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Mechanism of permanganate oxidation of aliphatic amines Wei, Min-Min 1965

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The University of B r i t i s h Columbia FACULTY OF GRADUATE STUDIES PROGRAMME OF THE FINAL ORAL EXAMINATION FOR THE DEGREE OF DOCTOR OF PHILOSOPHY of MIN-MIN WEI B.Sc, The University of B r i t i s h Columbia TUESDAY, JUNE 29th, 1965, AT 10:00 A.M. IN ROOM 261, CHEMISTRY BUILDING COMMITTEE IN CHARGE Chairman: I. McT. Cowan External Examiner: Harold Shechter Department of Chemistry Ohio State University Columbus, Ohio 1961 G. G, S. Dutton T. Money R. E.' Pincock G. B. Porter R. Stewart D. C. Walker S. H. Zbarsky A STUDY OF THE MECHANISM OF THE PERMANGANATE OXIDATION OF AMINES ABSTRACT The mechanism of the permanganate o x i d a t i o n of benzylamine and benzylamine-o<-d2 has been i n v e s t i g a t e d i n the pH region 2 to 14. The deuterium isotope e f f e c t , kft/kD, was found to be 7.0 from pH 8 to 10.7. The absence of s a l t e f f e c t s and the observation that the o x i d a t i o n r a t e followed the i o n i z a t i o n process of the benzyl ammonium i o n show that, benzylamine i s o x i d i z e d v i a the n e u t r a l molecule. Beyond pH 12 the r a t e of o x i d a t i o n was found to be d i r e c t l y p r o p o r t i o n a l t o the hydroxyl i o n concentra-t i o n . A study of 11 meta- and p a r a - s u b s t i t u t e d ben-zylarnines shows e x c e l l e n t Hammett c o r r e l a t i o n w i t h f o r 8 of the compounds, w i t h the p - n i t r o , m-nitro, and m-t r i f l u o r o m e t h y l d e r i v a t i v e s d e v i a t i n g considerably from the Hammett p l o t . was -0.28. The c o r r e l a t i o n w i t h C T + and the very negative A S * values obtained f o r the o x i d a t i o n r e a c t i o n show that the t r a n s i t i o n s t a t e must be an i o n i c one i n v o l v i n g extensive charge separa-t i o n . The rate-determining step i s c o n s i s t e n t w i t h hydrogen t r a n s f e r from benzylamine to permaganate but the choice of a hydride i o n t r a n s f e r mechanism or a hydrogen atom t r a n s f e r mechanism cannot be unequivo-c a l l y made from the r e s u l t s . For the o x i d a t i o n s i n the h i g h l y a l k a l i n e regions beyond pH 12, termolecular mechanisms are suggested, Whereas 0 - a l k y l a t i o n p r o t e c t s a l c o h o l s from oxida-t i o n by permanganate, N - a l k y l a t i o n g r e a t l y increases the o x i d a t i o n r a t e of amines. However, N - a c y l a t i o n tends to protect the amine from o x i d a t i o n . L i m i t e d studies, of the k i n e t i c s of permanganate o x i d a t i o n of ammonia, cyclohexylamine, N,N-dimethyl-benzylamine, and (-)-o^ - methylbenzylamine were c a r r i e d out to compare t h e i r rates of o x i d a t i o n w i t h those f o r benzylamine. The mechanism of the permanganate o x i d a t i o n of t -butylamine to t - n i t r o b u t a n e was studied from pH 8 to 12. As i n the benzylamine o x i d a t i o n t-butylamine i s o x i d i z e d v i a i t s n e u t r a l molecule. The absence of an c* -hydrogen and the absence of a s u b s t a n t i a l isotope e f f e c t i n t - b u t y l a m i n e - N D 2 suggest t h a t t h e mechanism i n -v o l v e s an o x i d a t i v e a t t a c k on t h e n i t r o g e n by permanganate. The f o r m a t i o n of a q u a t e r n a r y h y d r o x y l a m i n e d e r i v a t i v e between t - b u t y l a m i n e and permanganate has been proposed f o r t h e r a t e - d e t e r m i n i n g s t e p . The k i n e t i c s of permanganate o x i d a t i o n of b e n z y l a -mines a t -10° i n f r o z e n H^O and has been i n v e s t i g a -t e d from pH 7.5 t o 9.3= The r e a c t i o n o r d e r remains un-changed from t h a t a t 25° . The r a t e s of o x i d a t i o n a r e more t h a n 10 t i m e s g r e a t e r i n i c e a t -10° t h a n i n l i q u i d w a t e r a t -10°, and t h i s a c c e l e r a t i o n i n c r e a s e s w i t h d e c r e a s i n g pH. An a p p a r e n t p K B H f of 8.70 was o b t a i n e d f o r ben-z y l a m i n e at\-10° i n i c e . No change i n t h e r a t e was ob s e r v e d when t h e o x i d a t i o n was c a r r i e d out i n f r o z e n D2O and when t h e i o n i c s t r e n g t h o f t h e medium was i n c r e a s e d . The a c c e l e r a t i n g e f f e c t s o b s e r v e d i n t h e f r o z e n systems a r e d i s c u s s e d i n terms of pH, c o n c e n t r a t i n g e f f e c t of t h e f r e e z i n g , and t h e o r i e n t a t i n g e f f e c t of t h e i c e s t r u c t u r e . GRADUATE STUDIES F i e l d o f Study: P h y s i c a l - O r g a n i c C h e m i s t r y T o p i c s i n P h y s i c a l C h e m i s t r y C h e m i c a l K i n e t i c s T o p i c s i n O r g a n i c C h e m i s t r y O r g a n i c S t e r o c h e m i s t r y P h y s i c a l O r g a n i c C h e m i s t r y O r g a n i c R e a c t i o n Mechanisms Recent S y n t h e t i c Methods i n O r g a n i c C h e m i s t r y J . A. R. Coope R. F. S n i d e r A. V. Bree D. G. L. James E„ A. O g r y z l o J . P. Kutney D. E» McGreer Ri E l P i n c o c k L. D„ Hayward R. S t e w a r t R. E„ P i n c o c k A. R o s e n t h a l G. G. S. D u t t o n ( c o n t i n u e d ) GRADUATE STUDIES (con't) Related Studies: D i f f e r e n t i a l Equations Walter H. Gage Topics i n Inorganic Chemistry N. B a r t l e t t W. R. Cullen H. C, Clark The Chemistry of Organometallie Compounds H. C. Clark MECHANISM OF PERMANGANATE OXIDATION OF ALIPHATIC AMINES by MIN-MIN WEI B.Sc, University of British Columbia, 1961 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of Chemistry We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA June, 1965 I n p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s t u d y . I f u r t h e r a g r e e t h a t p e r -m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e Head o f my D e p a r t m e n t o r by h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t . c o p y i n g o r p u b l i -c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . D e p a r t m e n t o f CHEMISTRY The U n i v e r s i t y o f B r i t i s h C o l u m b i a , V a n c o u v e r 8, C a n a d a D a t e ^ 5 i i ABSTRACT The mechanism of the permanganate oxidation of benzylamine and benzylamine-^-d^ has been investigated i n the pH region 2 to Ik. The deuterium isotope e f f e c t , kg/kp, was found to be 7-0 from pH 8 to 10.7- The absence of s a l t effects and the observation that the oxidation rate followed the io n i z a t i o n process of the benzylam-monium ion show that benzylamine i s oxidized v i a the neutral mole-cule . Beyond pH 12 the rate of oxidation was found to be d i r e c t -l y proportional to the hydroxy1 ion concentration. A study of 11 meta- and para-substituted benzylamines shows excellent Hammett correlation with cr-+ f o r 8 of the com-pounds, with the p-nitro, m-nitro, and m-trifluoromethyl deriva-tives deviating considerably from the Hammett p l o t . f was -0.28. The corre l a t i o n with ^ and the very negative ^ values obtained for the oxidation reaction show that the t r a n s i t i o n state must be an i o n i c one involving extensive charge separation. The rate-determining step i s consistent with hydrogen transfer from benzyl-amine to permanganate but the choice of a hydride ion transfer mech-anism or a hydrogen atom transfer mechanism cannot be unequivocally made from the res u l t s obtained i n t h i s thesis. For the oxidations i n the highly a l k a l i n e regions beyond pH 12, termolecular mechanisms are suggested. Whereas O-alkylation protects alcohols from oxidation by permanganate, N-alkylation greatly increases the oxidation rate of amines. However, N-acylation tends to protect the amine from i i i oxidation. Limited studies of the kinetics of permanganate oxidation of ammonia, cyclohexylamine, N,N-dime thy lbenzylamine, and (-)- <X-methylbenzylamine were carried out to compare their rates of oxida-tion with those for benzylamine. The mechanism of the permanganate oxidation of t-butyl -amine to t-nitrobutane was studied from pH 8 to 12. As i n the benzylamine oxidation t-butylamine i s oxidized via i t s neutral molecule. The absence of an o(-hydrogen and the absence of a sub-stantial isotope effect i n t-butylamine-NDg suggest that the mech-anism involves an oxidative attack on the nitrogen by permanganate. The formation of a quaternary hydroxylamine derivative between t-butylamine and permanganate has been proposed for the rate-determining step. The kinetics of permanganate oxidation of benzylamines at -10° i n frozen BgO and DgO has been investigated from pH 7«5 to 9'3- The reaction order remains unchanged from that at 25°. The rates of oxidation are more than 10 times greater in ice at -10° than i n liq u i d water at -10°, and this acceleration increases with decreasing pH. For p-nitrobenzylamine there i s only a 3-fold increase i n rate i n going from liquid to frozen water at -10°. An apparent p%[j+ of 8.70 was obtained for benzylamine at -10° i n ice. No change i n the rate was observed when the oxida-tion was carried out i n frozen DgO and when the ionic strength of the medium was increased. The accelerating effects observed i n the frozen systems are discussed i n terms of pH, concentrating effect of the freezing, i v and t h e o r i e n t a t i n g e f f e c t o f t h e i c e s t r u c t u r e . V ACKNOWLEDGEMENTS I would like to express my sincere appreciation to Professor Ross Stewart for suggesting this research problem and for guiding i t to i t s completion. Many thanks are extended to Dr. R. E. Pincock for his valuable suggestions. And f i n a l l y , I would like to thank the National Research Council for the financial assistance. v i TABLE OF CONTENTS Page INTRODUCTION 1 SCOPE OF PRESENT RESEARCH 19 PART I: OXIDATION OF BENZHiAMTJKS AND RELATED COMPOUNDS A. Synthesis, purification and identification of amines and 2. Synthesis of m-methylbenzylamine, m-methoxybenzyl-amine and m-chlorobenzylamine by LiAlH^ reduction of the corresponding amides 3 . Synthesis of p-nitro, m-trifluoromethyl, m-nitro and p-ethyl derivatives of benzylamine by a mod-i f i e d Sommelet method B. Kinetic methods 25 1. Standardization of potassium permanganate solutions 2. lodometric method 3 . Oxidation by manganate k. Oxidations i n deuterium oxide 5. Oxidation of (-)- -methylbenzylamine C . Benzylamine product analysis 30 1. Determination of ammonia 2. Determination of benzaldehyde related compounds 21 1. Synthesis of benzylamine- ex^-dg v i i A. Stolchiometry 31 B. Product analysis .. . 31 C. Order of the reaction 3 2 D. Ef f e c t of i o n i c strength 32 E. pH-rate p r o f i l e 35 F. Act i v a t i o n parameters 1*6 G. Isotope effects 50 H. Oxidation of benzylamine i n DgO... 51 I . Substituent e f f e c t . . . . . . 52 J. Oxidation of (-)- ©<.-methylbenzylamine 5^ K. Miscellaneous reactions 58 (a) Oxidation of N,N-dimethylbenzylamine (b) Oxidation of NH^ (c) Oxidation of eyelohexylamine (d) Oxidation of acetamide (e) Oxidation of N,N-dimethyIformamide and N-benzyl-formamide (f) Oxidation of methylamine, dimethylamine, trimethyl-amine, t-butylamine and tetramethylammonium hydroxide DISCUSSION 62 PART I I : OXIDATION OF t-BUTYXAMINE EXPERIMENTAL. 76 A. Synthesis of possible oxidation intermediates 76 1. Synthesis of t-b\xtylhydroxylamine 2, S y n t h e s i s o f t - n i t r o s o b u t a n e v i i i B. Product analysis 76 1. Synthesis of t-rnitrobutane from t-butylamine 2. Synthesis of t-nitrobutane from t-butylhydroxylamine C. Kinetic studies 77 1. Buffers of high concentration 2. Purification of t-butylamine 3. Kinetic method !+. Studies i n D 2 0 RESULTS 80 A. Stoichiometry ... 80 B. Order of reaction 80 C. Effect of pH on the oxidation rate 82 D. Oxidations i n D 2 0 82 DISCUSSION 86 PART III: OXIDATION OF BENZYIiAMTJNES IN FROZEN SYSTEMS EXPERIMENTAL 90 RESULTS 92 DISCUSSION 98 BIBLIOGRAPHY 102 APPENDIX 107 SUGGESTIONS FOR FURTHER WORK 1.15 ix TABLES Page I Product Study of the Oxidation of Benzylamines 32 II Oxidation of Benzylamine i n the Region pH 2 to lk: Variation of the Rate Constant with pH... 33 III Oxidation of Benzylamines: Activation Parameters 46 IV pH Variance of Phosphate Buffer with Temperature !+9 V Oxidation of Benzylamine, Protio and Deuterio Analogues. i n the Region pH 8 to 11: Deuterium Isotope Effect..... 50 VI Data for the Oxidation of Benzylamine i n DgO 51 VII Data for the Hammett Plots 52 VIII Data for the Hammett Plot Using the Yukawa-Tsuno Equation 56 IX Polarimeter Data for the Oxidation of (-)- -methyl-benzylamine 58 X Oxidation of Ammonia: Variation of Rate with pH 59 XI Oxidation of Cyclohexylamine: Variation of Rate with pH 59 XII Oxidation of t-Butylamine: Variation of Rate with pH... 85 XIII Comparison of Rates for Benzylamine and p-Nitrobenzyl-amine i n Liquid and i n Frozen Systems 92 XIV Rate Studies i n HgO and DgO at -10° (in ice) 97 XV Relative Rates of Permanganate Oxidation between Reactions i n Frozen Systems at -10° and those at 25° with respect to pH. 98 XVI Comparison of Rate Constants between Liquid and Frozen Systems at -10°..... 99 X FIGURES Page 1. Oxidation of Benzylamine: Typical Rate Plot, pH = 9.90. 33 2. Oxidation of Benzylamine: Typical Rate Plot, pH = 7.62. 3*f 3. Oxidation of Benzyl amine: Relation between Rate C O l t X S * t £ L U " t b S T I C ! . • a«ea»»«ge««e«)««0«oee»0e«eovo<»0oe*)***a*«« 3^ k. Oxidation of Benzylamine: Linear Relation between , i max > pH and log (kg/kvj - k 2) 37 5. Oxidation of Benzylamine: Relation between Rate Constant and Neutral Benzylamine Concentration hi 6. Oxidation of Benzylamine: Relation Between log kg and log [CgH^CHgNHg] k2 7. Oxidation of Benzylamine i n Alkaline Solutions: Relation between Rate Constant and [OH-].. k-3 8. Oxidation of Benzylamine: Typical Rate Plot, pH = 13-78 hk 9. Oxidation of p-Methylbenzylamine: Variation of Rate Constant with Temperature 10. Oxidation of p-Methylbenzylamine: Variation of log k^ T with Temperature kQ 11. Oxidation of Benzylamine s : Hammett Plot... 53 12. Oxidation of Benzylamine s : Hammett Plot..... 55 13. Oxidation of Benzylamines: Hammett Plot Using the Yukawa-Tsuno Equation 57 Ik. Oxidation of NH^: Typical Pseudo F i r s t Order R&^6 Plot ••s*«*«»a»e«»*a0»«a*o0*9»tt«oos«o««»a0**a«OQB»«« 15. Oxidation of t-Butylamine: Typical Rate Plot, pH = 9.83 8 l x i Page +4 16. Oxidation of t-Butylamine: Effect of Mn on the O x i d a t i o n . g . . . . . . . . . . « . