 40 and 41. Two features are evident from these p l o t s : ( i ) B i f u n c t i o n a l c a t a l y s i s i s obvious ly not important s ince the measured k ^ - values are genera l ly of the same order of magnitude as the monoprotic acids and conjugate bases i n the same pK reg ion . ( i i ) The p l o t of the monoanions ac t ing as bases, F i g . 41, has some sca t t er and produces a negative s lope, which makes no sense at a l l . On the other hand the p l o t of the monoanions a c t i n g as a c i d s , F i g . 40, shows a much be t t er c o r r e l a t i o n , with again a negative s lope , which i n t h i s case i s the appropriate one. Therefore we conclude that general a c i d c a t a l y s i s i s the observed route for the monoanions of d i c a r b o x y l i c a c i d s . 2. I t i s i n t e r e s t i n g that these monoanions, a c t i n g as general a c i d s , are more e f f e c t i v e as c a t a l y s t s than the n e u t r a l monoprotic ac ids . The t r a n s i t i o n s ta te for the l a t t e r process involves hydrogen a b s t r a c t i o n - 177 -Q. O) O - 6 . 6 -pK + log p/q F i g . 40: Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by the monoanions of d i c a r b o x y l i c ac ids ( s o l i d l i n e ) ; monoanions a c t i n g as a c i d s , i n v o l v i n g pK£, p = 1, q = 4; Bronsted l i n e f o r c a r b o x y l i c monoprotic ac ids added f o r comparison (dotted l i n e ) . -B-r CO o F i g . 41: r 1 2 3 4 6 pK + log p/q Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by the monoanions of d i c a r b o x y l i c ac ids ( s o l i d l i n e ) ; monoanions a c t i n g as bases, i n v o l v i n g pK^, p = 2, q = 2; Bronsted l i n e f o r carboxylate bases added for comparison (dotted l i n e ) . - 178 -from protonated acetone by the conjugate base, A", while i n the former process , the base i s the conjugate d ian ion , A^". When the substrate i s acetone base c a t a l y s i s by dianions i s l ess e f f e c t i v e than monoanion c a t a l y s i s (Sect ion 4 . 1 . 2 ) . These two e f f ec t s seem independent of the distance separat ing the two carboxylate moiet ies i n the c a t a l y s t , but r a t h e r , j u s t dependent on the presence of the a d d i t i o n a l carboxylate u n i t , and whether the substrate i s acetone or protonated acetone. 3. The data i n F i g . 40 are shown i n F i g . 42 with a c l a s s i f i c a t i o n of the types of monoanion present . One of our aims i n examining the i s o p h t h a l i c ac ids i s to probe fur ther the e f f e c t of ortho subst i tuents on the rate constants of benzoic a c i d and benzoate anion d e r i v a t i v e s . Unfortunate ly , due to r e l a t i v e l y poor c a t a l y s i s by the dianions of these a c i d s , we are unable to study the ortho e f f e c t i n benzoate anion d e r i v a t i v e s . However, the values of k ^ - for the i sophthalate monoanions can provide some i n s i g h t into the ortho e f f e c t i n benzoic a c i d d e r i v a t i v e s . (These c a t a l y s t s can be considered as benzoic a c i d d e r i v a t i v e s which possess a 3-CO2" subst i tuent and e i t h e r a 5- or a 2 - subst i tuent a l s o ) . A f i r s t step i n eva luat ing any e f fec t s i n the i sophthalate mono-anions i s to def ine the general a c i d - c a t a l y z e d Bronsted l i n e for the 5 - s u b s t i t u t e d monoanions. (We have inc luded the unsubst i tuted species i n t h i s ca tegory . ) The r e s u l t of a l i n e a r c o r r e l a t i o n i s given i n eq. [4 .15] , p r o v i d i n g an a value of 0.321 ( ± 0.056, F i g . 43). Th i s slope i s s i g n i f i c a n t l y lower than that observed for the a l i p h a t i c carboxy l i c - 179 -5 -6.5-, 0 " CO o -6--8.6-O CD Q O A - 7 -O A -7.5 6 pK + log p/q Fig . 42: Bronsted plot for catalysis of acetone enolization by the monoanions of dicarboxylic acids; al iphatic monoanions (open triangles) , phthalate monoanion (open diamond), 5-substituted isophthalate monoanions (open c irc les) and 2-substituted isophthalate monoanions (closed c i rc l e s ) . acids and benzoic acid and i ts meta derivatives, i . e . 0.598 (± 0.024). The range of (pK + log p/q) for the isophthalate monoanion is 3.4 - 4.2, while for the neutral carboxylic acids, the range is 2.6 - 4.7. 5 monoanions log ( k ^ / P ) = - 5.17 - 0.321(pK + log p/q) [4.15] r = 0.9581 ± ± 0.22 0.056 - 180 i — 1 1 2 3 4 pK + log p/q 43: Bronsted plot for catalysis of acetone enolization by isophthalate monoanion; data from Table 16, p. 114; 5-substi-tuted isophthalate monoanions (open c i rc l e s , so l id l ine) and 2-substituted isophthalate monoanions (closed c i rc l e s , dashed l ine ) . 181 -The low c o r r e l a t i o n c o e f f i c i e n t of eq. [4.15] r e f l e c t s the random s c a t t e r of the po ints i n a r e l a t i v e l y small pK range. A poor c o r r e l a -t i o n i s a lso evident for benzoic a c i d and i t s meta d e r i v a t i v e s , acids which also cover a narrow span of pK va lues , eq. [4 .16] . Thus the s i g n i f i c a n t drop i n the a value i n the case of eq. [4.15] from that observed for uncharged c a r b o x y l i c acids (whether a l i p h a t i c and/or benzoic ac ids) cannot be w r i t t e n o f f as a meaningless slope of a poor ly c o r r e l a t e d l i n e a r regres s ion . 4 benzoic ac ids l og ( k ^ / p ) = - 4.37 - 0.593 (pK + log p/q) [4.16] r = 0.9655 ± ± 0.41 0.113 An i n t e r p r e t a t i o n of the a value (0.32) for 5- i sophthalate monoanions i n terms of the Hammond postulate and Marcus theory reads as fo l l ows . The B value for a b s t r a c t i o n of the hydrogen from protonated acetone by the i sophthalate d ian ion i s 0.68 (1-a) . Th i s suggests a l a t e t r a n s i t i o n s tate with the proton t r a n s f e r over h a l f complete. I t may be r e c a l l e d that when the base involved i s a monobasic carboxylate , an e a r l i e r t r a n s i t i o n s tate i s impl ied by the smaller B value (0.38 ± 0 .02) . The apparent h igh B value for the i sophthalate dianions i s i n d i r e c t c o n f l i c t with the value expected on the bas i s of the Hammond p o s t u l a t e . The more r e a c t i v e i sophthalate dianions should l ead to an e a r l i e r t r a n s i t i o n s tate as compared to the monobasic carboxylates . An e a r l i e r t r a n s i t i o n s tate i s l i n k e d to a smal ler B va lue . However the l e s s r e a c t i v e monobasic anions have the smal ler B va lue . A s i m i l a r c o n t r a d i c t o r y e f f e c t i s evident i n the system i n v o l v i n g 182 -n e u t r a l acetone and carboxylate bases. The more r e a c t i v e monobasic c a t a l y s t s have the l a r g e r B va lue , 0.89, whereas the less reac t ive d i b a s i c c a t a l y s t s have the s l i g h t l y smal ler 0 va lue , 0.78. The 2 - s u b s t i t u t e d i sophthalate monoanions show an a c c e l e r a t i o n r e l a t i v e to the 5 - s u b s t i t u t e d monoanions. While the two groups of c a t a l y s t s only share a l i m i t e d range of pK va lues , the 2 - s u b s t i t u t e d monoanions i n t h i s range (2-CH3O and 2-CH3) deviate p o s i t i v e l y r e l a t i v e to the l i n e def ined by 5-substituted i sophthalate monoanions i n the same range. This e f f e c t can be a t t r i b u t e d to the presence of the ortho subs t i tuent i n the c a t a l y s t . This i s cons i s tent with the e f fec t s observed with o r t h o - s u b s t i t u t e d benzoic ac ids . I t i s d i f f i c u l t to est imate the ra te a c c e l e r a t i n g fac tor for a l l the 2 - s u b s t i t u t e d mono-anions as t h i s would involve a tenuous extension of the 5 - s u b s t i t u t e d monoanion l i n e . However the values of k H A-°k s/k£r A- c a''- c for 2-methyl and 2-methoxyisophthalate monoanion can be estimated on the bas i s of e .q . [4.15], the 5 - s u b s t i t u t e d Bronsted l i n e . The r e s u l t s are 1.52 for 2-CH3O and 1.75 f or 2-CH3; these values roughly agree with the r e s u l t s for 2-ethoxybenzoic a c i d , 1.57, and 2-methylbenzoic a c i d , 1.52, which are based on the monocarboxylic a c i d Bronsted l i n e . The set of 2 - s u b s t i t u t e d i sophthalate monoanions i n F i g . 43 forms a reasonably l i n e a r Bronsted c o r r e l a t i o n , def ined by eq. [4.17]. I t can be seen that two of the h a l o - s u b s t i t u t e d monoanions (bromo and iodo) are on the p o s i t i v e s ide of t h i s l i n e , and cons ider ing the r o l e of. p o l a r i z a -b i l i t y e f f ec t s i n the general a c i d ca ta lyzed mechanism (p. 155), these monoanions could very we l l be dev ia t ing from the Bronsted l i n e due to a p o l a r i z a b i l i t y e f f e c t . The Bronsted l i n e for the four other monoanions - 183 (exc luding 2-1 and 2-Br) i s given by eq. [4.18] and i s a s t a t i s t i c a l improvement upon eq. [4.17] . 6 monoanions l og ( k ^ / p ) 3.95 - 0.592 (pK + l o g p/q) [4.17] r = 0.9829 ± ± 0.17 0.055 4 monoanions l og ( k ^ / p ) = - 4.11 - 0.551 (pK + log p/q) [4.18] r = 0.9960 ± ± 0.11 0.034 A measure of the degree of d e v i a t i o n from eq. [4.18] for 2-1 and 2-Br w i l l be given by k ^ - 0 1 ^ / ^ - 0 3 1 0 . The r e s u l t s are 1.41 for 2-1 and 1.20 for 2 -Br , a trend that i s expected s ince iodine has the l a r g e r p o l a r i z a b i l i t y e f f e c t . The absence of an e f f ec t for the 5-1 and 5-Br monoanions must be due to the large distance separat ing the c a t a l y t i c centre and the halo atom. The 2 - subs t i tu ted i sophthalate monoanions seem to form a good l i n e a r Bronsted c o r r e l a t i o n d i sp laced above, and having a l a r g e r a value than, the 5 - s u b s t i t u t e d monoanion Bronsted l i n e . A l a r g e r a value impl ies a smal ler B value for the rate -determining proton a b s t r a c t i o n . Thus for the 5 - s u b s t i t u t e d monoanions, B = 0.68, whereas the 2 - subs t i tu ted monoanions have a smal ler va lue , B = 0.45. This smal ler B value may r e f l e c t the more r e a c t i v e system for the 2 - subs t i tu ted c a t a l y s t s , a greater r e a c t i v i t y which seems to a r i s e as a r e s u l t of the ortho-s u b s t i t u t i o n . The e a r l i e r t r a n s i t i o n s tate i n t h i s system would then be c r e d i t e d to a s t e r i c rate a c c e l e r a t i n g e f f e c t . Having s a i d that , evidence for such a s i t u a t i o n i n the ortho-benzoic - 184 -ac ids when compared to other monocarboxylic ac ids (whether a l i p h a t i c ~ o r meta-benzoic) has not been found. The f i v e ortho-benzoic ac ids s tudied do give a good l i n e a r Bronsted c o r r e l a t i o n , eq. [4 .19] , but the a value i s comparable to that obtained for the other monocarboxylic a c i d s . 5 acids ( log k ^ / p ) 4.30 - 0.581 (pK + log p/q) [4.19] r = 0.9990 ± ± 0.05 0.016 A l l the e f fec t s discussed for the 2- and 5 - subs t i tu ted i sophthalate monoanions have invo lved the data i n Table 16, k j ^ - values determined by i g n o r i n g the over lapping d i s s o c i a t i o n s of the d i a c i d s . I f the values of k HA" a r e u s e d from Table 17, values determined by cons ider ing the over lapping d i s s o c i a t i o n s , these monoanions deviate to a s l i g h t l y higher degree from the n e u t r a l c a r b o x y l i c l i n e ( fac tor of 1.2) . However the r e l a t i v e p o s i t i o n of the i sophthalate monoanions with respect to each other does not change as shown by F i g . 44. 4.4 ARYLPHOSPHONIC ACIDS. SUBSTITUENT EFFECTS ON THEIR FIRST AND SECOND DISSOCIATIONS Before d i s c u s s i n g the c a t a l y t i c rate constants for the ary lphos-phonic ac ids and r e l a t e d species , an ana lys i s of t h e i r f i r s t and second d i s s o c i a t i o n s w i l l be presented (Table 18, p. 117). - 185 -- 7 H 1 1 • 2 J 4 pK + log p/q F i g . 44: Bronsted p l o t for c a t a l y s i s of acetone e n o l i z a t i o n by i sophthalate monoanions; data from Table 17, p. 115, deter-mined by cons ider ing the over lapping d i s s o c i a t i o n s of the d i a c i d ; 5 - subst i tu ted i sophthalate monoanions (open c i r c l e s , s o l i d l i n e ) and 2 - subs t i tu ted i sophthalate monoanions (c losed c i r c l e s , dashed l i n e ) . 4.4.1 Meta and Para Subst i tuents The re-bonding a b i l i t i e s of phosphorus and carbon are known to be qui te d i f f e r e n t (M79) . With regard to arylphosphonic a c i d s , the degree of conjugat ion between a r y l r i n g and the a c i d i c f u n c t i o n a l group appears - 186 to be cons iderably l e ss than i s the case with a r y l c a r b o x y l i c ac ids , judg ing from the ortho e f fec t s to be discussed l a t e r . A c c o r d i n g l y , one might expect that ordinary Hammett a values would overestimate the e l e c t r o n r e l e a s i n g capac i ty of groups such as alkoxy i n the para p o s i t i o n of arylphosphonic a c i d s . Thus the modif ied subst i tuent constant a n , which i s intended for use with systems that have no through conjugat ion , might be be t t er for c o r r e l a t i n g the pK values of these ac ids (T60, HW73). We f i n d that our data for p K 2 are c o r r e l a t e d very w e l l by crn ( F i g . 45 and eq. [4.19]) and rather poor ly by a ( F i g . 46 and eq. [4 .20]) , i n d i c a t i n g the degree of n bonding between the a r y l r i n g and phosphorus to be s m a l l . The values of a and a n are l i s t e d i n Table 31. 17 ac ids p K 2 = 7.55 - 1 .140a n [4.19] r = 0.9970 ± ± 0.01 0.023 17 ac ids p K 2 = 7.48 - 0.980CT [4.20] r = 0.9778 ± ± 0.02 0.054 I t i s c l e a r l y evident from F i g s . 45 and 46 and the r e l a t e d equations that CTn i s the subst i tuent constant of choice for the Hammett c o r r e l a -t i o n of the subst i tuents and the e q u i l i b r i u m constants . The s i t u a t i o n with respect to pK^ i s l ess c l e a r , p a r t l y because the be l lwether amino subst i tuent i s absent and p a r t l y because the p r e c i s i o n of the values i s l e s s . In contras t to the r e s u l t s with p K 2 , the 187 8 F i g . 46: Plot of pK 2 for arylphosphonic acids against the substituent constant a - 188 Table 31: Subst i tuent constant values (cr and on) f or meta and para subs t i tuent s . Data from r e f s . (PD81, HW73) Substituent a ax\ H 0. 00 0. 00 3-CH3 -0. .06 -0. ,06 4-CH3 -0. ,14 -0. ,10 4 - C 2 H 5 -0. ,15 -0, .12 3-CH3O 0. ,11 0. ,11 4-CH3O -0. .28 -0, .09 4 - C 2 H 5 0 -0. .24 -0, .14 3 - F 0. ,34 0. ,34 3 - C l 0. ,37 0. ,37 4 - C l 0. ,24 0. ,29 4-Br 0. ,22 0. ,30 4-CN 0. 70 0. 70 3 -N0 2 0. 74 0. 74 4 - N 0 2 0. 78 0. 78 4 - N H 2 -0. .57 -0. ,24 3 , 4 - ( C H 3 ) 2 -0. ,20 -0. ,16 3 , 5 - ( C H 3 ) 2 -0. ,12 -0. ,12 - 189 -c o r r e l a t i o n between pK^ and an ( F i g . 47 and eq. [4.21]) i s not d r a m a t i c a l l y b e t t e r than for a ( F i g . 48 and eq. [4.22]) when a l l points are i n c l u d e d . 