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Study of 19F-1H couplings in nuclear magnetic resonance. Jones, David Llewellyn 1970

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19 1 A STUDY OF F- H COUPLINGS IN NUCLEAR MAGNETIC RESONANCE by DAVID LLEWELLYN JONES B . S c , Uni v e r s i t y of B r i t i s h Columbia, 1965 A THESIS'SUBMITTED IN FULFILMENT OF THE REQUIREMENTS j FOR THE DEGREE OF MASTER OF SCIENCE i n the department of CHEMISTRY We accept t h i s t hesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA A p r i l , 1970 ) In p r e s e n t i n g t h i s t h e s i s in p a r t i a l f u l f i l m e n t o f the requirements f o r an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia, I agree that the 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 reference and study. I f u r t h e r agree tha permiss ion fo r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Department or by h i s r e p r e s e n t a t i v e s . I t i s understood that copying or 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 ga in s h a l l not be a l lowed without my w r i t t e n p e r m i s s i o n . The U n i v e r s i t y of B r i t i s h Columbia Vancouver 8 , Canada Department of ( i i ) ABSTRACT A new method of synthesizing organic f l u o r i d e s s t e r e o s p e c i f i c a l l y was developed; the elements 'BrF' and 'IF' were added q u a n t i t a t i v e l y across the double bond of simple o l e f i n s such as cyclohexene, using elemental halogen and s i l v e r f l u o r i d e at room temperature i n benzene. Ap p l i c a t i o n of t h i s r e a c t i o n to the a c t i v a t e d o l e f i n , acenaphthylene, r e s u l t e d i n a v a r i e t y of products, depending on solvent; with pus-e a c e t o n i t r i l e solvent, quantitative 'BrF' a d d i t i o n occurs, but with an increasing proportion of benzene various side reactions take place, i n c l u d i n g d i f l u o r i n a t i o n and dimerization. o— Another s e r i e s of compounds was synthesized from f l u o r o - acenaphth-ylene by various addition and s u b s t i t u t i o n r e a c t i o n s , and a l l together f i f t e e n acenaphthene f l u o r i d e s were made, in c l u d i n g t h i r t e e n new compounds. 1 19 The H and F N.M.R. spectra of these substances were measured and a 3 set of J values obtained f o r a wide v a r i a t i o n i n the e l e c t r o n e g a t i v i t y of the substituents, and f o r two values of d i h e d r a l angle (0°and 100°). 3 This data showed that the dependence of upon e l e c t r o n e g a t i v i t y was f a r from l i n e a r , as had h i t h e r t o been supposed, but rather exponential, which i s i n retrospect more l o g i c a l . 3 A p p l i c a t i o n of t h i s data on J to some f l e x i b l e systems, d e r i v a t i v e s of indene and benzofuran, allowed t h e i r conformations to be determined. In a l l cases the pucker of the five-membered r i n g i s small (^25°), except i n the cis-bromofluoride of benzofuran where i t i s much l a r g e r , (45-50°). (.Ui) A separate study was made of the conformational inversion of trans-1-fluoro-2-iodocyclohexane (I) and i t s s p e c i f i c a l l y deuterated analogue, derived from 3,3,6,6-tetradeutero-cyclohexene. Several methods were employed to measure the p o s i t i o n of the conformational equilibrium and t h i s permitted a comparison of the methods themselves. I t was found ; that a l l chemical s h i f t s and coupling constants were temperature 19 . dependent, those i n v o l v i n g F being p a r t i c u l a r l y s usceptible. The only r e l i a b l e methods were found to be area measurements (at -90°C), 19 linewidth measurements (at -45°C), and temperature-corrected F chemical s h i f t measurements; thus the compound i n question was found to have a preference f o r the d i e q u a t o r i a l form, with AG° = 0.650 4 0.025 kcal./mole (at -90°C to 0°C), and a near zero entropy, AS° = 0.0 ± 0.5 e.u. This value of AG° i s only 0.1 kcal./mole smaller than the sum of the A-values f o r iodine and f l u o r i n e , and indicates that the re p u l s i o n between these two halogens i n the d i e q u a t o r i a l form i s quite small, about one tenth that between iodine and c h l o r i n e , or between .chlorine and c h l o r i n e , e tc. A k i n e t i c study of I was made by applying the general lineshape equation of Gutowsky and Holm f o r two-site exchange; calculated l i n e -19 widths and positi o n s were matched to the experimental F spectra (with a l l "'"H couplings removed by i r r a d i a t i o n ) at various temperatures, and thus an Arrhenius p l o t was made and a c t i v a t i o n parameters derived. AFt = 10.38 kcal./mole; ASt = 2.1 e.u. ( i v ) TABLE OF CONTENTS I INTRODUCTION 1 A V i c i n a l ^H-^H couplings 1 19 1 B_ V i c i n a l F- H couplings...... 3 C_ Synthesis of model compounds... 5 D Conformation analysis of cyclohexane d e r i v a t i v e s by N.M.R. ... 6 E_ Conformation analysis of 1,2-disubstitued indans 12 RESULTS S DISCUSSION II SYNTHESES OF FLUORINATED DERIVATIVES 16 A_ Addition of IF and BrF to some alkenes 17 B_ 'XF' additions to acenaphthylene 20 C Other acenaphthyl f l u o r i d e s 25 III CONFORMATIONAL ANALYSIS OF CYCLOHEXANE IF 31 A N.M.R. spectra 31~ B_ Conformational equilibrium 38 -C_ Discussion. 45 D_ Rate c a l c u l a t i o n s 48 IV DEPENDENCE OF 3 J u r , UPON ELECTRONEGATIVITY AND DIHEDRAL ANGLE 54 A_ E l e c t r o n e g a t i v i t y ' 54 B_ Dihedral angle 59 V APPLICATION OF 3 J U T , TO CONFORMATIONAL ANALYSIS OF INDAN BrF nr ; . AND SOME RELATED COMPOUNDS 61 A Indan BrF (VIII) 61 B_ Benzofuran d e r i v a t i v e s 72 VI EXPERIMENTAL '. 77 (v) VII APPENDICES 98 A Computer programs 98 B_ A p p l i c a t i o n of NMDRS 100 C N.M.R. s p e c t r a l analysis 103 VIII REFERENCES 109 ( v i ) LIST OF TABLES Table I N.M.R. Parameters of Cyclohexane IF i n Various Solvents.... 36 19 Table II F Spectra of Cyclohexane IF as a Function of Temperature 39 Table III Repulsion Between Substituents i n the Die q u a t o r i a l Form of some 1,2-dihalide Cyclohexanes 47 Table IV K i n e t i c Data f o r Conformational Inversion of Cyclohexane IF... 50 Table V Nuclear magnetic resonance parameters f o r fluoro-halo d e r i v a t i v e s of acenaphthene 55 1 19 Table VI V i c i n a l H- F Coupling Constants Dependence on E l e c t r o n e g a t i v i t y — A Comparison of Exponential and Linear f i t s to the Data 57 1 19 Table VII V i c i n a l H- F Coupling Constants as a Function of E l e c t r o n e g a t i v i t y and Dihedral Angle 60 Table VIII Wavefunctions and Energy l e v e l s f o r the ABXY approximation. 104 Table IX Tran s i t i o n s i n the ABXY approximation 106 ( v i i ) LIST OF FIGURES Figure 1 "*"H N.M.R. spectrum of cyclohexane IF-d^- at room temperature 33 Figure 2 1 H N.M.R. spectrum of cyclohexane IF-d^ at -100°C -. 34 19 -Figure 3 F N.M.R. spectrum of cyclohexane IF at -100°C 37 Figure 4 Arrhenius Plot f o r the conformational i n v e r s i o n of cyclohexane IF 51 3 3 Figure 5 Plot of J ( c i s ) and J u r , (trans) as a function Hr Hi of e l e c t r o n e g a t i v i t y 58 Figure 6 P a r t i a l "Si N.M.R. spectrum of indan BrF.H^ region 62 Figure 7 P a r t i a l "Si N.M.R. spectrum of indan BrF:H 2 region... 63 Figure 8 P a r t i a l "*"H N.M.R. spectrum of indan BrF:H region 64 Figure 9 P a r t i a l "'"H N.M.R. spectrum of indan BrF with a small impurity: H , region...... 66 Figure 10 P a r t i a l 1H N.M.R. spectrum of indan BrF:H region with simultaneous i r r a d i a t i o n of a si n g l e l i n e i n region 68 Figure 11 P a r t i a l 1H N.M.'R. spectrum of indan BrF:H 3, H region with simultaneous i r r a d i a t i o n of a si n g l e l i n e i n region 69 19 Figure 12 F N.M.R. spectra of the three main products of the - 'XF' r e a c t i o n to acenaphthylene 84 Figure 13 P a r t i a l "*"H N.M.R. spectra of c i s - and t r a n s - d i f l u o r i d e s of acenaphthene 85 Figure 14 P a r t i a l "*"H N.M.R. spectrum of acenaphthene BrF 87 1 Figure 15 P a r t i a l Hi N.M.R. spectrum of acenaphthene f l u o r i d e . . . 98 ( v i i i ) 19 Figure 16 F N.M.R. spectrum of l-bromo-2,2-fluoroacenaphthene... 101 Figure 17 Expansion of F i g . 16 102 A,B Normal spectrum C Double resonance spectrum of F^ with i r r a d i a t i o n of one t r i p l e t i n F^ D Double resonance spectrum of with i r r a d i a t i o n of one t r i p l e t i n F^ E,F T h e o r e t i c a l analogues of C,D c a l c u l a t e d by NMDRS ( i x ) LIST OF FLOW SHEETS Flow Sheet 1 . 18 Flow Sheet 2 21 Flow Sheet 3 . 27 Flow Sheet 4 28 (x) ACKNOWLEDGEMENT I am very g r a t e f u l to Dr. L. D. H a l l both f o r h i s encouragement and enthusiasm i n t h i s p r o j e c t , and also f o r h i s having kept the f a i t h throughout i t s many meanderings. Many thanks are also due to Ben Malcolm, John Manville and Paul Steiner f o r t h e i r many h e l p f u l suggestions. I INTRODUCTION The p r i n c i p a l aim of t h i s thesis i s to elucidate some of the factors 19 1 3 which affect v i c i n a l F- H couplings, which are encountered i n nuclear magnetic resonance (N.M.R.) spectroscopy, and then to apply t h i s knowledge to determining the position of the e q u i l i b r i a of some conformationally mobile 3 systems containing f l u o r i n e . This p a r t i c u l a r coupling, w a s c n o s e n because i t has been demonstrated that s t e r i c factors have a marked effect on 3 . . 1 2 the size of J U R , , and th i s effect appears, on the evidence available ' , to be several times greater than that affecting the analogous v i c i n a l H^-^ H coupling, 3 J H H . V i c i n a l "^ H-^ H coupling 3 In the N.M.R. of organic compounds, J has proved to be one of Hn the most useful-parameters available from the experimental spectra. The chief reason for th i s i s the marked dependence on the dihedral angle between the two protons; i n the case of saturated systems, t h i s dependence i s generally 3 2 recognized to approximate the Karplus curve , i . e . J = J Q C O S $ + K. JQ = 8-9 cps. , K = -0.3 cps. , and <j> i s the dihedral angle. 9 8 7 6 x 5 H -3 A 3 2 I H o -I " I — I — 1 — I — I — I 1 — I — I 0° 40° 80° 120° 160° 3 Another dependence of J..U that has been observed i s the e l e c t r o -nn n e g a t i v i t y dependence, i n which the coupling i s attenuated by the presence of a strongly electronegative s u b s t i t u t e n t , such as a h a l i d e . A number of workers have i n v e s t i g a t e d t h i s phenomenon, but always from an e m p i r i c a l H-12 point of view ; i n a l l cases, a l i n e a r r e l a t i o n s h i p was deduced. Thus Williamson measured the two v i c i n a l couplings J and JN i n a s e r i e s of s i x AX X J A monosubstituted hexachlorobicycloheptenes ( I ) , 5 . while Laszlo and Schleyer , i n a p a r a l l e l i n v e s t i g a t i o n , examined ten compounds , \ • 13 i n the s e r i e s ( I I ) . Using values f o r the e l e c t r o n e g a t i v i t y of R c a l c u l a t e d from N.M.R. chemical s h i f t s , and p l o t t i n g these against J and J , a AX si A reasonable l i n e a r c o r r e l a t i o n was found i n both cases, although the range of these p l o t s was not l a r g e . Abraham and Pachler_ i n a more extensive i n v e s t i g a t i o n , examined a s e r i e s of 1,2-disubstituted ethanes and determined 1 1 3 1 the average value of the v i c i n a l H- H coupling, J l t r t(av.) = - (J + & ^ HH 3 trans 2 l^gauche^' Pl°~Lt-'-n6 i b i s value against the sum of the Huggins e l e c t r o n e g a t i v i -1H t i e s , these workers a l s o concluded that there was reasonable good l i n e a r c o r r e l a t i o n . These r e s u l t s imply what was stated e x p l i c i t l y by Abraham and - 3 -Pachler, that an a d d i t i v i t y r u l e should be v a l i d ; i . e . " i f a substituent group X causes a change i n J , the i n t r o d u c t i o n of a second group X should produce the- same change i n J i f t h i s change i s s o l e l y due to the electronega-t i v i t y of X." Another important point, which was mentioned by the f i r s t workers, i s that the magnitude of the e l e c t r o n e g a t i v i t y e f f e c t , as measured by the slope of the l i n e , may depend on the dihedral angle; t h e i r r e s u l t s , however, indicated that t h i s was not a marked e f f e c t . 19 1 B V i c i n a l F- H coupling 3 1 1 J u r , has received f a r l e s s a t t e n t i o n than the H- H coupling nr discussed above, but such work as has been done has indicated that i t depends on e l e c t r o n e g a t i v i t y and dihedral angle i n a way that i s roughly p a r a l l e l to 3 3 that of J,.„. Several r e s u l t s have i n d i c a t e d that J u r,(trans) (<j>=180°) i s Hn . nr 3 3 greater than J„„ (gauche) ($=60°), as i n the J couplings. This was found nr • till ' ^ 15 • " h •» . 16 to be the case i n cyclohexyl f l u o r i d e , 1,1-difluorocyclohexane , CH 2F-CH 2C1 and CH 2F-CH 2Br 1 7, CHC1 2-CFC1 2 1 2, and i n several f l u o r i n a t e d carbo-18 19 hydrates , f o r example. Furthermore, Williamson found that i n the 3 3 f l u o r o d e r i v a t i v e of s e r i e s ( I ) , J I T _ ( c i s ) (<f>=0°) i s greater than J„„ (trans) nr n r 3 (<j)=120°). Thus the dihedral angle dependence of J^p appears to be s i m i l a r to 3 that of J o t J . Hn 2 Abraham and C a v a l l i , examined a s e r i e s of f l u o r i n a t e d ethanes and 3 concluded that J u „ (av.) ; , ; i n any CH-CF fragment i s l i n e a r l y dependent on the n r sum of the e l e c t r o n e g a t i v i t i e s of the substituents, and that the magnitude of 3 t h i s dependence i s about four times that of (av.). In a l a t e r paper, 3 3 3 3 J H F (av.) = J H F (trans) + 2[ J H p (gauche)] or rather J H p (av.) i s the experimentally observed coupling corresponding (roughly) to the above. 17 Abraham et ->.al considered the rather scanty data a v a i l a b l e f o r the separate 3 3 dependence of J u (trans) and of J ( c i s ) on e l e c t r o n e g a t i v i t y , and concluded Hi lit that " J (trans) i s much more dependent on the substituents on the carbon than J (gauche). The l a t t e r i s only dependent on the nature of the substituents which are i n a trans o r i e n t a t i o n to the coupling n u c l e i . " This conclusion, 3 3 20 which applied also to J as well as J ,.followed on previous suggestions ' nn Hi and thus introduced two new complications. The picture which now emerges can be stated as follows: 3 (I) The magnitude of the e l e c t r o n e g a t i v i t y dependence of J^p depends on the dihedral angle involved. ( i i ) The " e f f e c t i v e e l e c t r o n e g a t i v i t y " of substituents depends on t h e i r o r i e n t a t i o n . 3 ( i i i ) J u „ depends l i n e a r l y on the sum of the e l e c t r o n e g a t i v i t i e s of the Hi substituents, keeping ( i ) and ( i i ) i n mind. This p i c t u r e was supported to some extent by the work of H a l l and M a n v i l l e \ who considered two se r i e s of carbohydrates: CHj-OAc H, (p-v>-gluco-) 0 F (a-D-manno-) -5-.In the a-D-Manno se r i e s ( I I I ) , where the strongly electronegative 3 oxygen atom i s t r a n s - a n t i - p a r a l l e l to H , J varied from 5.3 (X =H) to 2e 1.5 cps. (X = OAc); whereas i n the B-D-Gluco s e r i e s (IV), J v a r i e d from F H 2 a 10.7 (X = H) to 12.0 cps. (X = OAc), and there i s no strongly electronegative substituent t r a n s - a n t i - p a r a l l e l to e i t h e r of the spins involved (F or H ). 2 a 3 However, an unexpected r e s u l t was the large s i z e of J f o r the F H 2 e • d e r i v a t i v e with X = H which was e i t h e r 10.7 or 15.3 cps.*; t h i s i s at l e a s t double the corresponding coupling i n the a-D-Manno compound, which nominally has the same di h e d r a l angle (§=60°). E i t h e r the pyranose r i n g must be deformed or else yet another f a c t o r , p o s s i b l y the s o - c a l l e d " o r i e n t a t i o n dependence", i s being exhibited here. It can be seen therefore, that there i s not a great deal of 3 unequivocal data on J couplings, and that most of i t i s concerned with nr systems i n which the dihedral angle i s e i t h e r 60° or 180°. The present work aims to shed more l i g h t on the s i t u a t i o n , and i n p a r t i c u l a r to examine two . 3 T s e r i e s of J u r , : nr ( i ) i n which the e l e c t r o n e g a t i v i t y i s constant and the dihedral angle v a r i e s . and ( i i ) the reverse of (i).° C Synthesis of model compounds With the above requirements ( i ) and ( i i ) i n mind, i t was decided that the a d d i t i o n of 'XF' ( i . e . BrF, IF, C1F) to a-variety of alkenes would be an e x c e l l e n t way of synthesizing the required model compounds. Such a r e a c t i o n acting upon cyclohexene had already been described 22 by Bowers , using anhydrous l i q u i d HF and N-halo-succinimide. Thus a set of compounds to provide data f o r s e r i e s ( i i ) were already a v a i l a b l e . '''Undetermined. -6-• However, there were two l i m i t a t i o n s to the Bowers procedure: (a) the possible products had a small v a r i a t i o n i n e l e c t r o n e g a t i v i t y . (b) the r e a c t i o n didn't work on the 'activated' alkene, acenaphthylene. I t was p a r t i c u l a r l y desirable to use the acenaphthene system, since 23 i t should provide dihedral angles of 0° and 100° , but the only acenaphthyl f l u o r i d e s given i n the l i t e r a t u r e are the c i s and trans d i f l u o r i d e s . These 24 were obtained by M e r r i t t and Johnson , using d i r e c t f l u o r m a t i o n on acenaphthylene at -78°C. The usual methods of s p e c i f i c f l u o r i n a t i o n which do e x i s t i n the l i t e r a t u r e aren't l i k e l y to work on the acenaphthylene system i because i t i s so a c t i v e . For these reasons, a new XF ad d i t i o n r e a c t i o n , o r i g i n a l l y suggested 25 by J . F. Manville , was u t i l i z e d . It was subsequently learned that t h i s sequence, i n v o l v i n g s i l v e r f l u o r i d e and elemental halogen, had previously been the subject of some controversy. 