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 17. Oxidation of t-Butylamine: Relation between Rate Constant and pH.................................... 8"+ 18. Oxidation of Benzylamine: Typical Rate Plot at -10.0° (in ice ) , pH = 7-53 (22°) 93 19. Oxidation of Benzylamine at -10.0° (in i c e ) : Relation between Rate Constant and pH................... 95 20. Oxidation of Benzylamine at -10.0° (in ice); Relation between log [CgH^CHgNHg] and log kg. 96 1 INTRODUCTION Permanganate has been extensively used for the oxidation of organic compounds. The mechanisms by which these oxidations oc-cur are usually complex; and, depending on the acidity of the medium in which they take place, the extent of oxidation may vary quite considerably. In highly alkaline solutions, permanganate i s re-duced via a one-equivalent change to manganese(VI); i n alkaline, neutral and weakly acidic solutions permanganate i s reduced to man~ ganese(lV); and i n strongly acidic solutions permanganate may be re-duced by certain reducing agents to manganese(II). Manganese(ill) and manganese(V) are important intermediates of permanganate oxida-tions, but since they undergo rapid disproportionation to higher and lower valencies, they are rarely observed i n these reactions. They have been prepared under special conditions, however, and their chem-is t r y has been studied. The properties of each manganese species and their reac-tions have been reviewed by Stewart (l) and only a brief summary w i l l be presented here. Manganese(VI) i s stable i n solutions of pH 1 3 or above. In more acidic media i t disproportionates to manganese(VII) and mangan-ese(lV), the rate of disproportionation increasing with increasing acidity ( 2 ) . Except i n the case of aromatic aldehyde oxidations ( 3 ) manganate oxidations are usually much slower than the corresponding permanganate oxidations {k,5). Studies with manganate have been made on 1 , 2 - d i o l s , phenols and olefinic acids ( 6 ) . The potassium salt of hypomanganate, manganese(V), was 2 f i r s t prepared by Lux (7). Pode and Waters (6) found that hypomanganate is stable i n solutions more basic than ION a l k a l i , but below 8N a l k a l i i t disproportionates to manganese(VI) and manganese(IV). Hypomanganate is a much weaker oxidizing agent than manganate. It can slowly oxidize primary and secondary alcohols, but does not react with unsaturated acids, tertiary alcohols or phenols (6). In alkaline and weakly acidic media manganese dioxide i s the reduction product of permanganate. The use of phosphate buffers can delay the precipitation of manganese dioxide i n solution by forming a complex with i t . Heterogeneous reactions with manganese dioxide dis-persed i n organic solvents are often used for the oxidation of various alcohols, amines, and diarylmethanes (8,9,10,11,12,13,lk). Such reac-tions of manganese dioxide seem to follow radical mechanisms. The manganic ion {Wx^) i s stable i n concentrated sulfuric acid solutions. In less acidic media i t easily disproportionates to manganese(II) and manganese(IV), unless i t i s complexed by fluoride or pyrophosphate ions ( l 5 , l 6 ) . In concentrated perchloric acid solu-tions (1-6M) manganic ions can be generated through anodic oxidation of manganese(II) (17). Recent studies of oxidations by manganese(ill) have been made on malonic acid ( l 8 ) , pinacol (l9)> formaldehyde and formic acid (20). Manganous ions are end-products of permanganate oxidation i n acidic media when strong reducing agents such as iodide, ferrous ions or oxalic acid are used as substrates. The well-known Guyard reaction between manganous and permanganate ions occurs in weakly acidic or neutral solution: 2 MnO^ '" + 3 Mn + 2 + 2 H 20 5 Mn02 + k H + (l) 3 Mechanistic studies on this reaction have been reviewed by Ladbury and Cullis (21). PERMANGANATE OXIDATIONS OF ORGANIC SUBSTRATES The reactions of many different classes of substrates with per-manganate have recently been examined. A selection of those reactions whose mechanisms have been studied i n aqueous solutions and which are pertinent to the present investigation w i l l be reviewed here. Oxidation of aromatic aldehydes The oxidation of benzaldehydes from pH 5 to 13 has been studied by Wiberg and Stewart (3). Two mechanisms were proposed for the oxida-tion: one for the reaction i n acidic medium and one for the reaction in basic medium. In basic solutions from pH 11 to 13 the rates increased with increasing pH, and were subject to specific hydroxyl ion catalysis ac-cording to the expression: d[Mn01i ] = k [PhCHO] [MnOii"] [OH"] (2) dt A negligible deuterium isotope effect was observed for PhCDO, and most of the oxygen i n the product came from the solvent. A large, positive rho was obtained from the Hammett plot. For the reaction i n the basic solutions, a free radical chain mechanism was suggested. From pH 6.8 to 11 the rates levelled off and did not change with changing pH. The lowest second order rate constant i n this re-gion was 0.370 l.mole _ 1sec 1 . In more acidic solutions the rates gradually increased again, although the rate of increase was not nearly so great as that i n the basic region. The reactions were general-acid catalyzed, and an iso-tope effect of 7 was found for PhCDO. The Hammett reaction constant, p , for the reaction was small and negative. The mechanism for the oxidation i n acid solutions involves a fast ester formation between the aldehyde hydrate and permanganate, followed by rate-determining proton removal from the aldehydic hydrogen. In solutions below pH 5 an autocatalytic reaction takes place between permanganate and benzaldehyde. Oxidation of alcohols From the observations of a positive salt effect, a large ne-gative entropy of activation, and hydroxyl ion catalysis, Stewart con-cluded that benzhydrol was being oxidized through the benzhydrylate ion (22). Oxygen-18 studies showed no oxygen transfer from permanganate to substrate, and an isotope effect of 6.6 for PhCDOHPh showed C-H bond breaking i n the rate-determining step. The following mechanism was proposed: PhgCHOH + OH" , PhgCHO" + H20 Ph2CH0" + MnO£ • Products (3) Stewart's proposed hydride transfer mechanism for benzhydrol led Mocek to study the electronic requirements for this reaction (k). Experimental d i f f i c u l t i e s prevented conclusive results, but i t appeared that both electron-withdrawing and electron-donating substituents ac-celerated the oxidation rate. Stewart and Van der Linden (23) observed that the rates of oxidation of aryl trifluoromethyl carbinols followed their ionization curves, which could be easily determined i n the pH region. Observations 5 of positive salt effects, linear rate versus alkoxide ion dependence, and large entropies of activation support Stewart's previous assumption that the alkoxide ion i s responsible for the oxidation with permanganate. An unusually large isotope effect of l6 was found for the 1-deuterio compound, but there was no solvent deuterium isotope effect. The evi-dence points to a hydride ion transfer mechanism, but substituent ef-fects showed the reaction to be rather insensitive to electronic changes at the reaction s i t e . Various explanations were offered for the latter observation. Oxidation of fluoral hydrate Stewart and Mocek (2*0 studied the permanganate oxidation of fluoral hydrate from k6f$> sulfuric acid to pH Ik. In this wide range of acidities f l u o r a l hydrate manifests i t s e l f as the monoanion, the d i -anion, and the neutral molecule with the relative oxidation rates of these species being as follows: 0" 0* OH F3C-C-H )>> F3C-C-H ^> F3C-C-H 0" OH OH In the highly acidic solutions - up to k6$> sulfuric acid - the rate of oxidation was dependent upon the H_ function. This was inter-preted as the reaction between permanganic acid and the neutral fluoral hydrate. In the oxidation of 1-deuterio fluoral hydrate, normal isotope effects were observed for the oxidation of the dianion and neutral species, but as with the fluoro alcohols, a large isotope effect, kg/kD=10, was obtained for the monoanion. A l l of the above results appear to favor 6 a hydride ion transfer mechanism. However, only a four-fold increase in rate was observed for CF^CHgO" compared with (CF^gCHO*, whereas i n a hydride transfer mechanism one would expect a much greater difference in rate since the groups -CF^ a n d " H d i f f e r so greatly i n their res-pective inductive effects. The following radical mechanism was also suggested: o" 0" OH 1 - \ l F3C-C-H + MnO^  — * F3C-C. + HMnO^  (k) ' I VI VTT OH fast, Mn or MnVJ"L F CCOOH 3 In a recent paper, Kurz (25) examined the results of the oxidation of fluoral hydrate and observed that the kinetic terms for each of the four processes, i . e . the oxidation of neutral fluoral hy-drate by permanganic acid, the oxidation of the monoanion by permangan-ate, the oxidation of neutral fl u o r a l hydrate by permanganate, and the oxidation of the dianion by permanganate, di f f e r only i n the extent of protonation of the reactants, so that he was able to calculate, from previously derived equations ( 2 6 ) , the three successive pK^ 's cor-responding to the equilibria between the four transition states. From these parameters, which must satisfy the required condition that their values l i e between the pK a of the reactants (zero bond formation) and the pKa of the products (complete bond formation), he was able to es-timate the structures of the various transition states, and to give upper and lower limits to bond-making and bond-breaking i n these tran-sition states. He found that i f a l l the mechanisms of fluoral hydrate oxidation involved hydride ion transfer, then the calculated pK^* 's 7 s a t i s f i e d t h e n e c e s s a r y r e q u i r e m e n t t h a t t h e i r v a l u e s he between t h e e s -t i m a t e d p K a ' s f o r t h e i n i t i a l and f i n a l s t a t e s o f t h e r e a c t a n t s . On t h e o t h e r hand, i f h y d r o g e n atom t r a n s f e r s a r e assumed t o he t a k i n g p l a c e i n t h e f o u r r e a c t i o n s , t h e n t h e r e q u i r e d c o n d i t i o n was n o t s a -t i s f i e d . I f two r e a c t i o n s c o n t a i n i n g n o n a d j a c e n t t o t a l numbers o f p r o t o n s i n t h e r e a c t a n t s p r o c e e d b y h y d r o g e n atom t r a n s f e r and t h e o t h e r two p r o c e e d b y h y d r i d e t r a n s f e r , t h e r e q u i r e d c o n d i t i o n f o r pKg* c a n s t i l l be met. The q u e s t i o n o f w h e t h e r a h y d r o g e n atom t r a n s f e r o r a h y d r i d e i o n t r a n s f e r mechanism i s t a k i n g p l a c e i n a r e a c t i o n a r i s e s i n t h e o x i d a t i o n o f a l c o h o l s and f l u o r a l h y d r a t e . The s t r o n g e s t e v i d e n c e i n f a v o r o f h y d r i d e i o n r e m o v a l i s t h e f a c t t h a t t h e r a t e - c o n t r o l l i n g s t e p i n t h e o x i d a t i o n o f a l c o h o l s i s between t h e a n i o n and permanganate. M o r e o v e r , i n t h e f l u o r a l h y d r a t e o x i d a t i o n l a r g e i n c r e a s e s i n r a t e a r e e n c o u n t e r e d w i t h e a c h a d d i t i o n a l i o n i z a t i o n o f t h e h y d r a t e m o l e c u l e . A h y d r i d e i o n t r a n s f e r mechanism s h o u l d be f a v o r e d b y e l e c t r o n -d o n a t i n g s u b s t i t u e n t s ; and i n t h e c a s e o f t h e f l u o r o a l c o h o l s , ArCHOHCF^, one w o u l d e x p e c t a l a r g e n e g a t i v e Hammett ^ v a l u e (27)- Most r e a c t i o n s t h a t a r e known t o i n v o l v e h y d r i d e i o n t r a n s f e r s a r e c o m p l i c a t e d b y p r e -e q u i l i b r i u m s t e p s (28) so t h a t t h e r h o f o r s u c h r e a c t i o n s i s n o t r e -p r e s e n t a t i v e o f t h e h y d r i d e r e m o v a l s t e p a l o n e . However, r h o v a l u e s o f a p p r o x i m a t e l y +2.6 have b e e n o b t a i n e d f o r t h e a d d i t i o n o f h y d r i d e i o n t o c a r b o n y l groups ( l , 29) . F o r t h e f l u o r o a l c o h o l o x i d a t i o n r h o was a p p r o x i m a t e l y z e r o a t pH 13, where p r e - e q u i l i b r i a a r e u n i m p o r t a n t . S t r u c t u r a l changes s h o u l d a l s o have a p r o nounced e f f e c t i n a h y d r i d e t r a n s f e r mechanism:.. As m e n t i o n e d b e f o r e , o n l y a f o u r - f o l d d i f f e r e n c e i n r a t e was o b s e r v e d f o r ( C ^ ^ C H O H and CF^CH^OH. 8 Swain et a l (30) have suggested that, due to the nature of the bonding i n the transition state of a hydride transfer reaction, deuter-ium isotope effects should not vary too much with different substituents on the reacting molecule. However, the observed isotope effects for Ph2CD0H (22), PhCDOHCF3 (23), and (CF3)2CDOH (2k) are 7:1, l 6 : l , and 19:1, respectively, at 25°. A hydrogen atom transfer mechanism should also be considered. Taking the fluoro alcohols as an example, the following mechanism is suggested by Stewart (31): 0" Ar-C-CFg . + MnO^  *• Ar-C-CF^ + HMnO^  (5) I VI I fast, Mn or Mn x Ar-C-CF^ At f i r s t glance i t i s d i f f i c u l t to see why there should be such large differences i n rate of hydrogen atom removal from the anion and the neutral molecule. An examination of the probable transition states of the hydrogen atom transfer reaction may help c l a r i f y the situation. H I Ph-C-OH »-[PhpC-0H] A Ph H 1 (6) Ph-C-0" •[Ph.C-O"] B I Ph II Recently, i t was shown by Porter and Wilkinson (32) that the ketyl, 6 Ph^C-OH, has a pK near 9, which makes i t at least. IO times more acidic 9 than benzhydrol, PhgCHOH. This means that the ketyl radical anion (II) must be much more stable with respect to the ketyl radical (I) than i s the benzhydrylate ion with respect to benzhydrol. It follows then, that reaction B must be much more energetically favorable than reaction A. Similar arguments can be applied to the case of fl u o r a l hydrate oxidation. Oxidation of formatopentaammine c o b a l t ( i l l ) Recently Halpern and Gandlin (33) reported the observation that formatopentaammine c o b a l t ( i l l ) can be oxidized by permanganate in a stepwise mechanism i n which the f i r s t step involves hydrogen atom re-moval from the formato ligand to give a radical ion intermediate. The similarity of isotope effects and activation parameters for the above reaction to those for the oxidation of formic acid i n aqueous solution (3^, 35) led the authors to suggest that the reaction of formate ion with permanganate may also proceed by hydrogen atom transfer rather than hydride ion transfer. Oxidation of tertiary hydrogens In the oxidation of S-(+)-^-methylhexanoic acid to R-(+) -J+-hydroxy-4-methylhexanoate lactone by permanganate, Wiberg and Fox (36) observed a 42$ retention of configuration i n the lactone at pH 7 and a 35$ retention at pH 13. However, i n the oxidation of optically active p-sec-butyl benzoic acid to c\-hydroxy-p-sec-butylbenzolc acid there was 100$ racemization at pH 7 and only 6$ retention at pH 13. 0xygen-l8 studies showed oxygen transfer not only from the permanganate but also from the carboxyl group to the tertiary carbon center. A hydride transfer mechanism was dismissed on account of the 10 small rate differences between the two substrates. Wiberg and Fox pro-posed the following hydrogen atom transfer mechanism, followed by three different modes of decomposition to give the observed stereochemistry i n the products and to account for the oxygen transfers: R^H + MnOi^ " *• [R^-MnO^-H]" • (7) /CHg -CHg 0=C -CRg -CHg " ~ 1 RgC-O-MnO^ H *• R2C + HMnO^  HgO R3C-0-Mn03H" ^ -^R3C-OfMn03H" R3C0H + HMnO^  HgO 'R^O-MnO^' • R CQH + HgMnO^" The above mechanism assumes that the C-O-Mn bond i s formed while the products are s t i l l i n the solvent cage. Step 1 i n the subsequent de-composition of the manganese ester involves the attack of the carboxy-late group on the tertiary carbon, which accounts for the oxygen trans-fer from carboxyl group and results i n 100$ inversion of configuration. Step 2 shows the cleavage of the Mn-0 bond by hydrolysis to give com-plete retention and oxygen transfer from permanganate to product. In step 3 the intermediate undergoes an Sjjl reaction to give the carbonium ion which subsequently reacts with water to give the product. This step involves no oxygen transfer. In the case of p-sec-butylbenzoic acid step 3 must be favored since the carbonium ion could be stabilized by the phenyl group. This was shown in the observed decrease in reten-tion of configuration and the decrease in oxygen transfer. PERMANGANATE OXIDATION OF AMINES Primary aliphatic amines are usually rapidly oxidized by per-11 manganate to give aldehydes and acids (37)• Benzylamine is oxidized by alkaline permanganate to give benzaldehyde, benzoic acid and benzamide ( 3 8 ) . Kornblum and Clutter (39) found that t-butylamine can be oxid-ized i n good yield to t-nitrobutane. The reaction was slow, however, and required heating. Secondary dialkylamines are often oxidized to a variety of products. Permanganate oxidizes diethylamine to ethanol, ammonia, acetic acid and acetohydroxamic acid (ho) •. It was found by Labriola et a l {hi) that trlbenzylamine is oxidized by acidic permanganate to benzaldehyde and benzoic acid, but that N,N-dimethylbenzylamine is resistant to this type of oxidation. The parent compound, ammonia, i s oxidized by alkaline perman-ganate to the n i t r i t e ion, and by acidic permanganate to the nitrate ion (^2) Both reactions occur extremely slowly, and the latter reac-tion requires a high concentration of the ammonium ion. Hydrazine can be exhaustively oxidized by acid permanganate to give nitrogen , hut controlled oxidation of 1,2-disubstituted hydrazines in acetone solution give high yields of the 1,2-disubstituted azo compounds (kk). Under similar conditions, 1,1-disubstituted hydra-zines are oxidized to tetrazenes by permanganate (^5)* Although permanganate has often been used i n the oxidation of amines, the detailed mechanism of reaction has received l i t t l e study. Recently, Shechter, Rawalay and Tubis (^6,V7) made a systema-t i c study of the products of permanganate oxidation of primary, second-ary, and tertiary amines i n neutral aqueous t-butyl alcohol solutions, and discussed the possible mechanisms for the various reactions. They found that using an excess of permanganate, o-, m-, and p-substituted 12 benzylamines are rapidly oxidized to the corresponding substituted N-[<K-(benzylidene-amino)-benzyl]-benzamides,(I), and N,N'-(imino-dibenzylidene)-bls-[benzamides], (II), as well as to benzoic acids and ammonia. Ar-CH=N-CH-NH-C-Ar (I) I II Ar 0 Ar -C -NH-CH -NH -CH-NH-C -Ar (II) II I I II 0 Ar Ar 0 The precise mechanism for the formation of these complex molecules was not known but i t was assumed that benzallmines are the immediate pro-ducts of the oxidation of benzylamines and that condensation of these imines with the parent benzylamines together with further oxidation by permanganate takes place to give (I) and (II). Studies of the oxidation of benzhydrylamine, dlbenzy1ami ne, and N-phenylbenzhydrylamine with neutral permanganate a l l follow the same pattern i n that the i n i t i a l step involves dehydrogenation to the Schiff base which then rapidly condenses with the parent amine. Taking N-phenylbenzhydrylamine as an example, the reaction sequence i s as follows: -HpO Ph2CH-NHPh + MnO^  • Ph2C=NPh PhgCBNHPh I • Ph2C-N-CHPh2 (8) NHPh The products, N,N-dibutylf ormaml,de, N,N-dibutylbutyramide, dibutylamine, butyraldehyde, and butyric acid from the oxidation of the tertiary amine, tributy1amine, suggest that the reaction i n i t i a l l y yields the enamine, which then reacts with water to form the precursor 13 to the observed products: MnOj" HoO Bu^CH^CIL^CIL^CH^ • [Bu2NCH=CHCH2CH3] • BUgNH + CH3CH2CH2CH0 [Bu pN-CH(0H)-CH 2CHpCHo]v (9 ) J X MnO" 0 Bu 2N-C-CHCH2CH 3 When tribenzylamine, which could not give an enamine intermediate, was oxidized by permanganate, the usual products, benzaldehyde and benzoic acid, are obtained. OXIDATION OF AMINES BY OTHER OXIDIZING AGENTS Oxidation by t-butyl hydroperoxide The reactions of t-butyl hydroperoxide and alkylamines have been extensively studied by De La Mare et a l ( 4 8 , ^ 9 ) and a l l the evi-dence support a radical chain mechanism. The reactions may be summar-ized as follows: (1) Primary amines RCHgNHg +' tR'OOH • RCH=NH + tR'OH + HgO (10) (2) Secondary amines (RCHg^NH + tR'OOH •*• RCH=NCHgR +tR ' 0 H + H20 ( l l ) (3) Tertiary amines (RCH2)3N + tR'OOH • RCHO + (RCH^gNH + tR 'OH (12) (k) When there are no <K-hydrogens adjacent to the amino function, the reaction becomes extremely slow and proceeds by an oxidative at-tack on the nitrogen to give the nitro compound. Electron paramagnetic studies showed that an amine oxide free radical, RR' -CH-NO-CHR 'R, i s produced i n these reactions (1*9). A mech-anism i n which this radical takes part i n the chain transfer steps to produce other radicals which lead to the products was proposed by De La Mare. Oxidation by di-t-butyl peroxide Henbest and Patton (50) observed that the reaction of t -butoxy radicals with dimethylaniline gives tetra-N-substituted 1,2-diamines. Presumably the reaction proceeds by hydrogen atom abstraction from the c<. -carbon by the t-butoxy radical to give the following alkyl radical (I), Ph-N-CHo + (CHJ.C-O- • Ph-N-CB^* + (CHj COH (13) ^CE^ 2 5 NCH 3 3 5 I which then dimerizes to give the diamine. Oxidation by hydrogen peroxide Tertiary aliphatic amines are oxidized by hydrogen peroxide to amine oxides. It was suggested by Wieland (51) that the reaction occurs by the addition of hydrogen peroxide to the amine to form an ammonium peroxide. Subsequent decomposition yields the amine oxide and water. Oswald and Guertin (52) confirmed this course of reaction from infrared studies but found that the adducts are hydrogen-bonded com-plexes , not ammonium salts. Oxidation by benzoyl peroxide Recently a detailed study was made by Fayadh et a l (53) on the reaction of dimethylaniline and benzoyl peroxide. They isolated and characterized the product, N-(p-dimethylaminobenzyl)-N-methylaniline, 15 (I), and use the previously suggested mechanism by Walling and Indictor (5*0 to interpret i t s formation. [Ph-NMep0-C0Ph]+PhC02 • [Ph-N=CH2 < > Ph-N-GB^PhCO;; NCHo III CHj II J C + PhCOOH (lk) The rate-determining step involves a nucleophilic displacement on the benzoyl peroxide by dimethylaniline to give a quaternary hydroxyl-amine derivative (II), which then decomposes by homolytic N-0 bond cleavage and hydrogen atom abstraction from the N-methyl group. The product, (I), arises from a substitution reaction of ion III on d i -methy laniline . Oxidation by Ozone According to Horner et a l (55) formation of N-oxides from tertiary amines i n chloroform or methanol occurs by electrophilic at-tack by ozone on the nitrogen atom, followed by loss of oxygen. R3N + 0 3 - — • R 3N -6%5" • R3N+-0" + Og ( 1 5 ) In hydrocarbon solvents, however, Henbest and Stratford ( 5 6 ) found that tri-n-butylamine with ozone gave mainly di-n-butylamine at - 7 8 ° > and N,N-di-n-butylformamide at 1 5 ° • They suggested that an intermediate carbinolamine, (I), i s formed which hydrolyzes to di-n-butylamine and butanol i n the working-up with water; at higher temperatures i t i s de-hydrated to the.enamine, (II), which then reacts with ozone to give N ,N-di-n-butylf ormamide . H2O Bu2NCH=CHEt '5=* BugNCH(OH)-Pr • BugNH + PrCHO (l6) O3 BuWCHO + EtCHO 16 Oxidation by Chromlum(Vl) Oxidations of aliphatic primary amines by potassium dichromate usually yields the corresponding aldehydes or acids (57) • Bottini and Olsen (58) found that N-aILkyl-2,lt-dinitroanillnes are oxidized by chrom-i c acid to the corresponding carbonyl compounds and 2, 1+-dinitroanilines. They found no isotope effect when the »<.-hydrogen on the alkyl group was substituted with tritium. oxygen difluoride to the nitroso or oxime compounds at -k2° (59)• The OX1me i s formed i f there are hydrogens geminal to the amino group. The greatest reactivity i s found with t-carbinamines. Aromatic amines are oxidized slowly to give polymeric products, and aromatic and a l i -phatic amides are unreactive. Presumably the reaction occurs by oxid-ative attack on the nitrogen and not on the °C-hydrogen, since the products are oximes and nitroso compounds. Merritt and Ruff proposed the following mechanism for the oxidation of primary amines by OF2'. Oxidation bjr QF_2 Primary aliphatic amines and ammonia are easily oxidized by H F H R-N-OF H + F RN=0 + 2 HF (17) R-N-OF H + HF The amine reacts by a nucleophilic attack on the oxygen of 0 F 2 > which is made electropositive by the strongly electron-withdrawing fluorine atoms. Elimination of HF gives the nitroso product. 17 Oxidation by manganese dioxide Oxidation of primary aromatic amines with active manganese dioxide produces azobenzenes (13). It was suggested that two amine molecules are f i r s t adsorbed onto adjacent "active sites " on the sur-face of the MnOg polymer before being oxidized. It was observed that the more basic amines are preferentially adsorbed. No oxidation was found for nitroanilines and aminobenzoic acids, and i t was suggested that this may be due to the preferential adsorption of the nitro and carboxyl groups on the manganese dioxide, which prevents the oxidation of the amino groups. Recently Pratt and McGovern (60) studied the oxidation of N-alkylanilines to benzalanilines by manganese dioxide. They interpret the observed lack of correlation and small differences i n rate with respect to substituent effects as evidence for a radical mechanism. RCHgNHR1 + 0=Mn=0 • RCHNR' + HO-Mn=0 RCHgNR' + HO-Mn=0 • RCH=NR1 •+ HO-Mn-OH HO-Mn-OH »• RgO + MnOg (l8) Further support for this mechanism arises from the observations that N-benzylaniline is oxidized more rapidly than dibenzyl and more slowly than hydrazobenzene, and from the fact that effects from substituents are more pronounced when they are attached to the anilino group of N-benzylaniline. Reactions in Frozen Systems Studies by Grant et a l (6l) i n 1961 showed that the imidazole-catalyzed hydrolysis of various penicillins proceeds with greater speed 18 i n ice between -5° and -30° than in liquid water. The rates i n frozen HgO were twice those i n frozen D 20. Recently, kinetic studies on various bimolecular reactions i n frozen systems at -10° were carried out by Butler and Bruice (62). They found large rate enhancements over the same reactions i n liquid water and suggested that this increase i n rate may be due to a concen-tration of the reactants i n liquid pockets between the ice crystals. To test the v a l i d i t y of this assumption, Bruice and Butler (63) studied a typical third order reaction which should give an even more pronounced rate enhancement effect. The observed increases i n rate for the general acid and general base catalyzed reactions of thiolactones with morpho-3 line were about 6-7 x 10 -fold on freezing. A solvent deuterium isotope effect was found to be 1.6. However, freezing changed the reaction mechanism from third order to second order. This last observation does not reconcile with the concentration mechanism suggested formerly, and i t was suggested that the enhanced rates may, i n fact, be due to a phe-nomenon which involves the ice structure i t s e l f i n promoting the ac-celeration . 19 SCOPE OF PRESENT RESEARCH Studies of the oxidation of fluoro alcohols and benzhydrol by permanganate have shown that the reaction takes place between the alkoxide ion and permanganate. As an extension to the work on alcohols i t was decided to study the oxidation of a structurally similar class of compounds, aryl alkyl amines. The i n i t i a l purpose was to determine whether the oxidative attack occurs at nitrogen or at carbon. I f , as i n the case of alcohols, oxidation, occurs via hydrogen removal from the alpha-carbon, i t would be pertinent to determine whether i t i s removed as a proton, a hydrogen atom or a hydride ion. Benzhydrylamine i s the logical analogue of benzhydrol, but because of i t s very low solubility i n water, a thorough study could not be made on i t . Benzylamine was chosen for i t s much greater solubility i n water, and because substituted benzylamines can be prepared without too much d i f f i c u l t y . I t was important to determine whether amines are oxidized through the neutral molecule or through the corresponding anion or cation. The effect of substituents was not too illuminating i n the case of alcohols. The ease of preparation of substituted benzylamines and their greater solubility i n water would provide a much larger range of substituents that could be examined. Tertiary carbinamines are known to react very slowly with alkaline permanganate to give the corresponding nitro compounds (39)• This i s clearly a case of oxidative attack on the nitrogen. The pro-blem was to determine whether this oxidative route i s general for a l l 20 amine oxidations or whether i t i s chosen because i n this case there are no alpha-hydrogens to be removed. Another aspect of this research was to examine the effect of N-alkylation or N-acylation on the oxidation, to observe whether i t protects the amine from oxidation as 0-alkylation of the alcohol does. Recently, various reactions have been found to proceed much more rapidly in frozen systems than i n corresponding liquid systems (61,62,63). One of the theories advanced by Bruice and Butler (63) was that the ice structure may assist i n orientating the reactants i n such a way as to make the approach of the attacking species more facile. It was decided to study the oxidation of benzylamines i n ice to determine i f there might be some orientation of the amino protons by the ice structure i n such a way as to f a c i l i t a t e the reaction. Furthermore, since the oxidation process involves hydrogen removal from the substrate, the interaction of the ice lat t i c e and the protons of the substrate might have a profound effect on the reaction. PART I: OXIDATION OF BENZYLAMINES AND RELATED COMPOUNDS 21 EXPERIMENTAL A. Synthesis, purification and identification of amines and related  compounds. 1. Synthesis of benzylamine-^X-dg Following the method of Halevi (6k) dry benzonitrile (2.22g.) i n 20 ml. dry ether was added dropwise to a stirred solution of lithium aluminum deuteride (0.86 g.) i n 30 ml. dry ether. The mixture was refluxed for one hour, and decomposed with 20 ml. of 20$ sodium po-tassium tartrate solution. The ethereal solution was separated and dried with sodium sulfate. After removal of the ether, a yellow o i l was obtained (1.12 g., 97-5$). The liquid was vacuum d i s t i l l e d and i t s purity was checked on the Aerograph model A-90 gas chromatograph from which a single sharp peak was obtained. The ultraviolet spectrum of benzyl amine- "K-dg i n water gave a sharp peak at 250 mjn and a shoulder at 256 mu. Benzonitrile i n 1$ ethanol solution gave peaks at 270 mu, 278 mu and a shoulder at 263 mu. The infrared spectrum showed C-D stretching and bending frequencies and complete absence of C-E and -C=N absorptions. 2. Synthesis of m-methylbenzylamine, m-methoxybenzylamine and m-chloro-benzylamlne by LiAlH^ reduction of the corresponding amides. A typical procedure was carried out as follows: 23.k g. m-chlorobenzoic acid and 28 g. thionyl chloride were refluxed i n a 200 ml. Erlenmeyer flask over the steam bath for one hour. The eon-denser was then removed and heating continued u n t i l a l l the excess thionyl chloride had been expelled. The flask was then immersed in an 22 ice bath and 120 ml. concentrated ammonia solution was cautiously added. The resulting solid was f i l t e r e d and washed with ice-water. Recrystal-lizations i n aqueous ethanol gave white needles, m p., 13^°; l i t . 13^.5° (65). Following the method of Micovic and Mihailovic (66) k g. m-chlorobenzamide was placed i n the thimble of a 100 ml. Sohxlet extractor and 50 ml. dry ether was added. In a 250 ml. round bottom flask below the extractor was placed 5-7 g. LiAlHj^ and 150 ml. dry ether. With vigorous s t i r r i n g the reaction mixture was refluxed for 85 hours, after which time a l l the benzamide had dissolved. While the flask was cooled i n ice the reaction mixture was quenched with 6 ml. water, 8 ml. 20$ sodium hydroxide solution and 20 ml. water, successively. The ethereal part was separated from the white granular part by decan-tation and the latter was washed several times with ether. A l l the washings were combined and dried with sodium sulfate. Removal of the ether gave approximately 3 ml. of the crude mrchlorobenzylamine. It was possible to purify the acetate and hydrochloride salts by succes-sive sublimations. Physical properties and analyses (a) m-chlorobenzylamine Acetate salt: m.p. 8l-2°; calculated for C^H-^ClNOg: C, 53.59; H, '5-96; W, 6.95J Found: C, 53-69; H, 5-88; N, 6.87. (b) m-methylbenzylamine Acetate salt: m.p. 92-1+°; calculated for C 1 0 H i 5 N 0 2 : w> 7-73-Found: N, 7.65. 23 (c) m-methoxybenzylamine Hydrochloride salt: m.p. ikl-2° ( l i t . 165.5-166.5° (67)); calculated for CgH^ClNO: N, 8.07- Found: H, 8.16. Acetate salt: m.p. 9k-6°; calculated for C^E^NO^: N, 7 - l l j H, 7-62; C, 60.90. Found: N, 7-02; H, 7-89; C, 60-92. 3. Synthesis of p-nitro, m-trifluoromethyl, m-nitro, and p-ethyl derivatives of benzylamine by a modified Sommelet method (68). A typical method was carried out as follows: a mixture of lk g. finel y ground hexamethylene tetramine, 200 ml. chloroform and 17.2 g. p-nitrobenzyl chloride was refluxed for two hours. The resulting white salt was f i l t e r e d and dried i n a i r . To the salt a solution of 17 ml. concentrated ammonium hydroxide solution and 78 ml water was added; the resulting mixture was refluxed for one hour, during which time an orange syrup formed. The condenser was removed and the mixture was heated on a steam bath for another hour, during which time the syrup s o l i d i f i e d . The supernatant liquid was decanted and 100 ml. dilute hydrochloric acid (1:10 dilution of concentrated acid) was added and the mixture heated over the steam bath u n t i l a l l the liquid had eva-porated. The p-nitrobenzylamine hydrochloride was recrystallized from 95$ ethanol. M.p. 252°d; l i t . 250° (69). Base was added to part of the hydrochloride salt and the re-sulting amine was quickly extracted with ether. Glacial acetic acid was then added to the ethereal extract and the resulting acetate salt was sublimed twice. 2k Physical properties and analyses (a) p-nitrobenzylamine Acetate salt: m.p. 1^5-7°; calculated for C^EL^NgO^: C, 50-9^; H, 5.66; N, 13-21. Found: C, 50-75; H, 5-91; N, 13-20. Hydrochloride salt: m.p. 252°d; l i t . 250° (69). Sulfate salt: m.p. 219-220°; l i t . 232° (48, uncorrected value). (b) m-nitrobenzylamine . Sulfate salt: m.p. 151-2°; calculated for C^H^NgOgS: N, 11.15. Found: N, 10.80. (c) p-ethylbenzylamine Hydrochloride salt: m.p. 202-5°d; calculated for C^H^CIN: CI, 20.7- Found: C l , 20-3-The starting compound, p-ethylbenzyl chloride,was synthesized according to the method given by Vogel (70), b.p. 92-100° at 15 mm. (d) m-trifluoromethylbenzylamine Calculated for CQHQFJH: C, 3k.83; H, 4.62; N, 8.00. Found: C, 5k.9k; H, 4.83; N, 8.11. Because of the anomalous oxidation rate found for this compound (see Results section) further checks on the identity of m-trifluoro-methy lbenzylamine were carried out. A single sharp peak was obtained by vapor phase chromatography. A weighed sample of the liquid amine dissolved i n water to a known volume agreed with i t s concentration ob-tained by t i t r a t i o n with standard acid to within kfi. A solution of the amine was oxidized with basic permanganate, and the intermediate, m-trifluoromethylbenzaldehyde, was isolated as i t s 2,4-dinitrophenyl-hydrazone derivative, m.p. 262°; l i t . 259-60° ( ? l ) . Yield, 91.1$. 25 Further oxidation by basic permanganate produced m-trifluoromethylben-zoic acid which could be r e c r y s t a l l i z e d from carbon tetrachloride. M.p. 100-2°; l i t e r a t u r e , 103-104.5° (72). The Infrared spectra of the acetate s a l t of benzylamine (m.p. 97°; l i t . 