UBC Theses and Dissertations

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UBC Theses and Dissertations

Permanganate oxidations and the carboxyl group MacPhee, John Anthony 1970

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ERMANGANATE OXIDATIONS AND THE CARBOXYL GROUP by J . ANTHONY MacPHEE B . S c . , S t . F r a n c i s X a v i e r U n i v e r s i t y , 1965 A THESIS SUBMITTED I N P A R T I A L FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n t h e D e p a r t m e n t o f C h e m i s t r y We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d THE UNIVERSITY OF F e b r u a r y , B R I T I S H 1970 COLUMBIA 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 r e q u i r e m e n t s f o r an advanced degree at the U n i v e r s i t y o f B r i t i s h Co lumb ia , I a g ree tha t 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 r e f e r e n c e and s tudy . I f u r t h e r agree tha p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y purposes may be g r a n t e d by the Head o f my Department o r by h i s r e p r e s e n t a t i v e s . It i s u n d e r s t o o d tha t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . Department o f The U n i v e r s i t y o f B r i t i s h Co lumbia Vancouver 8, Canada ABSTRACT Supervisor: Professor Ross Stewart I n o r d e r t o s t u d y t h e p o s s i b l e e f f e c t s on p e r m a n g a n a t e o x i d a t i o n r e a c t i o n s o f a c a r b o x y l s u s t i t u e n t n e a r t h e r e a c t i n g c e n t r e , t h r e e s y s t e m s w e r e i n v e s t i g a t e d . The f i r s t o f t h e s e s y s t e m s c o n s i s t e d o f t h e 2-and 4 - b e n z h y d r o l c a r b o x y l i c a c i d s . I t was f o u n d t h a t t h e 2-compound r e a c t e d more s l o w l y t h a n t h e 4-compound. The a c t i v a t i o n p a r a m e t e r s a t pH 5.45 show t h a t t h e r a t e d i f f e r e n c e i s a c c o u n t e d f o r e n t i r e l y i n t e r m s o f t h e d i f f e r e n c e i n e n t r o p y o f a c t i v a t i o n b e t w e e n t h e two compounds. S o l u b i l i t y d i f f i c u l t i e s p r e v e n t e d a s t u d y o f t h e r e a c t i o n b e l o w a b o u t pH 5. rPVia k i ^ e ^ i c r e s u l t s i n more b a s i c s o l u t i o n i n d i c a t e t ^ a t t h e pK c o r r e s p o n d i n g t o e i l c o h o l i c OH i o n i z a t i o n i s g r e a t e r f o r t h e 2 - i s o m e r t h a n t h e 4 - i s o m e r . T h i s b e h a v i o u r i s r e a d i l y e x p l a i n e d b y e x a m i n i n g t h e p K 1 s o f s e v e r a l m o d e l compounds. The s e c o n d s y s t e m c o n s i s t e d o f p h t h a l a l d e h y d i c a c i d a n d t e r e p h t h a l a l d e h y d i c a c i d . The b e h a v i o u r e x p e c t e d f o r a l d e h y d e s i s o b s e r v e d e x c e p t f o r p h t h a l a l d e h y d i c a c i d a t pH 1.55. The k i n e t i c r e s u l t s f o r p h t h a l a l d e h y d i c a c i d suggest r a t h e r s t r o n g l y that i t e x i s t s as 3-hydroxy-p h t h a l i d e i n a c i d s o l u t i o n (pH 1.55) a n d a s t h e f r e e a l d e h y d e a b o v e pH 6. T h i s r e s u l t i s shown t o be i n a c c o r d w i t h p r e v i o u s w o r k d e a l i n g w i t h t h e d i v e r s e c h e m i c a l b e h a v i o u r o f p h t h a l a l d e h y d i c a c i d . The t h i r d s y s t e m was t h e 2 - c a r b o x y c y c l o h e x a n o l s y s t e m . The p H - r a t e p r o f i l e s o f a number o f i s o m e r i c 2 - c a r b o x y c y c l o h e x a n o l s were i n v e s t i g a t e d as w e l l a s - t h a t o f t h e p a r e n t compound, c y c l o h e x a n o l . I t was f o u n d t h a t c i s - 2 - h y d r o x y - c y c l o h e x a n e c a r b o x y l i c a c i d (XIV) showed a b e l l - s h a p e r a t e maximum i n i t s p H - r a t e p r o f i l e a r o u n d pH 6, w h i l e t r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d d i d n o t . The p a r e n t compound, c y c l o h e x a n o l , d o e s n o t show s u c h an e f f e c t - t h e p H - r a t e p r o f i l e i s a l m o s t f l a t i n t h e r e g i o n pH 4 t o 8. The p H - r a t e p r o f i l e s o f c i s - 5 - t - b u t y l - c i s - 2 -h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X ) , c i s - 5 - t - b u t y l - t r a n s - 2 h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X I ) , and t r a n s - 5 - t -b u t y l - c i . s _ - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y . l i c a c i d ( X I I ) were a l s o i n v e s t i g a t e d . A mechanism ;-.is p r o p o s e d w h i c h involves two o p p o s e d d i s s o c i a t i o n e q u i l i b r i a i n v o l v i n g h y d r o g e n i o n s . A c o m p a r i s o n o f t h e r e a c t i v i t y o f XIV i n p r o t i u m o x i d e w i t h t h a t i n d e u t e r i u m o x i d e g i v e s e v i d e n c e c o n s i s t e n t w i t h t h e mechanism. The c o n f o r m a t i o n a l a s p e c t s o f t h e r e a c t i o n ( e l u c i d a t e d by means o f t h e c o n f o r m a t i d n a l l y b i a s e d compounds -X, XI and X I I ) were f o u n d a l s o t o be c o n s i s t e n t w i t h t h e p r o p o s e d mechanism. I t was p o s s i b l e t o make a d e c i s i o n b etween t h e two k i n e t i c a l l y i n d i s t i n g u i s h a b l e f o r m s o f t h e p r o p o s e d .mechanism on t h e b a s i s o f t h e a s s e m b l e d . d a t a - i i i -Table of Contents Page Int r o d u c t i o n . 2 Object of the Research 19 General Experimental 21 K i n e t i c Methods 21 K i n e t i c Equations 24 Temperature Con t r o l 27 Buf f e r System 28 A c t i v a t i o n Parameters 28 Compounds and Reagents 30 S e c t i o n A O x i d a t i o n of 2- and 4-Benzhydrolcarboxylie Acids Experimental 41 Product A n a l y s i s 45 Results 45 A c t i v a t i o n Parameters 50 D i s c u s s i o n 52 S e c t i o n B The O x i d a t i o n of P h t h a l a l d e h y d i c A c i d and Terephthalaldehydic A c i d Experimental 60 Products 63 Results 65 D i s c u s s i o n 66 - i v -Page S e c t i o n C The Cyclohexanol System Experimental . 79 Products 81 Results . 83 Cyclohexanol 84 C i s - and trans-2-hydroxycyclohexanecarboxylic acids 87 The 5-t-butyl-2-hydroxycyclohexanecarboxylic a c i d s S5 Conformations 98 A c t i v a t i o n Parameters 106 D i s c u s s i o n 107 Suggestions f o r Further Work , 144 Observations 146 - V -L i s t of Tables Table Page I Rate data f o r 2-benzhydrolcarboxylic a c i d 46 I I Rate data f o r 4-benzhydrolcarboxylic a c i d 46 I I I O x i d a t i o n of 4-benzhydrolcarboxylic a c i d i n base 50 IV Temperature s t u d i e s on 2- and 4-benzhydrolcarboxylic a c i d s . . 52 V Rate data f o r t e r e p h t h a l a l d e h y d i c a c i d and p h t h a l a l d e h y d i c a c i d 65 VI Temperature s t u d i e s on p h t h a l a l d e h y d i c a c i d and t e r e p h t h a l -aldehydic a c i d 66 VII Rate data f o r cyclohexanol 87 VI I I Rate data f o r cis-2-hydroxycyclohexanecarboxylic a c i d 91 IX Rate data f o r trans-2-hydroxycyclohexanecarboxylic a c i d 91 X Rate data i n deuterium oxide f o r cis-2-hydroxycyclohexane-c a r b o x y l i c a c i d 92 XI Rate data f o r trans-2-deuterio-cis-2-hydroxycyclohexane-c a r b o x y l i c a c i d 95 XII Rate data f o r c i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e -c a r b o x y l i c a c i d 96 X I I I Rate data f o r cis- 5 - t - b u t y l - t r a n s - 2 - h y d r o x y c y c l o h e x a n e -c a r b o x y l i c a c i d and t r a n s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o -hexanecarboxylic a c i d 98 XIV Temperature s t u d i e s on cis-2-hydroxycyclohexane-c a r b o x y l i c a c i d 106 XV A n a l y s i s of r a t e data f o r cis-2-hydroxycyclohexanecarboxylic-a c i d according t o Reaction Schemes I and I I 119 XVI A n a l y s i s of r a t e data f o r compound XIV i n deuterium oxide according to Reaction Schemes I and I I . . • 120 XVII A n a l y s i s of r a t e data f o r compound X according to Reaction Schemes I and I I 122 XVIII C o l l e c t i o n of data f o r compounds XIV(H 20), XIV(D20) and X(H20) according to Reactions Schemes I and I I 123 XIX A c t i v a t i o n parameters at pl-l 5.88 of c i s - 2 - h y d r o x y c y c l o -hexanecarboxylic a c i d , 139 - v i -L i s t of Figures Figure Page I Rate p l o t f o r the o x i d a t i o n of 2-benzhydrolcarboxylic a c i d . . 43 I I Rate p l o t f o r the o x i d a t i o n of 4-benzhydrolcarboxylic a c i d . . 44 I I I pH-rate p r o f i l e f o r 2-benzhydrolcarboxylic a c i d o x i d a t i o n . . . 47 IV pH-rate p r o f i l e f o r 4-benzhydrolcarboxylic a c i d o x i d a t i o n . . . 48 V K i n e t i c behaviour of 4-benzhydrolcarboxylic a c i d i n base.... 51 Vi a Temperature dependence of 2-benzhydrolcarboxylic a c i d o x i d a t i o n i 53 VIb Temperature dependence of 4-benzhydrocarboxylic a c i d o x i d a t i o n 54 VII Rate p l o t f o r the o x i d a t i o n o f phthalaldehyde a c i d 61 V I I I Rate p l o t f o r the o x i d a t i o n of t e r e p h t h a l a l d e h y d i c a c i d .... 62 IX pH-rate p r o f i l e s f o r o x i d a t i o n of p h t h a l a l d e h y d i c a c i d and t e r e p h t h a l a l d e h y d i c a c i d 64 X Temperature dependence of p h t h a l a l d e h y d i c a c i d o x i d a t i o n ... 67 XI Temperature dependence of t e r e p h t h a l a l d e h y d i c a c i d o x i d a t i o n 68 XII P h t h a l a l d e h y d i c a c i d o x i d a t i o n at pH 3.68 74 X I I I P h t h a l a l d e h y d i c a c i d o x i d a t i o n at pH 1.55 76 XIV Rate p l o t f o r cyclohexanol o x i d a t i o n 85 XV pH-rate p r o f i l e f o r cyclohexanol o x i d a t i o n 86 XVI Rate p l o t f o r o x i d a t i o n of cis-2-hydroxycyclohexanecarboxylic a c i d 88 XVII Rate p l o t f o r o x i d a t i o n of trans-2-hydroxycyclohexane c a r b o x y l i c a c i d 89 XVIII pH-rate p r o f i l e s f o r the o x i d a t i o n of c i s - 2 - h y d r o x y c y c l o -hexanecarboxylic a c i d and trans-2-hydroxycyclohexane-c a r b o x y l i c a c i d 90 - v i i -Figure Page XIX pD-rate p r o f i l e i n deuterium oxide f o r c i s - 2 - h y d r o x y c y c l o -hexanecarboxylic a c i d ^3 XX pH-rate p r o f i l e f o r the o x i d a t i o n of t r a n s - 2 - d e u t e r i o - c i s - 2 -hydroxycyclohexanecarboxylic a c i d 94 XXI pH-rate p r o f i l e f o r the o x i d a t i o n of c i s - 5 - t - b u t y l - c i s - 2 -hydroxycyclohexanecarboxylic a c i d ^7 XXII NMR of cis-2-hydroxycyclohexanecarboxylic a c i d "^0 XXIII NMR of t r a n s - 2 - d e u t e r i o - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c \ a c i d 1 0 1 1 n 7 XXIVa NMR of trans-2-hydroxycyclohexanecarboxylic a c i d XXIVb NMR of c i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d - v i i i -A l w a y s we d r a w t h a t l i n e b e t w e e n f o r m a n d v o i d a n d s t e p a c r o s s i t s o l e m n l y a s t h o u g h e a c h d a y w e r e g e n e s i s a n d i t i s . G w e n d o l y n MacEwen - i x -ACKNOWLEDGEMENT I w o u l d l i k e t o t h a n k P r o f e s s o r R o s s S t e w a r t f o r h i s g u i d a n c e a n d e n c o u r a g e m e n t d u r i n g t h e c o u r s e o f t h i s w o r k . I w o u l d a l s o l i k e t o t h a n k t h e N a t i o n a l R e s e a r c h C o u n c i l o f C a n a d a f o r i t s f i n a n c i a l m u n i f i c e n c e , 2 INTRODUCTION The o x i d a t i o n o f s e c o n d a r y a l c o h o l s by p e r m a n g a n a t e i s a t o p i c t h a t h a s r e c e i v e d a c o n s i d e r a b l e amount o f 2 2 3 4 5 a t t e n t i o n ' ' ' ' ' . D e t a i l e d m e c h a n i s t i c s t u d i e s h a v e b e e n c a r r i e d o u t b y s e v e r a l r e s e a r c h e r s a p p l y i n g t h e t h e o r i e s and m a k i n g u s e o f t h e d e v i c e s o f modern c h e m i c a l k i n e t i c s . A s a r e s u l t o f t h e s e s t u d i e s , c e r t a i n m e c h a n i s t i c c o n c l u s i o n s may be d r a w n a b o u t t h e p e r m a n g a n a t e o x i d a t i o n o f s e c o n d a r y a l c o h o l s , a l t h o u g h some o f t h e f i n e r p o i n t s a r e n o t f r e e o f a m b i g u i t y . The i n v e s t i g a t i o n s o f S t e w a r t o n b e n z h y d r o l " 1 , 2 D i c w d i i. ci.nu. vein u e i J - J J L I I C L C H U H p i i e u y J . L I J . J. i U U J . Oiuc u i y JL CCL.L. yj j.nCJ X & , 5 S t e w a r t a n d Mocek on f l u o r a l h y d r a t e , and L i t t l e r on 3 4 c y c l o h e x a n o l '' a l l l e n d i m p o r t a n t i n f o r m a t i o n u s e f u l i n f r a m i n g a m e c h a n i s t i c p i c t u r e o f t h e r e a c t i o n . The m e c h a n i s t i c i n f e r e n c e s a r e , i n t h e m a i n , d r a w n f r o m t h e f o l l o w i n g e x p e r i m e n t a l f a c t s ; a . The o b s e r v e d r e a c t i o n s a r e f i r s t o r d e r i n p e r m a n g a n a t e and f i r s t o r d e r i n a l c o h o l , w i t h t h e e x c e p t i o n o f t h e o x i d a t i o n o f b e n z h y d r o l s i n s u l f u r i c a c i d s o l u t i o n s ^ . b . The p r o d u c t i s a k e t o n e . I f t h e k e t o n e i s e n o l i z a b l e f u r t h e r d e g r a d a t i o n o f t h e m o l e c u l e may t a k e p l a c e m a k i n g k i n e t i c s t u d i e s more d i f f i c u l t and l i m i t i n g t h e u s e f u l n e s s o f t h e r e a c t i o n s y n t h e t i c a l l y . 3 c . The s t o i c h i o m e t r y o f t h e r e a c t i o n d e p e n d s u p o n t h e a c i d i t y o f t h e medium a n d t o some e x t e n t on t h e c h a r a c t e r o f t h e r e d u c t a n t . T h i s o f c o u r s e h a s b e e n known f o r some t i m e . I n s t r o n g a c i d ( d e s i g n a t i n g t h e r e d u c t a n t a s H^Z a n d t h e p r o d u c t k e t o n e as Z) we h a v e : 2MnO~ + 5H 2Z —* 2 M n 2 + + 5Z + 6 0H~ + 2H 20 I n g e n e r a l , t h e r e d u c t i o n o f manganese f r o m M n ( V I I ) t o t J n ( I I ) r e q u i r e s a s t r o n g r e d u c t a n t s u c h a s o x a l i c a c i d a s w e l l a s s t r o n g a c i d . The o x i d a t i o n o f b e n z h ' y d r o l i n a c i d s o l u t i o n ^ y i e l d s M n ( I V ) as p r o d u c t b u t L i t t l e r ^ a p p e a r s t o o b s e r v e M n ( I I ) as p r o d u c t i n t h e o x i d a t i o n o f c y c l o h e x a n o l i n 1 m o l a r s u l f u r i c a c i d . I n s t r o n g b a s e we h a v e : 2MnO~ + H Z + 20H~ -> 2Mn0 2~ + Z + H 20 . I n n e u t r a l , w e a k l y a c i d a n d w e a k l y a l k a l i n e s o l u t i o n s t h e s t o i c h i o m e t r y i s : 3H ?Z + 2MnO~ —> 3Z + 2Mn0 2 + 20H~ + 2H ?0 . d. The r a t e v e r s u s pH p l o t s f o r s e c o n d a r y a l c o h o l s e x h i b i t t h r e e r e g i o n s o f c o n t r a s t i n g b e h a v i o u r . 3 The r e a c t i o n i s c a t a l y s e d b y s t r o n g a c i d s , L i t t l e r h a s f o u n d t h a t t h e r a t e o f o x i d a t i o n o f c y c l o h e x a n o l i n 4 s u l f u r i c a c i d s o l u t i o n s o b e y s t h e f o l l o w i n g k i n d o f e q u a t i o n : k = a + b [ H 3 0 + ] , w h e r e a a n d b a r e c o n s t a n t s . F l u o r a l h y d r a t e o x i d a t i o n " 3 i n s u l f u r i c a c i d s o l u t i o n s shows a f i r s t o r d e r d e p e n d e n c e on t h e a c i d i t y (H ) o f t h e medium-. The r e a c t i o n i s a l s o c a t a l y s e d b y s t r o n g base"*". The r a t e o f r e a c t i o n o f b e n z h y d r o l i n b a s i c s o l u t i o n i s g i v e n b y -d[Mn0~] = k [ H 2 Z ] [MnO~][OH~] . d t B e n z h y d r o l d o e s n o t i o n i z e c o m p l e t e l y i n a q u e o u s s o l u t i o n s o f s t r o n g b a s e s o t h a t i t i s n o t p o s s i b l e t o d e c i d e w h e t h e r t h e r o l e o f h y d r o x i d e i s t h e i o n i z a t i o n o f b e n z h y d r o l o r s o m e t h i n g e l s e . S t u d i e s on f l u o r o a l c o h o l s ( s u c h a s 2 5 a r y l t r i f l u o r o m e t h y l c a r b x n o l s " , f l u o r a l h y d r a t e a n d g 1 , 1 , 1 , 3 , 3 , 3 - h e x a f l u o r o - 2 - p r o p a n o l ) , w h i c h i o n i z e c o m p l e t e l y i n a q u e o u s s o l u t i o n s , r e v e a l t h e f u n c t i o n o f t h e b a s e i n p r o d u c i n g a l k o x i d e i o n . The a l k o x i d e i o n i s more r e a c t i v e t h a n t h e n e u t r a l a l c o h o l . I n t h e r e g i o n b e t w e e n pH ~ 2 to 10 t h e r a t e ( e x c l u d i n g t h e f l u o r o a l c o h o l s w h i c h i o n i z e i n t h i s r e g i o n ) i s a l m o s t , b u t n o t q u i t e , i n d e p e n d e n t o f a c i d i t y ^ - ' 3 . . A s m a l l i n c r e a s e i n t h e r a t e i s o b s e r v e d as t h e a c i d i t y i s i n c r e a s e d f r o m pH 10 t o 2. 5 e. E x p e r i m e n t s u s i n g MnO^ i n d i c a t e t h a t t h e o x y g e n f o u n d i n t h e p r o d u c t k e t o n e d o e s n o t o r i g i n a t e i n t h e oxidant"'",. f . S u b s t a n t i a l d e u t e r i u m i s o t o p e e f f e c t s have b e e n o b s e r v e d . F o r t h e o x i d a t i o n o f b e n z h y d r o l i n n e u t r a l a s w e l l a s i n 1 9 b a s i c s o l u t i o n t h e v a l u e o f k^/k^ i s a b o u t 7 ' , w h i l e f o r 3 c y c l o h e x a n o l a t pH 4.6 i t i s 4.4 . S t i l l l a r g e r e f f e c t s 2 o c c u r i n t h e o x i d a t i o n o f a r y l t r i f l u o r o m e t h y l c a r b i n o l s ( 16 i n t h e r e g i o n o f pH 7 up t o 0.2N NaOH) and i n t h e o x i d a t i o n o f f l u o r a l h y d r a t e ^ (^14 i n t h e pH r a n g e 5 - 1 0 ) . T h e s e r e s u l t s a f f o r d c o m p e l l i n g e v i d e n c e f o r t h e s e v e r i n g o f t h e h y d r o g e n a t t a c h e d t o t h e a l p h a - c a r b o n o f t h e a l c o h o l i n t h e r a t e c o n t r o l l i n g s t e p o f t h e o x i d a t i o n . The d i s t u r b i n g l y l a r g e i s o t o p e e f f e c t i n t h e o x i d a t i o n o f a r y l t r i f l u o r o m e t h y l c a r b i n o l s w i l l m e r i t some d i s c u s s i o n l a t e r on i n t h i s t h e s i s . j g . I n two i n s t a n c e s t h e e f f e c t o f s u b s t i t u t i o n i n t h e a r o m a t i c r i n g on t h e o x i d a t i o n o f s e c o n d a r y a l c o h o l s h as b e e n 4- A 2 ' 9 s t u d i e d . 2 A r y l t r i f l u o r o m e t h y l c a r b i n o l s , when o x i d i z e d u n d e r c o n d i t i o n s s u c h t h a t t h e a l c o h o l i s p r e d o m i n a t e l y i o n i z e d , g i v e t h e s t a r t l i n g r e s u l t o f a l m o s t n e g l i g i b l e s u b s t i t u e n t e f f e c t . The Hammett p l o t y i e l d s a d i s p i r i t i n g c u r v a t u r e w h i c h ha s n o t y e t b e e n a d e q u a t e l y e x p l a i n e d . The c u r v a t u r e i s s l i g h t however and i t i s c l e a r t h a t a ny a p p r o p r i a t e v a l u e o f P must a p p r o a c h z e r o c l o s e l y . 6 I n t h e b e n z h y d r o l s y s t e m a t pH 7 t h e r a t e s o f p-Me and p-CC^H, as w e l l a s t h e u n s u b s t i t u t e d compound, h a v e b e e n 9 m e a s u r e d * A l t h o u g h t h e number o f compounds i s s m a l l , s t a t i s t i c a l a n a l y s i s o f t h e d a t a d o e s p o i n t o u t t h a t t h e c o r r e l a t i o n i s p r o b a b l y r e a l a n d t h a t t h e v a l u e o f ; p: i s - 0 . 7 2 . h. The a c i d c a t a l y s e d p a r t o f t h e r e a c t i o n b e a r s some d i f f e r e n c e s t o w a r d s t h e r e a c t i o n u n d e r o t h e r c o n d i t i o n s . 3 The a.sotope e f f e c t f o r c y c l o h e x a n o l o x i d a t i o n c h a n g e s f r o m k^/k = 4.4 f o r t h e a c i d i n d e p e n d e n t r e a c t i o n t o a v a l u e o f 1.7 i n 1.1 m o l a r s u l f u r i c a c i d . I n a d d i t i o n t o t h i s t h e u n c a t a l y s e d r e a c t i o n a p p e a r s t o be u n a f f e c t e d when t h e s o l v e n t i s c h a n g e d f r o m p r o t i u m o x i d e t o d e u t e r i u m o x i d e , w h i l e t h e r e i s a l a r g e s o l v e n t i s o t o p e e f f e c t i n 0.45 m o l a r s u l f u r i c a c i d o f k^ n / k t I n = 2.37 f o r t h e a c i d c a t a l y s e d r e a c t i o n " ^ , 2 2 A c h a n g e o f r e a c t i o n o r d e r f r o m s e c o n d t o f i r s t a s t h e medium becomes more a c i d i c t h a n -0.5 h a s b e e n o b s e r v e d f o r t h e o x i d a t i o n o f b e n z h y d r o l ^ . When t h e t o t a l , o r d e r i s f i r s t t h e r e i s a f i r s t o r d e r d e p e n d e n c e on s u b s t r a t e c o n c e n t r a t i o n a n d z e r o o r d e r d e p e n d e n c e on p e r m a n g a n a t e c o n c e n t r a t i o n . T h i s b e h a v i o u r o f b e n z h y d r o l i s q u i t e d i f f e r e n t f r o m t h a t o f c y c l o h e x a n o l a n d i s p u r p o r t e d t o be c a u s e d b y r a t e d e t e r m i n i n g f o r m a t i o n o f c a r b o n i u r n whose 6 9 r e a c t i o n w i t h p e r m a n g a n a t e i s e x t r e m e l y f a s t . 7 H a v i n g a s s e m b l e d a t l e a s t a quorum o f t h e f a c t s t h e p r o p o s e d mechanisms w i l l now be d e l i n e a t e d . The r e a c t i o n i n b a s i c s o l u t i o n between b e n z h y d r o l and permanganate c l e a r l y i n v o l v e s f o r m a t i o n o f a l k o x i d e i o n w h i c h t h e n r e a c t s w i t h p e r m a n g a n a t e t o l o s e h y d r o g e n e i t h e r a s h y d r i d e i o n o r h y d r o g e n atom. The o b s e r v a t i o n t h a t t h e d e u t e r i u m i s o t o p e e f f e c t i s l a r g e and t h a t t h e o x y g e n o f t h e o x i d a n t d o e s n o t a p p e a r i n t h e o x i d i z e d p r o d u c t l e a d s t o t h i s c o n c l u s i o n ^ , . The mechanism, i f one c o n s i d e r s a h y d r i d e t r a n s f e r as t h e r a t e c o n t r o l l i n g s t e p , c a n be w r i t t e n a s : l . a . (C,.H_) oCH0H + 0H~ ^  ( C r H c ) „ C H O ~ + H_0 b b 2. b o 2 2 s l o w _ b. ( C v H c ) „ C H O " + MnOT • (C,.H_) oC0 + HMnO. o 5 4 6 b 2 4 _ f a s t _ c . HMnO" + MnO~ —>• 2MnO~ + 2H R e a c t i o n I . e . h a s b e e n i n d i c a t e d by Pode and W a t e r s ' ^ t o be a v e r y r a p i d r e a c t i o n so t h a t t h e Mn(V) s p e c i e s HMnO^ w o u l d n o t be o b s e r v e d d u r i n g t h e r e a c t i o n i f t h e r e a c t i o n s e q u e n c e r e p r e s e n t e d b y E q u a t i o n 1 r e p r e s e n t s t h e t r u e s i t u a t i o n . I f one v i s u a l i z e s a r a t e c o n t r o l l i n g s t e p i n v o l v i n g h y d r o g e n atom t r a n s f e r f r o m t h e a n i o n t o p e r m a n g a n a t e i t i s p o s s i b l e t o d e s c r i b e i t i n t h e f o l l o w i n g way: 8 2.a. ( C v H j ^ C H O H + OH ~ y IC. H,.)c"HO + H_0 O D 2 O 5 2 b. (CvH c)„CHO~ + MnO" S l ° - W ( C ^ H c ) n C O ~ + HMnO~ b o 2 4 o b z A 4 * - - f f l ^ t - = c . (C rH c)„CO + MnO. , (C r H c ) „ C O + MnO. 6 b z 4 6 5 2 4 M e c h a n i s m 2 h a s g a i n e d c o n s i d e r a b l e p o p u l a r i t y o v e r m e c h a n i s m l 7 ' 3 ' 1 f o r r e a s o n s w h i c h we w i l l now c o n s i d e r . The p r i n c i p a l r e a s o n f o r t h e l a c k o f f a i t h i n m e c h a n i s m 1, w h i c h was i n i t i a l l y f a v o u r e d , r e s t s c h i e f l y u p o n t h e i n s e n s i t i v i t y o f t h e o x i d a t i o n o f a r y l t r i f l u o r o m e t h y l c a r b i n o l s t o s u b s t i t u t i o n i n t h e a r o m a t i c r i n g . F o r r a t e - d e t e r m i n i n g h y d r i d e t r a n s f e r a n e g a t i v e v a l u e o f p i s a n t i c i p a t e d w h i l e , a s p o i n t e d o u t ^ l~v -~>T r ^  / " l , "1 s~> r* -F -p / ~ i •!-- l ^ T o i l l J ry f-\ / J_» w v v^ - , -J_ ^ -l_ -L ^ I l-v«_.»_^ w I - W . The e n h a n c e d r a t e o f o x i d a t i o n o f b e n z h y d r o l i n b a s e c a n be r a t i o n a l i z e d , e a s i l y i n t e r m s o f a h y d r o g e n a t o m t r a n s f e r 11 1? m e c h a n i s m . The p K 1 s o f b e n z h y d r o l " a n d k e t y l r a d i c a l c o r r e s p o n d i n g t o t h e f o l l o w i n g e q u a t i o n s h a v e b e e n e s t i m a t e d . ( C , H J _CHOH > (C rH_)_CHO~ + H + pK ^ 15 6 5 2 < D 3 2 • — (C rH_)_COH -: > ( C c H r ) o C 0 ~ + H + pK ^ 9 . 2 6 5 2 6 5 2 i. — The h i g h e r a c i d i t y o f t h e k e t y l r a d i c a l t e l l s u s t h a t k e t y l r a d i c a l a n i o n i s more s t a b l e r e l a t i v e t o k e t y l r a d i c a l t h a n b e n z h y d r o l a n i o n i s r e l a t i v e t o b e n z h y d r o l i t s e l f . C o n s e q u e n t l y t h e r e a c t i o n , i f i t p r o c e e d s w i t h h y d r o g e n a t o m t r a n s f e r a n d t h e t r a n s i t i o n s t a t e r e s e m b l e s p r o d u c t s , s h o u l d be f a s t e r f o r 9 b e n z h y d r o l a n i o n t h a n f o r u n i o n i z e d b e n z h y d r o l . U n f o r t u n a t e l y t h e f o r e g o i n g c o n s t i t u t e s an argument t h a t i s n o t u n i q u e . A d i s c u s s i o n o f t h e same k i n d c a n r e a d i l y be made t o i n c l u d e a h y d r i d e t r a n s f e r mechanism as w e l l . One w o u l d e x p e c t h y d r i d e l o s s t o be e a s i e r f r o m t h e a n i o n t h a n f r o m t h e u n c h a r g e d s u b s t r a t e b e c a u s e t h e f o r m e r i s more e l e c t r o n r i c h b u t t h e argument u s e d t o r a t i o n a l i z e a h y d r o g e n atom t r a n s f e r mechanism may a l s o be u s e d h e r e . The pK o f be/izophenone, c o r r e s p o n d i n g t o t h e f o l l o w i n g e q u i l i b r i u m , h a s ] 3 b e e n m e a s u r e d ' i n s u l f u r i c a c i d s o l u t i o n . (C(.H;.) 2 C 0 H + 1 y ( C c H 5 ) 2 C ° + H + ' P K = _ 6 - 2 • T h i s pK s a y s t h a t b e n z o p h e n o n e i s more s t a b l e r e l a t i v e t o p r o t o n a t e d b e n z o p h e n o n e ( b o t h i n i t i a l p r o d u c t s o f h y d r i d e r e m o v a l f r o m b e n z h y d r o l and b e n z h y d r o l a n i o n r e s p e c t i v e l y ) t h a n b e n z h y d r o l a n i o n i s t o b e n z h y d r o l . So t h e r e a c t i o n o f b e n z h y d r o l a n i o n t o f o r m b e n z o p h e n o n e s h o u l d be f a s t e r t h a n . t h e r e a c t i o n o f b e n z h y d r o l t o f o r m p r o t o n a t e d b e n z o p h e n o n e , i f t h e t r a n s i t i o n s t a t e r e s e m b l e s p r o d u c t s s u f f i c i e n t l y f o r t h e s e s t a b i l i t y r e l a t i o n s h i p s t o a p p l y . The r e a c t i o n i n n e u t r a l s o l u t i o n i s much s l o w e r 1 . P r e s u m a b l y t i e r e a c t i n g s p e c i e s a r e n e u t r a l b e n z h y d r o l and p e r m a n g a n a t e i o n . The i s o t o p e e f f e c t u n d e r t h e s e c o n d i t i o n s g i s s t i l l l a r g e (k-./k- = 7.3 a t pH 7) and as m e n t i o n e d 1 0 9 p r e v i o u s l y a r h o v a l u e o f -0.72 was o b s e r v e d . T h e s e r e s u l t s a r g u e more s t r o n g l y i n f a v o u r o f a h y d r i d e a b s t r a c t i o n m e c h a n i s m (3) t h a n one w h i c h i n v o l v e s h y d r o g e n atom a b s t r a c t i o n . 3 . a . (C rH_) _CH0H + MnOT ( C r H c ) n C O H + + HMnO" o b z 4 6 5 2 4 b. HMnO^ + MnO~ 2MnO^ + H+ c. 2 H 2 0 + 3MnO^ £f£? MnC»2 + 2MnO~ + 40H~ R e a c t i o n 3.b. i n v o l v i n g M n ( V I I ) a n d Mn(V) was shown b y Pode an d W a t e r s " ^ t o be i n s t a n t a n e o u s . R e a c t i o n 3 . c , t h e d i s p r o p o r t i o n a t i o n o f m a n g a n a t e t o p e r m a n g a n a t e a n d manganese d i o x i d e i s known t o o c c u r i n s o l u t i o n s w h i c h a r e l e s s b a s i c t h a n a b o u t 1 m o l a r i n h y d r o x i d e i o n . I n s o l u t i o n s w h i c h a r e 14 n e u t r a l o r a c i d i c t h e d i s p r o p o r t i o n a t i o n i s i n s t a n t a n e o u s The p e r m a n g a n a t e o x i d a t i o n o f c y c l o h e x a n o l i n a c i d 3 s o l u t i o n h a s b e e n s t u d i e d b y L i t t l e r . The d e p e n d e n c e o f r a t e c o n s t a n t on a c i d i t y h a s a l r e a d y b e e n m e n t i o n e d . On t h e b a s i s o f t h e r e d u c e d d e u t e r i u m i s o t o p e e f f e c t (1.7 a t 27°C) and t h e r a t e e n h a n c e m e n t • ( 2 . 