2 6 2 7 2 8 Schmidt and Meinert ' '• reported that i n a c e t o n i t r i l e solvent the elements of iodine monofluoride could be added across the double bond of cyclohexene, to form trans 1-fluoro-2-iodocyclohexane* i n 60% y i e l d . However, 29 Andreatta and Robertson , attempting to repeat t h i s r e a c t i o n , i s o l a t e d only N-acetyl-2-iodocyclohexylamine i n 17% y i e l d ; t h i s work w i l l show that the ''IF' addition r e a c t i o n to cyclohexene i s indeed a v i a b l e r e a c t i o n , and can be extended to a v a r i e t y of other alkenes, and also to 'BrF' additions. D Conformational analysis of cyclohexane d e r i v a t i v e s by N.M.R. ( l ) Thermodynamics The cyclohexane system can e x i s t i n two chair forms; thus cyclohexane IF has two possible conformations, one having, both the iodine and f l u o r i n e substituents d i a x i a l l y oriented and the other having them d i e q u a t o r i a l l y oriented. '•Hereafter designated "cyclohexane IF". -7-F H le There have been several i n v e s t i g a t i o n s i n the past of the various conformational aspects of substituted cyclohexanes and these have been 30 summarized i n a recent review . At room temperature, most substituted cyclohexanes interconvert so r a p i d l y between the two possible chair conforma-tions that the N.M.R. s i g n a l obtained at t h i s temperature i s that of the time-averaged spectrum of both conformers, weighted accordingly with population. At .lower temperatures (-100°C), i t i s possible to d i s t i n g u i s h the spectra of the i n d i v i d u a l conformers, since the rate of interconversion i s now slow compared with the time required f o r the N.M.R. t r a n s i t i o n . Most studies have been concerned with the p o s i t i o n of the conformational equilibrium f o r some p a r t i c u l a r substituted cyclohexane, and. have r e l a t e d the free energy, -AG° associated with the equilibrium constant, K: AG°= -RTlnK (I) where R = gas constant T = absolute temp. -8-A few workers have determined the equilibrium over a range of temperature, and thus have been able to ca l c u l a t e the enthalpy, AH° and entropy, AS^ differences between the conformers: AG° = AH°- TAS° (2) There are at le a s t s i x methods of determining the equilibrium constant K from N.M.R. spectra, but only one i s r e a l l y t h e o r e t i c a l l y sound, ( i . e . i t has no inherent assumptions which are questionable), and that i s the ^ di r e c t measurement of the areas of the i n d i v i d u a l conformers at low tempera-ture. However, t h i s method has two serious drawbacks: (1) I t i s only applicable over a low temperature range where the N.M.R. measurements are d i f f i c u l t and the values are of le s s i n t e r e s t than at room temperature, and (2) the errors i n area measurements are usually l a r g e , p a r t i c u l a r l y at low temperatures where the peaks may s t i l l be broadened somewhat by exchange. The best known method i s that of measuring the chemical s h i f t of some nucleus i n the averaged spectrum, and then comparing t h i s value with the chemical s h i f t of the same nucleus i n the i n d i v i d u a l conformers; the problem of course i s to obtain the l a t t e r (reference) chemical s h i f t s , and f o r these there are two possible sources: ( i ) Low temperature spectra, i n which the i n d i v i d u a l conformers are 1 frozen out'. ( i i ) Reference compounds, which have a large substituent group attached, and are thus 'frozen out' even at room temperaturedue to the large energy of a c t i v a t i o n f o r interconversion. Both of these methods have fundamental assumptions which must be examined. Using the chemical s h i f t s of the low temperature spectra implies, of course., that the chemical s h i f t s themselves are independent of temperature, but t h i s assumption has r a r e l y even been stated, l e t alone examined f o r i t s v a l i d i t y . However, a recent i n v e s t i g a t i o n of various cyclohexyl d e r i v a t i v e s in d i c a t e d that even under conditions where chemical exchange had ceased there i s s t i l l a v a r i a t i o n of the "purely a x i a l " and "purely e q u a t o r i a l " "^H chemical 31 s h i f t s with temperature. In the second method, due to E l i e l , the.use of reference compounds such as 4-t-butyl d e r i v a t i v e s to determine the chemical s h i f t s assumes that there i s no e f f e c t of the a l k y l group on the chemical s h i f t i n question; t h i s 32 33 • assumption has been the subject of some controversy ' , and was therefore 314 'examined' by E l i e l . He compared the r e s u l t s ( i . e . -AG values) obtained using 4-t-butyl- and 3-t-butyl-cyclohexyl h a l i d e s , with the r e s u l t s already i n the l i t e r a t u r e . These l a t t e r r e s u l t s , which themselves e x h i b i t a large s c a t t e r , are obtained from various methods. E l i e l used as h i s c r i t e r i o n of a v a l i d method the agreement with ( i . e . within the range of) these l i t e r a t u r e  values of AG. On t h i s b a s i s , he concluded that the 4-t-butyl compounds were s a t i s f a c t o r y models, but that the 3-t-butyl d e r i v a t i v e s were not. 31 However, Jensen and Beck i n the recent paper r e f e r r e d to above, , threw a d i f f e r e n t l i g h t on the s i t u a t i o n , and i n f a c t demonstrated that the E l i e l method i s i n v a l i d . They simply measured the chemical s h i f t of the methine "^H resonance of f i v e cyclohexyl d e r i v a t i v e s , and the corresponding c i s - and t r a n s - 4 - t - b u t y l cyclohexyl compounds at varying temperatures. "At low temperatures (between -80°C and -105°C) s i g n i f i c a n t d i f f e r e n c e s were observed between the various a x i a l and e q u a t o r i a l methine "Hi resonances of the cyclohexyl d e r i v a t i v e s , and those of the corresponding 4-t-butylcyclohexyl d e r i v a t i v e s . " They were f u r t h e r able to show that at low temperatures the temp-erature dependencies of the a x i a l and e q u a t o r i a l peaks of the cyclohexyl d e r i v a t i v e s approximated those of the corresponding 4-t-butyl d e r i v a t i v e s ; hence they could extrapolate t h e i r low temperature values of the a x i a l and -10-e q u a t o r i a l peaks to room temperature, and thus obtain values f o r 'AG from the observed (averaged) resonance. Comparison of these r e s u l t s with those based on the E l i e l method, showed that the l a t t e r was always lower, by 0.20-0.27 kcal./mole. The other two methods of determining conformational equilibrium from N.M.R. spectra both u t i l i z e spin-spin couplings and are analogous to the chemical s h i f t methods above, i . e . couplings of the 'pure' conformers are obtained e i t h e r from locked compounds, or from low temperature spectra. The assumptions i m p l i c i t i n these methods are of course the same as those i n the chemical s h i f t methods, but here the assumptions, though they don't appear to have been examined experimentally, appear more reasonable. The reason f o r t h i s i s that the chemical s h i f t s are a c t u a l l y extremely small differences i n very large numbers, ( t y p i c a l l y 0.5 parts per m i l l i o n i n 100,000,000 cps. f o r "'"H s h i f t s ) , whereas the coupling constants measured are the whole numbers. The d i f f i c u l t y with these-methods i s that of measuring the couplings accurately, since the order of p r e c i s i o n required here i s approximately ten times that of the chemical s h i f t method, and often the spectra are so complex that only f i r s t order s p l i t t i n g s can be obtained. A v a r i a t i o n which gets around the l a s t d i f f i c u l t y i s the use of the band width ( i . e . the sum of the couplings) of a p a r t i c u l a r n u c l e u s . ^ A n o t h e r technique has been to use s p e c i f i c a l l y deuterated compounds, i n which the spectra can be f u l l y analyzed. In summary then, i t can be seen that each of the methods a v a i l a b l e has i t s drawbacks and that probably the best approach i s to use as many of them as possible simultaneously; f o r t h i s reason a s p e c i f i c a l l y deuterated . 1 9 cyclohexyl f l u o r i d e d e r i v a t i v e i s an i d e a l system to study, since both F » and chemical s h i f t s and couplings are a v a i l a b l e , and one can then check on the r e s u l t s of each approach. -11- , (2) K i n e t i c s t t t The a c t i v a t i o n free energy AF , enthalpy AH , and entropy AS , associated with the c h a i r - t o ^ c h a i r inversion of a cyclohexane d e r i v a t i v e may r e a d i l y be determined from a p l o t of r a t e , K, versus inverse temperature, 1/T. 1 5 A HIT) = A E * " R T = R C s f i % ] - R T (3> ; AFJ t ) = 2.303 RT (10.319 + log T + log(2x)* (4) AS1T) = T K T ) " A F1T) ] ( 5 ) 37 Gutowsky and Holm , by applying the e f f e c t s of chemical exchange to the Bloch equations, have derived a general line-shape-expression for two-s i t e exchange. When the c o n t r i b u t i o n of the transverse r e l a x a t i o n T^, to the linewidth i s small compared with that of the exchange process, (as i t 38 ..generally i s i n high r e s o l u t i o n , t h i s expression becomes: adsorption at frequency v = g(v) = ^ R „] (6) 4TT P + R where X = constant, depending on instrument P = T [ ( ^ - ) 2 - (Av) 2] Q = X [ A V _ _ P B ) ] R = AV + (P A - PB) T = average l i f e t i m e i n s i t e A T •= average l i f e t i m e i n s i t e B < 15 "In Bovey's paper , t h i s l a s t tegm, (log 2x), i s i n c o r r e c t l y given as log T, In the o r i g i n a l paper by Gutowsky , the rate constant i s defined as v _ 1 -12-A B X + X A I 2K P. - P = f r a c t i o n a l population difference 6v = chemical s h i f t between resonances Av = distance between applied radio-frequency and the centre of the two resonance components From t h i s equation (6) i t can be seen that the line-shape i s determined by the residence time, equilibrium constant and chemical s h i f t . It i s possible to obtain r e l i a b l e values f o r the l a t t e r two quantities (from l a s t section) and thus the only v a r i a b l e l e f t i s the residence time. Hence by generating a set of t h e o r e t i c a l spectra, using equation (6), with varying x, i t i s possible to match the experimental spectra with values of the rate constant, as derived. E Conformational analysis of 1,2-disubstituted indans The cyclopentene r i n g of a trans-1,2-disubstituted indan may adopt a puckered shape, i . e . an envelope, and thus there are two possible non-planar conformations associated with the molecule. -13-For cyclopentene i t s e l f , the most favourable conformation was cal c u l a t e d to be non-planar with a pucker of 20-25° i n agreement with 39 microwave r e s u l t s . The same forces which lead to a non-planar conformation i n cyclopentene ( i . e . bond angle s t r a i n , t o r s i o n a l s t r a i n and e c l i p s i n g ) could also be expected to apply i n the case of substituted indans. i The two conformations are l i k e l y to have d i f f e r e n t energies and N.M.R. spectroscopy provides a good method of determining which one i s favoured. This idea has been u t i l i z e d i n two other studies which have . 4 0 re c e n t l y been published i n the l i t e r a t u r e ; Buys and Havinga considered t r a n s - l , 2 - d i c h l o r o - , trans-1,2-dibromo-, and trans-2-bromo-l-chloroindan; combining dipole moment data with "Hi N.M.R. spectra and using some parameters f o r dipole moments from previous s t u d i e s , they were able to a r r i v e at the constant i n the Karplus equation (see page 1) which applies to the v i c i n a l 1H-"'"n couplings. In order to do t h i s , however, they needed to assume the following: (a) the pucker of the r i n g f o r a l l three molecules was 25° ( i n both conformations). (b) the d i f f e r e n t molecules would have the same coupling constant i n each conformer ( i . e . the increased e l e c t r o n e g a t i v i t y of chlorine over bromine would have n e g l i g i b l e e f f e c t . ) (c) the Karplus equation could be s t r i c t l y applied. -14-(d) s some parameters. f o r r e l a t i n g dipole moments and coupling constants (eg. the p a r t i a l moment along the C-X bond, the valency angle C-C-X, and others). The f i r s t three assumptions have no supporting evidence, but the v a l i d i t y of the l a s t i s beyond the scope of t h i s i n v e s t i g a t i o n . From the observed v i c i n a l "'"H-1H couplings and the ca l c u l a t e d value of JQ, the p o s i t i o n of the conformational equilibrium could be c a l c u l a t e d ; the mole f r a c t i o n of d i a x i a l conformer increased from 0.67 i n the d i c h l o r i d e to >0.95 i n the dibromide. 41 In the second work, Austin and L i l l y a took a d i f f e r e n t approach; f i r s t , they measured the "*"H N.M.R. spectra of 22 1,2-disubstituted indans (both c i s and trans) and extracted the three v i c i n a l '^ H-^ H couplings from each. They then assumed that these couplings were subject to a l i n e a r attenuation 42 due to the e l e c t r o n e g a t i v i t y of the substituents, as theorized by Karplus. J = J U (1 - mAX) ' (7) where J = observed coupling constant J U = unperturbed coupling constant m = constant, depending on dihedral angle 43 The data of Smith and Cox from s i x 2-substituted hexachloro-5-norbenes (see s e r i e s I on page 2) was analyzed to determine m i n equation (7) (fo r $ = 120°), J U values c a l c u l a t e d f o r t h e i r own spectra, and then some conclusions were made concerning the preferred conformations. Small values 3 3 of J ^ a n <3 f o r > the tr a n s - d i h a l i d e s implied the predominance of the d i a x i a l forms. However, t h i s work i s subject to some severe c r i t i c i s m : 3 (a) the v a r i a t i o n i n J „ „ ((J> =120°) i n the data of Smith and Cox i s tin small (2.4 cps. to 4.4 cps.) -15-3 (b) a l i n e a r e l e c t r o n e g a t i v i t y e f f e c t on i s obviously i n c o r r e c t (from t h e i r own data), since two substituents have les s than twice the e f f e c t of one (c) the e l e c t r o n e g a t i v i t y corrections are based on <|> = 120° (which i s not correct i n e i t h e r conformation), and vary with <j>. Cd) aromatic decoupling was not used, leading to large errors (up to 1.0 cps.) i n measuring spectra. As a r e s u l t of these drawbacks i s not equal to (which i t ought to by symmetry) and some u n l i k e l y high values of are obtained. No j conclusions were drawn regarding the degree of pucker of the r i n g . In t h i s t hesis a trans-1,2-disubstituted indane which has a f l u o r i n e atom as one of the substituents i s studied. With the known 3 dependence of J upon e l e c t r o n e g a t i v i t y and dihedral angle (gained from the n r model compounds studied h e r e i n ) , the degree of pucker can be determined with 3 f a i r accuracy. Values of J can then be used to estimate the p o s i t i o n of the conformational equilibrium. -16-II SYNTHESES OF FLUORINATED DERIVATIVES In t h i s s e c t i o n , the syntheses of various f l u o r i n a t e d d e r i v a t i v e s are reported, with a view to the o v e r a l l p i c t u r e . The d e t a i l s of i n d i v i d u a l r e a c t i o n s , together with N.M.R. spectra are given i n the Experimental s e c t i o n . The compounds described i n Parts A and B were i s o l a t e d i n the pure form and characterized, with considerable d i f f i c u l t y " ; t h i s was necessary as an e n t i r e l y new reaction'sequence was involved here. On the other hand, the acenaphthyl f l u o r i d e s described i n Part C 1 19 were characterized only by t h e i r H and F N.M.R. spectra,, and thus t h e i r i d e n t i f i c a t i o n may appear to r e s t on shakier ground. However, i n each case the r e a c t i o n involved allows a very l i m i t e d range of possible monomeric products; thus, with the N.M.R. data of Parts A and B i n mind, there i s no 1 19 ambiguity at a l l i n assigning structures purely on the basis of H and F N.M.R. spectra and (sometimes) chromatographic behaviour. Nevertheless, there i s no attempt here to present the products noted i n Part C as being the whole story of the respective r e a c t i o n s . The object of the exercise, as d i s t i n c t 3 from that of Parts A and B, i s purely to obtain values of Jf from i d e n t i f i -nr * able s t r u c t u r e s . F i n a l l y , i t should be noted that each of the products i n Part C i s a new compound, as f a r as i s known. _ *With the exception of the indane d e r i v a t i v e s which were just too unstable to be handled i n the pure s t a t e . - 1 7 -A Addition of IF and BrF to some alkenes (1) Cyclohexene Trans-l-fluoro-2-iodocyclohexane was prepared i n e s s e n t i a l l y quantitative y i e l d by slowly adding a d i l u t e s o l u t i o n of I^ i n benzene to a s t i r r e d suspension of AgF i n cyclohexene and benzene. The product had 22 i d e n t i c a l N.M.R. spectra with that prepared by the Bowers method. The 'trans' r e l a t i o n of the substituents i s shown c l e a r l y i n the N.M.R. spectra, which are discussed i n some d e t a i l i n Section III of t h i s t h e s i s . Several c r i t i c a l conditions were necessary f o r the success of the r e a c t i o n : (a) The iodine must be f u l l y dissolved i n benzene before addition. (b) The cyclohexene must also be d i l u t e d with benzene. (c) The i n i t i a l a d d i t i o n of the I^/benzene s o l u t i o n must be very slow; i . e . the s o l u t i o n should never a t t a i n a permanent iodine colour. (d) The AgF must be dry and f i n e l y d ivided, ( i t i s hygroscopic). The condition of the AgF i s the key to the r e a c t i o n . I f a trace of iodine colour was allowed to p e r s i s t ( i . e . by too r a p i d addition or i n s u f f i c i e n t a g i t a t i o n ) the AgF was apparently deactivated and the r e a c t i o n would not proceed. ( S i m i l a r to the 'poisoning' of a c a t a l y s t ) . However, once -the r e a c t i o n was st a r t e d (say 10% of the iodine had been added), i t proceeded very much f a s t e r , and the remaining iodine could be added much more quickly. Seemingly, the r e a c t i o n was i n one sense a u t o c a t a l y t i c . The a d d i t i o n of BrF to cyclohexene was also c a r r i e d out success-f u l l y , again producing a 'trans' product. However t h i s r e a c t i o n d i f f e r e d s i g n i f i c a n t l y from the IF r e a c t i o n , and i n p r a c t i c e i s more d i f f i c u l t to carry out. P r i m a r i l y , the condition of the AgF was f a r more c r i t i c a l i . e . i t had to be absolutely dry, otherwise the dibromide i s formed. However, given i-18-FLOW SHEET 1 F H -19-dry AgF, the Br^ could be added somewhat more quickly than could I and the a u t o - c a t a l y t i c nature of the r e a c t i o n was not quite so obvious. For AgF that was apparently too moist f o r the BrF r e a c t i o n , i t was sometimes possible to carry out the r e a c t i o n by f i r s t adding I f o r i n i t i a t i o n purposes. It became evident, from l a t e r analysis of the products, that the appearance of large q u a n t i t i e s of a voluminous p r e c i p i t a t e (AgF-Agl) was a sure sign of a s u c c e s s f u l r e a c t i o n . Two possible r a t i o n a l i z a t i o n s can be given f o r the above observa-tions : (a) The a c t i v i t y of the surface of the AgF i s increased during the r e a c t i o n . (eg, an unreactive layer i s s t r i p p e d o f f ) or (b) A product of the r e a c t i o n (eg. AgF'AgI) i s capable of taking part i n the r e a c t i o n . The r e l a t i v e d i f f i c u l t y of the BrF r e a c t i o n (compared with the IF) can be explained by r e a l i s i n g that the formation of the BrF product must be extremely f a s t i f i t i s to prevent the formation of the stable dibromide. Experimentally, one can v e r i f y the speed of the dibromide formation, and i n r e t r o s p e c t , i t i s s u r p r i s i n g that 100% BrF product can be obtained. In f a c t t h i s strongly suggests that the Br^ molecules are being blocked o f f from t h e i r normal mode of a d d i t i o n , eg. there i s some kind of complexing taking place. At l e a s t four species present i n t h i s r e a c t i o n are known to be t capable of complexing, i . e . bromine, benzene, cyclohexene and Ag , and just which species i s complexing to which i s impossible to p r e d i c t . The hetero-geneous nature of the r e a c t i o n i s a major complicating f a c t o r . ,(2) 3,3,6 ,6-Tetradeutero-cyclohexene For the purposes of a conformational study, (see Section I I I ) , the IF r e a c t i o n was also performed on t h i s s p e c i f i c a l l y deuterated cyclohexene. The deuterated product, cyclohexane IF-d (I-d ), has