97«5-98'5° (73)) and of p-nitrobenzylamine were were very s i -milar In that both had broad peaks from 3000 to 2500 cm 1 and from 1575 to 1525 cm"1, which were assigned to the protonated amino group. The substituted compound had two very strong peaks at 1523 and 1342 cm"" which were assigned to the n i t r o group. An attempted synthesis of p-cyanobenzylamine was carried ac-cording to the modified Sommelet method described e a r l i e r . No product was obtained. An attempt was made to exchange the bromine i n p-bromo-benziylamina for the cyan© group according to the method described by Friedman and Shechter (?4). The y i e l d was very low and infrared studies of the product shoved Incomplete exchange. The following amines were obtained from commercial sources: p-methylbenzylamine (Columbia Organic Chemical Co.), DL- -methylben-zylamine, benzylamine, p-methoxybenzylamine, t-butylamine, N,N-dimethyl benzylamine, hexamethylene tetramine (Eastman Organic Chemical Co.), p-chlorobenzylamine (Matheson). B. Ki n e t i c methods - Aqueous solutions were prepared from f r e s h l y d i s t i l l e d amines and d i s t i l l e d water, which had been boiled and saturated with nitrogen i n a l l cases except p-nitrobenzylamine and m-nitrobenzylamine. The acetate s a l t s of these two amines were weighed and solutions were made up i n volumetric f l a s k s . The concentrations of a l l other amines were 26 d e t e r m i n e d b y t i t r a t i o n w i t h s t a n d a r d h y d r o c h l o r i c a c i d , u s i n g m e t h y l r e d a s i n d i c a t o r . 1. S t a n d a r d i z a t i o n o f p o t a s s i u m permanganate s o l u t i o n s A l i q u o t s o f 0.1 N sodium o x a l a t e s o l u t i o n , p r e p a r e d a c c o r d i n g t o V o g e l (75), were t i t r a t e d w i t h t h e permanganate s o l u t i o n u n t i l j u s t b e f o r e t h e end p o i n t . Then c o n c e n t r a t e d s u l f u r i c a c i d (7-5 ml.) was added t o t h e f l a s k , and t i t r a t i o n was c o m p l e t e d t o a p i n k end p o i n t . 2. l o d o m e t r i c method A t y p i c a l r u n was c a r r i e d o u t as f o l l o w s : i n a 125 m l . s t o p p e r e d r e d E r l e n m e y e r f l a s k were mi x e d 10 m l . o f 1 M d i s o d i u m h y d r o -gen phosphate b u f f e r , 0.15 n i l . o f 2.6 M p o t a s s i u m h y d r o x i d e , 3.94 m l . o f 0.0253 M b e n a y l a m i n e and 33-83 m l . o f w a t e r . The s o l u t i o n was t h e r -m o s t a t e d a t 25.0t 0.02° f o r one h o u r . The r e a c t i o n was i n i t i a t e d b y i n j e c t i n g , f r o m a 10 m l . s y r i n g e , f i t t e d w i t h a Chaney a d a p t e r , 2.08 m l . o f 0.0319 M p o t a s s i u m permanganate s o l u t i o n . The a l i q u o t s were w i t h d r a w n w i t h a f a s t d e l i v e r y p i p e t and p a s s e d i n t o a q u e n c h i n g s o l u -t i o n c o n t a i n i n g 10 m l . 3M s u l f u r i c a c i d and 3 m l . 5$ sodium b i c a r b o n a t e s o l u t i o n c o n t a i n i n g a n e x c e s s o f p o t a s s i u m i o d i d e . The l i b e r a t e d i o d i n e was t i t r a t e d w i t h a n a p p r o p r i a t e t h i o s u l f a t e s o l u t i o n u s i n g Thyodene as i n d i c a t o r . F o r v e r y s l o w r e a c t i o n s , t h e a l i q u o t s were d e l i v e r e d a t t h e s t a r t o f t h e r e a c t i o n i n t o s t o p p e r e d v o l u m e t r i c f l a s k s w h i c h were c o -v e r e d w i t h aluminum f o i l and i n d i v i d u a l l y t h e r m o s t a t e d . A t a p p r o p r i a t e t i m e s t h e e n t i r e c o n t e n t o f t h e f l a s k was quenehed and t i t r a t e d a s b e f o r e . F o r r e a c t i o n s f r o m pH 12 t o lk no b u f f e r was u s e d , s i n c e t h e h y d r o x y l i o n c o n c e n t r a t i o n i s h i g h enough, t o a c t as a b u f f e r . From pH 2 t o 10.8 t h e r a t i o o f s u b s t r a t e t o permanganate u s e d was 3:2. T h i s c o r r e s p o n d s t o t h e t h r e e e q u i v a l e n t change f r o m M n ( V I I ) t o M n ( l V ) and t h e two e q u i v a l e n t change o f t h e s u b s t r a t e . I t was f o u n d t h a t f r o m p i 11 t o 11.8 t h i s same r a t i o c o u l d s t i l l be u s e d t o g i v e l i n e a r r a t e p l o t s , a l t h o u g h i n t h i s r e g i o n t h e s t o i c h i o m e t r i c r a t i o o f s u b s t r a t e t o permanganate i s d i f f i c u l t t o d e t e r m i n e s i n c e t h e d i s p r o -p o r t i o n a t i o n o f any manganate t h a t i s formed i s n o t i n s t a n t a n e o u s b u t i s t i m e and pH dependent. I n a d d i t i o n t h e i m i n e and a l d e h y d e i n t e r m e -d i a t e s a r e p o s s i b l y s u b j e c t t o o x i d a t i o n b y permanganate and manganate. F o r t h e s e r e a s o n s o n l y i n i t i a l r a t e s up t c 30$ r e a c t i o n were t a k e n . Above pH 12 manganate i s s t a b l e and t h e s t o i c h i o m e t r i c r a t i o o f s u b -s t r a t e t o permanganate u s e d was 1:2. F o r t h e 3:2 r a t i o o f s u b s t r a t e t o permanganate, t h e f o l l o w i n g i n t e g r a t e d second o r d e r r a t e e x p r e s s i o n was u s e d (3): 1 V -V x v o v t k 2 ~ X [amine] t V.- 2 V o t — o where V = volume o f t h i o s u l f a t e a t t=0 o V^= volume o f t h i o s u l f a t e a t t i m e t 2V = volume o f t h i o s u l f a t e a t i n f i n i t e t i m e ( c a l c u l a t e d ) 5 ° t i n m i n u t e s [amine] o=amine c o n c e n t r a t i o n a t t=0 F o r t h e a l k a l i n e r e g i o n f r o m pH 12 t o 14, t h e r a t i o o f s u b s t r a t e t o permanganate o f 1:2 was f o u n d t o be i n e r r o r s i n c e i n t h i s r e g i o n t h e o x i d a t i o n o f t h e amine b y manganate was q u i t e a p p r e c i a b l e and s i n c e t h e i n t e r m e d i a t e , b e n z a l d e h y d e , I s r a p i d l y o x i d i z e d b y permanganate and 28 manganate t o b e n z o i c a c i d . A c c o r d i n g l y a 3°k r a t i o w o u l d be r e q u i r e d . However, t h e f o l l o w i n g i n t e g r a t e d e x p r e s s i o n (see d e r i v a t i o n i n t h e A p p e n d i x ) c o r r e c t i n g f o r t h e e x c e s s permanganate was u s e d w i t h s a t i s -f a c t o r y r e s u l t s : v e r s u s t i m e gave s t r a i g h t l i n e s . 3 . O x i d a t i o n b y manganate Manganate was p r o d u c e d i n s i t u b y a d d i n g an e q u i v a l e n t amount o f sodium s u l p h i t e t o a s o l u t i o n o f permanganate a t pH 1 3 . B e n z y l a m i n e was added t o t h e r e s u l t i n g manganate s o l u t i o n and t h e r a t e o f r e a c t i o n was f o l l o w e d i o d o m e t r i c a l l y . The f o l l o w i n g i n t e g r a t e d s econd o r d e r e x -p r e s s i o n employed b y S t e w a r t f o r manganate o x i d a t i o n s o f b e n z a l d e h y d e s ( 3 ) was u s e d : k 2 = 1 x _VQ£V. l a m i n e I t V + - l \ o z - u I n i t i a l r a t e s were t a k e n s i n c e t h e i n t e r m e d i a t e , b e n z a l d e h y d e , i s r a -p i d l y o x i d i z e d b y manganate. 4 . O x i d a t i o n s i n d e u t e r i u m o x i d e S e p a r a t e 2 5 m l . s t o c k s o l u t i o n s o f t h e f o l l o w i n g compounds were p r e p a r e d i n w a t e r and i n DgO: p o t a s s i u m permanganate (O.II852 g . ) , d i p o t a s s i u m h y d r o g e n phosphate ( 0 . 4 3 5 5 5 g-)> and b e n z y l a m i n e ( 0 . 1 2 2 2 5 g . ) . The r e a c t i o n v e s s e l c o n s i s t e d o f 1 0 m l . o f amine s o l u t i o n , 1 0 m l . o f 29 phosphate buffer, 20 ml. water or D 20, and 10 ml. potassium permangan-ate solution. The rate measurements were carried out at 25.0 - 0.02° i n the usual manner . The ratio of. exchangeable deuterons and protons in the amine-buffer-deuterium oxide system above i s 1:2800, meaning that the substrate i s approximately 99-9$ PhCHgNDg. 5- Oxidation of (<••)- o<_ -me thy lbenzylamine Optically active (-)- o(-methylbenzylamine was prepared by converting the racemic starting compound to i t s salt with d-tartaric acid (76). Fractional recrystallization yielded the (-)-isomer which was then regenerated with base and d i s t i l l e d . Rotations were taken on an ETL-NFL automatic polarimeter, type l43A, with a 0.5 dm. c e l l . The amine obtained from this method gave an optical purity of 33$. The rate of oxidation of (-)- c<-methylbenzylamine was f o l -lowed iodometrically on a solution consisting ofs 10 ml. of 1 M phos-phate buffer, 25 ml. of (-)- 0^-methylbenzylamine solution (0.0295 M), 11 ml. of water, 0-34 ml. of 2 M potassium hydroxide, and'3.66 ml. of 0.134 M potassium permanganate. Another solution was allowed to react for O.95 minutes at which time a 25 ml. aliquot was withdrawn and passed into a quenching solution of 5 ml. of 5$ sulfuric acid and 5 ml-of 0.5 M sodium b i s u l f i t e solution. A 25 ml. aliquot from a blank using the same reactants but substituting the potassium permanganate with water was quenched in the same manner. The rotations of the two quenched solutions were then taken. 30 C. Benzyl amine product analysis 1. Determination of ammonia Into a 250 ml. round bottom f l a s k equipped with dropping fun-ne l and r e f l u x condenser were placed 10 ml. of 1 M phosphate buffer, 10 ml. of 0.0412 M benzylamine, 1 ml. of 1 N sodium hydroxide, 12 ml. of water, and 17 ml. of O.O323 M potassium permanganate. The pH of the solution was 10.32. After the solution had stood for two hours and 32 minutes (the calculated time f o r 9856 reaction), 8 ml. of 0.5 N sodium b i s u l f i t e was added v i a the dropping funnel. This addition was followed by k ml. of 10 M sodium hydroxide and 40 ml. of water. The apparatus was immediately set up f o r d i s t i l l a t i o n . The d i s t i l l a t e was collected i n an ice-cooled volumetric f l a s k containing 25 ml. of 0.15 N s u l f u r i c acid. After more than ha l f of the reaction solution had d i s t i l l e d the contents i n the receiver were t i t r a t e d with standard base, using methyl red as indicator. 2 Determination of benzaldehyde The same reaction as described above was carried out at pH 10.^3 f o r 16 minutes. The solution was quenched with an a c i d i c sodium b i s u l f i t e solution. A f t e r cooling i n an i c e bath, 15 ml. of 0.04 M 2,4-dinitrophenylhydrazine solution was added and the mixture was stored overnight i n the r e f r i g e r a t o r . The 2,4-dinitrophenylhydrazone was f i l t e r e d onto a weighed crucible, dried f o r four hours i n a 60° oven, cooled i n a vacuum desiccator over phosphorous pentoxide and weighed. The corresponding"aldehydes from the substituted benzylamines were analyzed i n the same manner. 31 RESULTS Stoichiometry In the pH region below 12 permanganate i s reduced via a three-equivalent change to manganese dioxide. Benzylamine i s i n i -t i a l l y oxidized by permanganate to benzalimine, which then condenses with the parent benzylamine to form various polymers (kf). The s t o i -chiometry for the f i r s t part of the reaction between permanganate and benzylamine can be represented as: , 3 PhCH2NH2 '+ 2 MnO~ » 3 PhCH=NH + 2 Mn02 + 2 HO -t 2 0H~ ' ' ' .." ' (19) In the acidic solutions the imine is rapidly hydrolyzed to benzaldehyde (77) and the reaction i s then complicated by the subsequent oxidation of benzaldehyde. Since benzaldehyde oxidation i s very much faster i n acid solutions than that of benzylamine, two equivalents of permanganate were used, thus converting the amine to the carboxylic acid. Product analysis As stated i n the Experimental section the benzaldehyde or benzalimine was isolated as the 2,4-dinitrophenylhydrazone derivative. Since both the imine and the aldehyde give the same derivative, and since the imine cannot be isolated, the aldehyde w i l l henceforth be shown as the product. 32 Table I Product Study of the Oxidation of Benzylamines Amine j X-C6HkCHO (a) MLp^ M.p. ( l i t . ) 237° (65) CgH^CHgNHg m - C F 3 C 6 H l t C H 2 N H 2 (CH 3 ) 2 W C H 2 C 6 H 5 94.8 235-239° 91-1 262° 259-260° (71) 94.8 234-238 237° (65) (a) Isolated as the 2,4-dinitrophenylhydrazone derivative After 98$ reaction, a yield of 93$ ammonia was obtained from the oxidation of benzylamine. Order of the reaction amine the rate data were found to f i t second order integrated rate ex-pressions used by Stewart (3), using iodometric t i t r a t i o n methods of analysis (Figure l ) . The rate plots were linear i n most cases up to at least 50$ reaction before levelling off. In very acidic solutions the rate plots are linear for approximately 20$ reaction and then rise sharply i n an autocatalytic manner. This latter phenomenon was partly subdued when enough permanganate was added to oxidize the benzaldehyde (see Figure 2). But i t must be pointed out that the permanganate oxi-dation of benzaldehyde i t s e l f becomes autocatalytic i n acid regions (3). Effect of ionic strength Oxidations of benzylamine at pH 10.43 with increasing con-centrations of potassium sulfate (p. varied from 0.4 to 1.2) showed no ionic strength effect on the rate of reaction. Using stoichiometric quantities of permanganate and benzyl-l.oH F I G . 1 OXIDATION OF BENZYLAMINE TYPICAL.RATE PLOT pH = .9.90 V -V o t V - 2V t ? o 0.5 J ^ e V W o = 2 [ M n 0 4 J o = 8.24 x 10~^ M TIME IN MINUTES F I G . 2 OXIDATION OF BENZYLAMINE TYPICAL RATE PLOT pH = 7.62 0 100 200 300 T I M E I N M I N U T E S 35 pH-Rate Profile The rate of benzylamine oxidation increases with increasing pH, but the dependence i s not linear (see Table 2). A plot of the rate constant versus pH produced a typical ionization curve (Figure 3) Since the concentration of permanganic acid i n this region i s negli-gible (78,4) the rate must be following the ionization process of benzylamine. If the ionization i s indeed that of benzylamine and i f in the following relation p KBH + = p H + l o g ( 2°) l-oc where o<^ = fraction of unionized benzylamine, one substitutes the identity log . = log max K2 2 max \ max then the plot of log ^ kg/kg - kg J versus pH, where kg is read from the graph, should give a straight line of unit slope whose inter-cept i s the pKgg+ of the benzylammonium ion. Figure h shows that this relation i s indeed obeyed, and the pKgg+ of benzylamine i s 9-28. This value i s very slightly lower than the literature value of 9.3^ (79)• Although Mocek found a lowering of the pKQ of fluoral hydrate with i n -creasing ionic strength (4), i t is not certain how ionic strength w i l l affect the ionization of substituted ammonium ions. In the former case, Ions are produced from a neutral molecule, whereas i n the latter case, there i s no net change i n charge upon dissociation. Consider the following acid-base equilibrium: A x + B 2 — A g + Bi (21) 36 F I G . 3 OXIDATION OF BENZYLAMINE RELATION BETWEEN RATE CONSTANT AND pH 30 H 20 J 10 -\ 0 0 2 4 6 8 pH 37 33 T a b l e I I O x i d a t i o n o f B e n z y l a m i n e I n t h e R e g i o n pH 2 t o 14 V a r i a t i o n o f t h e R a t e C o n s t a n t w i t h pH pH &P (l.moie""Wn~1) pH k 2 (l.mole_1min 2 . 6 2 0 . 0 3 3 (a) 1 0 . 3 2 2 8 . 3 (a) 5.12 0 . 0 1 4 7 1 0 . 6 5 2 9 . 0 5 . 3 7 0 . 0 4 9 1 1 0 . 7 0 2 9 . 2 5 - 9 9 6 . 0 6 3 8 8 . 2 5 2 . 9 5 (b) 6 . 5 2 0 . 0 9 0 0 1 0.21 3 2 . 8 7 . to O . 6 9 1 1 1 . 1 9 3 2 . 3 ( c ) 7 - 5 3 0 . 3 5 0 11.42 3 3 - 3 7 . 6 2 0.142 1 1 - 7 7 3 3 - 0 3.12 1 - 7 7 1 2 . 0 4 3 2 . 6 (d) 8 . 6 0 5 . 3 9 1 3 . 0 0 3 5 - 3 8 . 9 2 9 - 1 0 1 3 . 7 8 5 0 . 1 9 - 3 1 1 4 . 5 1 4 . 0 0 6 1 . 2 9 - 5 9 2 0 . 2 9 . 9 0 2 2 . 3 -1 ( a ) [ B e n z y l a m i n e 3 Q = 3 tMn0£ ] Q = 0.00824 M (b) [ B e n z y l a m i n e ] = 3 [MnO^ ] = 0.00199 M 2 ( c ) [ B e n z y l a m i n e ] Q = 3 [MnO£ ] q = • 0.00197 M (d) [ B e n z y l a m i n e ] = 1 [MnOr ] = O . O O O 6 6 3 M, no b u f f e r s u s e d 2 0 Temperature = 2 5 . 