4 ) i n D 2 S 0 4 / D 2 0 t h e f o l l o w i n g m e c h a n i s m 3 f o r t h e a c i d c a t a l y s e d m e c h a n i s m was p r o p o s e d : 4. a. MnO~ + H +- HMnO^ b . HMnO. + R-CHOH > R-CHOMnO- + H o 0 4 2 -< 2 3 2 c. R^CHOMnO -^S- W R„C0H + M n 0 o 2 3 2 3 11 d. R 2COH + MnO~(HMn0 4) - ^ 5 - R 2 C O H + + MnC>4 (HMnC>4* e. Mn(VI) ^ M n ( I V ) + M n ( V I I ) I f one c o n s i d e r s t h e l a r g e d e u t e r i u m i s o t o p e e f f e c t s commonly 7 o b s e r v e d m p e r m a n g a n a t e o x i d a t i o n s , t h e s m a l l e f f e c t n o t e d i n t h i s c a s e seems i n d i c a t i v e o f some c h a n g e i n v o l v i n g t h e r a t e c o n t r o l l i n g s t e p . The c h a n g e p r o p o s e d i n 4.b. and c. i s p r o b a b l y a r e a s o n a b l e a l t e r n a t i v e . The r a t e e n h a n c e m e n t i n d e u t e r a t e d a c i d s o l u t i o n i s e n t i r e l y i n a c c o r d w i t h t h e 15 known w e a k e n i n g o f a c i d s m d e u t e r i u m o x i d e . i n d e u t e r a t e d a c i d s o l u t i o n t h e e q u i l i b r i u m 4.a. w i l l be d i s p l a c e d t o t h e r i g h t c a u s i n g 4.b. t o be d i s p l a c e d t o t h e r i g h t a s w e l l , . r e s u l t i n g i n a n a c c e l e r a t i o n o f t h e s l o w s t e p 4.c. I n s u l f u r i c a c i d s o l u t i o n s t h e o x i d a t i o n o f b e n z h y d r o l h a s b e e n i n v e s t i g a t e d i n some d e t a i l b y Banoo a n d 6 9 S t e w a r t ' . The m o s t u n u s u a l f e a t u r e o f t h i s r e a c t i o n i s t h e c h a n g e f r o m s e c o n d o r d e r k i n e t i c s t o f i r s t o r d e r i n s o l u t i o n s more a c i d i c t h a n H - 0 . 5 . The r e a c t i o n was f o u n d t o be f i r s t o o r d e r i n b e n z h y d r o l a n d z e r o o r d e r i n p e r m a n g a n a t e o v e r a f i v e - f o l d v a r i a t i o n i n p e r m a n g a n a t e c o n c e n t r a t i o n . The i s o t o p e e f f e c t ( k T I / k ^ ) i n t h e r e g i o n H = -0.5 t o -1.2 i s Ir D ^ o 1.1, c o n t r a s t i n g w i t h t h e r e s u l t a t pH 7 w h e r e t h e i s o t o p e e f f e c t i s 7.3. The r a t e c o n s t a n t i s f o u n d t o c o r r e l a t e w i t h t h e a c i d i t y o f t h e medium a s r e f l e c t e d bv t h e H f u n c t i o n . o The m e c h a n i s m u n d e r t h e s e c o n d i t i o n s i s t h o u g h t t o be t h e 12 f o l l o w i n g : 5.a. (C rH c ;)„CHOH + H + ( C r H c ) _ C H + + H o 0 6 5 2 6 5 2 2 b. (C J L ) _CH + + MnO~ p r o d u c t s . 6 5 2 4 The r a t e d e t e r m i n i n g i o n i z a t i o n o f b e n z h y d r o l was p r o v e d by m e a s u r i n g t h e r a t e o f i o n i z a t i o n a t c o m p a r a b l e a c i d i t i e s i n t h e a b s e n c e o f p e r m a n g a n a t e . The a g r e e m e n t b e t w e e n t h e r a t e o f i o n i z a t i o n a n d t h e r a t e o f o x i d a t i o n i s c l o s e . The f a s t s t e p p r e s u m a b l y c o n s i s t s o f t h e f o r m a t i o n o f an e s t e r (CgHj.) 2CH-0-MnC>2 whose v a r i o u s modes o f d e c o m p o s i t i o n a r e d i s c u s s e d b y Banoo a n d S t e w a r t ^ . A d i s c u s s i o n o f t h e a l k a l i n e o x i d a t i o n o f a r y l t r i f l u o r o m e t h y l c a r b i n o l s w o u l d be s i m i l a r t o t h a t f o r b e n z h y d r o l . I n t h e c a s e o f t h e f l u o r o a l c o h o l s i t i s p o s s i b l e t o d e m o n s t r a t e t h e f u n c t i o n o f h y d r o x i d e i o n b e c a u s e o f t h e e n h a n c e d a c i d i t y r e s u l t i n g f r o m t h e a t t a c h e d f l u o r i n e . The 2 a l c o h o l s s t u d i e d b y S t e w a r t a n d V a n d e r L i n d e n h a d pK v a l u e s i n t h e v i c i n i t y o f 12. U n d e r c o n d i t i o n s s u c h t h a t t h e a l c o h o l was o n l y s l i g h t l y i o n i z e d t h e r a t e i s d i r e c t l y p r o p o r t i o n a l t o h y d r o x i d e i o n c o n c e n t r a t i o n . However a s t h e a l c o h o l becomes c o m p l e t e l y i o n i z e d t h e i n f l u e n c e o f h y d r o x i d e i o n l e v e l s o f f . T h i s s u r e l y i n d i c a t e s t h a t t h e k i n e t i c d e p e n d e n c e on h y d r o x i d e i o n i s t h e r e s u l t o f a p r e - e q u i l i b r i u m o f t h e k i n d i n E q u a t i o n 1.a. and n o t a n y t h i n g more c o m p l i c a t e d t h a n t h a t . The f a i l u r e o f s u b s t i t u e n t s t o h a v e a n y m e a s u r a b l e e f f e c t on t h e r a t e h a s 13 a l r e a d y b e e n n o t e d . The p e r m a n g a n a t e o x i d a t i o n o f f l u o r a l h y d r a t e h a s r e c e i v e d some a t t e n t i o n " * a n d a l t h o u g h i t i s n o t a c t u a l l y a s e c o n d a r y a l c o h o l t h e r e s e m b l a n c e i s c l o s e e n o u g h f o r a p r o f i t a b l e d i s c u s s i o n o f i t h e r e . One o f t h e m o s t s t r i k i n g f e a t u r e s o f t h e r e a c t i o n i s t h e d i f f e r e n t r e a c t i v i t y shown by t h e v a r i o u s s p e c i e s d e r i v e d f r o m f l u o r a l h y d r a t e . The o r d e r o f r e a c t i v i t y t o w a r d s MnO^ i s a s f o l l o w s : 0" 0" OH CF-X-H >> cee-H >> CFC-H 3 J 3| 31 0- OH OH T h i s i s t h e o r d e r t o be e x p e c t e d i f t h e o x i d a t i o n i n v o l v e s h y d r i d e i o n r e m o v a l f r o m t h e f l u o r a l h y d r a t e s p e c i e s . H o w e v e r , b e c a u s e o x i d a t i o n i n v o l v e s a l o s s o f e l e c t r o n s , t h i s i s t h e b e h a v i o u r t h a t m i g h t be o b s e r v e d , no m a t t e r w h a t t h e m e c h a n i s m m i g h t be ( h y d r i d e o r atom l o s s ) . T h i s same p o i n t h a s b e e n b r o u g h t f o r w a r d e l s e w h e r e 1 ^ . A m o s t i n t e r e s t i n g s i d e l i g h t o f t h i s w o r k i s t h e 17 18 t h e o r e t i c a l d i s c u s s i o n g i v e n b y K u r z ' i n v o l v i n g a t r e a t m e n t t e r m e d b y t h a t a u t h o r a s " T r a n s i t i o n S t a t e C h a r a c t e r i z a t i o n " . I f i t i s p o s s i b l e t o o b s e r v e a r e a c t i o n w h i c h i s c a t a l y s e d and t h e same r e a c t i o n u n c a t a l y s e d , one i s a b l e , u s i n g K u r z ' t r e a t m e n t , t o c a l c u l a t e t h e v i r t u a l e q u i l i b r i u m f o r t h e d e c o m p o s i t i o n o f t h e t r a n s i t i o n s t a t e w i t h t h e c a t a l y s t p r e s e n t t o a t r a n s i t i o n s t a t e i n w h i c h t h e c a t a l y s t i s a b s e n t . The scheme i 14 p r e s e n t e d by K u r z w i l l c l a r i f y t h i s A + C — A T + C • AC AC1 Products H e r e A i s t h e r e a c t a n t and C i s t h e c a t a l y s t . The v i r t u a l e q u i l i b r i u m o f i n t e r e s t i s r e p r e s e n t e d by K . The e q u i l i b r i u m i s t e r m e d v i r t u a l b e c a u s e e x p e r i m e n t a l l y i t d o e s n o t t a k e p l a c e s i n c e t r a n s i t i o n s t a t e s have v e r y s h o r t l i f e t i m e s . A k n o w l e d g e o f K , K] and K T e n a b l e s one t o i n f e r K as i n any t h e r m o d y n a m i c c y c l e . T h a t a c t i v a t i o n e q u i l i b r i a and a v i r t u a l e q u i l i b r i u m a r e i n v o l v e d i n no way a l t e r s t h e v a l i d i t y o f t h e t r e a t m e n t . I f k^ r e f e r s t o t h e u n i m o l e c u l a r r e a c t i o n (Rate = k^[A] ) and k 2 t o t h e b i m o l e c u l a r r e a c t i o n ( R a t e = k 2 [ c ] [ A ] ) , t h e e q u a t i o n s o f K u r z f o r t h e d i s s o c i a t i o n o f t h e c a t a l y s e d t r a n s i t i o n s t a t e i n t o t h e u n c a t a l y s e d t r a n s i t i o n s t a t e a r e : 6. a. F o r H + c a t a l y s i s P K a = log(k^/k^) b . F o r OH c a t a l y s i s p K ^ = l o g ( k ^ k 2 ) + p K ^ . S i n c e h y d r o x i d e i o n c a t a l y s i s w i l l be r e f e r r e d t o i t i s b e s t t o c l a r i f y what i s meant by t h i s . I t c o n s i s t s o f a p r e -e q u i l i b r i u m p r o t o n r e m o v a l f r o m t h e s u b s t r a t e and s u b s e q u e n t r e a c t i o n n o t i n v o l v i n g c a t a l y s t . S u ch a p r e - e q u i l i b r i u m 15 d i s t i n g u i s h e s s p e c i f i c h y d r o x i d e i o n c a t a l y s i s f r o m g e n e r a l b a s e c a t a l y s i s a n d h e r e we a r e c o n c e r n e d w i t h t h e f o r m e r . The a p p l i c a t i o n o f 6.a. o r 6.b. i s s i m p l e . F r o m t h e e x p e r i m e n t a l r e s u l t s i t i s p o s s i b l e t o c a l c u l a t e v/hat t h e v i r t u a l e q u i l i b r i u m c o n s t a n t i s . By a s s u m i n g a l t e r n a t e l y t h a t t h e t r a n s i t i o n s t a t e i n v o l v e s no r e a c t i o n o r c o m p l e t e r e a c t i o n i t i s p o s s i b l e , i n p r i n c i p l e , t o compute a v a l u e o f t h e c o n s t a n t f o r t h e s e e x t r e m e c a s e s . The e x p e r i m e n t a l v a l u e s h o u l d l i e b e t w e e n t h e two e x t r e m e s a n d b y a s s u m i n g a l i n e a r c h a n g e i n pK a' r e s u l t i n g f r o m v a r i o u s d e g r e e s o f b o n d f o r m a t i o n one c a n c a l c u l a t e t h e d e g r e e o f bond f o r m a t i o n c o r r e s p o n d i n g t o t h e r e a l s i t u a t i o n . To be more c o n c r e t e one m i g h t c a l c u l a t e t h e e q u i l i b r i u m c o n s t a n t f o r t h e f o l l o w i n g , u s i n g t h e d a t a o f 5,17. S t e w a r t a n d Mocek OH CF. H . . , OMnO.. 3 OH 4 CF, OH OH .. OMnO 3 The a p p r o p r i a t e e q u a t i o n t o u s e i n t h i s c a s e i s 6.a. To make an e s t i m a t e o f K, ' one f i r s t c o n s i d e r s w h a t t h e m e c h a n i s m m i g h t b e . T h i s d i s c u s s i o n f o l l o w s c l o s e l y t h a t g i v e n by Kurz" 1 a n d we w i l l u s e h i s e s t i m a t e s o f t h e pK's o f t h e v a r i o u s s p e c i e s o f i n t e r e s t . 16 I f t h e m e c h a n i s m f o r b o t h c a t a l y s e d and u n c a t a l y s e d r e a c t i o n s i n v o l v e s t r a n s f e r o f h y d r i d e i o n f r o m s u b s t r a t e t o p e r m a n g a n a t e , one c a n s a y t h a t i n t h e c a s e o f 0% bond f o r m a t i o n a t t h e t r a n s i t i o n s t a t e t h e i o n i z a t i o n r e s e m b l e s t h a t o f HM n 0 4 ( p K = -5.1p w h i l e f o r 100% r e a c t i o n a t t h e t r a n s i t i o n s t a t e t h e i o n i z a t i o n r e s e m b l e s t h a t o f E^MnO^ (pK e s t i m a t e d a t 9 ) . The v a l u e o f pK,. c a l c u l a t e d f r o m t h e e x p e r i m e n t a l c l f ,. ^  c  d a t a i s 0.4. T h e s e t h r e e numbers g i v e a . v a l u e o f 39% f o r t h e e x t e n t o f bond m a k i n g a t t h e t r a n s i t i o n s t a t e . The a l t e r n a t i v e m e c h a n i s m , h y d r o g e n atom t r a n s f e r , may be t r e a t e d i n t h e same way. F o r 0% bond f o r m a t i o n t h e pK e s t i m a t e i s s t i l l t h e same. F o r 100% r e a c t i o n a t t h e t r a n s i t i o n s t a t e t h e d i s s o c i a t i o n r e s e m b l e s t h a t o f E^MnO^ ( e s t i m a t e d pK = - 1 . 0 ) . The e x p e r i m e n t a l v a l u e o f 0.4 f a l l s o u t s i d e t h e r a n g e a l l o w e d a n d c o n s e q u e n t l y t h e m e c h a n i s m i n v o l v i n g h y d r o g e n atom t r a n s f e r i s n o t c o n s i d e r e d v a l i d . Of c o u r s e , i f t h e c a t a l y s e d a n d u n c a t a l y s e d r e a c t i o n s d i f f e r i n m e c h a n i s m t h i s f o r m a l i s m b r e a k s down. K u r z h a s e x a m i n e d t h e f l u o r a l h y d r a t e o x i d a t i o n f o r t h e s i t u a t i o n s i n w h i c h e a c h o f t h e p r o t o n s number b e l o w c a n be c o n s i d e r e d a s i o n i z i n g f r o m t h e t r a n s i t i o n s t a t e OH (3) I C F 3 — C ... H ... Mn0 3H(l) OH (2) 17 and t h e r e s u l t i s i n v a r i a b l y s i m i l a r t o t h a t q u o t e d - t h e e x p e r i m e n t a l pK ^ i s c o m p a t i b l e w i t h h y d r i d e i o n t r a n s f e r b u t n o t h y d r o g e n atom t r a n s f e r . K u r z h a s s u g g e s t e d t h a t t h i s r e s u l t c o u l d be i n v a l i d a t e d i f t h e s u c c e s s i v e r e a c t i o n s b e t w e e n f l u o r a l h y d r a t e a n d p e r m a n g a n a t e a l t e r n a t e d w i t h r e s p e c t t o m e c h a n i s t i c t y p e b u t t h i s l o g i c a l a l t e r n a t i v e h a s n o t b e e n c o n s i d e r e d s e r i o u s l y . 4 B a r t e r a n d L i t t l e r h a v e o b s e r v e d t h a t a v a r i e t y o f o n e - e l e c t r o n o x i d a n t s ( V ( V ) , Ce (IV) , M n ( I I I ) , Co ( I I I ) ) a t t a c k e t h e r s v e r y much more s l o w l y t h a n a l c o h o l s u n d e r n e u t r a l o r m i l d l y a c i d i c c o n d i t i o n s , w h i l e p e r m a n g a n a t e d o e s n o t . T h e s e o n e - e l e c t r o n o x i d a n t s p r e s u m a b l y h a v e no mode o f r e a c t i o n o t h e r t h a n h y d r o g e n atom t r a n s f e r o r e l e c t r o n t r a n s f e r . P e r m a n g a n a t e h a s a c h o i c e b e t w e e n h y d r i d e a n d h y d r o g e n atom t r a n s f e r a n d i t s f a i l u r e t o b e h a v e l i k e t h e s e o t h e r o x i d a n t s may i n d i c a t e a d i f f e r e n t m e c h a n i s m - n a m e l y h y d r i d e t r a n s f e r . A n e t h e r i s f o r m a l l y s i m i l a r t o a s e c o n d a r y a l c o h o l , R^R^CHOX, wh e r e X r e p r e s e n t s a n a l k y l g r o u p i n s t e a d o f h y d r o g e n . I n d e e d an e t h e r , w e re i t o x i d i z e d b y h y d r i d e l o s s , m i g h t r e a c t more r e a d i l y t h a n t h e c o r r e s p o n d i n g s e c o n d a r y a l c o h o l b e c a u s e o f t h e i n d u c t i v e e f f e c t o f t h e a l k y l g r o u p ^ . 18 SUMMARY The m a i n p o i n t o f a r g u m e n t w i t h r e s p e c t t o t h e p e r m a n g a n a t e o x i d a t i o n o f a l c o h o l s c o n c e r n s w h e t h e r h y d r o g e n atom o r h y d r i d e i o n i s b e i n g a s s u m e d b y p e r m a n g a n a t e i n t h e t r a n s i t i o n stateZ The p r i n c i p a l a r g u m e n t u s e d i n f a v o u r o f t h e f o r m e r v i e w p o i n t i s t h e f a i l u r e o f a r y l t r i f l u o r o m e t h y l c a r b i n o l s t o e x h i b i t a s u b s t i t u e n t e f f e c t ^ . A r g u m e n t s b a s e d on t h e e f f e c t o f s u b s t i t u e n t s on t h e o x i d a t i o n o f b e n z h y d r o l i n n e u t r a l s o l u t i o n ^ a n d t h e o r e t i c a l c o n s i d e r a t i o n s e v o l v e d b y K u r z 1 ^ i n d i c a t e t h a t t h e h y d r i d e m e c h a n i s m i s more p r o b a b l e . H o w e v e r t h e s i t u a t i o n m i g h t be r e g a r d e d a s o p e n a n d c a l l i n g f o r f u r t h e r i n v e s t i g a t i o n s w h i c h m i g h t s o l v e t h e m e c h a n i s t i c . d i l e m m a i n a more c o n c l u s i v e way. 19 OBJECT OF THE RESEARCH The m o t i v a t i o n b e h i n d i n v e s t i g a t i n g t h e p e r m a n g a n a t e o x i d a t i o n o f c a r b o x y l s u b s t i t u t e d s e c o n d a r y a l c o h o l s l i e s i n t h e a b i l i t y o f t h i s s u b s t i t u e n t t o i n f l u e n c e t h e c o u r s e and r a t e o f a r e a c t i o n b y b o n d i n g d i r e c t l y w i t h t h e r e a c t i n g c e n t r e i n t h e t r a n s i t i o n s t a t e . " N e i g h b o u r i n g g r o u p 19 20 21 p a r t i c i p a t i o n " o f t h i s k i n d i s w e l l d o c u m e n t e d ' ' A v a r i e t y o f r o l e s c a n be assumed by t h e c a r b o x y l f u n c t i o n d e p e n d i n g on t h e e n e r g e t i c s o f t h e r e a c t i o n i n q u e s t i o n . S u b s t i t u t i o n r e a c t i o n s o c c u r r i n g a t a s a t u r a t e d c a r b o n c e n t r e c a n b e g r e a t l y a c c e l e r a t e d b y s u i t a b l y p l a c e d c a r b o x y l a t e b u t t h i s e f f e c t i s n o t o b s e r v e d f o r t h e u n i o n i z e d c a r b o x y l . g r o u p . The n a t u r e o f t h e p a r t i c i p a t i o n i s c l e a r l y i n d i c a t e d f o r t h e c a s e o f t h e solve- l y s i s o f s o d i u m 4 - b r o m o b u t y r a t e i n n e u t r a l 22 s o l u t i o n . The o b s e r v e d p r o d u c t i s n o t 4 - h y d r o x y b u t y r a t e b u t r a t h e r t h e c o r r e s p o n d i n g l a c t o n e . E s t e r h y d r o l y s e s i n v o l v i n g e s t e r s o f v a r i o u s k i n d s 20 h a v e r e c e i v e d a g r e a t d e a l o f a t t e n t i o n . I n t r a m o l e c u l a r e f f e c t s i n v o l v i n g b o t h c a r b o x y l a n d c a r b o x y l a t e c a t a l y s i s h a v e 21 23 b e e n d i s c o v e r e d b y many w o r k e r s ' 20 I n v i e w o f t h i s a n d c e r t a i n s p e c u l a t i v e f e a t u r e s o f p e r m a n g a n a t e o x i d a t i o n s o u t l i n e d i n t h e i n t r o d u c t i o n a n d t o be c o n s i d e r e d l a t e r , i t seemed w o r t h w h i l e t o u n d e r t a k e an e x a m i n a t i o n o f p e r m a n g a n a t e o x i d a t i o n s i n r e l a t i o n t o c a r b o x y l e f f e c t s . 21 GENERAL EXPERIMENTAL K i n e t i c M e t h o d s Two a n a l y t i c a l m e t h o d s w e r e u s e d t o d e t e r m i n e r e a c t a n t c o n c e n t r a t i o n a s a f u n c t i o n o f t i m e i n t h i s w o r k - a. t i t r a t i o n a n d b. s p e c t r o p h o t o m e t r y . a. The m o s t commonly u s e d t e c h n i q u e i s t h e s t a n d a r d i o d o m e t r i c d e t e r m i n a t i o n o f manganese s p e c i e s w i t h o x i d a t i o n l e v e l g r e a t e r t h a n t w o . T h i s mode o f a n a l y s i s h a s b e e n u s e d i n p e r m a n g a n a t e 7 24 o x i d a t i o n w o r k v e r y f r e q u e n t l y ' '. The m e t h o d c o n s i s t s o f m i x i n g t h e manganese s o l u t i o n t o be a n a l y s e d w i t h a d i l u t e s o l u t i o n o f s u l f u r i c a c i d (0.2M) c o n t a i n i n g e x c e s s i o d i d e . The manganese i s r e d u c e d t o manganese o f o x i d a t i o n s t a t e two and a t t h e same t i m e an e q u i v a l e n t amount o f i o d i n e i s f o r m e d . The i o d i n e i s t i t r a t e d w i t h s t a n d a r d t h i o s u l f a t e s o l u t i o n u s i n g a s t a r c h i n d i c a t o r . I t i s c u s t o m a r y t o c a r r y o u t t h e a n a l y s i s u n d e r a b l a n k e t o f c a r b o n d i o x i d e . The i o d i d e s o l u t i o n i s p r e p a r e d b y a d d i t i o n o f c a r b o n a t e t o w a t e r , t h e n an e x c e s s amount o f s u l f u r i c a c i d a n d f i n a l l y s o l i d p o t a s s i u m i o d i d e . The c a r b o n d i o x i d e l i b e r a t e d when t h e s u l f u r i c a c i d i s a d d e d p u r g e s t h e s o l u t i o n o f d i s s o l v e d o x y g e n and p r o v i d e s , a p r o t e c t i v e l a y e r d u r i n g t h e a n a l y s i s . O x y g e n o x i d i z e s i o d i d e t o i o d i n e and t h e p r e c a u t i o n i s n e c e s s a r y when t h e t o t a l number o f e q u i v a l e n t s o f i o d i n e p r o d u c e d i n t h e a n a l y s i s i s s m a l l . 22 b. Some o f t h e k i n e t i c e x p e r i m e n t s , i n p a r t i c u l a r t h o s e c o n d u c t e d i n b a s i c s o l u t i o n , i n d e u t e r i u m o x i d e and i n t h e p r e s e n c e o f l o w c o n c e n t r a t i o n s o f s u b s t r a t e , w e r e f o l l o w e d u s i n g a s p e c t r o p h o t o m e t r y t e c h n i q u e . The o x i d a t i o n i n b a s i c s o l u t i o n p r o d u c e s a d i f f e r e n t manganese p r o d u c t t h a n i n n e u t r a l a n d a c i d s o l u t i o n . I n s o l u t i o n s more b a s i c t h a n a b o u t pH 12 t h e manganese p r o d u c t i s m a n g a n a t e , MnO^. The v i s i b l e s p e c t r a o f p e r m a n g a n a t e and m a n g a n a t e a r e q u i t e d i s t i n c t w i t h maximum a b s o r b a n c e s a t d i f f e r e n t w a v e l e n g t h s . H o w e v e r , t h e r e a p p e a r s t o be no s u i t a b l e w a v e l e n g t h a t w h i c h o n l y one o f t h e s e s p e c i e s i s f o u n d t o a b s o r b . C o n s e q u e n t l y i t i s n e c e s s a r y t o m e a s u r e t h e a b s o r b a n c e a t two d i f f e r e n t w a v e l e n g t h s and c a l c u l a t e t h e c o n c e n t r a t i o n o f e a c h s p e c i e s f r o m t h e known e x t i n c t i o n c o e f f i c i e n t s a t t h e s e w a v e l e n g t h s . The w a v e l e n g t h c h o s e n 7 w e r e t h o s e n o t e d b y S t e w a r t a f t e r Zimmerman, n a m e l y 426 my a n d 522 my. A b s o r b a n c e m e a s u r e m e n t s w e r e made u s i n g a B a u s c h a n d Lomb 502 r e c o r d i n g s p e c t r o p h o t o m e t e r . T h i s i s t r u e f o r a n a r b i t r a r y m i x t u r e o f m a n g a n a t e and p e r m a n g a n a t e . I n t h e p r e s e n t c a s e i n i t i a l l y t h e r e i s o n l y p e r m a n g a n a t e and w i t h t i m e m a n g a n a t e g r a d u a l l y r e p l a c e s i t k e e p i n g t h e t o t a l amount o f manganese c o n s t a n t . At 522 my t h e e x t i n c t i o n c o e f f i c i e n t o f p e r m a n g a n t e i s 2370 7 and o f m a n g a n a t e 387 . Thus f o r a 1 cm. p a t h l e n g t h t h e a b s o r b a n c e A i s 23 A 5 2 2 = 2 3 7 0 [ M n O 4 ] + 3 8 7 [ M n 0 4 ] Flowever we know t h a t t h e m a n g a n a t e i s g e n e r a t e d a s t h e p e r m a n g a n a t e i s u s e d up g i v i n g us MnO~ - ( A 5 2 2 ~ 3 8 7 t M n ° 4 J Q ) / 1 9 8 3 • Thus with t h e a d d i t i o n a l c o n s t r a i n t o f h a v i n g t h e sum o f MnC>4 and MnO^ a c o n s t a n t i t i s p o s s i b l e t o d e t e r m i n e t h e c o n c e n t r a t i o n o f b o t h s p e c i e s f r o m t h e a b s o r b a n c e at a s i n g l e w a v e l e n g t h . The r e a c t i o n i n n e u t r a l and a c i d i c s o l u t i o n p r o d u c e s MnC>2 a s t h e manganese p r o d u c t . The pH o f t h e s o l u t i o n s was m a i n t a i n e d w i t h p h o s p h a t e b u f f e r s and i t was n o t e d t h a t t h e p r o d u c t MnC» 2 shows no t e n d e n c y t o w a r d s p r e c i p i t a t i o n , u n d e r t h e c o n d i t i o n s u s e d , u n t i l a d a y o r more h a d e l a p s e d . T h i s i s c o n t r a s t e d w i t h t h e l e s s v e r s a t i l e c a r b o n a t e b u f f e r s w h i c h t e n d t o d e p o s i t MnC>2 s o l i d e a r l y i n a k i n e t i c r u n and make them u n s u i t a b l e . T h i s r e l u c t a n c e 24 o f p h o s p h a t e b u f f e r s t o d e p o s i t M n 0 2 h a s b e e n n o t e d b e f o r e a n d makes them u s e f u l f o r s t u d i e s i n w h i c h p e r m a n g a n a t e i s r e d u c e d t o M n ( I V ) . I n t h e p r e s e n t w o r k t h e s p e c t r o p h o t o m e t r i c m e t h o d was e m p l o y e d f o r r u n s c a r r i e d o u t i n d e u t e r i u m o x i d e s o l v e n t and t h o s e i n w h i c h t h e c o n c e n t r a t i o n o f s u b s t r a t e h a d t o be s m a l l b e c a u s e o f l o w s o l u b i l i t y . I n t h e s e c a s e s t h e 24 a b s o r b a n c e was m e a s u r e d a t 525 my and t h e r a t e c o n s t a n t d e t e r m i n e d i n a manner d i s c u s s e d b e l o w . F o r a b s o r b a n c e m e a s u r e m e n t s a t 525 mp a C a r y 16 s p e c t r o p h o t o m e t e r was u s e d . K i n e t i c E q u a t i o n s The r e a c t i o n s w e r e i n v a r i a b l y f i r s t o r d e r i n s u b s t r a t e c o n c e n t r a t i o n a n d f i r s t o r d e r i n p e r m a n g a n a t e c o n c e n t r a t i o n . B e c a u s e manganese s p e c i e s w e r e t h e o n l y o n e s o b s e r v e d a n a l y t i c a l l y a n d b e c a u s e two d i f f e r e n t s t o i c h i o m e t r i c s p r e v a i l a t d i f f e r e n t a c i d i t i e s t h e e x a c t f o r m o f t h e k i n e t i c e q u a t i o n s i s d e p e n d e n t on s e v e r a l f a c t o r s . a. When t h e pH o f t h e medium i s g r e a t e r t h a n a b o u t 12 t h e f o l l o w i n g s t o i c h i o m e t r y h o l d s : 2MnO~ + H 2Z + 20H~ — y 2MnO^ + Z + H 2 0 . A s p e c i a l f o r m o f t h e k i n e t i c e q u a t i o n o b t a i n s when t h e r e a c t a n t s a r e m i x e d i n p r e c i s e l y t h e i r s t o i c h i o m e t r i c q u a n t i t i e s . I n t h i s c a s e s t a r t i n g w i t h 7. - d[MnO~] = k [ M n O ~ ] [ H 2 Z ] d t we h a v e , a f t e r e x p r e s s i n g t h e s u b s t r a t e c o n c e n t r a t i o n i n t e r m s o f p e r m a n g a n a t e c o n c e n t r a t i o n 8. k t = 1 1 . 2 |MnO- ] [ MnO" ] Q 25 H e r e [MnO^] r e p r e s e n t s t h e c o n c e n t r a t i o n o f p e r m a n g a n a t e a t t i m e t and [MnO^ ] i s t h e i n i t i a l c o n c e n t r a t i o n . E q u a t i o n 8. c a n be e x p r e s s e d , i n t e r m s o f t h e v o l u m e (V^) o f t h i o s u l f a t e n e e d e d t o t i t r a t e a l i q u o t s o f t h e r e a c t i o n m i x t u r e , g i v i n g : 9. k t = V -V, o t '5 [H„Z ] V, - 4\ L 2 Jo t — F - o I f , h o w e v e r , t h e r e a c t a n t s a r e i n i t i a l l y c o m b i n e d i n a n o n - s t o i c h i o m e t r i c r a t i o a = [ H 2 Z J Q / [ M n 0 4 - 1 0 ' t h e k i n e t i c e x p r e s s i o n t a k e s t h e f o l l o w i n g f o r m : 10. k t = 4.606 a l o g [ H 2 Z ] o ( 2 a - l ) V. + V ( 2 a - 5 ) / 5 t o_ 2a ( V t - f o j b. I f t h e medium i s more a c i d i c t h a n a b o u t pH 12 t h e f o l l o w i n g s t o i c h i o m e t r y o p e r a t e s : 2Mn0 4 + 3H 2Z —->• 2MnC>2 + 3Z + 20H + 2H 20 M i x i n g t h e r e a c t a n t s i n i t i a l l y i n s t o i c h i o m e t r i c p r o p o r t i o n s l e a d s t o 11. 3 k t = 1 2 Mn0 4] [ M n 0 4 ] o 26 and a l s o 12. k t = V -V. o . t [ H 2 Z ] o V t . 2 V o When t h e r a t i o a = [H.Z ] / [ M n O J i s L 2 Jo' L 4J o n o n - s t o i c h i o m e t r i c we h a v e : 13. k t = 4.606a l o g [H 2Z] Q ( 2 a ~ 3 ) 3 ( V t + V o ( 2 a - 5 ) / 5 ) 2 a ( V . - 2 V ) t o B e c a u s e o f t h e i r s i m p l i c i t y E q u a t i o n s 12. and 9. w e r e m o s t f r e q u e n t l y u s e d . E q u a t i o n s 13 a n d 10. a p p l y t o a f e w k i n e t i c r u n s a nd t h e i r u s e i s n o t e d w h e r e a p p l i c a b l e . The more g e n e r a l E q u a t i o n s 13. and 10, h a v e n o t b e e n p r e v i o u s l y d e r i v e d a nd t h e i r d e r i v a t i o n s a r e c o n s e q u e n t l y g i v e n i n A p p e n d i x A. The r e m a i n i n g e q u a t i o n s h a v e b e e n i n u s e f o r 7 some t i m e and t h e i r d e r i v a t i o n s a r e t o be f o u n d e l s e w h e r e . The r a t e c o n s t a n t s w e r e d e t e r m i n e d u s i n g t h e v a r i o u s e x p r e s s i o n s by p l o t t i n g t h e a p p r o p r i a t e f u n c t i o n a g a i n s t t i m e . The s l o p e o f t h i s s t r a i g h t l i n e i s d i r e c t l y r e l a t e d i f n o t a c t u a l l y e q u a l t o t h e r a t e c o n s t a n t . The s l o p e c a n be d e t e r m i n e d e i t h e r g r a p h i c a l l y o r by t h e m e t h o d o f l e a s t s q u a r e s . I f was f o u n d t h a t i f t h e p o i n t s do n o t h a v e much s c a t t e r t h e v a l u e s o f t h e r a t e c o n s t a n t d e t e r m i n e d . g r a p h i c a l l y a n d b y l e a s t s q u a r e s w e r e c l o s e r t o e a c h t h a n t h e r e p r o d u c i b i l i t y o f t h e r a t e d e t e r m i n a t i o n . 