a much simpler N.M.R. -20-spectrum than does the undeuterated m a t e r i a l , ( I ) , and more information can therefore be extracted by the use of t h i s compound. The r e a c t i o n was performed on a small s c a l e , and the crude product used without f u r t h e r p u r i f i c a t i o n or i d e n t i f i c a t i o n ; no impurities were 1 19 detectable i n e i t h e r the H or the F N.M.R. spectrum, thus confirming the quantitative nature of the r e a c t i o n . (3) Methylene cyclohexane, Indene, and Styrene These three alkenes s i m i l a r l y underwent BrF and IF additions and demonstrate the general u t i l i t y of the r e a c t i o n . In each case the f l u o r i n e was found to be present at the more substituted p o s i t i o n . The N.M.R. spectrum of the indane BrF adduct i s discussed i n Section V, f o r conformational purposes. B XF additions to acenaphthylene (1) BrF Additions ( i ) In benzene s o l u t i o n : As described i n the previous s e c t i o n , the a d d i t i o n , of 'BrF'.and of 'IF' to a 'normal' alkene proceeds smoothly and q u a n t i t a t i v e l y i n benzene s o l u t i o n . Attempts to extend t h i s r e a c t i o n to acenaphthylene were at f i r s t unsuccessful; 'BrF' addition i n benzene s o l u t i o n r e s u l t e d i n the production of no *BrF' adduct, but instead a low y i e l d of the c i s and trans d i f l u o r i d e s (IX, X). The major product of the r e a c t i o n contained no f l u o r i n e and was high melting; furthermore, i t was f a r les s soluble ~in the common organic solvents than the majority of acenaphthene d e r i v a t i v e s . I t was not i n v e s t i -gated further but presumed to be some kind of polymeric material. In addition to these products, there were also two others, both i n 19 trace q u a n t i t i e s , which were observed i n the F N.M.R. spectrum of the crude product. One was l a t e r shown to be 1-fluoro-acenaphthylene (XI), and the -21-FLOW SHEET 2 I 2 + A g F C H C N 3 H , II p o l y m e r F F I 2 + A g F C H C N / C H ( 6 0 - 9 0 % C H ) i -IX I O % 1 H F F + B r 2 + A g F C H 3 C N XIV Br F XIII - F I °/o H F XI B r 2 - + - A g F C H C N / C _ H o 6( o F F + IX Br H F F H + XII XI -22-other the 'BrF' adduct of t h i s compound, i . e . l-bromo-2,2-difluoro-acenaphthene (XII), (designated hereafter as the 'BrF^ adduct'). ( i i ) In a c e t o n i t r i l e s o l u t i o n : I f , however, the r e a c t i o n was 50/50 benzene/acetonitrile*, a quantitative y i e l d of the trans 'BrF' product (XIII) r e s u l t e d . Increasing proportions of benzene i n the solvent produced a mixture of a l l three p r o d u c t s — t r a n s BrF, c i s and trans d i f l u o r i d e s - - a s well as the ubiquitous polymeric m a t e r i a l . A l t e r i n g the time of the r e a c t i o n seemed to have some e f f e c t on the r e l a t i v e amounts, but t h i s was not fur t h e r investigated. An important r e s u l t was obtained at t h i s time; i t was not possible to convert the 'BrF' product to d i f l u o r i d e using AgF, with e i t h e r benzene. or a c e t o n i t r i l e as solvent. However, addi t i o n of Br^ to acenaphthylene 4 4 produced only trans-dibromide, confirming C r i s t o l ' s r e s u l t , and subsequent shaking with AgF y i e l d e d only trans-BrF (XII I ) . The second bromine atom i s d e f i n i t e l y more strongly held than the f i r s t , but the f a c t that even one i s exchangeable indicates a marked departure from the cyclohexene case; t h i s i s discussed below. (2) IF Additions Reactions of I + AgF with acenaphthylene were s i m i l a r to those with Br^ + AgF, but with one important d i f f e r e n c e : Any IF product, i f i t ever exist e d , was too unstable to be i s o l a t e d and led to fur t h e r products. In benzene, the major f l u o r i n a t e d products were once again the c i s and trans d i f l u o r i d e s , and i n low y i e l d . Trace q u a n t i t i e s of fluoro-acenaphthylene and the IF^ adduct (XIV) were also observed, and i s o l a t e d . With increasing quantities of a c e t o n i t r i l e i n the solvent, le s s of the above products are observed, and the best y i e l d s are obtained i n 80% to "Acenaphthylene dissolved i n benzene/acetonitrile, but Br^ added as a benzene s o l u t i o n . -23-90% benzene* Below 50% benzene, none of these compounds are formed i n 19 s u b s t a n t i a l quantities but other f l u o n n a t e d products are observed i n the F N.M.R. spectrum; however, they decomposed with every attempted i s o l a t i o n (such as column chromatography). From the chemical s h i f t and m u l t i p l i c i t y of the 19 . F N.M.R. spectrum, i t was evident that the unknown products could well contain a trans-IF adduct, which would be expected to be very unstable indeed.** The r a t i o of c i s : t r a n s d i f l u o r i d e s - was found to be close to 1:2, and e s s e n t i a l l y independent of solvent, i n the range 40/60 benzene/acetonitrile to pure benzene. , F i n a l l y i t was observed that a number of other compounds were formed 19 i n trace q u a n t i t i e s , and from the pattern of t h e i r F N.M.R. spectrum they appeared very s i m i l a r to the t r a n s - d i f l u o r i d e , but a l l with s l i g h t l y d i f f e r e n t . chemical s h i f t s . The o r i g i n of these absorptions was not known, but the p o s s i b i l i t y of aromatic s u b s t i t u t i o n might be considered. (3) Mechanisms The anomalous r e s u l t s obtained with 'XF' additions to acena-phthylene can be a t t r i b u t e d to the increased r e a c t i v i t y brought about by the aromatic system. This r e a c t i v i t y , which i s apparent i n many of the reactions of acenaphthylene, i s well i l l u s t r a t e d by the e f f e c t of AgF on 1-bromo-acenaphthene, 1-bromo-indan, and bromo-cyclohexane r e s p e c t i v e l y . As shown i n the following sections, the acenaphthene d e r i v a t i v e i s converted to the f l u o r i d e i n minutes, whereas the indan compound requires twenty-four hours f o r the same r e a c t i o n , and bromo-cyclohexane i s unreactive. S i m i l a r l y , t h i s same r e a c t i v i t y of acenaphthene systems i s responsible f o r the extremely *volume measurement **0bserved order of s t a b i l i t y of BrF adducts: Cyclohexane > indan > acenaphthene and: Cyclohexane BrF >> Cyclohexane IF, and even more so f o r the indan p a i r . -24-f a c i l e decomposition of nearly a l l acenaphthene halides and f l u o r i d e s (at bridge p o s i t i o n ) . 'BrF' additions to cyclohexene i n a c e t o n i t r i l e s o l u t i o n produce no f l u o r i n a t i o n whereas those i n benzene do. On the other hand, 'BrF' additions to acenaphthylene i n a c e t o n i t r i l e s o l u t i o n y i e l d s a clean f l u o r i n a t i o n , and those i n benzene s o l u t i o n give some d i f l u o r i n a t i o n and sponsor several other side reactions besides. The inference i s c l e a r that benzene i s i n some way enhancing the r e a c t i v i t y of the acenaphthene system. Considering f i r s t the 'BrF' reactions i n a c e t o n i t r i l e s o l u t i o n there appear to be two possible routes. One would involve attack of f l u o r i d e ion upon a bromonium io n , or something s i m i l a r , i n the cyclohexene r e a c t i o n , and the other formation of dibromide intermediate and subsequent exchange. In view of i t s demonstrated f e a s i b i l i t y , the second sequence must be considered a p o s s i b i l i t y , however, there i s some a d d i t i o n a l experimental evidence that i n f a c t the p r e v a i l i n g r e a c t i o n sequence i s the former one i . e . not in v o l v i n g the dibromide as intermediate. This extra evidence i s the p h y s i c a l appearance of the s i l v e r s a l t s produced; i n the case of cyclohexene, e t c . , the addition of 'XF' i s always accompanied by a voluminous p r e c i p i t a t e , (usually f i l l i n g the re a c t i o n v e s s e l ) , which assumes c h a r a c t e r i s t i c colours during the r e a c t i o n . Exactly t h i s sort of phenomenon was observed during the addition of 'XF' to acena-phthylene, i n benzene or a c e t o n i t r i l e . This i s i n sharp contrast to the p h y s i c a l appearance of the s o l u t i o n and p r e c i p i t a t e i n an exchange rea c t i o n (eg. r e a c t i o n of dibromide, gem-bromo-fluoride (XV), or bromide (XXIV) with AgF), where a very much smaller amount of a l i g h t - g r e y p r e c i p i t a t e (presumably AgBr) i s formed. Thus i t appears that the AgF e i t h e r reacts d i r e c t l y with the bromine as i t i s added, or else i t reacts with something akin to a bromine ion -25-intermediate of acenaphthene; the reason why the other sequence (dibromide formation and exchange) probably does not contribute s i g n i f i c a n t l y to the reac t i o n i s that i t doesn't have time. The addi t i o n of bromine to acenaphthylene to form dibromide is.demonstrably slow. Turning now to the rea c t i o n i n benzene s o l u t i o n , i t i s not obvious j u s t how the d i f l u o r i d e s are formed. The s u r p r i s i n g f a c t that the trans-BrF adduct ( X I I I ) , cannot be converted i n t o d i f l u o r i d e (IX, X), with ordinary AgF, means one of two things: (1) An 'activated' form of AgF, such as i s possibly generated i n the rea c t i o n of Br^ + AgF, i s required f o r the formation of the d i f l u o r i d e s . Or (2) The course of the rea c t i o n i s changed before the BrF adduct has had a chance to f o r m — t h i s seems more l i k e l y , since the v a r i e t y of other products formed i n benzene s o l u t i o n seems to indic a t e some sort of d r a s t i c change i n the nature of the re a c t i o n , C Other acenaphthyl f l u o r i d e s The unexpected products obtained with the XF rea c t i o n with acenaphthylene suggested that many other acenaphthyl f l u o r i d e s could be obtained by a s e r i e s of simple re a c t i o n s , c h i e f l y u t i l i z i n g fluoro-acena-phthylene; such compounds would provide the necessary data to determine the 3 e f f e c t of e l e c t r o n e g a t i v i t y on J u r , . nr (1) Fluoro-acenaphthylene (XI) This compound was prepared by the method described by M e r r i t t and 24 Johnson , i . e . e l i m i n a t i o n of HF, using a r e f l u x i n g s o l u t i o n of KOH m ethanol, from e i t h e r the c i s or the trans d i f l u o r i d e of acenaphthene. The y i e l d from t h i s r e a c t i o n was found to be les s than q u a n t i t a t i v e , and i t was necessary to recycle the recovered s t a r t i n g m a t e r i a l . (2) Products from fluoro-acenaphthylene ( i ) Addition of HC1 or HBr, followed by AgF exchange: -26-' Addition of HC1 or HBr gas to a s o l u t i o n of fluoro-acenaphthylene (at -78°C) y i e l d e d the corresponding gem-CIF (XVI) and gem-BrF (XV) adducts; i n neither case was any v i c i n a l product observed. Shaking e i t h e r of these compounds with AgF powder i n a c e t o n i t r i l e s o l u t i o n at room temperature produced the gem-difluoride (XVII). Addition of HI, instead of HC1 or HBr, produced only decomposition, even at -78°C. ( i i ) BrF Addition: Using i d e n t i c a l conditions as f o r acenaphthylene i t s e l f (Part B ( 1 ) ) , bromine was added to a s t i r r e d suspension of powdered AgF i n a s o l u t i o n of fluoro-acenaphthylene. In ad d i t i o n to smaller quantities of two uniden-t i f i e d products, the main f l u o r i n a t e d m a terial was the expected BrF^ adduct (XI I ) , i d e n t i c a l s p e c t r o s c o p i c a l l y with the trace material i n the e a r l i e r r e a c t i o n (with acenaphthylene, see part B). However, the y i e l d was not high. ( i i i ) IF Addition: The analogous r e a c t i o n between I^, AgF and fluoro-acenaphthylene produced only s t a r t i n g m a t e r i a l ; t h i s rather s u r p r i s i n g r e s u l t then posed an i n t e r e s t i n g question, how did the IF^ adduct form i n the o r i g i n a l reaction? A l l that can be s a i d at present i s that the r e a c t i o n conditions were d i f f e r e n t , or else there i s another r e a c t i o n sequence. ( i v ) B r 2 Addition: When elemental bromine was added to fluoro-acenaphthylene, i n e i t h e r CC1 or CH CN s o l u t i o n , both c i s and trans products (XVIII, XIX), ( i . e . Br atoms c i s or t r a n s ) , were observed; the r a t i o of c i s / t r a n s was measured to be l l % / 8 9 % . (v) IC1 Addition: Analogous treatment of fluoro-acenaphthylene with an IC1 s o l u t i o n , i n CCl^, gave very s i m i l a r r e s u l t s , i . e . c i s and trans products (XX, XXI) i n the r a t i o 16%/8i4%. (Here the notation c i s / t r a n s r e f e r s to the I and CI atoms). ' FLOW SHEET 3 ( 1 6 % ) XX I H F CI (84%) XXI Br H Br F Br H" F ' Br ( 1 1 % ) . XVIII (89%) XIX I C I , C C ! 4 X 2 0 ° C B r , C C L 2 0 ° c F H H F v_v CIS Or T R A N S IX X H K O H , E t O H A HI P e n t a n e - 7 8 ° C / D E C O M P O S I T I O N XI H B r , H C I P e n t a n e - 7 8 ° c H H X F XV, XVI 7 ft A g F C H 3 C N 2 0 ° C • H H F F B r 2 + A g F C H X N , 0 0 C I 2 + A g F C H 3 C N o ° c Br H F F XII N O R E A C T I O N -28-FLOW SHEET 4 I C l / A g F 2 0 ° C b H 3 C N CI + 8 5 % XXIII CL V A F CI 15% XXII Br H B r , P e n t a n e - 7 8 % / A g F , C H 3 C N 2 0 0 C J XXIV XXV -29-Some apparently anomalous additions have been observed with acenaphthylene by several other workers; thus Cl^ addition can be made to go c i s or trans, depending on reagents, whereas only a trans dibromide i s 44 45 known . Furthermore, HBr and HC1 add i t i o n has been shown to go 75-90% c i s 4 4 However, i t seems not impossible that e a r l i e r workers , might have missed a small quantity of a minor product, such as a cis-dibromide, f o r example. (3) C i s - and Trans-CIF Adducts (XXII, XXIII) These compounds were prepared by 'XF' add i t i o n to acenaphthylene, i n the usual manner, but using IC1 and AgF, i n CH^CN s o l u t i o n . Once again, the trans-adduct predominated, (85%), but the proportion of the c i s isomer was quite r e v e a l i n g , f o r t h i s i n d i c a t e d that the reaction might a c t u a l l y be proceeding through the intermediate IC1 adducts (see flow sheet 4). Thus the mechanism f o r t h i s r e a c t i o n may be d i f f e r e n t from the one operating i n the case of XF add i t i o n to cyclohexene and the other 'normal' alkenes. An a d d i t i o n a l product, which was f u l l y characterized,'was the trans-d i c h l o r i d e ; i t i s not hard to v i s u a l i z e some reaction- scheme whereby t h i s product could a r i s e , (such as exchange of an I atom f o r a CI), and t h i s can be taken as supporting evidence f o r the mechanism proposed f o r t h i s r e a c t i o n . (4) Acenaphthene f l u o r i d e (XXV) Following the procedure of Dewar and Fahey, acenaphthene bromide 45 (XXIV) was synthesized from acenaphthylene and HBr ; t h i s compound r e a d i l y exchanged i t s bromine atom f o r a f l u o r i n e of AgF, i n a c e t o n i t r i l e s o l u t i o n at room temperature. Unfortunately, t h i s r e s u l t i n g f l u o r i d e was extremely unstable, and a l l attempts at p u r i f i c a t i o n or i s o l a t i o n r e s u l t e d i n decompo-s i t i o n ; thus i t 'was found impossible to run the compound on any a v a i l a b l e chromatographic apparatus, ( i . e . a c i d , n eutral or basic s i l i c a g e l or alumina on e i t h e r columns or p l a t e s ) . A d d i t i o n a l l y , i t was decomposed by washing with a weakly basic aqueous s o l u t i o n , and also by warm chloroform f o r example. -30-Th e mode of decomposition i s an i n t e r e s t i n g subject i n i t s e l f ; there was no charring or l i b e r a t i o n of noxious fumes, such as accompanied the auto-c a t a l y t i c decomposition of the 'XF' adducts. Furthermore, addition of s o l i d Na CO to an organic s o l u t i o n of acenaphthene f l u o r i d e did not seem to s t a b i l i z e the l a t t e r s i g n i f i c a n t l y , whereas i t d i d have a marked e f f e c t i n s t a b i l i z i n g acenaphthene BrF (XIII) f o r example. Therefore i t seems that the l a t t e r c l a s s of compounds ( i . e . v i c i n a l XF adducts) are subject to a c i d -catalyzed decomposition, whereas acenaphthene f l u o r i d e (and the gem-XF compounds (XV, XVI) which behaved s i m i l a r l y ) have an e n t i r e l y d i f f e r e n t mechanism a v a i l a b l e to them f o r decomposition. • -31-III CONFORMATIONAL ANALYSIS OF CYCLOHEXANE IF A N.M.R. Spectra (1) At room temperature The spectrum of the IF adduct of cyclohexene (I) consists of two regions; ( i ) 5T- 6T, showing resolvable f i n e structure and assignable to the methine protons; and ( i i ) a high f i e l d region, of poorer r e s o l u t i o n , which integrates to four times the area of ( i ) . This spectrum w i l l not be -32-considered f u r t h e r , owing to the greater s i m p l i c i t y of I-d^, which i s the IF adduct of cyclohexene-3 ,3 ,6 ,6-d^. Part of the "'"H N.M.R. spectrum of the crude product I-d^ i s shown i n Figure IA; Figure IB shows the same spectrum with i r r a d i a t i o n of the 1 2 deuterium n u c l e i to remove H- D coupling. This spectrum i s now c l e a r l y the AB part of an ABX", and the 8 cps. coupling, J , between the two protons i s d^g- This large v i c i n a l 1H-"'~H coupling indicates that H and are d i a x i a l , and hence trans to one another. This immediately i d e n t i f i e s the primary conformation of the molecule as that, having both the Br and F substituents e q u a t o r i a l l y oriented. 19 The room temperature F spectra of both I and I - d ^ consist of 2 broad doublets spacing approximately 50 cps., corresponding to J^ps a n ( i l i t t l e information can be gained from them alone. (2) At low temperatures (a) spectra 1 2 The H spectrum (with D-decoupling) of i n s o l u t i o n at -100°C i s shown i n Figure 2A; here the two chair conformations of the molecule have been 'frozen out' i . e . the rate of c h a i r - t o - c h a i r conversion i s now slower than the N.M.R. t r a n s i t i o n time, and two ABX spectra are observed. The small J._ of 3 cps. (J" n ) i n the l o w - f i e l d (minor) conformer, i d e n t i -AB le,2e f i e s t h i s as the one i n which the protons are d i e q u a t o r i a l i . e . the substituents are d i a x i a l . D 2 *Also there i s some long-range coupling to be seen i . e . , which fo r some reason, i s l a r g e r than ^. ' F i g . 1: H spectrum of cyclohexane IF-d at room temperature., (bottom) Single resonance spectrum. 2 (top) Double resonance spectrum; i r r a d i a t i o n of D. F i g . 