0 ± 0.02° u = 0.6 39 If K Q i s the equilibrium constant i n water and K is the equilibrium constant i n any other solvent, then K = J A , fa*. (22) where $ is the activity coefficient i n water. Equation 22 expresses the relative strengths of k-^ and Ag i n water and in any other solvent. In order for these relative strengths to be the same, the function, presented by the following equation ^AI^BJ . / - ^ i ^ B m u s t ^ e u n i " f c y ' ^ n "tbe case where the equilibrium i s re-R-j_NH^  + RgNHg , RgNH^ + R^NHg (23) Bell ( 8 0 ) predicts that the function, -o w i l l not deviate too greatly from unity, such that the relative strengths of K and K Q w i l l be constant over a wide range of solvents. Analogously, the ionization of benzylammonium ion i n water can be re-presented by the following equation: PhCHgNH^ + H 2 0 * EhCH^NH + H 3 0 + where HgO replaces RgNRg i n equation 23 . If the same assumption holds for the benzylammonium ion ionization, i.e. that the ratio of the a c t i -vity coefficients be unity over a wide range of concentrations, then i t i s not surprising that the pKgg+ value obtained i n the solutions used for the present kinetic studies, where the ionic strength ap-proaches unity, agrees so closely with the value obtained i n water (79) The preceding results suggest that the rate i s dependent on the free amine. Since the pKgg+ i s already determined the concentra-tion of the free amine for each pH can be easily calculated using the 4o relation, [B] = [B]+ [BH+] (24) 1 + x where [B] = concentration of free amine [BH+] = concentration of henzylammonium ion x = [BH+]/[B] log x = pKjjjj+ - pH the plot of kg versus [B] i s linear (Figure 5 ) and the plot of log kg versus log [B] i s also linear giving a slope of 1.0 (Figure 6). This clearly shows that the oxidation i s dependent on the f i r s t power of the free amine as well as on the f i r s t power of the permanganate. Although the rate-pE profile for the oxidation of benzylamine levelled off i n the region pH 1 1 to 1 2 as a l l the ammonium ion was con-verted to free amine, a further increase i n rate occurred i n strongly basic media. The rates from pE 12.04 to 14 were found, i n fact, to increase linearly with increasing hydroxyl ion concentration (see Figure 7 ) . The extrapolated rate constant at [OH-] = 0 was 3 2 l.mole "Snin"1 which corresponded approximately to the rate constant obtained at the maximum of the ionization curve of the benzylammonium ion. A typical rate plot i s shown i n Figure 8 for the rates i n the highly basic region. It appears that benzylamine i s oxidized i n the highly basic region to benzoic acid, since the intermediate, benzaldehyde, i s ra-pidly degraded to benzoic acid by both permanganate and manganate under the conditions. Oxidation of benzylamine by manganate at pH 1 3 gave a -1 -1 . second order rate constant of 1 5 - 3 l.mole min , which i s about 2/5 as fast as the rate of oxidation of benzylamine by permanganate at the 1+2 *3 [OH-] M 45 same pH. The correct ratio of substrate to permanganate on this basis i s 3"^ « The actual ratio used i n the kinetic runs was 1:2, and a rate expression correcting for the presence of excess permanganate was derived (see Appendix). 2 laminej t \ V . o \ t k.60 log! V - 5 V ° \ (25) ™ \ V t " I Vo The rate plots of log / V + - 5 1 versus time were linear (Figure 8), I f one assumes that at pH 11.77, where the ratio of 3:2 for substrate:permanganate was used, the benzylamine i s oxidized to benzoic acid instead of to the imine, then a rate expression can also be der-ived to account for the presence of excess amine (See Appendix). k 2 ~ 1*' 6 0 log / 2 V+ \ (26) Laminej- t 5 V - 2' v \ 3 * 5 9 The plot of log (2 V, \ versus time was linear, but the rate 5 v? - 2 V 3 * 5 ° / -1 -1 constant was 25-2 1. mole min , which i s lower than the value of 33.0 1. mole _ 1min 1 obtained when one assumes benzylamine i s oxdized only as far as the imine. It must be pointed out that i n the pH region 11 to 12, the stoichiometry of permanganate reactions cannot be pre-dicted with certainty since the disproportionation of manganate i s very much dependent on the time of reaction and the pH of the solution. The assumptions accompanying the use of the 3'2 ratio seem to be cor-rect in the pH 11.77 reaction since the resulting rate constant, -1 -1 k2=33«0 1-mole min , agrees with those obtained in the region pH 10-5 to pH 10.7. 46 Activation parameters A series of kinetic runs w^re performed at pH values chosen at or near the maximum of the ionization curve so that the ionization process would not interfere with measurements of the activation process. The activation energy was obtained from a plot of log kg versus l/T (Figure 9) and the enthalpy and entropy of activation were obtained from a plot of log kg versus 1/T (Figure 10). The data for T benzylamine, m-trifluorobenzylamine, p-nitrobenzylamine, and p-methyl-benzylamine are presented i n Table III. Table III Oxidation of Benzylamines  Activation Parameters X-C<H^ CHgNHo E a (kcal/mole) AH* (kcal/mole) AS* (e.u.) p-CH3 12.3 11-7 (11-3) -20.6 (-21.6) H 11.6 11.0 -22.5 m-CF3 11.9 11.3 ( H - 7 ) -21.4 (-21.9) p-N02 11.0 10.4 -24.8 The values i n the brackets are those corrected for incomplete ionization and temperature effects thereon. The activation parameters were determined at pH values where the amines were largely unprotonated i n order to reduce interference from the temperature effect on the ionization process. The corrections for the latter were made as follows: Table IV gives the measured pH changes o 49 of the phosphate buffer with temperature. Table IV pH Variance of Phosphate Buffer with Temperature Temperature, °C pH 23.OO 10.68 26.90 10.61 30.70 10.53 35.70 10.47 40.00 10-37 15 10-33* 20 10.28 25 10.20 30 10.12 35 10.06 40 10.00 *The second set of values are taken from the Ph.D. thesis of M.M. Mocek (4). The corrections for the variation of pK B H+ with temperature were taken from Perrin's paper ( 8 l ) . In the case of m-trifluoromethylbenzylamine, whose calculated pKgg+ at 25° was 8.96, a value of 0.025 was chosen for -d( PK B H+)/dT. Using the corrected pEgjj+ and pH values, and correcting for incomplete ionization, the rate constants for m-trifluoromethylbenzyl-amine were recalculated and replotted to give the corrected activation 50 parameters. A comparison of the corrected activation parameters with the original ones i n Table III showed very l i t t l e change i n the actual values, thus corroborating the original assumption that i f the activa-tion parameters were determined at f a i r l y high pH, then there would be l i t t l e interference from the ionization process. Isotope effects Benzylamine- ©C-dg oxidized in the pH range 8 to 11 and the plot of kg versus pH also gave a. typical ionization curve. A unit slope was obtained from a log (kg/kgj^-kg) versus pH plot, and the intercept gave a pK B H+ of y.kl. Table V gives a comparison of the rate constants for the protio and deuterio compounds. The average isotope effect, kg/k^, was found to be 7-0-Table V Oxidation of Benzylamine, Protio and Deuterio Analogues in the Region pH 8 to 11  Deuterium Isotope Effect pH k p(H) (l.mole^min" 1) kg(D) ( l . m o l e ' W ) kg/kp 10.60 32.8 4.78 6.87 IO.38 32.2 4.73 6.81 9.95 26.4 3.72 7.10 9.48 I8.6 2.50 7-44 8.68 5.80 0.788 7.36 8.33 2.90 0.445 6.53 Mean =7.0 51 Halevi et a l (64) measured a ApK B H+ for benzyl amine and benzylamine -<X -d 2 of 0.051*-, while the oxidation results gave a ApKgg+ of 0.l4. However, i t must be pointed out that Halevi's method was the more pre-cise one, and i t would be sufficient to note that i n both cases deu-teration caused a decrease i n the acid strength of the benzylammonium ion. Oxidation of benzylamine in DgO The kinetic runs were carried out at pH values where benzyl-amine was almost completely i n the neutral amine form. Presumably in such a region the isotope effect on the ionization of the amine w i l l have a negligible effect on the concentration of free amine. That there was no measurable isotope effect shows the oxidation does not i n -volve a rate-determining N-H bond cleavage. Table VI gives the data for the kinetic runs in D o0. Table VI Data for the Oxidation of Benzylamine in DpO pH = 10.42 [PhCHgNHg] = 3/2 [MnO£] = 0.00913 M [KpHPO^] = 0.02 M Temperature = 25.0 ± 0.02° k (H20) = k (D20) = 32.4 l . m o l e ' V i n " 1 52 Substituent Effects To obtain information regarding the electronic requirements at the o<-carbon, eleven meta and para substituted benzylamines were oxidized at pH values at or near their maximum ionization. The rate constants were then corrected for incomplete ionization using the pK-gg+ values calculated from the and p values derived by Blackwell et a l (82) (see Table V I I ) . Figure 11 illustrates the nonlinear Hammett re-lation that one obtains when log k was plotted against <f values ( 2 8 ) . Table V I I Data for the Hammett Plots X-CgH^CHgNHg P K B H + 0 " ( 2 8 ) cr(82) <r+(83) log k p-CH30 9 . 3 9 - 0 . 2 6 8 - 0 . 1 1 - 0 . 7 7 8 1 .762 p-CH3 9 . 4 2 - 0 . 1 7 0 - 0 . 1 4 - 0 . 3 1 1 1 .612 P-C2H5 9 . 4 3 - 0 . 1 5 1 - 0 . 2 9 5 I . 6 1 6 m-CH^  9 . 3 3 -O .O69 - 0 . 0 6 - 0 . 0 6 6 1-565 p-H 9 . 2 8 0 0 . 0 1 0 1 . 5 4 9 m-CH^ O 9 . 1 6 0 . 1 1 5 0 . 1 0 0 . 0 4 7 1 .513 p-Cl 9 . 0 2 0 . 2 2 7 0.24 0.114 1.515 m-Gl 8 . 8 9 0 . 3 7 3 O.36 0 . 3 9 9 1 . 4 4 2 m-CF^  8 . 8 3 0 . 4 1 5 0 . 5 2 0 1 . 6 2 4 m-WOg 8 . 5 3 0 . 7 1 0 0 . 7 0 0 . 6 7 4 1.448 p-N0 2 8 . 3 8 0 . 7 7 8 0.84 0 . 7 9 0 1 . 6 0 8 However, when log k was plotted against <T values a l l the points f e l l 1.70" FIG. 11 OXIDATION OF BENZYLAMINES HAMMETT PLOT t = 25.0 * 0.02° LOG k 1.60H O O O O 1.50J O o o -0.2 0.2 cr 0.4 o 0.6 0.8 54 on a straight line with the exception of m-trifluoromethylbenzylamine, m-nitrobenzylamine, and p-nitrobenzylamine (Figure 12) The slope of the linear part of the graph was -0.28. A least squares treatment of the same points (excluding the three "anomalous" ones) also gave a slope of -0.28. In reactions where the rates cannot be satisfactorily cor-related with either the Hammett cr constants or the o~'t" constants, Yukawa and Tsuno have derived a Hammett relation which involves a linear combination of both constants (84): log k/k Q = p'( <r + r^jjj (27) where r i s the reaction constant describing the extent of resonance i n the transition state and i s the substituent constant numerically equal to ((T +- <T )• I f one assumes that ( 0"+ - a" ) i s zero for meta substituents, then a plot of log k/kQ versus <T for the meta-substituted compounds may be used to evaluate p . Then r i s obtained from the plot of log k/k Q versus p The p' i n the Yukawa-Tsuno equation i s ob-tained from the plot of log k/k Q versus ( C + rao*) (Figure 13)• Table VIII gives the data for Figure 13. The jo1 from Figure 13 i s -0.2"+, which agrees roughly with the value -0.28 obtained i n Figure 12. Of the three Hammett plots (Figures 11,12,13), the best f i t i s s t i l l i n Figure 13 where log k i s plotted against . To determine i f the exalted rate for p-nitrobenzylamine might be due to some condensation reaction between the amino and the nitro groups prior to the oxidation step a pH 10.10 solution of equi-molar amounts of benzylamine and nitrobenzene was oxidized with per-manganate. No difference was found i n the rates for the solution con-55 1.70 -LOG k 1.60 -1.50 -1.40 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 + c r 56 taining no nitrobenzene and that containing nitrobenzene. A test was also carried out to determine whether the acetate ion might have any effect on the oxidation rates since the stock solu-tions of some of the amines were prepared from the amine acetate salts. No change i n rate was again observed for benzylamine solutions con-taining no sodium acetate and for those containing equimolar amounts of sodium acetate at pH 1 0 , 1 0 . Table VIII X-C^CHgNHg log k/kQ A< r £ ( 8 5 ) PAff^(a) <T+- rA<T+ (b) p-CR"30 0 . 2 1 3 - O A 9 6 0 . 1 4 4 - 0 . 9 7 7 p-CH3 O.O63 - 0 . 1 3 1 O.O38 - 0 . 3 5 7 p-CgHj 0 . 0 6 7 -0.141 0-04l - 0 . 3 5 3 P - C I - 0 . 0 3 4 - 0 . 1 0 6 0 . 0 3 1 0 075 m-CH30 -O.O36 m-CH3 0 . 0 1 6 m-Cl 0 . 1 0 7 (a) O - - 0 . 2 9 , obtained from a plot of log k/kQ versus (T for the meta-substituted benzylamihes (b) r = 1 . 4 3 , obtained from a plot of log k/k Q versus pA<5"j^ ~ 0.4 LOG k 0.3 0.2 -0.1 --0.1 -0.2 -0.3 FIG. 13 OXIDATION OF BENZYLAMINES HAMMETT PLOT USING THE YUKAWA^TSUNO EQUATION 0 0 0 t J O = -0.24 —] • 1.0 -0.5 0 0.5 r A C T + O " 58 Oxidation of (-)-<=< -methylbenzylamine Good second-order kinetics were observed for the reaction of (-)- -methylbenzylamine with permanganate at pH 10.39. The calcu-lated rate constant after 60$ reaction was 32.2 l.mole'-^nin"1. In an identical run, the solution was quenched after 31$ reaction had oc-curred. Polarimeter readings taken of this solution revealed a 74$ loss of optical activity. Table EC Polarimeter Data for the Oxidation of (-)- oC -methylbenzylamine Rotation of (-)- ©C -methylbenzylamine, neat, [<* ]i -40.3° (76) Calculated rotation for 0.01M amine concentration -0.024° Rotation of blank solution -0.0088° Rotation after 31$ reaction -0.0021° Temperature at which readings were taken 22 ± 1° Miscellaneous reactions (a) Oxidation of N,N-dimethylbenzylamine Linear second order kinetics were observed to only 35$ reaction before the plot curves upwards. The estimated rate constant for the linear portion was 115 l.mole" 1min" 1, which i s approximately eight times as fast as the rate for benzylamine at the same pH (9-32) and about six times as fast as the-rate for benzaldehyde (3). 59 (b) Oxidation of NH^ Two pseudo f i r s t order kinetic runs were carried out on the oxidation of ammonia. The rates were very slow, but the plot of log V. versus time was roughly linear i n the time examined (Figure lk) and hence quantitative values for the rate constants were obtained. Table X Oxidation of Ammonia: Variation of Rate with pH PH II .63 8.5^ (c) Oxidation of cyclohexylamine Good second order rate plots were obtained by using 3"2 molar ratios of cyclohexylamine to permanganate, up to pH 11, Beyond pH 11.2, the plots appear autocatalytic and no rate constants could be obtained from them. The rates are i n general about one-tenth of the rates for benzylamine. Table XI gives the rate constants for four pH regions. Table XI Oxidation of Cyclohexylamine: Variation of Rate with pH pH kg ( l .mole min 7.46 0.0117 9.19 0.319 9.86 1.0k 10.17 1-92 kg (l.mole"1hour"''*) 0.107 O.OO689 TIME IN HOURS 6i The plot of kg versus pH gave only what appears to he a part of an ion-ization curve. Cyclohexanone at pH 9-33 and 11.29 oxidized at about the same rate as cyclohexylamine for about 10$ of the reaction before the rate greatly speeded up i n an autocatalytic manner. (d) Oxidation of acetamide Permanganate f a i l e d to oxidize acetamide after 30 hours of reaction both i n acidic and basic solutions. (e) Oxidation of N,N-dimethyIformamide and K-benzylformamide Both these compounds were slowly oxidized by permanganate at pH values higher than 13, but below pH 13, there appears to be no reaction during five or six hours. (f) Oxidation of methylamine, dimethylamine, trimethylamine, t-butyla-mine, and tetramethy"! ammonium hydroxide In the qualitative reactions which were carried out on these compounds, i t was observed that while methylamine, dimethylamine, and trimethylamine were almost instantaneously oxidized by permanganate, t-butylamine, whose kinetics has been studied i n a later section, and tetramethylammonium hydroxide exhibited no appreciable reaction after three to four hours. 62 DISCUSSION The stoichiometry of the i n i t i a l reaction between permanganate and benzylamine in the pH region investigated may be represented by the following equation: : 3 PhCH NH 2 + 2 Mn0~ *3 PhCH=NH + 2 Mn0 2 + 2 H 20 + 2 0H~ (28) 3 ) The highly reactive imine intermediate is never isolated from the reac-tion mixture since i n acidic and highly basic solutions i t hydrolyzes rapidly to benzaldehyde (77) and i n neutral and weakly basic solutions i t reacts with benzylamine to produce condensation products (47). These two reactions effectively limit the rate determinations to the f i r s t 50$ of reaction, since i n acidic solutions benzaldehyde i s ox-idized autocatalytlcally by permanganate, and i n neutral and weakly basic solutions the condensation reactions tend to cause the rate of oxidation of benzylamine to level off after about 40-50$ reaction. In strongly alkaline solutions, pH 12 to l4, the stoichiometry changes. 3 PhCHgNHg + 4 Mn0£ • 3 PhCOg + 3 NH^ + HgO + 4 Mn02 + OH" (29) Benzoic acid is the" f i n a l product in the highly basic region since the chief oxidation intermediate of benzylamine, benzaldehyde, i s rapidly oxidized both by permanganate and by manganate to benzoic acid. Pre-sumably the rates of the hydrolysis of the imine intermediate to ben-zaldehyde far exceed the rate of condensation which occur at lower pH regions between the imine and benzylamine. The reduction of Mn(VIl) to Mn(lV) i s i n accord with the observation that manganate rapidly oxidizes 63 benzylamine. The overall kinetics of the oxidation of benzylamine i s second order; i n particular, i t i s f i r s t order i n benzylamine and f i r s t order in permanganate. The intermediate manganese species, manganese(V) or manganese(VI), undergoes rapid disproportionstion to yield Mn02> which i s stable i n the entire pH region except i n the highly basic solutions where MnOi).= tends to accumulate. The dependence of the reaction rate on pH i s graphically represented in the form of an ionization curve (Figure 3) The mid-point of this curve corresponds to an apparent pKgjj+ of 9-28, which agrees within 0.1 pK unit with the previously measured pKgH+ of the benzylammonium ion (79)• No appreciable salt effects were observed for benzylamine oxidation at pH 10.70 and 25°. The kinetics are consistent with a mechanism which involves the reaction of permanganate ion and the neutral amine in the rate-determining step. K C^H CHgHHg + H20 > C^CHgNH* + 0H~ (30) k CgH^CH2NHg + MnO^  ^ Products The rate law corresponding to this mechanism i s : - d[MnO)?j. k [MnO£] [CgH CH HHg] (31) dt 0 * or d[MnO)"] = k [MnO£] [CgH CBgHH*] [OH-] (32) dt K • ? 