16 acids pK x = 1.88 - 0.924 on [4.21] r = 0.9954 ± ± 0.01 0.024 16 acids p K x = 1.84 - 0.857 a [4.22] r = 0.9872 ± ± 0.01 0.037 When a l i n e i s drawn with respect to the compounds for which a = a n ( i . e . meta compounds and the para n i t r o and cyano compounds), the values of the slope and in tercept are — 0.926 and 1.89, r e s p e c t i v e l y , for pK^. These values are almost i d e n t i c a l to those given i n eq. [4.21] but are cons iderab ly d i f f e r e n t from those given i n eq. [4.22] . This i s conc lu-s ive evidence that a n , and not a, i s the parameter of choice for pK^. The c o r r e l a t i o n i n v o l v i n g p K 2 for the compounds having equivalent a and a 1 1 va lues gives fur ther support to the choice of the l a t t e r subst i tuent constant for p K 2 ; the values of the slope and in tercept are 1.143 and 7.55, r e s p e c t i v e l y , and are almost i d e n t i c a l to those i n eq. [4 .19] , but s i g n i f i c a n t l y d i f f e r e n t from those i n eq. [4.20] . The r e a c t i o n constant for the f i r s t d i s s o c i a t i o n i s smal ler than for the second, = 0.924 p 2 n = 1.140 (F igs . 45 and 47 r e s p e c t i v e l y ) . We f i n d i t d i f f i c u l t to r a t i o n a l i z e the somewhat greater e f f e c t of s u b s t i -tuents on p K 2 than on pK^. Because of our concern that the pK^ values f o r the most a c i d i c phosphonic ac ids might be lower than the measured 190 -2.6 i-l 1 1 1 -0.6 0 0.6 1 O" Plot of pK^ for arylphosphonic acids against the substituent constant a 191 -values ( i . e . l a r g e r values than are measured), thus lowering the a c t u a l value of py, we considered analogous systems to which the present system could be compared. However, there i s l i t t l e known about the e l e c t r o n i c e f f e c t of a r y l subst i tuents on success ive d i s s o c i a t i o n s of oxygen a c i d s . I t may be r e c a l l e d that our r e s u l t for the p-y and p 2 values for 5 - subs t i tu ted i s o p h t h a l i c ac ids are very s i m i l a r (p. 112, p-y = 1 . 0 5 , P2 = 1.02). While only s i x acids have been used i n these c o r r e l a t i o n s and the degree of accuracy for pK^ i s poorer than for pK 2 due to low s o l u b i l i t y of the d i a c i d , a study i n 50 wt % aqueous methanol i n v o l v i n g eleven i s o p h t h a l i c acids a l so gives s i m i l a r py and p 2 va lues , 1.21 and 1.20 r e s p e c t i v e l y (GS84). The l i m i t e d prec i s e data a v a i l a b l e for meta and para a r y l a r s o n i c acids ind ica te that py i s l a r g e r than p 2 (NC73 and references t h e r e i n ) . The successive d i s s o c i a t i o n constants of CgH5C0 2 H 2 - have been determined but , unfor tunate ly , t h e i r meta and para d e r i v a t i v e s do not appear to have been s tudied (HS74). Our concern regarding the pK^ values of the most a c i d i c compounds, i n p a r t i c u l a r the n i t r o subs t i tu ted phenylphosphonic a c i d s , stems from observat ion of d i f f erences i n the degrees of i o n i z a t i o n and d i s s o c i a t i o n of s trong and moderately strong acids (S85h and references t h e r e i n ) . The p e r t i n e n t e q u i l i b r i a are shown i n eq. [4.23] A r P 0 3 H 2 + H 2 0 _ - A r P 0 3 H ' - H 3 0 + ^ *T ArP0 3 H" + H 3 0 + [4.23] For weaker ac ids i o n i z a t i o n and d i s s o c i a t i o n are synonymous and so pK values measured p o t e n t i o m e t r i c a l l y w i l l correspond to the i o n i z a t i o n process; for s tronger acids t h i s may not be so. I t would be expected - 192 -that the r e a c t i o n constant of a Hammett type c o r r e l a t i o n would corres -pond to the i o n i z a t i o n process , which would mean that the we have measured might be s l i g h t l y low. Since our main concern i s the determi-n a t i o n of c a t a l y t i c e f fec t s i n the e n o l i z a t i o n of acetone, which w i l l depend on d i s s o c i a t i v e phenomena, the p o t e n t i o m e t r i c a l l y determined pK^ values are a l l we r e q u i r e . (In the case of the s trong h a l o - a c e t i c acids i o n i z a t i o n and d i s s o c i a t i o n are a l so d i s t i n c t processes . ) I t should be noted, however, that i n a c i d ca ta lyzed A-Sg-2 react ions (which involves proton t r a n s f e r from the a c i d to the substrate i n the r a t e - c o n t r o l l i n g step) , the p e r t i n e n t c a t a l y t i c species for s trong and moderately strong ac ids may be the i on p a i r or the non- ion ized a c i d and i t i s not known i f the use of potent iometr ic pK values i s appropr ia te . I t may be r e c a l l e d that the rate determining step i n the a c i d ca ta lyzed e n o l i z a t i o n of acetone involves proton t rans fer from the protonated substrate to the conjugate base o f the a c i d . The p K 2 values of the 3- and 4-carboxyphenylphosphonic ac ids r e f e r to the d i s s o c i a t i o n of the carboxyl group and t h i s allows a check to be made of the p r e v i o u s l y reported subst i tuent e f f e c t of the -PO3H" group (JF53) . A f t e r be ing correc ted to zero i o n i c s trength our r e s u l t s suggest that the -PO3H" group i s e l e c t r o n donating r e l a t i v e to hydrogen ( < 7 m = — 0.17 and = — 0.07) . The values reported p r e v i o u s l y i n d i c a t e d that the an ion ic moiety i s e l e c t r o n withdrawing; however, the pK values were not c o r r e c t e d for i o n i c s trength , which can be quite large for the second and h igher d i s s o c i a t i o n s of p o l y p r o t i c a c i d s . The r e l a t i v e o r d e r i n g of the meta- and para-P03H" acids i s the same i n our r e s u l t s as the e a r l i e r study. Since charged groups are notorious for the incons i s -193 -tency of t h e i r Hammett subst i tuent constant values (HH78), the s i g n i f i -cance of the a values we have der ived i s u n c e r t a i n . 4.4.2 Ortho Substituents Unl ike benzoic a c i d s , where v i r t u a l l y any ortho group has a marked ac id - s trengthen ing e f f e c t , most arylphosphonic acids with ortho s u b s t i -tuents have a c i d i t i e s that are roughly comparable to those of t h e i r para analogues, at l e a s t when d i r e c t i n t e r a c t i o n s such as hydrogen bonding are absent, and t h i s has been remarked upon p r e v i o u s l y (JF54) . The genera l l y accepted explanat ion for the ac id - s trengthen ing e f f e c t of ortho groups i n benzoic acids involves s t e r i c hindrance to conjugat ion i n the n e u t r a l molecule (E69). In the case of arylphosphonic a c i d s , i n which conjugat ion between the a c i d u n i t and the r i n g i s s l i g h t , we would not expect the marked ac id-s trengthening e f f ec t of ortho groups that i s c h a r a c t e r i s t i c of benzoic ac ids . One of the obvious l i m i t a t i o n s to Hammett p l o t s i s that they h o l d for meta and para subs t i tu ted d e r i v a t i v e s only . Since ortho s u b s t i t u -ents i n aromatic systems involve a number of e f f ec t s ( s t e r i c and e l e c t r o n i c ) , the q u a n t i f i c a t i o n (parametrizat ion) of these e f f ec t s with a Hammett-type equation i s d i f f i c u l t . B i j l o o and Rekker have used a m u l t i v a r i a t e ana lys i s method to evaluate the ortho e f f e c t based on the work of F u j i t a and Nisk ioka (BR84, FN76). In 1976 these l a t t e r workers proposed that the ortho e f f e c t i s composed of a po lar e f f e c t and prox imi ty e f f ec t s which can be expressed as a l i n e a r combination of - 194 e f f e c t s (as had been pos tu la ted by Charton i n 1971, C71). B i j l o o and Rekker have modif ied t h i s approach s l i g h t l y and t h e i r ana lys i s for benzoic ac ids i s prasented a f t er a b r i e f explanat ion of the method. The e l e c t r o n i c e f f e c t of an ortho group i s the sum of the para-s u b s t i t u e n t e f f e c t ( < 7 p ) and an a d d i t i o n a l induct ive e f f e c t only v a l i d f o r ortho subst i tuents (aj°). The s t e r i c e f f e c t of an ortho group i s q u a n t i f i e d by the s t e r i c parameter E g ° . The c o r r e l a t i o n for ortho, meta, and para benzoic ac ids i s then def ined by eq. [4.24] with aj° and E g ° be ing zero for the meta- and p a r a - s u b s t i t u t e d acids and a values for the or tho - subs t i tuent s being equivalent to the values for the para-s u b s t i t u e n t s . pK = p K 0 + pa + pyoj0 + SES° [4.24] With the omission of the two ortho parameters, eq. [4.24] reduces to the r e a d i l y recognizable Hammett equation. B i j l o o and Rekker c o r r e l a t e 46 meta and para benzoic acids and 18 ortho benzoic acids with eq. [4 .24] , and o b t a i n eq. [4.25] (r - 0.9982) pK = 4.21 - 0.96CT - 1.32CTJ0 + 0 . 4 0 E S ° [4.25] The va lues o f p (0.96) and pK Q (4.21) agree reasonably w e l l with the values f o r the meta and para benzoic ac ids only (1.00 and 4.20 respec-t i v e l y ) . The separat ion of ord inary p o l a r e f fec t s (CT), proximity p o l a r e f f e c t s ( o - j ° ) and s t e r i c e f fec t s ( E g ° ) i s deemed a success. The s ign of the c o e f f i c i e n t for the s t e r i c parameter, S, i s p o s i t i v e i n d i c a t i n g that - 195 -the s t e r i c e f f e c t i s a c i d strengthening ( E g ° values are negat ive ) . When a l l the pK data for our set of phenylphosphonic ac ids (Table 18, p. 117) are subjected to m u l t i v a r i a t e ana lys i s us ing eq. [4.25] (using a n , not a), s a t i s f a c t o r y c o r r e l a t i o n s could be obtained provided the ortho alkoxy groups were omitted; these compounds show anomalously h igh pK^ and p K 2 va lues , presumably because of hydrogen bonding between the oxygen of the alkoxy u n i t and the proton(s) of the phosphonic a c i d (N74). The r e s u l t s are shown i n eqs. [4.26] and [4 .27] . 29 ac ids p K x = 1.86 - 0.87cr n - 0.32a]; 0 - 0 . 1 3 E S ° [4.26] r = 0.9864 ± ± ± ± 0.02 0.04 0.07 0.02 30 ac ids p K 2 = 7.52 - 1 .07a n - 0.29a;,;0 - 0 . 3 3 E S ° [4.27] r = 0.9884 ± ± ± ± 0.02 0.06 0.09 0.02 The values of an for the meta and para subst i tuents are a v a i l a b l e i n Table 31, while the three parameters for the ortho subst i tuents are l i s t e d i n Table 32. The high c o r r e l a t i o n c o e f f i c i e n t s , the closeness of the p values to those found when meta and para compounds only are used (eqs. [4.19] and [4.21]) and the c lose agreement between the experimen-t a l and c a l c u l a t e d pK values of the unsubst i tuted compound suggest that the ortho e f f ec t s have been s u c c e s s f u l l y treated us ing eq. [4 .24] . The agreement i s not near ly as good when a comparison i s made between the meta and para s er i e s alone (eqs. [4.19] and [4.21]) and the ortho s er i e s alone (eqs. [4.28] and [4.29]) although s a t i s f a c t o r y c o r r e l a t i o n c o e f f i c i e n t s are obtained i n a l l cases. - 196 -Table 32: an ( = c n para ) , oj° and E s ° values for ortho subs t i tuents . Data from re f s (HW73, BR84). Substituent an OT° E O ° 2-CH3 -0, .10 0 .00 -1 .24 2-C2H5 -0, .12 0 .00 -1 .31 2-(CH3)2CH -0. .14 0 .00 -1 .71 2-F 0, .18 0 .54 -0 .46 2-Cl 0. .29 0 .47 -0 .97 2-Br 0. .30 0, .47 -1 .16 2-1 0. ,31 0. .40 -1 .40 2-N02 0, .78 0. .67 -1. .01 2,3-(CH3)2 -0. .18 0. .00 -1. .24 2,4-(CH3)2 -0. 20 0. .00 -1. ,24 2,5-(CH3)2 -0. 18 0. 00 -1. 24 2,6-(CH3)2 -0. 20 0. 00 -2. 48 2,4,6-(CH3)3 -0. 30 0. 00 -2. 48 197 -17 ac ids r = 0.9970 meta, para p K 2 = 7.55 - 1 .14a n ± ± 0.01 0.02 [4.19] 14 ac ids r = 0.9889 ortho p K 2 = 7.42 0.60tr n - 0 . 6 3 a ! 0 - 0 . 4 3 E S ° [4.28] + + + + 0.03 0.22 0.25 0.04 16 ac ids r = 0.9884 meta, para p K x = 1.88 - 0.92cr n [4.21] + + 0.01 0.02 14 ac ids r = 0.9879 ortho pK! = 1 . 8 2 0.05 + 0.49c7n - 0 . 6 4 ^ ! ° - 0 . 1 9 E S ° ± ± ± 0.17 0.19 0.03 [4.29] The poor agreement between the i n d i v i d u a l sets of meta/para com-pounds and ortho compounds i s a weakness i n t h i s ana lys i s (BR84). Perhaps the poor agreement r e f l e c t s the fac t that for the ortho com-pounds, eqs. [4 .28] , we are c o r r e l a t i n g four v a r i a b l e s for only fourteen compounds; t h i s a l so r e s u l t s i n the r e l a t i v e l y large standard d e v i a t i o n of the constants and, p a r t i c u l a r l y , the c o e f f i c i e n t s i n both of these equations. The standard deviat ions are grea t ly reduced i n eqs. [4.26] and [4 .27] , i n which the meta/para s er i e s i s added g i v i n g m u l t i v a r i a t e equations that involve over twice the number of compounds as p r e v i o u s l y c o r r e l a t e d . Thus a f a i r e r comparison may involve the meta/para s e r i e s and the meta/para/ortho s e r i e s , where the agreement has been shown to be very good. What i s the s i g n i f i c a n c e of the c o e f f i c i e n t s r e l a t e d to the ortho subs t i tuents? The values of pj, the o r t h o - i n d u c t i v e r e a c t i o n constant, - 198 are f a i r l y modest, (0.32 for pK^, 0.29 for p K 2 ) , and are much smaller than the value for benzoic ac ids , (1.32, eq. [4.25]). This i s not s u r p r i s i n g s ince there i s less conjugat ion i n t h i s system compared to the benzoic a c i d s . The c o e f f i c i e n t s of the s t e r i c parameters, 6, are negat ive , meaning that s t e r i c e f fec t s are a c i d weakening, the reverse of the s i t u a t i o n with benzoic ac ids . The values of —0.13 and —0.33 for pK^ and p K 2 can be compared with the value of +0.40 for benzoic ac ids (eq. [4.25]). The s t e r i c e f f ec t of ortho groups i n t h i s case i s probably assoc ia ted p r i n c i p a l l y with hindrance to s o l v a t i o n and, i f t h i s i s so, the l a r g e r 5 for p K 2 than for pK^ i s reasonable, i n d i c a t i n g a greater change i n s o l v a t i o n going from monoanion to d ian ion than from n e t u r a l a c i d to monoanion (MG64). Indeed, the n e u t r a l molecule, being highly , a c i d i c , may be quite h i g h l y so lvated , p a r t i c u l a r l y i f the i o n - p a i r form i s present i n s i g n i f i c a n t amounts (eq. [4.23]). The d i f f e r e n t i a l s t e r i c e f f e c t of ortho groups can be seen i n F i g . 49 where pK^ i s p l o t t e d against p K 2 . The h o r i z o n t a l displacement of the ortho compounds from the l i n e f or the meta and para compounds can be considered to be a measure of the enhanced s t e r i c e f f ec t on the second d i s s o c i a t i o n . 4.5 ARYLPHOSPHONATE DIANION CATALYSIS The data i n Table 21, p. 124, contains 16 meta- and para- and 13 o r t h o - s u b s t i t u t e d phosphonate d ian ion rate constants . For these c a t a l y s t s p and q have values of 1 and 3, r e s p e c t i v e l y . - 199 -PKZ F i g . 49: P lo t of pK^ against p K 2 f or arylphosphonic ac ids ; meta and para compounds (open c i r c l e s ) and ortho compounds (c losed c i r c l e s ) . Line drawn from meta and para compounds. 1. For a l l these phosphonate dianions a very good Bronsted r e l a t i o n s h i p i s obtained when the points for the charged subst i tuent -CO2" are omitted. The e f f e c t of t h i s subst i tuent w i l l be discussed l a t e r . The Bronsted p l o t i s shown i n F i g . 