2: H spectrum of cyclohexane IF-d at -100°C. (top) Experimental. (bottom) Calculated. Each o f t h e s e tv?o ABX s p e c t r a were a n a l y z e d w i t h o u t u s i n g t h e X par t * , * t h i s a n a l y s i s y i e l d s t h e v a l u e s o f t h e v a r i o u s c o u p l i n g c o n s t a n t s i n each c o n f o r m e r a t -100°C, i n C S 2 s o l u t i o n . A c a l c u l a t e d c o m p o s i t e s p e c t r u m , b a s e d on t h i s a n a l y s i s i s shown i n F i g u r e 2B. U s i n g t h e s e v a l u e s , t h e p o s i t i o n o f t h e c o n f o r m a t i o n a l e q u i l i b r i u m a t room t e m p e r a t u r e may be c a l c u -l a t e d from t h e v a l u e o f t h e c o u p l i n g c o n s t a n t s i n t h e t i m e - a v e r a g e d s p e c t r u m ( o b t a i n e d a t room t e m p e r a t u r e ) , F i g u r e 1. F u r t h e r m o r e , t h e p o s i t i o n o f t h e e q u i l i b r i u m may a l s o be d e t e r m i n e d i n o t h e r s o l v e n t s by use o f t h e s e l o w - t e m p e r a t u r e v a l u e s ; t h e s p e c t r u m o f I - d ^ i n b e n z e n e , c h l o r o f o r m , a c e t o n e , and pentane were t h e r e f o r e o b t a i n e d , and t h e r e s u l t s a r e summarized i r i T a b l e I. A l s o shown a r e e q u i l i b r i u m c a l c u l a -t i o n s b a s e d on t h e "Hi c h e m i c a l s h i f t s . " " 19 (b) F s p e c t r a 19 The " F s p e c t r u m o f I i n CS^ s o l u t i o n a t -100°C i s shown i n F i g u r e 3B, and f o r c o m p a r i s o n t h e room t e m p e r a t u r e s p e c t r u m i s shown below i t , F i g u r e 3A. The s e p a r a t e r e s o n a n c e s o f each c o n f o r m e r can be seen i n t h e " I t i s p o s s i b l e t o a n a l y z e an ABX s p e c t r u m p u r e l y from t h e AB p a r t i f one i s a b l e t o a s s i g n t h e l i n e s i n t h e AB p a r t c o r r e c t l y , ( t h e r e a r e two c h o i c e s ) . To do t h i s , i t i s n e c e s s a r y Jjo have some p , r i o r knowledge o f and J g ^ - I n t h i s c a s e , t h e g e m i n a l H- F c o u p l i n g , J y F ( - J ^ ) , gan s a f e l y be assumed t o be a p p r o x i m a t e l y 50 c p s . , and ^he v i c i n a l c o u p l i n g J ( = J„„) can be assumed t o be o f t h e same s i g n as J H F » b u t c o n s i d e r a b l y s m a l l e r A l l t h e s e p a r t i a l ABX s p e c t r a were s u b j e c t e d t o i t e r a t i v e computer a n a l y s i s , u s i n g TWOSUM (see A p p e n d i x A ) ; i n o r d e r t o l i n k up t h e e nergy l e v e l s , i t i s n e c e s s a r y t o put i n a ' f a l s e ' X - t r a n s i t i o n , t h e f r e q u e n c y o f w h i c h may be c a l c u l a t e d from t h e AB p a r t , w i t h t h e above c o n s i d e r a t i o n s i n mind. " " A l l o f t h e s e c a l c u l a t i o n s assume t e m p e r a t u r e independence o f t h e r e s p e c t i v e p a r a m e t e r s ; t h i s i s d i s c u s s e d f u r t h e r l a t e r on. -35-u'vBLE I ar; . • a n o u s olvent CDC1„ . Pentane Benzene . Acetone CS CS 9 CS ° Room Temp. -100'"C'C -100°C Diequat. Diax. arameter AB ):iaxial 1.315 7.760 8.423 8.845 7.852 10.063 3.027 J / v X 47.562 47.502 47.664 47.825 47.635 57.596 67.463 'J < 7.577 7.598 7.346 7.155 7.423 6.089 9.922 ^ 547.053 550.148 571.217 548.419 554,442 565.350 518.412 v.- 591,098 591,929 620.868 585.688 596.727 613.869 555.078 Average Deviation 0.043 0.059 0.012 0.014 0,022 0.019 0.046 by / J J „ t I 25.0 32.8 23.4 . 17.3 31,4 3 J i n ? 38.9 34.3 28.5 27.8 34.3 Mr v A 23.2 A v B 27.2 - 3 7 -F i g . 3: 1 9 F spectrum of cyclohexane IF. (A) Room temperature; (B) -100°C; (C) Expansion of minor resonance i n B. Chemical s h i f t s are r e l a t i v e to CFC1„ ( i n t e r n a l ) . l o w - t e m p e r a t u r e spectrum., and t h e expanded s p e c t r u m c f t h e m i n o r c o n f o r m e r i s shown i n F i g u r e 3C; t h i s r e s o n a n c e e x h i b i t s a second l a r g e s p l i t t i n g , 1 19 ( b e s i d e s tnat due t o t h e g e m i n a l H- F c o u p l i n g ) o f a p p r o x i m a t e l y 43 cps. w h i c h can be a s s i g n e d t o a d i a x i a l °J T I P. T h i s i s c o n f o r m a t o r y e v i d e n c e t h a t iiL t h e m i n o r .conf ormer i s t h e d i a x i a l one. I 19 U s i n g H - d e c o u p l i n g , the. F s p e c t r a o f i was r e c o r d e d m CS^ s o l u t i o n a t v a r i o u s t e m p e r a t u r e s between 0°C and -85°C. With "*"H c o u p l i n g s r emoved 5 t h e m a j o r c o n t r i b u t i o n t o t h e l i n e w i d t h i n t h i s r e g i o n i s t h e exchange broadening. B y m e a s u r i n g t h i s latter" q u a n t i t y as a f u n c t i o n o f t e m p e r a t u r e , i n f o r m a t i o n can be deduced about t h e r a t e o f c o n f o r m a t i o n a l i n v e r s i o n , v.'hich i s d i s c u s s e d l a t e r on. The w i d t h s and p o s i t i o n s o f v a r i o u s r e s o n a n c e s from t h e s e s p e c t r a a r e g i v e n i n T a b l e I I A . I t can be seen t h a t a t e i t h e r end o f t h e t e m p e r a t u r e scale> t h e peak p o s i t i o n s a r e n o t s t a t i c ; t h i s was c o n t r a r y t o r e s u l t s a l r e a d y i n t h e l i t e r a t u r e and t h e r e f o r e t o c o n f i r m i t ; t h e low t e m p e r a t u r e 1 , . . s p e c t r a were l a t e r r e - t a k e n , b u t w i t h o u t H - d e c o u p l i n g . T h i s d a t a i s a l s o i n c l u d e d i n T a b l e I I A ; t h e r e i s a d i f f e r e n c e i n t h e a b s o l u t e v a l u e o f t h e peak p o s i t i o n s o f t h e two s e t s o f d a t a ( d e c o u p l e d and s i m p l e s p e c t r a ) . T h i s i s because d i f f e r e n t samples were used;, t h e o r i g i n a l one h a v i n g decomposed. B C o n f o r m a t i o n a l e q u i l i b r i u m ( 1 ) C o u p l i n g C o n s t a n t s U s i n g ^J r i r, t h e f r a c t i o n o f I-d., e x i s t i n g i n t h e d i a x i a l c o n f o r m a t i o n t> HH 4 ° 3 i s c a l c u l a t e d t o be .314; from v a l u e s o f J t h e f r a c t i o n i s .348. These Hi c a l c u l a t i o n s a p p l y t o CS^ s o l u t i o n a t ambient t e m p e r a t u r e . From e q u a t i o n (1) 5 .page 7. t h e s e numbers l e a d t o v a l u e s , o f AG° = 0.478 k c a l . / m o l e and AG° - 0 .,'397 k c j i l . / m o l e r e s p e c t i v e l y ; t h e d i f f e r e n c e between t h e s e numbers may r e p r e s e n t a s y s t e m a t i c ' error i n t h e 'method, I n -39-TABLE IIA F Spectra of Cyclohexane IF as a Function of Temperature Temp. °K Hi-decoupled Spectra Simple Spectra Major Peak Minor Peak Major Peak Minor Peak P o s i t i o n i Width P o s i t i o n 273 i 14,920.0 ! 5.0 263 908.0 j 9.5 i 258 902.6 i 13.5 253 896.2 ! 20 248 889.5 ! 29 243 882.5 ' 36 j 238 871.0 i 55 233 858.0 [ 89 228 82.5.5 1 114 223 792.5 ! 86 218 764.0 1 69.5 i 213  i 14,711 15,213 208 746.5 ' 21.4 15,264 704 221 203 1 ! 701 227 198 736.5 [ 5.6 265.5 695 227 193 [ 693 224 188 14,727.5 ! '260.5 689 222 183 i i 684 219 178 (frozen sample) 15,253.5 14.678 215 TABLE IIB Area Measurements Decoupled Simple Diequatorial D i a x i a l •Diequatorial D i a x i a l 183° K 85.0% 15.0% 1 15.25% 84.75% Notes: (a) Peak posit i o n s are u p f i e l d of CFC1„ resonance ( i n t e r n a l ) . (b) Two d i f f e r e n t samples were used, one f o r the data on the l e f t hand side of Table IIA ( i . e . H-decoupled spectra) and the data i n Table IIB, and the other f o r the data on the right-hand side of Table IIA, (simple spectra). The f i r s t was approximately 20% i n CS^ s o l u t i o n (by volume), but the second one was more d i l u t e , to permit more lengthy low-temperature measurements. -40-p a r t i c u l a r a temperature dependence of the coupling constants, or i t may just r e f l e c t the inaccuracy of experimental data. I t i s worth noting that an er r o r 3 of only 0.4 cps. i n the value of i n e i t h e r conformer would account f o r the d i f f e r e n c e , and the spectrum of the d i a x i a l conformer i s rather d i f f i c u l t to measure accurately (see Figure 2A). 3 To be more s p e c i f i c , the f i r s t - o r d e r value of J„ taken from the nr 19 low-temperature F spectrum of I (Figure 3 C ) i s a c t u a l l y 11 cps., 1.1 cps. more than the value c a l c u l a t e d from the low-temperature "Hi spectrum (Figure 3 A ) . Thus t h i s inaccuracy of measurement appears to be a most l i k e l y source of e r r o r . It i s i n t e r e s t i n g at t h i s point to consider some s i m i l a r work by 46 Anet who used a s p e c i f i c a l l y - d e u t e r a t e d cyclohexanol and i t s associated reference compounds ( c i s - and trans-4-t-butyl d e r i v a t i v e s ) . From the various observed coupling constants, two independent c a l c u l a t i o n s of the p o s i t i o n of the equilibrium can be made ( s i m i l a r to above); the f r a c t i o n of the minor conformer i s r e s p e c t i v e l y c a l c u l a t e d as 0.16 and 0.29. The reason f o r t h i s discrepancy was not given. However, i t seems possible that there i s an appreciable temperature dependence of the coupling constants involved i n both Anet"s work and the present study. Turning to solvents other than C S 2 , the data i n Table I indicates that f o r solvents which are non-polar l i k e CS^ ( i . e . pentane, benzene) the 3 3 agreement between J and J o r , c a l c u l a t i o n s i s reasonable, whereas f o r the Hn nr polar solvents acetone and chloroform, the agreement i s quite poor. In f a c t , 3 3 " -the gap between J u u and J c a l c u l a t i o n s i s too large to be a t t r i b u t a b l e HH nr to experimental err o r (14% f o r chloroform) and t h i s seems to i n d i c a t e that the coupling constants are subject to a solvent dependence. 47 There i s c e r t a i n l y some precedent f o r t h i s phenomenon; thus Stothers determined the e q u i l i b r i a of 2-halocyclohexanones by comparison with the -41-spectra of the c i s and trans-4-t-butyl derivativesand used | d A X + a s well as chemical s h i f t s . A v a r i e t y of solvents were t r i e d , and + Jg^j i n the c i s compound was found to vary from 5.7 cps. ( i n cyclohexane) to 7.1 cps. ( i n a c e t o n i t r i l e ) . (2) Areas 19 By i n t e g r a t i n g the i n d i v i d u a l peaks of the low-temperature F spectrum (eg. Figure 3B), the f r a c t i o n of I i n d i a x i a l form was c a l c u l a t e d as 0.1525 at -90°C; t h i s corresponds to AG° = 0.625 kcal./mole. 19 The areas of the e q u a t o r i a l and a x i a l F peaks were also measured under conditions of ^H-decoupling. The i n t e n s i t i e s of both peaks were increased by about a f a c t o r of two, but the r a t i o stayed approximately constant ( f r a c t i o n d i a x i a l = 0.150, Table IIB). Thus there appears to be a general (and favourable) Overhauser e f f e c t with "''H-decoupling, but i n t h i s case i t i s not s t e r e o s p e c i f i c . 19 (3) F Chemical S h i f t s 19 The F peak po s i t i o n s of I l i s t e d m Table IIA show that from -65°C to -95°C there i s a f a i r l y regular decrease5'5 of 0.9 cps. per °C, and from 0°C to -30°C there i s an average decrease of 1.2 cps. per °C. In the next s e c t i o n , where some t h e o r e t i c a l c a l c u l a t i o n s on exchange phenomena are discussed, i t w i l l be shown that, from exchange considerations alone, the peak p o s i t i o n i s e s s e n t i a l l y i n v a r i a n t of temperature approximately 20°C on e i t h e r side' of the coalescence point; i n t h i s case the coalescence point can r e a d i l y be seen to be approximately -45°C, (from examination of the width of the l i n e at various temperatures). These c a l c u l a t i o n s of when the peak "This r e f e r s to the major, d i e q u a t o r i a l , conformer. - i m -p o s i t i o n s are independent of temperature are .not i n agreement with the 15 19 statement i n reference : "Approximate c a l c u l a t i o n s of the F peak s h i f t vs. temperature ... showed that at temperatures of about 15-20°C and above, the s h i f t has become independent of the rate of conformational change ..." The input parameters f o r t h e i r c a l c u l a t i o n are of course d i f f e r e n t from the present one, but i t can be shown that t h i s doesn't s i g n i f i c a n t l y a l t e r the 15 conclusion. Examination of Table II i n reference shows the same kind of behaviour described here, i . e . the peak posit i o n s continue to move to low f i e l d f a r away from the coalescence point. E v i d e n t l y , e i t h e r the i n d i v i d u a l chemical s h i f t s of the two conformers are temperature dependent, or else the chemical s h i f t of CFC1 3 i s temperature dependent, or both. The l a r g e r temperature dependence above the coalescence point i s expected because the peak p o s i t i o n now depends on the value of K, the equilibrium constant, which i n turn depends on the temperature, AG° being constant. Thus supposing a AG° value of 0.625 kcal./mole*, one may c a l c u l a t e the rate at which K i s changing with temperature: AG° = -RTlnK At 273°K log K = ^ 5 g 2 ^ 2 ? 3 = .499 K = 24.1 % ( d i a x i a l ) = 24.1 At 263° K % ( d i a x i a l ) =23.3 I f the chemical s h i f t between conformers i s 515 cps., ( t h i s i s a r r i v e d at by extrapolating low temperature data, see below), then the time-averaged posi t i o n s at 273°K and 263°K are 124.2 cps. and 120.1 cps. r e s p e c t i v e l y . '''Fortunately, t h i s value i s not c r i t i c a l . -43-Thus the peak p o s i t i o n increases at a rate 0.4 cps. /°K i n t h i s temperature region, given the above assumptions. Using the data i n Table II to estimate the p o s i t i o n of equilibrium requires a quantitative value f o r the temperature dependence of each conformer. For the d i a x i a l conformer t h i s quantity i s not so well defined, because i t i s slower to recover from the exchange e f f e c t s (hence the necessity f o r the extra data i n Table I I ) . However, i t does appear that the temperature depen-dence of the d i a x i a l conformer i s less than that of the d i e q u a t o r i a l ; from Table I I , values of 0.7 cps./°K and 0.9 cps./°K can be taken. Extrapolating the peak po s i t i o n s of each conformer at -85°C to 0°C by these amounts then, the averaged peak p o s i t i o n at 0°C i s 116 cps. from the d i e q u a t o r i a l resonance and 400 cps. from the d i a x i a l . This leads to values . of 22.5% d i a x i a l and AG° = 0.672 kcal./mole (at 0°C). Now combining t h i s value f o r % d i a x i a l along with temperature dependence of the i n d i v i d u a l conformers (0.9 and 0.7 cps./°K), and the temperature dependence of K i t s e l f (0.4 cps./°K, above) we may c a l c u l a t e the net change i n the averaged peak p o s i t i o n = [(.775)0.9 + (0.225)0.7 + 0.4] = 1.25 cps./°K. Observed increase with temperature i s 1.2 cps./°K, which i s reasonable agreement. (4) "Si Chemical S h i f t s Using the chemical s h i f t s of H^ and H^ derived from the low-temperature (-100°C) spectra of 1-d^ y i e l d s values .of 23.2% and 29.2% d i a x i a l r e s p e c t i v e l y at ambient temperature (-35°C). This corresponds to AG 0 values of 0.544 and 0.735 kcal./mole r e s p e c t i v e l y (at 35°C). Variable temperature "*"H spectra were not run, so no c o r r e c t i o n f o r temperature dependence of the 19 chemical s h i f t s could be made, as was done f o r the F spectra; t h i s 31 undoubtedly introduces s i g n i f i c a n t errors , and could well account f o r most of the difference i n values from and . (5) 1 9 F Linewidths 37 Using the general lineshape expression of Gutowsky and Holm , a set of t h e o r e t i c a l spectra may be generated, i n which the residence time x, and the equilibrium constant K may be v a r i e d . For any given value of K, there i s a unique value of x which gives r i s e to the l a r g e s t linewidth; t h i s i s the coalescence point f o r that value of K. Thus the linewidth at the coalescence point i s a function of K, and from the experimental linewidth, a value of K may be deduced. These Gutowsky-Holm c a l c u l a t i o n s are discussed i n more d e t a i l i n part D on rate c a l c u l a t i o n s . 19 1 The F spectra of I, with H-decoupling, can be treated i n t h i s way and the maximum experimental linewidth i s 114 cps. (at 228°K, see Table I I ) ; from the c a l c u l a t e d spectra (see part D), t h i s implies that K = 4.26, which corresponds to AG° = 0.659 kcal./mole. A c r i t i c i s m of t h i s method of deducing K might be that, i n f a c t , the maximum may not have been obtained, since the spectra were recorded at i n t e r v a l s of 5°K, and the linewidth i s a r a p i d l y varying function of temperature. However, t h i s c r i t i c i s m may be countered as follows: ( i ) With a t y p i c a l k i n e t i c b a r r i e r to i n v e r s i o n (say 10 kcal./mole) a temperature increase of 5°K decreases the residence' time, x, by a f a c t o r of approximately 1*.7 (see part D on rate c a l c u l a t i o n s ) . ( i i ) Near coalescence, the linewidth i s a more slowly varying function of temperature and a f a c t o r of 1.7 i n x i s not enough to allow a s i g n i f i -cantly l a r g e r linewidth to come between 89 and 114 cps. (at 233 and 228°K). This can be seen from the tables of c a l c u l a t e d linewidths. -45-C Discussion (1) Results -In the previous s e c t i o n , the value of AG° has been c a l c u l t e d by s i x separate methods, and there i s considerable diff e r e n c e i n the r e s u l t s . In order to pin down the p o s i t i o n of the equilibrium with any degree of accuracy, some r e s u l t s must therefore be discarded i n favour of some others. The only c r i t e r i o n f o r such a decision must be that the more r e l i a b l e r e s u l t s are those i n which there are fewer assumptions of unknown v a l i d i t y . On t h i s b a s i s , the coupling constant r e s u l t s and the ^ "H chemical 19 s h i f t c a l c u l a t i o n s must be classed as less r e l i a b l e than the F s h i f t c a l c u l a t i o n s , since no temperature dependence was accounted f o r . The preferred values are therefore: (20% i n CS^ solution) 19 AG° = 0.625 kcal./mole (-90°C) - areas of F resonances 1 9 AG° = 0.672 " ( 0°C) - extrapolated F s h i f t s AG° = 0.659 " (-45°C) - linewidth of 1 9 F resonance The other values are: AG° = 0.397 kcal./mole (35°C) - 3 J u r , Hi AG° = 0.478 " 11 - 3 J U U nn AG° = 0.735 " " - chemical s h i f t of AG° = 0.544 " " chemical s h i f t of H 2 Taking these three 'preferred' values together, i t appears that AG° i s nearly independent of temperature, i f we state reasonable experimental l i m i t s , say ±0.0 25 kcal./mole. This implies a zero or i n s i g n i f i c a n t l y small entropy (AS° = -0.5 e.u. or lower) which i n t u i t i v e l y i s not unreasonable. 15 Bovey , examining cyclohexyl f l u o r i d e , a r r i v e d at AG° values of 19 0.242 kcal./mole (at 218°K, from F area measurements), and 0.153 kcal./mole 19 (at 302°K, from F chemical s h i f t s ) . This implies a p o s i t i v e entropy, AS° = 1.05 e.u. However, there was no allowance made i n t h i s work f o r -46-19 temperature dependence of F chemical s h i f t s , and i t can be seen from the 15 published data (Table I I , reference ) that both the averaged resonance at high temperatures, and the eq u a t o r i a l resonance at low temperatures are strongly dependent on temperature; however, the a x i a l resonance appears to be temperature independent. A quantitative estimate i s hard to make because of the comparatively large amount of s c a t t e r i n the points, but the equa t o r i a l resonance data i s f i t t e d quite well by 0.0095 ppm/°C ( i . e . same as above f o r cyclohexyl IF). I f a zero temperature dependence i s assumed f o r the a x i a l resonance, one can ca l c u l a t e that the AG° value i s now 0.231 kcal./mole at 302°K which i s very close to the low temperature value given by Bovey. This would imply that AS 0 f o r t h i s system i s also close to zero.