5 where K = [CgH CHjm^] [OH"3 [CgH^HgNHg] 6k The experimental rate law was found to be: - d[MnOJ*3 = kg [MnO£] [amine] dt where [amine] = [CgH^CHgNHg] + [CgH^CHgNH^] As the pH of the system i s raised the concentration of benzylamine approaches the total amine concentration, kg approaches k, the rate constant of the rate-controlling step, and one observes a le v e l -ling -off of the rate. The oxidation of the benzylammonium ion i s extremely slow, the rate of benzylamine oxidation exceeding that of benzylammonium ion oxidation by a factor of more than 10^. Alkoxide ions, produced by the ionization of alcohols i n basic solution, are generally much more reactive than neutral amines towards permanganate. The maximum rates observed for the aryl trifluoromethyl carbinol oxidations are more than ten times higher than the maximum rates for the benzylamines. Benzhydrol ion oxidation rates appear to exceed those of benzylamine by an even greater extent. The further increase i n rate that Is observed as the pH i s raised from 12 to Ik indicates a second reaction exists. It seems most unlikely that the hydrpxyl ion dependence i s due to the ioniza-tion of the benzylamine molecule. The amino protons are far too weakly acidic to be sufficiently ionizt..ed at pH ik. Aniline has a pKa of about 27 (86) and benzylamine should be an even weaker nitrogen acid. Hence i f the reaction were even diffusion controlled, the concentration of the benzylamine anion, CgH^CHgNH , would s t i l l not be nearly high enough to produce the observed rate. 65 It i s also doubtful whether a proton can be removed from the -carbon of benzylamine at pH ik. The h a l f - l i f e of the ionization of p-nitrobenzyLamine i s approximately 30 minutes at H_ = 17-9 (86), and one would expect the ionization of benzylamine to be much slower at pH lk. Hence the rise i n rate beyond pH 12 cannot be due to the par-t i a l formation of the benzylamine carbanion. The following mechanisms are consistent with the experimental results for the oxidation of benzylamine from pH 12 to l 4 . (1) Hydrogen atom transfer H x gr~\ k MnOjT V G - N C ' OH" — * HMnOj" + czS^ H-NH + HgO t E \ \ X H <fi -CH-NH + MnOJJ • Products (3^) (2) Hydride ion transfer r w . $ n - k = , MnO (H_3 c ~ n ^ o h * HMnO, + 9&CH=NH + H.O k H 4 2 Mn(VII) or Mn(V) 9ZS-CH=NH — : • Products (35) fast (3) Electron transfer to permanganate ^H^H k g-p-N—H M^nO~ *• Cp -CH-NHg + MnO^  +1^ 0 Mn(VII) or Mn(VI) - • Products (36) fast 66 The rate law corresponding to mechanisms 1, 2, and 3 i s : _ d [MnO);] = k [MnO£] [OH"] [PhCHgNHg] (37) dt A l l three mechanisms are termolecular. In mechanism 1, permanganate removes a hydrogen atom from the <"<-carbon while the hydroxyl ion re-moves a proton from the amino group. In mechanism 2, permanganate removes the <K-hydrogen as a hydride ion as the hydroxyl ion removes a proton from the amino hydrogen. In mechanism 3, the hydroxyl group removes the e<-hydrogen as a proton while permanganate abstracts an electron from the nitrogen. Activation parameters The activation parameters for the oxidation of benzylamines were obtained in pH regions where the amine is almost completely i n the neutral form. The small corrections which were required for incom-plete ionization together with corrections for pH changes with temper-ature made only slight differences to the actual values of the para-meters (see Table III). The energies of activation are, on the whole, 1-2 kcal. higher than those observed for the fluoro alcohols. This is i n accord with the slower rates observed for the amines. The results for the entropies of activation for the benzylami are somewhat unexpected. The very large negative A S values for the reaction of the neutral amine with permanganate are of the same order of magnitude as the A S * values for anions with permanganate (23, 2k, 3^). In general, when two anions come together to form the activated 67 complex the resulting A S for the reaction is large and negative (87,88). However, in this respect, previous studies of the reaction of neutral molecules with permanganate have also revealed abnormally acid with permanganate i s -19 e.u. (3*0 . For a l l these reactions i n -volving a neutral substrate with permanganate, one can postulate an ionic transition state vrhich has extensive charge separation resulting from the transfer of either electrons or hydride ions. In the case of benzylamine the transition state may be represented by the following: The mechanism represented by equation (38) involves a hydride ion trans-fer from the amine to permanganate. Transition state I i s a highly ionic one and should be more hydrated than the reactants i n the ground state. Shown also i s the participation of the amino group and the phenyl group i n the derealization of the charge which develops at the reaction center. However, results from studies of ring substituent effects, which w i l l be discussed i n a later section, suggest that re-sonance stabilization by the ring of any charge which develops at the alpha-carbon, as shown i n transition state I, i s not a large factor contributing to the s t a b i l i t y of the transition state. Further evidences showing the importance of the amino group i n absorbing some of the charge developed at the alpha-carbon are found in the studies of the oxidation rate of benzylamine with different N-substituents. Alkyl groups, which negative entropies of activation. The AS for the reaction of MnO^  and Hg i s -17 e.u. (89) and A S ^ for the reaction of neutral formic cfi -C-H + MnO^  H 68 are electron-donating, increase the rate of oxidation, but acyl groups, which are electron-withdrawing, cause the rate to drop considerably. When benzylamines are protonated, the rates are greatly diminished, indicating the importance of structures such as Ib 0 Of the four benzylamines whose activation parameters were measured, the nitro compound had the lowest activation energy and the most negative entropy of activation. The lowered energy of activa-tion may be due to increased resonance interaction between the phenyl ring and the reaction center, although i t i s not clear how resonance effects can be important with the nitro group i f hydride transfer were the mechanism. If the mechanism of reaction for the nitro compound did, i n fact, involve a hydrogen atom transfer, then the following equation shows how resonance can occur between the nitro group and the reaction center: ^— — . +N-<^  ^-CHgNHg + MnO^  •o V W2 E---OMnO; NH2 = C — H — OMnO; H (39) In structure II for the transition state there i s even greater charge separation than i n I, and as such, should be the most highly solvated species. This is i n agreement with the more negative AS obtained for p-nitrobenzylamine. 69 An a l t e r n a t e e x p l a n a t i o n f o r t h e d e c r e a s e i n / i S T f o r p - n i -t r o b e n z y l a m i n e i s t h a t t h e g round s t a t e s o l v a t i o n o f t h i s compound i s l e s s t h a n t h a t o f t h e o t h e r b e n z y l a m i n e s s i n c e p - n i t r o b e n z y l a m i n e had t h e l o w e s t pKgg+. T h i s assumes t h a t t h e e x t e n t o f s o l v a t i o n o f t h e amino p r o t o n s i s a p p r o x i m a t e l y t h e same f o r a l l t h e b e n z y l a m i n e s and t h a t d i f f e r e n c e s l i e c h i e f l y i n t h e e x t e n t o f s o l v a t i o n o f t h e amino n i t r o g e n . I f t h e above a s s u m p t i o n i s v a l i d , t h e n t h e more n e g a t i v e A S* a s s o c i a t e d w i t h p - n i t r o b e n z y l a m i n e must be due t o t h e l a r g e r d i f f e r e n c e between t h e s o l v a t i o n i n t h e g round s t a t e and t h e s o l v a t i o n i n t h e t r a n s i t i o n s t a t e . I s o t o p e e f f e c t s The m a n i f e s t a t i o n o f a r a t h e r l a r g e i s o t o p e e f f e c t f o r t h e b e n z y l a m i n e r e a c t i o n , k (PhCHpNHpJ/k (PhCDpNHg) = 7.0, shows t h a t t h e r a t e - d e t e r m i n i n g s t e p i n v o l v e s t h e c l e a v a g e o f t h e C-H bond. The f a c t t h a t t h e i s o t o p e e f f e c t r e m a i n s c o n s t a n t t h r o u g h o u t t h e pH range i n v e s t i g a t e d s u g g e s t s t h a t t h e same mechanism must be o p e r a t i n g i n t h a t r a n g e . The absence o f a s o l v e n t (HgO/DgO) i s o t o p e e f f e c t s u p p o r t s t h e p r o p o s e d mechanism, w h i c h does n o t ' i n v o l v e t h e amino h y d r o g e n s i n th e r a t e - d e t e r m i n i n g s t e p . S u b s t i t u e n t e f f e c t s E x c e p t f o r m - t r i f l u o r o m e t h y l b e n z y l a m i n e , p - n i t r o b e n z y l a m i n e and m - n i t r o b e n z y l a m i n e , t h r e e compounds w h i c h have h i g h l y e l e c t r o n -w i t h d r a w i n g s u b s t i t u e n t s , t h e l o g a r i t h m o f t h e r a t e c o n s t a n t s f o r a l l t h e p a r a - and m e t a - s u b s t i t u t e d b e n z y l a m i n e s was f o u n d t o c o r r e l a t e 70 better with G~ constants than with 6~ constants. The reaction constant, ^ + , was - 0 . 2 8 , which i s i n accord with the proposed hydride transfer mechanism. The rather small value for shows that the reaction i s not subject to large nuclear substituent effeets, and that most of the positive charge i n the transition state remains at the oc-carbon or at the nitrogen atoms. In the log k versus IT* plot, the three points corresponding to p-nitrobenzylamine, m-trifluoromethylbenzylamine and m-nitroben-zylamine a l l lay well above the straight line through the other points (Figure 12). For p-nitrobenzylamine, a change i n mechanism may be taking place, the most probable one being a hydrogen atom transfer mechanism since the activation parameters for the p-nitro compound are not too vastly different from those for benzylamine. The Increased rate could be due to enhanced resonance interaction with the ring. However, this mechanism cannot explain the higher rates for m-trifluoromethylbenzyl-amine and m-nitrobenzylamine, since there can be no direct resonance with meta-substituents. Another possible explanation for the high rates observed for the three "anomalous" benzylamines Is based on the ionization at the <X_-carbon. J^ T^ -CHg-NHg + OH" 1 — w ^7^) ^ H-NHg + HgO (kl) Presumably such an equilibrium must be shifted far to the l e f t i n the ordinary pH range. However, with strongly electron-withdrawing groups such as nitro and trifluoromethy1, the equilibrium might be shifted towards the right to such an extent that at pH 10, for example, even 71 a very small concentration of the anion could contribute to a large i n -crease i n rate. One assumes the anion i s oxidized much more quickly than the neutral molecule. Qualitative studies i n this laboratory (86) have shown that p-nitrobenzylamine appears to be only slightly ionized i n 6o# dimethylsulfoxide solution ( H _ =-17.9). The ionization pro-cess was time dependent, however, the h a l f - l i f e at H_ =-17-9 being 33 minutes. This i s slower than the oxidation rate and i t i s highly probable that in the lower pH regions, the ionization' reaction would be even slower. Furthermore, i t can be shown that involvement of the anion, p-NOgCgH^CHNHg , i n the rate-determining step would require the oxidation rate to be proportional to the square of the hydroxyl ion concentration i n the region well below the pK of the amine, i n -stead of the f i r s t order dependence that was observed. Oxidation of (-)- o£-methylbenzylamine Studies of the oxidation of (-)- &£ -methylbenzylamine have provided some new insight into the oxidation mechanism for benzylamines. The loss of 7*$ optical activity i n the starting compound corresponding to only 31$ reaction suggests that a racemization pro-cess may be occurring prior to the rate-determining step. Further-more, this observation gives some information regarding the nature of the hydrogen that i s transferred to the permanganate. If a hydrogen atom transfer mechanism were taking place i n -volving the transitory existence of a benzyl radical, then i t i s con-ceivable that there can be an exchange of the hydrogen atom between the radical and permanganate within the solvent cage before the atom i s f i n a l l y removed by the permanganate. 72 I s l o w (6-C-H + MnO" s I k C H 3 A l t h o u g h i n m o s t c a s e s t h e e s c a p e f r o m t h e s o l v e n t c a g e w i l l h e more r a p i d t h a n t h e r o t a t i o n o f a n y m o l e c u l e w i t h i n t h e s o l v e n t c a g e , L e f f l e r a n d G r u n w a l d (83) s t a t e t h a t t h e r e i s e v i d e n c e f o r r o t a t i o n , a l t h o u g h i n c o m p l e t e , o f r a d i c a l s w i t h i n t h e s o l v e n t c a g e . F o r e x a m p l e , t h e p r o d u c t f r o m t h e p r i m a r y r e c o m b i n a t i o n o f t h e a l k y l a n d a c y l o x y r a d i c a l s d e r i v e d f r o m t h e d e c o m p o s i t i o n o f o p t i c a l l y a c t i v e @ - p h e n y l i s o b u t y r y l p e r o x i d e was f o u n d t o b e 15% r a c e m l z e d . T h e y p o i n t o u t t h a t t h e r e s u l t s f r o m t h e s t u d i e s o f t h e p o l a r d e c o m p o s i t i o n o f d e c a -l y l p e r b e n z o a t e a n d o f p - m e t h o x y - p ' - n i t r o b e n z o y l p e r o x i d e s u g g e s t t h a t i t i s u n l i k e l y f o r c a g e d i o n s t o r o t a t e b e f o r e t h e y r e c o m b i n e (90,91> 92) S u c h d e c o m p o s i t i o n s o c c u r i n s t e a d t h r o u g h a n i n t i m a t e i o n - p a i r m e c h a n i s m . I t i s l i k e l y , t h e n , t h a t r o t a t i o n w o u l d n o t o c c u r i n t h e h y d r i d e i o n t r a n s f e r m e c h a n i s m p r o p o s e d f o r t h e o x i d a t i o n o f ( - ) - <^-m e t h y l b e n z y l a m i n e , b u t m i g h t o c c u r , t o a s m a l l e x t e n t , i n t h e r a d i c a l m e c h a n i s m ( e q u a t i o n 42). R e s u l t s f r o m t h e o x i d a t i o n o f b e n z y l a m i n e - o ^ - d g s u g g e s t t h a t a n y h y d r o g e n e x c h a n g e i n t h e t r a n s i t i o n s t a t e m u s t o c c u r b e t w e e n t h e r a d i c a l a n d t h e p e r m a n g a n a t e , f o r i f e x c h a n g e o c c u r r e d b e t w e e n t h e r a -d i c a l a n d t h e s o l v e n t , t h e n one s h o u l d o b s e r v e a n i n c r e a s e i n t h e r a t e o f r e a c t i o n f o r t h e d e u t e r a t e d compound a s t h e r e a c t i o n p r o c e e d s s i n c e t h e d e u t e r i u m w o u l d b e e x c h a n g i n g f o r t h e p r o t i u m . No s u c h r i s e i n r a t e was o b s e r v e d f o r b e n z y l a m i n e - o ^ - d ^ . NHp 0-C" HMnO, GIL NRo HMnO£ (42) S o l v e n t cage C H , Summary The t r a n s i t i o n state f o r the permanganate-benzylamine r e a c t i o n has been shown to be the following: NH 2 CH,- - C - — H — — OMnCi 6 5 i 3 H The way i n which charge i s d i s t r i b u t e d In t h i s t r a n s i t i o n state i s not known with c e r t a i n t y , however. That i s , the choice of a hydride i o n t r a n s f e r mechanism or a hydrogen atom tr a n s f e r mechanism f o r the o x i -dation of benzylamines cannot be unequivocally made from the r e s u l t s obtained i n t h i s t h e s i s . I t seems that the same predicament also e x i s t s i n other permanganate oxidations (23,24,34), and i t i s not obvious whether a c l e a r - c u t d i f f e r e n t i a t i o n f o r the two mechanisms w i l l ever be p o s s i b l e . The r e s u l t s from the oxidation of benzylamines seem to support both mechanisms. The d i r e c t c o r r e l a t i o n of the r e a c t i v i t y and 0~ + values f o r most substituents and the negative rho value of the reaction support the hydride t r a n s f e r mechanism gi v i n g a carbonium ion i n the t r a n s i t i o n state. R a d i c a l reactions have also been known to give good Hammett co r r e l a t i o n s with and moreover, to give l a r g e , nega-t i v e rho values (93>94>95) which i n d i c a t e the importance of resonance e f f e c t s i n the t r a n s i t i o n s t a t e . For such reactions, t r a n s i t i o n states with some carbonium i o n character have been postulated. On the other hand, r e s u l t s from the study of (-)- oc-methyl-benzylamine and of p-nitrobenzylamine suggest a hydrogen atom tr a n s f e r mechanism. 