27 T e m p e r a t u r e C o n t r o l M o s t k i n e t i c e x p e r i m e n t s w e r e c a r r i e d o u t i n a f l a s k i m m e r s e d i n a w a t e r b a t h w h i c h i s f u r n i s h e d w i t h a 100 W a t t h e a t e r , a m o v a b l e - c o n t a c t t h e r m o r e g u l a t o r , and an e l e c t r o n i c r e l a y . C o o l i n g was a f f o r d e d b y a c o p p e r c o i l i m m e r s e d i n t h e b a t h t h r o u g h w h i c h t a p w a t e r f l o w e d . The f l o w - r a t e c o u l d be a d j u s t e d s o t h a t t h e h e a t e r w e n t t h r o u g h an o n - o f f c y c l e e v e r y m i n u t e o r s o . The b a t h was s t i r r e d b y a m o t o r - d r i v e n p r o p e l l o r s t i r r e r . The p r e c i s i o n o f t h e t e m p e r a t u r e c o n t r o l i s b e l i e v e d t o be a b o u t + 0.05°C. F o r r u n s i n v o l v i n g l o w e r t e m p e r a t u r e s t h a n c o u l d be p r o d u c e d by t h e w a t e r - b a t h s y s t e m a t h e r m o e l e c t r i c i m m e r s i o n c o o l e r was u s e d . The c o o l e r was i m m e r s e d i n a b a t h o f e t h y l e n e g l y c o l i n a l a r g e w i d e - m o u t h Dewar f l a s k . S t i r r i n g was a c c o m p l i s h e d b y b u b b l i n g a i r b r i s k l y t h r o u g h t h e b a t h by means o f a c o p p e r t u b e l e a d i n g t o t h e b o t t o m o f t h e Dewar. The p r e c i s i o n o f t h e t e m p e r a t u r e c o n t r o l i s a b o u t t h e same o r b e t t e r t h a n t h a t u s i n g t h e c o n v e n t i o n a l w a t e r b a t h . The r u n s f o l l o w e d s p e c t r o p h o t o m e t r i c a l l y w e r e i n v a r i a b l y p e r f o r m e d a t 25°C. T e m p e r a t u r e c o n t r o l was m a i n t a i n e d b y c i r c u l a t i n g w a t e r f r o m a t h e r m o s t a t e d w a t e r b a t h t h r o u g h a t h e r r n o s t a t i n g b l o c k c e l l - h o l d e r w i t h i n t h e s p e c t r o p h o t o m e t e r . 28 Buffer System Since the reaction either generates or consumes hydroxide ion depending upon the conditions and i s , i n any case, pH dependent, the use of buffers i s necessary. In t h i s work phosphate buffers were used almost ex c l u s i v e l y . The desired pH was attained by s t a r t i n g with about 0.15 molar K^HPO^ and adding either droplets of concentrated s u l f u r i c acid or p a r t i c l e s of potassium hydroxide s o l i d . A c a l c u l a t i o n of the i o n i c strength taking into account the i o n i c species r e s u l t i n g from the buffer as well as sulfate ion indicates that t h i s quantity i s remarkably constant i n the pH- range 3 to 9. If the buffer concentration i s 0.143 molar the -io n i c strength at pH 9 i s 0.43 and i t f a l l s to 0.37 at pH 3. So, considering the usefulness of t h i s buffer system with respect to dissolved Mn(IV) and the near constancy of the i o n i c strength over such a wide range of a c i d i t y , phosphate buffers seemed a suitable choice. A c t i v a t i o n Parameters Enthalpies ( A H * * ) and entropies (AS**) of a c t i v a t i o n were calculated from rate versus temperature data using the well-known Eyring equation 29 where k i s t h e s e c o n d o r d e r r a t e c o n s t a n t i n u n i t s o f l i t e r s p e r mole p e r s e c o n d , k_ i s Boltzmann' s c o n s t a n t , h i s P l a n c k ' s c o n s t a n t , R i s t h e g a s c o n s t a n t and T t h e a b s o l u t e t e m p e r a t u r e . The t r a n s m i s s i o n c o e f f i c i e n t < i s assumed t o be u n i t y as i s c u s t o m a r y 2 ^ . The a c t u a l c o m p u t a t i o n was done u s i n g t h e l o g a r i t h m i c f o r m o f t h e E y r i n g e q u a t i o n . log = l o g AS' 2.303R 2.303RT a g a i n s t l/T r e s u l t s i n a s t r a i g h t l i n e + «tiS^/2. 30 3R. A p l o t o f l o g o f s l o p e - AH^/2.303R and an i n t e r c e p t o f l o g The s l o p e and i n t e r c e p t were d e t e r m i n e d u s i n g a l e a s t s q u a r e s c o m p u t e r p r o g r a m . The p r o g r a m a l s o c a l c u l a t e d t h e s t a n d a r d • e r r o r i n t h e s l o p e and i n t e r c e p t as w e l l a s t h e c o e f f i c i e n t o f c o r r e l a t i o n . W h e r e v e r a c t i v a t i o n p a r a m e t e r s a r e c i t e d h e r e i n t h e s e d a t a a r e a l s o s u p p l i e d . 30 COMPOUNDS AND REAGENTS 3 - P h e n y l p h t h a l i d e F i r s t 2 ~ b e n z o y l b e n z o i c a c i d was p r e p a r e d f r o m b e n z e n e and p h t h a l i c a n h y d r i d e u s i n g t h e p r o c e d u r e g i v e n b y 27 V o g e i T h i s compound was r e d u c e d u s i n g s o d i u m b o r o h y d r i d e . To 5 grams o f 2 - b e n z o y l b e n z o i c a c i d i n 50 m l . o f w a t e r , an e x c e s s o f s o d i u m b o r o h y d r i d e was added, s l o w l y w i t h s t i r r i n g . The 2 - b e n z o y l b e n z o i c a c i d was n o t c o m p l e t e l y d i s s o l v e d , a t t h e b e g i n n i n g o f t h e r e a c t i o n b u t became s o a s t h e a q u e o u s s o l u t i o n became b a s i c on a d d i t i o n o f s o d i u m b o r o h y d r i d e . A f t e r s t i r r i n g f o r a few m i n u t e s t h e s o l u t i o n was c a r e f u l l y a c i d i f i e d b y a d d i t i o n o f d r o p l e t s o f c o n c e n t r a t e d s u l f u r i c a c i d w h i l e s t i r r i n g v i g o r o u s l y . The w h i t e p r e c i p i t a t e , o b t a i n e d i n a l m o s t q u a n t i t a t i v e y i e l d , was f i l t e r e d w i t h s u c t i o n a n d w a s h e d s e v e r a l t i m e s w i t h w a t e r . A f t e r two r e c r y s t a l l i z a t i o n s f r o m c a r b o n t e t r a c h l o r i d e and d r y i n g u n d e r r e d u c e d p r e s s u r e t h e compound m e l t e d a t 113-114 ( L i t . m.p. 1 1 3 - 1 1 4 2 8 ) . B e n z h y d r o l - 4 - - c a r b o x y l i c a c i d F r o m 4 - b e n z o y l b e n z o i c a c i d ( A l d r i c h # B1240) b e n z h y d r o l - 4 - c a r b o x y l i e a c i d was p r e p a r e d b y s o d i u m b o r o h y d r i d e r e d u c t i o n . To 5 grams o f 4 - b e n z o y l b e n z o i c a c i d m 50 m l . o f w a t e r , e x c e s s s o d i u m b o r o h y d r i d e was a d d e d s l o w l y w i t h s t i r r i n g . F i v e m i n u t e s a f t e r t h e compound went c o m p l e t e l y i n t o s o l u t i o n t h e s o l u t i o n v/as a c i d i f i e d w i t h c o n c e n t r a t e d s u l f u r i c a c i d , a d d e d d r o p w i s e w i t h v i g o r o u s s t i r r i n g . A w h i t e p r e c i p i t a t e f o r m e d w h i c h was f i l t e r e d w i t h s u c t i o n , washed, w i t h w a t e r s e v e r a l t i m e s a nd d r i e d . The amount v/as a l m o s t q u a n t i t a t i v e . A f t e r two r e c r y s t a l l i z a t i o n s f r o m C H C l - j ' EtOH-4:1 a n d d r y i n g u n d e r r e d u c e d p r e s s u r e a compound was o b t a i n e d whose m e l t i n g p o i n t was 29 1 6 5 - 6 6 ( L i t . m.p. 164-65 ) . P h t h a l a l d e h y d i c a c i d T h i s compound was p u r c h a s e d f r o m t h e A l d r i c h C h e m i c a l Co. (# 1 1 , 6 0 1 - 7 ) . A f t e r a t r e a t m e n t v / i t h d e c o l o r i z i n g c a r b o n i n e t h e r s o l u t i o n i t was r e c r y s t a l l i z e d f r o m w a t e r t o c o n s t a n t m e l t i n g p o i n t . The f i n a l compound 29 c o n s i s t e d o f w h i t e p l a t e s m e l t i n g a t 96.5-97.5 ( L i t . m.p. 97 ) . T e r e p h t h a l a l d e h y d i c a c i d O b t a i n e d f r o m F l u k a C h e m i s c h e F a b r i k (# 2 1 8 7 0 ) , t h i s compound was p u r i f i e d b y r e c r y s t a l l i z a t i o n t o c o n s t a n t m e l t i n g p o i n t f r o m w a t e r c o n t a i n i n g a t r a c e o f e t h a n o l . The 30 f i n a l m e l t i n g p o i n t was 2 5 5 - 5 6 ( L i t . m.p. 256 ) . 32 C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d B o t h i s o m e r s o f 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d w e r e p r e p a r e d b y t h e c a t a l y t i c h y d r o g e n a t i o n o f e t h y l 2 - o x . o c y c l o h e x a n e c a r b o x y l a t e . T h i s l a t t e r compound was p r e p a r e d b y t h e m e t h o d o f O r g a n i c S y n t h e s e s , C o l l . V o l . I I , p . 5 3 1 . The p r o c e d u r e u s e d f o r t h e r e d u c t i o n a n d w o r k - u p 31 was s i m i l a r t o t h a t g i v e n b y P a s c u a l , S i s t a r e and R a g a s A s o l u t i o n o f 17 grams o f e t h y l 2 - o x o c y c l o h e x a n e c a r b o x y l a t e i n a b o u t an e q u a l v o l u m e o f m e t h a n o l was r e d u c e d i n a P a a r 2 h y d r o g e n a t i o n a p p a r a t u s a t an i n i t i a l p r e s s u r e o f 50 l b s . / i n . a b o v e a t m o s p h e r i c p r e s s u r e . A s c a t a l y s t 200 mg. o f Adams' C a t a l y s t was used. The d u r a t i o n o f t h e r e d u c t i o n was a b o u t 20 h o u r s a f t e r w h i c h t i m e t h e c a t a l y s t was r e m o v e d b y f i l t r a t i o n a n d t h e m e t h a n o l t a k e n o f f u s i n g t h e r o t a r y e v a p o r a t o r . The r e m a i n i n g l i q u i d was d i s t i l l e d a t 18 mm/Hg p r e s s u r e . The f i r s t f r a c t i o n c o n s i s t e d o f u n r e d u c e d s t a r t i n g m a t e r i a l a n d t h e r e d u c t i o n p r o d u c t was c o l l e c t e d a t 115-120°C. The d i s t i l l a t e was p o u r e d i n t o 45 m l o f h o t 8N NaOH w i t h s t i r r i n g . Some f r o t h i n g o c c u r r e d . When t h e l i q u i d became homogeneous ( a f t e r a few m i n u t e s ) , t h e s t i r r i n g was i n t e r r u p t e d a n d t h e s o l u t i o n a l l o w e d t o c o o l . A c o p i o u s w h i t e p r e c i p i t a t e d f o r m e d w h i c h was f i l t e r e d w i t h s u c t i o n . The f i l t r a t e was wa s h e d w i t h 2 m l o f e t h a n o l a n d d r i e d . The w h i t e s a l t 33 was d i s s o l v e d i n t h e s m a l l e s t p o s s i b l e amount o f w a t e r , a c i d i f i e d w i t h 6N H C l , s a t u r a t e d w i t h ammonium s u l f a t e and e x t r a c t e d c o n t i n u o u s l y w i t h e t h e r o v e r n i g h t . The e t h e r e x t r a c t was d r i e d and t h e e t h e r r e m o v e d t o y i e l d 7 grams o f an o i l w h i c h s o l i d i f i e d s l o w l y on s t a n d i n g . S e v e r a l r e c r y s t a l l i z a t i o n s o f t h i s s o l i d f r o m e t h e r y i e l d e d p u r e c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d , m.p. 8 1 - 8 2 ( L i t . m.p. 8 2 ) . T r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d T h i s compound was o b t a i n e d b y c o m b i n i n g t h e a l c o h o l wash s o l u t i o n and t h e m o t h e r l i q u o r r e m a i n i n g f r o m t h e h y d r o l y s i s o f t h e r e d u c e d e t h y l e s t e r and r e f l u x i n g f o r a b o u t a d a y . The m o t h e r l i q u o r c o n t a i n e d a s u b s t a n t i a l amount o f b a s e and a n y c i s — i s o m e r p r e s e n t was t r a n s f o r m e d i n t o t r a n s - i s o m e r d u r i n g t h e r e f l u x i n g . T h i s t r a n s f o r m a t i o n t o a more s t a b l e i s o m e r . i s p r a c t i c a l l y a p r o o f o f s t r u c t u r e f o r b o t h compounds. The b a s i c r e f l u x e d s o l u t i o n was a c i d i f i e d t o C o n g o - r e d w i t h 6N H C l and w o r k e d up j u s t a s was t h e c i s -i s o m e r . The p r o d u c t , p u r e t r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c 31 a c x d , m e l t e d a t 1 1 0 - 1 1 1 ( L i t . m.p. I l l ) . T r a n s - 2 - d e u t e r i o - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d The s y n t h e s i s o f t h i s compound i n v o l v e s t h e 34 reduction of ethyl 2-oxocyclohexanecarboxylate with sodium -borodeuteride. About 20 ml, of absolute ethyl alcohol were added to 0.985 gm of sodium borodeuteride (0.024 mole ) and the mixture was c h i l l e d i n an ice-water bath. The ester (11.7 gm, 0.069 mole ) was added to 20 ml of absolute ethyl alcohol and t h i s solution was also c h i l l e d . The solut i o n containing the borodeuteride was added dropwise with s t i r r i n g to the ethanolic solution of the ester. Addition was complete i n about a half-hour. The solut i o n was s t i r r e d at room temperature for another half-hour and then made a c i d i c to Congo-red with 6N HC1.Water(30 ml) was added and ethanol and water were removed together at reduced pressure u n t i l only water and the reduced ester remained. Basic hydrolysis was accomplished by addition of 8 gm. of s o l i d sodium hydroxide dissolved i n 20 ml. of water. This basic solution was extracted with ether to remove any cyclohexanone derived from unreduced ester and the ether extract was discarded. The basic solution was c h i l l e d and a c i d i f i e d with 6N HC1 to Congo-red. A f t e r saturation with ammonium sulfate the solution was extracted continuously with ether, the extract dried and the ether removed to y i e l d an o i l which slowly s o l i d i f i e d . This crude material (6.6 gm) was dissolved i n 5% sodium bicarbonate and a f t e r further p u r i f i c a t i o n by 35 e x t r a c t i o n w i t h e t h e r was r e g e n e r a t e d i n t h e u s u a l way. To t h i s m a t e r i a l was a d d e d h o t 8M s o d i u m h y d r o x i d e s o l u t i o n (50 ml) and t h e c l e a r s o l u t i o n w h i c h r e s u l t e d was a l l o w e d t o r e t u r n t o room t e m p e r a t u r e w i t h s t i r r i n g . C h i l l i n g i n an i c e - w a t e r b a t h c a u s e d t h e s o l u t i o n t o c l o u d s l i g h t l y a n d ' a f t e r s t a n d i n g o v e r n i g h t a c o p i o u s w h i t e p r e c i p i t a t e was d e p o s i t e d . T h i s p r e c i p i t a t e was c o l l e c t e d by f i l t r a t i o n w i t h s u c t i o n a n d t h e n e u t r a l a c i d was o b t a i n e d i n t h e m anner d e s c r i b e d f o r c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d . S e v e r a l r e c r y s t a l l i z a t i o n s f r o m e t h y l a c e t a t e g a v e a compound (m.p. 8 0 - 8 1 ) , whose s t r u c t u r a l p r o o f w i l l be c o n s i d e r e d l a t e r a s d e d u c e d f r o m N.M.R. e v i d e n c e . E t h y l 5 - t - b u t y l - 2 - o x o c y c l o h e x a n e c a r b o x y l a t e The p r o c e d u r e u s e d i n t h i s s y n t h e s i s i s s i m i l a r t o t h a t o f O r g a n i c S y n t h e s e s , C o l l . V o l . I I , 5 3 1 f o r e t h y l 2 - o x o c y c l o h e x a n e c a r b o x y l a t e . A q u a n t i t y o f s o d i u m (0.33 m o l e ) was a d d e d t o 150 m l o f a n h y d r o u s e t h a n o l i n a 2 l i t r e t h r e e - n e c k r o u n d -b o t t o m e d f l a s k f i t t e d w i t h a c o n d e n s e r t o p p e d b y a d r y i n g t u b e . The l i q u i d was s t i r r e d u s i n g a m a g n e t i c s t i r r e r a n d when t h e s o d i u m h a d c o m p l e t e l y r e a c t e d t h e f l a s k was s u r r o u n d e d by an i c e - w a t e r b a t h t o b r i n g t h e t e m p e r a t u r e o f t h e e t h o x i d e s o l u t i o n b e l o w 10°C. A s o l u t i o n o f e t h y l o x a l a t e (0.33 m o l e ) 36 a n d 4 - t - b u t y i c y c l o h e x a n o n e (0.33 m o l e ) t o g e t h e r , c o m b i n e d w i t h 50 m l o f a n h y d r o u s e t h y l a l c o h o l , was a d d e d o v e r a p e r i o d o f an h o u r t o t h e s o d i u m e t h o x i d e s o l u t i o n . S t i r r i n g was c o n t i n u e d o v e r n i g h t a n d t h e r e a c t i n g m i x t u r e g r a d u a l l y came t o room t e m p e r a t u r e as t h e i c e i n t h e i c e - w a t e r b a t h was d e p l e t e d . T h e n c o n c e n t r a t e d s u l f u r i c a c i d (10 m l ) i n 75 gm o f i c e was added, f o l l o w e d b y 1 l i t r e o f w a t e r . A f t e r s t i r r i n g f o r a f e w m i n u t e s a h e a v y o i l s e t t l e d t o t h e b o t t o m o f t h e f l a s k . T h i s o i l was s e p a r a t e d f r o m t h e r e s t o f t h e l i q u i d w h i c h was e x t r a c t e d w i t h f o u r 200 m l p o r t i o n s o f b e n z e n e . The b e n z e n e e x t r a c t s a n d t h e o i l w e r e c o m b i n e d a n d wa s h e d t w i c e w i t h 200 m l p o r t i o n s o f w a t e r . A f t e r s t a n d i n g f o r s"ome t i m e t o a l l o w t h e w a t e r t o s e p a r a t e f r o m t h e b e n z e n e l a y e r , t h e b e n z e n e was r e m o v e d u s i n g t h e r o t a r y e v a p o r a t o r . The r e m a i n i n g l i q u i d was d i s t i l l e d a t a p r e s s u r e o f 0.5 mm/Hg and was c o l l e c t e d b e t w e e n 120 and 130°C. The d i s t i l l a t e was h e a t e d f o r two h o u r s a t 165°C and 40 mm/Hg p r e s s u r e i n t h e p r e s e n c e o f a b o u t a gram o f c r u s h e d g l a s s a n d a t r a c e o f i r o n p o w d e r (0.2 mg). A t t h e e n d . o f t h e two h o u r p e r i o d t h e e x p u l s i o n o f c a r b o n m o n o x i d e a p p e a r e d t o h a v e c e a s e d . The t e m p e r a t u r e was r e d u c e d t o a b o u t 130°C and t h e p r e s s u r e r e d u c e d t o 0.5 mm/Hg. D i s t i l l a t i o n o c c u r r e d a n d t h e p r o d u c t was c o l l e c t e d b e t w e e n 90 and 92°C, The 37 w e i g h t o f p r o d u c t (37.8 gm) c o r r e s p o n d e d t o a y i e l d o f 5 1 . 5 % . A n a l y s i s f o r C 1 3 H 2 2 0 3 ( 2 2 6 * 3 ) F o u n d ( c a l c u l a t e d ) : 69 .12 (68 .99)%C,10.00 (9.80)%H. - 1.4805 C i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d T h i s compound was p r e p a r e d b y c a t a l y t i c r e d u c t i o n o f e t h y l 5 - t - b u t y l - 2 - o x o c y c l o h e x a n e c a r b o x y l a t e . The e s t e r ( 1 0 , 1 gm) was a d d e d t o 50 m l o f g l a c i a l a c e t i c a c i d a l o n g w i t h 800 mg o f Adams' c a t a l y s t . R e d u c t i o n was c a r r i e d o u t i n a P a a r t y p e h y d r o g e n a t o r u s i n g a n i n i t i a l p r e s s u r e o f 2 50 l b . / i n t a b o v e a t m o s p h e r i c p r e s s u r e . The d u r a t i o n o f r e d u c t i o n was 48 h o u r s . The s o l u t i o n was f i l t e r e d t o remove t h e c a t a l y s t a n d c o m b i n e d w i t h 10 0 m l o f w a t e r . T h i s was e x t r a c t e d w i t h two 10 0 m l p o r t i o n s o f l o w - b o i l i n g p e t r o l e u m e t h e r . The e x t r a c t s w e r e c o m b i n e d a n d s h a k e n w i t h 5% s o d i u m c a r b o n a t e s o l u t i o n and d r i e d . The s o l v e n t was re m o v e d u s i n g t h e r o t a r y e v a p o r a t o r a n d t h e l i q u i d r e s i d u e was d i s t i l l e d a t 0.6 mm/Hg p r e s s u r e a n d c o l l e c t e d a t 92-95°C. The d i s t i l l a t e was h y d r o l y s e d w i t h 30 m l o f h o t 6N s o d i u m h y d r o x i d e s o l u t i o n f r o m w h i c h t h e s o d i u m s a l t p r e c i p i t a t e d on c o o l i n g . The s a l t was d i s s o l v e d i n . w a t e r a n d t h e a c i d p r e c i p i t a t e d b y a c i d i f y i n g t o C o n g o - r e d w i t h 6N HC1. T h i s s l u r r y o f compound and w a t e r was e x t r a c t e d w i t h e t h e r . The e t h e r was d r i e d 38 and r e m o v e d t o y i e l d a c r u d e s o l i d . T h i s s o l i d was r e c r y s t a l l i z e d t o c o n s t a n t m e l t i n g p o i n t f r o m a m i x t u r e o f l o w - b o i l i n g p e t r o l e u m e t h e r and b e n z e n e . A f t e r f i v e r e c r y s t a l l i z a t i o n s t h e m e l t i n g p o i n t r o s e t o a c o n s t a n t 1 4 9 - 5 0 ( L i t . m.p. 1 4 9 - 1 4 9 . 5 3 2 ) . C i s - ~ 5 - t - b u t y l - t r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d T h i s compound wa's s y n t h e s i z e d b y r e d u c t i o n o f e t h y l 5 - t ~ b u t y l - 2 - o x o c y c l o h e x a n e c a r b o x y l a t e w i t h s o d i u m b o r o h y d r i d e , h y d r o l y s i s w i t h s t r o n g b a s e and s e p a r a t i o n o f . t h e a p p r o p r i a t e i s o m e r f r o m t h e m i x t u r e by f r a c t i o n a l c r y s t a l l i z a t i o n o f t h e s o d i u m s a l t f r o m a s o l u t i o n o f s o d i u m h y d r o x i d e . S o d i u m b o r o h y d r i d e (0.9 45 gm) a n d e t h y l 5 - t - b u t y 1 - 2 - o x o c y c l o h e x a n e c a r b o x y l a t e (10.0 gm) w e r e s e r a r a t e l y d i s s o l v e d i n two 20 m l p o r t i o n s o f a b s o l u t e e t h a n o l . The s o d i u m b o r o h y d r i d e s o l u t i o n was a d d e d t o t h e s o l u t i o n o f t h e e s t e r o v e r a p e r i o d o f f i f t e e n m i n u t e s . A f t e r c o m p l e t e a d d i t i o n t h e m i x t u r e was s t i r r e d a t room t e m p e r a t u r e f o r a n o t h e r t h i r t y m i n u t e s . T h e n w a t e r (15 ml) was a d d e d and s t i r r i n g c o n t i n u e d f o r a n o t h e r h o u r . • The s o l u t i o n was made a c i d t o C o n g o - r e d by a d d i t i o n o f 6N H C l a n d more w a t e r (100 ml) was a d d e d . R e m o v a l o f t h e e t h a n o l u s i n g t h e r o t a r y e v a p o r a t o r c a u s e d t h e r e d u c e d e s t e r t o 39 s e p a r a t e f r o m t h e r e m a i n i n g a q u e o u s l a y e r . The e s t e r was t a k e n up w i t h e t h e r and t h e a q u e o u s l a y e r e x t r a c t e d t w i c e more w i t h 50 m l v o l u m e s o f e t h e r . The c o m b i n e d e x t r a c t s w e r e d r i e d and t h e s o l v e n t r e m o v e d . The r e s u l t i n g l i q u i d was s u b j e c t e d t o r e d u c e d p r e s s u r e d i s t i l l a t i o n a s m e n t i o n e d i n t h e i m m e d i a t e l y p r e c e e d i n g s y n t h e s i s . The d i s t i l l a t e was h y d r o l y s e d i n 3N s o d i u m h y d r o x i d e s o l u t i o n a n d r e f l u x e d f o r an h o u r . Upon c o o l i n g a p r e c i p i t a t e d f o r m e d w h i c h was c o l l e c t e d . The p r e c i p i t a l e and t h e m o t h e r l i q u o r w e r e w o r k e d up s e p a r a t e l y i n t h e u s u a l way. The p r e c i p i t a l e was f o u n d t o c o n t a i n two i s o m e r s w h i c h a c c o u n t e d f o r n e a r l y a l l o f t h e a v a i l a b l e m a t e r i a l . The m i x t u r e o f a c i d s was d i s s o l v e d i n 50 m l o f I N s o d i u m h y d r o x i d e and on c o o l i n g g a v e a p r e c i p i t a t e . T h i s p r e c i p i t a t e , a f t e r w o r k - u p , g a v e a p u r e 32 compound w h i c h m e l t e d a t 144-45 ( L i t . m.p. 145-46 ) a f t e r r e c r y s t a l l i z a t i o n f r o m b e n z e n e . The m o t h e r l i q u o r y i e l d e d a m i x t u r e o f two c o m p o n e n t s i n n e a r l y e q u a l a m o u n t s . The m e l t i n g p o i n t s o f t h i s compound and t h e i m m e d i a t e l y p r e c e e d i n g i s o m e r a r e v e r y c l o s e b u t d i f f e r e n c e s i n I R a n d NMR s p e c t r a show t h a t t h e y a r e d i s t i n c t compounds. T r a n s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d T h i s compound was i s o l a t e d f r o m a m i x t u r e o f i s o m e r i c a c i d s o b t a i n e d f r o m e t h y l 5 - t - b u t y l - 2 -o x o c y c l o h e x a n e c a r b o x y l a t e b y r e d u c t i o n w i t h s o d i u m 40 borohydride. The mixture of acids (10 gm) was dissolved i n the minimum amount of hot saturated sodium bicarbonate so l u t i o n . Upon cooling i n an ice-water bath a p r e c i p i t a l e was formed. The mother liquor and the p r e c i p i t a l e were separated and the l i q u i d worked up as usual to y i e l d a s o l i d which when r e c r y s t a l l i z e d three times from petroleum ether-benzene gave a compound of melting point 133-34(Lit. m.p. 133-35 3 2). 5-t-Butyl-2-oxocyclohexanecarboxylic acid This compound was prepared according to the 32 procedure of Sicher et a l Sodium deuteroxide and deuterio s u l f u r i c acid Both of these compounds (NaOD and D^O^) were prepared using methods given in Inorganic Isotopic Syntheses (Procedures 7A and 31A). Dipotassium deuterium phosphate q Several exchanges of K^HPO^ with afforded K_DPO. with no detectable hydrogen content. 41 SECTION A THE OXIDATION OF 2~ AND 4-BENZHYDROLCARBOXYLIC ACIDS E x p e r i m e n t a l The s y n t h e s e s o f 3 - p h e n y l p h t h a l i d e a nd 4-b e n z h y d r o l c a r b o x y l i e a c i d h a v e b e e n i n d i c a t e d p r e v i o u s l y . A s o l u t i o n o f t h e a n i o n o f 2 - b e n z h y d r o l c a r b o x y l i c a c i d was p r e p a r e d f o r u s e i n t h e k i n e t i c e x p e r i m e n t s b y t h e h y d r o l y s i s o f 3 - p h e n y l p h t h a l i d e u s i n g 0.IN p o t a s s i u m h y d r o x i d e . F o r t h e k i n e t i c r u n s on 4 - b e n z h y d r o l c a r b o x y l i c a c i d a s t o c k s o l u t i o n c o n t a i n i n g t h a t compound and an e q u i v a l e n t amount o f 0.IN p o t a s s i u m h y d r o x i d e was used. K i n e t i c e x p e r i m e n t s a t pH v a l u e s l e s s t h a n 12 had an i n i t i a l s u b s t r a t e t o p e r m a n g a n a t e r a t i o o f 1 . 5 , w h i l e t h o s e a b o v e pH 12 h a d a r a t i o o f 0.5. T h e s e r a t i o s c o r r e s p o n d t o t h e known s t o i c h i o m e t r i c s o p e r a t i v e i n t h e s e r e g i o n s a n d n e c e s s i t a t e t h e u s e o f k i n e t i c e q u a t i o n s 9. and 12. The r u n s a t t h e 3:2 s t o i c h i o m e t r y w e r e f o l l o w e d b y t i t r a t i o n a n d t h o s e a t t h e 1:2 s t o i c h i o m e t r y w e r e f o l l o w e d s p e c t r o p h o t o m e t r i c a l l y . . S e v e r a l r u n s w e r e c a r r i e d o u t u s i n g n o n - s t o i c h i o m e t r i c p r o p o r t i o n s o f r e a c t a n t s and w e r e a n a l y s e d by t h e a p p r o p r i a t e e q u a t i o n s ( 1 0. and 1 3 . ) . T h e s e r e s u l t s d e m o n s t r a t e t h e v a l i d i t y o f e q u a t i o n s 10. and 13. b u t due t o t h e i r a w k w a r d n e s s t h e y w e r e n o t u s e d f u r t h e r . 42 Figures I and II display two f a i r l y representative rate p l o t s . The run described by Figure I was c a r r i e d out as follows: To a 100 ml erlenmeyer f l a s k , f i t t e d with a B-24 stopper and two side arms s u f f i c i e n t to admit a glass-electrode and a calomel-electrode, were added 15 ml of 0 .02370M 2-benzhydrolcarboxylate, 10 ml of 1M K2HPC>4 and 25 ml of water. The pH of the solution was adjusted by c a r e f u l addition of s o l i d KOH. Mixing was effected using a magnetic s t i r r e r . After adjusting the pH, the f l a s k was placed i n a water bath at 25°C and allowed to approach thermal equilibrium for about 30 minutes. Then 10 ml of 0.02370M potassium permanganate solution, also at 25°C, was added. The so l u t i o n was s t i r r e d quickly and 5 ml aliquots were then withdrawn at i n t e r v a l s . These aliquots were quenched with a c i d i c iodide solution and the l i b e r a t e d iodine t i t r a t e d with 0.01945M sodium t h i o s u l f a t e . The procedure for the run of Figure II i s i d e n t i c a l to that of the run i n Figure I, except of course for the change of substrate. For the more rapid runs a wide-mouth 5 ml pipette was used. This i s the case for the run of Figure I I . For slower runs, such as that of Figure I, a conventional volumetric pipette was found to be more precise. 4 3 T — i r 36.0 72.0 108.0 TIME MIN 144.0 180.0 Rate p l o t f o r 2 - b e n z h y d r o l c a r b o x y c l i c a c i d o x i d a t i o n [MnCV] = 0.00395M pH = 10.75 T = 25° C [3-phenylphthalide] = 0.00593M Ionic Strength = 0.5 k = 0.251(L/M/Minj* . *L/M/Min abbreviated f o r l i t r e mole"-'' minute"* throughout. 44 T 16.0 TIME MIN Rate p l o t f o r 4-benzhydrolcarboxylic "axrj.d o x i d a t i o n [4-benzhydrolcarboxylic acid] = 0.00593M [MnOiJ] = 0.00395M T = 25° C pH - 10.45 Io n i c Strength = 0 . 5 • k =5.12 (L/M/Min) 40 45 P r o d u c t A n a l y s i s U s i n g c o n d i t i o n s s i m i l a r t o t h o s e o f k i n e t i c e x p e r i m e n t s s e v e r a l s o l u t i o n s w e r e q u e n c h e d a t a b o u t 60% r e a c t i o n b y . t h e a d d i t i o n o f a c i d i c s o d i u m b i s u l f i t e . I n t h e c a s e o f t h e 2-compound t h e q u e n c h e d m i x t u r e was f o u n d t o c o n t a i n o n l y 3 - p h e n y l p h t h a l i d e a n d 2 - b e n z h y d r o l c a r b o x y l i c a c i d i n amounts q u a n t i t a t i v e l y c o r r e s p o n d i n g t o t h e e x t e n t o f r e a c t i o n . The a c i d a n d l a c t o n e w e r e t a k e n up i n e t h e r a n d s e p a r a t e d u s i n g a q u e o u s b i c a r b o n a t e s o l u t i o n . The a c i d was t i t r a t e d a g a i n s t s t a n d a r d NaOH and t h e l a c t o n e was h y d r o l y s e d w i t h NaO.H and b a c k t i t r a t e d . The p h y s i c a l p r o p e r t i e s o f t h e a c i d a n d l a c t o n e w e re m e a s u r e d ( I . R . , i n . p . ) a n d f o u n d i d e n t i c a l w i t h t h o s e o f a u t h e n t i c s a m p l e s . F o r t h e 4-compound s e p a r a t i o n o f p r o d u c t a n d r e a c t a n t m i x t u r e s was n o t a t t e m p t e d . The r e a c t i o n was a l l o w e d t o go t o a b o u t 100% c o m p l e t i o n as i n d i c a t e d b y t h e r a t e c o n s t a n t a p p r o p r i a t e t o t h e c o n d i t i o n s u s e d . The p h y s i c a l p r o p e r t i e s o f t h e p r o d u c t o b t a i n e d f r o m t h e q u e n c h i n g w e r e i d e n t i c a l , t o t h o s e o f 4 - b e n z h y d r o l c a r b o x y l i c a c i d a n d t h e q u a n t i t y was 98% o f t h a t e x p e c t e d . R e s u l t s Two f a i r l y t y p i c a l r a t e p l o t s were g i v e n i n F i g u r e s I and I I , one f o r t h e 2- and t h e o t h e r f o r t h e 4-compound. The f u n c t i o n p l o t t e d a s o r d i n a t e i n e a c h c a s e i m p l i e s t h a t t h e 46 r e a c t a n t s w e r e p r e s e n t i n i t i a l l y i n s t o i c h i o m e t r i c a m o u n t s . The v a r i a t i o n o f r a t e w i t h t h e pH o f t h e medium i s g i v e n i n T a b l e s I a n d I I . T h e s e r e s u l t s a r e a l s o e x h i b i t e d g r a p h i c a l l y i n F i g u r e s I I I a n d I V . TABLE I 2 - b e n z h y d r o l c a r b o x y c l i c a c i d o x i d a t i o n pH k (L/M/MIN) T=25 C [H 2Z| / [MnC>4] Q=3/2 6.37 0,690 6.83 ' 0.609 I o n i c S t r e n g t h = 0.5 7 .58 0 .417 _ .... 