* For cyclohexane IF, the r e s u l t s are: (20% i n CS 2) AG° = 0.650 0.025 kcal./mole (183°K - 273°K) AH° = AG° AS° = 0 ±0.5 e.u. This value of AG° i s close to the sum of the i n d i v i d u a l AG° values 31 reported f o r iodine and f l u o r i n e i n the l i t e r a t u r e . AG° (I) = 0.468 AG° (F) = 0.276 Slim: AG° (IF) = 0.744 kcal./mole This sum i s expected to be somewhat higher than the observed AG° f o r cyclohexane IF, since the repulsions between the halogen atoms ( i n the d i e q u a t o r i a l conformer) would be expected to reduce the l a t t e r value. The rather small reduction, 0.1 kcal./mole i n d i c a t e s , however, that t h i s r e p u l s i o n i s quite small. This i s i n contrast to the case of * A more l i k e l y f i n i t e value f o r the temperature c o e f f i c i e n t of the a x i a l resonance would increase the value of AG° and thus improve the.compari-son with the low temperature value. cyclohexane IC1 , i n which the d i a x i a l form predominates and AG° = 0.24 kcal./mole. The sum of the A values f o r I and CI i s 0.996 kcal./mole; thus i n t h i s case the repulsion between I and CI i n the d i e q u a t o r i a l form must be v c o n t r i b u t i n g approximately 1.2 kcal./mole, or twelve times that between I and F. The repulsion between two bromine atoms or between two chlorine atoms can be s i m i l a r l y c a l c u l a t e d , and both are found to be large (Table I I I ) . TABLE III Repulsion Between Substituents i n the Diequatorial Form  of some 1,2-dihalP - Cyclohexanes Substituents(s) A value Reference Sum of A values of substituents Repulsion between halogens F 0.276 kcal./mole 31 CI 0.528 31 Br 0.476 31 I 0.468 31 IF 0.650 t h i s work 0.744 kcal/mole 0.1 IC1 -0.250 48 0.996 1.2 kcal/mole . Cl-'Cl 0.200 49 1.056 0.8 Br-Br -0.300 49 0.952 1.2 I-I -1.000 50 0.936 1.9 Note: measurements were a l l taken i n CS 2 s o l u t i o n except f o r the l a s t compound ( d i - i o d i d e ) , f o r which benzene was-used. This may be expected to make a s i g n i f i c a n t d i f f e r e n c e to the A value of the di - i o d i d e (see Table I ) , and lower the ca l c u l a t e d r e p u l s i o n from 1.9 kcal./mole to approximately 1.6 - 1.7 kcal./mole. (2) Methods The most i n t e r e s t i n g part of the above r e s u l t s appears not to be the f i n a l value of AG°, but the a p p r a i s a l of the various methods. Thus we conclude that the chemical s h i f t s and v i c i n a l coupling constants are a l l -48-19 temperature dependent, those i n v o l v i n g F being p a r t i c u l a r l y s u s c e p t i b l e ; there i s no reason to suppose that t h i s i s a unique case, and instead i t i s l i k e l y that these phenomena are general. I t can be c a l c u l a t e d that i n order to b r i n g the AG° values obtained from coupling constants i n t o l i n e with the above value, temperature c o e f f i c i e n t s -3 3 -3 3 of +3 x 10 cps./°K ( f o r J u r,) and -3 x 10 cps./°K ( f o r J U 1 T ) are required. nr Hn 51 A recent review by Laszlo presents some other evidence of temperature dependence of various coupling constants. AG°, c a l c u l a t e d from the chemical s h i f t of H^ i s 'high', whereas that from H- i s 'low'; however, a s h i f t of only 2.5 cps. i n vTJ. , or 1 cps. i n 2 H 31 v I T , would account f o r the d i f f e r e n c e . Jensen , has shown recently that t h i s H l 15 phenomenon i s i n f a c t general. Bovey noted that the conformer r a t i o of cyclohexyl f l u o r i d e as determined by "Hi chemical s h i f t s d i f f e r e d from the value obtained from area measurements. This discrepancy i s now explained. D Rate c a l c u l a t i o n s Using the Gutowsky-Holm equation, equation (6), a computer program GUTHO was written which c a l c u l a t e s the width, height and p o s i t i o n of a l l resonances i n a one-spin system undergoing chemical exchange. Input data required are the f r a c t i o n a l population diff e r e n c e PD, the chemical s h i f t s of both resonances i n the slow exchange l i m i t SA and SB, and the residence time 19 1 T. This program was then applied to the F spectra of I, i n which H couplings had been removed by i r r a d i a t i o n . SA and- SB were f i x e d and then PD and T were var i e d i n i n t e g r a l steps. Since, i n our case, (SA - SB) only v a r i e s about 4% (from 188°K to 273°K), t h i s i s not a bad approximation. However, PD varies considerably due to the temperature dependence of the equilibrium constant, throughout the range of experimental spectra. -49-Using the value AG° = 0.650 kcal./mole, values of PD were ca l c u l a t e d f o r each of the experimental spectra, and then the residence time T"(=x) 15 picked which most c l o s e l y f i t t e d the experimental peak width . The data i s shown i n Table IV. 3 •The p l o t of In x vs. 10 /T i s shown i n Figure 4, and has a slope which corresponds to an a c t i v a t i o n energy of 10.72 kcal./mole. t t t From t h i s p l o t , and equations (3), (4) and (5), AF AH and AS may be c a l c u l a t e d . However, these formulas contain the inherent assumption that the c h a i r - t o - c h a i r i n v e r s i o n involves.only one b a r r i e r ; i t has been 38 pointed out , that i n the event of there being two b a r r i e r s to the process, then the observed rate constant K i s a c t u a l l y equal to one-half of the a c t u a l rate constant f o r passing over each b a r r i e r . In t h i s case of a cyclohexane d e r i v a t i v e , i t seems l i k e l y that a boat form i s an intermediate i n the process, and of those molecules which become boats, one-half w i l l go on to the inverted chair form and the others w i l l r e v e r t to t h e i r i n i t i a l c h air forms. Thus K , , the rate constant f o r cb the chair-to-boat process i s equal to twice the observed rate constant. Thus AF ^ as c a l c u l a t e d by equation (4) should be smaller by 2.3. RT log 2, f while A S ^ i s l a r g e r . AF^ b = 2.3 RT (10.319 + log T + logx) (4*) Using (3), ( 4 ' ) , (5) and Figure 4 then: At 216.5°K (-56.5°C): /'AF^ = 9.65 kcal./mole AH + ,= 10.27 kcal./mole AS 1 U = 3.0 e.u. cb At 266°K (- 7°C) /'AF+, = 9.45 kcal./mole cb AH = 9.99 kcal./mole 4* AS = 2.0 e.u. -50-TABLE IV K i n e t i c Data f o r Conformational Inversion of Cyclohexane IF Temp. °K 10 3/T°K PD = P -P A B 19 F Linewidth ( H-decoupled) Residence Time, T 273 3 .66 0.536 5.0 cps. 0.0000066 sec. 263 3.80 0.552 9.5 0.000013 258 3.88 0.560 13.5 0.000020 253 3.96 ' 0.568 20 < 0.000031 248 4.03 0.578 29 0.000047 243 4.115 0.586 36 0.000059 238 4.20 0.595 55 0.000095 233 4.295 0.604 89 0.000173 228 4.39 0.614 114 0.00028 223 4.49 0.623 86 0.00064 218 4.59 0.634 69.5 0.00080 208 4.81 0.655 21.4 0.0027 198 5.05 0.677 5.6 0.012 -51-F I G . 4 Arrhenius plot for Conformational Inversion of Cyclohexane IF. - 2 . 0 - i log-r - 3 . 5 -- 5 . 0 H -52-15 Bovey , has pointed out that a c t i v a t i o n parameters such as these are a c t u a l l y composite values of the forward and backward reac t i o n s , and he has given a set of equations to f i n d the i n d i v i d u a l parameters: AF + = AF + - RTlnX ea ax AF + = AF + - RTlnX ae eq AH + = AH + + X AH ea eq AH + = AH + - X AH ae ax AS + = AS + + X AS + R(X InX + X lnX ) ea eq eq eq ax ax • AS + = AS + - X AS + R(X InX + X lnX ) ae eq eq eq ax ax (7) (8) (9) (10) (11) (12) where X and X are the mole f r a c t i o n s of the a x i a l and e q u a t o r i a l ax eq conformers ( i . e . P , P_). Using the equations (7) - (12), we f i n d : 216.5°K 266°K AF + (cb) ea 10 .38 kcal./mole 10 .23 kcal./mole AF + (cb.) ae 9 .714 " 9 .59 " AH + ea ' 10 .83 " 10 .49 " AH + ae 10 .17 9 .84 " AS + (cb) ea 2 .1 e.u. 0 .9 e.u. AS f (cb) ae 2 .1 11 0 .9 These then are the f i n a l a c t i v a t i o n parameters f o r t r a n s - l - f l u o r o -2-iodo-cyclohexane. -53-The most r e l i a b l e work done on the conformational inversion of 38 cyclohexane systems appears to be that of Anet and Bourn , who studied t t t cyclohexane-d.,.. Their values f o r AF , , AH and AS , are r e s p e c t i v e l y 11 cb cb ^ J 10.22 kcal./mole, 10.8 kcal./mole and 2.8 e.u. ( a l l at -67°C). The comparable values i n t h i s study are ( f o r d i e q u a t o r i a l chair-to-boat process, since t h i s has the lowest ground s t a t e ) , 10.38 kcal./mole, 10.83 kcal./mole and 2.1 e.u. This i s remarkably close agreement. t 15 38 The small p o s i t i v e value of AS (cb) i s , as has been pointed out, ' ea exactly as expected, on the basis of symmetry grounds, eg. f o r cyclohexane, there are s i x possible paths f o r reaching a cyclohexene-like t r a n s i t i o n 52 t state , and thus AS ^ = Rln6 = 3.6 e.u. (neglecting v i b r a t i o n a l and r o t a t i o n a l entropy c o n t r i b u t i o n s ) . E r r o r l i m i t s on a c t i v a t i o n parameters have i n most inv e s t i g a t i o n s apparently been determined by the authors' estimate of the accuracy of the measurement, rather than t h e i r evaluation of the v a l i d i t y of the method. This can be seen by considering the disagreement between workers using d i f f e r e n t 38 methods. Anet and Bourn , i n a r e f r e s h i n g departure, have taken the opposite view i . e . systematic er r o r i s not so'small as to allow the random erro r to become dominant, and t h i s appears to be f a r more l o g i c a l . t ' t Thus subjective estimates f o r errors i n AH and AF ^ might be t ±0.2 kcal./mole, and ±1.0 e.u. f o r AS cb -54-IV DEPENDENCE OF 3 J L I T , UPON ELECTRONEGATIVITY AND DIHEDRAL ANGLE HF A E l e c t r o n e g a t i v i t y 19 1 From the F and H spectra of the acenaphthyl f l u o r i d e s reported 3 3 i n Section I I , two sets of data were taken, J ( c i s ) and J 0 „ ( t r a n s ) . nr nr The assumption made here i s that the dihedral angle between the C-H and the C-F bonds i s constant throughout the seri e s of compounds; X-ray d i f f r a c t i o n 23 r e s u l t s on acenaphthene i t s e l f give the dihedral angles as 0° and 100°. The coupling constant data along with the t o t a l e l e c t r o n e g a t i v i t y of the remaining two substituents i s l i s t e d i n Table V; e l e c t r o n e g a t i v i t y values 14 used are those of Huggms . 2 It has been claimed by Abraham et a l . , and v e r i f i e d by H a l l and Manville"'", that the o r i e n t a t i o n of the substituent i s important i n determin-3 ing the e f f e c t of i t s e l e c t r o n e g a t i v i t y upon J (60°). 'Trans'* substituents were found to be e f f e c t i v e i n attenuating the coupling whereas 3 'gauche' substituents were not; f o r J (180°), only gauche substituents nr were possible i n the experimental systems used. Since the 60° dihedral angle doesn't occur i n the acenaphthene system, t h i s claim cannot be tested here; however, f o r the 0° and 100° dihedral angles i t can be shown that there i s l i t t l e , i f any, o r i e n t a t i o n a l dependence of the substituent. Thus i n compounds XIII and XV (trans- and 3 gem-acenaphthene BrF) J (0°) i s 21.4 cps. and 23.0 cps. r e s p e c t i v e l y . nr ' In XVI (gem-acenaphthene C1F) the sum of the two couplings i s 32.8, whereas * i . e . 'trans' 1 to e i t h e r the H or the F involved i n the coupling. -55-' TABLE V N u c l e a r m a g n e t i c r e s o n a n c e p a r a m e t e r s f o r f l u o r o - h a l o d e r i v a t i v e s o f a c e n a p h t h e n e S u b s t i t u e n t s Sum o f S u b s t i t u e n t ^ C o u p l i n g C o n s t a n t E l e c t r o n e g a t i v i t i e s (Hz) A B C .HF . J CIS .HF J t : H H F 4 . 4 2 9 . 5 2 1 . 4 H B r F 5 . 1 5 2 3 . 0 1 0 . 0 B r F H 5 . 1 5 2 1 . 5 --H C I F 5 . 2 5 (Sum = 3 2 . 8 ) C I H F 5 . 3 5 -- 1 0 . 0 C I . F H 5 . 3 5 2 1 . 0 --I C I F 5 . 8 0 6 . 0 I F C I 5 . 8 0 1 9 . 7 --B r B r F 5 . 9 0 -- 3 . 1 B r F B r 5 . 9 0 1 8 . 9 --H F F 6 . 1 0 (Sum = 2 6 . 4 ) F F H 6 . 1 0 1 8 . 8 --F H F 6 . 1 0 -- 5 . 2 I F F 6 . 5 5 1 6 . 0 4 . 8 B r F F 6 , 8 5 1 5 . 3 3 . 7 F F F 7 . 8 0 1 2 , 8 d 1 . 2 -56-i n the trans-CIF and cis-CIF compounds (XXII and XXIII) the couplings are 21.0 and 10.0 r e s p e c t i v e l y , a sum of 32.0. S i m i l a r l y , iri XVII (gem-difluoro-acenaphthene) the sum of the two couplings i s 26.4, and from the i n d i v i d u a l trans- and c i s - d i f l u o r i d e s (X, IX) the couplings are 19.1 and 5.2 r e s p e c t i v e l y , a sum of. 24.3. Hence o r i e n t a t i o n of substituents i s neglected i n assembling the data of Table V. As o u t l i n e d i n Section I, a l l previous i n v e s t i g a t i o n s of the r e l a t i o n s h i p between e l e c t r o n e g a t i v i t y and coupling constants have concluded, that i t was a negative l i n e a r r e l a t i o n s h i p . This may seem l o g i c a l at f i r s t s i g h t , since a strongly electronegative substituent X should ' p u l l ' the electron density out of the neighbouring bonds and thus decrease the coupling constants which are transmitted along them.' This e f f e c t may reasonably be supposed to be proportional to the 'electronegative strength' of X. However, there i s a basic f a u l t with t h i s reasoning, f o r i t supposes that the source of electron density i n the neighbouring bonds i s i n f i n i t e and has no 'electronegative strength' of i t s own. Both of these inherent assumptions are of course impossible and i t i s f r u i t f u l to consider the opposite assumptions, i . e . a f i n i t e source of e l e c t r o n e g a t i v i t y with a c e r t a i n a t t r a c t i n g power of i t s own. I f one substituent X with e l e c t r o n e g a t i v i t y e reduces the coupling constant J from to ( J ^ - Y ) , then a second ( s i m i l a r ) substituent would not have the same e f f e c t ( i . e . reduce J to ( J -2Y) as i n the l i n e a r case), but ( J Q - Y ) rather i t should reduce J by the same f r a c t i o n , i . e . from ( J -Y) to — - 0 J Q ( J Q - Y ) . TO put i t another way, the rate of decrease with e l e c t r o n e g a t i v i t y i s proportional to the remaining electron density and thus coupling constant: "1 -57-dJ . _ dJ , , -3— = -kJ or = -kde de J hence: InJ = -ke + constant (13) -ke J = ae where 'a' i s some constant Thus a negative exponential decay of coupling constant with electro-n e g a t i v i t y i s a more l o g i c a l r e l a t i o n s h i p to expect than a l i n e a r one.* The data from Table V was f i t t e d by a computer program** to both exponential and l i n e a r r e l a t i o n s h i p s , and the r e s u l t s are shown i n Table VI. TABLE VI 1 19 . V i c i n a l H- F Coupling Constants Dependence on E l e c t r o n e g a t i v i t y — A Comparison of Exponential and Linear F i t s to the Data. Exponential F i t Linear F i t Deviation Deviation Q (~\ O R O O tr J u r , ( c i s ) J = 87.75e~ 0.87 J = -4.52e + 46.37 1.32 rlr 3 T , _ n o c c n -0.8749e 1.18 J = -5.15e + 38.13 3.35 JUT, (trans) J = 985.68e nr Note: Deviation i s the root mean square of the differences between c a l c u l a t e d and experimental points. It can be seen that the exponential f i t i s decidedly b e t t e r e s p e c i a l l y f o r J (trans) and a graph of the data i s shown i n Figure 5. *In both cases, coupling constants are assumed to be d i r e c t l y r e l a t e d to electron density. **LQF, a l i b r a r y program of UBC computing centre, u t i l i z e s a l e a s t squares procedure. -58-4 5 6 7 8 T O T A L E L E C T R O N E G A T I V I T Y O F S U B S T I T U E N T S X A N D Y 3 F i g . 5: V a r i a t i o n of J H P with e l e c t r o n e g a t i v i t y . -59-From this'graph i t i s evident that the most important point i s the s i z e of 3 , J^P (trans) f o r the compound with the l e a s t electronegative substituents i . e . acenaphthene f l u o r i d e i t s e l f XXV. To support t h i s r e s u l t therefore, the corresponding 1-fluoro-indan was synthesized v i a the bromide from indene, using an i d e n t i c a l procedure as f o r acenaphthyl f l u o r i d e (see Section IIC). The extremely complex "*"H N.M.R. spectrum of t h i s compound (an ABCDMX with long range couplings) i s not amenable to analysis within the l i f e t i m e of 19 even a graduate student, but the F spectrum i s composed of two broad over-lapping t r i p l e t s , the bandwidth of which i s the sum of the v i c i n a l couplings 3 ' i n t o f l u o r i n e , ca. 55 cps. The l a r g e s t J u r , ( c i s ) that may be expected i s nr 19 about 30 cps. , even i f the flve-membered r i n g i s planar , thus leaving a 3 value of about 25 cps. f o r J ( t r a n s ) ; t h i s c e r t a i n l y supports the value obtained from acenaphthyl f l u o r i d e . The reasons f o r the l i n e a r p l o t s a r r i v e d at experimentally by previous workers can now be seen: 3 ( i ) The dependence of J on e l e c t r o n e g a t i v i t y i s much less than rin 3 f o r J u r , , thus leading to a shallower curve which i s quite e a s i l y approxi-nr mated by a s t r a i g h t l i n e . 3 ( i i ) The J ^ p values considered previously had dihedral angles of 60° and 180°, which may have les s of an e l e c t r o n e g a t i v i t y dependence than at 100°, where i t i s r e a l l y evident that a l i n e a r r e l a t i o n s h i p i s inadequate. ( i i i ) The ranges of e l e c t r o n e g a t i v i t y considered previously were not very wide, again leading to an e f f e c t i v e l y shallower curve. B_ Dihedral Angle 3 Since J couplings have such a large dependence on electronega-Hr t i v i t y , a general Karplus-type curve which i s usually drawn, showing dihedral angle dependence, i s not p r a c t i c a l . However, one can p l o t several curves, -60-each f o r a given e l e c t r o n e g a t i v i t y , and thus describe the three-dimensional surface. In Table VII there i s l i s t e d a set of data c o l l e c t e d from various references and t h i s work; i t can be seen that there are s t i l l some gaps to be f i l l e d i n but enough data i s a v a i l a b l e f o r i t to be us e f u l i . e . we should be able to make reasonable deductions concerning structure i n most cases. TABLE VII 1 19 V i c i n a l H- F coupling constants as a function of e l e c t r o n e g a t i v i y and dihedral angle. (from various references as well as t h i s work) Dihedral angle + 0° 60° 100° 120° 180° E l e c t r o n e g a t i v i t y 4.4 "29.5 11.5 21.4 43.5 4.85 25.1 6,11 12.8 45 5.15 23.0 10.0 21.5 6.1 19.1 10,11 5.1 • ' 35 6.55 16.0 4.8 6.7 5-11 23-25 6.85 15.3 3.7 7.8 12.8 1.2 Note: ' E l e c t r o n e g a t i v i t y ' i s the sum of the i n d i v i d u a l e l e c t r o n e g a t i v i t i e s of two substituents and i n the fragment: x i h -61-V APPLICATION OF J u r , TO CONFORMATIONAL ANALYSIS OF Hi INDAN BrF AND SOME RELATED COMPOUNDS- '" A Indan BrF (VIII) F H ( l ) Spectral Analysis The "'"H N.M.R. spectrum of VIII consists of four regions: ( i ) An aromatic region, exceedingly complex and not shown here, ( i i ) A l o w - f i e l d region a t t r i b u t a b l e to and shown i n Figure 6A. ( i i i ) A s l i g h t l y h i g h e r - f i e l d region expected f o r (Figure 7A). (i v ) A high f i e l d region c h a r a c t e r i s t i c of methylene protons and assigned to H and H (Figure 8A). Each of these three spectra (Figures 6A, 7A, 8A) were run on a neat s o l u t i o n and with i r r a d i a t i o n of the aromatic region to sharpen the l i n e s . The spectra were subjected to i t e r a t i v e computer analysis using TWOSUM (see Appendix A) and the simulated spectra are shown i n Figures 6B, 7B and 8B r e s p e c t i v e l y . The f i t between the ca l c u l a t e d and experimental Iridan B r F F i g . 6: P a r t i a l H s p e c t r u m , H r e g i o n . (A) S i n g l e r e s o n a n c e s p e c t r u m . (B) C a l c u l a t e d s p e c t r u m . (C) Double r e s o n a n c e , i r r a d i a t i o n o f F. -65-1 19 spectra ( H only, ignoring F) was s a t i s f a c t o r y with an average deviation of only 0.049 cps.