74 A mechanism w h i c h t a k e s i n t o a c c o u n t t h e p r o p e r t i e s o f b o t h h y d r i d e i o n and h y d r o g e n atom r e m o v a l i s p r e s e n t e d b e l o w : ~<T+NH2 s _ 0 _ ( J * - _ » H — -OMnO. H The t r a n s i t i o n s t a t e s I and I I i n e q u a t i o n (43) may be o f e q u a l o r n e a r l y e q u a l e n e r g y s u c h t h a t t h e c h o i c e o f e i t h e r one c a n be i n -f l u e n c e d b y t h e n a t u r e o f t h e groups a t t a c h e d t o t h e a l p h a - c a r b o n . The s t a b i l i t i e s o f b e n z y l c a r b o n i u m i o n s and b e n z y l r a d i c a l s l e n d s u p p o r t t o t h e e x i s t e n c e o f b o t h t r a n s i t i o n s t a t e s . Depending on t h e p a r t i c u l a r n u c l e a r s u b s t i t u t i o n , t r a n s i t i o n s t a t e 1 o r t r a n s i t i o n s t a t e I I may be on t h e more f a v o r e d pathway. I n g e n e r a l , e l e c t r o n - w i t h d r a w i n g s u b s t i t u e n t s t e n d t o s t a b i l i z e b e n z y l r a d i c a l s ( 9 6 ) , b u t e l e c t r o n - d o n a t i n g s u b s t i t u e n t s e x e r t v e r y " l i t t l e i n f l u e n c e on t h e i r s t a b i l i t y . The c o r r e l a t i o n o f r e a c t i v i t y w i t h (J""*" and t h e n e g a t i v e r h o v a l u e f o r t h e . . o x i d a t i o n o f b e n -z y l a m i n e s w i t h e l e c t r o n - d o n a t i n g and w e a k l y e l e c t r o n - w i t h d r a w i n g s u b -s t i t u e n t s s u g g e s t t h a t r e s o n a n c e s t a b i l i z a t i o n o f t h e c a r b o n i u m i o n may NHg ^-C--~H---OMhCL 7 5 be important i n the transition state. On the other hand, the enhanced reactivity of the benzylamines with strongly electron-withdrawing sub-stituents may be explained by the increased importance of the radical transition state II. It should be pointed out that I and II may, in fact, simply be different formulations of the same transition state since the only difference between them i s the way i n which electrons are distributed. To be sure, one leads to a radical intermediate and the other to a cation Intermediate and this means that two distinct paths can be envisaged for the overall reaction. It i s possible, however, that the decomposition of the activated complex to the two types of products Is nicely balanced and can be influenced by many factors such as the electronic effect of ring substituents, vibra-tional effects i n the transition state, etc. It may indeed be pre-ferable to consider a common activated complex whose decomposition i s normally controlled by a probability factor but which can be i n f l u -enced by changes i n the electron density at the reaction s i t e , i.e., ArCHgNH + MnO^  > NH2 Ar~C---H---0Mn03 H -»ArCEtNRg + HMnO^  ArCH-NHg + EMnO,. t ArCE-pg PART II: OXIDATION OF t-BUTYLAMINE 76 EXPERIMENTAL A. Synthesis of Possible Oxidation Intermediates 1. Synthesis of t»butylhydroxylamine Zinc dust (10-5 g.) was added to a stirred mixture of am-monium chloride (9.8 g.) and t-nitrobutane (23.5 g ) i n 300 ml. water over a period of 15 minutes. The temperature of the reaction was kept at 35° for 35 minutes. The zinc oxide was f i l t e r e d and washed with 50 ml- warm water. The f i l t r a t e was saturated with sodium chloride and cooled i n an ice bath. A small amount of unreacted t-nitrobutane crystallized out and was f i l t e r e d with crushed ice. The f i l t r a t e was extracted with ether and dried with sodium sulfate. The ether was then d i s t i l l e d off under nitrogen and the residue was recrystallized i n 30-60° petroleum ether. M.p. 6l-62° ( l i t . 64-65°)(97). The oxa-late salt of t-butylhydroxylamine was prepared by adding the latter to an ethereal solution of oxalic acid. The salt was recrystallized from water, m.p. 200° ( l i t . 200-202°) (98). 2. Synthesis of t-nitrosobutane When a i r was bubbled through an aqueous solution of t-butyl-hydroxy lamine blue t-nltrosobutane was produced. The ultraviolet spec-trum of this solution showed the typical nitroso peak at 287 mu (99)• B. Product Analysis 1. Synthesis of t-nitrobutane from t-butylamine Following the method of Kornblum (39) 28.8 ml (0.274 mole) t-butylamine was slowly added to a stirred mixture of 130 g. (0.823 mole) 77 o f p o t a s s i u m permanganate and 600 m l . w a t e r . The m i x t u r e was s t i r r e d a t room t e m p e r a t u r e f o r n i n e h o u r s , warmed t o 60° f o r l 6 h o u r s , and t h e n s t i r r e d w i t h o u t h e a t i n g f o r 15 h o u r s . The t - n i t r o b u t a n e was s e -p a r a t e d f r o m t h e r e a c t i o n m i x t u r e b y steam d i s t i l l a t i o n and a f t e r a -c i d i f i c a t i o n w i t h d i l u t e h y d r o c h l o r i c a c i d and c o o l i n g i n i c e , i t c r y -s t a l l i z e d i n w h i t e lumps. The y i e l d o f t h e cr u d e p r o d u c t was 23.5 g•> o r 83%. 2. S y n t h e s i s o f t - n i t r o b u t a n e f r o m t - b u t y l h y d r o x y l a m i n e To a n aqueous s o l u t i o n o f t - b u t y l h y d r o x y l a m i n e (3-5 g-d i s s o l v e d i n 10 m l . w a t e r ) a s o l u t i o n o f p o t a s s i u m permanganate (0.1M) was added u n t i l t h e s o l u t i o n t u r n e d p u r p l e . The compounds were a l l o w e d t o ~ r e a c t f o r 30 m i n u t e s , a f t e r w h i c h t i m e t h e t - n i t r o b u t a n e was r e -moved b y steam d i s t i l l a t i o n . The d i s t i l l a t e was s l i g h t l y b l u e i n c o -l o r , p r e s u m a b l y due t o some t r a c e s o f t - n i t r o s o b u t a n e . The y i e l d o f the t - n i t r o b u t a n e was 1.9 g-, o r V7#, and i t s I n f r a r e d s p e c t r u m was i d e n t i c a l w i t h t h e sample o f t - n i t r o b u t a n e s y n t h e s i z e d p r e v i o u s l y b y th e K o r n b l u m method. C. K i n e t i c S t u d i e s 1. B u f f e r s o f h i g h c o n c e n t r a t i o n S i n c e t h e permanganate t - b u t y l a m i n e r e a c t i o n was so v e r y s l o w t h e c o n c e n t r a t i o n o f t h e components was g r e a t l y i n c r e a s e d i n o r d e r t o g i v e m e a s u r a b l e r a t e s . S i n c e t h e f i n a l c o n c e n t r a t i o n o f h y d r o x y l i o n formed d u r i n g t h e r e a c t i o n w i l l e q u a l t h a t o f t h e i n i t i a l permanganate (0.1M), t h e b u f f e r c o n c e n t r a t i o n was r a i s e d t o lo2M. A s t o c k s o l u t i o n o f 2M d i p o t a s s i u m h y d r o g e n p h o s p h a t e was p r e p a r e d and was d i l u t e d a c -78 c o r d i n g l y f o r t h e k i n e t i c r u n s . 2. t - B u t y l a m i n e t - B u t y l a m i n e was t w i c e d i s t i l l e d and a m i d d l e f r a c t i o n b o i l -i n g a t kk° was c o l l e c t e d and u s e d f o r t h e k i n e t i c r u n s . S t o c k s o l u -t i o n s were p r e p a r e d f r o m f r e s h l y d i s t i l l e d amine and d i s t i l l e d w a t e r w h i c h had been b o i l e d and s a t u r a t e d w i t h n i t r o g e n . The c o n c e n t r a -t i o n s were d e t e r m i n e d f r o m t i t r a t i o n s w i t h s t a n d a r d • h y d r o c h l o r i c a c i d u s i n g m e t h y l r e d a s I n d i c a t o r . The p u r i t y o f t h e t - b u t y l a m i n e was c h e c k e d b y v a p o r phase chro m a t o g r a p h y and o n l y one peak was o b s e r v e d . 3 . K i n e t i c method A t y p i c a l r u n was c a r r i e d o u t as f o l l o w s : i n a 125-ml r e d E r l e n m e y e r f l a s k were mix e d 30 m l . o f 2M p h o s p h a t e b u f f e r , 5.96 m l . o f ku p o t a s s i u m h y d r o x i d e , k.Qk m l . o f O.615M t - b u t y l a m i n e . The s o l u t i o n was t h e r m o s t a t e d a t 25*0 - 0.02° f o r one hour. The r e a c t i o n was s t a r t e d when 10 m l . o f 0.497M p o t a s s i u m permanganate was i n j e c t e d f r o m a 10 m l . Chaney-adapted s y r i n g e i n t o t h e s o l u t i o n . One m l . a l i q u o t s were i m m e d i a t e l y removed w i t h a 2 m l . Ghaney-adapted s y r i n g e and d e -l i v e r e d i n t o 5 m l . v o l u m e t r i c f l a s k s . E a c h f l a s k was wrapped w i t h aluminum f o i l t o e x c l u d e l i g h t and t h e n t h e r m o s t a t e d a t 25.0 - 0.02°. The pH was 11.20. A t a p p r o p r i a t e t i m e s t h e c o n t e n t s o f t h e e n t i r e f l a s k was quenched w i t h e x c e s s a c i d i f i e d p o t a s s i u m i o d i d e . A n a l y s e s were c a r r i e d o u t b y i o d o m e t r i c t i t r a t i o n . S i n c e t h e r e a c t i o n s were v e r y s l o w t h e pH o f t h e s o l u t i o n s were c h e c k e d r e g u l a r l y and were f o u n d t o v a r y b y o n l y - 0.02 u n i t f o r a l l t h e s o l u t i o n s . 7 9 k. S t u d i e s i n D 20 S i n c e t h e b u f f e r c o n c e n t r a t i o n s must be v e r y h i g h , d i p o t a s s i u m h y d r o g e n phosphate was r e p l a c e d w i t h t r i p o t a s s i u m p h o s p h a t e , i n o r d e r t o m i n i m i z e t h e number o f e x c h a n g e a b l e p r o t o n s . The most c o n c e n t r a t e d s t o c k s o l u t i o n o f t r i p o t a s s i u m p hosphate w h i c h c o u l d be p r e p a r e d was 1.0M, however. S e p a r a t e s t o c k s o l u t i o n s o f b u f f e r , t - b u t y l a m i n e , and p o t a s s i u m permanganate were p r e p a r e d i n DgO and HgO. I n e a c h case t h e c o n c e n t r a t i o n s were i d e n t i c a l . 0.5 m l . D g S ( \ ( a P P r o x i m a ' b e l y 10$) was u s e d i n t h e p r o t i o as w e l l as t h e d e u t e r i o r e a c t i o n s o l u t i o n s i n o r d e r t o b r i n g t h e pH down t o 11.50. 80 RESULTS S t o i c h i o m e t r y S t u d i e s c a r r i e d o u t on t - b u t y l h y d r o x y l a m i n e and t - n i t r o s o b u -t a n e , w h i c h a r e p r o b a b l e i n t e r m e d i a t e s i n t h e o x i d a t i o n o f t - b u t y l a m i n e b y permanganate, have shown t h a t t h e y a r e a l m o s t i n s t a n t a n e o u s l y o x i -d i z e d b y a c i d i c o r b a s i c permanganate. H a l f - l i f e o f t h e r e a c t i o n b e -tween permanganate and t - b u t y l h y d r o x y l a m i n e a t pH 8.86 and a h y d r o x y l -amine c o n c e n t r a t i o n o f 2 x 1 0 " 2 M was l e s s t h a n 0.6 o f a m i n u t e . Be-cause o f t h e " r a p i d i t y w i t h w h i c h t h e s e compounds a r e o x i d i z e d t h e s t o i -c h i o m e t r y o f t h e much s l o w e r r e a c t i o n between b a s i c permanganate and t - b u t y l a m i n e c a n be e x p r e s s e d as f o l l o w s : 2 Mh0£ + RNH 2 • RN0 2 + 2 MnOg + 2 OH" (1*5) O r d e r o f r e a c t i o n The k i n e t i c d a t a gave good l i n e a r s econd o r d e r p l o t s up t o a p p r o x i m a t e l y 20-30$ r e a c t i o n , a f t e r w h i c h t h e p o i n t s became s c a t t e r e d . ( F i g u r e 15). A p o s s i b l e e x p l a n a t i o n i s t h a t t h e cause o f t h e e r r a t i c and r e d u c e d r a t e m i g h t be due t o a n a c c u m u l a t i o n o f manganese d i o x i d e . I t was o b s e r v e d t h a t a f t e r a b o u t 20-30$ r e a c t i o n t h e r e was v i s i b l e p r e c i p i t a t i o n o f manganese d i o x i d e i n t h e r e a c t i o n f l a s k . I t i s known t h a t t h e -OH group o f a l c o h o l s c a n be o x i d i z e d 4>y Mn0 2 a f t e r b e i n g a d s o r b e d o n t o t h e l a t t e r " s s u r f a c e ( 1 0 ) . C o r r e s p o n d i n g l y , i t i s p o s -s i b l e t h a t t h e amino group o f t - b u t y l a m i n e c a n a l s o be a d s o r b e d b y t h e p r e c i p i t a t e d Mn0 2. A l t h o u g h t h e t - b u t y l group i s n o t a c t i v a t i n g enough t o cause t h e amino group t o be o x i d i z e d b y Mn0 o, t h e a d s o r p t i o n 0.6 0,4 0.2 0 FIG. 15 OXIDATION OF t-BUTYLAMINE TYPICAL RATE PLOT p.H = 9=83 I 1 I 0 50 100 150 TIME IN HOURS 82 process i t s e l f must serve to deactivate the amine to permanganate oxid-ation. To test this assumption, MnOg, corresponding to 25$ of the total Mn(VIl) concentration, was generated i n situ according to the equation (21): 3 Mn + 2 + 2 Mn04" + 2 HgO • 5 MnOg + 4 H + (46) When this was done prior to the addition of the t-butylamine at pH 9.87 the resulting second order plot was erratic from the very begin-ning of the reaction (Figure 16). Effect of pH on the oxidation rate The plot of the rate constants versus pH gave a typical ion-ization curve (Figure 17). Table XII l i s t s the data for Figure 17. The rate plots for pH 13 and higher were autocatalytic i n character, and hence no rate constants were calculated from them. To show that the ionization i s due to that of t-butylamine, a plot of log (kg/kg38* - kg) versus pH was made, where kg** was es-timated from the graph. A slope of 1.1 was obtained and the intercept at zero gave the pKgjj+ of 10.98 for t-butylamine. The literature value for the pKgg+ of t-butylamine was 10.45 (100). Oxidations i n DgO The rate i n HgO at pH 11.50 and 25.0 t 0.02° was 0.886 1. mole""Lhour 1 , compared with O.630 1. mole^hour" 1 i n DgO. The isotope effect was 1.4. 2 V -TV t 5 o 0.5 FIG. 16 OXIDATION OF t-BUTYLAMINE +4 EFFECT OF Mn ON THE OXIDATION pH = 9.87 0.4 0.3 0.2 -0.1 - -.-Or .0 — - - 0 - - 0 -.o' JO' CD oo 50 100 TIME IN HOURS 150 85 Table XII Oxidation of t-Butylamine  Variation of Rate with pH pH k„ (l.mole^hr" 1) 8.62 3.28 X 10 " 3 9.60 3.40 X l O " 2 9.83 5.81 X -2 10 9.89 7.32 X lO" 2 9-99 7.55 X lO" 2 10.12 1.09 X i c " 1 10.26 X -1 10 10.32 2.24 X 10" 1 10.40 2.26 X -1 10 10.67 5.03 X l O " 1 10.68 5.42 X l O " 1 10.90 7.5^ X l O " 1 11.20 1.02 11.34 9.57 X l O " 1 11.42 1.14 11.56 1.23 11.81 1.27 12.04 1.26 .max 1.30 86 DISCUSSION The stoichiometry of the reaction between permanganate and t-butylamine may be represented in the following equation: The product, t-nitrobutane, i s not further attacked by permanganate and can be isolated i n very good yields. i s second order, f i r s t order i n permanganate and f i r s t order i n t -butylamine. As i n the oxidation of benzylamine, the permanganate reacts with the neutral amine. Accordingly, a plot of the second order rate constant versus pH resembles an ionization curve (Figure 17)> the midpoint of which i s 1 0 . 9 8 . This value differs considerably from the reported pR-g^ of t-butylamine, 1 0 . 4 5 ( 1 0 0 ) . However, i t i s possible that the pKgg+ i s altered by the very high ionic strength (approaching 3 * 6 ) that was used. The mechanism of the reaction can be expressed by the f o l -lowing equations: RNHg + 2 MnO, > RN0_ + 2 Mn0o + 2 OH <*5) The kinetics of the oxidation of t-butylamine by permanganate CH3 K + + OH CH k (*7) + MnO, -*• Products 87 The rate law corresponding to the proposed mechanism i s : dt k [MnOn [ (CE_) CNE~] [0H _] K * ' 3 3 3 The rate of oxidation of t-hutylamine i s very much slower than that of benzylamine. Permanganate reacts 30 times more rapidly with benzylamine than with t-butylamine. Ammonia, on the other hand, i s oxidized by permanganate at l/lOth the rate of the oxidation of t-butylamine. ida t i o n i n EgO at the same pH gives a solvent isotope e f f e c t , k (HgCO/k (D 20) of 1.4. This value i s not s u f f i c i e n t l y large to suggest the cleavage of the N-H bond i n the rate - c o n t r o l l i n g step. The only alternative pathway f o r permanganate to take i n the oxidation process i s an oxidative attack on the nitrogen, since i n t-butylamine there i s no -hydrogen to react with. The following mechanism i s proposed to accommodate the observed r e s u l t s : The oxidation of t-butylamine i n D-0 compared with the ox-E (I) f a s t + MnO 3 Disproportionation RNHOE Mn(lV) + Mn(VII) Fast Mn(VIl) RNO2 (*9) 88 The ra t e - c o n t r o l l i n g step involves an e l e c t r o p h i l i c attack on the t -butylamine "by permanganate to give a quaternary hydroxylamine deriva-t i v e ( I ) . I t seems doubtful that the formation of I could be rever-s i b l e since the manganese i s already i n the oxidation state of +5 i n t h i s ion. Moreover, e f f o r t s made to detect the permanganate-t-butyl-amine (and NH^) interaction spectrophotometrically i n the v i s i b l e and u l t r a v i o l e t regions f a i l e d to show ( l ) any change i n the o r i g i n a l Mn(VIl) spectrum and (2) any appearance of the manganese(V) species. I f an equilibrium does occur i t must be sh i f t e d very f a r to the l e f t . Since there i s a small isotope e f f e c t , probably a solvent isotope e f f e c t , i t seems l i k e l y that the formation of (I) i s rate-c o n t r o l l i n g . Solvent Isotope effects of s i m i l a r magnitude (20-40$) as that observed f o r t-butylamine have been found f o r numerous reac-tions where decreases i n rates were observed on changing the solvent from HgO to DgO (101,102,103,104). In a l l these cases the solvent does not take part i n the actual reaction, but i t i s involved i n the solvation of a l l the species which are i n solution. The isotope effects which are observed must therefore be due to the difference i n the s o l -vatlng powers of HgO and D^ O f o r the reactants or f o r the t r a n s i t i o n state. The s i m i l a r i t y between the t r a n s i t i o n state f o r the hydrolysis of methyl bromide and the t r a n s i t i o n state f o r the permanganate oxida-t i o n of t-butylamine and t h e i r respective solvent isotope effects are compared below: H H t .s. 89 D > CH^Br D H D Hi -Br •H t .8 , kCB^CO/kCDgO) = 1.25 at 70° (|Ql) H(D) tBu-N + 0-MnO" I, 3 H(D) k(H 20)/k(D 20) H(D) tBu-N 0 MnO, 4 l.lfO at 25c (D) t .8 , PART I I I : OXIDATION OP BENZYLAMINES I N FROZEN SYSTEMS 9o EXPERIMENTAL Oxidation of benzylamine i n ice at -10° A typical run was carried out as follows: a pH 9.31 solution made up of 10 ml. of 1M buffer (KgHPO^) 3.94 ml. benzylamine (O.O253M) 33.93 ml. of water 2.08 ml. of potassium permanganate (0.0319M) was prepared i n a 125 ml. red Erlenmeyer flask which was cooled i n an ice water bath. Immediately after the last reagent, the permanganate, was added, a k ml. sample was delivered into a 10 ml. screw-capped bottle and immersed i n a Dry Ice-acetone bath. This sample was used for the blank. Eight more samples were then prepared and they were a l l simultaneously placed undisturbed into the Dry Ice-acetone bath for k minutes. During this s o l i d i f i c a t i o n process, the blank was warmed under hot tap water (ea. 50°), quenched with excess warm acidic KI solution and transferred quantitatively into a 50 ml. flask containing 10 ml. of 0 .3M sulfuric acid. The contents were then titrated with thiosulfate solution. After four minutes the eight samples i n the Dry Ice-acetone bath were transferred to an Ice-water bath for 1 minute, during which time the temperature of the samples was found to rise to approximately -10°. The samples were f i n a l l y transferred to a salt-ice bath which had been adjusted to -10 t 0.2°. The various baths were prepared in covered Dewar flasks, so that temperatures were constant for the duration of the entire experiment. I n i t i a l time was taken when the samples were placed 91 i n t o t h e -10° b a t h . A t a p p r o p r i a t e i n t e r v a l s , t h e f r o z e n samples were removed and warmed and a n a l y s e d i n t h e same manner as f o r t h e b l a n k . The pH o f t h e s o l u t i o n s were t a k e n when t h e samples were a t room temp-e r a t u r e . 