50 and the l i n e def ined by the fourteen meta and para phosphonate dianions i s given by eq. [4.30]. The value of B, 0.71 (± 0.02), suggests a t r a n s i t i o n state i n which the proton i s j u s t under three quarters t r a n s f e r r e d . I t i s i n t e r e s t i n g that t h i s more r e a c t i v e s er i e s of dianions has a smal ler B value than e i t h e r the carboxylate monoanion (0.89) or d ian ion (0.78) bases. This trend i s i n agreement with the Hammond postulate where the more r e a c t i v e system has an e a r l i e r t r a n s i t i o n s ta te . - 200 -pK + log p/q F i g . 50: Bronsted plot for catalysis of acetone enolization by arylphosphonate dianions; meta and para compounds (open c i r c l e s ) , ortho compounds (closed c irc les) and 3- and 4-CO2" compounds (open squares); l ine drawn with respect to the meta and para compounds - 201 -14 dianions log (k A 2- /q ) 10.0 + 0.712 (pK 2 + l og p/q) [4.30] r = 0.9960 ± ± 0.1 0.018 2. Ortho subst i tuents i n the d ian ion conform w e l l to the Bronsted l i n e drawn with respect to the meta and para compounds. De f in ing a l i n e for the ortho s u b s t i t u t e d dianions leads to eq. [4.31] which i s very s i m i l a r to eq. [4 .30] . 13 dianions log (k A 2- /q ) 10.1 + 0.712 (pK 2 + log p/q) [4.31] r = 0.9907 ± ± 0.2 0.029 However, i t can be seen that while eleven of these dianions f a l l e i t h e r on or j u s t below the meta and para l i n e , the 2-iodo and 2-bromo-s u b s t i t u t e d compounds deviate j u s t above such a l i n e . The standard dev ia t ions of the points i n F i g . 50 i s adequately represented by the span of the c i r c l e s and squares shown, and the d e v i a t i o n cannot be blamed on experimental e r r o r . The fac t that i t i s the bromo and iodo compounds which dev iate , and cons ider ing our experience with these subst i tuents i n both i sophthalate monoanions and a l i p h a t i c c a r b o x y l i c a c i d s , we c r e d i t t h e i r enhanced c a t a l y t i c a c t i v i t y to p o l a r i z a b i l i t y . We can estimate the degree of a c t i v a t i o n invo lved by c a l c u l a t i n g the k A 2 " 0 b S / k A 2 " ° a ' ' ' C v a l u e - The c a l c u l a t e d d ian ion rate constant i s that expected on the bas i s of the other eleven ortho d ian ions . The Bronsted l i n e for t h i s set of c a t a l y s t s i s given by eq. [4.32] and i s a s t a t i s t i -c a l improvement upon eq. [4.31]; a fac t which fur ther favours the 202 -e x c l u s i o n o f the iodo and bromo compounds from the ortho d ian ion Bronsted l i n e . 11 dianions l o g (k A 2- /q ) 1 0 . 3 + 0 . 7 4 2 (pK 2 + l og p/q) [4.32] r = 0.9986 ± ± 0.1 0.013 The r e s u l t i n g k A 2 - o b s / k A 2 - c a l c values are 1.37 for 2-1 and 1.21 for 2 -Br . These values are almost i d e n t i c a l to the r e s u l t s i n v o l v i n g 2-1 and 2-Br s u b s t i t u t e d i sophthalate monoanions; values of k j j ^ ^ / k ^ 0 3 1 0 i n tha t system are 1.41 for 2-1 and 1.20 for 2-Br , p. 183. Since there i s l e s s conjugat ion between the r i n g and the a c i d moiety i n t h i s system, we might have expected a l essening of the ortho p o l a r i z a b i l i t y e f f e c t but t h i s appears not to be the case. 3. With the except ion of iodo and bromo, there appears to be no s p e c i a l p r o x i m i t y e f f e c t on the rate of r e a c t i o n . That i s , ortho groups exert e s s e n t i a l l y the same e f f e c t on the d i s s o c i a t i o n e q u i l i b r i u m of the monoanions as on the rate of proton a b s t r a c t i o n by the arylphosphonate d ian ions ; t h i s i s i n agreement with the r e s u l t observed for carboxylate monoanion bases, both a l i p h a t i c and aromatic . While t h i s l a t t e r ser ies inc ludes a number of s t e r i c a l l y bulky a l i p h a t i c bases, i t does not prov ide the scope of ortho benzoate anion c a t a l y s t s one would wish for i n such a study. However, the phosphonate d ian ion ser i e s i s more extens ive i n t h i s regard and c l e a r l y no s i g n i f i c a n t rate a c c e l e r a t i n g or d e c e l e r a t i n g e f f ec t s are p r e s e n t . . I t should be noted that the ortho compounds inc lude both the 2-CH(CH3)2 and the 2 , 6 - ( 0 1 3 ) 2 compounds. I t 203 -i s a l so i n t e r e s t i n g to consider the carboxylate d ian ion set discussed p r e v i o u s l y from t h i s perspect ive ; while the s i ze of the ser i e s i s very l i v i i t e d and a number of hidden e f fec t s could be operat ing due to the range of s t r u c t u r a l - t y p e s of c a t a l y s t invo lved , phthalate d ian ion ( i n e f f e c t an ortho benzoate base) does not show an enhanced a c t i v a t i o n ( F i g . 30(b), p . 139). 4. When the arylphosphonate d ian ion includes a negat ive ly charged subs t i tuent , a small negative d e v i a t i o n i s observed. S i m i l a r dev iat ions for d i carboxy la te ions compared to monocarboxylate ions have been observed p r e v i o u s l y i n th i s work (p. 147) and by others (SS76a). The degree of d e v i a t i o n i n the rate constant k A 3 - from the Bronsted l i n e def ined by the meta and para d ianions , (eq. [4 .30]) , i s a fac tor of 1.8 ± 0.2 (average of the deviat ions for the 3 -CO2" and 4 -CO2" phosphonates). These fac tors are less than we observed i n the case of carboxylate dianions i n comparison to carboxylate monoanions, where dev ia t ions by fac tors of between 2 and 3 were observed. Consider ing the l a r g e r i o n i c s trength e f f ec t on pK values i n the case of d ian-i o n / t r i a n i o n d i s s o c i a t i o n s than for monoanion/dianion d i s s o c i a t i o n s , the degree of d e v i a t i o n for the phosphonate t r i a n i o n s i s probably l ess than i s suggested by F i g . 50. At an i o n i c s trength of 0.05 (as i s used for the phosphonates), pK^ 1 = — 0.26 whereas P K 3 1 = PK3T — 0.43. Taking account of the d i f f erence i n p K 1 due to the i o n i c s trength e f f ec t (0.17 pK u n i t s ) , the d e v i a t i o n fac tor i s only between 1.35 ± 0.15. C l e a r l y , whi le the phosphonate t r i a n i o n s deviate s l i g h t l y from the d ian ion l i n e , the d e v i a t i o n i s smal l , e s p e c i a l l y i n comparison to the - 204 -carboxylate s i t u a t i o n . A s i m i l a r i t y between the two s i t u a t i o n s i s that the d is tance separat ing the negat ive ly charged u n i t s does not seem s i g n i f i c a n t . Perhaps the rate r e t a r d a t i o n e f f ec t i n going from A" to A 2 " to A^~ i s a progres s ive ly weakening one; a comparison of a carboxylate t r i a n i o n with the set of dianions would be i n t e r e s t i n g i n t h i s regard . 4.6 ARYLPHOSPHONIC ACID CATALYSIS The data i n Table 23, p . 128, contains 10 meta- and para- and 10 o r t h o - s u b s t i t u t e d phosphonic a c i d rate constant . For these d i a c i d s , p and q are both equal to 2. 1. For c a t a l y s i s by the n e u t r a l phosphonic ac ids the Bronsted p l o t shows some divergence between the meta and para compounds on the one hand and the ortho compounds on the other , F i g . 51. The l i n e def ined by the ten meta and para acids i s given by eq. [4.33] . The value of a, 0.38 ( ± 0 .02) , impl ies a B value of 0.62 for the proton a b s t r a c t i o n from the conjugate a c i d of acetone by the phosphonate monoanions. 10 ac ids l og (k H A / p ) = - 4.35 - 0.383 (pK + log p/q) [4.33] r = 0.9890 2 ± ± 0.03 0.020 The value of B suggests a t r a n s i t i o n state i n which the proton i s more than h a l f t r a n s f e r r e d . This i s an e a r l i e r t r a n s i t i o n s tate than we - 205 -F i g . 51: Bronsted plot for catalysis of acetone enolization by arylphosphonic acid; meta and para compounds (open c irc les) and ortho compounds (closed c i rc le s ) ; l ine drawn with respect to the meta and para compounds 206 -observed with phosphonate dianions when n e u t r a l acetone i s the sub-s t r a t e . This may r e f l e c t the degree of a c t i v a t i o n conferred on the system by protonat ing the substrate , l ead ing to an e a r l i e r t r a n s i t i o n s t a t e . This i s dramat i ca l l y i l l u s t r a t e d i n the comparison of carboxy-l a t e anions when acetone i s the substrate (B = 0.89) and when protonated acetone i s the substrate (8 = 0 .38) . However, i n t h i s case the c a t a l y s t s are d i f f e r e n t (phosphonate monoanions with protonated acetone and phosphonate dianions with n e u t r a l acetone), and a comparison of the B va lues may be u n f a i r . 2. The ortho compounds deviate to a small extent i n the p o s i t i v e d i r e c t i o n i n comparison to the meta and para compounds. The dev ia t ions , which are not l a r g e , are more pronounced for the more a c i d i c compounds, suggest ing a s l i g h t l y l a r g e r Bronsted c o e f f i c i e n t may govern the r e a c t i v i t y of the ortho rather than that of the meta and para compounds. Even when the ortho compounds are omitted, there i s more s c a t t e r i n the Bronsted p l o t for c a t a l y s i s by ArP03H2 ( F i g . 51) than i n that for c a t a l y s i s by A r P 0 3 2 " ( F i g . 50), an e f f e c t that i s probably due to the p r e c i s i o n of the measurements of both pK^ and kj^A being somewhat lower than the measurements of p K 2 and k^2-. A s i m i l a r e f f e c t for the 2-1 and 2-Br c a t a l y s t s i s observed i n t h i s case, as i s evident i n phosphonate d ian ion c a t a l y s i s ; the c a t a l y s t s possess ing these o r t h o - p o l a r i z a b l e subst i tuents show enhanced r e a c t i -v i t y . The other two ortho-halo c a t a l y s t s , which possess l e ss p o l a r i z -able halogens, show no such e f f e c t , as i n the case of the dianions ( i . e . 2 - C l and 2 - F ) . This example of a rate a c c e l e r a t i n g e f f e c t has now been - 207 observed i n four d i f f e r e n t ser ies of c a t a l y s t s and shows two expected trends; the degree of p o s i t i v e d e v i a t i o n i s d i r e c t l y r e l a t e d to the p o l a r i z a b i l i t y of the subs t i tuent , and i s a lso r e l a t e d to the proximity of the subs t i tuent to the c a t a l y t i c centre . The Bronsted l i n e def ined by the ortho subs t i tuents , exc luding the iodo and bromo compounds, i s g iven by eq. [4 .34] . The values of k H 2 A O D S / k H 2 A C a l c for 2-Br and 2-1 are 1.12 and 1.09, r e s p e c t i v e l y ; these values are smal ler than i s observed f o r the d ian ions , and are a l so more prone to e r r o r due to the inherent s c a t t e r i n the Bronsted p l o t . However, i t may have some s i g n i f i c a n c e i n that the r e a c t i o n constant for pK^ i s lower than for p K 2 and a c c o r d i n g l y a proximity p o l a r i z a b i l i t y e f f e c t may w e l l be expected to be l e ss for k ^ A than the k A 2 - . 8 ac ids l og (k H A / p ) = - 4.26 - 0.419 (pK + log p/q) [4.34] r = 0.9893 2 ± ± 0.05 0.025 3. While the s c a t t e r i n F i g . 51 i s a hindrance to ana lys i s of the r e s u l t s , the ortho compounds do appear to form a l i n e with a s l i g h t l y h igher s lope than that for the meta and para compounds. This impl ies a smal ler 8 va lue for the rate determining second step of the general a c i d c a t a l y z e d e n o l i z a t i o n . I t may be r e c a l l e d that the 2- i sophthalate d ian ions wi th protonated acetone as the substrate had a smal ler B value than the 5 - i sophthalate d ian ions , a f a c t , we suggested, that can be l i n k e d to a s t e r i c a c t i v a t i o n e f f e c t l ead ing to an e a r l i e r t r a n s i t i o n s tate ( smal ler 0 v a l u e ) . A s i m i l a r s i t u a t i o n might be operat ive here, - 208 -wi th the e f f e c t being apparently smaller than for the i sophthalate system. 4.7 ARYLPHOSPHONATE MONOANION CATALYSIS We had hoped to determine a number of arylphosphonate monoanion rate constants , but unfor tunate ly , as was mentioned i n Sect ion 3.2.4, accurate k ^ - va lues were inacces s ib l e due to the much l a r g e r k ^ A and k^2- va lues . Table 24, p. 130, does conta in three k j ^ - values but the v e r y large standard deviat ions for two of these values makes an ana lys i s of the rate constants d i f f i c u l t . 1. I f the arylphosphonate monoanions are a c t i n g as ac ids the second d i s s o c i a t i o n constant i s involved and we can p r e d i c t an estimate of the k HA" values by extending the H 2 A Bronsted l i n e in to the p K 2 range (eq. [4.33], ArP03H2 c a t a l y s i s ) . For example, the 3-nitrophenylphosphonate monoanion (pK 2 = 6.69) should have a k j ^ - value of 1.9 x 10" 7 M " 1 sec" 1 on t h i s bas i s (p = 1, q = 3 for HA" as an a c i d ) . On the other hand, i f the monoanions are a c t i n g as bases, the f i r s t d i s s o c i a t i o n constant i s i n v o l v e d . An extension of the A 2 " Bronsted l i n e in to the pK^ range (eq. [4 .30] , ArP03^" c a t a l y s i s ) provides a rough value for k ^ - a c t i n g as a base. The r e s u l t f or the 3 -n i t ro monoanion (pK^ =1.20, p = 2, q = 2) suggests a k j ^ - value of 1.4 x 10" 9 M " 1 s ec" 1 . Furthermore, i f b i f u n c t i o n a l c a t a l y s i s were important, the c a t a l y t i c constants would be expected to be cons iderably increased over the values c a l c u l a t e d on the - 209 -bas i s of the Bronsted p l o t s for both ArPG^H^ and ArPC>3 2". The value of k ^ - determined for the 3 - n i t r o monoanion (1.1 x 10" 7 M " 1 s e c ' l ) i s of the same order of magnitude as that p r e d i c t e d on the bas i s of t h i s species a c t i n g as an a c i d . The value expected, i f the monoanion acts as a base, i s two orders of magnitude smal ler than the exper imental ly determined rate constant . We conclude that the phospho-nate monoanions are ac t ing as general a c i d s , not general bases, and b i f u n c t i o n a l c a t a l y s i s appears to be absent. The monoanions of the d i c a r b o x y l i c ac ids that were s tudied a lso act as general a c i d s . 2. Since the -PO3H" group behaves as an a c i d i n the e n o l i z a t i o n of acetone, the phosphonic a c i d with the lower p K 2 value has the more e f f e c t i v e monoanion c a t a l y s t , while s imultaneously having the less e f f e c t i v e d ian ion c a t a l y s t . Thus phosphonic acids with lower p K 2 values than those i n the extensive set a lready examined might al low an accurate determinat ion of some k ^ - va lues . On t h i s bas i s we decided to study a few alkylphosphonic a c i d s , whose p K 2 range spans from 4.93 (CI3CPO3H;)) to 8.71 ( ( C H 3 ) 3 C P 0 3 H 2 ) (KT77). In a s i m i l a r manner to that employed for the arylphosphonates, us ing o buf fers of HA" and A , we attempted to measure k A 2 - and kjj^- . For the two weaker a c i d s , HA", ( i . e . the phosphonate monoanions, h igh p K 2 values) c a t a l y s i s by the monoanion was not detectable while values of k A 2 - cou ld be obtained (methyl phosphonate and t-butylphosphonate d i a n i o n s ) . In the case of chloromethylphosphonate b u f f e r s , we were able to detect a small c a t a l y t i c e f f e c t a t t r i b u t a b l e to the monoanion, though the d ian ion i s more e f f e c t i v e as a c a t a l y s t by a f a c t o r of at l ea s t 15 ; 210 -a p l o t of the (slope of k o b s v s . [AH"]) against 1/m had a no t i ceab le , but s m a l l , i n t e r c e p t i . e . k ^ - , eq. [3.21] (see p. 118). k obs " k sum + [HA"] AHA- + ( l /m)k A 2-} [3.21] When we examined buf fers of tr ichloromethylphosphonate, we found an i n t e r e s t i n g r e s u l t ; the monoanion i s more e f f e c t i v e as a c a t a l y s t than the d i a n i o n ( fac tor of 5, approximately) . The r e s u l t s for the a l k y l phosphonates are given i n Table 33. Table 33: k A 2 - values and k ^ - values (where measurable) f o r acetone e n o l i z a t i o n cata lyzed by alkylphosphonates at 25°C and 0.05 M i o n i c s trength A c i d p K 2 a 10 7 k ^ - 10 6 k A 2 - b r b Method 0 M " 1 sec" 1 M " 1 s e c ' 1 (CH 3 )3CP0 3 H2 8.71 - 206 ± 3 2 1 C H 3 P 0 3 H 2 8.00 - 60.8 ± 3 2 I C 1 C H 2 P 0 3 H 2 6.59 3.05 ± 2.74 4.42 ± 0.27 3 II C l 3 C P 0 3 H 2 4.93 7.62 ± 0.09 0.157 ± 0.004 3 II a Thermodynamic pK2 values from r e f . (KT77). D Number of buf fer r a t i o s c Method I p l o t s of k o b s v s . [A 2"] Method II (slope of k o b s v s . [HA"]) v s . 