* The f i n a l c a l c u l a t e d coupling constants are: 3 J 1 2 = 3.15 cps. 3 J 2 3 = 6.74 cps.  2J^ = -17.06 cps. " J13 = °'° 3 j24 = 4 - 5 6 4 j 3 F = 1 ' 2 ° . \N = 0-0 3 J 2 F = 17.27 \ F = 2.45 2 J 1 F = 55.73 19 (2) F Spectrum 19' The F spectrum i s a broad mass which i s of l i t t l e use without s o p h i s t i c a t e d heteronuclear double resonance experiments. However, 19 1 19 [ F] - H double resonance spectra were taken ( i r r a d i a t i n g F and observ-1 ' . . ing H) and are shown i n Figures 6C, 7C and 9B.»« These spectra help to confirm the s p e c t r a l a n a l y s i s . * * * .' s ' (3) Spin t i c k l i n g With continued aromatic i r r a d i a t i o n three s e l e c t i v e spin t i c k l i n g experiments were then c a r r i e d out. The purpose of these was twofold: (a) to determine the r e l a t i v e signs of the couplings and (b) to t e s t out a new double resonance computer program, NMDRS (see Appendix A). 19 ""'One imaginary F t r a n s i t i o n was put into the experimental set m order to l i n k the energy l e v e l s together. 19 1 * * I t was necessary to run the [ F] - H experiment on the H^jH^ region on a d i f f e r e n t sample, since the o r i g i n a l one decomposed. This unfortunately contained a small impurity. 19 1 &&&These C F] - H spectra are a c t u a l l y t r i p l e resonance since i r r a d i a t i o n of the aromatics was being c a r r i e d out simultaneously. J, X F i g . 9: P a r t i a l . H s p e c t r u m o f i n d a n B r F , r e s o n a n c e . (B) Double r e s o n a n c e , The s m a l l d o u b l e t i n t h e c e n t r e ii H - H ^ r e g i o n . (A) Exr w i t h i r r a d i a t i o n o f . due t o an i m p u r i t y . p i m e n t a l s i n g l e F r e s o n a n c e . -67- . ( i ) I r r a d i a t i o n of H g at 6.5698 T ( t h i r d l i n e from l e f t i n Figure -8A) and observation of H^. Experimental spectrum i s shown i n Figure 10A, with computer simulated spectrum' below i n Figure 10B. I t can be seen that the 3r<^, 5"*"^ , 7 ^ and 8^ l i n e s i n are s p l i t . Since'the t h e o r e t i c a l spectrum was generated by putting i n the coupling constants given above, t h i s confirms 4' 3 the signs used. In p a r t i c u l a r i t ind i c a t e s that J„_ and J \ _ have the same or 2F 2 3 sign , but J and J^^ have opposite signs. However, the t h e o r e t i c a l l i n e shapes are rather poor reproductions of the experimental (the l a s t four 'new' l i n e s are much too sharp); t h i s may r e f l e c t the inadequacy of NMDRS, which neglects a l l r e l a x a t i o n e f f e c t s i n c a l c u l a t i n g the l i n e shapes. Other experimental comparisons of computer simulated spectra showed that t h i s was not an i s o l a t e d r e s u l t ; the program frequently predicted extremely sharp l i n e s which are v i r t u a l l y never observed i n p r a c t i c e . Whether or not t h i s was the f a u l t of NMDRS as noted above or simply an instrumental problem (e.g. the saturation l e v e l of a very sharp l i n e may be much lower than normal) was not determined. ( i i ) I r r a d i a t i o n of H^ at 6.5822 x (fourth l i n e from the l e f t i n Figure 8A) and observation of H2*. Experimental spectrum i s shown i n Figure IOC, with the computer simulated spectrum below i n Figure 10D. This experiment gives the same r e s u l t s as ( i ) . The same r e l a t i v e signs may be i n f e r r e d and h a l f the 'new' t r a n s i t i o n s have t h e o r e t i c a l l i n e shapes not i n agreement with experimental. ( i i i ) I r r a d i a t i o n of at 5.5263 x ( f i r s t l i n e from l e f t i n Figure 7A) and observation of H and H . The experimental and t h e o r e t i c a l spectra are shown i n Figures 11A and 11B. -Lines 5 and 7 of both H^ and H^ are s p l i t ; t h i s indicates that 3 4 4 3 3 J has the same sign, as both J and J,,R, but J and J have Z.Y or 4r AO 2 1 19 3 opposite signs to J„ . Since v i c i n a l H- F couplings ( J u„) are o4 Hr cn 03 F i g . 10: P a r t i a l s p e c t r u m o f i n d a n B r F , H r e g i o n , w i t h s i m u l t a n e o u s i r r a d i a t i o n o f a s i n g l e l i n e m t h e r e s o n a n c e (C) I r r a d i a t i o n o f l i n e t i n H (A) I r r a d i a t i o n o f l i n e 3 i n H . (B) C a l c u l a t e d s p e c t r u m o f A. (D) C a l c u l a t e d s p e c t r u m o f C. -69--70-p o s i t i v e ( r e f e r e n c e 48 and S e c t i o n IV o f t h i s t h e s i s ) t h i s i n d i c a t e s t h a t 1 19 4 4 b o t h l o n g - r a n g e H- F c o u p l i n g s i n t h i s m o l e c u l e ( J„ and J a r e p o s i t i v e . b e t t e r i n t h i s c a s e , t h a n i n t h e p r e v i o u s two. Each t r a n s i t i o n i s now s p l i t i n t o three, l i n e s r a t h e r t h a n t h e u s u a l two f o r s p i n t i c k l i n g , s i n c e t h e o r i g i n a l t r a n s i t i o n i n t h e ( o r H ) s p e c t r u m i s . a c t u a l l y an u n r e s o l v e d d o u b l e t (due t o t h e c o u p l i n g o f H ) and o n l y one l i n e o f each d o u b l e t - i s s p l i t i n t h e s p i n t i c k l i n g e x p e r i m e n t . (4) C o n f o r m a t i o n a n a l y s i s o f V I I I The f l u o r i n e and bromine s u b s t i t u e n t s a r e assumed t o have a t r a n s r e l a t i o n s h i p , s i n c e a l l 'XF' a d d i t i o n s have so f a r p r o d u c e d t h i s ( c y c l o h e x e n e , a c e n a p h t h y l e n e , u n s a t u r a t e d sugars"*"). The p r o b l e m , t h e n i s t o d e c i d e upon . 3 t h e shape o f t h e five-membered r i n g . C o n s i d e r a t i o n o f t h e s i z e o f J^p (17.3 c p s . ) i n c o m p a r i s o n w i t h d a t a f o r systems w i t h s i m i l a r e l e c t r o n e g a t i v e (e = 5.15) s u b s t i t u e n t s ( p r e s e n t e d i n T a b l e V I I ) i n d i c a t e s t h a t t h e d i h e d r a l a n g l e between and F i s e i t h e r - 10-25° o r about 110-125°. However, t h e s e c o n d p o s s i b i l i t y i s r u l e d o u t s i n c e t h e five-membered r i n g w o u l d have t o bend an a b s u r d amount t o a c h i e v e s u c h a l a r g e d i h e d r a l a n g l e between atoms i n i t i a l l y e c l i p s e d (when r i n g i s p l a n a r ) . Hence t h e bend o f t h e r i n g i s d e t e r m i n e d t o be i n t h e r e g i o n 10-25°, b u t t h i s d o e s n ' t d e c i d e w h i c h way t h e r i n g i s b e n t : The agreement between t h e o r e t i c a l and e x p e r i m e n t a l s p e c t r a i s 3 3 Since J and J must be nearly equal, by symmetry, we can assign the l a r g 3 45 coupling (6.7 cps.)' to ^23* ^ o r l - D r o m o - a c e n a p h t : h e n e 5 with s i m i l a r 3 e l e c t r o n e g a t i v i t y , J (0°) = 6.8 cps., and f o r the v i n y l f l u o r i d e adduct 19 3 of hexachlorocyclopentadiene " J (0°) = 7.0 cps. Hence a small bend of Hn the five-membered r i n g i s also to be expected from t h i s piece of informa-3 t i o n . However, also has approximately the same value with e i t h e r conformation A or B. The r e l a t i v e amounts of each conformer may however, be deduced by 3 3 comparison of J with other data i n t h i s study. J u u (<j> = 180°) i s ±2. tin 3 obtained from cyclohexane IF (I-d.,) (10.1 cps.) and J I J T, (<j> = 100°) from 4 , nn acenaphthene BrF (XIII) (1.0 cps.). Thus f o r <j> .= 145° a value of say 7.0 cps. i s reasonable, and the experimental, value of 3.15 cps. indicates that the d i a x i a l conformer predominates to the extent of say 60% 3 The values of 40,41 t r a n s - l , 2 - d i h a l i d e s : 3 3 The values of J and J ^ may be compared with those i n other J12 J24 Br - F 3.15 4.56 Br - Br 1.2 1.3 Br - CI 2.7 3.1 CI - CI 3.3 3.8 CI - I 2.9 ~ 3.2 Since the bromo-fluoride has the highest e l e c t r o n e g a t i v i t y , there appears to be more d i e q u a t o r i a l conformer present i n t h i s compound than i n the other di-halogens, once again i n d i c a t i n g the small amount of halogen-halogen r e p u l s i o n when f l u o r i n e i s involved, (see Section III) -72-(5) Conclusion 3 ( i ) The pucker of the r i n g i s determined from J to be 10-25°. n r ( i i ) A s i g n i f i c a n t amount of d i e q u a t o r i a l conformer i s present, but the d i a x i a l one again predominates. 1 19 ( i i i ) Two long-range H- F couplings were observed, both p o s i t i v e , ( i v ) The computer program NMDRS gives an adequate p r e d i c t i o n of spin t i c k l i n g spectra, except that some l i n e s have an unobserved sharpness. Benzofuran d e r i v a t i v e s The following four compounds were provided by Dr. B. Webster, working i n t h i s laboratory, ( l ) C i s - d i f l u o r i d e of benzofuran From the F spectra two f l u o r i n e resonances were measured. v ( F 1 ) = 13,681 cps. ( u p f i e l d of CFClg) couplings: 15.0, 17.0, 61.5 cps. v ( F 0 ) = 18,741 cps. ( u p f i e l d of CFC1„) 2 o • couplings: 2.15, 17.0, 55.0 cps. From the Hi N.M.R. spectra J„„ was measured as 4.5 cps. -73-I f the r i n g was planar, or a l t e r n a t i n g equally between two equally 3 3 puckered conformations, then J = J ; but comparison of the two H 1 F 2 H 2 F 1 , f l u o r i n e resonances shows that they are i n f a c t not equal: H 1 F 2 3 j H F = 1 5  H 2 F 1 3 This assignment i s made by equating the two 17.0 couplings to J and 2 25 assuming that i s l a r g e s t , when i t i s next to an oxygen . Hence i t seems that one p a r t i c u l a r non-planar conformation i s preferred, and obviously i t must be the one shown (since f o r the other case, the dihedral angle between H and F 2 i s > 120°, and between H 2 and F 1 i t i s < 120°; t h i s would lead to J u being greater than J ). H 1 F 2 H 2 F 1 The carbon-carbon fragment (C - C^) has the following substituents attached: 1 oxygen, 1 carbon, 2 hydrogen, and 2 f l u o r i n e . Discounting 1 hydrogen, 1 f l u o r i n e , and 1 carbon, and adding 1 e l e c t r o n e g a t i v i t y unit f o r oxygen, we get e = 2.2 + 3.9 + 1.0 = 7.1. This approximates B r F 2 case 3 (e = 6.85) i n acenaphthene s e r i e s , where J u „ (<(> = 0°) = 15.3 cps. and n r 3 3 J„„ ((j) = 100°) = 3.7 cps. Another u s e f u l number i s the value of J u „ U = 180°) HF nr 25 from pyranosyl f l u o r i d e which varies between 23-26 cps. From t h i s data, the di h e d r a l angle between H 2 and F^ can be estimated 150°and that between H and F 2 as 90°, corresponding to a 30° pucker of the r i n g as shown. This means that <j)„ „ = 30° and since 1 2 3 • ' . J T I =4.5 cps., i t i s not unreasonable. The pseudo-axial p o s i t i o n of F H 1 H 2 _ 1 i n t h i s conformation i s to be expected i n view of the strong anomeric e f f e c t observed i n sugars.* * * i . e . molecules tend to adopt the conformation i n which the substituent next to the r i n g oxygen i s a x i a l . -74-(2) T r a n s - d i f l u o r i d e of benzofuran 19 From the F N.M.R. spectra two f l u o r i n e resonances were measured. v(F )• = 12,150 cps. ( u p f i e l d of CFClg) couplings: 10.4, 11.5, 58.0 cps. v ( F 0 ) = 16,478 cps. ( u p f i e l d of CFC1 ) couplings: 11, 11, 55 cps. 3 3 The e q u a l i t y of J„ and J i s good confirmation of the trans 1 2 2 1 r e l a t i o n s h i p , since cj)IT and (}>.. „ w i l l be equal no matter how the r i n g i s H 1 F 2 H 2 F 1 puckered. Using the previous data, these angles are estimated to be 20°*. 3 The value of Jpp> H cps. i s evidence that the d i a x i a l conformation i s favoured, since i n the d i e q u a t o r i a l conformation <j> i s approximately equal to 3 90°, and t h i s should lead to a near-zero Jpp- ( I n cis-acenaphthene d i f l u o r i d e , 3 J^P (<j> = 100°) = 1.2 cps.) Thus the r i n g i s again puckered i n the same sense as the c i s - d i f l u o r i d e of benzofuran ( i . e . obeying the anomeric r u l e ) but not as much. -'There i s also a p o s s i b i l i t y of a mixture of two conformations, i n which varies between say 160° and 100°, g i v i n g an average value equivalent to 140°. This cannot be checked, however. -75-(3) Cis-bromo-fluoride of benzofuran The only two couplings of i n t e r e s t here were measured as: \ H 2 ' - 3 - 5 3 J H 2 F = 3 0 - 8 ' Using the same scale f o r e l e c t r o n e g a t i v i t y as before, z - Br + H + 1.0 = 2.95 + 2.2 + 1.0 = 6.15. This i s close to that f o r the acenaphthene d i f l u o r i d e s (e = 6.1), where 3 J H f , (0°) = 19 cps. and 3 J H F (100°) = 5 cps., 16 3 and 1,1-difluoro-cyclohexane (e = 6.1) where J R F (180°) = 35 cps. The only possible <j> i s approximately 165° - 170°; t h i s means that the pucker 2 of the r i n g i s very high and that cL, „ i s approximately equal to 45° - 50°, 3 1 2 ' which i s reasonable i n view of J u „ =3.5 cps. H 1 H 2 This-contrasts with the much milder puckering estimated f o r the c i s - d i f l u o r i d e , and can be a t t r i b u t e d to the greater s t e r i c hindrance between bromine and f l u o r i n e (rather thari'between two f l u o r i n e s ) . -76-(4) Trans-bromo-fluoride of benzofuran. Again, there are only two important couplings of i n t e r e s t here; From the previous data, <j>„ „ = 25°; the corresponding <|> may be 2 H 1 H 2 95° or 145°, depending on which conformation i s adopted. The very low value 3 of J , however, determines that the d i a x i a l conformation i s favoured. H 1 H 2 (.5) Conclusion Thus a l l four benzofuran d e r i v a t i v e s adopt the conformation with anomeric f l u o r i n e a x i a l . This contrasts with the indan d e r i v a t i v e (VIII) which has a much lower preference f o r the d i a x i a l conformation. However, i n a l l cases the pucker i s small (20 - 30° from planar) with the exception of the cis-bromo-fluoride d e r i v a t i v e of benzofuran. The advantages of using f l u o r i n a t e d d e r i v a t i v e s i n conformational analysis have been w e l l i l l u s t r a t e d here, as the uncertainties i n the 1 40 41 conclusions are much"less than i n previous attempts using only H N.M.R. ' VI EXPERIMENTAL GENERAL (1) Solvents: Benzene and a c e t o n i t r i l e were d r i e d over calcium sulphate, and petroleum ether and dichloro-methane were f r a c t i o n a l l y d i s t i l l e d before use. (2) Reagents: S i l v e r f l u o r i d e (from Harshaw Go.) was stored i n a vacuum desic c a t o r , and ground to a f i n e powder j u s t p r i o r to a r e a c t i o n . Cyclohexene was d i s t i l l e d before a r e a c t i o n , but a l l other reagents were used as received. 3,3,6,6,-tetradeuter-cyclohexene was also used as received from Merck, Sharp and Dohm Co. and was stored i n a sealed glass v i a l at 0°C before use. (3) Chromatography: S i l i c a g e l used f o r chromatographic columns was Mallinckrodt CC-7, a neutral high-purity grade. Trans-l-fluoro-2-iodo-cyclohexane (I) 3.1 ml. (2.5g.) of cyclohexene and 12g. of powdered AgF were added to 50 ml. of benzene and the r e s u l t i n g mixture s t i r r e d thoroughly and cooled, i n an i c e bath. Dropwise add i t i o n of 8g. of iodine (dissolved i n benzene 10% w/v) was then c a r r i e d out over h a l f an hour, with continued s t i r r i n g . . The re a c t i o n mixture was worked up by f i l t e r i n g and then washing successively with bicarbonate s o l u t i o n , t h i o s u l f a t e s o l u t i o n , bicarbonate s o l u t i o n again and then f i n a l l y water. The organic l a y e r was separated and -78-evaporated under reduced pressure to produce a c l e a r l i q u i d whose N.M.R. spectrum was v i r t u a l l y i n d i s t i n g u i s h a b l e from the d i s t i l l e d m a t e r i a l . D i s t i l l a t i o n under reduced pressure gave 4.4g. of I ( Y i e l d = 63%) whose 22 N.M.R. spectrum matched that of the product of the Bowers rea c t i o n 23 90 99 n D = 1.5310 ( l i t . njj = 1.5318) 99 B.pt. = 50°C (2mm) ( l i t . 64°C (9mm) ) cf>c = 159.9 ppm Analysis: Calc. f o r C gH IF:' C, 31.59; H, 4.42; F, 8.32 Found : C, 31.76; H, 4.63; F, 8.11 Trans-l-iodo-2-fluoro-3,3,6,6,-tetradeutero-cyclohexane (I-d^) The above r e a c t i o n on cyclohexene was repeated on 3,3,6,6-tetradeutero-cyclohexene on a smaller scale (0.25g of deuterated material was used). To avoid possible decomposition on heating, no d i s t i l l a t i o n was c a r r i e d out; the "^H N.M.R. spectrum of the crude product showed no detectable i m p u r i t i e s , however. (Figure 1) Trans-l-bromo-2-fluoro-cyclohexane (II) The same procedure as f o r preparation of I was used except that of course bromine was substituted f o r iodine, and no t h i o s u l f a t e washing was necessary i n the workup. 6g. of bromine i n 25 ml. of benzene was added dropwise, and a l l other procedures and quantities remained the same. The N.M.R. spectra of crude and d i s t i l l e d m a t erial again were very s i m i l a r , and also matched that of the product of the Bowers r e a c t i o n . n 2 5 = 1.4825 ( l i t . n 2 ° = 1.4830) B.pt. = 58°C (9mm) ( l i t . 30°C (13 mm)*) '•The l i t e r a t u r e value of the b o i l i n g point of^I appears to be i n er r o r ; a sample of II prepared by the l i t e r a t u r e method had a b o i l i n g point i n agreement with that reported here. -79-Analysis: Calc. f o r CgH Q B r F : C, 39.78; H, 5.56; F, 10.49 Found: C, 39.90; H, 5.65; F, 10.61 1-iodomethyl-cyclohexyl f l u o r i d e ( I I I ) Prepared i n a s i m i l a r procedure as used f o r I. Quantities used were: lOg. AgF, 2.5g. methylene cyclohexene dissolved i n 35 ml. benzene. 8.5g. iodine d i s s o l v e d i n 85 ml. benzene. Reaction time was 90 min. Crude y i e l d 6.0g.; d i s t i l l e d y i e l d 4.4 g . (70%) 25 n D = 1.5175 Calc. f o r C ^ ^ I F : C, 34.73; H, 4.97 4>c = 151.2 ppm F o u n d : C, 34.88; H, 5.02 B.pt. = 61°C (1 mm) 1-Bromomethyl cyclohexyl f l u o r i d e (IV) Sim i l a r procedure as f o r I I : to 2.5g. methylene cyclohexene and lOg. AgF i n 40 ml. benzene was added 8g. bromine i n 40 ml. benzene aver 1 hour at 0°C. D i s t i l l a t i o n afforded 3.0g. of IV ( y i e l d 59%). n 2 5 = 1.4825 $ c - 156.3 ppm B.pt. = 47°C (1mm) The p o s i t i o n of the substituents i s obtained from the N.M.R. 2 spectrum; the lack of an i d e n t i f i a b l e coupling ( c h a r a c t e r i s t i c a l l y about 50 cps.) locates the f l u o r i n e at the t e r t i a r y p o s i t i o n . A n a l y s i s : Calc. f o r C ^ ^ B r F : C, 43.12; H, 6.15 Found: C, 42.89; H, 6.25 -80-2-iodo-l-fluoro-l-phenylethane (V) Id e n t i c a l procedure as fo r preparation of I, except that 2.5g. of styrene was used as s t a r t i n g m a t e r i a l . D i s t i l l a t i o n i n vacuo, however, r e s u l t e d i n decomposition. Crude y i e l d ( a f t e r workup and removal of solvent) = 4.7g. (78%). This material appeared from the N.M.R. spectra to be e s s e n t i a l l y free of impurities. The structure of the material ( i . e . the placing of the substituents) can also be deduced from the N.M.R. spectra, which however was very s i m i l a r to that of the bromo-derivative VI, which i s discussed below. (j>c = +166.8 ppm. 2-bromo-l-fluoro-l-phenylethane (VI) Same procedure as fo r I I , except that 2.5g. styrene and 5g. Br^ ( i n 40 ml. benzene) were used; time of addit i o n was 1 3/4 hours. D i s t i l l a t i o n under reduced pressure produced 3.5g. of a c l e a r l i q u i d (VI) ( y i e l d 71%). 