8.7 5 0.37 2 [MnOi,] = 0.00395M,! 8.75 ' 0 .355 * ' '• 9.58 0,262 .10.45 0.254 10.75- 0.251 12.73 1.13 TABLE I I 4 - b e n z y h d r o l c a r b o x y l i c a c i d o x i d a t i o n pH k(L/M/MIN) 5.45 8.33 T=25°C [HZ] /[MnO~] =3/2 6.12 5.53 6.38 4.61 I o n i c S t r e n g t h = 0.5 6.83 4.49 7.63 3 . 4 9 [MnOi,] = 0.00395M 10.00 3.35 10.81 4.20 11.13 5.12 4 7 FIGURE I I I 2 - b e n z h y d r o l c a r b o x y l i c a c i d T = 25t: I o n i c Strength =0.5 48 49 The m o s t o b v i o u s f e a t u r e o f t h e s e two F i g u r e s i s t h e g r e a t e r r e a c t i v i t y o f t h e 4-compound. A t pH 8, f o r e x a m p l e , t h e r a t e r a t i o o f t h e 4-compound t o t h e 2-i s a b o u t 9. I n t h e r e g i o n b e l o w pH 8 b o t h compounds r e a c t f a s t e r a s t h e pH i s l o w e r e d . The o x i d a t i o n o f b e n z h y d r o l e x h i b i t s a s i m i l a r e f f e c t b u t t h i s o c c u r s a t much h i g h e r a c i d i t y ( a t pH 1) s o t h a t t h e two phenomena c a n n o t be r e l a t e d . The s i m p l e s t e x p l a n a t i o n i s t h a t t h e n e u t r a l a c i d m o l e c u l e r e a c t s f a s t e r t h a n i t s a n i o n . I f t h i s w e r e t h e c a s e t h e o b s e r v e d r a t e s s h o u l d r e f l e c t t h e i o n i z a t i o n o f t h e a c i d . U n f o r t u n a t e l y t h i s i s d i f f i c u l t t o e s t a b l i s h . F o r t h e 2-compound f o r m a t i o n o f 3 - p h e n y l p h t h a l i d e , t h e c o r r e s p o n d i n g l a c t o n e , t a k e s p l a c e d u r i n g t h e o x i d a t i o n r e a c t i o n b e l o w a b o u t pH 5. The l a c t o n e i s v e r y i n s o l u b l e i n w a t e r a n d p r e c i p i t a t e s l e a v i n g t h e c o n c e n t r a t i o n o f s u b s t r a t e i n s o l u t i o n u n c e r t a i n . I n a d d i t i o n , t h e s o l u b i l i t y , o f t h e 4-compound, when u n i o n i z e d , a p p e a r s t o be v e r y l o w a s w e l l . . I n t h e v i c i n i t y o f pH 10 t o 11 F i g u r e I I I shows b e h a v i o u r d i s t i n c t f r o m t h a t o f F i g u r e I V . F o r t h e 2-compound t h e r a t e d o e s n o t seem t o v a r y much b e t w e e n pH 9.5 a n d 1 1 . The 4-compound sho\vs a r a t e i n c r e a s e i n t h i s r e g i o n o f a l m o s t t w o - f o l d a n d i n t h i s r e s p e c t i t r e s e m b l e s b e n z h y d r o l . The d a t a o f T a b l e I show t h a t t h e o x i d a t i o n r a t e o f t h e 2-compound d o e s i n c r e a s e as t h e b a s i c i t y i n c r e a s e s t o pH 1 2 . 7 5 . T h i s 50 i n c r e a s e i s a b o u t f i v e - f o l d r e l a t i v e t o t h e r a t e a t pH 1 1 . The 4-compound shows a much more d r a m a t i c r a t e i n c r e a s e . The r a t e a t pH 12.75 r e l a t i v e t o t h a t a t pH 10 i s g r e a t e r by a f a c t o r o f 125. The d a t a o f T a b l e I I I (and F i g u r e V) show t h a t t h e r e i s a f i r s t o r d e r d e p e n d e n c e on h y d r o x i d e i o n c o n c e n t r a t i o n f o r t h e o x i d a t i o n o f t h e 4-compound. B e n z h y d r o l a l s o b e h a v e s i n t h i s way. TABLE I I I 4 - b e n z h y d r o l c a r b o x y l i c a c i d o x i d a t i o n b a s i c s o l u t i o n T = 25°C k (L/M/SEC) [0H~ 1 , , 2.80 0.024 5.17 0.04 7.80 0.0 6 10.30 0.08 [ M n 0 4 ] r t = 0.000290M 10.20 0.08 A c t i v a t i o n P a r a m e t e r s T e m p e r a t u r e s t u d i e s on b o t h compounds a t pH 5.45 w e r e p e r f o r m e d . The r e s u l t s a r e g i v e n i n T a b l e I V a n d F i g u r e s V i a a n d VTb . As c a n be s e e n f r o m t h e d a t a , t h e r a t e , d i f f e r e n c e b e t w e e n t h e two compounds a t pH 5.45 i s , w i t h i n e x p e r i m e n t a l e r r o r , d e t e r m i n e d e n t i r e l y b y t h e d i f f e r e n c e i n e n t r o p y o f a c t i v a t i o n . 51 52 TABLE IV T e m p e r a t u r e S t u d i e s 4 - b e n z h y d r o l c a r b o x y l i c a c i d 2 - b e n z h y d f o l c a r b o x y l i c a c i d T ° C k(L/M/SEC) k(L/M/SEC) 0 0.0328 0.00562 15 0.0808 0.0138 25 0.139 0.0237 40 0.310 50 0.0819 AH^(Kcal/°Mole) 8.94-0 .1 8 .80-0.1 AS^(eu) -32.4 +0.3 -36.4 +0.5 C o r r . C o e f f . 0.999 0.999 pH = 5.45 D i s c u s s i o n One r e a s o n f o r i n v e s t i g a t i n g t h e o x i d a t i o n o f 2 - b e n z h y d r o l c a r b o x y l i c a c i d was t o l o o k f o r r a t e enhancement e f f e c t s w h i c h m i g h t be p r o d u c e d by t h i s g r o u p i n p r o x i m i t y t o t h e r e a c t i n g c e n t r e . C o n s e q u e n t l y t h e 4-compound i n w h i c h t h e c a r b o x y l g r o u p i s r e m o t e f r o m t h i s c e n t r e was t o s e r v e as a c o n t r o l . The f a c t t h a t t h e 4-compound r e a c t s f a s t e r t h a n t h e 2- f r u s t r a t e s t h i s a p p r o a c h . The 2-compound has d i m i n i s h e d r e a c t i v i t y f o r r e a s o n s w h i c h w i l l now be c o n s i d e r e d . ~ E a r l i e r t h e m e c h a n i s t i c p o s s i b i l i t i e s o f t h i s r e a c t i o n were o u t l i n e d . The r e a c t i o n i n n e u t r a l s o l u t i o n p r o b a b l y i n v o l v e s a o n e - s t e p r e a c t i o n i n w h i c h e i t h e r h y d r o g e n atom o r h y d r i d e i o n i s t r a n s f e r r e d t o p e r m a n g a n a t e . The t r a n s i t i o n s t a t e f o r s u c h a r e a c t i o n m i g h t be w r i t t e n as I . 53 to CO cn <n. i cn o I . ID ^ rg CD ' O "3-in CD in in I 0.305 0.318 0.331 0.-344 1/T f X 1 0 * 2 ) ~ i 0.35? 0.37 2 - b e n z h y d r o l c a r b o x y l i c a c i d . o x i d a t i o n pH = 5.88 AH^ = 8.8 + 1 AS7* = -36.4 ± 0.5 C o r r e l a t i o n C o e f f i c i e n t = 0.999 cn ' 0.319 o'.329 u'.339 G\. 349 o'.359 0 1/T (X10+ 2 ) 4 - b e n z h y d r o l c a r b o x y l i c a c i d o x i d a t i o n ^ j AH^ = 8.9 ± 0.1 (Kcal/°Mole) AS^ = -32.4 ±0.3 (eu) C o r r e l a t i o n C o e f f i c i e n t = 0.999 55 HO-C •H--OMnO H02C~fS 3 At pH 7 t h e c a r b o x y l g r o u p m u s t be i o n i z e d a n d we m i g h t c o n s i d e r t h e t r a n s i t i o n s t a t e t o l o o k more l i k e I I . I n t h e e v e n t o f h y d r i d e t r a n s f e r t o p e r m a n g a n a t e t h e o r g a n i c p r o d u c t i s a p r o t o n a t e d b e n z o p h e n o n e ( p K ^ ^ - 6 ) a n d f o r JDH — h y d r o g e n atom t r a n s f e r i t i s t h e k e t y l r a d i c a l ( p K = 9 . 2 ) . B e c a u s e o f t h e i n s t a b i l i t y o f p r o t o n a t e d b e n z o p h e n o n e i n n e u t r a l s o l u t i o n i t i s p o s s i b l e t h a t t h e t r a n s i t i o n s t a t e c o u l d be s t a b i l i z e d b y a s i m u l t a n e o u s l o s s o f h y d r i d e i o n and a p r o t o n t o f o r m a t r a n s i t i o n s t a t e r e s e m b l i n g I I I . H 0 - G - H - 0 M n 0 3 H-O^....H---OMnO 3 I I I 56 No s u b s t a n t i a l s t a b i l i t y w o u l d be a c h i e v e d b y s u c h a t r a n s i t i o n s t a t e f o r a h y d r o g e n a tom t r a n s f e r m e c h a n i s m s i n c e , i n n e u t r a l s o l u t i o n , t h e k e t y l r a d i c a l a n d i t s a n i o n a r e o f c o m p a r a b l e s t a b i l i t y . So f o r a h y d r i d e t r a n s f e r m e c h a n i s m one might e x p e c t t h e c a r b o x y l a t e g r o u p t o i n t e r a c t f a v o u r a b l y w i t h t h e r e a c t i n g c e n t r e t o p r o d u c e a l o w e r i n g o f e n e r g y and a f a s t e r r a t e . F o r t h e c a s e o f h y d r o g e n a tom t r a n s f e r s u c h i n t e r a c t i o n w o u l d n o t n e c e s s a r i l y s t a b i l i z e t h e t r a n s i t i o n s t a t e t o a g r e a t e x t e n t . A n o b s e r v a t i o n o f r a t e e n h a n c e m e n t due t o c a r b o x y l a t e p a r t i c i p a t i o n i n t h e t r a n s i t i o n s t a t e w o u l d p r o b a b l y mean a g r e a t d e a l . However t h e f a i l u r e t o o b s e r v e s u c h an e f f e c t i s i n c o n c l u s i v e . I t d o e s n o t a r g u e i n f a v o u r o f e i t h e r • m e c h a n i s m . The t r a n s i t i o n s t a t e may be t o o r e a c t a n t - l i k e t o b e n e f i t f r o m t h e s t a b i l i z i n g i n f l u e n c e o f t h e s u b s t i t u e n t ( f o r h y d r i d e t r a n s f e r ) o r t h e g e o m e t r y may n o t be q u i t e w h a t i s r e q u i r e d . The n e g a t i v e o b s e r v a t i o n c a n e a s i l y a c c o m o d a t e e i t h e r m e c h a n i s m . The r e a c t i o n i n b a s i c s o l u t i o n i s o f i n t e r e s t . T h e r e i s a l a r g e r a t e e n h a n c e m e n t f o r t h e 4-compound i n b a s i c s o l u t i o n a n d a d e p e n d e n c e o f t h e r a t e on h y d r o x i d e i o n c o n c e n t r a t i o n . The 2—compound shows o n l y a s l i g h t r a t e i n c r e a s e i n t h i s r e g i o n . 57 I t i s now well established ' that the reason f o r th i s hydroxide ion dependence, also observed for benzhydrol, i s the greater r e a c t i v i t y of the alkoxide ion r e l a t i v e to the neutral alcohol. The pK of benzhydrol has been estimated at about 15. At pH 13 benzhydrol i s then about 1% ionized so that the alkoxide ion must be very reactive. A s u f f i c i e n t increase i n the pK (about 1 unit) produced by a substituent would make the degree of i o n i z a t i o n too small to observe a dependence on hydroxide ion i n aqueous solu t i o n . This would be the case when the quantity of alcohol ionized i s so s l i g h t as to make i t s contribution to the rate less than or of the same order as the contribution from the unionized alcohol. I t appears then that for OH i o n i z a t i o n L-2-benzhydrolcarboxylate i s a weaker acid than 4-benzhydrolcarboxylate. This i s not an unusual observation since for example the second pK of phthalic acid i s about 1 pK unit higher than the corresponding pK of terephthalic .,35 acid The slope of the l i n e i n Figure V should be given by k K a/K w i f the reaction sequence i s the following: _ K A / K W ROH + OH ' RQ" + H„0 MnO. + RO ( > Products. 58 K a i s t h e a c i d d i s s o c i a t i o n c o n s t a n t o f t h e a l c o h o l , K w t h e i o n - p r o d u c t o f w a t e r and t h e r a t e c o n s t a n t o f t h e r a t e c o n t r o l l i n g s t e p . F o r 4 - b e n z h y d r o l c a r b o x y l a t e t h e s l o p e i s 132-3 and f o r b e n z h y d r o l i t i s 89-4. One m i g h t be a b l e t o i n f e r s o m e t h i n g . a b o u t t h e e l e c t r o n i c r e q u i r e m e n t s o f t h e r e a c t i o n were p - c a r b o x y l a t e n o t s u c h an u n f o r t u n a t e c h o i c e o f s u b s t i t u e n t . The Hammett (J v a l u e i s , w i t h i n e x p e r i m e n t a l 36 e r r o r , z e r o m a k i n g t h i s c l e a r l y i m p o s s i b l e The a c t i v a t i o n p a r a m e t e r s a r e w o r t h y o f comment. I t a p p e a r s t h a t w i t h i n e x p e r i m e n t a l e r r o r t h e a c t i v a t i o n e n t h a l p i e s o f t h e two compounds a r e i d e n t i c a l . The d i f f e r e n c e i n r a t e i s a c c o u n t e d f o r e n t i r e l y by t h e d i f f e r e n c e i n e n t r o p y o f a c t i v a t i o n - t h e a c t i v a t i o n e n t r o p y o f t h e 2-compound i s more n e g a t i v e t h a n t h a t o f t h e 4-compound b y 4.0-0.6 e u . I t i s p e r h a p s u n u s u a l t h a t t h e e n t i r e r a t e d i f f e r e n c e i n v o l v e s t h e e n t r o p y o f a c t i v a t i o n o n l y b u t i t c a n be p l a u s i b l y e x p l a i n e d . The a p p r o a c h o f t h e p e r m a n g a n a t e i o n t o f o r m t h e t r a n s i t i o n s t a t e p r o b a b l y r e s t r i c t s t h e f r e e d o m o f t h e a r o m a t i c r i n g s . The p r e s e n c e o f t h e o r t h o c a r b o x y l g r o u p p r e s u m a b l y c a u s e s r e s t r i c t i o n o f i n t e r n a l m o t i o n t o be more s e v e r e and t h e e f f e c t o f t h i s r e s t r i c t i o n i s r e f l e c t e d i n t h e e n t r o p y o f a c t i v a t i o n . 9 The a c t i v a t i o n p a r a m e t e r s f o r b e n z h y d r o l o x i d a t i o n a r e A H ^ = 5 . 7 K c a l / ° M o l e and A S ^ = -44.0 eu a t pH 7. 59 T h e s e v a l u e s a r e s i g n i f i c a n t l y d i f f e r e n t f r o m t h o s e d e t e r m i n e d f o r p - b e n z h y d r o l c a r b o x y l a t e o x i d a t i o n ( A = 8 . 9 Kcal/°Mole and A S ^ = 32.4 eu) a n d t h e a b i l i t y t o c o r r e l a t e b o t h r a t e s i n t h e same Hammett p l o t i s a n o t h e r e x a m p l e o f t h e a r c a n e i n t e r p l a y b e t w e e n e n t h a l p y and e n t r o p y w h i c h g i v e s r i s e t o l i n e a r f r e e e n e r g y r e l a t i o n s h i p s . 60 SECTION B THE OXIDATION OF PHTHALALDEHYDIC ACID AND TEREPHTHALALDEHYDIC ACID E x p e r i m e n t a l A q u e o u s s t o c k s o l u t i o n s o f b o t h compounds w e r e p r e p a r e d o f c o n c e n t r a t i o n 0.03473M. The i n i t i a l c o n c e n t r a t i o n o f s u b s t r a t e f o r k i n e t i c r u n s was u s u a l l y 0.00248M a n d t h e p e r m a n g a n a t e c o n c e n t r a t i o n t w o - t h i r d s o f t h i s . The b u f f e r s y s t e m a nd o t h e r c o n d i t i o n s p e r t i n e n t t o t h e k i n e t i c e x p e r i m e n t s w e r e e s s e n t i a l l y t h e same as f o r t h e k i n e t i c s t u d i e s on b e n z h y d r o l s . Two f a i r l y r e p r e s e n t a t i v e r a t e p l o t s a r e g i v e n i n F i g u r e s V I I and V I I I . The r u n i n F i g u r e V I I r e f e r s t o t h e o x i d a t i o n o f p h t h a l a l d e h y d i c a t pH 7.12 and 25°C. The r u n was c a r r i e d o u t b y a d d i n g t o t h e r e a c t i o n f l a s k 40 m l o f w a t e r , 10 m l o f 0.03473M p h t h a l a l d e h y d i c a c i d a n d 10 m l o f IM K HPO-4. A f t e r a d j u s t i n g t h e pH t o a v a l u e o f 7.12 b y a d d i n g d r o p s o f c o n c e n t r a t e d s u l f u r i c a c i d , t h e f l a s k was p l a c e d i n t h e w a t e r b a t h and a l l o w e d t o come t o t h e r m a l e q u i l i b r i u m f o r a h a l f - h o u r . T h e n 10 m l o f 0.02316M p o t a s s i u m p e r m a n g a n a t e , a l s o a t 25°C, was p i p e t t e d i n t o t h e f l a s k . A f t e r m i x i n g , a l i q u o t s w e r e w i t h d r a w n f r o m t i m e t o t i m e as t h e r e a c t i o n p r o c e e d e d . The 61 4 . 4 8 . 8 13.2 TIME(MINUTES) 1 7 . B 22.0 R a t e p l o t f o r p h t h a l a l d e h y d i c a c i d o x i d a t i o n [ M n O ^ = 0.00332M pH = 7.12 T = 25°C J p h t h a l a l d e h y d i c a c i d j = 0 . 0 0 4 9 6 M I o n i c S t r e n g t h - 0.43 •k - 11.2 L/M/MIN FIGURE V I I I R a t e p l o t f o r t e r e p h t h a l d e h y d i c a c i d o x i d a t i o n { t e r e p h t h a l a l d e h y d i c a c i d } = 0.00496M pH = 8.90 [MnO~^j = 0.00332M T = 25°C I o n i c S t r e n g t h = 0 . 4 3 k = 16.8 L/M/MIN 63 i n i t i a l c o n c e n t r a t i o n r a t i o o f p h t h a l a l d e h y d i c a c i d t o p e r m a n g a n a t e was 3:2 and t h e a p p r o p r i a t e k i n e t i c e x p r e s s i o n was u s e d . The r u n r e f e r r e d t o i n F i g u r e V I I I c o n c e r n s t e r e p h t h a l a l d e h y d i c a c i d a t pH 8.9 0 and was c a r r i e d o u t i n v i r t u a l l y t h e same way as t h e r u n o f F i g u r e V I I . P r o d u c t s S e v e r a l e x p e r i m e n t s w e r e c a r r i e d o u t i n w h i c h t h e o x i d a t i o n was p e r m i t t e d t o p r o c e e d t o n e a r l y 100% c o m p l e t i o n . The q u e n c h e d s o l u t i o n s a p p e a r e d t o c o n t a i n o n l y p h t h a l i c a c i d o r t e r e p h t h a l i c a c i d i n n e a r l y q u a n t i t a t i v e a m o u n t s . R e s u l t s S e c o n d o r d e r r a t e c o n s t a n t s w e r e d e t e r m i n e d f r o m a b o u t pH 6 t o 1 0 : 5 . The k i n e t i c b e h a v i o u r o f t h e compounds i n t h i s r e g i o n i s d i s p l a y e d i n F i g u r e I X a n d t h e d a t a a r e g i v e n i n T a b l e V. 64 65 TABLE V O x i d a t i o n o f P h t h a l d e h y d i c A c i d pH k(L/M/MIN) 6.12 14.4 7.12 12.0 7.70 11.2 [H Z] /[MnO ] = 3/2 7.9.5 10.5 z ° 4 ° 9.00 • 3.88 [ H Z ] = 0.00496M 9.90 9.19 ° 10.20 9.40 T = 25°C I o n i c S t r e n g t h = 0 . 4 3 10.28 9.76 10.2 8 10.10 O x i d a t i o n o f T e r e p h t h a l a l d e h y d i c A c i d pH k (L/M/MIN) 6,23 16.40 r i - I - Z l /TMnOTl = 3/2 6.95 14.90 * 2 4"'° 7.83 14.10 [ H Z ] = 0.00496M 8.90 16.80 ° 10.35 23.70 T = 25°C I o n i c S t r e n g t h = 0 . 4 3 66 A t e m p e r a t u r e s t u d y was c a r r i e d o u t on e a c h compound a t pH 8.1. F i g u r e s X and XI g i v e t h e l o g (k/T) a g a i n s t 1/T p l o t s f o r e a c h compound and t h e r e s u l t s a r e t a b u l a t e d i n T a b l e V I . TABLE V I k(L/M/SEC) k(L/M/SEC) T°C P h t h a l a l d e h y d i c a c i d T e r e p h t h a l a l d e h y d i c a c i d 5 0.0458 0.0663 15 0.0895 0.147 25 0.184 0.278 3 5 , ' 0.308 0.534 AH , (Kcal/° mole) 10.4 ± 0 . 4 11.2 ± 0 . 3 AS (eu) -27.1 ± 1 . 2 -23.4 ± 1 . 0 C o r r . C o e f f 0.999 0.999 D i s c u s s i o n The c u r v e s g i v e n i n F i g u r e IX a r e v e r y s i m i l a r t o . 37 t h o s e g i v e n b y Wiberg and S t e w a r t f o r t h e p e r m a n g a n a t e o x i d a t i o n o f b e n z a l d e h y d e and s u b s t i t u t e d b e n z a l d e h y d e s . The k i n e t i c b e h a v i o u r i s e v e r y w h e r e s e c o n d o r d e r w i t h t h e o b s e r v a t i o n t h a t t h e r e a c t i o n t e n d s t o become a u t o c a t a l y t i c as t h e medium becomes more a c i d i c t h a n a b o u t pH 5. T h i s 16 b e h a v i o u r i s w e l l - k n o w n and i s t h o u g h t t o be c a u s e d by t h e a c t i o n o f l o w e r o x i d a t i o n s t a t e s o f manganese w h i c h w o u l d be p r e s e n t a f t e r t h e r e a c t i o n h a d p r o c e e d e d t o some e x t e n t . 67 CD U .315 0.325 1 r 1.335 0. I/T ) P h t h a l a l d e h y d i c a c i d o x i d a t i o n 0.355 0.365 pH = 8.1 AH ^ = 10 . 4*0 . 4 ,(Kcal/° m o l e ) AS = -27 . 1 ±1.2(eu) C o r r e l a t i o n C o e f f i c i e n t = .0.999 68 0.315 0.325 0.335 1/1 0.345 (X10 +2 J 0.355 0.365 T e r e p h t h a l a l d e h y d i c a c i d o x i d a t i o n pH = 8.1 A H X = 11.2"-0.3 (Kcal/° m o l e ) C o r r e l a t i o n C o e f f i c i e n t 0 .999 A S = - 2 3 . 4 - 1 . 0 ( e u ) 69 The r a t e b e h a v i o u r o f t h e two compounds i n t h i s study-i s s l i g h t l y d i f f e r e n t . I n t h e pH r e g i o n 5.5 - 7.5 t h e r a t e o f t h e o r t h o compound i s a b o u t 10% l o w e r t h a n t h e p a r a compound an d b o t h d e c r e a s e i n r e a c t i v i t y i n t h i s r e g i o n . A t a b o u t pH 7.5 t h e p a r a compound b e g i n s t o u n d e r g o a r a t e i n c r e a s e w h i c h r e s u l t s i n a t w o - f o l d e x a l t a t i o n by pH 1 0 . 5 . The r a t e o f t h e o r t h o compound c o n t i n u e s t o d e c r e a s e a f t e r pH 7.5 b u t t h e d e c r e a s e h a l t s a t a b o u t pH 9.5 and becomes a v e r y s l i g h t i n c r e a s e b y pH 1 0 . 5 . 37 The s t u d i e s o f Wiberg and S t e w a r t i n d i c a t e t h a t t h e r e a c t i o n c o r r e s p o n d i n g t o t h a t p a r t o f t h e c u r v e a t l o w e r pH d e p e n d s u pon t h e b u f f e r c o n c e n t r a t i o n w h i l e t h e r e a c t i o n a t h i g h e r pH i s b a s e c a t a l y s e d a n d i s i n d e p e n d e n t o f t h e b u f f e r . The e f f e c t o f s u b s t i t u e n t s on t h e r e a c t i o n h a s b e e n d e t e r m i n e d b y Wiberg • and S t e w a r t a t pH 6.5 a n d 12.6 who f i n d a p v a l u e o f -0.25 a t t h e f o r m e r pH and a p o f -1.8 f o r t h e l a t t e r . Some d o u b t h a s b e e n r a i s e d c o n c e r n i n g t h e e x a c t 3 8 m e c h a n i s t i c i m p l i c a t i o n s o f t h e s e v a l u e s . C o n s e q u e n t l y t h e m e c h a n i s m m u s t be v i e w e d a s r e q u i r i n g more e l u c i d a t i n g e x p e r i m e n t a l w o r k and a d i s c u s s i o n a t t h i s p o i n t n o t f r u i t f u l . The r a t e c o n s t a n t s m e a s u r e d f o r t e r e p h t h a l a l d e h y d i c a c i d i n t h i s w o rk a p p e a r t o be o f t h e c o r r e c t m a g n i t u d e a l t h o u g h a d i r e c t c o m p a r i s o n i s n o t p o s s i b l e s i n c e t h e b u f f e r 70 c o n c e n t r a t i o n s and i o n i c s t r e n g t h s a r e n o t t h e same i n b o t h c a s e s . The a c t i v a t i o n p a r a m e t e r s d e t e r m i n e d i n t h i s work f o r p h t h a l a l d e h y d i c a c i d (A . = 10.4 - 0.4 . (Kcal ./°Mole) , AS^ = -27.1 - 1.2(eu) a r e , w i t h i n e x p e r i m e n t a l e r r o r , t h e same as t h o s e d e t e r m i n e d b y Wiberg and S t e w a r t f o r b e n z a l d e h y d e (AH^ = 10.0 - 0.3 Kcal/"Mole, J i + AS • = -26.2 - L e u ) . The a c t i v a t i o n p a r a m e t e r s r e f e r r i n g t o t h e o x i d a t i o n o f t e r e p h t h a l a l d e h y d i c a c i d a r e n o t s i g n i f i c a n t l y d i f f e r e n t f r o m t h i s ( A H ^ = 11.2 - 0.3 Kcal/°Mole . AS^, = -23.4 - 1.0 eu) . I t d o e s n o t a p p e a r that any m e a n i n g f u l c o n c l u s i o n c a n be drawn f r o m t h e m a g n i t u d e o f t h e s e p a r a m e t e r s . I t s u f f i c e s t o s a y t h a t t h e y a r e " n o r m a l " . o - B e n z a l d e h y d e c a r b o x y l i c a c i d o r , as i t i s more commonly known, p h t h a l a l d e h y d i c a c i d h a s b e e n r e p r e s e n t e d 39 as e i t h e r one o f t h e f o l l o w i n g s t r u c t u r e s : CHO c 11 0 / 0 71 E v i d e n c e b a s e d on t h e i n f r a r e d s p e c t r u m o f t h e compound a s a s o l i d a n d a s a s o l u t e i n w a t e r h a s b e e n o b t a i n e d w h i c h i n d i c a t e s t h a t t h e compound e x i s t s i n t h e r i n g - c l o s e d f o r m r a t h e r t h a n t h e r i n g - o p e n form'* 3, The c h e m i c a l p r o p e r t i e s o f t h i s compound a r e n o t e x c l u s i v e l y t h o s e t h a t one w o u l d c o n s i d e r a p p r o p r i a t e f o r a r i n g - c l o s e d compound ( t h e l a c t o l ) . I t h a s , f o r e x a m p l e , a pK o f 4.56, d e t e r m i n e d b y t i t r a t i o n w i t h b a s e f ^ . T h i s i s n o t a n u n u s u a l pK. The a c i d i t y o f p h t h a l a l d e h y d i c a c i d c a n be c o m p a r e d w i t h t h a t o f o - - a c e t o x y b e n z o i c a c i d ^ 1 (pK = 4 . 5 7 ) . The pK' s o f 41 p - f o r m y l b e n z o i c a c i d (3.98) a n d p - a c e t o x y b e n z o i c a c i d (3.89) a r e c l o s e , s h o w i n g t h e s e s u b s t i t u e n t s t o h a v e s i m i l a r e f f e c t s on a c i d i t y i n b o t h o r t h o a n d p a r a p o s i t i o n s . . The 42 compound h a s b e e n shown t o u n d e r g o t h e C a n n x z z a r o r e a c t i o n , a t y p i c a l r e a c t i o n o f a l d e h y d e s l a c k i n g C l - h y d r o g e n s . B o t h o f t h e s e l a t t e r o b s e r v a t i o n s p o i n t t o t h e r i n g - o p e n a l d e h y d e r a t h e r t h a n t h e r i n g - c l o s e d 3 - h y d r o x y p h t h a l i d e . Hov/ever, t h e r e i s c h e m i c a l b e h a v i o u r o f a v e r y s t r i k i n g k i n d t h a t 39 c a n o n l y be a c c o m o d a t e d b y t h e r i n g - c l o s e d compound A l c o h o l s , s u c h a s m e t h a n o l , e t h a n o l e t c . , r e a c t w i t h o u t a c a t a l y s t i n a few h o u r s t o g i v e a 3 - a l k o x y p h t h a l i d e a n d w a t e r . The r e a c t i v i t y o f p h t h a l a l d e h y d i c a c i d h a s b e e n s t a t e d t o a p p r o a c h t h a t o f a n a c i d c h l o r i d e o r a n h y d r i d e f o r e v e r y r e a c t a n t e x c e p t w a t e r . 72 Phthalaldehydic acid i s not alone i n t h i s behaviour. 4 3 On the basis of i n f r a r e d and N.M.R. spectra i t was shown that o-acetylbenzoic acid e x i s t s in .methylene chloride solution as 3-hydroxy-3-methylphthalide. The p r e c i s i o n of these experimental techniques did not rule out the p o s s i b i l i l t y of an equilibrium between the ring-open and the ring-closed form but i t shows that the equilibrium strongly favours the 4 4 4 5 l a t t e r . In t h i s case also, there i s chemical evidence ' favouring the ring-open structure so that an equilibrium i s more l i k e l y . well as comparing them with those of Wiberg and Stewart ) reveals that we are dealing i n t h i s instance with two rather t y p i c a l aldehyde oxidations. The magnitude of the rate constants and the shape of the rate versus pH p l o t i s not i n accord with a ring-close structure which, i n view of the pK, would have to be ionized i n the pH region considered. Examination of the curves shown i n Figure IX (as 37 73 The i o n I V r e s e m b l e s a l k o x i d e i o n and p r e s u m a b l y w o u l d h a v e t h e l a r g e r e a c t i v i t y o f t h e s e i o n s . The s e c o n d o r d e r r a t e c o n s t a n t f o r t h e o x i d a t i o n o f t h e i o n V I by p e r m a n g a n a t e i s a b o u t 7.2 L/M/Sec w h i l e t h e r a t e c o n s t a n t r e f e r r i n g t o t h e o x i d a t i o n o f t h e a n i o n o f p h t h a l a l d e h y d i c a c i d i s a b o u t 0.2:. L/M/Sec i n t h e pH r a n g e s t u d i e d . a c i d i t i e s g r e a t e r t h a n pH 5 show c u r v a t u r e a n d i t was n o t p o s s i b l e t o d e t e r m i n e r a t e s i n t h i s r e g i o n e x c e p t a p p r o x i m a t e 46 . . . u s i n g t h e i n i t i a l s l o p e s . T o m p k i n s s t u d i e d t h e i n i t i a l r a t e s o f o x i d a t i o n o f b e n z a l d e h y d e f r o m pH 4.1 t o 0.4 o b s e r v i n g a r a t e i n c r e a s e b y a f a c t o r f i v e t o w a r d s t h e more s t r o n g l y a c i d i c s i d e . I n t h e p r e s e n t work, r a t e s t u d i e s w e r e a t t e m p t e d a t pH 3.7 a n d t h e r a t e p l o t was f o u n d t o be c u r v e d as i n F i g u r e X I I . No a c c u r a t e r a t e c o n s t a n t c a n be e x t r a c t e d f r o m s u c h d a t a b u t a n a p p r o x i m a t e one w o u l d be a b o u t 8 L/M/Min. The s t r a i g h t l i n e c o r r e s p o n d i n g t o t h i s v a l u e h a s b e e n s k e t c h e d i n . H o w e v e r , when t h e a c i d i t y i s i n c r e a s e d t o pH 1.55 K i n e t i c e x p e r i m e n t s on p h t h a l a l d e h y d i c a c i d a t 74 ~ r — — r 4.0 ^ _ 8.0 12.0 TIMEtMINUTESJ P h t h a l a l d e h y d i c A c i d O x i d a t i o n pH = 3 . 