1/m g i v i n g k A 2 - , slope and k H A " ' i n t e r c e p t . 211 -While the k ^ - value for CICH2PO3H" (pK, 6.59) has a large ..standard d e v i a t i o n i t i s s l i g h t l y l a r g e r than the value for 3-nitrophenylphospho-nate monoanion (pK, 6.69) and smaller than the value for CI3CPO3H" (pK, 4 .93); a general a c i d c a t a l y s i s Bronsted l i n e based on these monoanions w i l l only give an approximate value of a as the dev iat ions of the two smal ler k ^ - values i s rather l arge . The r e s u l t i n g a value i s 0.24 wi th the combination of CI3CPO3H" and CICH2PO3H" , o r , on the other hand, 0.48 with the combination of CI3CPO3H" and 3-N0 2 -ArP03H". Obviously an i n t e r p r e t a t i o n of these Bronsted c o e f f i c i e n t s i s very d i f f i c u l t as the 0 value for -~P0^' (1-a) has a large average d e v i a t i o n , being roughly equal to 0.64 ± 0.12. Further work i n t h i s area with a set of a l k y l -phosphonates i n a pK range of 4 to 6 would provide a more r igorous 0 va lue . 3. The k^2- values determined for the alkylphosphonates can be compared with the set of a r y l dianions discussed p r e v i o u s l y . The Bronsted p l o t for a l l these phosphonate dianions i s shown i n F i g . 52 and shows an i n t e r e s t i n g t rend . The values for ch loro - and e s p e c i a l l y t r i c h l o r o -methyl phosphonate f a l l s l i g h t l y below the extension of the Bronsted l i n e for the meta and para arylphosphonates. The fac t that the methyl-and t -butyl-phosphonates f a l l on or c lose to that l i n e i l l u s t r a t e s the v a l i d i t y of cons ider ing the a l k y l and a r y l dianions as a homogeneous group. The t rend , obvious from F i g . 52, i s that a s l i g h t l y curved l i n e may be a b e t t e r representat ion of the Bronsted l i n e than a l i n e a r c o r r e l a t i o n . The curvature i s i n the d i r e c t i o n p r e d i c t e d by the Hammond pos tu la te and Marcus theory; the l e ss r e a c t i v e c a t a l y s t s possess ing the 212 -4.0 4.9 6.8 6.7 7.6 8.6 pK + log p/q 52: Bronsted plot for catalysis of acetone enolization by phosphonate dianions; meta and para aryl compounds (open c i r c l e s ) , ortho aryl compounds (closed c irc les) and a lkyl compounds (open squares), sol id l ine drawn with respect to the meta and para arylphosphonates, dotted l ine (quadratic, eq. [4.45]) drawn with respect to a l l the phosphonates - 213 -larger B values, implying a later transition state. For example, the Bronsted line defined by the meta and para aryl dianions and the alkyl dianions, inclusive of phenylphosphonate dianion and weaker bases (pK2 <7.51), is given by eq. [4.35]; the linear correlation is quite good for this set of catalysts and a B value of 0.875 (± 0.025) results. A Bronsted line for the same type of catalysts inclusive of phenylphos-phonate dianion and stronger bases (pK2 >7.51) is defined by eq. [4.36]; once again, the linear correlation is quite good but a smaller 8 value is evident, 0.732 (± 0.019). 11 dianions log (kA2-/q) = - 11.1 + 0.875 (pK2 + log p/q) [4.35] r = 0.9964 ± ± 0.2 0.025 8 dianions log (kA2-/q) 10.2 + 0.732 (pK2 + log p/q) [4.36] r = 0.9979 ± ± 0.1 0.019 The curvature present in Fig. 52 would be undetectable, i f only the alkylphosphonates had been studied; this set of four dianions gives a very acceptable linear correlation, r = 0.9996 and B = 0.83. A further point is that the trichloromethylphosphonate dianion may be enhanced due to a polarizability effect (which is evident in the 2-iodo and 2-bromo-phenylphosphonate dianions), and the 'true' curve may possess a greater degree of curvature than is evident from Fig. 52. A study involving a set of phosphonates in the lower regions of the curve is needed (as suggested earlier in order to obtain monoanion rate constants). We will return to an analysis of these results when we discuss 214 -general aspects of a l l t h i s work, before f i n a l l y summarizing the conc lus ion der ived from our ana lys i s of these r e s u l t s . 4.8 GENERAL DISCUSSION 4 .8 .1 Curvature i n General A c i d Catalyzed Bronsted P lo t s I t may be r e c a l l e d that the c a r b o x y l i c a c i d data, a f t e r removing those ac ids that are prone to e i t h e r a s t e r i c e f f e c t or a p o l a r i z a b i l i t y e f f e c t , was i n t e r p r e t e d as a curved Bronsted p l o t , ( F i g . 36, p. 160, eq. [4 .11] , p . 161 or eq. [4.13] , p. 166). Obviously t h i s i n t e r p r e t a t i o n i s open to c r i t i c i s m and i t may w e l l be eas i er and s impler to define a l i n e a r c o r r e l a t i o n and leave i t at that . However our approach i s to quest ion the l i k e l i h o o d of such curvature , rather than ignore i t . So we set about fur ther research i n t h i s area . 1. One of the explanations advanced for curvature i n r a t e - e q u i l i b r i a r e l a t i o n s h i p s has been deso lvat ion of i n c r e a s i n g l y bas i c anions (see p. 35). While t h i s p a r t i c u l a r cons idera t ion i s not a p p l i c a b l e to the general a c i d ca ta lyzed mechanism, i t does r a i s e the matter of a solvent e f f e c t on the rate constants causing n o n - l i n e a r c o r r e l a t i o n s of rate and e q u i l i b r i u m constants . We f a i l to see how the so lvent could have such an e f f e c t i n our system. However, reported values of k ^ i n D 2 0 when compared to the values i n H 2 0 for a c i d ca ta lyzed bromination of acetone show a trend; the r a t i o of k ^ values (H 2 0 /D 2 0) increases along the - 215 -s e r i e s C1CH 2 C0 2 H (1.22) , HOCH 2 C0 2 H (1.37) , CH 3 C0 2 H (1.54) (RK39). Perhaps the trend continues for the stronger c a r b o x y l i c acids and i s somehow causing curvature i n the Bronsted p l o t ; thus we decided to measure k p ^ values i n D 2 0 ( k ^ ) . For three acids with both measurable k j ^ and k A - va lues , we simply repeated the procedure fol lowed for measurements i n H 2 0 , r e p l a c i n g H 2 0 wi th D 2 0 at a l l stages. The r e s u l t s are given i n Table 34, along with the r e s u l t s for four other acids with n e g l i g i b l e k A - va lues . These a c i d s , c h l o r o a c e t i c and stronger, were s tudied i n the same manner as be fore . Th i s necess i ta ted a measurement of kj)+ i n order to evaluate ( k o b s — k n +[D30 + ] ) , and hence k n A . This was done i n a s i m i l a r fashion to that for k^+; as i n that case, both a s t o i c h i o m e t r i c and a pH(pD)-der ived rate constant were obtained, the pD-derived value (6.54 ± 0.08 x IO"-* M _ 1 s e c - 1 ) being used i n subsequent determinations of k j ^ f ° r the h a l o - a c i d s . The pD values are obtained from the r e l a t i o n s h i p , pD = 'pH reading ' + 0 . 4 0 (SS76a and references t h e r e i n ) . The s t o i c h i o m e t r i c r e s u l t f or k D + i s 4.62 ± 0.10 x I O ' 5 M " 1 sec" 1 (slope of k o b s against [D 3 0 + ] f or 11 k i n e t i c runs ) , g i v i n g a k H +(H 2 0) /k D +(D 2 0) value of 0.543 ± 0.013. Thi s r a t i o agrees with that of Tou l l ec and Dubois and impl ies that D 3 0 + i s a b e t t e r c a t a l y s t than H30 + . This enhanced c a t a l y t i c a c t i v i t y i s due to the greater protonat ing power of D30 + , despite the poorer base capac i ty of D 2 0 r e l a t i v e to H 2 0 . The general acids that were examined show a n e g l i g i b l e solvent isotope e f f e c t except for the weaker acids which e x h i b i t a very s l i g h t e f f e c t ; knA .(H 2 0) seems to be greater than k p A ( D 2 0 ) for these a c i d s . The e f f e c t on of changing the solvent to D 2 0 i s an a c i d 216 -weakening one, and i s genera l ly given by eq. [4.37] at 25°C (ML62). Th i s pK c o r r e c t i o n - f a c t o r v a r i e s l i t t l e and i s u n l i k e l y to be a cause of the smal l e f f ec t s evident i n Table 34. Table 34: k p A values for acetone e n o l i z a t i o n at 2 5 ° C , measured i n D 2 0 and r e s u l t i n g k H A ( H 2 0 ) / k H A ( D 2 0 ) A c i d 1 0 ? k D A ( D 2 ° ) k H A ( H 2 ° ) / k D A ( D 2 0 ) a n k b b r c M " 1 sec" 1 F 3 C C 0 2 D 218 + 13 0. ,94 + 0. 07 3 -F 2 CHC0 2 D 62.7 + 1.4 1. ,02 + 0. ,03 5 -C1 2 CHC0 2 D 101 + 3 0. .92 + 0. ,03 6 -C1CH2C02D 11.4 + 0.2 0, .96 + 0. .10 4 -HOCH 2C0 2D 2.47 + 0.04 1. .25 + 0. .05 - 3 CH 3 C0 2 D 0.541 + 0.037 1, .52 + 0. .11 - 3 ( C H 3 ) 3 C C 0 2 D 0.513 + 0.044 1. .40 + 0. ,13 - 3 k H A (H20) values from Tables 7 and 9, pp. 81 and 88. Number of k i n e t i c runs Number of buf fer r a t i o s - 217 -p K D A = 0 . 4 1 + 1 . 0 2 V K m [ 4 . 3 7 ] As mentioned e a r l i e r , the r e s u l t s of Re i t z and Kopp show a solvent e f f e c t ; the e f f e c t i s s i m i l a r to the one that we observe and has not been adequately expla ined (LR69). The f a c t that the weaker ac ids e x h i b i t a decreased c a t a l y t i c a c t i v i t y while the stronger ac ids remain unchanged, gives r i s e to a greater degree of curvature for the Bronsted p l o t i n D2O. The s i g n i f i c a n c e of these r e s u l t s i s not evident to us . The absence and presence of solvent e f f ec t s i n the kjj^ values does not provide any i n s i g h t into the nature of the Bronsted c o r r e l a t i o n i n H2O; i n f a c t , i t r a i s e s new questions that merit a more thorough ana lys i s than i s presented here . 2 . I f the c a r b o x y l i c a c i d curvature i s due to a changing t r a n s i t i o n s ta te , i . e . d i f f e r e n t degrees of proton t r a n s f e r , an ana lys i s of the r e s u l t s us ing Marcus theory may be informat ive . Fol lowing on our d i s c u s s i o n i n Chapter 1, such an ana lys i s makes use of a quadrat ic express ion for the Bronsted curved l i n e . For a complete treatment, i t i s more appropriate to c a l c u l a t e rate constants for proton a b s t r a c t i o n from protonated acetone by the conjugate base of the a c i d , k ' A - , eq. [ 1 . 7 7 ] (p. 5 1 ) . This requires that three parameters be known , k j ^ , K J I A and K ^ H + I the l a t t e r i s the d i s s o c i a t i o n constant of protonated acetone, eq. [ 4 . 3 8 ] - 218 k ' A - = SkHAkzH+AHA [1-77] K Z H + = [Z][H+]/[ZH + ] [4.38] There i s disagreement about the a c i d s trength of protonated acetone; estimates of pK-2M+ range from -2.2 to -7.2 (A82 and references t h e r e i n ) . Values of -2.9 and -6 have both been used i n previous s tudies (S85d, A82); i n order to see how c r i t i c a l the magnitude of the values are to our a n a l y s i s , we chose to use both pK^H"1" values ( l eading to k ' A -values which d i f f e r by 10 ) . The data i n Table 35 contains the k ' A -r e s u l t s for the set of carboxylate bases which we wish to examine, i . e . the e ight carboxylates free of both p o l a r i z a b i l i t y and s t e r i c e f f e c t s . The quadrat ic expression for th i s data i n terms of eq. [1.53] , p. 25 i s g iven by eq. [4.39] (p and q have values of 1 and 2, r e s p e c t i v e l y ) . The use of pKj^ A instead of log K ^ A r e s u l t s i n a change of s i gn i n the c o e f f i c i e n t of the l i n e a r term, E , eq. [4.40]. We w i l l use the form of eq. [4 .39] , as i t c l e a r l y i l l u s t r a t e s the log k - log K r e l a t i o n s h i p as w e l l as being a t i d i e r express ion than eq. [4.40] . log k B = D + E ( log K B H +) + F ( log K B H + ) 2 [1.53] log ( k ' A - / q ) = D + E ( log K ^ q / p ) + F ( log K ^ q / p ) 2 [4.39] l o g ( k ' A - / q ) = D - E (pK + log p/q) + F (pK + log p / q ) 2 [4.40] 219 -T a b l e 35: C a l c u l a t e d k ' A - v a l u e s f o r a c e t o n e e n o l i z a t i o n c a t a l y z e d by c a r b o x y l a t e b a s e s u s i n g e q . [ 1 . 7 7 ] w i t h k Z H + = 800 M ( k ' A - [ l ] ) o r 1 0 6 M < k ' A - [ 2 ] ) B a s e k ' A - [ l ] M ' 1 s e c 4 1 0 3 k ' A - [ 2 ] M ' 1 s e c " 1 P % A A F 3 C C 0 2 _ 0 . 0 5 6 4 .0711 0 . 5 4 F 2 C H C 0 2 " 0 . 1 0 1 .127 1 . 3 0 C 1 C H 2 C 0 2 " 0 . 6 3 3 .797 2 . 8 6 C H 3 0 C H 2 C 0 2 - 1 .42 1 .78 3 .57 H 0 C H 2 C 0 2 _ 1 .66 2 . 0 9 3 . 8 3 C H 3 C 0 2 _ 3 . 7 6 4 . 7 4 4 . 76 C D 3 C 0 2 * 3 . 9 1 4 . 9 3 4 . 7 7 C H 3 C H 2 C 0 2 " 3 . 8 5 4 . 8 5 4 . 8 7 P^HA v a l u e s a t z e r o i o n i c s t r e n g t h - 220 -Using a value of -2.9 for pK-7jj+ the r e s u l t i n g quadrat ic i s given by eq. [4 .41] . The s i ze of the c o e f f i c i e n t , as w e l l as the d e v i a t i o n for the squared term, (-0.016 ± 0.010), i l l u s t r a t e s the debatable nature of the choice of a quadrat ic vs . l i n e a r c o r r e l a t i o n , eq. [4 .42] . The c o r r e l a t i o n c o e f f i c i e n t i s s l i g h t l y be t t er for the quadrat ic express ion, whi le the large standard d e v i a t i o n of the squared term w i l l l ead to a comparable large d e v i a t i o n i n the i n t r i n s i c b a r r i e r . 8 bases; r = 0.9985 log ( k ' A - / 2 ) - - 1.72 - 0.518 ( log 2 ^ ) - 0.0156 ( log 2 ^ ) 2 [4.41] ± ± ± 0.05 0.050 0.0098 8 bases; r = 0.9975 log ( k ' A - / 2 ) - - 1.67 - 0.440 ( log 2 ^ ) [4.42] + + 0.04 0.013 Use of eqs. [1 .54] - [1 .56] , p. 25, provides values of A G Q , W r and Wp. The r e s u l t s are given i n Table 35 and apart , from the W r term, the large standard dev ia t ions of the AG Q and Wp term r e f l e c t the poor s t a t i s t i c s of the c o e f f i c i e n t preceding ( log 2KJJ I A) . This s i t u a t i o n i l l u s t r a t e s the d i f f i c u l t y i n analyz ing Bronsted p l o t s us ing the Marcus equation; unless the degree of curvature i s w e l l def ined, the r e s u l t i n g i n t r i n s i c b a r r i e r and work terms can only be very rough est imates . I f the data i n Table 35 i s analyzed a f t er d e l e t i n g the t r i f l u o r o a c e -tate anion (which may show enhanced c a t a l y t i c a c t i v i t y due to p o l a r i z a -b i l i t y ) , a much improved quadrat ic equation i s obtained from a s t a t i s t i -c a l po in t of view, eq. [4 .43] . The r e s u l t i n g parameters have now acceptable degrees of d e v i a t i o n , and these are a l so l i s t e d i n Table 36. 