25 <|)c= +174.5 ppm. n D = 1.5409 B.pt. 69°C (1 mm.) The N.M.R. spectra demonstrated the p o s i t i o n of the substituents; the p a r t i a l Hi spectra has two i d e n t i f i a b l e regions, an AB and M region of 19 an ABMX spectra (where X= F). The 50 cps. J positi o n s the f l u o r i n e i n the secondary p o s i t i o n . 2-iodo-l-fluoro-indan VII Again, same procedure was used as fo r I, (2.8g. of indene was reacted with 9 g. of iodine and 13g. of AgF) but l i k e V, although i t could not be d i s t i l l e d without decomposition, the crude product a f t e r workup was a cle a r l i q u i d , whose N.M.R. spectra showed no impurities. Crude y i e l d was 4.8 g. (66%). -81-2 3 <J> = 155.2 ppm. = 5.6 cps., = 18 cps. Once more, the structure i s derived from the N.M.R. spectra which i s s i m i l a r to that of the bromo-compound discussed below. This compound was extremely unstable and the pure l i q u i d (which was obtained by e l u t i n g o f f a neutral s i l i c a g e l column with l i g h t petroleum ether) decomposed at room temperature i n seconds. It i s i n t e r e s t i n g that t h i s material was also s e n s i t i v e to base; e l u t i o n down an alumina column produced indene. The increasing i n s t a b i l i t y to acid of the 'XF' adducts going from cyclohexane to phenylethane to indan (and f i n a l l y acenaphthene) was also noted. S o l i d NaCO was e f f e c t i v e in'preventing acid-catalyzed decomposition. 2-bromo-l-fluoro-indan (VIII) 2.8g. of indene was reacted with 6g. of bromine and 13g. of AgF over 1 1/2 hours and worked up i n the usual way. Crude y i e l d was 5.1g. (88%). 2 3 <(>c = 160.4 ppm.; J H f , = 55 cps., = 17 cps. D i s t i l l a t i o n wasn't p o s s i b l e , but ( i n contrast to VII) the material could be p u r i f i e d by e l u t i o n down an alumina column with l i g h t petroleum ether. The expected increase i n s t a b i l i t y going from iodide to bromide was observed, (VII to VI I I ) . In the "*"H spectra the proton next to f l u o r i n e 2 ( i d e n t i f i e d by the c h a r a c t e r i s t i c J^p = 55 cps.) has only one other coupling i n t o i t (Figure 6A). Hence the f l u o r i n e must be i n the 1-position. Furthermore, the proton to s l i g h t l y higher f i e l d (Figure 7A), which must be geminal to the bromine atom, i s s p l i t into 16 l i n e s (thus four couplings) and must be i n the 2-position. The N.M.R. spectra and conformation of VIII are discussed more f u l l y i n Section V. -82-C i s - and trans-l,2-difluoro-acenaphthene(IX, X) 2g. of acenaphthylene were dissolved i n a s t i r r e d mixture of 4-0 ml. benzene, 10 ml. a c e t o n i t r i l e and lOg. AgF. 4g. of iodine was then dissolved i n 40 ml. more of a 4:1 mixture of benzene and a c e t o n i t r i l e ; t h i s s o l u t i o n was then added dropwise to the acenaphthylene/AgF mixture over one hour,, with cooling (ice-bath) and s t i r r i n g . The whole mixture (a heavy p r e c i p i t a t e was formed) was then poured into a l a r g e r volume of a saturated NaHCO aqueous s o l u t i o n and mixed thoroughly to remove any traces of ac i d . This three-phase system (organic and aqueous l i q u i d s , plus s o l i d phase) was f i l t e r e d and.the organic layer separated from the f i l t r a t e and worked with more water. Drying over Na^SO^ and ^ 200^ and removal of solvent produced a dark red viscous 19 l i q u i d , whose F N.M.R. spectrum revealed the presence of at l e a s t two compounds. This crude product mixture was then separated chromatographically by e l u t i n g down a neutral s i l i c a g e l column with l i g h t petroleum ether (B.pt. 37°C). The column f r a c t i o n s were monitored by t h i n - l a y e r chroma-1 19 tography, H N.M.R. (on A-60) and F N.M.R. (on HA-100). F i r s t to come o f f the column was a small amount of s t a r t i n g m a t e r i a l , acenaphthylene, quickly followed by fluoro-acenaphthylene (XI) and l-iodo-2,2-difluoro-acenaphthene (XII) both i n trace q u a n t i t i e s . Then came a major product, trans-1,2-difluoro-acenaphthene (X); fur t h e r e l u t i o n with 20% CH^C^ i n l i g h t petroleum ether produced cis-l,2-difluoro-acenaphthene (IX), contaminated with some high l y coloured ma t e r i a l . The f r a c t i o n s containing and (X) were then p u r i f i e d twice more by e l u t i n g them down s i l i c a g e l columns as above. The i d e n t i f i c a t i o n of these products was pr i m a r i l y by N.M.R., f o r the "^H spectrum of each i s 19 i d e n t i c a l with i t s F spectrum. This unusual feature i s a c h a r a c t e r i s t i c 19 of AX systems such as (IX) and (X); the F spectra of each i s shown i n -83-Figure 12B and 12C, and the H spectra* i n Figures 13A and 13C. Decoupling of the aromatic protons of (X) produced a marked sharpening of the l i n e s , as shown i n Figure 13B, but a s i m i l a r decoupling experiment on(lX) was a f a i l u r e . C r y s t a l l i n e samples of (IX) and (X), which were obtained by slow cooling of an ethanol/water s o l u t i o n , gave s a t i s f a c t o r y elemental analyses. Analysis: Calc. f o r C H F_: C, 75.79; H, 4.21; F,.20.00 Found (transT : C, 75.55; H, 4.00; F, 20.30 Found ( c i s ) : C, 75.95; H, 4.20; F, 19.80 c i s 113°C 5.2 cps. 5.1 cps. 16.4 cps. 190.68 ppm. 3.24T Quantitative values of the y i e l d s i n the r e a c t i o n were not obtained as some material i s l o s t i n the various p u r i f i c a t i o n steps. However, subjective estimates are 10% f o r the trans isomer (IX) and 5% f o r the c i s . . A s e r i e s of experiments were c a r r i e d out to optimize the y i e l d , and determine 19 the r a t i o of t r a n s / c i s (conveniently done by i n t e g r a t i n g the F spectra of the crude product). The % benzene i n the solvent was v a r i e d from 50 - 100% (the remainder being a c e t o n i t r i l e ) and an optimum y i e l d was obtained i n the range 80 - 90° benzene. However, the r a t i o of t r a n s / c i s was constant at 2:1. The analysis of the A^X 2 N.M.R. spectra was done by hand;** agreement with ''Actually they are p a r t i a l H spectra, since the aromatic region i s not shown. **A X^ spectra consist of two unconnected sub-spectra and as such cannot be analyzed by an i t e r a t i v e computer procedure. trans gin.pt. 47°C J u r , 19.13 cps. 3 HF J,,., 1.23 cps. nil Jpp 1.23 cps. <f>c 177.36 ppm. 6 R 4.32 T -84-F i g . 12: F s p e c t r a o f t h e t h r e e main p r o d u c t s o f t h e 'XF' a d d i t i o n t o a c e n a p h t h y l e n e . (A) T r a n s - b r o m o f l u o r i d e . (B) T r a n s - d i f l u o r i d e . (C) C i s - d i f l u o r i d e . -85-1 — I , I I , • , I I I I • . , I . . . . I . J . . . . . I 3.24 4.24 F i g . 13: P a r t i a l H s p e c t r a o f t r a n s - and c i s - d i f l u o r i d e s o f acenaphthene. (A) T r a n s - d i f l u o r i d e , s i n g l e r e s o n a n c e . (B) T r a n s - d i f l u o r i d e , d o u b l e r e s o n a n c e ( I r r a d i a t i o n o f a r o m a t i c r e g i o n ) . (C) C i s - d i f l u o r i d e , r e s o n a n c e . -86-24 M e m t t and Johnson's values i s good f o r the c i s isomer but rather poorer f o r the trans. This i s understandable since the previous analysis would have been c a r r i e d out on a spectra such as Figure 13A rather than Figure 13B. The c i s isomer may be i d e n t i f i e d by: 19 ( i ) l a r g e r F chemical s h i f t from CFClg. 3 and ( i i ) l a r g e r J T I U coupling. rin Trans-l-bromo-2-fluoro-acenaphthene (XIII) A s o l u t i o n containing 2.5g. Br^ i n 25 ml. benzene was added dropwise to a vigorously s t i r r e d suspension of f i n e l y powdered AgF i n 50/50 benzene/acetonitrile at 0°C. Simultaneously, another s o l u t i o n containing 2.0g. of acenaphthylene i n 25 ml. of benzene was also added. This a d d i t i o n was c a r r i e d out over a period of 20 minutes, a f t e r which the r e a c t i o n mixture was immediately f i l t e r e d , washed with NaHCO^ so l u t i o n and then dri e d over Na^SO^/CaSO^. The r e s u l t i n g l i g h t yellow s o l u t i o n was evaporated under vacuum to 5 - 10 ml.* and then eluted down an alumina column with l i g h t petroleum ether. Apart from a small quantity of 19 s t a r t i n g m a terial (which runs very f a s t ) the only product was (XI); the F spectrum i s shown i n Figure 12A and a p a r t i a l "*"H spectrum i n Figure 14B. Decoupling of the aromatic protons revealed that t h i s l a t t e r spectrum was the AB part of an ABX; t h i s i s shown above i n Figure 14A. S e l e c t i v e decoupling, not shown, of the left-hand doublet of collapsed the correspond-ing left-hand doublet i n H^. This confirms the analysis of spectra, and 3 2 3 indicates that has the same sign as J^p The small J ^ = 1.0 cps. also i n d i c a t e s a trans r e l a t i o n s h i p between Br and F. •'Further concentration increases the p o s s i b i l i t y of decomposition. Br H. H ? F 3 . 0 0 3 5 0 4 . 0 0 r 4 . 5 0 F i g . 14: P a r t i a l H s p e c t r u m o f acenaphthene B r F . (B) S i n g l e r e s o n a n c e . (A) d o u b l e r e s o n a n c e , ( i r r a d i a t i o n o f a r o m a t i c r e g i o n ) . -88-The product (XI) i s very unstable and has to be kept well below 0°C unless s t a b i l i z e d by some s o l i d a l k a l i such as Na C0„. A concentrated pentane s o l u t i o n which was cooled i n Dry Ice deposited yellow c r y s t a l s ; however, they proved to have some solvent i n them. A s i m i l a r experiment with ethanol had the same r e s u l t , but c r y s t a l s deposited from t h i s s o l u t i o n were then warmed up to -25°C (Dry Ice/CCl^) and pumped on f o r 4 hours. The r e s u l t of t h i s freeze-drying procedure was a crop of white-yellow c r y s t a l s which had a sharp m.p. of 35°C and whose "Si N.M.R. showed no solvent present; they also gave s a t i s f a c t o r y elemental analysis A n a l y s i s : Calc. f o r C ^ H ^ B r F : C, 57.39; Br, 31.85; F, 7.57 Found : C, 57.16; Br, 31.59 F, 7.13 6 = 4.32x; 6 = 3.52x; cj> = 157.66 ppm. I 2 ^ 3 3 JHF = 2 1 ' 4 C P S > ' JHH = 1 - 0 C p S ' The c r y s t a l s were extremely unstable, being decomposed within minutes at room temperature. The melting point of 35°C i s c u r i o u s l y low, i n comparison with that of s i m i l a r compounds e.g. trans-dibromide m.p. 124°C; 44 t r a n s - d i c h l o r i d e m.p. 67°C ; t r a n s - d i f l u o r i d e m.p. 47°C ( t h i s work). Possibly t h i s has some connection with the i n t r i n s i c tendency to spontaneously decompose. The product (XIII) could be d i s t i n g u i s h e d from the s t a r t i n g m a t e r i a l , acenaphthylene, with t h i n layer chromatography; the two compounds ran very close together (XIII l a s t ) but upon charring with cone. H^SO^, acenaphthylene gives a green colour whereas XIII turns brown. -89-1-fluoro-acenaphthylene (XI) 24 Following the procedure of Me r r i t t and Johnson , c i s -difluoroacenaphthene (X) (1 g.) was refluxed with 3g. of KOH i n 50 ml. of 19 ethanol f o r f i v e hours. The F N.M.R. spectrum of the crude product indicated that most of the s t a r t i n g material had reacted. The product mixture was worked up by removing most of the ethanol i n vacuo, d i s s o l v i n g i n petroleum ether and washing with water. The organic l a y e r was d r i e d , f i l t e r e d and concentrated again, p r i o r to separation on a neutral s i l i c a g e l column with pentane/benzene (70/30). The product (XI) ran ahead of the s t a r t i n g material (IX) and gave a c h a r a c t e r i s t i c yellow colour to the s o l u t i o n . 1 19 Spect r o s c o p i c a l l y , ( H and F N.M.R.) t h i s material appeared to be free of impur i t i e s ; however small amounts of acenaphthylene i t s e l f which were undetected i n the N.M.R. spectrum, were picked out on a TLC plate (very s l i g h t l y ahead of XI). Therefore the material was rerun down an extra long column (60") of neutral s i l i c a g e l with pentane; t h i s removed the r e s i d u a l acenaphthylene. The two compounds could be distinguished on a TLC plate by the f a c t that fluoro-acenaphthylene (XI) fluoresces under UV l i g h t whereas acenaphthylene does not. A c r y s t a l l i n e sample of XI was obtained by cooling a pentane 1 19 . so l u t i o n to -78°C. The H and F N.M.R. of these c r y s t a l s showed no impuri-t i e s or entrapped solvent. m.pt. 3 7 ° C , yellow plates (previously reported as an o i l ) N.M.R. s i n g l e t at 4.00x (besides aromatic region) 19 F N.M.R. s i n g l e t at <j> = 99.4 ppm. The r e a c t i o n y i e l d , which was not measured, was evidently high (from 19 F N.M.R.) but not q u a n t i t a t i v e . S i g n i f i c a n t .amount.s__of s t a r t i n g material remained even with long r e a c t i o n times (24 hours) or high a l k a l i n i t y of the s o l u t i o n . Use of trans-difluoro-acenaphthene (X) lowered the y i e l d somewhat. -91-l-iodo-2,2-difluoroacenaphthene (XIV) The attempted add i t i o n of IF to fluoro-acenaphthylene XI was a f a i l u r e . Iodine (250 mg.) was added i n the usual way ( i n 2.5 ml. of benzene) to a s o l u t i o n of 150 mg. of XI containing 2g. of AgF. Three d i f f e r e n t solvents were t r i e d f o r the r e a c t i o n : pure a c e t o n i t r i l e , 60/40 benzene/ a c e t o n i t r i l e , and pure benzene. In no case was any recognizable product formed, and only i n benzene was a l l the s t a r t i n g material consumed. (Once again pointing up the increased r e a c t i v i t y i n benzene). However, a small quantity of the desired product (XIV) was r e t r i e v e d from the IF r e a c t i o n with acenaphthylene. In the e l u t i o n of the crude product mixture from t h i s r e a c t i o n , the IF^ adduct ran s l i g h t l y ahead of compound X, and was e a s i l y detected by the pink colouration of i t s s o l u t i o n which developed i n a few hours at room temperature. A f t e r two chromato-graphic separations, a s p e c t r o s c o p i c a l l y pure sample was obtained. Y i e l d of XIV from t h i s r e a c t i o n was estimated at only 0.2%. The large geminal F-F coupling (252 cps.) and the presence of only one other spin coupling into 19 1 each F resonance i d e n t i f i e d the product. The quartet m the H spectrum confirmed t h i s . * c ( F l ) = 7 5 - 8 P p m " ' * c ( F 2 ) = 8 7 , 5 P p m * ' 6H = t | , 2 4 ' T 2 J T , r , = 252 cps.; 3 J u r , ( c i s ) = 16.26 cps.; 3 J u r , (trans) = 4.24 cps. r r 2 1 Gem-1,1-bromofluoro-acenaphthene XV 30 mg. of fluoro-acenaphthylene (XI) were dissolved i n dichloromethane and cooled to -78°C; HBr gas was then bubbled i n slowly u n t i l the character-i s t i c yellow colour of XI had disappeared (15 minutes), leaving a cream-coloured s o l u t i o n . The solvent and excess HBr were then removed i n vacuo, leaving a l i g h t brown s o l i d . A l l chromatographic treatment of t h i s material ended i n decomposition. The "*"H spectrum showed only a si n g l e ABX spectrum (AB-part) i n the 19 methylene.region; the F spectrum contained only a quartet at low f i e l d , with t o t a l width of 33 cps., thus r u l i n g out any geminal H-F coupling. The product must then be XV. 6 = 6.14T; 6 = 6.00x: <j) =79.8 ppm. 2 ^ 2 3 3 J o u = 18.3 cps.; J U T , ( c i s ) = 22.8 cps.; J u _ (trans) = 10.3 cps. tin nr rir Gem-1,1-chlorofluoro-acenaphthene (XVI) The same re a c t i o n was performed as above, s u b s t i t u t i n g HC1 f o r HBr, with s i m i l a r r e s u l t s . . The N.M.R. spectra were d i f f e r e n t , however; the s h i f t s of the two protons now coincided very c l o s e l y g i v i n g r i s e to an 1 19 apparent AA'X spectra i . e . a doublet (.H) and a t r i p l e t ( F ) . Again no v i c i n a l products were observed. Pentane was an equally good solvent f o r the r e a c t i o n , which appeared ( s p e c t r o s c o p i c a l l y ) to be qua n t i t a t i v e . 6 ' - 6 U = 5.775-1;$ = 81.3 ppm. H 1 H 2 c 3 3 [ J H F ( c i s ) + J H F (trans)] = 32.8 cps, Gem-1,1-difluoroacenaphthene (XVII) A s o l u t i o n of XV (40 mg.) i n a c e t o n i t r i l e was shaken with 200 mg. of AgF at 20°C. f o r 20 minutes. The s o l i d matter was f i l t e r e d o f f and the a c e t o n i t r i l e removed i n vacuo; TLC showed two compounds both running f a s t , on 19 s i l i c a g e l . F N.M.R. of t h i s material indicated two resonances, a weak one which was fluoro-acenaphthylene (XI) and the other a new ( t r i p l e t ) resonance XVII at s l i g h t l y higher f i e l d of e i t h e r XV or XVI. 1H N.M.R. again showed the s i n g l e t at low f i e l d , c h a r a c t e r i s t i c of XI and also a t r i p l e t at lower f i e l d than that f o r e i t h e r XV or XVI. Integration of t h i s region -93-showed i t to contain two protons (by comparison with aromatic region). 