6 8 T = 25°C S t r a i g h t l i n e c o r r e s p o n d s t o k = 8.0 4M/MIN 75 a new b e h a v i o u r i s o b s e r v e d . I n s t e a d o f t h e r e a c t i o n b e i n g a u t o c a t a l y t i c i t a p p e a r s t o be a t r u e s e c o n d o r d e r r e a c t i o n whose r a t e p l o t r e m a i n s a s t r a i g h t l i n e up t o a b o u t 50% r e a c t i o n . T h i s i s n o t t h e u s u a l b e h a v i o u r o f a l d e h y d e s . The w o r k o f T o m k i n s shows t h a t t h e a u t o c a t a l y t i c n a t u r e o f t h e r e a c t i o n c o n t i n u e s t o h i g h e r a c i d i t i e s ^ . M o r e o v e r , T o m k i n s h a s f o u n d t h a t t h e i n i t i a l r a t e i n c r e a s e s a b o u t f i v e - f o l d on r a i s i n g t h e a c i d i t y f r o m pH 4.1 t o 0.4. I n t h e c a s e o f p h t h a l a l d e h y d i c a c i d t h i s i s n o t o b s e r v e d . The r a t e a t pH 1.55 i s i n f a c t s m a l l e r , b y a f a c t o r o f t h r e e , t h a n t h e r a t e d e t e r m i n e d a t pH 6.1 . The r a t e p l o t f o r two s e p a r a t e r u n s d i s p l a y e d on t h e same g r a p h i s shown i n F i g u r e X I I I . The v a l i d i t y o f t h e r u n a t pH 1.55 was c h e c k e d by r e p e t i t i o n as w e l l as by u s i n g a s a m p l e o f t h e same s t o c k s o l u t i o n u s e d a t pH 1.55 a t h i g h e r pH (6.1 ) . The b e h a v i o u r a t pH 1.55 i s f o u n d t o be r e p r o d u c i b l e a n d t h e r a t e c o n s t a n t s d e t e r m i n e d a t h i g h e r pH a g r e e w i t h t h o s e p r e v i o u s l y d e t e r m i n e d i n t h i s w o r k . The u n e x p e c t e d b e h a v i o u r a t pH 1.55 t h u s a p p e a r s t o be a v a l i d o b s e r v a t i o n . The b e h a v i o u r o f p h t h a l a l d e h y d i c a c i d c a n be e x p l a i n e d i n t e r m s o f t h e s p e c i e s w h i c h a r e p r e s e n t i n s o l u t i o n s o f v a r i o u s a c i d i t i e s . F o r t h e s a k e of- a r g u m e n t t h e r e a r e f o u r s p e c i e s : 76 r -o TIME(MINUTES) P h t h a l a l d e h y d i c a c i d o x i d a t i o n pH = 1.55 k = 4.95L/M/MIN 77 V V VII X S i n c e t h e pK i s 4.56 t h e c u r v e s i n F i g u r e I X r e f e r t o t h e o x i d a t i o n - o f t h e a n i o n . I t h a s a l r e a d y b e e n i n d i c a t e d t h a t t h e s i m i l a r i t y o f t h e s e c u r v e s ' t o t h o s e a l r e a d y i n v e s t i g a t e d ' f o r o t h e r a l d e h y d e s a s w e l l a s t h e s i m i l a r i t y o f t h e a c t i v a t i o n p a r a m e t e r s i n d i c a t e s an a l d e h y d e t o be r e a c t i n g 3 ^ . A t pH 3.7 t h e c u r v e d r a t e p l o t i s i n d i c a t i v e o f an a l d e h y d e o x i d a t i o n a s w e l l . The i n i t i a l r a t e a t t h i s pH ; (^8 L/M/MIN -) i s s m a l l e r t h a n t h e r a t e d e t e r m i n e d a t pH 6.1 w h e r e s e c o n d o r d e r k i n e t i c s p r e v a i l s . S i n c e t h e compound i s o n l y ~ 9 % i o n i z e d t h e l o w e r i n g i n r a t e c o u l d mean e i t h e r a s m a l l e r r e a c t i v i t y o f t h e n e u t r a l a l d e h y d e ( V I I ) o r t h e a b s e n c e o f a n y a l d e h y d e o t h e r t h a n t h e i o n i z e d s p e c i e s ( I X ) . The b e h a v i o u r a t pH = 1.55 i s more c h a r a c t e r i s t i c o f a n a l c o h o l o r a l c o h o l - l i k e compound. The g o o d s e c o n d o r d e r k i n e t i c s a n d t h e l o w e r r a t e c o n s t a n t (4.95 L/M/MIN), c l o s e t o t h a t o f b e n z h y d r o l (~2 L/M/MIN )^ , a r e more i n a c c o r d w i t h t h e b e h a v i o u r e x p e c t e d f o r t h e a l c o h o l - l i k e V I t h a n t h e a l d e h y d e V I I . T h i s i n e l u ' c t a b l y l e a d s one t o s a y t h a t u n i o n i z e d p h t h a l a l d e h y d i c a c i d e x i s t s a l m o s t e n t i r e l y a s V I , w h i l e t h e a n i o n e x i s t s a s t h e a l d e h y d e I X . C o n s i d e r i n g t h e 78 r e a c t i v i t y o f a l k o x i d e i o n , a n y a p p e a r a n c e o f t h e i o n V I I I w o u l d r e s u l t i n a much h i g h e r r a t e t h a n h a s b e e n o b s e r v e d . T h i s e x p l a i n s why p h t h a l a l d e h y d i c a c i d u n d e r g o e s t h e C a n n i z z a r o r e a c t i o n w h i c h i s c a r r i e d o u t i n s t r o n g b a s e . I t a l s o i n d i c a t e s t h a t t h e n e u t r a l m o l e c u l e w o u l d r e a c t a s 3 - h y d r o x y p h t h a l i d e r a t h e r t h a n a s 2 - f o r m y l b e n z o i c a c i d . 79 SECTION C THE CYCLOHEXANOL SYSTEM E x p e r i m e n t a l I n t h i s s t u d y , some o f t h e compounds w e r e s u f f i c i e n t l y s o l u b l e i n w a t e r t o p e r m i t t h e p r e p a r a t i o n o f s t o c k s o l u t i o n s d i r e c t l y . T h us a q u e o u s s o l u t i o n s (0.03 M) o f c y c l o h e x a n o l , c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d and t r a n s - 2 -h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d w e r e p r e p a r e d . The compounds b e a r i n g a t - b u t y l s u b s t i t u e n t w e r e i n g e n e r a l much l e s s s o l u b l e t h a n compounds w i t h o u t t h i s g r o u p . I n t h e c a s e o f c i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X ) , c i s - 5 - t - b u t y l - - t r a n s - - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X I ) an d t r a n s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X I I ) s t o c k s o l u t i o n s o f a b o u t 0.0 3 M w e r e p r e p a r e d by m i x i n g t h e o r g a n i c a c i d and a n e q u i v a l e n t - a m o u n t o f p o t a s s i u m h y d r o x i d e i n warm d i s t i l l e d w a t e r . 80 S i n c e t h e t - b u t y l s u b s t i t u t e d a l c o h o l s a r e n o t v e r y s o l u b l e t h e i r c o n c e n t r a t i o n i n t h e r e a c t i o n m i x t u r e c o u l d n o t be v e r y much g r e a t e r t h a n a b o u t 0.005 M and was g e n e r a l l y k e p t c l o s e t o t h i s v a l u e . The more s o l u b l e a l c o h o l s w e r e u s u a l l y c o n c e n t r a t e d t o t h e e x t e n t o f 0.015 M f o r t h e k i n e t i c e x p e r i m e n t s a l t h o u g h some r u n s a t c o n c e n t r a t i o n s c o m p a r a b l e t o t h o s e u s e d f o r t h e l e s s s o l u b l e a l c o h o l s w e r e c a r r i e d o u t . K i n e t i c r u n s on c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d w e r e p e r f o r m e d i n d e u t e r i u m o x i d e s o l v e n t a s w e l l as p r o t i u m o x i d e . The d e u t e r i u m o x i d e u s e d was 99.7 atom p e r c e n t d e u t e r i u m a n d s t o c k s o l u t i o n s o f t h e v a r i o u s c o m p o n e n t s i n v o l v e d i n t h e r e a c t i o n m i x t u r e w e r e p r e p a r e d i n t h i s s o l v e n t . As b u f f e r K^DPO^ was u s e d a n d t h e pD was a d j u s t e d u s i n g 10M D^O^. The m e a s u r e m e n t o f t h e pD o f t h e medium was a c c o m p l i s h e d a c c o r d i n g t o t h e d i r e c t i o n s o f G a r y , B a t e s and 47 R o b i n s o n u s i n g t h e g l a s s e l e c t r o d e a n d t h e s a t u r a t e d c a l o m e l e l e c t r o d e . To a v o i d u s i n g e x c e s s i v e amounts o f d e u t e r i u m o x i d e t h e r e a c t i o n s w e r e f o l l o w e d s p e c t r o p h o t o -m e t r i c a l l y r a t h e r t h a n b y t i t r a t i o n . A s e r i e s o f r u n s i n b a s i c s o l u t i o n on c i s - 2 -h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d w e r e p e r f o r m e d u s i n g a s u b s t r a t e c o n c e n t r a t i o n o f 0.018 M and a n i n i t i a l c o n c e n t r a t i o n r a t i o o f s u b s t r a t e t o p e r m a n g a n a t e o f 1 t o 2. The r a t e c o n s t a n t s w e r e d e t e r m i n e d s p e c t r o p h o t o m e t r i c a l l y b y m e a s u r e m e n t o f o p t i c a l d e n s i t i e s a t t w o w a v e l e n g t h s . 81 Products The oxidation of cyclohexanol by permanganate i n neutral solution under conditions i n which three moles o f substrate are consumed for every two moles of permanganate can reasonably only give r i s e to cyclohexanone as product. 3 L i t t l e r has made a product study on t h i s reaction and finds that cyclohexanone i s obtained i n quantitative y i e l d . In the case of 2-carboxy substituted alcohols the s i t u a t i o n i s a b i t more complicated. The ketone product expected would be a 6-keto acid, which species i s known t o 48 undergo decarboxylation r e a d i l y . Thus, i f the reaction i s permitted to proceed i n the usual way and a product analysis made, the product found i s sure to be a ketone which does not possess a carboxyl function. Analysis at some early stage of the reaction, accomplished i n a b r i e f time span so that the B-keto acid i s not extensively decomposed, i s necessary t o prove whether any B-keto acid i s formed i n the oxidation. Absence of 6-keto acid could mean that decarboxylation i s concomitant with rather than subsequent to oxidation. Because permanganate ion and other oxidation states of manganese of a 8-keto i n t e r f e r e with spectrophotometry i d e n t i f i c a i o n acid i t was necessary to separate the organic products from the reaction mixture. Extraction with ether was u t i l i z e d and because of favourable s o l u b i l i t y c h a r a c t e r i s t i c s compound X was used. The product could be more conveniently I 82 e x t r a c t e d i f i t c o n t a i n e d a t - b u t y l g r o u p w h i c h r e d u c e s i t s s o l u b i l i t y i n w a t e r . A c c o r d i n g l y , 5 - t - b u t y l - 2 - o x o c y c l o h e x a n e c a r b o x y l i e a c i d ( X I I I ) 32 was p r e p a r e d u s i n g t h e p r o c e d u r e o f S i c h e r . T h i s compound i s t h e supposed p r o d u c t i n t h e p e r m a n g a n a t e o x i d a t i o n o f X.-Some s p e c t r a l p r o p e r t i e s o f t h i s compound w e r e e x a m i n e d f o r a n a l y t i c a l u s e , I n e t h e r s a t u r a t e d w i t h w a t e r t h e s e a r e * = 254 my , e = 5570 max The e x t r a c t i o n p r o c e d u r e was c h e c k e d u s i n g known amounts o f X I I I d i s s o l v e d i n w a t e r . The a q u e o u s s o l u t i o n was e x t r a c t e d w i t h e t h e r and t h e c o n c e n t r a t i o n o f X I I I d e t e r m i n e d b y m e a s u r i n g t h e o p t i c a l d e n s i t y a t 254my. The amount o f X I I I t h u s d e t e r m i n e d was u s u a l l y g r e a t e r t h a n 90% o f t h e t h e o r e t i c a l amount b u t n e v e r c o m p l e t e l y q u a n t i t a t i v e . A l l o w i n g t h e a q u e o u s s o l u t i o n t o s t a n d f o r s e v e r a l h o u r s i n n e u t r a l b u f f e r r e v e a l e d o n a n a l y s i s , t h a t m o s t o f t h e compound was d e c a r b o x y l a t e d , The p r o d u c t o f d e c a r b o x y l a t i o n , 4 - t - b u t y l c y c l o h e x a n o n e , h a s a v e r y s m a l l a b s o r p t i o n ( e = 1 5 . 8 , \ = 288mn) an d i s IflclX n o t o b s e r v e d i n t h e a n a l y s i s . 83 I n a n a c t u a l r u n a l i q u o t s (5 ml) w e r e w i t h d r a w n f r o m t i m e t o t i m e a n d e x t r a c t e d w i t h a q u a n t i t y o f e t h e r (10 m Some o f t h i s e t h e r e x t r a c t was p l a c e d i n a q u a r t z c e l l a n d t h e o p t i c a l d e n s i t y a t 254mIJ, r e c o r d e d . The r e s u l t s show t h a t t h e e x p e c t e d 3 - k e t o a c i d i s a c t u a l l y p r o d u c e d b u t t h e a g r e e m e n t i s o n l y s e m i - q u a n t i t a t i v e . A t a b o u t 25% r e a c t i o n t h e amount o f X I I I o b s e r v e d a c c o u n t s f o r 8 1 % o f t h e t h e o r e t i c a l maximum a n d f a l l s o f f a f t e r t h i s p o i n t . I t i s r e a s o n a b l e t h a t a t l a t e r s t a g e s i n t h e r e a c t i o n t h e q u a n t i t y o f 3 - k e t o a c i d f o u n d s h o u l d be l e s s t h a n q u a n t i t a t i v e b e c a u s e o f i t s d e c o m p o s i t i o n . E a r l i e r on t h e a g r e e m e n t s h o u l d be b e t t e r . B e c a u s e o f t h e n a t u r e o f X I I I t h e a n a l y t i c a l t e c h n i q u e c a n n o t p r o d u c e q u a n t i t a t i v e r e s u l t s b u t must f a l l somewhat s h o r t o f t h i s . I t i s shown, h o w e v e r , t h a t s u b s t a n t i a l l y t h e e x p e c t e d p r o d u c t i s p r o d u c e d a nd t h e r e i s no r e a s o n t o b e l i e v e t h a t i t i s n o t t h e s o l e p r o d u c t . The a n a l y s i s l e a d s t o t h e c o n c l u s i o n t h a t t h e i m m e d i a t e o x i d a t i o n p r o d u c t i s 5 - t - b u t y l - 2 - o x o c y c l o h e x a n e c a r b o x y l i c a c i d w h i c h l a t e r d e c a r b o x y l a t e s t o g i v e 4 - t - b u t y l c y c l o h e x a n o n e . R e s u l t s F o r t h e c a s e o f s e c o n d a r y a l c o h o l s w h i c h p o s s e s s h y d r o g e n atoms i n t h e 2- p o s i t i o n , t h e o x i d a t i o n h a s one c o m p l i c a t i n g f e a t u r e . The p r o d u c t i s a k e t o n e b e a r i n g a h y d r o g e n s and t h e r e f o r e i s e n o l i z a b l e . E n o l s a r e r e a d i l y 84 a t t a c k e d by p e r m a n g a n a t e and t h e s e c o n d o r d e r r a t e p l o t s w i l l n o t r e m a i n s t r a i g h t l i n e s o v e r a v e r y l a r g e e x t e n t o f r e a c t i o n o w i n g t o t h e r e a c t i v i t y o f t h e p r o d u c t . I n n e u t r a l s o l u t i o n i t i s p o s s i b l e t o o b s e r v e g o o d s e c o n d - o r d e r k i n e t i c s 2 up t o 50% r e a c t i o n ( ( V -V )/(V,~=V ) = 1 ) . I n s o l u t i o n s more a c i d i c t h a n pH 7 i t i s f o u n d t h a t s t r a i g h t l i n e s a r e o b s e r v e d f o r s m a l l e r e x t e n t s o f r e a c t i o n b e c a u s e o f t h e e n o l i z a t i o n o f t h e p r o d u c t k e t o n e w h i c h i s c a t a l y z e d b y a c i d . I t m ust be p o i n t e d o u t t h a t a t r u e s t r a i g h t l i n e whose s l o p e c a n be d e t e r m i n e d r e p r o d u c i b l y i s o b s e r v e d and n o t a c u r v e whose l i m i t i n g s l o p e i s u s e d t o c a l c u l a t e t h e r a t e . C y c l o h e x a n o l A r e p r e s e n t a t i v e r a t e p l o t f o r t h e o x i d a t i o n o f c y c l o h e x a n o l i s g i v e n i n F i g u r e X I V . The p H - r a t e p r o f i l e , f o r t h i s o x i d a t i o n o v e r t h e pH r a n g e 1-10.5 i s g i v e n i n F i g u r e XV a n d t h e c o r r e s p o n d i n g d a t a a r e f o u n d i n T a b l e V I I . 85 CO rv o ° _______ o n i — — — \ 1 1 — 0.0 33.0 05.0 99.0 132.0 165.0 . TIME(MINUTESJ C y c l o h e x a n o l . o x i d a t i o n T = 25°C pH = 5.88 [ c y c l o h e x a n o l ] = 0 . 0 0 9 9 3 M i o n i c S t r e n g t h = 0.43 [ M n 0 4 ] Q = 0.00662M k' = 0.16 2L/M/MIN 87 TABLE V I I P e r m a n g a n a t e o x i d a t i o n o f C y c l o h e x a n o l pH k (L/M/MIN) T 1.19 3.58 5.8 8 8.11 10.48 0.362 0.214 0.162 0.152 0.160 [ c y c l o h e x a n o l ] = 0.00993M o [MnO.l = 0.00662M L 4 J o I o n i c S t r e n g t h = 0.43 The pH-rate p r o f i l e i s q u i t e u n r e m a r k a b l e i n t h e r e g i o n i n v e s t i g a t e d . The v e r y g e n t l e i n c r e a s e i n t h e r a t e t o w a r d s h i g h e r a c i d i y a n d t h e f l a t p o r t i o n i n t h e r e g i o n o f n e u t r a l i t y a r e s i m i l a r t o t h e p r o f i l e o b s e r v e d f o r t h e b e n z h y d r o l o x i d a t i o n " ' " . The e x a c t e x p l a n a t i o n o f t h i s b e h a v i o u r h a s n o t b e e n o b t a i n e d b u t t h e s i m i l a r i t y i n b e h a v i o u r i s e v i d e n t . C i s - a n d T r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d s A t y p i c a l r a t e p l o t f o r t h e c i s - c o m p o u n d i s g i v e n i n F i g u r e X V I a n d f o r t h e t r a n s - c o m p o u n d i n F i g u r e X V I I . The p H - r a t e p r o f i l e s f o r b o t h t h e s e compounds a r e p l o t t e d i n F i g u r e X V I I I a n d t h e d a t a p r e s e n t e d i n T a b l e s V I I I a n d I X . OH H XIV CIS XV TRANS 88 40.0 80.0 120.0 TIME(MINUTES) 20Q.0 C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d o x i d a t i o n [ S u b s t r a t e ] Q = 0.002481M T = 25°C pH = 6.20 [MnO~J Q • •= 0.001654M I o n i c S t r e n g t h = 0.43 k = 0.9 44L/M/MIN 89 I 50.0 loo.a 150 TIME(MINUTESJ 200.0 250. D T r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d o x i d a t i o n [ S u b s t r a t e ] q = 0.01499M [MnO~] = 0.0100 0M T = 25"C pH = 5.00 I o n i c S t r e n g t h = 0.43 k = 0.06 71L/M/MIN 90 pH -- r a t e p r o f i l e s -A' - t r a n s - 2 - h y d r o x y c y c l q h e x a n e c a r b o x y l i c a c i d B - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ,The. s o l i d l i n e i s o b t a i n e d f r o m t h e a n a l y s i s o f t h e d a t a o f T a b l e V I I I a c c o r d i n g t o E q u a t i o n 15 o f t h e D i s c u s s i o n s e c t i o n , The c o n s t a n t s u s e d i n t h e c a l c u l a t i o n a r e f r o m T a b l e XV. The x ' s r e p r e s e n t t h e e x p e r i m e n t a l p o i n t s . 91 TABLE V I I I C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d pH 1. 1. 3, 3 3, 3 4 4 , 5 5, 6 6 7, 7, 11 55 05 05 62 80 45 90 05 88 20 65 10 10 7.10 7.58 8.11 8. 86 9.20 10 .48 11. 03 5.88 5 . 8 8 k(L/M/MIN) 0.548 0.470 0.341 0.375 0.407 0.457 0 .560 0 . 730 0 .786 0 .985 0.935 0 .820 0 .700 0.660 0.635 0 .482 0 .413 0.262 0 .163 0 .160 0 .206 0 . 9 7 5 a n o op,fo r i - M N 0 4 J o ^ S u b s t r a t e J Q I o n i c S t r e n g t h [OH"] 0.016 0.045 0 . 080 0 .126 0 .158 0.305 25°C 0.00333 M 0.00500 M 0 . 43 k(L/M/MIN) 2 3, 3. 4, 80 20 60 80 7 . 4 0 9 . 8 0 a. p h o s p h a t e c o n c e n t r a t i o n r e d u c e d b y a f a c t o r o f two and i o n i c s t r e n g t h m a i n t a i n e d w i t h s o d i u m p e r c h l o r a t e b. b u f f e r c o n c e n t r a t i o n r e d u c e d b y a f a c t o r o f f i v e . TABLE I X T r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d pH k(L/M/MIN) T = 25 C 1.55 0 .0785 [ S u b s t r a t e ] = 0.015 M. 3.58 0.0470 _ ° 5.00 0.0671 [MnO.] = 0.010 M 6 .00 0.0718 ° 6.97 0 .0490 = 0.43 7.28 0.0442 8.11 0.0452 92 Two f a c t s a r e i m m e d i a t e l y e v i d e n t f r o m F i g u r e X V I I I - f i r s t l y , t h e s t r i k i n g b e l l - s h a p e p r o f i l e f o r t h e c i s -compound and s e c o n d l y , t h e a b s e n c e o f s u c h an e f f e c t f o r t h e t r a n s - c o m p o u n d and i t s l o w e r r e a c t i v i t y . T h e s e e f f e c t s w i l l r e c e i v e a d i s c u s s i o n f u r t h e r on when o t h e r r e l e v a n t i n f o r m a t i o n h a s b e e n p r e s e n t e d . K i n e t i c s t u d i e s on t h e c i s - c o m p o u n d w e r e c a r r i e d o u t i n d e u t e r i u m o x i d e s o l v e n t as w e l l . The s e c o n d o r d e r r a t e c o n s t a n t s ( s p e c t r o p h o t o m e t r i c ) as a f u n c t i o n o f pD a r e g i v e n i n T a b l e X and F i g u r e X I X . TABLE X C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d O x i d a t i o n i n d e u t e r i u m o x i d e pD k (L/M/MIN) T = 25°C 2.18 0.20 6 [ S u b s t r a t e ] = 0.00 29 2M 2.91 0.240 L J ° 3.70 0.430 4.65 0.58 l M n 0 , i | = 0.0019 5M 5.65 0.640 4 0 6.58 0.640 I o n i c S t r e n g t h = 0.43 7.56 0.555 8.10 0.420 9.03 0.190" As m e n t i o n e d i n t h e G e n e r a l E x p e r i m e n t a l s e c t i o n t r a n s - 2 - d e u t e r i o - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d was p r e p a r e d . The o x i d a t i o n r a t e o f t h i s compound was m e a s u r e d u s i n g a t i t r a t i o n m e t h o d . The d a t a a r e g i v e n i n F i g u r e XX and T a b l e X I . 93 10.0 pH - r a t e p r o f i l e c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d O x i d a t i o n i n d e u t e r i u m o x i d e . The s o l i d l i n e was d e r i v e d f r o m t h e d a t a o f T a b l e X u s i n g E q u a t i o n 15. The c o n s t a n t s u s e d i n t h i s E q u a t i o n a r e f r o m T a b l e X V I . The x ' s r e p r e s e n t t h e e x p e r i m e n t a l p o i n t s . 94 pH - r a t e p r o f i l e T r a n s - 2 - d e u t e r i o - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d U n f o r t u n a t e l y t h e a t t e m p t e d c o r r e l a t i o n a c c o r d i n g • t o . E q u a t i o n 15 d i d n o t w o r k . The c o r r e l a t i o n c o e f f i c i e n t was n o t h i g h e r t h a n 0.93 w h i c h i s t o o l o w t o be. m e a n i n g f u l . P r e s u m a b l y t h e e r r o r i n t h e r a t e c o n s t a n t s , i s t o o g r e a t " t o p e r m i t c o r r e l a t i o n . 95 TABLE XI Trans-2-deuterio-cis-2-hydroxycyclohexanecarboxylic acid OH pH 2. 3, 4. 5. 6. 6, 7, 00 20 11 01 11 73 46 k(L/M/MIN) 10.38 0.0719 0.0575 0560 107 149 103 0 .0872 0.0214 T = 25 C [Substrate] = 0.0104 M [MnO~]o = 0.00693 M Ionic Strength = 0.43 The 5-t-butyl-2-hydroxycyclohexanecarboxylic acids Of the four isomers possible (each having the t-butyl group i n the equatorial position) three are used i n the present work. As mentioned e a r l i e r they are c i s - 5 - t -butyl-cis-2-hydroxycyclohexanecarboxylic acid (X), c i s - 5 -t-butyl-trans-2-hydroxycyclohexanecarboxylic acid (XI) and trans-5-t-butyl-cis-2-hydroxycyclohexanecarboxylic acid (XII). Because of the large conformational energy of the t-butyl group i t must remain almost e x c l u s i v e l y i n the ! 49 equatorial p o s i t i o n . Because of t h i s the conformations of each of the three isomers e x i s t predominately ( 99.9%) 96 i n t h e p r e f e r r e d c o n f o r m a t i o n . T h i s i s c o n t r a s t e d w i t h t h e two i s o m e r s o f 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d whose c o n f i g u r a t i o n s a r e n o t s o r i g i d l y b i a s e d i n f a v o u r o f one c o n f o r m a t i o n . E v i d e n c e w i l l be p r e s e n t e d t o i n d i c a t e t h a t compounds X, X I , X I I , X I V and XV do a c t u a l l y h a v e t h e c o n f o r m a t i o n s a l r e a d y i m p l i e d . Compound X h a s t h e p H - r a t e p r o f i l e g i v e n i n F i g u r e X X I a n d T a b l e X I I . The d a t a f o r compounds X I a n d X I I i s p r e s e n t e d i n T a b l e X I I I . H e r e i t i s n o t e d t h a t t h e b e l l - s h a p e TABLE X I I C i s - 5 - t - b u t y l - c i pH k(L/M/M: 2. 00 1.1 2,55 0.820 3. 00 0.255 4. 30 1. 45 4.50 2.10 4.48 2.30 5.46 3.59 5.50 3.12 5.80 4. 25 6 .19 3.25 6 .39 3.50 7.00 2 .50 7.85 1.31 8. 11 0.447 T = 2 5°C S u b s t r a t e = 0.00100 M L o [ M n O ~ ] o = 0.0006 67 M I o n i c S t r e n g t h = 0.43 97 10.0 pH - r a t e p r o f i l e C i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d S o l i d l i n e r e p r e s e n t s t h e f i t o f E q u a t i o n 15 to> t h e d a t a o f T a b l e X I I . The c o n s t a n t s u s e d i n E q u a t i o n 15 a r e t a b u l a t e d i n T a b l e X V I I . The x ' s r e p r e s e n t t h e e x p e r i m e n t a l p o i n t s . 98 TABLE X I I I C i s - 5 - t - b u t y l - t r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X I ) T r a n s - 5 - t ~ b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d ( X I I ) T = 25°C [ S u b s t r a t e ] = 0.00293 M [MnO~] = 0.00195 M I o n i c S t r e n g t h = 0.43 PH k(L/M/MIN) Compound 4.68 1. 55 X I I 6.01 1.11 X I I 7.53 0.863 X I I 1. 36 0.242 X I 3.13 0 .130 X I 3. 60 0.133 X I 5.05 0 .183 X I 5.98 0.183 X I 6.67 0.150 X I 7.88 0 .084 X I 9.18 0 .043 X I f o r compound X r i s e s , at i t s maximum, t o a h i g h e r r a t e t h a n d e e s t h e b e l l - s h a p e c o r r e s p o n d i n g t o c i s - 2 - h y d r o x y c y c l o -h e x a n e c a r b o x y l i c a c i d o x i d a t i o n . Compound X I e x h i b i t s a v e r y s l i g h t maximum w h i c h i s s c a r c e l y o u t s i d e o f e x p e r i m e n t a l e r r o r . Compound X I I d o e s n o t a p p e a r t o g i v e a b e l l - s h a p e e f f e c t a t a l l . C o n f o r m a t i o n s The c o n f o r m a t i o n s o f a l l t h e compounds u s e d i n t h i s w o r k a r e b e l i e v e d t o be known w i t h a r e a s o n a b l e d e g r e e ' o f c e r t a i n t y . We w i l l c o n s i d e r f i r s t t h e p a i r o f i s o m e r s c i s - a n d t r a n s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d s . 99 OH H ^ O H ^ f C 0 2 H H XIV CIS TRANS The f a c t t h a t i n t h e p r e s e n c e o f s t r o n g b a s e one i s o m e r c h a n g e s t o t h e o t h e r i n d i c a t e s c l e a r l y t h a t t h e f o r m e r i s t h e c i s -compound a n d t h e l a t t e r t h e t r a n s - c o m p o u n d . The a v a i l a b l e i n f o r m a t i o n c o n c e r n i n g t h e c o n f o r m a t i o n a l e n e r g i e s o f t h e h y d r o x y l a n d t h e c a r b o x y l g r o u p i n d i c a t e t h a t t h e c o n f o r m a t i o n w r i t t e n a b o v e f o r t h e c i s - i s o m e r i s p r e d o m i n a n t . I t i s d i f f i c u l t t o i m a g i n e t h e t r a n s i s o m e r as a d o p t i n g a n y c o n f o r m a t i o n o t h e r t h a n t h a t w i t h b o t h s u b s t i t u e n t s e q u a t o r i a l . t h e c h r o m i c a c i d o x i d a t i o n o f t h i s i s o m e r i c p a i r a n d o b s e r v e t h a t t h e c i s - i s o m e r i s a b o u t t h r e e t i m e s a s r e a c t i v e a s t h e t r a n s - i s o m e r . T h i s i s s i m i l a r t o t h e e f f e c t n o t e d b y o t h e r w o r k e r s i n t h e c h r o m i c a c i d o x i d a t i o n o f c i s - a n d t r a n s - 4 -t - b u t y 1 - c y c l o h e x a n o l s - n a m e l y , t h a t t h e a x i a l h y d r o x y l r e a c t s f a s t e r t h a n t h e e q u a t o r i a l b y a f a c t o r o f a p p r o x i m a t e l y t h r e e . 5 2 t h e compound ( o f s i m i l a r m e l t i n g - p o i n t ) o b t a i n e d f r o m t h e s o d i u m b o r o d e u t e r i d e r e d u c t i o n o f e t h y l 2 - o x o c y c l o h e x a n e -c a r b o x y l a t e a r e g i v e n i n F i g u r e s X X I I a n d X X I I I . The p r o t o n s I n a d d i t i o n t o t h i s S i c h e r 32 e t a l . h a v e s t u d i e d The NMR s p e c t r a o f t h e c i s - i s o m e r t o g e t h e r w i t h 100 FIGURE X X I I 100 MH S p e c t r u m S o l v e n t - CHC1. OH 1 H ° u J ! ' I ' ' • r i l__> 1 i 1 • 1 ! !.!.. 1 t .1 .,1 I .. _J J ! ..,. }. ' 6 7 r 8 9 101 FIGURE XXIII 100 MH Spectrum Solvent - CHCl^-102 i n v o l v e d i n t h e h y d r o x y l a n d c a r b o x y l g r o u p s a r e n o t shown. A g l a n c e a t t h e s p e c t r u m o f F i g u r e X X I I i n d i c a t e s an a x i a l 50 a n d an e q u a t o r i a l p r o t o n . A x i a l - a x i a l c o u p l i n g s a r e w e l l -known t o be l a r g e r t h a n a x i a l - e q u a t o r i a l and e q u a t o r i a l -e q u a t o r i a l c o u p l i n g s . The l a t t e r two a r e q u i t e s m a l l a n d o f c o m p a r a b l e m a g n i t u d e . The NMR s p e c t r u m o f t h e d e u t e r i o d e r i v a t i v e c l e a r l y i n d i c a t e s t h a t t h e e q u a t o r i a l p r o t o n i s t h e one a t t a c h e d t h e c a r b o n b e a r i n g t h e h y d r o x y l g r o u p b e c a u s e o f t h e d i s a p p e a r a n c e o f t h e a b s o r p t i o n o f t h i s p r o t o n a n d t h e c o r r e s p o n d i n g l o s s o f c o u p l i n g i n t h e r e s o n a n c e o f t h e a x i a l p r o t o n . The p r e d o m i n a n t c o n f o r m a t i o n o f t h e c i s - i s o m e r may t h e n be t a k e n as r e p r e s e n t e d b y X I V . The t r a n s - i s o m e r c a n be t a k e n a s g i v e n b y XV. On t h e b a s i s o f pK m e a s u r e m e n t s i n s o l v e n t s o t h e r t h a n w a t e r 51 p r e v i o u s a u t h o r s h a v e c o n c l u d e d t h a t t h i s i s o m e r m i g h t . e x i s t i n a d i - a x i a l c o n f o r m a t i o n i n s o l v e n t s o f l o w e r d i e l e c t r i c c o n s t a n t t h a n w a t e r . I n w a t e r h o w e v e r t h i s i s n o t t h e c a s e and t h e NMR s p e c t r u m b e a r s t h i s o u t ( F i g u r e X X I V a ) . O n l y one r i n g p r o t o n i s o b s e r v a b l e s e p a r a t e d f r o m t h e r e m a i n i n g p r o t o n s . T h i s p r o t o n - p r e s u m a b l y a d j a c e n t t o t h e h y d r o x y l o r c a r b o x y l g r o u p - h a s a b r o a d r e s o n a n c e composed o f two l a r g e c o u p l i n g s a n d one s m a l l e r c o u p l i n g . T h i s p r o t o n m u s t t h e n be a x i a l a n d t h e m o l e c u l e h a v e t h e c o n f i g u r a t i o n XV. 103 FIGURE X l V a 6 0 MH S p e c t r u m S o l v e n t - D„0 I I I I L I I I I I I I I I I I I I I 1 I I ' I I I I I I - 1—1 L-!