221 -Table 36: Results of Marcus Theory Analysis of Carboxylate Anion Data (Table 35) f o r Protonated Acetone E n o l i z a t i o n ; Units of k c a l mol" 1, pKZ H+ = - 2.9 Equation np a AGQ Wr Wp [4.41] 8 5.5 ± 3.4 14 ± 4 19 ± 20 [4.43] 7 2.4 ± 0 . 4 16 ± 1 23 ± 3 a Number of data points 7 bases, excluding F3CCO2", r = 0.9995 log (k' A-/2) - - 1.92 - 0.652 (log 2 ^ ) - 0.0363 (log 2 % ^ [4.43] ± ± ± 0.05 0.035 0.0060 The r e s u l t s of the analysis using a pK£H + value of -6 are quite s i m i l a r to the values i n Table 36, i . e . within the deviations quoted. C l e a r l y , while the Marcus parameters from eq. [4.41] are question-able, as i s the use of a quadratic c o r r e l a t i o n , the r e s u l t s of eq. [4.43] seem to be quite rigorous; a quadratic c o r r e l a t i o n ( Fig. 53) i s a good improvement upon a l i n e a r one (r = 0.9995 and 0.9955, respec-t i v e l y ) . However, an analysis based on eq. [4.43] i s both greatly dependent on excluding t r i f l u o r o a c e t a t e ion and in c l u d i n g difluoroace-tate ion. Bearing t h i s i n mind, does the Marcus treatment give r e s u l t s which support, or question, the assumed curvature i n the Bronsted plot? - 222 Fig. 53: Curved Bronsted plot for catalysis of 'protonated acetone' enolization by carboxylate bases, open circles, eq. [4.43]; trifluoroacetate ion, closed square. 5* The consequence of AG Q being small as compared to Wr (the work term needed to 'set-up' the reactants for proton transfer) has been observed before in a number of proton transfer reactions (K73). It is worth recalling the meaning of AG Q, the intrinsic barrier; i t is the kinetic factor of the reaction barrier for a hypothetical system where AG° = 0. A small value of AG Q implies a rapid proton transfer, which when linked to a large Wr term, indicates a system where organizing the reactants for the actual proton transfer is the major energy cost involved in the 223 -r e a c t i o n . I f we could compare our r e s u l t s with some c l o s e l y r e l a t e d system for which the Marcus parameters have been determined, an evalua-t i o n of the v a l i d i t y of our ana lys i s can be made. Unfortunate ly , no such data e x i s t s that allows an eva luat ion of these parameters for a set of general bases and a protonated ketone. The reason for t h i s i s s imple; curvature i n the Bronsted p l o t has not been observed for a set of s t r u c t u r a l l y s i m i l a r general a c i d c a t a l y s t s . ( A c t u a l l y , there i s one report of such curvature i n an a c i d cata lyzed e n o l i z a t i o n , but i t i s due to a s o l v a t i o n e f f e c t i n DMSO, see p. 36). On the other hand, a number of s tudies i n v o l v i n g n e u t r a l ketones and curved Bronsted p l o t s have been reported and t h i s subject has been discussed i n some d e t a i l prev ious ly (Sect ion 1.10.1, p. 44). There are at l ea s t two i n t e r p r e t a t i o n s of the a v a i l a b l e data; one c r e d i t s r a p i d l y changing Bronsted slopes (usua l ly with a range of s t r u c t u r a l l y d i s s i m i l a r c a t a l y s t s , see p. 45, K073) with small A G Q values (= 3 k c a l mol x ) and large W r terms (~ 12 k c a l mol ; another favours a gradual ly changing t r a n s i t i o n state with large A G Q values (~ 10 k c a l mol" 1 ) and small W r terms (see p. 45, HW77). 3. Primary isotope e f fec t s would be informative as to the degree of proton t r a n s f e r i n the t r a n s i t i o n s tate and hence to the degree of change of proton t r a n s f e r along the c a t a l y s t ser ies (See Sect ion 1.8, p. 28) . As expla ined p r e v i o u s l y , s i m i l a r procedures were used to determine a number of k ^ values with acetone-dg as the substrate . Using the b u f f e r - r a t i o method values of kjj^ were determined for a couple of ac ids , ( ace t i c a c i d kn measurement could not be measured, as the acetate anion - 224 swamped the a c i d c o n t r i b u t i o n to k o b s ) . In the case of the stronger c a r b o x y l i c a c i d s , th i s required a determination of for the deuterated substrate . As i n the case of acetone i n and D2O, both a s t o i c h i o m e t r i c and a pH-derived value of k H + are determined. The value of the s t o i c h i o m e t r i c k H+ i s 4.23 ± 0.03 x I O " 6 M " 1 sec" 1 (12 k i n e t i c runs , slope of p l o t of k o b s against [l^O"1"]). The value of k^/kp for hydronium ion i s therefore 5.9 ± 0 . 1 . This value compares with e a r l i e r values of 6.5 (HK72) and 6.7 (TD74) , (see p. 50). The pH-derived value i s 4.96 ± 0.04 x 10"^ M " 1 sec" 1 and i t i s t h i s value that i s used to subtrac t the kH+[H.30+] term from k o b s i n determining k^A va lues . A l l the k H A v a l u e s measured us ing acetone-d^ are l i s t e d i n Table 37 . An examination of the k^/kj) values i l l u s t r a t e s two important po in t s : ( i ) the values are genera l ly c lose to the t h e o r e t i c a l expected maximum of 6.9 (p. 4 7 ) , i n d i c a t i n g h a l f t rans fer of the proton i n the t r a n s i t i o n s ta te ; ( i i ) there i s no apparent trend i n the values that could be r e l a t e d to changing pK of the a c i d c a t a l y s t s . Consider F3CCO2H, C 1 C H 2 C 0 2 H and H 0 C H 2 C 0 2 H ; values of k H / k D r i s e and f a l l along the set , 7.9, 7.3 and 7.9. There may w e l l be a trend i n the isotope e f f e c t s , but , i f so, i t i s a small e f f ec t and i s masked by the large standard dev iat ions of the rate constant r a t i o s . The absence of a no t i ceab le change i n the primary isotope e f f ec t argues against a changing t r a n s i t i o n s tate; such a t r a n s i t i o n state would involve changes i n the degree of proton t rans fer and accord ing ly changes i n k^/k^ va lues . Thus, these r e s u l t s undermine the v a l i d i t y of apply ing Marcus theory to the r a t e - e q u i l i b r i a c o r r e l a t i o n . In other words, while curvature may or may not be present , the isotope e f f ec t s i n d i c a t e that a Table 37: values for acetone-dg enolization at 25°C, measured in and the resulting kjj/kj) values A c i d 10 8 k ^ k H / k D a n k b b r ° M " 1 s ec* 1 F 3 C C 0 2 H 258 + 22 7. 9 + 0. 8 5 -C1 2 CHC0 2 H 132 + 7 7. ,0 + 0. 4 8 -2-N0 2 C 6 H4C0 2 H 44.7 + 3.3 8. .8 + 0. .8 3 -C1CH 2 C0 2 H 15.1 + 1.9 7, .3 + 1. .1 4 -H0CH 2 CO 2 H 3.92 + 0.38 7 .9 + 0, .8 - 3 C 6 H 5 C H 2 C 0 2 H 2.54 + 0.06 7 .6 + 0 . 5 - 3 k H values from Tables 7, 9, and 11, pp. 81, 88 and 94. Number of k i n e t i c runs Number of buf fer r a t i o s changing t r a n s i t i o n state i s not occurr ing i n the range of acids s t u d i e d . The fac t that /3 i s c lose to 0.5 should lead us to expect i sotope e f f ec t s near the maximum and indeed t h i s i s so. At t h i s po int we w i l l leave the issue of general a c i d c a t a l y s i s . We f e e l the d i s c u s s i o n of t h i s subject has i l l u s t r a t e d the experimental and the i n t e r p r e t a t i v e d i f f i c u l t i e s i n dec id ing whether curvature i s present i n Bronsted p l o t s or not . - 226 One l a s t po in t that the reader may have no t i ced i n Table 37. The isotope e f f e c t for 2 -n i trobenzo ic a c i d i s 8.8 ± 0.8; t h i s i s the l arges t one measured and i t may be s i g n i f i c a n t . I t may be r e c a l l e d that large isotope e f f ec t s have been assoc iated with s t e r i c a l l y crowded c a t a l y s t s , an e f f e c t that has been l i n k e d to t u n n e l l i n g (see p. 60). Obviously a study of ortho-benzoic acids would be informat ive . However, i f k^/kj) i s h igh f o r these a c i d s , t h i s w i l l make accurate determinations of kp values d i f f i c u l t . 4 . 8 . 2 Curvature i n General Base Catalyzed Bronsted Plots A set of a l k y l and arylphosphonates gives a n o n - l i n e a r Bronsted c o r r e l a t i o n , F i g . 52, p. 212. This i s a more evident case of curvature than we observed with the c a r b o x y l i c a c i d s , and i t merits fur ther a n a l y s i s . 1. Combining 27 A r P 0 3 2 _ and 4 RPO32- species into one set provides us wi th a very wide range of c a t a l y s t e q u i l i b r i u m a c i d strengths and a very large number of c a t a l y s t s . As was mentioned p r e v i o u s l y , a l i n e a r c o r r e l a t i o n of a l l the data i s not the best representat ion of the r e l a t i o n s h i p between log k and log K. In f a c t , as shown i n F i g . 52 and by the equations below, a second degree curve i s a b e t t e r c o r r e l a t i o n of the data; a t h i r d degree curve provides no improvement whatsoever i n the r e l a t i o n s h i p . 227 -31 dianions log (k A 2- /3 ) - - 10.6 - 0.785 ( log 3K 2 ) [4.44] r = 0.9940 ± 0.1 r = 0.9995 l o g (k A 2- /3 ) 12.6 - 1.42 ( log 3K 2 ) - 0.0489 ( log 3 K 2 ) 2 ± ± ± 0.3 0.10 0.0078 [4.45; We can use eqs. [1 .54] - [1 .56] , p. 25, to determine the Marcus parameters. The r e s u l t i n g i n t r i n s i c b a r r i e r i s 1.7 ± 0.3 k c a l mol"-'-; the work term, W r , i s determined to be 21 ± 3 k c a l m o l ' l . In order to determine the work term, Wp, which accounts for the separat ion of products , a value of i s needed, i . e . the e q u i l i b r i u m constant for the d i s s o c i a t i o n of acetone as an a c i d . A h i g h l y accurate value of p K z has been a v a i l a b l e s ince 1984, based on measurements of enol-keto conversion rates i n aqueous s o l u t i o n at 2 5 ° C : K z = 19.16 ± 0.04 (CK84). The value of K z used i n eq. [1.56] i s the s t a t i s t i c a l l y correc ted one, i . e . Kq/p where p = 6 and q = 1 (thus log ( K z q / p ) = - 19.94). Hence, Wp i s 21 ± 5 k c a l m o l _ l . The r e s u l t s of the Marcus ana lys i s are s t a t i s t i c a l l y quite good; t h i s i s a measure of the exce l l en t f i t of the log k - log K c o r r e l a t i o n to a quadrat ic expression i n l og K. The very low i n t r i n s i c b a r r i e r (2 k c a l mol--'-) and the large work term necessary to b r i n g the reactants together (21 k c a l mol"-'-) are of i n t e r e s t ; a n a l y s i s of other ketones with carboxylate bases gives s i m i l a r r e s u l t s , though values of W r are h a l f as large as the value we have determined (K073, AC72). One of these s tud ies , which involves a c e t y l -acetone as the substrate , inc luded c a t a l y s t s of d i f f e r e n t s t r u c t u r a l types , a device that was requ ired to 'observe' curvature (see p. 45). - 228 -C l e a r l y our study i s a more r igorous one, though i t s t i l l has room for improvement; s p e c i f i c a l l y , other c a t a l y s t s i n the lower pK range could be s tud ied , and primary isotope e f fec t s could be evaluated. The study by Hupe and Wu i n v o l v i n g the base ca ta lyzed e n o l i z a t i o n of a ketone with 30 oxyanions has been discussed i n some d e t a i l (HW77, see p. 34). This study i s re levant to our r e s u l t s , e s p e c i a l l y as the * 1 1 authors' values of A G D (2.5 k c a l mol i ) and W r (15.1 k c a l mol 3-) are very c lose to ours . However, the curvature i n t h e i r Bronsted p l o t i s c r e d i t e d to a s o l v a t i o n e f f ec t and the authors suggest a AG Q value of 10 k c a l m o l " 1 f or such systems (see p. 45). Primary isotope e f fec t s i n t h e i r system showed no s i g n i f i c a n t c o r r e l a t i o n with pK, a f a c t that favours t h e i r argument (HP84, see p. 35). We decided to examine the primary isotope e f f e c t i n our system. A number of dianions were s tudied with acetone-dg at a s ing l e buf fer r a t i o , the slope of k o b s against [A^~] being k A 2 - . A c o r r e l a t i o n of 8 values and k^/k^, values i s pred ic ted by Marcus theory, and i n p a r t i c u l a r eq. [4 .46] , which expresses the rate of change of log k A - as a funct ion of changing HA, i . e . 8 (Sect ion 1.8, p. 28). - / 3 - d log k / d log K = — 1.42 - 0.0978 ( log 3K 2 ) [4.46] Thus, f or a p a r t i c u l a r base, 8 can be c a l c u l a t e d and, i f a changing t r a n s i t i o n s tate i s causing the curvature , the 8 values should c o r r e l a t e with the kjj/kn va lues . ( S t a t i s t i c a l fac tors have been omitted from the l e f t hand s ide of eq. [4.46] for c l a r i t y , however k should be read as k A - / 3 and K as 3 K 2 ) . The r e s u l t s for seven phosphonates are given i n - 229 -Table 38. The d e v i a t i o n of the k A 2 - values with acetone-dg i s assumed to be ± 3%, (average d e v i a t i o n of a l l k A 2 - values with acetone), i n order to c a l c u l a t e the d e v i a t i o n of k^/kp. The dianions which were examined were p a r t l y chosen on the bas i s of a smal ler than average standard d e v i a t i o n i n k A 2 - . Table 38: k A 2- values for acetone-dg enolization at 25°C, in water, and the resulting k H / k D values; B values calculated from eq. [4.46] on the basis of log K 2 q / p , q = 3, p = 1. Base log K 2 q / p 10' k A z " k H / k D $ M " 1 see"-1 C 1 C H 2 P 0 3 2 " -6 .11 15, .0 2 .9 + 0, .2 0 .82 4 - C N C 6 H 4 P 0 3 2 - -6 .31 24, .9 3. .2 + 0 .1 0, .80 3 - C l C 6 H 4 P 0 3 2 _ -6, .62 42. .7 3. .5 + 0. .1 0. .77 3 , 4 - ( C H 3 ) 2 C 6 H 3 P 0 3 2 - -7, .28 92, ,8 4. .5 ± 0. .2 0, .71 2 , 4 - ( C H 3 ) 2 C 6 H 3 P 0 3 2 ' -7 , .59 141 4. .6 + 0. .1 0. .68 2 , 6 - ( C H 3 ) 2 C 6 H 3 P 0 3 2 " -8. .14 303 5. .2 + 0. ,2 0. ,62 ( C H 3 ) 3 C P 0 3 2 _ -8, .23 298 6. .9 + 0. .2 0. .62 k H va lues from Tables 21 and 32 (pp. 124 and 210) - 230 -Since the k A 2-va lues for both acetone and acetone-dg are p r e c i s e , the values of k j j /k n show a low standard d e v i a t i o n . There i s a trend i n the primary isotope e f f e c t , the value i s a maximum when ApK i s a minimum, A pK being the d i f f erence i n pK between the monoanion, HA" and acetone. There i s a l so a c l e a r l i n k between the c a l c u l a t e d B values and the measured kjj/kjj va lues ; the l a r g e s t isotope e f f e c t i s assoc ia ted with the B va lue nearest to 0.5 whereas when B i s 0.82 the isotope e f f e c t i s smal l (2 .9 ) . We be l i eve that these r e s u l t s i l l u s t r a t e , ra ther e l e -gant ly , the changing p o s i t i o n of the proton i n the t r a n s i t i o n s ta te . The Hammond postu late and i t s mathematically der ived form, the Marcus equat ion, i s fo l lowed almost p e r f e c t l y by our substrate and set of c a t a l y s t s . In f a c t , the r e s u l t s for base c a t a l y s i s can be considered as evidence of the a p p l i c a b i l i t y of these concepts. I t i s unc lear why the study by Hupe and Wu gives fundamentally d i f f e r e n t r e s u l t s . While both systems involve base -cata lyzed e n o l i z a -t i o n , the c a t a l y s t s used i n each study are quite d i f f e r e n t ; i t would be i n t e r e s t i n g to combine t h e i r substrate and our extensive set of phos-phonate d ian ions . T h e i r work as ide , the values of A G Q , W r and Wp deter-mined for our system are given credence by the isotope e f fec t s study, which i l l u s t r a t e s a changing t r a n s i t i o n s ta te . While Marcus theory may underestimate AG Q by a f a c t o r of roughly two (p. 26), the end r e s u l t of our a n a l y s i s i s that the bulk of the energy r e q u i r e d for the r e a c t i o n comes from W r , the work needed to 'organize ' or ' se t -up' the two reagents i n a p o s i t i o n to al low r e l a t i v e l y f a c i l e t r a n s f e r of the pro ton . The two analyses of curved Bronsted p l o t s (Sect ion 4 .8 .1 and 4.8.2) - 231 -stand i n s tark contras t to one another. One i s an i n t e r p r e t a t i v e maze whi le the other i s a c l a s s i c example of a b lending of t h e o r e t i c a l concepts and experimental r e s u l t s . Some f i n a l po ints concerning base c a t a l y s i s and curvature can be made. I t can be seen from F i g . 