19 Integration of the F resonances.gave the product r a t i o of XVTI/XI as 81%/19% (allowing f o r two f l u o r i n e s i n XVII). Sub s t i t u t i n g XVI f o r XV i n t h i s r e a c t i o n and allowing one hour, gave s u b s t a n t i a l l y the same r e s u l t . This i s conclusive evidence that the new product XVII i s the gem-difluoride. The i d e n t i c a l t r i p l e t s observed i n both 1 19-th e H and F spectra are again c h a r a c t e r i s t i c of an AA'XX' system; t h i s 2 time the large J . . , (= J ™ - 250 cps.) e f f e c t i v e l y reduces the spectra to a AA r r true A X ( i n which J = J . , v , e t c . ) . This feature, which was v e r i f i e d by generating a t h e o r e t i c a l spectrum using a reasonable set of parameters, i s lather unfortunate since only the sum of the v i c i n a l couplings may be extracted. The geminal couplings cannot be measured at a l l . An attempt was made to get around t h i s problem by s e l e c t i v e deuteration; DBr was synthesized from PBr^ (15 ml.) and B^O (9 ml.) according 53 to the procedure i n Shoemaker and Garland . This was then reacted with XI i n the same way as before to produce XV-d^, and exchanged with AgF to give XVII-d^. This product was p u r i f i e d s u c c e s s f u l l y by e l u t i n g down neutral s i l i c a g e l with petroleum ether, but the N.M.R. spectra were once again unusable. The spectrum again showed a broad t r i p l e t with shoulders which couldn't be decoupled from the aromatic region. The l a t t e r region i t s e l f was very broad (>75 cps.), probably due to the p o l a r i z a t i o n of the f i v e -membered r i n g by the gem-difluoro group ( i . e . the CF 2 group might chemically s h i f t one aromatic r i n g r e l a t i v e to the other). The spectrum of a deuterated compound such as XVII-d^ has been 54 thoroughly investigated by Baldeschewieler , and as such i s capable of a n a l y s i s , provided that a reasonably well-resolved spectrum can be obtained. However, the extreme broadness of the l i n e s prevents one from observing the -94-weak t r a n s i t i o n s which are necessary to obtain the f u l l analysis of the spectrum. It turns out, upon examination of t h i s system, that the i n t e n s i t y of these weak l i n e s are proportional to the chemical s h i f t between the two f l u o r i n e s ; normally ( i n XVII i t s e l f ) there i s none, but i n XVII-d^ there i s t h e o r e t i c a l l y a small s h i f t due to the deuterium isotope e f f e c t . From 54 reference , t h i s i s probably of.10 cps. or l e s s ; plugging t h i s chemical s h i f t into the analysis of the system shows that the i n t e n s i t y of the needed weak t r a n s i t i o n s i s vanishingly small. . The only parameters which can be extracted therefore are: <f>c = 84.5 ppm. ; 6 R = 6.52x [ 3 J H F ( c i s ) + 3 J H F (trans)] =26.4 cps. CIS-l,2-dibromo-l-fluoro-acenaphthene (XVIII and TRANS-l,2-dibromo-l- fluoro-acenaphthene (XIX) To 200 mg. of fluoro-acenaphthylene (XI) was added 200 mg. of Br^ 1 19 as a CCl^ s o l u t i o n , over 15 minutes at 20°C. H and F N.M.R. showed that 3 there were two products, of which the predominant one (89%) had a small J ^ F and was therefore assigned as the trans adduct. Cis (XVIII) (11%) <j>c = 83.8 ppm.; 6 R = 4.30T 3 J u r , ( c i s ) = 18.9 cps. Hi Trans (XIX) (89%) cj> = 89.7 ppm.; 6 U =~3.94T C n 3 J ^ F (trans) = 3.1 cps. ( a l l i n benzene solution) 19 The product r a t i o was determined by in t e g r a t i n g the F N.M.R. The rea c t i o n was performed i n CH^CN with the same r e s u l t . -95-CIS-l,2-iodochloro-l-fluoro-acenaphthene (XX) and TRANS-1,2-iodochloro-l- fluoro-acenaphthene (XXI) IC1 (220 mg.) was added to fluoro-acenaphthylene (XI) i n the same 1 19 way as above; H and F N.M.R. again revealed two products, with the 3 predominant one having the smallest J^p and thus was assigned the configuration with iodine and chlorine trans. The product r a t i o was also s i m i l a r , 84/16, i n favour of the t r a n s ( I C l ) adduct. Cis (XX) (16%) $ = 82.2 ppm; &H = 3.67x; 3 I J H F = 19.7 cps. 1 Trans (XXI) (84%) <(> = 74.9 ppm.;6H = 3.68x; 3 J H F = 6.0 cps. (both i n CCl^ s o l u t i o n ) CIS-1- chloro-2-fluoro-acenaphthene (XXII) and TRANS-l-chloro-2-fluoro- acenaphthene (XXIII) 8g. of powdered AgF was added to an a c e t o n i t r i l e s o l u t i o n (50 ml.) cf 2g. of acenaphthylene, and the mixture cooled with an ice bath. 2g. of I C l , d issolved i n 30 ml. of a c e t o n i t r i l e , was then added over 20 minutes to t h i s mixture, with s t i r r i n g . At the end of t h i s period, the r e a c t i o n was worked up i n the usual way—washing with bicarbonate s o l u t i o n , f i l t e r i n g and 19 concentrating. F N.M.R. of t h i s crude product revealed two resonances i n the r a t i o 85/15, and i t was immediately eluted down a neu t r a l s i l i c a g e l column with petroleum ether/benzene. Three compounds were separated; the f i r s t and major component contained no f l u o r i n e and showed a sharp s i n g l e t at 4.45x i n the "H spectrum. This i n d i c a t e d that i t was the trans d i c h l o r i d e of acenaphthene. The mass spectrum, melting point and elemental analysis confirmed t h i s . -96-19 1 The second compound, running close behind, gave F and H N.M.R. spectra almost i d e n t i c a l with that of XIII (see Figures 12A and 14A) and was assigned as the t r a n s - c h l o r o f l u o r i d e (XXIII). The l a s t component, a minor one, was evidently .the c i s - c h l o r o f l u o r i d e (XXII), since there were two low-3 f i e l d protons with a coupling between them of 6.0 cps. (expected f o r J Hn (<f> = 0°)), which were coupled to f l u o r i n e . trans c i s 3 J R F 21.0 cps. 10.0 cps. 2 J u r , 53.5 53.7 nr 3 jHH 1 - ° 6 ' ° 6„ 4.53T 4.87x H l 6„ 3.77T 4.36x H2 $ c 162.5 ppm. 173.3 ppm, (both i n benzene) 1-bromo-acenaphthene (XXIV) 45 Following the procedure of Dewar and Fahey , a s o l u t i o n of acenaphthylene ( l g . ) i n pentane was cooled to -78°C. and then HBr gas bubbled i n u n t i l the yellow colour disappeared. The s o l u t i o n was then immediately placed on a f l a s h evaporator to remove excess HBr and solvent, a f t e r which a cream-coloured s o l i d remained, which was r e c r y s t a l l i z e d from pentane to give white needles, m. pt. 70°C. The "*"H spectra gave the c h a r a c t e r i s t i c ABX pattern, and was ( s p e c t r o s c o p i c a l l y ) free of impurities. -97-1-fluoro-acenaphthene (XXV) • l g . of XXIV was shaken with 2g. powdered AgF f o r 20 minutes i n a c e t o n i t r i l e at room temperature. The grey p r e c i p i t a t e and excess AgF was f i l t e r e d o f f and water and chloroform added to the s o l u t i o n (to remove dissolved AgF). The organic l a y e r was separated, dried and concentrated down c a r e f u l l y without heat. The spectrum showed a set of broad l i n e s i n the methylene region and an.octet at low f i e l d . By c a r e f u l adjustment of the solvent, the complexity of the spectrum was reduced as much as possible (with 60% chloroform, 40% acetone). The l i n e s were furt h e r sharpened by decoupling of the aromatic protons, and t h i s double resonance (Hi) spectra i s shown i n Figure 15, bottom. The spectrum was then analyzed by hand as an ABMX system; values from t h i s a nalysis were used as the input numbers f o r an i t e r a t i v e computer analysis of the spectrum using TWOSUM. The f i n a l computer spectrum, which i s shown above i n Figure 15, top, had an average deviation of only 0.028 cps. from the experimental. Some impurity l i n e s are v i s i b l e i n Figure 15; i t was found impossible to p u r i f y XXV i n any way at a l l , since i t decomposed on alumina and s i l i c a g e l , and with gentle heat, weak acid or base. J u _ ( c i s ) = 29.52 H 3 F J„ „ ( c i s ) = 6.68 H 1 H 2 J u „ (trans)= 21.39 2 J„ „ (trans)= 1.485 H 1 H 3 "J (gem) =-18.30 H 2 H 3 ,(H 1) 3.665T 'J (gem) = 55.59 1 '(H 2) 6.458x ( H3 > 6.661T 158.8 ppm. FLUORO-ACENAPHTHENE ! F i g . 15: P a r t i a l 1H. SDectrum o f acenaphthene f l u o r i d e , d o u b l e r e s o n a n c e ( i r r a d i a t i o n o f a r o m a t i c r e g i o n ) . (Bottom) E x p e r i m e n t a l s p e c t r u m . ( t o p ) C a l c u l a t e d s p e c t r u m ) . -98-APPENDIX A  COMPUTER PROGRAMS For simulation of simple ( i . e . s i n g l e resonance) N.M.R. spectra and analysis thereof the standard programs TWOSUM and LAOCOON were used; 55 these have already been described . To simulate double resonance spectra a program NMDRS^ was obtained from the National Physical Laboratory, Teddington, U.K.; t h i s program was i n ALGOL, and the necessary t r a n s l a t i o n to FORTRAN was kindly c a r r i e d out by Susan Boyd of the Computing Centre, U.B.C. The use of NMDRSis i l l u s t r a t e d i n Appendix B. A p l o t t i n g r o u t i n e , SMASH, f o r N.M.R. spectra, was written by John Coulthard of the Computing Centre; i t enabled the binary output of LAOCOON, TWOSUM or NMDRSto be mateched d i r e c t l y with exper-imental spectra. This was p a r t i c u l a r l y u s e f u l with NMDRS where the linewidths within a given spectrum are not constant. The analysis of the chemical exchange spectra of cyclohexane 37 IF was c a r r i e d out e m p i r i c a l l y ; based on the Gutowsky-Holm equation, a simple program GUTHO was written which ca l c u l a t e d a l l the peak heights, widths, and positi o n s f o r a two-site exchange, with c e r t a i n parameters f i x e d . F i r s t the chemical s h i f t s of each resonance were determined (from low temperature work) and the population r a t i o of the conformers c a l c u l a t e d (from area measurements, e t c . ) . Then the peak p o s i t i o n s , etc. were ca l c u l a t e d by GUTHO f o r a given residence time, T; T was vari e d over a range of 10^ and the calculated spectrum which most c l o s e l y matched the experimental could then e a s i l y be selected. Thus a x value was r e a d i l y obtained f o r each experimental -99-spectra, and allowed the c a l c u l a t i o n of a c t i v a t i o n parameters. This method, while not as rigorous as the l i n e - f i t t i n g approach, has the important advantage of speed; the loss i n accuracy i s believed to be small i f at a l l , on the basis of the-excellent Arrhenius p l o t obtained. 38 Anet and Bourn, i n a study of cyclohexane-d , came to the same conclusion. -100-APPENDIX B  APPLICATION OF NMDRS 19 The F spectrum of l-bromo-2,2-difluoroacenapthene (XII) i s shown i n F i g . 16 and i s b a s i c a l l y an ABX spectrum, with each f l u o r i n e f u r t h e r coupled to two of the r i n g hydrogens, y i e l d i n g a t r i p l e t f o r each AB resonance, ( F i g . 17A £ B). I r r a d i a t i o n of one t r i p l e t i n the weak resonance of F^ a f f e c t s the connected t r i p l e t i n the strong resonance of F^; had there been no extra ' t r i p l e t t i n g ' ( i . e . i f i t had been a simple ABX, instead of ABM^X), t h i s 'spin t i c k l i n g ' would cause the two connected resonance to s p l i t into.two new resonances, whose 59 s p l i t t i n g equals the strength of the i r r a d i a t i n g f i e l d . However, the extra coupling into F^ and F^, causes the t r a n s f e r of h a l f the s p l i t t i n g of the i r r a d i a t e d resonance (F^) to F^; t h i s new s p l i t t i n g , 1/2 J " M F , i s added or subtracted from J depending on 2 " 6 0 how the resonances are connected ( r e g r e s s i v e l y or pr o g r e s s i v e l y ) . The r e s u l t s of two such experiments are shown i n F i g . 17C £ D. I t can be seen that i n one case the t r i p l e t s p l i t t i n g has increased (from 1.7 cps to 2.5 cps) and i n the other i t has decreased. Shown below are the spectra c a l c u l a t e d by NMDRS; the agreement i s very s a t i s f a c t o r y . -101--102-A 1 I T * 1 M9.fi 832. U m.Jb M3.0J SO0.76 19 17: P a r t i a l F s p e c t r u m o f l - b r o m o - 2 , 2 - d i f l u o r o a c e n a p h t h e n e ( X I I ) , c e n t r a l r e s o n a n c e s . (A,B) S .le r e s o n a n c e . (C) Double r e s o n a n c e ( F , ) , w i t h i r r a d i a t i o n o f t h e h i g h f i e l d t r i p l e t i n weak r e s o n a n c e o f F . (D) The r e v e r s e e x p e r i m e n t on F 2 < (E,F) C a l c u l a t e d s p e c t r a . -103-APPENDIX C N.M.R. SPECTRAL ANALYSIS Analysis of the N.M.R. Spectra of Four Interacting Spins — ABXY . Approximation (1) Basic Theory The basic theory f o r the analysis of an ABXY system ( i . e . where i s small but a l l other s h i f t s are large, compared with the respective 57 couplings) has been l a i d down by R e i l l y and Swalen , but t h e i r work was dir e c t e d towards an i t e r a t i v e a n alysis ( i . e . using a computer), and consequently the expressions f o r the positions of the t r a n s i t i o n s and t h e i r i n t e n s i t i e s were not given. In order to analyze c e r t a i n spectra a r i s i n g i n t h i s work, i t was necessary to have the complete theory a v a i l a b l e . The t h e o r e t i c a l basis as given by R e i l l y and Swalen may be described b r i e f l y as follows: Basis functions used are the products of spin functions f o r a four spin system (e.g. aaaa, Baaa, e t c . ) , and the matrix 58 elements are ca l c u l a t e d i n the usual way giv i n g r i s e to a 16 x 16 Hamiltonian. This can be broken down into f i v e sub-matrices, according to the value of F ( t o t a l Z component of the spin angular momentum), since there i s Zi no mixing of functions with d i f f e r e n t F . In the ABXY approximation, there i s no mixing except between states which d i f f e r only i n the interchange of A and B n u c l e i . Thus a l l o f f - d i a g o n a l elements except 1/2 J are zero and the whole 16 x 16 matrix may be diagonalized by four 2 x 2 r o t a t i o n s ; the sixteen energy l e v e l s of the system are therefore given by these diagonal elements. This i s as f a r as the treatment of R e i l l y and Swalen goes; to obtain the wavefunctions corresponding to these energy l e v e l s , we use e i t h e r the basis functions or the row vectors of the r o t a t i o n s . -104-Table VIII Wavefunctions and Energy l e v e l s f o r the ABXY approximation State Wavefunction Energy -sin fa (p<A<Aji) * cos fioU^e) i ( Vx - Vr) -I-D-o M-VA-Va-Vx+vd+J^'x-jY -/+ -sin<ji,(fdjsjd-fcos^U^/f) i(.V*-VY) -J'-D-I z, Jf iz u o, a -2., H-VA -VB~VX-y)i)r)+J'*jx +JY -105-where: D,/COSZ<ft+, =£(VB-VA)-JX' -jr' /XoCOSZ&o =Z(VS-VA)+ jx' ~jr' D-oCosZ^-o =Z(V*-VA)-JX' +JY' D-ICOSZ^-, =Kv* - \k)+jx'+JY' J~~ 4= (JAB  +Jxr) J~~^(JAB ~JXY) Jx ^+(JAX ^JSK) JK- T(JAX ~JBX) JY ~ ~? (JAY  +TSY) I J/^ i~ (JAY ~JBY) DnsinZfa =IXosmZ&-o~iXoS/nZ<l>-0 =D-^//ZZ (/I/=^B (2) Transitions There are 32 allowed t r a n s i t i o n s and 8 combination t r a n s i t i o n s . These may be deduced by considering the f i r s t - o r d e r t r a n s i t i o n s that they go into as ( v n - v ) increases. The p o s i t i o n of each t r a n s i t i o n i s determined by the dif f e r e n c e between the relevant energy l e v e l s ; the i n t e n s i t y of each t r a n s i t i o n i s proportional to the squares of the appropriate matrix elements of the x component of the spin I s where X i s fhe type of n u c l e i whose spin i s changed. Thus i n t r a n s i t i o n -1 -2 , the i n t e n s i t y i s proportional to: H i ' ' -106-Table IX ' Tran s i t i o n s i n the ABXY Approximation T r a n s i t i o n O r i g i n P o s i t i o n Intensity / -I**- -z, z /~$mZ<f+0 3 4 *lz *-0, 5 a *• -k ~k(yA+vj A 7 V - / ; -jr -A, 6 i ( VA +VB) +f~j* +jr -DH> 1 +SW Z$+o 7 *L <- 0? 3 .£,<•/, i ( VA ^ V J ^ ' J V j x +JY-DH 1 +sm2<fH 3 i ( V A*VJ) -J'-J-jx - jY > Z L ; 1 + sinZj*-, 10 -k ( VA + VB) - J -T-Jx Jjr *D+0 I + sinZ&v II i(VA + Va) -J'~T*jx -jY +/Xo 1 -i-smZfco IZ +1, <- o, •k (VA •+ ))Z)-J'-T+jx *•JY+D+I I +3inZ<r>+i 13 <k*-U HVA +v^+J+T-jx -jr+D-/ 1 - smZ<fi, / 4 4 *• 03 i(v*+vZ) ff •f-J'-jx *jr -~&to !- sinZf+o 15 >k<-0.s 1-swZJz-o 16 +Zi<~>lz 4 ( V * + Vs) A 7 * / " ^ +JY+DH /- SinZf+r 17 V, +ILT~ZJx 1 18 VK+J'-J+D-O-D-, CQS2(</lr<f_Q) /9 Vt+J'-J+D-t-D-o Z0 -4<-a 1 -107-Table IX (continued) T r a n s i t i o n O r i g i n P o s i t i o n Intensity 21 / ZZ Vt-f+T'-lXi-lXo Z3 2 4 1 ZS -l,*~Z, 1 1 ' Z6 0z<~k Vr+J-J+IXo'D-,- cos2(<jlr <f{o) Z7 ZS VY+TLJ+ZJr 1 29 0, *- -k VY-T+T-2JY 1 30 31 VY-T*J-D«+D-O 32 *z, 1 33 K+J'-T+D-i+IXo 34 VxJ'-J-D-j-D-o 35 V,-J'*J-DH-&o 3G 37 Vr'T'-J-D-rOo 38 39 4*4 VY-J'+J'-IX.,'D-o sm*(jio- &) to 4<-0s VY-I*T+D+,*D-O sma-(<f>H-<f-o) - l o s -es) Assignment of Lines-(i)Grouping of AB l i n e s into quartets The i n t e r v a l J A T 3 (=2 ( J ' + J ) ) occurs eight times, allowing eight" pa i r s A D of l i n e s to be picked out; these can then be grouped as or Y^ l i n e s , g i v i n g four pa i r s i n each group. The d e c i s i o n as to which p a i r goes with which i s made by comparing the separation of the quartets (=2j ^ i n each assignment with the separation of the strongest pairs ( = 1 + J X ) i n the corresponding part of the X spectrum, (exactly analogous with 58 the ABX system. ( i i ) E x t r a c t i o n of data: ( J ' + J ) and j have been obtained already, i n the assignment of the quartets; -j may be be obtained s i m i l a r l y from the separation of any two AB quartets which d i f f e r i n the state of the X nucleus. The four D's can be measured from the intermediate, spacing i n each quartet ( i . e . between the f i r s t and t h i r d l i n e s ) . 2 ( J ' + J ) i s equal to the separation of the X-quartets; 2[D - D + Q | and 2 [ D_ q - [ come from the separation of the weak pair s i n each of the X-quartets. Thus a l l the data i s a v a i l a b l e except i i ' and (v„ - v.) which must be c a l c u l a t e d from the r e s t , c x y B A (from the d e f i n i t i o n s ) . To c a l c u l a t e intensities, values f o r <f>+1> e"tc., are necessary; these may be obtained from J • and D , etc. -109-? VIII REFERENCES 1. L.D. H a l l £ J . F. Manville, Chem. Comm. 37 (1968). 2. R. J . Abraham £ L. C a v a l l i , Mol. Phys. 9_ 67 (1965). 3. M. Karplus, J . Chem. Phys. 30_ 11 (1959). 4. K. L. Williamson, J. Amer. Chem. Soc. 85_ 516 (1963). 5. P. Laszlo £ P. Schleyer, J . Amer. Chem. Soc. 85_ 2709 (1963). 6. R..J. Abraham £ K. G. R. Pachler, Mol. Phys. 166 (1964). 7. N. Sheppard, C. N. Banwell £ J . J . Turner, Spectrochim. Acta. 16_ 794 (1960). 8. C. N. Banwell £ N. Sheppard Mol. Phys. 3_ 350 (1960). 9. C. N. Banwell £ N. Sheppard, Disc. Farad. Soc. 34_ 115 (1962). 10. T. Schaefer, Canad. J . Chem. 40_ 1 (1962). 11. R. E. Gli c k £ A. A. Bothner-By, J . Chem. Phys. 25 362 (1956). 12. H. S. Gutowsky, G. G. Belford £ P. E. McMahon, J . Chem. Phys. 36_ 3353 (1962). 13. J. .R. Cavanaugh £ B. P. Dailey, J . Chem. Phys. 34 1099 (1961). 14. M. L. Huggins, J . Amer. Chem. Soc. 75_ 4123 (1953). 15. F. A. Bovey, E. W. Anderson, F. P. Hood £ R. L. Kornegay, J . Chem. Phys. 40_ 3099 (1964) . 16. J . D. Roberts, Angew. Chem. 75_ 20 (1963). 17. R. J . Abraham, L. C a v a l l i £ K. G. R. Pachler, Mol. Phys. 11 471 (1966). 18. L. D. H a l l £ J . F. Manville, Chem. £ Ind. 991 (1965). . 19. K. L. Williamson, Yuan-Fang L i , F. H. H a l l £ Susan Swager, J . Amer. Chem. S o c , 88 5678 (1966). 20. N. S. Bhacca £ D. H. Williams, (1964) "Applications of N. M. R. Spectroscopy i n Chemistry" (San Francisco: Holden Day)., p. 164. 21. H. Booth Tetrahedron Letters 411 (1965). -110-22. A. Bowers, L. C. Ibanez, E. Denot £ R. Becerra, J. Amer. Chem. Soc. 8_2 4001 (1960). • 23. H. W. W. E h r l i c h , Acta Cryst. 10_ 699 (1957). 24. R. F. M e r r i t t £ F. A. Johnson, J . Org. Chem. 31_ 1859 (1. ). 25. J . F. Manville, Ph. D Thesis U.B.C. (1967). 26. H. Schmidt £ H. Meinert, Angew. Chem. 71 126 (1959). 27. H. Schmidt £ H. Meinert, Angew. Chem. 7_2 109 (I960). 28. H. Schmidt £ H. Meinert, Angew. Chem. 72_ 493 (1960). 29. R. H. Andreatta £ A. V. Robertson, A u s t r a l . J . Chem. 19 161 (1966). 30. E. L. E l i e l , Angew. Chem. Internat. E d i t . 4_ 761 (1965); see also the following paper by N. C. Fr a n k l i n and H. Feltkamp and a more recent review by J . D. Roberts,Chem. B r i t a i n 529 (1968). 31. (a) F. R. Jensen £ B. H. Beck, J . Amer. Chem. Soc. 90_ 3251 (1968). (b) F. R. Jensen, C. H. Bushweller £ B. H. Beck, J. Amer. Chem. Soc. 91 344 (1969). 32. F.R. Jensen £ L. H. Gale, J . Org. Chem. 25 2075 (1960). 33. E. L. E l i e l £ R. J. L. Martin, J . Amer. Chem. Soc. 9_0 689 (1968). 34. E. L. E l i e l £ R. J. L. Martin, J. Amer. Chem. Soc. 9_0 682 (1968). 35. S. Brownstein £ R. M i l l e r , J . Org. Chem. 24 188 (1959). 36. J . I. Musher, J . Amer. Chem. Soc. 83_ 1146 (1961). 37. H. S. Gutowsky £ C. H. Holm, J . Chem. Phys. 25_ 1228 (1956). 38. F. A. L. Anet £ A. J . R. Bourn, J . Amer. Chem. Soc. 89_ 760 (1967). 39. G. W. Rathjens, J . Chem. Phys. 36 2401.(1962). 40. H. R. Buys £ E.Havinga, Tetrahedron 24_ 4967 (1967). 41. R. A. Austin £\C. P. L i l l y a , J . Org. Chem. 34 1327 (1967). 42. M. Karplus, J . Amer. Chem. Soc. 85_ 2870 (1963). 43. S. L. Smith £ R. H. Cox, J . Phys. Chem. 7_2 198 (1968). 44. S. J . C r i s t o l , F. R. S t e r n i t z £ P. S. Ramey, J. Amer. Chem. Soc. .78/4939.(1956). 45. M. J . S. Dewar £ R. C. Fahey, J . Amer.' Chem. Soc. 85 2245 (1963). -111-46. ' F. A. L. Anet, J . Amer. Chem. Soc. £4 1053 (1962). 47. J . B. Stothers, Can. J . Chem. 45 2943 (1967). 48. E. Premuzic £ L. W. Reeves, Can. J . Chem. 4£ 1870 (1962). 49. L. W. Reeves S K. 0. Stromme, Trans. Farad. Soc. 57_ 390 (1961). 50. R. U. Lemieux S J. W. Lown, Can. J . Chem. 42_ 893 (1964). 51. P. Laszlo, i n Progress i n N.M.R. Spectroscopy III p.231. 52. T. B. Hendrickson, J . Amer. Chem. Soc. 83_ 4537 (1961). 53. D. P. Shoemaker S C . W. Garland, "Experiments i n Physical Chemistry" (McGraw-Hill: N.Y £ San Francisco) 1963. 54. Y. Kanazawa 6 J. D. Baldeschwieler, J . Mol. Spectroscopy 16_ 325 (1965). 55. P.R. Steiner, M.Sc. t h e s i s , U.B.C. 1969. 56. G. G o v i l £ D. H. Whiffen, Mol. Phys. 12 449 (1967). 57. C. A. R e i l l y £ J . D. Swalen, J . Chem. Phys. 34_ 980 (1962). 58. J . A. Fople, W. G. Schneider £ H. J . Bernstein, "High Resolution N.M.R." (McGraw-Hill: N.Y.) 1959. 59. R. Freeman £ W. A. Anderson, J . Chem. Phys. 37_ 2053 (1962). 60. R. Freeman £ Bo Gestblom, J . Chem. Phys. 47 1472 (1967). 

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