_l—L_I_J 1 I I I I i l i M 7 8 9 1 0 T 1 0 4 The c o n f o r m a t i o n s o f t h e t h r e e 5 - t - b u t y l - 2 -h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d s u s e d i n t h i s w o r k h a v e b e e n d e d u c e d b y S i c h e r . H i s t e c h n i q u e i n v o l v e d t h e d e t e r m i n a t i o n o f h y d r o x y l c o n f o r m a t i o n u s i n g as c r i t e r i o n t h e r a t e o f c h r o m i c a c i d o x i d a t i o n a n d t h e c o n f o r m a t i o n o f c a r b o x y l a c c o r d i n g t o t h e m o l e c u l e ' s a b i l i t y t o i s o m e r i z e i n b a s e . An a x i a l h y d r o x y l g r o u p w i l l be more r e a c t i v e t o c h r o m i c a c i d o x i d a t i o n t h a n an e q u a t o r i a l o n e . An a x i a l c a r b o x y l g r o u p ' . w i l l c h a n g e t o a n e q u a t o r i a l c o n f o r m a t i o n b y v i g o r o u s t r e a t m e n t w i t h s t r o n g b a s e w h i l e a n e q u a t o r i a l one w i l l r e m a i n u n c h a n g e d . T h u s t h e t h r e e compounds b e l o w h a v e t h e p r o p e r t i e s shown Chemical Behaviour of Three Isomers of 5-t-Butyl-2-hydroxycyclohexanecarboxylic Acid C O M P O U N D X XI XII Relative Rate of C h r o m i c A c i d O x i d a t i o n 3 i 1 I s o m e r ! z a t i o n w i t h b a s e - - + Su c h c h e m i c a l p r o p e r t i e s u n a m b i g u o u s l y d e t e r m i n e t h e c o n f o r m a t i o n s o f t h e s e t h r e e i s o m e r s . I f t h i s i s c o r r e c t a n d t h e p r e v i o u s c o n c l u s i o n c o n c e r n i n g t h e c o n f o r m a t i o n o f X I V i s c o r r e c t t h i s 10 5 FIGURE X X I V b 10 0 MH S p e c t r u m S o l v e n t - C H C 1 0 106 compound a n d compound X s h o u l d h a v e r a t h e r s i m i l a r NMR s p e c t r a . T h i s i s s o . Two p r o t o n s a r e o b s e r v a b l e s e p a r a t e d f r o m t h e r e m a i n i n g r i n g p r o t o n s i n t h e NMR s p e c t r u m . T h e s e a r e r e c o r d e d i n F i g u r e X X I V b w h i c h i s a t i m e - a v e r a g e d s p e c t r u m o f 19 s c a n s and c o n s i d e r a b l y e x p a n d e d . The NMR s p e c t r u m o f X s u p p o r t s t h e c o n f o r m a t i o n a l a s s i g n m e n t s made b y S i c h e r f o r t h i s p a r t i c u l a r compound and by i m p l i c a t i o n t h e c o n f o r m a t i o n s a s s i g n e d t o t h e o t h e r two i s o m e r s . A c t i v a t i o n P a r a m e t e r s The t e m p e r a t u r e - r a t e d e p e n d e n c e o f c i s - 2 - h y d r o x y -c y c l o h e x a n e c a r b o x y l i e a c i d was s t u d i e d a t t h r e e pH v a l u e s ( 2 , 0 , 5.88, 1 0 . 3 8 ) . T h e s e r a t e s a l o n g w i t h t h e a c t i v a t i o n p a r a m e t e r s c a l c u l a t e d f r o m them a r e g i v e n i n T a b l e X I V . TABLE X I V C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d o x i d a t i o n pH 2.00 5.88 10.38 k(L/M/SEC) T 5 0.00230 15 0.00325 0.00597 0.000950 25 0.00817 0.0156 0.002670 35 0.01535 0.0332 0.005155 45 0.02400 0.01630 AH^(Kcal/°mole) 11.5-1.1 15.9-0.4 16.1-1.3 A S ^ ( e u ) -29.7^2,0 - 1 3 . 9 - 1 . 1 -16.4±2.1 C o r r . c o e f f . 0 ,991 0.999 0.993 107 D i s c u s s i o n The b e l l - s h a p e p H - r a t e p r o f i l e s o b s e r v e d i n t h i s w o r k , a l t h o u g h t h e y a p p e a r t o be n o v e l f o r o x i d a t i o n r e a c t i o n s , a r e r a t h e r common i n c e r t a i n a r e a s o f m e c h a n i s t i c i n v e s t i g a t i o n ^ . I n d e e d , as f a r as enzyme c o n t a i n i n g s y s t e m s a r e c o n c e r n e d / s u c h b e h a v i o u r i s e n c o u n t e r e d w i t h r e m a r k a b l e 54 -f r e q u e n c y . The l i t e r a t u r e i s r e p l e t e w i t h s t u d i e s on s u c h s y s t e m s . A t h o r o u g h d i s c u s s i o n o f enzyme s y s t e m s and how t h e y g i v e r i s e t o b e l l - s h a p e c u r v e s i s g i v e n b y 54 D i x o n a n d Webb . A c c o r d i n g t o t h e s e a u t h o r s as w e l l a s s e v e r a l s t a n d a r d t e x t s d e a l i n g w i t h t h e s u b j e c t s o f enzyme 5 5 56 r e a c t i o n s and c h e m i c a l k i n e t i c s t h i s b e h a v i o u r comes a b o u t f o r t h e f o l l o w i n g r e a s o n . T h e r e e x i s t two e q u i l i b r i a ( o r more) i n v o l v i n g h y d r o g e n i o n s i n w h i c h t h e enzyme t a k e s p a r t . The enzyme s p e c i e s i n v o l v e d i n t h e s e e q u i l i b r i a a r e n o t a l l o f t h e same e n z y m a t i c a c t i v i t y ; i n f a c t , one s p e c i e s w h i c h c a n e x i s t o n l y a t i n t e r m e d i a t e pH v a l u e s and n o t a t h i g h e r and l o w e r a c i d i t i e s i s more a c t i v e t h a n t h e r e s t . I n t e r m s o f E q u a t i o n 7. K1 K2 . 7. AH2^ =± AH"^=: A" V 108 we 'would s a y t h a t s p e c i e s AH i s more r e a c t i v e t h a n e i t h e r AH^ a n d A = and t h a t t h e r a t e o f r e a c t i o n i s p r o p e r l y g i v e n b y k 1 | ^ A H ~ J . I n t e r m s o f t h e t o t a l amount o f s p e c i e s p r e s e n t , ^AH 2J t , t h e r a t e w o u l d be r e p r e s e n t e d a s k l [ A H 2 ] t R a t e = 1 X H I + Ji2_ t h e o b s e r v e d r a t e c o n s t a n t ( k - ^ - ) t h e n w o u l d be ^OBS 1 + [ H + ] K. K + 1 [ H + ] w h i c h h a s t h e p r o p e r m a t h e m a t i c a l f o r m t o r e s u l t i n a b e l l -s h a p e c u r v e . The c a s e w i t h enzyme r e a c t i o n s i s v e r y c o m p l e x i n v o l v i n g many e q u i l i b r i a w h i c h u s u a l l y c a n n o t a l l be s o r t e d o u t . T h e r e a r e , h o w e v e r , on r e c o r d a c o n s i d e r a b l e number o f r e a c t i o n s n o t i n v o l v i n g enzymes w h i c h e x h i b i t maxima i n 57 58 59 23 t h e i r p H - r a t e p l o t s ' ' ' . A number o f t h e s e r e a c t i o n s i n v o l v e two i o n i z a b l e c a r b o x y l f u n c t i o n s a n d a r e a d m i r a b l y a c c o u n t e d f o r i n t e r m s o f E q u a t i o n s 7. a n d 8. F o r e x a m p l e , 57 t h e h y d r o l y s i s o f X V I X V I 0-C-CH 9CH 0CO 9H 6 2 109 exhibits the bell-shape behaviour under consideration., The reaction of 2,2'-dicarboxytolan^ to form 3-(2-carboxy-benzylidene)-phthalide also behaves i n t h i s way. K i n e t i c deportment of t h i s kind i s adequately covered by Equation 8. and no other considerations seem to be involved. There are reactions which y i e l d bell-shape pH-rate p r o f i l e s i n which two c l e a r l y definable protonic e q u i l i b r i a 23 58 are not evident ' . In these cases the form of Equation 8. i s found to hold but one or both of the K's are replaced by functions involving two or more rate constants. The studies 0 61 of Chaturvedi on thioimidate ester hydrolysis i l l u s t r a t e t h i s point. A bell-shape pH-rate p r o f i l e i s observed for t h i s reaction whose reaction sequence, as a consequence of t h i s , i s thought t6 be the following: SR • „ SR S R -v- k SR H20 4 - J>=NHR -|- NHR + H+ k2 OH \=Q + RNH2 110 A s s u m i n g t h a t a s t e a d y - s t a t e c o n c e n t r a t i o n o f t h e i n t e r m e d i a t e e x i s t s , l e a d s t o t h e e x p r e s s i o n f o r t h e o b s e r v e d r a t e c o n s t a n t : k l k 0 B S "*2[»1 + J ! l _ + K l k 2 k 5 + k 5 [H +] k 3 + k 5 The d e s c e n d i n g l i m b o f t h e b e l l i s c o n t r o l l e d b y t h e e q u i l i b r i u m r e p r e s e n t e d b y K^; t h e a s c e n d i n g l i m b by t h e c o l l e c t i o n o f r a t e c o n s t a n t s k „ / ( k _ + k r ) . 2 6 0 A c a r e f u l c o n s i d e r a t i o n o f t h e ways i n w h i c h h y d r o l y s i s r e a c t i o n s may g i v e r i s e t o b e l l - s h a p e p H - r a t e 23 p r o f i l e s h a s b e e n made by Z e r n e r a n d B e n d e r . T h e s e a u t h o r s l i s t f i v e d i f f e r e n t r e a c t i o n s e q u e n c e s w h i c h c a n r e s u l t i n a b e l l - s h a p e p H - r a t e p r o f i l e . The f i r s t o f t h e s e s i t u a t i o n s i s t h a t r e p r e s e n t e d b y E q u a t i o n 7. T h i s i s t h e m o s t commonly o b s e r v e d c a s e and w h e r e enzymes a r e c o n c e r n e d E q u a t i o n 7. i s u s u a l l y b e l i e v e d t o r e p r e s e n t an a d e q u a t e e x p l a n a t i o n o f e v e n t s . One r e a c t i o n s e q u e n c e , c i t e d b y Z e r n e r a n d B e n d e r , t h a t w i l l c o n c e r n us t o some e x t e n t i s t h e f o l l o w i n g : 1 / K i 9. a. B + H + ft^t B H + A b. B H + + H 2 0 =?=r I H + k2 c. IH" I + H K 2 + f a s t ,. , „+ 3 . p r o d u c t s I l l B i s t h e s u b s t r a t e a n d c a n p a r t i c i p a t e i n t h e r e v e r s i b l e r a p i d e q u i l i b r i u m whose c o n s t a n t i s 1/K-^. A h y d r a t e d i n t e r m e d i a t e i s f o r m e d ( I H + ) w h i c h c a n decompose t o g i v e p r o d u c t o n l y a f t e r i t h a s l o s t a p r o t o n i n t h e r a p i d e q u i l i b r i u m r e p r e s e n t e d b y . I f we t a k e t h e r a t e t o be g i v e n b y ^ [ l - ] a n d a p p l y t h e s t e a d y - s t a t e a s s u m p t i o n t o [ i ] an d [ l H + j t h e r e s u l t i s k 3 k 1 [ B H + ] [ H 2 0 ] R a t e = > + i s ! K 2 If [BH + ] is expressed in terms of the total amount of substrate species the result is k 3 k l W t [ H 2 ^ I t Rate= T h i s e q u a t i o n , o f c o u r s e , d e s c r i b e s a b e l l - s h a p e p H - r a t e p r o f i l e . A g l a n c e a t t h e r e a c t i o n s e q u e n c e o f E q u a t i o n 9. shows q u a l i t a t i v e l y t h a t t h i s s h o u l d be t h e c a s e . A t l o w a c i d i t i e s t h e s u b s t r a t e B w i l l n o t be s u f f i c i e n t l y p r o t o n a t e d f o r r e a c t i o n t o o c c u r r e a d i l y . A t h i g h a c i d i t i e s t h e i n t e r -m e d i a t e v / i l l be c o m p l e t e l y p r o t o n a t e d a n d t h e e q u i l i b r i u m w i l l l i e t o o f a r t o t h e l e f t . At. i n t e r m e d i a t e a c i d i t i e s 112 t h e r e s h o u l d be an o p t i m u m pH a t w h i c h b o t h e q u i l i b r i a may c o n t r i b u t e t o t h e o v e r a l l r e a c t i o n . I t i s p r e c i s e l y t h i s o p p o s i t i o n o f e q u i l i b r i a i n t h e c a s e s e x a m i n e d b y Z e r n e r and B e n d e r w h i c h p r o d u c e s t h e b e l l - s h a p e p H - r a t e p r o f i l e 2 3 a n d i n g e n e r a l t h i s i s p r o b a b l y q u i t e t r u e A s i t u a t i o n k i n e t i c a l l y i n d i s t i n g u i s h a b l e f r o m E q u a t i o n 9. w o u l d be one i n w h i c h e a c h s p e c i e s i s s u b s t i t u t e d b y i t s c o n j u g a t e g i v i n g : + K l + 10. a. BH B + H k l b . B + H O ^ ± 1 I k 2 + 1 / K 2 + c. I + H z^± I H + k d. I H ._' 3 p P r o d u c t s t h e f o r m o f t h e k i n e t i c e x p r e s s i o n i s t h e same i n t h i s c a s e a s i t i s f o r E q u a t i o n 9. W i t h t h i s p r e a m b l e we c a n b e g i n an e x a m i n a t i o n o f t h e r e a c t i o n s i n v o l v e d i n t h i s w o r k . The d i s c u s s i o n w i l l f o l l o w l i n e s s i m i l a r t o t h o s e m e n t i o n e d a b o v e and t h e r e a c t i o n s e q u e n c e s w i l l i n v o l v e tv/o p r o t o n i c e q u i l i b r i a a c t i n g i n o p p o s e d d i r e c t i o n s . The r e a c t i o n s c o n s i s t o f t h e p e r m a n g a n a t e o x i d a t i o n s o f 2 - c a r b o x y s u b s t i t u t e d c y c l o h e x a n o l s and u n d o u b t e d l y i n 113 t h o s e c a s e s i n w h i c h t h e p H - r a t e p r o f i l e i s b e l l - s h a p e d t h e i o n i z a t i o n o f t h e c a r b o x y l g r o u p i s i m p o r t a n t . A b b r e v i a t i n g t h e s u b s t r a t e a s HA, we c a n w r i t e t h e f o l l o w i n g s e q u e n c e w h i c h w i l l be r e f e r r e d t o a s R e a c t i o n Scheme I . R e a c t i o n Scheme I . HA H + + A" ^ - k l HA + M n 0 4 C C- — ^ C~ + H + Q p r o d u c t s A c c o r d i n g t o R e a c t i o n Scheme I t h e n e u t r a l a l c o h o l HA r e a c t s w i t h p e r m a n g a n a t e t o f o r m an i n t e r m e d i a t e ; t h i s i n t e r m e d i a t e d i s s o c i a t e s ; and t h e r e s u l t i n g d i - a n i o n d e c o m p o s e s t o p r o d u c t s . F o r t h e moment t h e i d e n t i t y o f t h e i n t e r m e d i a t e s w i l l be l e f t , o p e n a n d we w i l l p e r s u e t h e k i n e t i c c o n s e q u e n c e s o f t h e r e a c t i o n scheme. The o v e r a l l r a t e i s g i v e n by R a t e = k 3[c~] 114 Assuming the e q u i l i b r i a involving protons to be rapid we make use of the steady-state assumption regarding [c~] and (c~3 to obtain - d ( ^  + ^  ) = k 3 [c=] + k 2 [a"] - k ^ H A J [MnO"] = 0 Because [cj - M M /K we have kxH [ M n 0ll [ e l - k„ + k„ [H +] /K "3 2 thus the rate i s given by k l k 3 N [ M n 0 4 ] . Rate = k 3 + k„ [H"1] /K If we^now, express the rate i n terms of the permanganate concentration and the t o t a l substrate concentration ( [HA]' = |HA] + ^  ) we get Rate = k 1k 3[HA] t[MnO"] ( k + k 0 [ H ^ /K) (1 + Ka/ [ H + ] ) The observed second order rate constant, k,..-.^ , becomes U r J o 115 T h i s e q u a t i o n (11) h a s t h e r e q u i s i t e f o r m t o r e s u l t i n a b e l l - s h a p e p H - r a t e p r o f i l e . The pH c o r r e s p o n d i n g t o t h e maximum r a t e c a n be o b t a i n e d b y d i f f e r e n t i a t i n g w i t h r e s p e c t t o [H +] and i s 12 P Hmax = * l o g ( k 2 / k 3 K K a ) E q u a t i o n 1 1 . may be r e a r r a n g e d t o g i v e "OBS 1_ k. 1 + ¥ a k 3 K k-K L [ H + J k 3 K a n d OBS 1_ (1+C) k l + (A+B) w i t h C = k^K A 3 K , A = K a / [ H + ] a n d B = k 2 [ H + ] / k . A p l o t o f l / k n n c a g a i n s t A+B s h o u l d t h e n g i v e a s t r a i g h t l i n e o f s l o p e 1/k^ and i n t e r c e p t (l+C)/k-^. T h u s we c a n o b t a i n k 1 a n d t h e t e r m k 3 K / k 2 f r o m t h e v a l u e s o f k Q B S . I t i s a l s o p o s s i b l e t o c o n s i d e r t h e same k i n d o f r e a c t i o n s e q u e n c e i n t e r m s o f t h e c o n j u g a t e s o f t h e a c i d a n d b a s e s p e c i e s i n Scheme I . T h i s g i v e s us R e a c t i o n Scheme I I . 116 R e a c t i o n Scheme I I HA H + + A _ A + MnO •1 H + + C = H> P r o d u c t s F o l l o w i n g t h e same p r o c e d u r e a s p r e v i o u s l y we g e t R a t e K 1* 3 HA T L M N 0 3 ( k ' 3 + k'.K/ H + ] ) ( 1 + [ H + ] / K a a n d 1 3 . k k ' l k ' 3 OBS (k' 3 + k 2 K / [ H + ] ) (1 + [ H + ] / K a ) The pH c o r r e s p o n d i n g t o maximum k 0 B g i s 14. . pH max ± l o a ( k ' / k ' KK ) We a l s o h a v e 15, kOBS 1 + k ' 2 K " k* K 3 a-X ' , L "^a + k ' 2 K K ' 3 [ H + J 117 and 1 = (1 + C + ( A ' + B ' ) / k , 1 16. k OBS w i t h C = k ' 2 K / k ' 3 K a , A I n t h i s c a s e as w e l l we c a n p l o t I / k OBS a g a i n s t (A'+B1) and o b t a i n a s s l o p e I / k ' ^ a n d as i n t e r c e p t (1 + C ' ) / k ' ^ . F r o m t h e v a l u e o f pH we c a n o b t a i n t h e t e r m k' / K k 1 „ . max o 2. The k i n e t i c a n a l y s i s r e s u l t i n g f r o m Schemes I and I I was a p p l i e d t o t h e e x p e r i m e n t a l r a t e d a t a f o r C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d . A w o r d a b o u t t h e c o m p u t a t i o n a l p r o c e d u r e i s i n o r d e r b e f o r e t h e a c t u a l r e s u l t s a r e g i v e n . r e c o r d e d i n T a b l e V I I I c o u l d n o t be made t o c o r r e l a t e ( c o r r e l a t i o n c o e f f i c i e n t ^ 0 . 9 ) a c c o r d i n g t o t h e e q u a t i o n s d e r i v e d f r o m R e a c t i o n Scheme I . A g l a n c e a t F i g u r e X V I I I as w e l l as t h e b e h a v i o u r o f c y c l o h e x a n o l w i t h c h a n g i n g pH i n d i c a t e t h a t t h e " n o r m a l " r e a c t i o n a n d t h a t i n v o l v i n g t h e b e l l - s h a p e b e h a v i o u r t a k e p l a c e s i m u l t a n e o u s l y . A s e p a r a t i o n o f t h e t w o . e f f e c t s m u s t be made i n o r d e r t o a n a l y s e n u m e r i c a l l y t h e a c t u a l b e l l - s h a p e r e a c t i o n . S e v e r a l a t t e m p t s w e r e made b u t t h e one r e p r e s e n t e d i n F i g u r e X V I I I seemed t h e s i m p l e s t a n d b e s t s o l u t i o n . The a r e a b e l o w t h e d o t t e d l i n e r e p r e s e n t s " n o r m a l " b e h a v i o u r and t h a t a b o v e t h e l i n e I t was f o u n d t h a t t h e raw e x p e r i m e n t a l d a t a a s 118 " b e l l - s h a p e " b e h a v i o u r . T h i s p r o c e d u r e was f o l l o w e d f o r t h e b e l l -s h a p e c u r v e s o f F i g u r e s X I X a n d X X I a s w e l l . . I n t h e w o r k 53 o f Z e r n e r a n d B e n d e r i t was a l s o f o u n d t h a t t h e d a t a h a d t o be . " c o r r e c t e d " t o e l i m i n a t e e x t r a n e o u s e f f e c t s . The m o s t c r i t i c a l i t e m i n v o l v e d i n t h e c a l c u l a t i o n i s t h e d e t e r m i n a t i o n o f t h e v a l u e o f pH . T h i s number ^ max c a n o f c o u r s e be e s t i m a t e d f r o m t h e e x p e r i m e n t a l r e s u l t s b u t a s u f f i c i e n t l y p r e c i s e v a l u e c a n n o t be o b t a i n e d i n t h i s . way. The p r o c e d u r e f o l l o w e d was t o e s t i m a t e a v a l u e and s e e how c l o s e l y t h e p l o t o f l / k Q B S a g a i n s t (A+B) a p p r o a c h e d a s t r a i g h t l i n e . The c r i t e r i o n u s e d f o r t h i s was t h e c o r r e l a t i o n c o e f f i c i e n t o f t h e l i n e . I t a p p e a r e d t h a t t h e c o r r e l a t i o n c o e f f i c i e n t w e n t t h r o u g h a maximum as t h e pH was v a r i e d o v e r a c e r t a i n i n t e r v a l . The pH c o r r e s p o n d i n g t o t h i s maximum c o r r e l a t i o n c o u l d be d e t e r m i n e d t o a n y d e s i r e d d e g r e e o f a c c u r a c y . T h i s pH was c o n s i s t e n t w i t h t h e v a l u e e s t i m a t e d J c max f r o m t h e b e l l - s h a p e p l o t b y i n s p e c t i o n . Once t h e a p p r o p r i a t e pH i s d e t e r m i n e d t h e n e x t ^ ^ *• max s t e p i s t o a d j u s t K s u c h t h a t k, d e t e r m i n e d f r o m t h e s l o p e a _L i s c o n s i s t e n t w i t h t h a t d e t e r m i n e d f r o m t h e i n t e r c e p t . T h i s c a n be done t o a n y d e s i r a b l e d e g r e e o f a c c u r a c y a s w e l l -t h e l i m i t i n g f e a t u r e b e i n g t h e s t a n d a r d e r r o r i n k^, A c h a n g e i n Ka i s f o u n d n o t t o p r o d u c e a n y c h a n g e i n t h e c o r r e l a t i o n c o e f f i c i e n t o r pH . C o n s e q u e n t l y Ka a n d pH c a n be . ^  max, ^ 2 ^ max 119 a d j u s t e d q u i t e i n d e p e n d e n t l y , w i t h P H m a x b e i n g d e t e r m i n e d f i r s t o f c o u r s e . T h e s e c a l c u l a t i o n s w e r e c a r r i e d o u t u s i n g a c o m p u t e r l e a s t - s q u a r e s p r o g r a m . The r e s u l t o f t h e c a l c u l a t i o n s f o r c i s ~ 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d a r e g i v e n i n T a b l e XV, TABLE XV C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d ( X I V ) i n p r o t i u m o x i d e pH = 6,020 c max pKa = 4.70 k x = 3151 24(L/M/MIN) C = 429.86 k , K / k 0 = 4.61 x 1 0 " 8 k ' ± = 0.130- 0.050 (L/M/MIN) C = 2.326 x 1 0 " 3 k ' 2 K / k ' 3 = 4.61 x 1 0 " 8 C o r r e l a t i o n C o e f f i c i e n t " ' =v"' 0.984 The same was done t o t h e d a t a f o r t h e o x i d a t i o n o f compound X I V i n d e u t e r i u m o x i d e . The r e s u l t s a r e g i v e n i n T a b l e X V I . 120 TABLE X V I C i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d (XIV) i n d e u t e r i u m o x i d e pD = 6 . 3 7 8 c max pKa = 4.96 k x = 2 88-5(L/M/MIN) C = 689.89 k 3 K / k 2 = 1.59 x 1 0 ~ 8 = 0 . 416 -0 .00 6 (L/M/MIN) C = 1.450 x 1 0 ~ 3 k ' 2 K / k ' 3 = 1.59 x 1 0 ~ 8 C o r r e l a t i o n C o e f f i c i e n t = 0.995 A c o m p a r i s o n o f t h e r e s u l t s i n p r o t i u m o x i d e and i n d e u t e r i u m o x i d e f o r Compound X I V c a n be made. The k-^  v a l u e s a r e n e a r l y t h e same i n t h e two s o l v e n t s , k^ (H 2 0 ) / k - ^ ( D 2 0 ) b e i n g 1.09. The k'^ v a l u e s h o w e v e r do show some c h a n g e w i t h k ' ^ ( H 2 0 ) / k 1 ^ ( D 2 0 ) = 1.75. T h i s d i f f e r e n c e i s s i g n i f i c a n t and w i l l be c o n s i d e r e d i n due c o u r s e . The q u a n t i t y k 3 K / k 2 ( o r k ' 2 K / k ' 3 ) shows some v a r i a t i o n w i t h k 3 K / k 2 ( H 2 0 ) / k 3 K / k 2 ( D 2 0 ) = 2 . 9 0 . I n t h e l i g h t o f w e l l known w o r k ' c o n c e r n i n g t h e b e h a v i o u r o f a c i d s t r e n g t h i n d e u t e r i u m o x i d e a n d p r o t i u m o x i d e , t h i s i s o t o p e e f f e c t c a n be e x p l a i n e d a d e q u a t e l y . I f k 3 and k ? a r e n o t i n f l u e n c e d , 121 o r i n f l u e n c e d t o t h e same e x t e n t , b y t h e i s o t o p i c c h a n g e i n t h e s o l v e n t , t h e n t h e e f f e c t o b s e r v e d i s due e n t i r e l y t o a c h a n g e i n K. A c i d w e a k e n i n g by a f a c t o r o f f r o m two t o t h r e e o r c h a n g i n g f r o m p r o t i u m o x i d e t o d e u t e r i u m o x i d e h a s b e e n o b s e r v e d i n a g r e a t many c a s e s ^ . T h i s i s p r e s u m a b l y w h a t i s h a p p e n i n g h e r e , a l t h o u g h i t a p p e a r s i m p o s s i b l e t o d i s t i n g u i s h t h i s f r o m more c o m p l i c a t e d b e h a v i o u r a r i s i n g f r o m c h a n g e s i n a l l t h r e e c o m p o n e n t s o f t h e f a c t o r k^K/k^-I t i s p o s s i b l e t o e x p l a i n t h e d i f f e r e n c e i n t h e maximum v a l u e s i n k 0 B S b e t w e e n Compound X I V i n p r o t i u m o x i d e and d e u t e r i u m o x i d e q u i t e s i m p l y , M a k i n g u s e o f E q u a t i o n s 6. an d 1 1. t h e f o l l o w i n g r e l a t i o n s h i p i s o b t a i n e d . k OBS x Ka A max) L J max The d i f f e r e n c e c a n be e x p l a i n e d i n t e r m s o f t h e f a i l u r e o f H i a n d Ka t o c h a n g e t o t h e same e x t e n t when t h e s o l v e n t L J max ^ i s c h a n g e d f r o m p r o t i u m o x i d e t o d e u t e r i u m - o x i d e . The a b i l i t y t o c a l c u l a t e d t h e r a t i o k Q B S ( m a x ) ( H 2 0 ) / k Q B S ( m a x ) (D.,0) f r o m t h e d a t a i n T a b l e s XV and X V I r e f l e c t s o n l y i n t e r n a l c o n s i s t e n c y i n t h e c a l c u l a t e d p a r a m e t e r s . The r e l a t i o n s h i p a b o v e d o e s h o w e v e r i n d i c a t e t h e o r i g i n s o f t h e i s o t o p e e f f e c t o b s e r v e d . 122 The d a t a f o r t h e o t h e r compound s h o w i n g a b e l l - s h a p e p H - r a t e p r o f i l e w e r e s u b j e c t e d t o t h e same m a t h e m a t i c a l t r e a t m e n t . The r e s u l t s f o r C i s - 5 - t - b u t y l - c i s ~ 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d (X) a r e g i v e n i n T a b l e X V I I . TABLE X V I I C i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d (X) pH = 5.964 max pKa = 4 . 8 5 k x = 559 - 27(L/M/MIN) C = 166.06 k 3 K / k 2 = 8.42 x 1 0 ~ 8 k ^ = 3.33 - 0 .16 (L/M/MIN) C* = 6.022 x 1 0 ~ 3 k ' 2 K / k ' 3 = 8.42 x 10 C o r r e l a t i o n C o e f f i c i e n t = 0.991 A t t h i s p o i n t we s h a l l a s s e m b l e t h e r e l e v a n t c a l c u l a t e d p a r a m e t e r s i n t o a s i n g l e t a b l e f o r more c o n v e n i e n t r e f e r r a l . T h i s i s T a b l e X V I I I . 123 TABLE X V I I I Compound P H m a x PKa k± k * ± k 3 K / k 2 ( k ' 2 K / k • 3 ) X I V ( H 2 0 ) 6.020 4.70. 315 0.730 4.61 x 1 0 _ 8 X I V ( D 2 0 ) 6.378 4.96 288 0.416 1.59 x 1 0 " 8 X 5.964 4.85 559 3.33 8.42 x 1 0 _ 8 The d i f f e r e n c e i n t h e v a l u e o f pH b e t w e e n ^ max Compound XIV i n p r o t i u m o x i d e and d e u t e r i u m o x i d e i s o f some i m p o r t a n c e . T h i s i s so b e c a u s e t h e v a l u e o f pH i n e a c h c * max c a s e i s d e r i v e d f r o m t h e e x p e r i m e n t a l numbers q u i t e i r r e s p e c t i v e o f m e c h a n i s t i c a s s u m p t i o n s . A d m i t t e d l y t h e v a l u e s o f pH i n T a b l e X V I I I a r e d e t e r m i n e d b y a m a t h e m a t i c a l p r o c e d u r e ^ max 1 i n v o l v i n g an a s s u m p t i o n o f mechanism b u t t h e s e v a l u e s do n o t v a r y s i g n i f i c a n t l y f r o m those t h a t w o u l d be o b t a i n e d f r o m an i n s p e c t i o n o f F i g u r e s XIX a n d X V I I I . The d i f f e r e n c e i s 0.358. I f we c o n s i d e r t h e e x p r e s s i o n d e r i v e d p r e v i o u s l y , i n c o n n e c t i o n w i t h R e a c t i o n Scheme I, w h i c h r e l a t e s pH t o t h e e q u i l i b r i u m ' max ^ c o n s t a n t s and r a t e c o n s t a n t s i n t h a t r e a c t i o n s e q u e n c e we h a v e P Hmax = % l o g ( k 2 / k 3 K K a ) . On t h e a s s u m p t i o n t h a t k 2 and k 3 a r e n o t s u b j e c t t o a d e u t e r i u m s o l v e n t i s o t o p e e f f e c t we a r e l e f t t o c o n s i d e r t h e two i o n i z a t i o n c o n s t a n t s K and Ka. The e f f e c t on a c i d s t r e n g t h o f c h a n g i n g f r o m p r o t i u m o x i d e t o d e u t e r i u m o x i d e i s w e l l -63 d o cumented t o be a w e a k e n i n g on by a f a c t o r o f f r o m two t o t h r e e . C o n s i d e r i n g t h e above e x p r e s s i o n then, we w o u l d e x p e c t 124 t h e pH t o be g r e a t e r i n d e u t e r i u m o x i d e by a b o u t 0.30 t o ^ max ^ 1 0.47. T hus i t c a n be s a i d t h a t t h e e x p r e s s i o n d e r i v e d f r o m R e a c t i o n Scheme I p r e d i c t s t h e d i r e c t i o n a n d r o u g h l y t h e m a g n i t u d e o f t h e s h i f t i n P H m a x on c h a n g i n g f r o m p r o t i u m o x i d e t o d e u t e r i u m o x i d e . Of c o u r s e , t h e c o r r e s p o n d i n g e x p r e s s i o n d e r i v e d f r o m R e a c t i o n Scheme I I , h a v i n g t h e same m a t h e m a t i c a l f o r m , p r e d i c t s e x a c t l y t h e same t h i n g . The v a l u e s o f k^ and k'^ and t h e d e u t e r i u m i s o t o p e e f f e c t h a v e a l r e a d y b e e n m e n t i o n e d . The f a c t t h a t k 1 ( H 2 0 ) / k 1 ( D 2 0 ) i s 1.09 w h i l e k' ( H 2 0 ) A ' x ( D 2 0 ) i s 1.75 i s p r o b a b l y i n f o r m a t i v e . I n v i e w o f c o n s i d e r a b l e w o r k o n 6 4 s o l v o l y s i s r e a c t i o n s i n b o t h d e u t e r i u m a n d p r o t i u m o x i d e s , i t i s s a f e t o s a y t h a t p r o c e s s e s w h i c h d o n o t i n v o l v e p r o t o n o r d e u t e r o n e x c h a n g e a nd w h i c h do n o t i n v o l v e t h e s o l v e n t ( o t h e r t h a n i t s r o l e a s s u c h ) do n o t h a v e d e u t e r i u m s o l v e n t i s o t o p e e f f e c t s s i g n i f i c a n t l y d i f f e r e n t f r o m o n e . I n t h e p r e s e n t c o n t e x t we m i g h t s a y t h a t a n y w h e r e f r o m 0.8 t o 1.2 i s n o t s i g n i f i c a n t l y d i f f e r e n t f r o m u n i t y . I n o t h e r c o n t e x t s t h e s e s m a l l o b s e r v e d d i f f e r e n c e s , u s u a l l y o b t a i n e d f r o m v e r y p r e c i s e m e a s u r e m e n t s , a r e o f c o u r s e s i g n i f i c a n t a n d w o r t h y o f c a r e f u l s c r u t i n y . The n a t u r e o f t h e s t e p d e s c r i b e d b y k^ o r k 1 ^ i s s u c h t h a t i t i s u n l i k e l y t o be i n f l u e n c e d by a s o l v e n t c h a n g e f r o m p r o t i u m o x i d e t o d e u t e r i u m o x i d e . No p r o t o n s a r e i n v o l v e d a n d t h e s o l v e n t p r e s u m a b l y p l a y s o n l y 125 a solvation r o l e . As a consequence of the large value of k ' ^ ( H 2 O ) / k 1 ^ ( D 2 O ) , derived from analysis-of the experimental data, Reaction Scheme II would appear to be dis c r e d i t e d i n favour of Reaction Scheme I for which k ^ ( H 2 O ) / k ^ ( D 2 0 ) i s near unity. As a means of d i f f e r e n t i a t i n g between Reaction Scheme I and Reaction Scheme II the data for compound X are pertinent. I t must be recognized that compound X i s fixed i n a single conformation because of the presence of the t-butyl group. Its conformation i s described, as before, byx OH t-Bu Cis - 2-hydroxycyclohexanecarboxylic acid (XIV), although favouring one conformation more than another, i s not constrained i n the same way, the conformational equilibrium can be represented i n the following way: OH H 04 H ( X ) A ( X , l ) B The experimental results, for compound XII indicate that a compound fixed i n a configuration of the kind represented by B does not exhib i t the bell-shape pH-rate p r o f i l e under consideration. On the other.hand the-data for compound X indicate that a conformation l i k e A does give t h i s e f f e c t . 