54 that the points for the carboxylate monoanions and dianons f a l l on or near extensions of the phosphonate curve . From our measurements of k ^ for a few c a r b o x y l i c ac ids we have three values of k A - for acetone-dg. The r e s u l t i n g k^/kn values are g iven i n Table 38 and are quite compatible with the r e s u l t s obtained with the phosphonates, i . e . the same trend i s present and the ten combined values make a reasonable set with a minimum isotope e f f e c t of 2.2 and a maximum of 6.9. The fac t that B = 0.89 for the monocarboxylates i s i n keeping with the B values increas ing as we move from the phosphonates to the carboxy la tes . Our l a s t comment concerns k-Q^. From measurements of the phospho-nate d ian ion rate constants we have determined a value of k-g^ ( for acetone) from the in tercepts of k 0 k s v s . [A 2"] p l o t s and pH. The r e s u l t i s 0.251 ± 0.034 M " 1 s e c - 1 (43 va lues ) , a value c lose to that of B e l l and L i d w e l l but higher than that of Hine (BL40, HK72). The same a n a l y s i s for acetone-dg gives a value of 2.56 ± 0.37 x 10~ 2 M - 1 sec" 1 for k-QH v a l u e s ) , a k j j /k n value for hydroxide i s therefore 9.8 ± 1.9. Th i s compares favourably with l i t e r a t u r e values (see p. 47). The ApK for hydroxide and acetone i s only about 3 pK u n i t s , and thus we have reached, or are c lose to , the maximum isotope e f f e c t . - 232 Fig . 54: Bronsted plot for acetone enolization catalyzed by phosphonate dianions (curve, open c i rc l e s ) , monocarboxylate anions (closed c irc les ) and dianions (closed squares). 233 -Table 39: k A - values for acetone-dg e n o l i z a t i o n at 25°C i n water, and the r e s u l t i n g k H / k D values Base - l o g K q/p 10 7 k A - k H / k D a M " 1 sec" 1 HOCH 2 C0 2 " 3.53 0.156 ± 0.014 2.2 ± 0.3 C 6 H 5 C H 2 C 0 2 " 4.01 0.441 ± 0.005 2.7 ± 0.2 C H 3 C 0 2 " 4.46 0.781 ± 0.041 3.1 ± 0.2 a k H values from Table 7, p. 81. I t may be r e c a l l e d that the curved Bronsted l i n e of Hupe and Wu incorporated hydroxide ion (HW77). The curved l i n e for the phosphonates i s such that k-g^ deviates negat ive ly , i . e . i t f a l l s below the l i n e , by a f a c t o r of 13 or 43 depending on the choice of p and q. 4 .9 . CONCLUSIONS A number of B values have been determined i n t h i s work, for both acetone, Z , and protonated acetone, Z H + , us ing a v a r i e t y of c a t a l y s t s . The r e s u l t s are l i s t e d i n Table 40, and a number of conclus ions can be - 234 Table 40: Bronsted c o e f f i c i e n t s for proton a b s t r a c t i o n from acetone (Z) and from protonated acetone (ZH + ) Row No. Substrate C a t a l y s t s 3 3 1 Z RC0 2 " 0.89 2 Z H + RC0 2 " 0.40 3 Z R ( C 0 2 - ) 2 , A r ( C 0 " ) 2 0.77 4 Z H + A r ( C 0 2 " ) 2 5 -subst 0.68 5 Z H + A r ( C 0 2 " ) 2 2 -subst 0.45 6 Z A r P 0 3 2 " meta, para 0.71 7 z A r P 0 3 2 " ortho 0.74 8 Z H + ArP0 3 H" meta, para 0.62 9 Z H + ArP0 3 H* ortho 0.58 3 R = a l k y l ; Ar = a r y l summarized on the bas i s of the s i ze of the Bronsted c o e f f i c i e n t s . 1. In a comparison between the same type of c a t a l y s t r e a c t i n g with protonated or n e u t r a l acetone, the smaller j3 value i s always observed with protonated acetone. This i s i n t e r p r e t e d as the more reac t ive system having an e a r l i e r t r a n s i t i o n state i . e . proton t r a n s f e r occurs sooner along the r e a c t i o n coordinate . This i s p r e d i c t e d by the Hammond p o s t u l a t e . (Compare rows 1 and 2; 3 and 4; and 6 and 8, although the - 235 l a t t e r involve s l i g h t l y d i f f e r e n t c a t a l y s t s . 2. In the case of 2 - subs t i tu ted i sophthalate monoanions, s t e r i c a c c e l e r a t i o n i s observed (when compared to 5 - subs t i tu ted i s o p h t h a l a t e s ) . This i s r e f l e c t e d i n the r e l a t i v e 0 values of react ions i n v o l v i n g Z H + and the conjugate d ianions; the more r e a c t i v e 2 - subs t i tu ted c a t a l y s t s l ead to an e a r l i e r t r a n s i t i o n s tate (rows 4 and 5) . A s i m i l a r but smal ler e f f e c t i s observed with arylphosphonate monoanions, rows 8 and 9, the o r t h o - c a t a l y s t s possess the smal ler B value and show a s t e r i c a c c e l e r a t i n g e f f e c t . 3. In the case of arylphosphonate dianions the ortho-compounds f a l l on or j u s t below the Bronsted l i n e for the meta- and para-compounds; the l a r g e r B f or the ortho ser ies (row 7) may r e f l e c t a s l i g h t s t e r i c r e t a r d a t i o n e f f e c t . 4. As was d iscussed p r e v i o u s l y , (p. xxx) , a comparison of the e f fec t s for monocarboxylate bases and d icarboxylate bases does not make sense i n terms of the Hammond postu late (compare rows 1 and 3, and 2 and 4) . Perhaps t h i s i s an example of a breakdown i n the concept of a more r e a c t i v e system having an e a r l i e r t r a n s i t i o n s ta te . I t i s a lso poss ib le that the a d d i t i o n a l u n i t of negative charge ( i n the dianion) i s having a large unexplained e f f e c t . In f a c t a comparison of the two types of c a t a l y s t , -CC^" and ( - C C ^ " ^ . may be inappropr ia te ; i t seems that a combination o f -PO32- and - C C ^ - r e s u l t s (rows 1 and 6) may be a more v a l i d comparison, cons ider ing our recent d i s c u s s i o n (p. 232). Despite - 236 -the d i f f e r e n c e i n the c a t a l y t i c moiety, the - P C ^ " charge i s more l o c a l i z e d than i n the carboxylate d ian ions , and therefore may resemble the - C O 2 " to a greater degree. As w e l l as the deductions concerning the magnitude of B va lues j u s t d iscussed , a number of other conclus ions have been made on the bas i s of our r e s u l t s . 5. A r e l a t i o n s h i p e x i s t s between the degree of hydrogen-bonding i n the monoanions of d i c a r b o x y l i c ac ids and the degree of d e v i a t i o n of the d i a n i o n from the Bronsted l i n e for dianions whose conjugate monoanions have no hydrogen bonding. 6. In both a c i d and base ca ta lyzed e n o l i z a t i o n , p o l a r i z a b l e s u b s t i t u -ents cause the c a t a l y s t to d i s p l a y an enhanced c a t a l y t i c a c t i v i t y . 7. Ortho benzoic a c i d s , 2 - subs t i tu ted i sophthalate monoanions and s t e r i c a l l y crowded a l i p h a t i c carboxy l i c acids a l l show v a r y i n g degrees of enhanced r e a c t i v i t y i n the a c i d cata lyzed e n o l i z a t i o n of acetone. The e f f e c t seems absent i n the general base ca ta lyzed process and therefore might be l i n k e d to the use of protonated acetone as opposed to n e u t r a l acetone as the substrate . However, why the protonated substrate should cause an e f f e c t while the n e u t r a l substrate does not , i s not obvious . The f a c t that B e l l and coworkers have observed s t e r i c acce l er -a t i o n i n base ca ta lyzed e n o l i z a t i o n with very bulky c a t a l y s t s and substrates (see p . 60, BG49) may mean that we w i l l not observe any e f f e c t u n t i l a bulky substrate i s used. In t h i s regard , the reported rate enhancement by a fac tor of three for p i v a l a t e anion i n cyclohexa-- 237 -none e n o l i z a t i o n seems re levant (LW69). The r o l e of s t e r i c fac tors i n these processes i s unc lear . I t has been suggested that hydrophobic bonding causes rate acce lerat ions i n some of these cases (BG49). 8. There appears to be curvature i n the Bronsted p l o t for c a r b o x y l i c a c i d c a t a l y s t s . Primary isotope e f fec t s suggest that the curvature i s not due to changes i n t r a n s i t i o n state s t r u c t u r e . 9. On the other hand, curvature i n a set of phosphonates has been r e l a t e d to isotope e f fec t v a r i a t i o n s , a l l of which suggests that there i s a change i n the degree of proton t rans fer (at the t r a n s i t i o n state) as the e q u i l i b r i u m base strength of the c a t a l y s t i s changed. Marcus theory ana lys i s implies that the proton t rans fer i t s e l f i s f a c i l e while se t t ing-up the reagents for such a t r a n s f e r i s e n e r g e t i c a l l y expensive. 10. A group of monoanions that were s tudied act as general a c i d s , not general bases, i n the e n o l i z a t i o n of acetone. 11. The i n c l u s i o n of c a t a l y s t s of d i f f e r e n t s t ruc ture and/or charge i n one Bronsted c o r r e l a t i o n must be done with caut ion . A glance at the scope of t h i s i n v e s t i g a t i o n as o u t l i n e d i n p. 65 i s recommended. We have answered many of our o r i g i n a l questions and some more bes ides . However, as always happens i n research, new questions a r i s e out of an ana lys i s of our r e s u l t s . These questions have assumed a h igher l e v e l of complexity than before and the answers to them must be - 238 -the next step i n our progress . 4.10 SUGGESTIONS FOR FURTHER WORK 1. A study i n v o l v i n g a s t e r i c a l l y bulky substrate (e .g . 2 ,4 -d imethyl -pentanone) would be informat ive . Would there be an increase i n the s t e r i c a c c e l e r a t i o n fac tors over that observed for general a c i d cata-lyzed e n o l i z a t i o n of acetone? Would s t e r i c a c c e l e r a t i o n be evident i n the general base ca ta lyzed process? 2. A number of h a l o - s u b s t i t u t e d alkylphosphonic ac ids would be very h e l p f u l i n fur ther eva luat ing the curved Bronsted p l o t for a l l the phosphonates. This would a lso al low the c o n s t r u c t i o n of a Bronsted p l o t for phosphonate monoanions. 3. As recommended p r e v i o u s l y , more work i s needed i n the c o r r e l a t i o n of d e v i a t i n g dianions and the degree of hydrogen-bonding i n t h e i r conjugate monoanions. In c l o s i n g t h i s d i s c u s s i o n , a r e t r o s p e c t i v e view of the main thrust of t h i s thes i s may be worthwhile. Throughout t h i s work, we have c r i t i -c a l l y examined the reasons for deviat ions from Bronsted l i n e s as w e l l as the causes f o r n o n - l i n e a r Bronsted c o r r e l a t i o n s . The n o n - l i n e a r i t y observed i n the case of phosphonate dianions has been c r e d i t e d to a changing t r a n s i t i o n s tate and t h i s r e s u l t gives support to the Hammond postulate and to Marcus theory. I t should be - 239 -remembered, however, that our present concepts and theories of transi-t ion state energetics are models and should be considered as such. These models require both experimental support and constructive c r i t i -cism. Results which agree with our present concepts suggest that we are on the right track. Results which appear to undermine our present concepts should not s o l i c i t blanket cr i t ic i sm of the model. On the contrary, they i l lus trate the limitations of our approach. There is a paucity of experimental evidence, devoid of debatable facets, for the Hammond postulate. We believe that the curved phospho-nate Bronsted plot and related primary isotope effects is a worthwhile contribution in this regard. - 240 -EXPERIMENTAL 5.1 General K i n e t i c Measurements Unless otherwise s ta ted , the fo l lowing are i m p l i e d . D i s t i l l e d water was used throughout t h i s work. Acetone was of spectrophotometry grade (BDH Chemicals) ; i t was re f luxed with potassium permanganate (0.1 g/400 mL) for 2 hours , f r a c t i o n a l l y d i s t i l l e d , and s tored overnight over ca lc ium carbonate. The l i q u i d was f i l t e r e d and f r a c t i o n a l l y d i s t i l l e d a second time, and was s tored i n a dark b o t t l e f i t t e d with a septum cap, for up to twelve weeks. Buffer so lut ions of the ac ids and t h e i r conjugate bases were prepared by the a d d i t i o n of e i t h e r h y d r o c h l o r i c a c i d to the sodium s a l t of the a c i d , or sodium hydroxide to the free a c i d . So lut ions of both sodium hydroxide and h y d r o c h l o r i c a c i d were prepared by d i l u t i o n of concentrated volumetr ic so lu t ions a v a i l a b l e from BDH chemicals . The sodium hydroxide was s tandardized by t i t r a t i o n with potassium hydrogen phthalate (gold l a b e l , A l d r i c h Chemical Co.) us ing phenolphthale in as i n d i c a t o r ; t h i s was done on a d a i l y b a s i s . The h y d r o c h l o r i c a c i d was s tandardized by t i t r a t i o n with the s tandardized sodium hydroxide , us ing the same i n d i c a t o r ; t h i s was done on a weekly b a s i s . The general method of prepar ing buf fer so lu t ions was as fo l lows . The free a c i d was p laced i n a 10 mL or 25 mL volumetr ic f l a s k . A volume of sodium hydroxide was added i n . o r d e r to obta in a chosen b u f f e r - r a t i o , n, ( [ H A ] / [ A " ] ) . The number of equivalents of hydroxide necessary for a 241 -p a r t i c u l a r n value i s given by l / ( n + 1) . In cases where the a c i d was used as i t s sodium s a l t , h y d r o c h l o r i c a c i d was added. The number of equivalents of h y d r o c h l o r i c a c i d necessary for a p a r t i c u l a r n value is g iven by n / ( l + n ) . A l i q u o t s from these stock so lut ions of buf fer were p laced i n 5 mL or 10 mL volumetr ic f l a s k s . The i o n i c s trength of these so lu t ions was made up to a constant value by the a d d i t i o n of sodium c h l o r i d e . Acetone was added v i a a 250 LIL syringe to each preweighed vo lumetr ic f l a s k ; the concentrat ions of acetone that were used v a r i e d from 0.1 to 0.5 M. Each s o l u t i o n was made up to the appropriate volume with water. Genera l ly four so lut ions were prepared from each stock s o l u t i o n at a p a r t i c u l a r n va lue . The rates of e n o l i z a t i o n of acetone were determined i o d o m e t r i c a l l y by fo l lowing the decrease i n the absorbance of the t r i i o d i d e ion at 353, 400 or 440 nm (pp. 66-68). A 3 mL sample of a p a r t i c u l a r s o l u t i o n was temperature e q u i l i b r a t e d at 25°C for 15 min i n a c losed cuvette . The i o d i n a t i o n was i n i t i a t e d by the a d d i t i o n of 50 LIW of t r i i o d i d e ion s o l u t i o n . The decrease i n absorbance was fol lowed with a Cary 16 spectrophotometer equipped with a c e l l holder thermostatted at 25 ± 0 . 