92 RESULTS Table XIII compares the rates obtained for identical solu-tions i n liquid and i n frozen states. Table XIII Comparison of Rates for Benzylamine and p-nitrobenzylamine  i n Liquid and i n Frozen Systems, kp i n l.mole" 1min" 1 Benzylamine kg ( 2 5 ° ) kg (-10°, ice) pH 9-31 14.50 15 . I I 8.25 2.96 5-02 7-53 0.350 0.834 p-Nitrobenzylamine pH 7.50 4.90 1.15 It was observed that whereas the second-order rate plots for the runs at 2 5 ° tended to curve downwards after about 35$ reaction, those for the frozen systems were entirely linear (Figure 18). However, in most of the rate plots, the line did not pass through the origin. This i s not observed i n the identical solutions oxidized at 25°. More-over, the departure from the origin increased as the pH of the solution increased. This may be due to the fact that during the preparation of the samples, which usually took about 3 minutes, the reaction was a l -ready occurring i n the liquid state. This assumption i s reasonable, since i n the oxidation of benzylamine at 2 5 ° , pH 7«53> "the # reaction at 3 minutes corresponded almost exactly to the % reaction at zero 100 200 300 400 T I M E I N M I N U T E S 94 t i m e f o r t h e f r o z e n r u n . S i n c e t h e s e s t u d i e s i n t h e f r o z e n systems a r e r a t h e r e x p l o r -a t o r y i n n a t u r e , a l l t h e p o s s i b l e e r r o r s i n h e r e n t i n t h e t e c h n i q u e have n o t been e n t i r e l y e l i m i n a t e d , a l t h o u g h a t t e m p t s t o m i n i m i z e them as much as p o s s i b l e were made. I n t h e f r o z e n s y s t e m s , t h e o x i d a t i o n r a t e a l s o i n c r e a s e d w i t h i n c r e a s i n g pH, a l t h o u g h t h e r e l a t i o n s h i p was n o t a l i n e a r one ( F i g u r e 19). To show t h a t t h e r a t e i s dependent on t h e f r e e amine, a p l o t o f l o g ( f r e e amine) v e r s u s l o g k^ was made ( F i g u r e 20) w h i c h was l i n e a r , b u t w i t h a s l o p e o f 1.37-I f one assumes t h a t t h e r a t e l a w i n t h e f r o z e n systems i s unchanged f r o m t h a t i n t h e l i q u i d s y s t e m , t h a t R a t e = k [MnO^] [ a m i n e ] , t h e n t h e r e a c t i o n s h o u l d be f i r s t o r d e r w i t h r e s p e c t t o t h e amine. I t was f o u n d t h a t i f one u s e d a n " a p p a r e n t " P^gg-*- o f 8.70 f o r b e n -z y l a m i n e t h e n t h e p l o t i n F i g u r e 20 assumed a u n i t s l o p e . I t i s n o t o b v i o u s a t p r e s e n t w h e t h e r t h e a c c e l e r a t e d r a t e s o b t a i n e d i n t h e f r o z e n systems a r e due t o a r e a c t i o n i n t h e s o l i d s t a t e o r t o a c o n c e n t r a t i n g o f t h e r e a c t a n t s i n p o c k e t s o f l i q u i d i n t h e i c e l a t t i c e . A k i n e t i c r u n a t pH 8.30 i n w h i c h a l a r g e e x c e s s o f sodium s u l f a t e was added (0.6M) showed no change I n r a t e compared t o t h e r e a c -t i o n w i t h o u t added s a l t a t t h e same pH. T a b l e X I V g i v e s t h e r a t e s o b t a i n e d f o r t h e o x i d a t i o n s o f b e n -z y l a m i n e i n HgO and D^O. U n f o r t u n a t e l y t h e pH o f t h e s o l u t i o n s were row n o t i d e n t i c a l , and hence i n t h e t h i r d A t h e kA r e p r e s e n t s t h e c a l c u l a t e d F I G . 19 OXIDATION OF BENZYLAMINE AT -10.0° (IN ICE) RELATION BETWEEN RATE CONSTANT AND pH / / / / 7.5 8.0 pH (22°) 8.5 9.0 FIG. 20 OXIDATION OF BENZYLAMINE AT -10.0° (IN ICE) ® LOG k 97 rate i n DgO i f the pH were 8.99. To calculate k£, the apparent P K B H + ; 8.70, was used. Table XIV Rate Studies i n H9O and D9O at -10° (in ice) Solvent pH kg k^ k^/kp HgO 8.99 17.01 DgO 9.23 24.10 20.60 O.83 DO IO.38 23.62 15.92 1.07 Mean = 0.95 It i s puzzling that the rate i n frozen HgO at pH 8.99, -1 -1 k 2 = 17-01 l.mole min , did not agree with the extrapolated value -1 -1 obtained from Figure 19, kg = 11.8 l.mole min . The discrepancy might be partly due to the fact that i n the former case, a l l the reagents are prepared by weight and i n the latter case, a l l the rea-gents are standardized through t i t r a t i o n . 98 DISCUSSION There was no detectable change i n the mechanism of permangan-ate oxidation of benzylamine when the reactions were carried out i n frozen systems at -10°. The overall kinetics was second order: f i r s t i n permanganate and f i r s t i n benzylamine. The stoichiometry i s s t i l l represented by the following equation: 3 PhCH2NH2 + 2 MnO~ . ' , >3 PhCH=NH +.2 Mn02 + 2 E^O + 2 0H~ ( 2 8 ) There was no marked solvent (H^O/DgO) isotope effect, and no salt effect. Significant changes i n the reaction rates were observed, how-ever. In general, the rates from the frozen systems were higher than the corresponding rates from identical reactions at 25°. The d i f f e r -ence i n rates between the two systems increases with decreasing pH (Table X V ) . Table X V Relative Rates of Permanganate Oxidation between  Reactions i n Frozen Systems at -10° and those at 25° with Respect to pH pH k „ (in frozen system)/kp (at 2 5 ° ) 9-31 1 8.25 5/3 7-53 ) 2 . 5 Compared to the calculated rate constants for liquid systems at -10°, the rates from the frozen systems at -10° showed very large 99 accelerations which again Increase with decreasing pH (Table XVI). Table XVI Comparison of Rate Constants between Liquid  and Frozen Systems at -10° PH k 2 (frozen, -10°)/k2 (liquid, -10°) 9.31 10 8.25 21 7.53 ko The acceleration i n rate i s comparatively small for p-nitro-benzylamine i n the frozen system. There was only a three-fold ac-celeration i n going from the liquid (-10°) to the frozen (-10°) system. The excellent linear second order plots which were obtained for the reactions i n the frozen systems showed that the tendency for the imine to condense with benzylamine i s minimized i n these reactions at low temperature i n ice. Another significant change resulting from studies in the frozen systems i s i n the pKgjj+ of benzylamine. An apparent pK^g+ of 8.70 was determined by benzylamine. Its pKgg+ a * 25° i s 9-28. It i s not known how the pH changes i n these frozen systems. Kavanau (105) suggests that going from 25° to -10° (frozen system) there i s a corresponding lowering of the acti v i t y of the hydrogen ion by a fac-tor of approximately 10 . This suggests a considerable increase i n pH going from the liq u i d system to the frozen system. It was originally thought that the ice la t t i c e might affect 100 the amino hydrogens i n some way so as to f a c i l i t a t e the removal of the hydrogens i n some way so as to f a c i l i t a t e the removal of the hydrogen from the c^-carbon by the permanganate. Such an effect would be par-t i c u l a r l y important i n the oxidation of the benzylammonium ions, where the transfer of an amino proton to the cavity walls might occur simul-taneously with the removal of the hydrogen from the o£-carbon by the permanganate, v i z . One i s tempted to conclude that the la t t i c e does remove a proton from the benzylammonium ion since the relative rate, k(frozen)/k(liquid)^ at -10° does increase with decreasing pH. However, It must be pointed out that the oxidation rate of benzylamine at pH 9'31 In ice is s t i l l more than ten times faster than that of the benzylammonium ion in ice at pH 7«53> and i f a proton i s removed by the lat t i c e at the lower pH values one would probably observe a much smaller difference between the rates at pH 9.31 and 7»53« centrosymmetric structure similar to that of the hexagonal form of s i l i c a , the tridymitle structure (105). Each oxygen atom i s tetra-hedrally surrounded by four other oxygen atoms to which i t is hydrogen-bonded. The unit c e l l contains four water molecules, and the inter-s t i t i a l regions are each bounded by six water molecules, the dimen-sions of these regions between the coordinated tetrahedra being greater wall Ordinary ice has been described by Kavanau as having an open 101 than those of the water molecules. Because ammonium ions have tetra-hedral structures resembling that of the water tetrahedron, they can occupy the i n t e r s t i t i a l areas between the ice molecules and form hy-drogen bonds with them without greatly disturbing the structural order of the ice l a t t i c e . 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Robertson, Can. J. Chem., 3J., 1491 ( 1 9 5 9 ) * 1 0 2 . P. M. Laughton and R. E. Robertson, Can. J. Chem., 3 4 , 171^ ( 1 9 5 6 ) . 1 0 3 . F. A. Long and D. Watson, J. Chem. Soc, 2 0 1 9 ( 1 9 5 8 ) . 1 0 4 . R. P. B e l l , J. A. Fendley and J R. Hulett, Proc Roy. Soc, A235, ^53 ( 1 9 5 6 ) . 105** J. Lee Kavanau, Water and Solute -Water Interactions, Holden-Day Inc., San Francisco, 1 9 6 4 . 107 APPENDIX Derivation of the rate expression for the kinetics i n the basic region pH 1 2 to lk: Assume the following stoichiometry: 3 RNHg + k MnO£ • 3 RCOOH + k MnOg Let y = [RNH^] x = [MnO£] Then dx _ kxy k (3x2 \ " d t = = \~k~) Integrating: dx 3 kt = IT kt t 0 3 x~ kt = x nr° x - -y Q k t • - x x t 1 I f the ratio of y 0:x Q were 1:2 instead of 3'k, then permanganate is in in excess, and at t o o , x = x o ^ 3 a n < i y = ^ According to the 1:2 ratio used, 3 3 IT 2° 108 The rate expression becomes dx kxy dt = _ 3 kx (x - 2y Integrating dx - 3 kt x x - 2 ^ " K 3 §7 r-n -°j - r 3_ i n fx - 2/3 y j j - 3 kt 1_ in fx - 2/3 y \ - kt y o ^ x j • 2 Let xn = AV , and x = A[V. - 2 (V - V )] where V = volume of standard thiosulfate solution o at t=0 V = volume of thiosulfate used at time t A = constant of proportionality Substituting ^ fx - 2/3 y\ = in fx - 1/3 x in j A j V t - 2 / 3 (V -V)3 - l / 3 A V C { \ i v ; - 2? 3 c v r n = l n - 2/3 V Q + 2/3 V t - 1/3 V ) I V t " 2/3 Vo + 2 /3 V t J 1 0 9 5 / 3 V t - 2 / 3 V Q = m ( I t - 3 / 5 V0_\ l Vt " 2 / 5 V o Hence y kt In / V -3/5 V ^ - "o—g- = - t ^ o-k = _ 4 , 6 0 log / V L - 3 / 5 V G \ " y 0* \ v t - 2 / 5 V o / At t = 0 log / V t - 3/5 V G \ = log ( 2 / 3 ) \ v t " 2 / 5 Vo ) Derivation of rate expression for the kinetics i n the pH region 1 1 . 0 to 1 1 . 8 : Assume the following stoichiometry: 3 RNH + 4 MnO." • 3 RCOOH + 4 MnO 2 4 2 Let y - [RNHg] x = [MnO^~] According to the above stoichiometry: y/x = 3/4 If one used the ratio of y:x = 3 : 2 , instead, then at t = °*> x = 0 7 = 1/2 y o = y ~ + 3A x • to + 3 A x 2 110 The rate expression becomes dx k xy dt = kx (y Q/2 + 3x/4) = kx (3x/4 + y 0/2) = 3 A kx (x + 2/3 y Q) Integrating dx x(x + 2/3 y Q) = 3 kt 4" 3 In 2y Q/3 + 2y 0 x 3 kt 4" 1 In | 2/3 y Q + x^  = kt/2 y_ V x Express i n terms of V Q , V (defined as before) l n ( 2 y w / 3 **) = i n (V t - 2/3 (V ?- V T ) + 3V?/2 V T - 2/3 ( V Q - V T ) \ - 2V^/ 3 + V , + 3V./2 V T - 2VQ/3 + 2 V t / 3 In 2 V, 5Vt/3 - 2Vt/3 k = 4.60 yo t log [ 2_V 5V+/3 " 2 V q / 3 At t - 0, log / 2_Vt  ,5V t/ 3 - 2V0/3 = log 2 I l l RATE CONSTANTS Oxidation of Benzaldehyde o -1 _x At pH 8.27: [PhCHO] = 3.75 x 10 D M, kg = 21.1 1. mole min [PhCHO] = [NH3] = 3.75 x 10"3M, kg = 21.1 l.mole^min^ Substituent Effects X-CgH^CH2NH2 pH kg (l.mole-1min 1) p-NOg 9.24 30.8 P-N0 2 9-03 29.3 P-N0 2 10.21 40.9 , 41.2 P-CH3 9.19 12.5 p-CH3 10.21 35-2 P-CH3 9-73 23.6 p-CH30 8 88 13-6 p-CB^O 10.21 50.25 m-CF 3 10.12 4o.o m-CF3 10.15 4o.o p-Cl 10.21 31-7 m-CH 3 10.21 33-9, 30.9 m-NO 2 10.22 27-5 P-CgH5 10.21 35-4 112 Temperature Studies X-CgH^CH2NH2 pH t° C k?(l .mole'-min"1) p-H 10.40 0.10 5-03 14.75 16.7 34.25 57-4 45.40 112 p-NOg 10.05 0.10 7.81 13 50 17.9 25.OO 39-7 38 60 89.2 m-CF3 10.12 0.10 6.42 16.00 21.8 25.00 40.0 35-20 81.1 43.40 127 P-CH3 10.19 0.10 4.88 16.10 17.5 25.25 33-5 35.75 62.8 44.35 106 113 SUGGESTIONS FOR FURTHER WORK 1. The kinetics of the permanganate oxidation of benzylamines i n the highly alkaline pH region requires further elucidation. A l l three of the proposed mechanisms (equations 34-6) require the C-H bond breaking i n the rate-determining step. This could be easily checked by studying the oxidation of benzylamine-oc-dg. Where-as mechanisms 34 and 35 require hydrogen atom and hydride ion removal respectively, mechanism 36 requires proton removal i n the rate-determining step. The f i r s t two mechanisms may be d i f -ferentiated from the last one by studying the substituent ef-fects. Mechanisms 34 and 35 also suggest proton removal from the nitrogen by the hydroxyl ion. Studies i n DgO should show a substantial isotope effect for PhCHgNDg. It would also be i n -teresting to study the N-H proton removal step i n frozen systems, since studies of the oxidation of benzylamine i n frozen systems at lower pH regions suggest that the ice la t t i c e might be re-moving a proton from the nitrogen simultaneously as the perman-ganate removes a hydrogen from the alpha carbon. In the previous studies of the oxidation of benzylamine i n frozen systems i t was not possible to decide whether the rate enhancements were due to a concentrating effect of the freezing or to an orientating ef-fect of the ice l a t t i c e . Since the oxidations i n the highly a l -kaline region are termolecular, the concentrating effect of the freezing should give much greater rate enhancements. 2 . The study of the permanganate oxidation of p-trifluoromethyl-benzylamine should shed some light on the anomalous behaviour 114 of the m-trifluoromethylbenzylamine. 3. The explanation suggested for the oxidation of p-nitrobenzylamine i s that permanganate i s removing a hydrogen atom from the amine and the enhanced rate that i s observed i s due to the extra sta-b i l i z a t i o n of the resulting radical by the nitro group. Since the rate of racemization of (-)- o<_-methylbenzylamine i s greater than i t s rate of oxidation, a radical mechanism has also been suggested i n which the permanganate removes the alpha-hydrogen as a hydrogen atom. The permanganate oxidation of benzaldehyde and benzhydrol both show "normal" isotope effects when deu-terium i s substituted i n the alpha-position, while the perman-ganate oxidation of fluoral hydrate (monoanion) and aryl t r i -fluoromethyl carbinols both exhibited very large isotope effects when deuterium i s substituted i n the alpha position. A l l of the above observations can be incorporated into one problem by studying the permanganate oxidation of optically active p-nitro-QC -trifluoromethylbenzylamine, and i t s alpha-deuterio analogue, H ( D ) i . e . the two compounds can be used (l) to examine the unusually large isotope effects which have been observed with a -CF^ group which i s located alpha to a reaction center, and (2) to make a more thorough examination of the rate of racemization and compare i t with the rate of oxidation. I t would be interesting to determine whether p-Nitro-=< -115 methylbenzylamine i s acidic enough to ionize to the carbanion in the pH region. If i t does ionize i n the pH region, i t should provide some Interesting kinetics i n i t s oxidation with permanganate. Its rate has been predicted to be much faster than that for the neutral molecule. 

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