126 T h i s i n d i c a t e s t h a t as f a r as t h e b e l l - s h a p e p r o f i l e i s c o n c e r n e d c o n f o r m a t i o n A i s r e a c t i v e and c o n f o r m a t i o n B i s i n e r t . A n e s t i m a t e o f t h e f r a c t i o n o f compound X I V w h i c h e x i s t s a s A and B i s now r e q u i r e d . T h i s c a n be done f r o m a c o n s i d e r a t i o n o f t h e c o n f o r m a t i o n a l e n e r g i e s o f t h e 6 5 h y d r o x y l a n d c a r b o x y l g r o u p s . The c o n f o r m a t i o n a l e n e r g y o f a s u b s t i t u e n t X i s d e f i n e d a s -A-G°of t h e f o l l o w i n g p r o c e s s To u s e c o n f o r m a t i o n a l e n e r g i e s i n c o n s i d e r i n g d i - s u b s t i t u t e d c y c l o h e x a n e s w o u l d t h e n seem t o be q u i t e i n c o r r e c t . I n t h e p r e s e n t c a s e i t c a n n o t be a v e r y b a d a p p r o x i m a t i o n h o w e v e r . The c o n f o r m a t i o n a l e n e r g y o f X i s d e t e r m i n e d b y i t s s t e r i c i n t e r a c t i o n s w i t h t h e h y d r o g e n s m a r k e d 1, 2 a n d ' 3 . The d i s p o s i t i o n o f X t o w a r d s h y d r o g e n 3 i s t h e same i n b o t h c o n f o r m a t i o n s s o t h a t r e p l a c e m e n t o f i t by some o t h e r g r o u p s h o u l d n o t p r e v e n t us f r o m c o n s i d e r i n g t h e c o n f o r m a t i o n a l e n e r g i e s o f t h e two g r o u p s s e p a r a t e l y . T h i s i s , o f c o u r s e , p r o v i d e d t h a t t h e r e p u l s i o n b e t w e e n t h e two c i s s u b s t i t u e n t s i s n o t s o g r e a t t h a t t h e m o l e c u l e i s d i s t o r t e d . T h i s s t a t e o f a f f a i r s comes a b o u t b e c a u s e o f t h e s y m m e t r y o f c i s - 1 , 2 -d i s u f o s t i t u t e d c y c l o h e x a n e s . B e c a u s e t h e £wo s u b s t i t u e n t s 1 2 7 are disposed s i m i l a r l y towards each other i n both conformations many e f f e c t s cancel. The same i s not true of the trans isomer. This being the case, from a knowledge of the conformational energies of -OH, - C 0 2 H and -C0 2 we can estimate the f r a c t i o n of compound e x i s t i n g as A or B or the anions obtainable from these (A or B ). In Reaction Scheme I the value of k^ includes only unionized substrate as reactant. If that part of the unionized substrate i n conformation B does not p a r t i c i p a t e i n the reaction the value of k^ i s reduced. The factor by which i t i s reduced i s [ A ] / ( [ " A ] + ["B] ) • This factor can be calculated once values for the conformational energies are obtained. The values used here are the "best values" given i n the 6 5 compilation of conformational energies made, by Hirsch ( - 0 H = 0 . 8 7 Kcal/mole; - C 0 2 H = 1 . 3 5 Kcal/mole; . - C C ^ = 1 . 9 2 Kcal) as they seem most appropriate to the present experimental conditions. An array of v a l u e s ^ ' ^ ' ^ does e x i s t however which makes the estimation something of an approximation. The above conformational energies give a value of 0.690 for the r a t i o [A]/([A] + CB1 ) • I f c w a s mentioned that the value of k^ was reduced by t h i s factor for compound XIV but was not i n the case of compound X. This * The value of k, i s lower than expectation because a l l unionized substrate i s regarded as reactive, while only that part of the unionized substrate i n conformation A is i n f a c t reactive. This i s not the case for compound X however. 1 2 8 w o u l d mean t h a t t h e f o l l o w i n g r e l a t i o n s h i p s h o u l d h o l d 1 7 . k ], ( X I V ) _ k x ( X ) [ A ] + [ B ] The v a l u e o f ^ ( X I V ) / k ( X ) i s 0 . 5 6 5 - 0 . 0 7 2 . T h i s v a l u e i s s u f f i c i e n t l y c l o s e t o t h a t c a l c u l a t e d f r o m c o n f o r m a t i o n a l e n e r g i e s t o s a y t h a t a g r e e m e n t e x i s t s . I n t h e c a s e o f R e a c t i o n Scheme I I we a r e d e a l i n g w i t h t h e a n i o n s o f t h e a c i d s c o n s i d e r e d i n R e a c t i o n Scheme I . The r a t i o [ A ^ / ( [ A ^ | + [B"J| ) i s 0 . 8 5 , c a l c u l a t e d f r o m t h e c o n f o r m a t i o n a l e n e r g i e s . The r a t i o k 1 ^ ( X I V ) / k ' ^ ( X ) i s 0 . 2 2 T h e r e i s no r e a s o n a b l e a d j u s t m e n t o f t h e c o n f o r m a t i o n a l e n e r g i e s t h a t c a n be made t o g i v e t h i s f i g u r e . E v e n i f t h i s w e r e p o s s i b l e , t h e NMR i n f o r m a t i o n t e l l s q u i t e c o n v i n c i n g l y t h a t A o r A i s t h e p r e d o m i n a n t c o n f o r m a t i o n m a k i n g 0 . 2 2 a p p e a r a p a t e n t l y i n c o r r e c t e v a l u a 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 c o n s t a n t . Thus R e a c t i o n Scheme I a p p e a r s t o be t h e more v a l i d f r o m a c o m p a r i s o n o f t h e r e a c t i v i t i e s o f compounds X I V a n d X. N a t u r e o f t h e I n t e r m e d i a t e B e f o r e c o n s i d e r i n g t h e s t r u c t u r e o f t h e i n t e r m e d i a t e ' i t s h o u l d be p o i n t e d o u t t h a t s u c h a s p e c i e s h a s n o t b e e n d i r e c t l y o b s e r v e d . The v i s i b l e s p e c t r u m o f p e r m a n g a n a t e d o e s n o t c h a n g e i n any way a s a r e s u l t o f a d d i t i o n o f a n y o f t h e s u b s t r a t e s a s s o c i a t e d w i t h b e l l - s h a p e p H - r a t e p r o f i l e s - o t h e r t h a n t o 129 d i m i n i s h w i t h t i m e . The s t e a d y - s t a t e a s s u m p t i o n , b e s i d e s r e q u i r i n g t h a t t h e c o n c e n t r a t i o n o f i n t e r m e d i a t e d o e s n o t c h a n g e w i t h t i m e u s u a l l y c a r r i e s t h e a d d e d i m p l i c a t i o n o f l o w c o n c e n t r a t i o n ^ . o x i d e a t pD 6 a n d 2. The two s p e c t r a w e r e v i r t u a l l y i d e n t i c a l t o t h a t o f F i g u r e X X I I , e x c e p t f o r a s l i g h t s h i f t t o w a r d s h i g h e r f i e l d o f t h e s p e c t r u m a t pD 6 r e l a t i v e t o t h a t a t pD 2. p r o f i l e s f o r c y c l o h e x a n o l and c i s - 2 - h y d r o x y c y c l o h e x a n e -c a r b o x y l i c a c i d (XIV) t h a t t h e c a r b o x y l g r o u p i s i m p l i c a t e d m e c h a n i s t i c a l l y . T h i s c o n s i d e r a t i o n a n d t h e b e h a v i o u r shown by t h e t h r e e i s o m e r s b e a r i n g a t - b u t y l s u b s t i t u e n t s p e c i f i e s more p r e c i s e l y t h e r o l e t h a t c o n f o r m a t i o n p l a y s i n t h e r e a c t i o n . W i t h t h i s i n m i n d a more e x a c t m e c h a n i s t i c v i e w c a n be p r o v i d e d i n t e r m s o f R e a c t i o n Scheme I . The f i r s t s t e p o f i m p o r t a n c e i s t h e f o r m a t i o n o f t h e s p e c i e s C f r o m t h e n e u t r a l a l c o h o l a n d p e r m a n g a n a t e i o n . The i n t e r m e d i a t e C may be r e p r e s e n t e d by s t r u c t u r e X V I , The NMR s p e c t r u m o f X I V was r e c o r d e d i n d e u t e r i u m I t i s c l e a r f r o m t h e d i s p a r i t y b e t w e e n t h e p H - r a t e OH O- OH C " , XVI 130 i n w h i c h t h e p e r m a n g a n a t e i o n h a s i n t r u d e d i n t o t h e c a r b o x y l g r o u p . A c o m p l e x s i m i l a r t o t h i s i n w h i c h p e r m a n g a n a t e i o n a d d s t o a c a r b o x y l h a s b e e n c o n s i d e r e d i n t h e c a s e o f f o r m a t e (TO o x i d a t i o n . ( I t c a n be s e e n t h a t t h e " p e r m a n g a n a t e i o n " i n X V I i s f a v o u r a b l y p l a c e d w i t h r e g a r d t o t h e h y d r o g e n w h i c h m u s t be r e m o v e d d u r i n g t h e r a t e c o n t r o l l i n g s t e p o f t h e o x i d a t i o n . The d a t a o f F i g u r e s X V I I I and XX show t h a t a s u f f i c i e n t l y l a r g e d e u t e r i u m i s o t o p e e f f e c t o p e r a t e s (k T T/k„ = 6.6) i n t h e v i c i n i t y o f pH t o j u s t i f y t h e H D max c o n c l u s i o n t h a t t h i s h y d r o g e n i s r e m o v e d i n t h e r a t e c o n t r o l l i n g s t e p . ) The f o l l o w i n g s t e p i n d i c a t e d i n R e a c t i o n Scheme I i s t h e d i s s o c i a t i o n o f C t o g i v e C~. The scheme a l s o r e q u i r e s t h a t C~ be c o n s i d e r a b l y more r e a c t i v e t h a n C . T h e r e a r e i n C o n l y two p r o t o n s a t a l l l i k e l y t o be r e m o v e d i n a d i s -s o c i a t i o n s t e p . One o f t h e s e i s a t t a c h e d t o an o x y g e n atom w h i c h h a s a n e g a t i v e c h a r g e v e r y c l o s e b y ; t h e o t h e r i s p a r t o f t h e a l c o h o l i c OH. I f t h i s l a t t e r p r o t o n i s removed, C -w o u l d t h e n be X V I I . cr O- OH C " . X V I I 131 I n X V I I , t h e h y d r o g e n t o be r e m o v e d i n t h e r a t e c o n t r o l l i n g s t e p i s a c t i v a t e d t o w a r d s o x i d a t i o n b y b e i n g p a r t o f an a l k o x i d e i o n . The r a t e e n h a n c i n g i n f l u e n c e o f a l c o h o l i o n i z a t i o n h a s b e e n l a b o u r e d s u f f i c i e n t l y i n t h e i n t r o d u c t i o n o f t h i s t h e s i s t o show t h a t C w o u l d n e c e s s a r i l y .be s i g n i f i c a n t - 1 2 5 more r e a c t i v e t h a n C , g i v e n t h e s t r u c t u r e s X V I a n d X V I I ' ' . t h e r o l e o f c o n f o r m a t i o n i n t h e r e a c t i o n becomes e x p l i c a b l e . F o r compound XV t h e i n t e r m e d i a t e e q u i v a l e n t t o C w o u l d be -t r a n s i t i o n s t a t e w o u l d i n v o l v e s u r m o u n t i n g s t e r i c i n t e r a c t i o n s o f t h e k i n d i n d i c a t e d i n t h e a b o v e f i g u r e . Compound XV, i n F i g u r e X V I I I , d o e s show a v e r y s l i g h t maximum a r o u n d pH 6. T h i s b e h a v i o u r may be due t o a m i n u t e c o n t a m i n a t i o n w i t h compound X I V o r i t may be r e a l . I n e i t h e r c a s e i t i n d i c a t e s t h a t a n i n t e r m e d i a t e o f compound XV o f t y p e C i s l e s s l i k e l y t o p r o c e e d t o p r o d u c t s t h a n a n i s o m e r i c i n t e r m e d i a t e o f compound X I V . I n t e r m s o f t h e i n t e r m e d i a t e s t r u c t u r e s p r e s e n t e d , O- OH The r e m o v a l o f t h e a p p r o p r i a t e h y d r o g e n a tom i n t h e 132 Compound X I I and t h e B c o n f o r m a t i o n o f compound X I V a r e c o n f o r m a t i o n a l l y i d e n t i c a l . The c o r r e s p o n d i n g C - t y p e i n t e r m e d i a t e w o u l d be as, f o l l o w s H '3 i n w h i c h i t a p p e a r s p h y s i c a l l y i m p o s s i b l e f o r t h i s i n t e r -m e d i a t e t o r e a c t b y r e m o v a l o f t h e r e q u i r e d h y d r o g e n a t o m . As w e l l as b e i n g u n a b l e t o r e a c t i n t h e n e c e s s a r y manner, t h i s i n t e r m e d i a t e w o u l d be o f h i g h e n e r g y r e l a t i v e t o a -s i m i l a r i n t e r m e d i a t e w i t h t h e c o m p l e x e d c a r b o x y l g r o u p i n t h e e q u a t o r i a l p o s i t i o n . Thus b o t h i n t e r m s o f t h e c o n f o r m a t i o n a l d a t a f o r t h e s e compounds and t h e known h i g h r e a c t i v i t y o f a l k o x i d e i o n t h e i n t e r m e d i a t e s C and C and R e a c t i o n Scheme I may be s a i d t o be c o n s i s t e n t . E a r l i e r R e a c t i o n Scheme I I was f o u n d t o be d i s c r e d i t e d on s e v e r a l c o u n t s . I t i s f o u n d t h a t t h e p r o p o s e d s t r u c t u r e s f o r C and C c a u s e d i f f i c u l t i e s i n t e r m s o f t h i s scheme. The d i f f i c u l t y comes f r o m t h e f a c t t h a t t h e i n t e r m e d i a t e s h a v e t h e same s t r u c t u r e i n b o t h r e a c t i o n - . scheme.s--but f o r R e a c t i o n Scheme I I i t becomes n e c e s s a r y t o 133 r e v e r s e t h e p r e v i o u s d e c i s i o n a s t o w h i c h i s t h e more r e a c t i v e . I t i s n o t e a s y t o i m a g i n e C b e i n g more r e a c t i v e t h a n C -a s t h e y a r e r e p r e s e n t e d a b o v e . However C may n o t e x i s t a s d r a w n b u t a s C' i n w h i c h c a s e a n a r g u m e n t c a n be made i n f a v o u r o f C' b e i n g more r e a c t i v e t h a n C . I n s u c h an a r g u m e n t i t w o u l d be o b s e r v e d t h a t HMnO^ i s a c o n s i d e r a b l y more r e a c t i v e s p e c i e s - 1 5 t h a n MnO^ ' and t h a t t h e manganese c o n t a i n i n g m o i e t y i n C r e s e m b l e s t h e f o r m e r more t h a n d o e s t h e manganese c o n t a i n i n g m o i e t y i n C~. A d i s t i n c t i o n b e t w e e n t h e two r e a c t i o n schemes m i g h t be d i f f i c u l t i f t h e o n l y c o n s i d e r a t i o n was t h e s t r u c t u r e o f t h e i n t e r m e d i a t e s n e c e s s a r y t o r a t i o n a l i z e t hem. H o w e v e r , w i t h t h e e v i d e n c e p r e s e n t e d p r e v i o u s l y i t w o u l d a p p e a r t h a t R e a c t i o n Scheme I a n d i n t e r m e d i a t e s C~ 134 and C a r e more i n a c c o r d w i t h t h e t o t a l r e s u l t s t h a n R e a c t i o n Scheme I I and i n t e r m e d i a t e s C - and C o r C' . D i s s o c i a t i o n C o n s t a n t s The d i s s o c i a t i o n c o n s t a n t o f c i s - 2 - h y d r o x y c y c l o -h e x a n e c a r b o x y l i c a c i d h a s b e e n d e t e r m i n e d u n d e r c o n d i t i o n s o f i o n i c s t r e n g t h d i r e c t l y c o m p a r a b l e t o t h a t u s e d i n t h e 51 p r e s e n t w o r k . The v a l u e o f t h e pK i s 4.80. T h i s v a l u e i s t o be c o m p a r e d t o t h e c o r r e s p o n d i n g v a l u e (4.70) n e c e s s i t a t e d b y t h e t r e a t m e n t o f t h e k i n e t i c d a t a a c c o r d i n g t o R e a c t i o n Schemes I a n d I I . A c o m p a r i s o n w i t h t h e w o r k 23 o f Z e r n e r and B e n d e r i n d i c a t e s t h a t t h i s a g r e e m e n t b e t w e e n i n d i r e c t k i n e t i c d e t e r m i n a t i o n and d i r e c t d e t e r m i n a t i o n i s q u i t e g o o d . The a g r e e m e n t i n d e e d , a r g u e s q u i t e f o r c e f u l l y t h a t t h e i o n i z a t i o n o f t h e a c i d i s i m p o r t a n t i n d e t e r m i n i n g t h e o v e r a l l k i n e t i c c h a r a c t e r o f t h e o x i d a t i o n . Were t h i s n o t t h e c a s e a g r e e m e n t r e f e r r e d t o w o u l d be q u i t e d i a b o l i c a l . The pK r e q u i r e d b y t h e k i n e t i c a n a l y s i s f o r c i s - 2 - h y d r o x y c y c l o h e x a n e c a r b o x y l i e a c i d i n d e u t e r i u m o x i d e 7 9 i s , a s e x p e c t e d , l a r g e r t h a n t h e c o r r e s p o n d i n g v a l u e f o u n d i n p r o t i u m o x i d e . The l i m i t • o f e r r o r w h i c h s h o u l d be p l a c e d on t h i s pK d i f f e r e n c e i s q u i t e u n c e r t a i n . I n a n y e v e n t , t h e d i f f e r e n c e i s o f t h e r i g h t o r d e r . The p K ( 4 . 8 5 ) o f c i s - 5 - t - b u t y l - c i s - 2 - h y d r o x y c y c l o -h e x a n e c a r b o x y l i e a c i d (X) i s n o t e x a c t l y as m i g h t be e x p e c t e d . 9 3 The w o r k o f S t o l o w c l e a r l y i n d i c a t e s t h a t , i n 135 cyclohexanecarbo'xylic a c i d s , the e q u a t o r i a l c a r b o x y l group i s more a c i d i c than the a x i a l c a r b o x y l group by about 0.4 pK u n i t s . Cis-2-hydroxycyclohexanecarboxylic a c i d (pK = 4.70) has a conformation w i t h the ca r b o x y l group i n the a x i a l p o s i t i o n i n which, according to our previous c a l c u l a t i o n , i t spends about 30% of i t s time. F r e e z i n g the molecule i n the more a c i d i c conformation (by the i n t r o d u c t i o n of a t - b u t y l group) would lower the pK by 0.1 u n i t s . This assumes th a t the pK d i f f e r e n c e between an a x i a l c a r b o x y l . and an e q u a t o r i a l c a r b o x y l i s 0.4. Consequently the pK of compound X i s s l i g h t l y higher than e x p e c t a t i o n . The discrepancy, however, i s s l i g h t . 136 V a r i a t i o n o f B u f f e r C o n c e n t r a t i o n B e c a u s e t h e a c t u a l c o m p o s i t i o n o f t h e b u f f e r a l t e r s c o n s i d e r a b l y i n t h e pH r a n g e s t u d i e d ( a l t h o u g h n o t t h e i o n i c s t r e n g t h ) a nd t h e s e c o n d i o n i z a t i o n c o n s t a n t o f O - p h o s p h o r i c a c i d i s n e a r t h e pH v a l u e (pK„ = 7.12), i t max 2. was c o n s i d e r e d n e c e s s a r y t o c a r r y o u t some o x i d a t i o n r u n s a t v a r i o u s b u f f e r c o n c e n t r a t i o n s . T a b l e V I I I shows t h a t a t pH 5.88 t h e s e c o n d o r d e r r a t e c o n s t a n t f o r t h e o x i d a t i o n o f compound X I V r e m a i n s c o n s t a n t o v e r a f i v e - f o l d c h a n g e i n b u f f e r c o n c e n t r a t i o n . T h u s , e f f e c t s due t o t h e b u f f e r ( e . g . g e n e r a l b a s e c a t a l y s i s ) , a r e n o t i m p o r t a n t . A c t i v a t i o n P a r a m e t e r s E n t h a l p i e s a n d e n t r o p i e s o f a c t i v a t i o n f o r c i s - 2 ~ h y d r o x y c y c l o h e x a n e c a r b o x y l i c a c i d a t t h r e e pH v a l u e s ( 2 . 0 0 , 5.88, 10.38) a r e g i v e n i n T a b l e X I V . To t h i s c a n 4 be, a d d e d t h e v a l u e s d e t e r m i n e d b y B a r t e r a n d L i t t l e r f o r c y c l o h e x a n o l a t pH 4.6 (AH^ = 14.0-0.4 Kcal/°mole, A S = - 2 3 . 3 - 1 . 2 e u ) . A t f i r s t g l a n c e i t i s e v i d e n t t h a t t h e p a r a m e t e r s f o r compound X I V a t pH 2.00 a r e s i m i l a r t o t h o s e f o r c y c l o h e x a n o l a t pH 4.6. T h i s i s a n e x p e c t e d 137 r e s u l t s i n c e b o t h s e t s o f p a r a m e t e r s r e f e r t o t h e o x i d a t i o n o f a n e u t r a l c y c l o h e x a n o l u n d e r c o n d i t i o n s i n w h i c h t h e " n e u t r a l " r e a c t i o n i s o c c u r r i n g . I n t h e c a s e o f compound X I V , t h e r e a c t i o n a t pH 2.00 i s as f a r away f r o m t h e b e l l - s h a p e b e h a v i o u r as i s e x p e r i m e n t a l l y f e a s i b l e , w i t h o u t b e i n g i n t h e r e g i o n i n v / h i c h c a t a l y s i s b y s t r o n g a c i d s t a k e s p l a c e . The a c t i v a t i o n p a r a m e t e r s d e t e r m i n e d a t pH 5.88, w h i c h a r e s i g n i f i c a n t l y d i f f e r e n t f r o m t h o s e a t pH 2.00, a r e n o t e a s y t o i n t e r p r e t . B e f o r e c o n s i d e r i n g t h e s e q u a n t i t i e s some comments c o n c e r n i n g t h e i r v a l i d i t y s h o u l d be v o i c e d . The o x i d a t i o n e x p e r i m e n t s w e r e c a r r i e d o u t a t a l l t e m p e r a t u r e s u s i n g t h e same b u f f e r s t o c k s o l u t i o n d i l u t e d a p p r o p r i a t e l y b y t h e s o l u t i o n s o f r e a c t a n t s . The pH o f t h e r e a c t i o n • o o m i x t u r e was 5.88 a t 25 C. A t a l l o t h e r t e m p e r a t u r e s (5 C t o 35°C) t h e pH o f t h e medium w o u l d be s u b j e c t t o a t e m p e r a t u r e e f f e c t on t h e b u f f e r s y s t e m . The d a t a t a b u l a t e d b y R o b i n s o n 69 and S t o k e s f o r s o l u t i o n s 0.025M i n b o t h f^HPO^ a n d N a H 2 P 0 4 (pH = 6.860 a t 25°C) i n d i c a t e t h a t t h e t o t a l c h a n g e i n pH b e t w e e n 5°C and 35°C s h o u l d be a b o u t 0.10 p H - u n i t s . The s m a l l s t a n d a r d e r r o r i n t h e a c t i v a t i o n p a r a m e t e r s p r o b a b l y means t h a t t h i s s m a l l pH c h a n g e i s o f no c o n s e q u e n c e . A c h a n g e i n pH w i t h t e m p e r a t u r e w o u l d t e n d t o \ ^ 1 max i n v a l i d a t e t h e m e a s u r e m e n t a s w e l l b u t a g a i n t h e s m a l l s t a n d a r d e r r o r i n t h e c a l c u l a t e d a c t i v a t i o n p r o b a b l y means t h a t t h i s i s n o t t h e c a s e . A s i g n i f i c a n t c h a n g e i n pH w i t h t e m p e r a t u r e 138 w o u l d p l a c e t h e p o s i t i o n o f r a t e m e a s u r e m e n t on t h e s t e e p s l o p e o f t h e b e l l - s h a p e c u r v e a n d t h e r e s u l t i n g l o g ( k / T ) a g a i n s t I/T p l o t w o u l d show c u r v a t u r e o r be o t h e r w i s e b a d l y b e h a v e d . T h a t t h i s i s n o t t h e c a s e i n d i c a t e s t h a t P H m a x c h a n g e s b u t s l i g h t l y i n t h e t e m p e r a t u r e r a n g e c o n s i d e r e d . The v a l u e o f k-^^ , . c a n be r e l a t e d b o t h t o OBS(max) k^ and k'^. The two e q u a t i o n s a r e k OBS(max) k „ (1 + -TTT > [ H + ] max and k 1 OBS (max) f H+] ( i + 1 J max^ 2 K a I f i t i s assumed t h a t i s n o t v e r y t e m p e r a t u r e d e p e n d e n t , i t i s p o s s i b l e t o c a l c u l a t e a c t i v a t i o n p a r a m e t e r s c o r r e s p o n d i n g t o s t e p s k^ a n d k' ^ . T h i s a s s u m p t i o n i s a c c e p t a b l e i f one c o n s i d e r s t h e t e m p e r a t u r e d e p e n d e n c e o f t h e pK's o f o r g a n i c a c i d s 70 t a b u l a t e d b y R o b i n s o n a n d S t o k e s The s q u a r e d t e r m i n t h e s e c o n d e q u a t i o n i s v e r y c l o s e t o u n i t y s o t h a t t h e a c t i v a t i o n p a r a m e t e r s , f o r t h i s s t e p a r e n e a r l y t h e same a s t h o s e d e t e r m i n e d f o r t h e o v e r a l l 139 r e a c t i o n . The parameters corresponding to k^ have been c a l c u l a t e d and are given i n Table XIX along w i t h the other . values r e l e v a n t to t h i s d i s c u s s i o n . TABLE XIX cis-2-hydroxycyclohexanecarboxylic a c i d A c t i v a t i o n Parameters pH 5.88 O v e r a l l Reaction k 1^ step. k^ step AH^(Kcal/°mole) 15.9 15.9 14.7-0.4 A S ^ (eu) -13.9 -13.9 -5.3-1.1 According to Reaction Scheme I the step described by k^ i s the formation of an intermediate from permanganate i o n and uni o n i z e d s u b s t r a t e . The step described by k ' ^  r e f e r s to the formation of an intermediate from permanganate i o n and subst r a t e anion. D i s r e g a r d i n g the a c t u a l magnitude of the ent r o p i e s f o r the moment i t can be s a i d t h a t the entropy f o r the k^ step should be more p o s i t i v e than the entropy f o r the k 1 step by an amount equal to the c o n t r i b u t i o n from 71 e l e c t r o s t a t i c r e p u l s i o n s between the r e a c t i n g ions . This f i g u r e i s regarded as about 20 eu but i s obtained from s u b s t a n t i a l a p p r o x i m a t i o n s ^ . Both entropy values may be considered, r e l a t i v e to one another, i n accord w i t h e x p e c t a t i o n Of course i t should not be f o r g o t t e n t h a t Scheme I and Scheme I 140 a r e m u t u a l l y e x c l u s i v e . E i t h e r t h e r e a c t i o n s t e p c o r r e s p o n d i n g t o k ' ^  i s f i c t i t i o u s o r t h a t c o r r e s p o n d i n g t o k^ i s . The a b s o l u t e v a l u e o f t h e s e c a l c u l a t e d p a r a m e t e r s i s a n o t h e r m a t t e r . A d i l i g e n t p e r u s a l o f t h e l i t e r a t u r e f o r a c t i v a t i o n p a r a m e t e r s o f r e a c t i o n s r e a s o n a b l y s i m i l a r t o s t e p s k^ a n d k'^ r e v e a l s a v e r y w i d e s p r e a d . B a s i c h y d r o l y s i s o f e s t e r s , b a s i c h y d r o l y s i s o f a r y l s u l f o r y l 7 2 c h l o r i d e s a n d n u c l e o p h i l i c s u b s t i t u t i o n r e a c t i o n s ( S N 2 ) 7 3 7 4 o f v a r i o u s k i n d s ' p o s s e s s a c t i v a t i o n p a r a m e t e r s ( i n w a t e r ) w h i c h a r e e x c e e d i n g l y d e p e n d e n t o n s u b s t r a t e s t r u c t u r e a n d s u b s t i t u t i o n . I n t h e f a c e o f t h i s i t w o u l d be f u t i l e t o t r y t o d e c i d e w h i c h s e t o f a c t i v a t i o n p a r a m e t e r s i s t h e more r e a l i s t i c . A c o m p a r i s o n o f t h e a c t i v a t i o n p a r a m e t e r s a t pH = 5.88 w i t h t h o s e a t pH 2.00 shows t h a t t h e f a s t e r r e a c t i o n h a s a much h i g h e r a c t i v a t i o n e n t h a l p y (3.8 K c a l ) b u t t h i s i s c o u n t e r a c t e d b y a much l e s s n e g a t i v e e n t r o p y o f a c t i v a t i o n (13.9 e u ) . I t i s d i f f i c u l t t o comment on t h e a c t u a l m a g n i t u d e o f t h e s e p a r a m e t e r s . The r e a c t i o n a t pH 5.88 i s c o m p l i c a t e d b y s e v e r a l s t e p s p r i o r t o t h e r a t e c o n t r o l l i n g s t e p , a l l o f w h i c h w i l l h a v e some i n f l u e n c e on t h e e n t r o p y a n d e n t h a l p y . The e n t r o p y o f a c t i v a t i o n a t pH 2.00 i s n o t u n u s u a l a n d c o m p a r e s w i t h v a l u e s a l r e a d y d e t e r m i n e d ^ . The a c t i v a t i o n p a r a m e t e r s a t pH 10.38 a r e s i m i l a r t o t h o s e a t pH 5.88. T h i s i s p r o b a b l y a c o i n c i d e n c e . One w o u l d e x p e c t t h e p a r a m e t e r s a t pH 10.38 t o be s i m i l a r t o t h o s e a t pH 2.00. T h a t t h e y a r e n o t p r o b a b l y i n d i c a t e s t h a t a t pH 10.3 8 t h e n e u t r a l r e a c t i o n i s n o t t h e o n l y r e a c t i o n t a k i n g p l a c e . The r a t e a t h i g h e r pH's i s f o u n d t o d e p e n d on t h e f i r s t p o w e r o f t h e h y d r o x i d e i o n c o n c e n t r a t i o n . A t pH 10.38 t h i s b a s e a s s i s t e d r e a c t i o n may be t a k i n g p l a c e a l o n g w i t h t h e n e u t r a l r e a c t i o n t o g i v e t h e o b s e r v e d a c t i v a t i o n p a r a m e t e r s . T h i s w o u l d r e n d e r t h e d e t e r m i n e d v a l u e s q u i t e m e a n i n g l e s s . T h e r e a r e s e v e r a l s t u d i e s i n t h e l i t e r a t u r e d e a l i n g w i t h t h e p e r m a n g a n a t e o x i d a t i o n o f h y d r o x y s u b s t i t u t e d 75 76 77 c a r b o x y l i c a c i d s ' ' . B a k o r e and Rama S h a n k a r h a v e s t u d i e d t h e o x i d a t i o n o f c i t r i c a c i d , t a r t a r i c a c i d and m a n d e l i c a c i d s i n w e a k l y a c i d i c s o l u t i o n s (pH = 2 t o 4 ) . T h e s e a u t h o r s p r e s e n t e v i d e n c e f o r c o m p l e x f o r m a t i o n betv/een p e r m a n g a n a t e a n d t a r t r a t e i o n , and p e r m a n g a n a t e and c i t r a t e i o n . I t i s c l e a r , h o w e v e r , f r o m t h e e v i d e n c e p r e s e n t e d b y t h e s e w o r k e r s t h a t s u c h o x i d a t i o n s a r e n o t r e l a t e d c l o s e l y t o t h e p r e s e n t w o r k . F i r s t l y t h e y c o n s i d e r C i - h y d r o x y a c i d s w h i l e i n t h e p r e s e n t c a s e / ^ " h y d r o x y a c i d s a r e i n v o l v e d . The s t o i c h i o m e t r y o f t h e r e a c t i o n s i s q u i t e d i s s i m i l a r - t h e 142 m anganese p r o d u c t i s M n ( I I ) and t h e o r g a n i c p r o d u c t s i n c l u d e c a r b o n d i o x i d e . The r e a c t i o n s a r e v e r y s t r o n g l y a u t o c a t a l y t i c n e c e s s i t a t i n g t h e e v a l u a t i o n o f i n i t i a l s l o p e s t o o b t a i n k i n e t i c d a t a . The p r e s e n t w o r k i n v o l v e s q u i t e d i f f e r e n t b e h a v i o u r . T h e r e d o e s n o t a p p e a r t o be any o b s e r v a t i o n o f a " b e l l - s h a p e " p H - r a t e p r o f i l e d e a l i n g w i t h an o x i d a t i o n b e t w e e n a t r a n s i t i o n m e t a l i o n a n d a n o r g a n i c s u b s t r a t e o t h e r t h a n a s h a s b e e n r e p o r t e d h e r e i n . The s t r u c t u r e s p r o p o s e d f o r t h e i n t e r m e d i a t e s do n o t i n v o l v e t h e f o r m a t i o n o f p e r m a n g a n a t e e s t e r s . T h i s p o s s i b i l i t y was c o n s i d e r e d u n l i k e l y b e c a u s e o f w h a t i s known a b o u t p e r m a n g a n a t e o x i d a t i o n s , b e c a u s e o f t h e d i f f i c u l t y i n c o n f o r m i n g s u c h a p o s s i b i l i t y w i t h t h e r e a c t i o n schemes n e c e s s a r y t o g i v e t h e o b s e r v e d b e h a v i o u r a n d b e c a u s e o f t h e d i f f i c u l t y w i t h w h i c h p e r m a n g a n a t e i o n e x c h a n g e s i t s o x y g e n 7 8 w i t h s o l v e n t Summary The d a t a f o r t h e o x i d a t i o n o f compound X I V i n w a t e r and d e u t e r i u m o x i d e , a n d compound X i n w a t e r w e r e f o u n d a m e n a b l e t o t r e a t m e n t i n t e r m s o f a k i n e t i c scheme i n v o l v i n g two a c i d i o n i z a t i o n e q u i l i b r i a . Tv/o m e c h a n i s t i c s chemes w e r e p r o p o s e d a n d t h e d a t a w e r e d i s c u s s e d w i t h r e g a r d t o d i s t i n g u i s h i n g b e t w e e n them. The s t r u c t u r e o f t h e i n t e r m e d i a t e p r o p o s e d was c o n s i s t e n t w i t h t h e o x i d a t i o n 143 b e h a v i o u r o f d i f f e r e n t c o n f o r m a t i o n s , a s w e l l a s the. b e h a v i o u r o f compound X I V i n d e u t e r i u m o x i d e . The d i s t i n c t i o n b e t w e e n h y d r i d e - t r a n s f e r a nd h y d r o g e n atom t r a n s f e r i n t h e r a t e c o n t r o l l i n g s t e p d o e s n o t e n t e r t h e s e c o n s i d e r a t i o n s a n d t h e r e s u l t s p r e s e n t e d h e r e i n do n o t i m p i n g e u p o n t h i s p r o b l e m 144 SUGGESTIONS FOR FURTHER WORK The decision between hydride-transfer and hydrogen-atom transfer i n permanganate oxidations has been a subject 2 7 16 for speculation ' ' since the substituent-effeet work of Stewart and Van der Linden. Because the p value for 90 borohydride reduction of substituted acetophenones and 91 fluorenones i s about +2 i t was anticipated that the removal 8 .of hydride should involve a s i m i l a r p with changed sign. The r e s u l t s f o r the oxidation of a r y l t r i f l u o r o m e t h y l carbinols did not bear t h i s out. To d i s t i n g u i s h between a legitimate r e s u l t and a s p e c i a l e f f e c t caused by the proximity of the -CF-j group to the reacting centre i t might prove f r u i t f u l to study the borohydride reduction of 0L,0L,(X-trif luoro-acetophenone. The in t e r p r e t a t i o n of the oxidation r e s u l t s might then be c l e a r . i r Attempts have been made to evaluate substituent 92 ef f e c t s for permanganate oxidation i n basic solution but f a i l e d because of s o l u b i l i t y d i f f i c u l t i e s . This d i f f i c u l t y could be surmounted by using a benzhydrol of the following composition -145 The i o n i z e d c a r b o x y l g r o u p w o u l d p r o v i d e r e a s o n a b l e s o l u b i l i t y a n d t h e s u b s t i t u e n t s c o u l d be v a r i e d i n t h e o t h e r r i n g . A p l o t o f t h e e x p e r i m e n t a l r a t e c o n s t a n t v e r s u s h y d r o x i d e i o n c o n c e n t r a t i o n s u c h as i s g i v e n i n F i g u r e V - w o u l d e n a b l e one t o d e t e r m i n e kK f r o m t h e s l o p e . The p r o d u c t kK comes f r o m t h e f o l l o w i n g r e a c t i o n s e q u e n c e K RoH + 0H~ "T^- Ro + H 2 0 k Ro + MnO^ ——* P r o d u c t s I t s h o u l d be s i m p l e t o s e p a r a t e t h e e f f e c t o f s u b s t i t u e n t s f o r t h e i o n i z a t i o n o f t h e a l c o h o l f r o m t h e e x p e r i m e n t a l r e s u l t s t o g i v e t h e e f f e c t f o r t h e r a t e c o n t r o l l i n g s t e p . I n f a c t t h e p v a l u e f o r t h e i o n i z a t i o n o f a r y l t r i f l u o r o m e t h y l c a r b i n o l i s known t o be v e r y c l o s e t o 1. 