1 ° C . The rate of r e a c t i o n i s given by eq. [3 .2] , p. 67; each observed f i r s t - o r d e r rate constant ( k o b s ) was c a l c u l a t e d from the l i n e a r slope of the p l o t of absorbance against time by use of the r e l a t i o n s h i p k o b s = - s l o p e / ( e j ^ - [acetone]) , where £ l ^ _ l s t n e e x t i n c t i o n c o e f f i c i e n t of t r i -i od ide ion at the chosen wavelength. The concentrat ion of acetone was c o r r e c t e d for the d i l u t i o n f a c t o r , caused by the a d d i t i o n of 50 LIL I 3 " s o l u t i o n , as were the concentrat ions of a c i d and base b u f f e r s . - 242 -The values of eT - used were 2.45 x 10 4 M " 1 cm" 1 at 353 nm (AB65), "•3 5.9 x 10 3 M " 1 cm" 1 at 400 nm (value determined i n t h i s work) and 1818 M " 1 cm" 1 at 440 nm (SS76b). A wavelength of 353 nm was used unless (a) the buf fer species absorb at that wavelength (e .g . n i t r o - s u b s t i t u t e d c a t a l y s t s ) (b) the disappearance of t r i - i o d i d e ion was too fas t to fo l low at that wavelength (e .g . h i g h l y a c i d i c buf fer s o l u t i o n s ) . The concentrat ions of t r i i o d i d e ion v a r i e d from 4 x 10"^ to 5 x 10" 4 M, and were chosen to give an i n i t i a l absorbance reading of approximately 0 .9 . The f a c t that a l l p l o t s of absorbance against time were l i n e a r from the time of the f i r s t reading (about 30 sec a f t er the a d d i t i o n of the t r i i o d i d e a l i q u o t ) u n t i l at l eas t 70% of the iodine had reacted show that the k i n e t i c s of iodine consumption are zero order . Stock so lut ions of t r i i o d i d e ion were prepared with 0.5 M KI and concentrat ions of I 2 that depended on the wavelength chosen; 2.2 x 10" 3 M at 353 nm, 6.9 x 10" 3 M at 400 nm and 2.1 x 10" 2 M at 440 nm. The e q u i l i b r i u m between K I , I 2 and K + I 3 " favours K + I 3 " (K = 714, AB65) and a l l the so lu t ions of t r i i o d i d e ion w i l l conta in n e g l i g i b l e amounts of I 2 . The pH values of buf fer so lut ions before and a f t er rate measurements showed l i t t l e change, ± 0.02 pH un i t s at the worst, genera l ly l e s s . A Radiometer Model 26 pH meter and a Radiometer GK2421C combined glass e l ec trode were used for pH measurements. The pH meter was standardized with aqueous b u f f e r so lut ions at pH 2.00 ± 0.02, 4.00 ± 0.01 and 7.00 ± 0.01 (BDH Chemicals and F i scher S c i e n t i f i c ) . For a l l the ac id /base p a i r s which were examined, a 'b lank' r e a c t i o n ( i . e . no acetone) with t r i i o d i d e ion was c a r r i e d out. In most cases, there was no r e a c t i o n between the buf fers and I 3 " . In some cases, a - 243 r a p i d n o n - l i n e a r decrease of 13" was observed, p r e c l u d i n g the measure-ments of rate constants assoc iated with that p a r t i c u l a r buf fer p a i r . In a few cases, the disappearance of t r i i o d i d e i n the absence of acetone was a slow f i r s t - o r d e r r e a c t i o n that could be s a t i s f a c t o r i l y correc ted f o r . The e n o l i z a t i o n process i s zero order i n iodine and i t could be shown that the r e a c t i o n of iodine with the buf fer anion has a n e g l i g i b l e e f f e c t on the measured rate of e n o l i z a t i o n . In the case of buf fer r a t i o s i n v o l v i n g d i p r o t i c acids and the conjugate monoanions, the treatment descr ibed for monoprotic ac ids i s a p p l i c a b l e . However, for any p a r t i c u l a r buf fer r a t i o of the monoanion and i t s conjugate base (the d i a n i o n ) , i . e . m, the number of equivalents of hydroxide needed for a p a r t i c u l a r m value i s (m + 2)/(m + 1). Thus the p r o p o r t i o n of d ian ion i s taken to be the f r a c t i o n i n excess of one equ iva lent , that of the monoanion to be un i ty minus t h i s f r a c t i o n , and that of the d i a c i d to be zero. This treatment presupposes two d i s t i n c t a c i d d i s s o c i a t i o n s . A method has been descr ibed p r e v i o u s l y which considers over lapping d i s s o c i a t i o n s , and allows a c a l c u l a t i o n of [ H 2 A ] , [HA"] and [A 2 *] (pp. 97-98). The e x t i n c t i o n c o e f f i c i e n t for t r i i o d i d e ion at 400 nm was deter-mined as fo l lows . A p l o t of [ I 3 " ] against absorbance gives el_^~ a s t b e s lope , with the in tercept being n e g l i g i b l e . The concentrat ion of I 3 " was determined by t i t r a t i o n with a standard sodium t h i o s u l f a t e s o l u t i o n that had j u s t been t i t r a t e d with potassium dichromate (V51). The r e s u l t of two determinations of eI^~ a t ^ 0 nm gave a value of 5.9 ± 0.2 x 10 3 M " 1 cm" 1 . Values of the e x t i n c t i o n c o e f f i c i e n t at 353 nm and 400 nm, which were a l so determined, are c lose to the reported values (2.52 ± - 244 -0.11 x 10 a M" cm'1 at 353 nm and 1824 ± 55 M ' 1 c m - 1 at 440 nm). 5.2 CARBOXYLIC ACIDS Most of the monoprotic a l i p h a t i c ac ids were p u r i f i e d as t h e i r sodium s a l t s . Commercially a v a i l a b l e acids were mixed with d i e t h y l ether and washed wi th 0.95 equivalents of sodium hydroxide. The aqueous layer was separated, washed twice with d i e t h y l ether , and the water was removed under reduced pressure to give the sodium s a l t of the a c i d . The s a l t s were r e c r y s t a l l i z e d from e t h a n o l / e t h y l acetate mixtures , d r i e d i n vacuo. Ac ids p u r i f i e d i n t h i s manner are l i s t e d i n Table 7, p. 80. In the case of i odoace t i c a c i d , the sodium s a l t was obtained from a commercial source ( A l d r i c h Chemical C o . ) , and washed with acetone to remove the ye l low c o l o u r , d r i e d at 80°C for two hours and used d i r e c t l y for the k i n e t i c measurements. Sodium acetate-d3 was obtained from MSD Isotopes. Buf fer s o l u t i o n s of these acids were prepared by the a d d i t i o n of h y d r o c h l o r i c a c i d . For the stronger a l i p h a t i c ac ids i n c l u s i v e of d i c h l o r o a c e t i c a c i d and s tronger h a l o - a c i d s , the a c i d was p u r i f i e d by d i s t i l l a t i o n at reduced pressure , except i n the case of tr ibromoacet ic a c i d , which was sublimed at 8 0 ° C / 2 mm Hg. As was descr ibed p r e v i o u s l y , b u f f e r - r a t i o c o n t r o l proved d i f f i c u l t f or these a c i d s . Consequently, a d i f f e r e n t k i n e t i c treatment was used, and t h i s has been discussed a lready , p. 82. Stock s o l u t i o n s of these ac ids were prepared and t i t r a t e d , and a subsequent d i l u t i o n was used to provide so lut ions of var ious concentra-- 245 -t i o n s . Hydroxide was then added i n vary ing amounts (between 1/3 and 4/5 equivalents ) and the k o b s values for each s o l u t i o n were measured. Three of the ammonio carboxy l i c acids are commercially a v a i l a b l e . G l y c i n e , N,N-dimethylg lyc ine hydrochlor ide and N , N , N - t r i m e t h y l g l y c i n e hydroch lor ide were a l l r e c r y s t a l l i z e d from a l c o h o l . Stock so lu t ions of the l a t t e r two compounds were t i t r a t e d and k i n e t i c r e s u l t s obtained i n the same manner as that used for the strong h a l o - a c i d s . Glyc ine hydroch lor ide buf fers were prepared by the a d d i t i o n of h y d r o c h l o r i c a c i d to var ious amounts of g l y c i n e . The concentrat ion of a c i d HA present i n any p a r t i c u l a r s o l u t i o n i s [A - ] + [HCI] — [ H + ] , where A" i s g lyc ine i t s e l f , and [H +] i s a v a i l a b l e from the pH measurements. 4-Trimethylammoniobutanoic a c i d c h l o r i d e was prepared from 4 - d i -methylaminobutanoic a c i d hydrochlor ide fo l lowing a reported method (AK81). In the same way 6-trimethylammoniohexanoic a c i d c h l o r i d e was synthes ized from 6-aminohexanoic a c i d . Both of these compounds were r e c r y s t a l l i z e d from DMF, and gave s a t i s f a c t o r y end points upon t i t r a t i o n with s tandardized hydroxide s o l u t i o n (±3% of the c a l c u l a t e d r e s u l t ) . The mel t ing po in t of the butanoic a c i d d e r i v a t i v e (213 — 216 °C) compares favourably with the reported value (214 — 2 1 9 ° C ) . The hexanoic a c i d d e r i v a t i v e (mp 2 0 0 - 2 0 2 ° C ) gave the fo l lowing elemental a n a l y s i s ; found; C: 51.6; H: 9.57; N: 6.64; expected: C: 51.5; H: 9.61; N: 6.68. The k i n e t i c treatment for these two acids was quite s t ra ight forward and has been descr ibed a lready . The benzoic ac ids that were s tudied were a l l r e c r y s t a l l i z e d from water. A number of a c i d buf fers reacted with t r i i o d i d e ion and thus we - 246 -could not measure any rate constants for these monoprotic acids or t h e i r conjugate bases. Included i n t h i s group are cyanoacet ic , 3 , 4 - d i n i t r o b e n z o i c , bromoacetic, dibromoacetic and 4-aminobutanoic a c i d . We synthes ized methy l th ioace t i c a c i d , fo l lowing a l i t e r a t u r e method (CS70), but i t a l so reacted with I 3" . An a c i d , which was to extend the upper pK range of the monoprotic acids i n our Bronsted p l o t , i s tr imeth-y l s i l y l a c e t i c a c i d (pK = 5.22); i t was prepared from the corresponding Grignard reagent but was found to react with I3" (SG49). The pK of t - b u t y l a c e t i c a c i d was determined i n water at 25°C and c o r r e c t e d for i o n i c s trength (AS84). This thermodynamic pK i s 5.01 ± 0.02. Values for propanoic a c i d and benzoic a c i d were a lso determined as a check on the experimental accuracy of the pK measurement. These r e s u l t s are c lose to the l i t e r a t u r e values (4.86 ± 0.03, and 4.20 ± 0.03) . The d i p r o t i c c a r b o x y l i c acids were a l l p u r i f i e d by r e c r y s t a l l i z a -t i o n , from water i n the case of aromatic ac ids , and from hexane/ethyl -ace ta te / e thano l mixtures i n the case of a l i p h a t i c ac ids . Reactions between the buf fer and t r i i o d i d e ion occurred with 1 , 2 - c i s - d i c a r b o x y l i c a c i d and methylmalonic a c i d . A slow r e a c t i o n occurred i n the case of 3 -methy lg lu tar ic a c i d , which prevented measurements being made of k^^. but allowed us to determine k j ^ - and k A 2 - . The 2- and 5 - subs t i tu ted i s o p h t h a l i c ac ids were synthes ized, and t h e i r pK^ and p K 2 values measured, by other members of our research group (GS84, NL87). 247 -5.3 PHOSPHONIC ACIDS Whereas, for a c i d c a t a l y s i s poor s o l u b i l i t y l i m i t s the range of ac ids for which we can measure kjj^A' f ° r phosphonate d ian ion c a t a l y s i s , a number of buf fers reacted with t r i i o d i d e . These inc luded a l l the b u f f e r s conta in ing appreciable concentrat ions of a r y l a l k o x y - d i a n i o n s . The synthes is and pK determinations of the arylphosphonic acids have been reported (NS87). The alkylphosphonic ac ids were synthes ized by other members of our group (NV87). 5.4 ISOTOPE MEASUREMENTS Deuterium oxide (99.8 atom % D) and acetone-dg (99.9 atom % D) were obtained from MSD isotopes . D 20 was used d i r e c t l y i n the preparat ion of b u f f e r s o l u t i o n , and i n the d i l u t i o n of concentrated NaOD and DC1 s o l u t i o n s ( laboratory s tock) . The rate measurements i n D 2 0 were obtained i n an i d e n t i c a l manner as that for H 2 0 . Solut ions of 13" were prepared i n D 2 0. While most of the ac ids were used i n the form of t h e i r sodium s a l t s d i f l u o r o a c e t i c and t r i f l u o r o a c e t i c a c i d - d were used d i r e c t l y . Acetone-dg was d i s t i l l e d and d r i e d i n an i d e n t i c a l manner to that o f acetone. - 248 -5.5 STATISTICS A l l l i n e a r c o r r e l a t i o n s are the r e s u l t of a l eas t - squares regress ion a n a l y s i s us ing the minitab program a v a i l a b l e on the UBC MTSG system. The same program was used for the quadrat ic c o r r e l a t i o n s . U n c e r t a i n t i e s ( i . e . ± dev ia t ions ) i n the case of a d d i t i o n , s u b t r a c t i o n , m u l t i p l i c a t i o n and d i v i s i o n are c a l c u l a t e d by the standard equations (R81d). - 249 -6. A P P E N D I X I . R A T E - A C I D I T Y P R O F I L E For each buffer-ratio a value of k s u m (contribution to k o b s from hydronium ion, hydroxide ion and water) is available and thus a plot of log k s u m against the pH gives the rate-acidity prof i le for acetone enolization, F ig . 55. This allows a check on the reported value of k^Q CO o O) - 7 -c? - 7 . 6 -o O -8- % o o -8.5- o o o -9- 8£% -8 .6-o 8 PH F i g . 55: Rate-acidity prof i le for the enolization of acetone. - 250 -(BL40). Knowing k H+ (2.51 x 10" 5 M " 1 sec" 1 ) and k - 0 H (0.251 M " 1 s ec" 1 ) , we can determine the pH value at which the c o n t r i b u t i o n to k o b s from these species i s a minimum (S85i) . The r e s u l t i s 5.0, a value which i s a lso suggested by F i g . 55 where a p la teau i s evident at that pH. The c o n t r i b u t i o n from H 3 0 + and "OH i s 5.0 x 1 0 - 1 0 M " 1 s e c - 1 while the k o b s from F i g . 55 i s 1.0 x 10" 9 M " 1 s e c - 1 . Thus, the d i f f erence (5 x 1 0 " 1 0 M " 1 sec" 1 ) can be c r e d i t e d to k H ^ 0 [ H 2 ° l > a n c l s i n c e [ H 2 O ] i s 55.5 M, the c a t a l y t i c constant for water i s 9.0 x 1 0 " 1 2 M " 1 sec" 1 which i s i n good agreement with the value of B e l l and L i d w e l l , 8.3 x 1 0 " 1 2 M " 1 sec" 1 . I I . SOLVENT ISOTOPE EFFECTS IN BASE CATALYSIS The solvent isotope e f f ec t ( H 2 O / D 2 O ) was measured for a number of bases and the r e s u l t s are given i n Table 41. The combination of the r e s u l t s for the three carboxylate bases with those of t h e i r conjugate ac ids (Table 34, p. 219) allows an es t imat ion of k Z H + / K Z D + , the r a t i o of e q u i l i b r i u m constants for protonated acetone i n H 2 O and D 2 O , given by the equation below (from eq. [1.77], p. 51). K Z H + / K Z D + - k ' A - ( H 2 0 ) / k ' A - ( D 2 0 ) x K H A / K D A x k H A ( D 2 0 ) / k H A ( H 2 0 ) The values of K ^ / K ^ (LR69, SS76a) and k H A ( D 2 0 ) / k H A ( H 2 0 ) are a v a i l a b l e and we can make the fo l lowing assumption; the so lvent isotope e f f e c t f o r base c a t a l y s i s i n v o l v i n g acetone i s equal to that for base c a t a l y s i s i n v o l v i n g protonated acetone. The r e s u l t i n g k Z^+/K Zj)+ value Table 41: k A - a values for acetone enolization at 25°C, measured in D 2 0 and resulting k A - ( H 2 0 ) / k A - ( D 2 0 ) values Base 10 6 k A - (D 20) k A - ( H 2 0 ) / k A - ( D 2 0 ) b M ' l sec" 1 HOCH 2 C0 2 - .0350 ± 0.0014 0.97 ± 0.10 C H 3 C 0 2 _ .181 ± 0.008 1.35 ± 0.07 ( C H 3 ) 3 C C 0 2 - .316 ± 0.012 1.27 ± 0.06 4 - C N - C 6 H 4 P 0 3 2 _ 7 . 8 9 ° 0.98 ± 0.03 4 - C H 3 - C 6 H 4 P 0 3 2 " 39.1 0.89 ± 0.03 2 , 6 - ( C H 3 ) 2 - C 6 H 3 P 0 3 2 " 162 0.98 ± 0.04 a k A 2 - values for phosphonate bases c D e v i a t i o n of k A 2 - values i n D 2 0 assumed to be ± 3 % (p. 229) b k A - ( H 2 0 ) values from Table 7 and 21, pp. 81 and 124. i s 2.81 ± 0.13, s l i g h t l y smaller than the e f fec t s for c a r b o x y l i c acids (3.09, 3.31 and 3.16 for t r i m e t h y l a c e t i c acetate and g l y c o l i c a c i d r e s p e c t i v e l y ) . 252 -BIBLIOGRAPHY A 82 W . J . A l b e r y , J . Chem. S o c , Faraday Trans . 1, 78, 1579 (1982). AB65 W . J . A l b e r y , R . P . B e l l , and A . L . Powell , Trans Faraday. Soc. 61, 1194 (1965). AC72 W . J . A l b e r y , A . N . Campbell-Crawford and J . S . Curran, J . Chem. Soc. Perk in I I , 2206 (1972). AE70 M . - L . Ahrens, M. Eigen, W. Kruse, and G. Maass, Ber. Bunsenges. Phys. Chem., 74, 280 (1970). AG82 W . J . A lbery and J . S . G e l l e s , J . Chem. S o c , Faraday Trans . I , 78, 1569 (1982). AK81 L . Andersson, T. Kuhler , and M. N i l s s o n , Synthes is , 468 (1981). AS84 A. A l b e r t and E . P . Serjeant , The Determination of I o n i z a t i o n Constants , 3rd edn . , Chapman and H a l l , New York, (1984). a) pp. 47-49. b) p . 51. c) p. 56. d) p. 60. e) p. 55. B 23 J . N . Bronsted, Rec. Trav . Chim. , 42, 718 (1923). B 59 R . P . B e l l , The Proton i n Chemistry, 1st e d . , p. 201, C o r n e l l U n i v e r s i t y , Press , I thaca, N . Y . , 1959. B 73 R . P . B e l l , The Proton i n Chemistry, 2nd e d . , C o r n e l l U n i v e r s i t y Press , I thaca , N . Y . , 1973. a) Chapter 2. b) p. 172. c) pp. 160- 164 d) pp. 197- 200 e) Chapter 10. f) pp. 202- 203 g) p. 270 B 78 R . P . B e l l , C o r r e l a t i o n Ana lys i s i n Chemistry, Recent Advances, Chapter 2, Chapman and Shorter , Plenum Press , 1978. B 80 R . P . B e l l , The Tunnel E f f e c t i n Chemistry, Chapman and H a l l , London, (1980). - 253 -B 87 C F . Bernasconi , Acc . Chem. Res . , 20, 301 (1987). BB65 T . C . Bruice and W.C. Bradbury, J . Am. Chem. S o c , 87, 4851 (1965). BB71 F . G . Bordwell and W . J . Boyle J r . , J . Am. Chem. S o c , 93, 512 (1971). BB75 F . G . Bordwell and W . J . Boyle J r . , J . Am. Chem. S o c , 97, 3447 (1975). BB85 C F . Bernasconi and R.D. Bunne l l , I s r . J . Chem., 26, 420 (1985). BC70 R . P . B e l l and B . G . Cox, J . Chem. Soc. (B), 194 (1970). BC78 N . A . Bergman, Y. Chiang, and A . J . Kresge, J . Am. Chem. S o c , 100, 3928 (1978). BG49 R . P . B e l l , E . G e l l e s , and E . M o l l e r , Proc. R. S o c A, 198, 308 (1949) . BG66 R . P . B e l l and D.M. Gooda l l , Proc. Roy. Soc. A, 294, 273 (1966). BG76 R . P . B e l l and S. Grainger , J . C . S . Perk in I I , 1606 (1976). BH85 F . G . Bordwell and D . L . Hughes, J . Am. Chem. S o c , 107, 4737 (1985) . BJ53 R . P . B e l l and P. Jones, J . Chem. S o c , 88, (1953). BL40 R . P . B e l l and O.M. L i d w e l l , P r o c Roy. Soc. (London), A176, 88 (1940). BL65 D.M. Bishop and K . J . L a i d l e r , J . Chem. Phys . , 42, 1688 (1965). BP24 J . N . Bronsted and K . J . Pedersen, Z. Phys. Chem., 108, 185 (1924). BP86 C F . Bernasconi and P. P a s c h a l i s , J . Am. Chem. S o c , 108, 2969 (1986) . BR84 G . J . B i j l o o and R . G . Rekker, Quant. S t r u c t . U c t . - A c t . Re la t . Pharmacol. Chem. B i o l . , 3, 91 (1984). BS59 R . P . B e l l and T . S . Spencer, Proc. Roy. Soc. A, 251, 41 (1959). BU79 N. Bruniche-Olsen and J . U l s t r u p , J . Chem. Soc. Faraday Trans . I , 75, 205 (1979). BW64 B . T . B a l i g a and E . Whalley, Can. J . Chem., 42, 1835 (1964). - 254 -BW66 M . L . Bender and A. Wi l l i ams , J . Am. Chem. S o c , 88, 2502 (1966). C 71 M. Charton, Prog. Phys. Org. Chem., 8, 235 (1971). C 75 J . E . Crooks, i n "Proton Transfer Reactions" ( E . F . C a l d i n and V. G o l d , e d s . ) , Chapter 6, Chapman and H a l l , London, 1975. CC69 J . P . Calmon, M. Calmon and V. Gold , J . Chem. Soc. (B), 660 . (1969) . CD81 B . G . Cox, P. De M a r i a , A. F i n i , and A . F . Hassan, J . Chem. S o c , P e r k i n Trans . 2, 1351 (1981). CE77 W.K. Chwang, R. E l i a s o n , and A . J . Kresge, J . Am. Chem. S o c , 99, 805 (1977). CH87 Y . Chiang, M. H o j j a t t i , J . R . Keefe, A . J . Kresge, N .P . Schepp, and J . Wirz , J . Am. Chem. S o c , 109, 4000 (1987) and references t h e r e i n . CJ81a M.M. Cox and W.P. Jencks, J . Am. Chem. S o c , 103, 572 (1981). CJ81b M.M. Cox and W.P. Jencks, J . Am. Chem. S o c , 103, 580 (1981). CK84 Y. Chiang, A . J . Kresge, Y . S . Tang and J . Wirz , J . Am. Chem. S o c , 106, 460 (1984). CM68 A . O . Cohen and R . A . Marcus, J . Phys. Chem., 72, 4249 (1968). CS70 J . M . Carpenter and G. Shaw, J . Chem. Soc. (C) , 2016 (1970). CS79 R . A . Cox, C R . Smith, and K. Yates , Can. J . Chem., 50, 3239 (1979). CW63 F . Cov i tz and F . H . Westheimer, J . Am. Chem. S o c , 85, 1773 (1963). DB70 J . E . Dixon and T . C . B r u i c e , J . Am. Chem. S o c , 92, 905 (1970). DK83 D . B . Dahlberg, M.A. Kuzemko, Y. Chiang, A . J . Kresge, and M . F . Powel l , J . Am. Chem. S o c , 105, 5387 (1983). DP13 H.M. Dawson and F . Powis, J . Chem. S o c , 2135 (1913). DS30 H.M. Dawson and E . Spivey, J . Chem. S o c , 2180 (1930). DT73 J . E . Dubois and J . T o u l l e c , Tetrahedron, 29, 2859 (1973). E 64 M. Eigen , Angew. Chemie, Internat . E d . , 3, 1 (1964). 255 -E 69 L . Eberson i n "The Chemistry of Carboxyl ic Acids and Esters" , ed. S. P a t a i , In tersc ience , New York, 1969, Chapter 6. EB83 K. Engdahl, H. Bivehed, P. Ahlberg , and W.H. Saunders, J r . , J . am. Chem. S o c , 105, 4767 (1983). EF79 J . T . Edward, P . G . F a r r e l l , J . H a l l e , J . Kirchnerova , R. Schaal , and F . T e r r i e r , J . Org. Chem., 44, 615 (1979). ES87 R . T . Eddin , J . M. S u l l i v a n and J . R . Norton, J . Am. Chem. S o c , 109, 3945 (1987). F 75 Faraday Symposia, 10, 89-99 (1975). FG65 J . A . Feather and V. Gold , J . Chem. S o c , 1752 (1965). FN76 T. F u j i t a and T. Nish ioka , Prog. Phys. Org. Chem., 12, 49 (1976). G 85 E . Grunwald, J . Am. Chem. S o c , 107, 4710 (1985). GR67 C D . Gutsche, D. Redmore, R . S . B u r i k s , K. Nowotny, H. Grassner, and C W . Armbruster, J . Am. Chem. S o c , 89, 1235 (1967). GS84 S . J . Gumbley and R. Stewart, J . Chem. Soc. Perkin Trans . I I , 529 (1984) . GW68 V. Gold and D . C . A . Waterman, J . Chem. Soc. B, 839 (1968). H 40 L . P . Hammett, P h y s i c a l Organic Chemistry, McGraw-Hi l l , New York, 1940. HH65 J . Hine , J . G . Houston, J . H . Jensen, and J . Mulders, J . Am. Chem. Soc . , 87, 5050 (1965). HH78 A . J . Hoefnagel , M.A. Hoefnagel, and B.M. Wepster. J . Org. Chem., 43, 4720 (1978). HJ75a A . F . Hegarty and W.P. Jencks, J . Am. Chem. S o c , 97, 7188 (1975). HJ75b E . S . Hand and W.P. Jencks, J . Am. Chem. S o c , 97, 6221 (1975) . HK72 J . Hine, J . C . Kaufmann, and M.S. Cholod, J . Am. Chem. S o c , 94, 4590 (1972). HK75 A . I . Hass id , M.M. Kreevoy, and T. L i a n g , Faraday Symposia, 10, 69 (1975). HP78 D . J . Hupe and E . R . Pohl , J . Am. Chem. S o c , 100, 8130 (1978). - 256 -HP84 D . J . Hupe and E .R . Pohl , J . Am. Chem. S o c , 106, 5634 (1984). HS74 E . Hayon and M. Simic . Acc . Chem. Res . , 7, 114 (1974). HW73 A . J . Hoefnagel and B.M. Wepster. J . Am. Chem. S o c , 95, 5357 (1973). HW77 D . J . Hupe and D. Wu, J . Am. Chem. S o c , 99, 7653 (1977). HW82 A . J . Hoefnagel a n d M . B . Wepster, J . Org. Chem., 47, 2318 (1982) and references there in . J 65 J . R . Jones, J . Chem. Soc. Faraday T r a n s . , 61, 95 (1965). J 69 W.P. Jencks, C a t a l y s i s i n Chemistry and Enzymology, Chap. 3, M c G r a w - H i l l , New York, 1969. JB82 W.P. Jencks, S.R. Bryant, J . R . Gandler, G. Fendrich and C. Nakamura, J . Am. Chem. S o c , 104, 7045 (1982). JF53 H . H . J a f f e , L . D . Freedman, and G.O. Doak. J . Am. Chem. S o c , 75, 2209 (1953). JG84 J . Jager , T. Graaf land, H. Schenk, A . J . K i r b y , and J . B . F . N . Engberts , J . Am. Chem. S o c , 106, 139 (1984). JF54 H . H . J a f f e , L . D . Freedman, and G.O. Doak. J . Am. Chem. S o c , 76, 1548 (1954). JJ77 D .A. Jencks and W.P. Jencks, J . Am. Chem. S o c , 99, 7948 (1977). JM67 J . R . Jones, R . E . Marks, and S . C . Subba Rao, J . Chem. Soc. Faraday T r a n s . , 63, 111 (1967). K 73 A . J . Kresge. Chem. Soc. Rev . , 2, 475 (1973). K 75 A . J . Kresge, i n "Proton Transfer Reactions", ( E . F . C a l d i n and V. G o l d , e d s . ) , Chapter 7, Chapman and H a l l , London, 1975. K 76 M.M. Kreevoy i n "Isotopes i n Organic Chemistry", (E . Buncel and C. Lee, e d s . ) , Chapter 1. E l s e v i e r , Amsterdam, 1976. K 83 J . L . Kurz , J . Org. Chem., 48, 5117 (1983). K 84 H . F . Koch, Acc . Chem. Res . , 17, 137 (1984). KC73a D . S . Kemp a n d M . L . Casey, J . Am. Chem. S o c , 95, 6670 (1973). KC73b A . J . Kresge and Y. Chiang, J . Am. Chem. S o c , 95, 803 (1973). KF69 J . L . Kurz and J . M . F a r r a r , J . Am. Chem. S o c , 91, 6057 (1969). 257 KK73 G. .W. Koeppl and A . J . Kresge , J . C . S . Chem. Commun., 371 (1973). KL84 M. .M. Kreevoy and I . H . Lee, J . Am. Chem. S o c , 106, 2550 (1984). K073 M .M. Kreevoy and S . Oh, J . . Am. Chem. S o c , 95, 4805 (1973). KS83 A . J . Kresge and T.S Straub, J . Am. Chem. S o c , 105, 3961 (1983) KT77 A. . J . Kresge and Y . C . Tang, J . Org. Chem., 42, 757 (1977). KV61 G. . Kortum, W. Voge l , and K. Andrusson, "Dis soc ia t ion Constants of Organic Acids i n Aqueous So lut ion" , Butterworths, London, 1961. KW85 H. Kwart and K . A . Wi lk , J . Org. Chem., 50, 817 (1985). L 04 A. Lapworth. J . Chem. S o c , 30 (1904). L 75 E . S . Lewis, i n "Proton Transfer Reactions", ( E . F . C a l d i n and V. G o l d , e d s . ) , Chapter 10, Chapman and H a l l , London, 1975. L 76 K . T . Lef fek i n "Isotopes in Organic Chemistry", (E. Buncel and C. Lee, e d s . ) , Chapter 3. E l s e v i e r , Amsterdam, 1976. LA67 G . E . Lienhard and F . H . Anderson, J . Org. Chem., 89, 2229 (1967). LF25 T . M . Lowry and I . J . Faulkner , J . Chem. S o c , 2883 (1925). LF67 E . S . Lewis and L . H . Funderburk, J . Am. Chem. S o c , 89, 2322 (1967). LG63 J . E . L e f f l e r and E . Grunwald, "Rates and E q u i l i b r i a of Organic React ions", John Wiley , New York, 1963, p. 156. LR69 P .M. Laughton and R . E . Robertson, i n "Solute - Solvent Interac-t ions" , ed. J . F . Coetzee and C D . R i t c h i e , Marcel Dekker, New York, 1969, Chapter 7. LR87 T . H . Lowry and K . S . Richardson, Mechanism and Theory i n Organic Chemistry, 3rd edn . , Harper and Row, New York, 1987. a) p. 662. b) pp. 212-214. c) pp. 222-229. LS81 E . S . Lewis, C C Shen and R .A . More O ' F e r r a l l , J . Chem. Soc. P e r k i n II, 1084 (1981). LS86 T.W.S. Lee and R. Stewart, Can. J . Chem., 64, 1085 (1986). LW69 G . E . Lienhard and T. Wang, J . Am. Chem. S o c , 91, 1146 (1969). - 258 M 70 R . A . More O ' F e r r a l l , J . Chem. Soc. (B), 274 (1970). M 75 R . A . More O ' F e r r a l l , i n "Proton Transfer Reactions", ( E . F . C a l d i n and V . Gold , e d s . ) , Chapter 7, Chapman and H a l l , London, 1975. M 79 T . A . Modro. Phosphorus S u l f u r , 5, 331 (1979). M 83 J . R . Murdoch, J . Am. Chem. S o c , 105, 2660 (1983). MG64 D . J . M a r t i n and C E . G r i f f i n , J . Organomet. Chem. 1, 292 (1964). ML62 A . O . McDougall and F . A . Long, J . Phys. Chem., 66, 429 (1962). N 74 C O . N u a l l a i n , J . Inorg. Nuc l . Chem., 36, 339 (1974). N 87 H. Neuvonen, J . Chem. Soc. Perkin Trans I I , 159 (1987). NC73 C O . N u a l l a i n and S.O. Cinneide . J . Inorg. N u c l . Chem., 35, 2871 (1973). NH87 P .O. N e i l l and A . F . Hegarty, J . Chem. Soc. Chem. Comm., 744 (1987) . NL86 K. Nagarajan, T.W.S. Lee, R.R. Perkins and R. Stewart, Can. J . Chem. , 64, 1090 (1986) . NS87 K. Nagarajan, K . P . S h e l l y , R.R. Perkins , and R. Stewart, Can. J . Chem., 65, 1729 (1987). NV87 K. Nagarajan, S. Venimadhavan, 0. Lee, and R. Stewart, unpub-l i s h e d r e s u l t s . P 34 K . J . Pedersen, J . Phys. Chem., 38, 590 (1934). P 59 Y. Pocker, Chem. and I n d . , 1383 (1959). P 87 P. Pruszynsk i , Can. J . Chem., 65, 2160 (1987). PD69 Y. Pocker and D . G . Dickerson, J . Phys. Chem., 73, 4005 (1969). PD81 D.D. P e r r i n , B. Dempsey, and E . P . Serjeant , "pK a P r e d i c t i o n for Organic Ac ids and Bases", Chapman and H a l l , London, 1981. PG84 A . G . Pinkus and R. Gopalan, J . Am. Chem. S o c , 106, 2360 (1984). PM67 Y. Pocker and J . E . Meany, J . Phys. Chem., 71, 3113 (1967). R 81 R.W. Ramette, "Chemical E q u i l i b r i u m and A n a l y s i s " , Addison-Wesley, Reading, MA, 1981. a) p . 91. - 259 b) p . 137. c) pp. 294-296. d) pp. 63-64. RK39 0. R e l t z and J . Kopp, Z. Physik Chem., A184, 429 (1939). RS71 J . D . Roberts , R. Stewart, and M.C. C a s e r i d , Organic Chemistry: Methane to Macromolecules, P. 203, W.A. Benjamin, New York, 1971. S 85 R. Stewart, The Proton: A p p l i c a t i o n s to Organic Chemistry. Academic Press , Orlando, 1985. a) P- 254. b) PP-, 259-260 c) pp. . 269-281 d) P- 292. e) P- 282. f) P- 154. g) PP • . 34-36. h) PP . 11-14. i ) P- 290. S 87 W.H. Saunders, J r . , J . Am. Chem. S o c , 107, 164 (1987). SA84 C . J . Schlesener, C. Amatore and J . K . Koch i , J . Am. Chem. S o c , 106, 3567 (1984). SB52 C . G . Swain and J . F . Brown, J . Am. Chem. S o c , 74, 2538 (1952) . SD58 C . G . Swain, A . J . D i M i l o , and J . P . Cordner, J . Am. Chem. S o c , 80, 5983 (1958). SD79 E . P . Serjeant and B. Dempsey, "Ionizat ion constants of organic ac ids i n aqueous s o l u t i o n " , Pergamon, Oxford, 1979. SG49 L . H . Sommer, J . R . Gold , G.M. Goldberg and N.S . Marans, J . Am. Chem. S o c , 71, 1509 (1949). SK63 A. S t r e i t w i e s e r J r . and H.S . K l e i n , J . Am. Chem. S o c , 85, 2759 (1963) . SK85 A. S t r e i t w i e s e r J r . , M . J . Kaufman, D.A. Bors , J . R . Murdoch, C . A . MacArthur, J . T . Murphy, and C C . Shen. J . Am. Chem. S o c , 107, 6983 (1985). SN87 K . P . S h e l l y , K. Nagarajan, and R. Stewart, Can. J . Chem., 65, 1734 (1987). SS58 C . G . Swain, E . C . S t i v e r s , J . F . Reuwer, J r . , and L . S . Schaad, J . Am. Chem. S o c , 80, 5885 (1958). - 260 -SS67 J . Steigman and D. Sussman, J . Am. Chem. S o c , 89 , 6406 (1967). SS76a R. S r i n i v a s a n and R. Stewart, J . Chem. Soc. Perk in Trans . 2, 674 (1976). SS76b R. S r i n i v a s a n and R. Stewart, J . Am. Chem. S o c , 98, 7648 (1976). 5577 J . Spaulding, J . E . S t e i n , and J . E . Meany, J . Phys. Chem., 81, 1359 (1977). 5578 R. Stewart and R. S r i n i v a s a n , Acc . Chem. Res . , 11, 271 (1978). SS81 R. Stewart, R. Sr in ivasan and S . J . Gumbley, Can. J . Chem., 59, 2755 (1981). T 60 R.W. T a f t . J . Phys. Chem., 64, 1805 (1960). T 82 J . T o u l l e c , i n "Advances i n P h y s i c a l Organic Chemistry" (V. Gold , and D. B e t h e l l , e d s . ) , Volume 18, Academic Press , London, 1982, p. 1. TD74 J . T o u l l e c and J . E . Dubois, J . Am. Chem. S o c , 96, 3524 (1974). V 51 A . I . Voge l . Quant i ta t ive Inorganic A n a l y s i s . 2nd edn . , Longmans, Green and C o . , London, 1951, pp. 342, 336. W 61 F . H . Westheimer, Chem. Revs . , 61, 265 (1961). WB56 F . H . Westheimer and O . T . Benfey, J . Am. Chem. S o c , 78, 5309 (1956) . WM78 M.D. Waddington and J . E . Meany, J . Chem. E d . , 55, 60 (1978). ZH39 L . Zucker and L . P . Hammett, J . Am. Chem. S o c , 61, 2791 (1939). 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0060243/manifest

Comment

Related Items