146 OBSERVATIONS In the Introduction the deuterium isotope e f f e c t determined i n the permanganate oxidation of phenyl 2 trifluoromethyl carbinol was mentioned . One explanation of t h i s large e f f e c t (k„/k_ = 16, at 25°C) was proton-tunnelling^'^This point w i l l now be considered further. To say that proton-tunnelling accounts f o r the large isotope e f f e c t i s to imply that tunnelling i s more s i g n i f i c a n t for the protium containing compound than for the deuterio compound. • The consequence of t h i s i s to make k^ "unnaturally" large thereby making k H / k D larger than i t would be i n the absence of tunnelling. 63 80 Current theories ' are quite e x p l i c i t as to the observations which may be interpreted i n terms of proton-tunnelling. If the a c t i v a t i o n energy for the reaction of the pro t i o compound becomes smaller as the temperature i s lowered - i . e . the p l o t of log k against l /T shows a curvature which tends to make the curve p a r a l l e l to the l/T axis at low temperatures, t h i s i s considered the best evidence f o r proton t u n n e l l i n g . In solution work, there i s only one case in 81 such an e f f e c t has been found . Bell's thorough discussion of the subject indicates that f o r the narrow temperature ranges avai l a b l e for temperature studies i n condensed phases, (most of the relevant work was done i n water or ethanol) i t 147 appears u n l i k e l y that most reactions which involve proton-tunnelling would show any curvature at a l l i n t h e i r Arrhenius p l o t s . B e l l ' s account of proton-tunnelling leads to a c r i t e r i o n much less stringent than the one just considered. He has been able to set c e r t a i n l i m i t s for the behaviour of the pre-exponential term of the.Arrhenius equation on iso t o p i c substitution. When no proton-tunnelling i s involved the l i m i t s are: l/i/2~ — A^/A^ ^ .2. Experimental evaluation of values for t h i s r a t i o outside these l i m i t s provides some j u s t i f i c a t i o n for the involvement of proton-tunnelling, according to B e l l ' s a n a l y s i s . There are two rather s i g n i f i c a n t pieces of experimental work which support t h i s conclusion. The bromi.nation of 2-carbomethoxycyclopentanone catalyzed by a variety" of bases was found to have a A^/A^ r a t i o greater than 2 i n a l l the cases studied. In the instance of c a t a l y s i s of fl u o r i d e the value of the r a t i o i s 24, much greater than 81 for the other base c a t a l y s t s . Hulett l a t e r showed, using a larger temperature range than o r i g i n a l l y considered,that the Arrhenius p l o t f o r t h i s reaction with f l u o r i d e ion ca t a l y s t i s curved, i n the manner considered above, at lower tempera, tures. This study and the one to be mentioned next are the r e s u l t of very c a r e f u l experimentation and the data cannot be dis c r e d i t e d by invoking experimental error. 148 I f t h e c r i t e r i o n m e n t i o n e d a b o v e i s c o r r e c t , i n . t h e a b s e n c e o f t u n n e l l i n g t h e r a t i o o f A f a c t o r s s h o u l d b e 8 3 w i t h i n t h e p r e s c r i b e d r a n g e . S h i n e r a n d S m i t h , a n d S h i n e r 84 and M a r t i n d e t e r m i n e d t h e r a t i o s A„/A„ a n d A m / A n f o r t h e e t h o x i d e p r o m o t e d e l i m i n a t i o n r e a c t i o n o f l - b r o m o - 2 -p h e n y l p r o p a n e . The v a l u e o f A D / A H was 2.53, c l o s e t o t h e l i m i t o f 2 b u t w i t h i n e x p e r i m e n t a l e r r o r g r e a t e r t h a n 2. F o r t h e e l i m i n a t i o n i n v o l v i n g d e u t e r i u m a n d t r i t i u m i t i s v e r y u n l i k e l y t h a t t u n n e l l i n g i s t a k i n g p l a c e . T h i s , a c c o r d i n g t o B e l l ' s t h e o r y , w o u l d n e c e s s i t a t e h a v i n g A^/A^ w i t h i n t h e p r e s c r i b e d l i m i t s . I n f a c t A T / A D i s 1.19 b e a r i n g o u t t h e t h e o r e t i c a l p r e d i c t i o n s . S h i n e r a n d M a r t i n h a v e v o i c e d t h e o p i n i o n t h a t t h e s e r e s u l t s c o n s t i t u t e i m p o r t a n t s u p p o r t f o r t h e t h e o r i e s a d v a n c e d b y B e l l . I n d e e d t h e i r r e s u l t s show t h a t A D / A H d o e s n o t v a r y c a p r i c i o u s l y b u t r e a l l y i n a c c o r d a n c e w i t h t h e o r y . The two e x a m p l e s c o n s i d e r e d a b o v e do n o t h a v e l a r g e p r i m a r y i s o t o p e e f f e c t s . I n t h e w o r k o f B e l l , F e n d l e y and H u l e t t t h e k_.7/kr. v a l u e s a r e f r o m 2 t o 3. I n t h e work o f S h i n e r a n d S m i t h k^/k^ a t 25°C i s 7.8. The i s o t o p e e f f e c t f o r t h e p e r m a n g a n a t e o x i d a t i o n o f f o r m a t e i o n i s 9.2. A c a r e f u l k i n e t i c s t u d y b y B e l l 8 5 and Onwood r e v e a l e d A n / A „ t o be 1.12. T h i s m i g h t l e a d 149 t o t h e c o n c l u s i o n t h a t t h e l i m i t s p l a c e d o n t h e p e r m i s s i b l e v a r i a t i o n o f A^/A^ i n t h e a b s e n c e o f t u n n e l l i n g a r e t o o g e n e r o u s and t h a t a v a l u e o f u n i t y i s more l i k e l y i n s o l u t i o n . T h i s c o n c l u s i o n h o w e v e r xvould be b a s e d on o n l y two p i e c e s o f e v i d e n c e . F o r t h e p e r m a n g a n a t e o x i d a t i o n o f p h e n y l t r i f l u o r o -m e t h y l c a r b i n o l t h e v a l u e o f Ap/A^ i s 3.4- 1.2 . A d m i t t e d l y t h e s t a n d a r d e r r o r i n t h i s q u a n t i t y i s l a r g e b u t t h e r a t i o i s s t i l l g r e a t e r t h a n 2. The c o n c l u s i o n b a s e d on w h a t h a s > p r e c e e d e d t h i s i s c l e a r . . The l a r g e i s o t o p e e f f e c t (16.2 a t 25°C) i s a t l e a s t p a r t l y a c c o u n t e d f o r b y p r o t o n - t u n n e l l i n g . T h i s d i s c u s s i o n w o u l d n o t be c o m p l e t e w i t h o u t a 86 c o n s i d e r a t i o n o f t h e w o r k o f L e w i s and R o b i n s o n . T h e s e a u t h o r s t a k e as a b a s i s f r o m w h i c h t o a t t a c k t h e q u e s t i o n o f p r o t o n t u n n e l l i n g w h a t h a s become known as t h e S w a i n e q u a t i o n . v kT = w1,442 8 7 The S w a i n e q u a t i o n was d e r i v e d w i t h o u t c o n s i d e r i n g t u n n e l l i n g a n d t h e a b i l i t y o f t h e e q u a t i o n t o d e a l w i t h t u n n e l l i n g i s e x p l o r e d . I t w o u l d a p p e a r f r o m t h e i r r e s u l t s t h a t i n c a s e s w h e r e t u n n e l l i n g i s e x t e n s i v e (A_/A T T i s l a r g e ) t h e S w a i n e q u a t i o n d o e s n o t h o l d e x a c t l y t r u e . D e v i a t i o n s a p p e a r t o l e a d t o a c o n c l u s i o n o f t u n n e l l i n g b e i n g i m p o r t a n t b u t s u c h d e v i a t i o n s do n o t r e a d i l y o c c u r . I n c o n n e c t i o n w i t h t h i s 150 the work of Shiner and Martin, i n which the values of A^/A^and Ap/A^ give clear evidence of tunnelling, shows rather 8 4 exact agreement with the Swain equation. . Lewis and Robinson determined k„/k m for the permanganate oxidation of phenyltrifluoromethyl carbinol and f i n d the Swain equation accurately r e l a t i n g k^/k^ to k„/k m. In the l i g h t of t h e i r conclusions regarding the Swain equation t h i s r e s u l t neither takes away from nor adds to the previous considerations. C l e a r l y a great deal more work i s required i f we are to understand the su b t l e t i e s of proton tunnelling and i t s importance i n chemical reactions: In accordance with the present understanding of the subject the conclusion made above concerning the permanganate oxidation of phenylthrifluoro-methyl carbinol appears j u s t i f i e d . The "Transition State Characterization" theory 17 18 of Kurz ' was considered i n the Introduction as i t was applied to the f l u o r a l hydrate oxidation by Kurz himself. I t appears possible to attack the permanganate oxidation of benzhydrol i n the same way. Benzhydrol reacts i n neutral sol u t i o n i n an acid independent reaction but the reaction i s base catalyzed i n solutions with pH exceeding**11 .'t 1 1 . The appropriate equation to use i s Equation 5.bw where i n t h i s case k^ refers to the bimolecular reaction between permanganate and benzhydrol and k 2 i s a t h i r d order rate constant fcr the base catalyzed reaction. That i s 151 R a t e - k i QI2^] [ M n 0 4 ] R a t e = k 2 [ O H " J [ m « 0 4 J [ H 2 Z ] 9 ¥• The v a l u e s f o r k, and k„ g x v e 11.3 f o r pK'. 1 2 a T h i s pK r e f e r s t o t h e f o l l o w i n g e q u i l i b r i u m OH l ( C R H E ) ~ C • • • H " * 0 M n 0 o b D Z • J o ( C 6 H 5 ) 2 C ^ • H•••OMnO. + H + F o r a h y d r i d e t r a n s f e r r e a c t i o n 0% b o n d f o r m a t i o n w o u l d r e s u l t i n t h e a b o v e e q u i l i b r i u m r e s e m b l i n g t h e i o n i z a t i o n o f b e n z h y d r o l i t s e l f ( p K ~ 1 6 ) 12 At 100'% r e a c t i o n the e q u i l i b -rium resembles the deprotonation of the conjugate a c i d of 13 b e n z o p h e n o n e ( p K B H + = -6.2) . A h y d r o g e n a t o m t r a n s f e r m e c h a n i s m w o u l d l e a d t o t h e k e t y l r a d i c a l a t 100% r e a c t i o n 11 4 (pK = 9 . 2 ) . I f t h e c o r r e c t i o n t o pK' s u g g e s t e d b y K u r z a i s a p p l i e d , t h e r e s u l t i s 29% C - H b o n d b r e a k i n g f o r h y d r i d e t r a n s f e r a n d 89% f o r h y d r o g e n a tom t r a n s f e r . The c o m p u t e d pK^ a p p e a r s t o be i n a c c o r d w i t h b o t h m e c h a n i s m s . I f one c o n s i d e r s t h e m a g n i t u d e o f t h e d e u t e r i u m i s o t o p e e f f e c t w h i c h h a s b e e n o b s e r v e d f o r t h i s r e a c t i o n , a c o n c l u s i o n c o n c e r n i n g w h i c h m e c h a n i s m i s t h e more p r o b a b l e 8 8 c a n be r e a c h e d . A c c o r d i n g t o t h e o r y t h e v a l u e o f t h e d e u t e r i u m i s o t o p e e f f e c t s h o u l d r e a c h i t s maximum v a l u e when t h e h y d r o g e n ( o r d e u t e r i u m ) i s h a l f - t r a n s f e r r e d i n t h e t r a n s i t i o n s t a t e . T h i s c o n c l u s i o n f o l l o w s f r o m t h e 152 s i m p l e t h e o r y w h i c h d e s c r i b e s t h e i s o t o p e e f f e c t a s o r i g i n a t i n g f r o m t h e d i f f e r e n c e i n t h e z e r o - p o i n t e n e r g y b e t w e e n t h e O H a n d C-D s t r e t c h i n g v i b r a t i o n s . I t h a s b e e n n o t e d a b o v e t h a t l a r g e i s o t o p e e f f e c t s 2 5 o c c u r v / i t h f l u o r i n a t e d a l c o h o l s ' and some r e m a r k s h a v e b e e n made c o n c e r n i n g t h e i n t e r p r e t a t i o n t h e s e o b s e r v a t i o n s may be g i v e n . A l c o h o l s w h i c h do n o t c o n t a i n f l u o r i n e a p p e a r t o 1 3 e x h i b i t s m a l l e r i s o t o p e e f f e c t s . ' I f i t i s g r a n t e d t h a t t h e i s o t o p e e f f e c t (*7) f o u n d i n t h e p e r m a n g a n a t e o x i d a t i o n o f b e n z h y d r o l i s n e a r i t s maximum v a l u e , t h e n a t t h e same t i m e i t m ust a l s o be g r a n t e d t h a t t h e amount o f b o n d - b r e a k i n g a f f o r d e d b y t h e h y d r i d e - t r a n s f e r m e c h a n i s m i s more a p p r o p r i a t e t o t h i s s t a t e o f a f f a i r s t h a n i s t h a t w h i c h c o r r e s p o n d s t o a h y d r o g e n - a t o m t r a n s f e r m e c h a n i s m . The e n t h a l p y o f a c t i v a t i o n f o r b e n z h y d r o l o x i d a t i o n 1 9 o i s q u i t e s m a l l ' . A t pH 13 i t i s 5.6 K c a l / m o l e and a t pH 7 i t i s 5.7 Kcal/°mole. I n v i e w o f t h e f a c i l i t y o f p e r m a n g a n a t e o x i d a t i o n s and c o n s i d e r i n g t h e "Hammond P o s t u l a t e " ' i t m i g h t be c o n c l u d e d t h a t t h e t r a n s i t i o n s t a t e f o r t h e p e r m a n g a n a t e o x i d a t i o n o f b e n z h y d r o l i s more r e a c t a n t - l i k e t h a n p r o d u c t - l i k e . C o m b i n i n g t h i s c o n c l u s i o n w i t h t h e c o n c l u s i o n r e l a t i n g t o t h e i s o t o p e e f f e c t i n t h i s r e a c t i o n l e a d s t o t h e f a v o u r i n g o f a h y d r i d e - t r a n s f e r m e c h a n i s m a s t h e more l i k e l y a l t e r n a t i v e . B i b l i o g r a p h y 1. Ross Stewart, J . Am. Chem. Soc. 79, 3057 (1957). 2. Ross Stewart and R. Van der Linden, Discussions Faraday Soc. No. 29, 211 (1960). 3. J.S. L i t t l e r , J . Chem. Soc. 2190 (1962). 4. R.M. Barter and J.S. L i t t l e r , J . Chem. Soc. B_, 205 (1967). 5. Ross Stewart and Michael M. Mocek, Can. J . Chem. 41_, 1160 (1963). 6. F a r i z a Banoo and Ross Stewart, Can. J . Chem. 47, 3199 (1969). 7. Ross Stewart, i n O x i d a t i o n i n Organic Chemistry, Part A, ed. K.B. Wiberg, Academic Press Inc., New York, 1965. 8. R. Van der Linden, Ph.D. T h e s i s , U n i v e r s i t y of B r i t i s h Columbia, 1960. 9. F a r i z a Banoo, Ph.D. Th e s i s , U n i v e r s i t y o f B r i t i s h Columbia, 1969. 10. J.S.F. Poue and W.A. Waters, J . Chem. Soc. 717 (1956). 11. G. Po r t e r and F. W i l k i n s o n , Trans. Faraday Soc. 57, 1686 (1961). 12. P. B a l l i n g e r and F.A. Long, J . Am. Chem. Soc. 82, 795 (1960). 13. Ross Stewart, M.R. Granger, R.B. Moodie and L.J . Muenster, Can. J . Chem. 41_, 1065 (1963). 14. F.R. Duke, J . Phys. Chem. 56_, 882 (1952). 15. C.K. Rule and V.K. La Mer, J . Am. Chem. Soc. 60, 1974 (1938). 16. J . Rocek, O x i d a t i o n of aldehydes by t r a n s i t i o n metals, from the Chemistry of the Carbonyl Group, ed. Saul P a t a i , I n t e r s c i e n c e , 1966. 17. J.L. Kurz, J . Am. Chem. Soc. 85_, 987 (1963). 18. J.L. Kurz, J . Am. Chem. Soc. 86, 2229 (1964). 19. B. Capon, Quart. Revs. 1_5_, 45 (1964). 20. W.P. Jencks, C a t a l y s i s i n Chemistry and Enzymology, McGraw-Hill Book Company, Inc., 1969. 21. T.C. Bruice and S.J. Benkovic, Bioorganic Mechanisms, V o l . 1, W.A. Benjamin, Inc., New York, 1966. 22. E.F. C a l d i n and J.H. Wolfenden, J . Chem. Soc. 1239 (1936). 23. B. Zerner and M.L. Bender, J . Am. Chem. Soc. 83_, 2267 (1961). 24. K.B: Wiberg and Ross Stewart, J . Am. Chem. Soc. 1J_, 1786 (1955). 25. S. Glasstone, K.J. L a i d l e r and Henry E y r i n g , the Theory of Rate Processes, McGraw-Hill Book Company, Inc., New York, 1941. 26. K.B. Wiberg, P h y s i c a l Organic Chemistry, John Wiley § Sons, Inc., 1964. 27. Arthur I. Vogel, A. Text-Book of P r a c t i c a l Organic Chemistry, 3rd ed. Longmans, Green and Co. L t d . , 1956. 28. Resinger and Thompson, Rec. t r a v . chim. 82(8), 801 (1953). 29. Handbook o f Chemistry and P h y s i c s , 43rd ed., the Chemical Rubber P u b l i s h i n g Co., 1961-62. 30. D i c t i o n a r y of Organic Compounds, 4th ed., Oxford U n i v e r s i t y Press, 1965. 31. J . Pascual, J . S i s t a r e , and J . Regas, J . Chem. S o c , 1943 (1949). 32. J . S i c h e r , F. Sipos, and M. Ti c h y , C o l l e c t i o n Czech. Chem. Commun. 26, 847 (1961). 33. Inorganic I s o t o p i c Syntheses, R o l f H. Herber ed., W.A. Benjamin, Inc., New York, 1962. 34. Donald G. Lee, i n O x i d a t i o n , V o l . 1, R.L. Augustine ed., Marcel Dekker, Inc., New York, 1969. 35. ;G. Kortiim, W. Vogel, and K. Andrussow, D i s s o c i a t i o n Constants o f Organic Acids i n Aqueous S o l u t i o n , Butterworths, London, 1961. 36. CD. R i t c h i e and W.F. Sager, Progr. Phys. Org. Chem. 2_, 323 (1964). 37. K.B. Wiberg and Ross Stewart, J . Am. Chem. Soc. 7_7, 1786 (1955). 38. J . Rocek, Ref. 16, p. 480. 39. D.D. Wheeler, D.C. Young, and D.S. E r l e y , J . Org. Chem. 22, 547 (1957). 40. J . T i r o u f l e t , Compt. rend. 236, 1426 (1953). 41. G.B. B a r l i n and D.D. P e r r i n , Quart. Revs. XX, 75 (1966). 42. S. Racine, Ber. deut. chem. Ges. 19_, 778 (1886). 43. D.S. E r l e y , IV.J. P o t t s , P.R. Jones, and P.J. Desio, Chem. § Ind. (London) 1915 (1964). 44. P.R. Jones and S.L. Congdon, J . Am. Chem. Soc. 81_, 4291 (1959). 45. P.R. Jones and A.A. Lavigne, J . Org. Chem. 25_, 2020 (1960). 46. F.C. Tompkins, Trans. Faraday Soc. 3_9, 280 (1943). 47. R. Gary, R.G. Bates, and R.A. Robinson, J . Phys. Chem. 68_, 3806 (1964). 48. Henry Dent Gardiner, W i l l i a m Henry P e r k i n , j u n . , and Hubert Watson, Trans. Chemical Soc. Pt. I I , 1756 (1910). 49. J.A. H i r s c h , Topics i n Stereochemistry 1_, 199 (1967). 50. Aksel A. Bothner-By, Advan. Mag. Resonance, 1_, 195 (1965). 51. M. K i l p a t r i c k and J.G. Morse, J . Am. Chem. Soc. 75_, 1896 (1953). 52. J.C. R i c h e r , A. P i l a t o , and E.L. E l i e l , Chem. $ Ind. (London) 2007 (1961) 53. Ref. 21, p. 4, ££ 54. M. Dixon and E.G. Webb, Enzymes, Academic Press Inc., New York, 1964. 55. K.J. L a i d l e r , Chemical K i n e t i c s of Enzyme A c t i o n , Oxford U n i v e r s i t y Press, 1958. 56. K.J. L a i d l e r , Chemical K i n e t i c s , 2nd ed., McGraw-Hill Book Company, 1965. 57. H. Morawetz and I. Oreskes, J . Am. Chem. Soc. 80, 2591 (1958). 58. R.B. M a r t i n , S. Lowey, E.L. E l s o n , and John T. E d s a l l , J . Am. Chem. Soc. 81_, 5089 (1959) . 59. L. A. Cohen and W.M. Jones, J . Am. Chem. Soc. 82_, 1907 (1960). 60. E.N. O f t e d a h l , J r . , Ph.D. T h e s i s , Northwestern U n i v e r s i t y , 1964. 61. Rama K. Chaturvedi, Andrew E. MacMahon, and Gaston L. Schmir, J . Am. Chem. Soc. 89, 6984 (.1967). 62. E. Hogfeldt and J . B i g e l e i s e n , J . Am. Chem. Soc. 8_2, 15 (1960). 63. R.P. B e l l , The Proton i n Chemistry, C o r n e l l U n i v e r s i t y P r ess, 1959. 64. R.E. Robertson, Progr. Phys. Org. Chem. 4_, 213 (1967). 65. J.A. H i r s c h , Topics i n Stereochemistry 1_, 199 (1967). 66. Michael Hanach, Conformation Theory, p. .103, Academic Press, 1965. 67. Ernest L. E l i e l , Stereochemistry of Carbon Compounds, p. 236, McGraw-Hill Book Company, Inc., 1962. 68. K.B. Wiberg and Ross Stewart, J . Am. Chem. Soc. 78,1214 (1956). 69. R.A. Robinson and R.H. Stokes, E l e c t r o l y t e S o l u t i o n s , Butterworths S c i e n t i f i c P u b l i c a t i o n s , 1959. 70. Ref. 69, pp. 517 and 526. 71. L.L. Schaleger and F.A. Long,Advan. Phys. Org. Chem. 1_, 1 (1963) . 72. 0. Rogne, J . Chem. Soc. B_, 1294 (1968). 73. J . M i l l e r , Aromatic N u c l e o p h i l i c S u b s t i t u t i o n , E l s e v i e r , 196.8. 74. C A . Bunton, N u c l e o p h i l i c S u b s t i t u t i o n at a Saturated Carbon, E l s e v i e r , 1964. 75. G.V. Bakore and Rama Shankar, Indian J . Chem. 1_, 108 (1963). 76. G.V. Bakore and Rama Shankar, Indian J . Chem. l_, 268 (1963). 77. G.V. Bakore and Rama Shankar, Indian J . Chem. 1_, 331 (1963). 78. J . C Sheppard and Arthur C. Wahl, J . Am. Chem. Soc. 79_, 1020 (1957). 79. Ref. 63, p. 188. 80. J.R.H. H u l e t t , Quart. Revs. 18_, 227 (1964). 81. J.R. H u l e t t , J . Chem. Soc. 468 (1960). 82. R.P. B e l l , J.A. Fendley, and J.R. H u l e t t , Proc. Royal Soc. 235, 453 (1956). 83. V.J. Shiner, J r . , and M.L. Smith, J . Am. Chem. Soc. 83, 593 (1961). 84. V.J. Shiner, J r . , and B r i a n M a r t i n , Pure and A p p l i e d Chemistry 8_, 371 (1964) . 85. R.P. B e l l and D.P. Onwood, J . Chem. Soc. B, 150 (1967). 86. E.S. Lewis and J.K. Robinson, J . Am. Chem. Soc. 90, 4337 (1968). 87. C.G. Swain, E.C. S t i v e r s , J.F. Reuwer, J r . , and L.J. Schaad, J . Am. Chem. Soc. 80_, 5885 (1958). 88. F.H. Westheimer, Chem. Revs. 61_, 265 (1961). 89. G. Hammond, J . Am. Chem. Soc. 7J_, 334 (1955). 90. John A. Muzzio, Ph.D. T h e s i s , Purdue U n i v e r s i t y , 1965. 91. G.G. Smith and R.P. Bayer, Tetrahedron 1_8, 323 (1962). 92. Michael M. Mocek, Ph.D. T h e s i s , U n i v e r s i t y of B r i t i s h Columbia, 1962. 93. Robert D. Stolow, J . Am. Chem. Soc. 81, 5806 (1959). APPENDIX A The d e r i v a t i o n s of Equations 10. and 13. from the General Exper-imental s e c t i o n are presented here. Equation 10. r e f e r s to the r e a c t i o n i n b a s i c s o l u t i o n i n which the s t o i c h i o m e t r y i s as f o l l o w s - -i 2MnO"4 + H 2Z + 20H" — > 2MnO% + Z + H 20. The r a t e constant k i s def i n e d by Equation i i . i i _ i l ^ j O j i i = k[MnO\][H 2Z] I f permanganate and su b s t r a t e are i n i t i a l l y present i n the s t o i c h i o -m e t r i c c o n c e n t r a t i o n r a t i o , a s p e c i a l i n t e g r a t e d form of Equation i i i s obtained,which i s Equation 9. However, i f the i n i t i a l r a t i o , which w i l l be c a l l e d 1/a, i s not 2, a d i f f e r e n t i n t e g r a t e d form r e s u l t s . Beginning w i t h Equation i i then, the r a t e may be expressed en-t i r e l y i n terms o f the instantaneous permanganate c o n c e n t r a t i o n ([MnOt f]) 7 the i n i t i a l permanganate c o n c e n t r a t i o n ([MnO LJO) a n d a> where a has been defined as [H 2Z]o/[MnO ii]o- The r e s u l t i s Equation i i i . i i i _ dJWnOjJ = k [ M n 0 \ ] j a [ M n 0 " \ ] o - \ ( [ M n O \ ] 0 - [MnO\])} Equation i i i s i m p l i f i e s to i v . i v - d [ d " ° h ] = \ k ^ n O M ^ M n O M + (2a-l) [MnO\] 0} I n t e g r a t i o n o f i v between the l i m i t s of [MnO^]Q to [MnO ^] and t = 0 to t leads to Equation v. i k t - 1 „_ [MnO"tJ + ( 2 a - l ) [ M n O \ ] 0 2*z (2a-l) [MnO-tJo 2a[MnO"4] The c o n c e n t r a t i o n terms w i t h i n the l o g a r i t h m i c f u n c t i o n i n Equation v can be expressed i n terms o f the volume of t h i o s u l f a t e needed to t i t r a t e an a l i q u o t o f the r e a c t i o n mixture. Let us assume for- s i m p l i c i t y that the volume of the a l i q u o t and the t h i o s u l f a t e c o n c e n t r a t i o n are unity, s i n c e these f a c t o r s w i l l cancel out e v e n t u a l l y . Bearing i n mind that the a n a l y s i s measures the o x i d i z i n g power of the s o l u t i o n f o r a l l manganese species above o x i d a t i o n s t a t e two, we have at t = 0 v i [MnO\] = ^ • At times other than the beginning of the r e a c t i o n we must r e l y on the known s t o i c h i o m e t r y to determine [MnO LJ . At time t the volume of t i t r a n t (V ) i s r e l a t e d to the composition of the s o l u t i o n by Equation v i i . v i i V = 5 [MnO" 4 ] + 4[MnO%] the manganate c o n c e n t r a t i o n ([MnO i j ) can be r e l a t e d to the concen-t r a t i o n of permanganate by Equation v i i i . v i i i [MnO%] = [MnO\] 0 - [Mn0" 4] Combining Equations v i , v i i and v i i i to e l i m i n a t e the manganate con-c e n t r a t i o n gives f i n a l l y Equation i x . i x [MnO"J = V 0 - i V t S u b s t i t u t i o n of v i and i x i n t o Equation v leads to Equation x. 2 (2a-l) [MnO-1, J 0 £n + V 0(2a-5)/5  2 a ( V - 4 V 0 5 -Expressing Equation x i n terms of the decadic logarithm and [ H 2 Z ] Q gives Equation x i a f t e r s l i g h t rearrangement. x i k t 4.606 a ( 2 a - l ) [ H 2 Z ] 0 l o S V t + V 0(2a-5)/5  2 a ( V - 4V 0) 5 - J Equation x i i s i d e n t i c a l to Equation 10, quoted i n the General Experimental s e c t i o n . Equation 13. i s used when the f o l l o w i n g s t o i c h i o m e t r y o b t a i n s : x i i 2Mn0\ + 3H 2Z —>• 2Mn02 + 3Z + 20H" + 2H 20. Expressing Equation i i i n terms of permanganate concentration, w h i l e c o n s i d e r i n g the s t o i c h i o m e t r y of Equation x i i , g ives Equation x i i i . x i i i l l L ^ O j J = k[MnO\]|a[MnO\] 0 - | ( [ M n O \ ] 0 - [MnO\]) S i m p l i f i c a t i o n o f x i i i g ives x i v x i v l U M B O j i i = | k [MnO\]|[MnO\] + (§ a-1) [Mn0\] 0 | By i n t e g r a t i o n of Equation x i v between the l i m i t s o f [MnO 4]Q to [MnO and t = 0 to t Equation xv i s obtained. 2 xv A v t - 1 o n [MnQ\] + (3a-l)[MnO"^] 0  X Y 2 K Z ~ (2a-l) [MnO-^lo 2a[Mn0"\] 3 Again we have x v i [MnO"\] = ^ and because of the new s t o i c h i o m e t r y x v i i V = SfMnO'tt] + 2[Mn0 2] and x v i i i [Mn0 2] = (MnO\] - [Mn0\] • E l i m i n a t i n g [Mn0 2] from x v i , x v i i and x v i i i leads to x i x x i x [MnOYJ = j CVt - | V 0) A f t e r s u b s t i t u t i o n of x i x and x v i i n t o xv, Equation xx_^is obtained, J L V t + Vo(2a-5)A 2a 1 V - 2V 0/5 3 u_ t Expressing xx i n terms of [H 2Z]Q and the decadic logarithm leads to 3 1 X X 2 k t = (2a-1)[MnO - 4Jo Equation x x i a f t e r s l i g h t rearrangement. 4.606 a k t = 2 a - 3 ) [ H 2 Z ] 0 l 0 g _3 V + V 0(2a-5)/5 2a ' V t - 2V 0/5 Equation x x i i s Equation 13 considered i n the General Experimental s e c t i o n . 

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