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60 The Mechanism of Alkane Oxidation by

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Ozone G O R D O N A . HAMILTON, BRUCE THOMAS M. HELLMAN

S.

RIBNER,

and

Pennsylvania State University, University Park, P a . , 16802 and Princeton University, Princeton, N. J. 08540

The characteristics of the initial step in the reaction of ozone with saturated hydrocarbons have been investigated. Ozonation of cyclohexane gives initially cyclohexanol and cyclohexanone in a 3:1 ratio. Cyclohexane is oxidized 4.5 times more rapidly than cyclohexane-d . The relative reactivity of primary, secondary, and tertiary hydrogens is approximately 1:13:110. The ozonation of tertiary hydrogens to tertiary alcohols occurs with 60 to 70% retention of configuration. The presence of good hydrogen atom donors, antioxidants, and a number of other reagents has only a small effect on the percent retention of configuration. These results and others are compared with those obtained for other hydrocarbon reactions, and a mechanism for the ozonation is suggested. 12

A s a result of o u r interest i n the m e c h a n i s m of b i o l o g i c a l oxidations of saturated h y d r o c a r b o n s ( I I ) , w e have i n v e s t i g a t e d the m e c h a n i s m s of several alkane oxidations (12, 13).

T h i s p a p e r reports o u r studies o n

the o x i d a t i o n of saturated h y d r o c a r b o n s b y ozone.

A l t h o u g h there are

f r e q u e n t references i n the literature to the o x i d a t i o n of alkanes b y ozone (2),

t h e m e c h a n i s m of the r e a c t i o n has r e c e i v e d r e l a t i v e l y little s t u d y .

D u r l a n d a n d A d k i n s (7) r e p o r t e d that cis- a n d J r a n s - D e c a l i n are o x i d i z e d i n reasonable y i e l d to tertiary alcohols w i t h r e t e n t i o n of c o n f i g u r a t i o n . S c h u b e r t a n d Pease (24)

s t u d i e d the gas-phase o z o n a t i o n of alkanes at

r o o m t e m p e r a t u r e a n d suggested that the p r o d u c t s arose f r o m the f o r m a ­ t i o n a n d f u r t h e r reactions of R O ' a n d H O O * .

A c o m p l i c a t i n g feature i n

these investigations w a s the necessity to c a r r y o u t the o x i d a t i o n to r e l a ­ t i v e l y h i g h conversions so that the p r o d u c t s c o u l d b e a n a l y z e d . 15 In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

Since

16

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O F ORGANIC

COMPOUNDS

III

the i n i t i a l alkane o x i d a t i o n p r o d u c t s are m o r e reactive t o w a r d ozone t h a n the alkane, t h e o b s e r v e d p r o d u c t s f r e q u e n t l y arise as t h e result of several steps.

W i t h t h e a v a i l a b i l i t y of sensitive gas c h r o m a t o g r a p h i c

methods

it is n o w possible to a n a l y z e f o r p r o d u c t s after v e r y l o w conversions, a n d thus t h e i n i t i a l step i n alkane o z o n a t i o n c a n b e s t u d i e d separately. investigation,

some

of t h e characteristics

of this

initial

step

In our were

determined.

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Experimental Materials. U n l e s s d e s c r i b e d o t h e r w i s e , c o m m e r c i a l materials, w h i c h w e r e u s u a l l y r e d i s t i l l e d a n d w h i c h w e r e s h o w n b y gas c h r o m a t o g r a p h y to b e either free of i m p u r i t i e s o r free of i n t e r f e r i n g i m p u r i t i e s , w e r e u s e d t h r o u g h o u t . C y c l o h e x a n e a n d 2 - m e t h y l b u t a n e w e r e refluxed w i t h l i t h i u m a l u m i n u m h y d r i d e before being distilled. cis-Decalin was obtained f r o m A l d r i c h C h e m i c a l C o m p a n y a n d frans-Decalin was obtained b y isomerizing commercial D e c a l i n w i t h aluminum trichloride followed b y fractional d i s t i l l a t i o n (14). G a s c h r o m a t o g r a p h i c analysis i n d i c a t e d that there w a s less t h a n 1 % trans i n t h e cis solvent a n d less t h a n 2 % cis i n t h e trans solvent. Cyclohexane-di2 w a s o b t a i n e d f r o m N u c l e a r E q u i p m e n t C h e m i ­ cal Corp. a n d h a d 99.3% deuterium. Cis- a n d £rans-l,2-dimethylcyclohexanol-l were prepared b y J. R. G i a c i n b y t h e m e t h o d of C h i u r d o g l u (6) a n d i s o l a t e d b y t h e p r o c e d u r e of N e v i t t a n d H a m m o n d (20). T h e d s - a l c o h o l w a s n o t o b t a i n e d p u r e b u t as a m i x t u r e of cis a n d trans. T h e c o m p o s i t i o n of the m i x t u r e w a s d e t e r m i n e d b y a c o m b i n a t i o n of gas c h r o m a t o g r a p h y a n d n u c l e a r m a g ­ netic resonance. T h e cis- a n d £rans-9-decalols w e r e p r e p a r e d b y J . R . G i a c i n b y oxidizing the corresponding hydrocarbons w i t h chromic an­ h y d r i d e i n acetic a c i d - a c e t i c a n h y d r i d e b y the m e t h o d of L e h r (16). T h e crude products were purified b y alumina chromatography followed b y s u b l i m a t i o n . Samples of the i s o m e r i c n o r b o r a n o l s a n d norbornanones w e r e o b t a i n e d f r o m P a u l v o n R . Schleyer. Reaction Conditions. T h e o z o n e - o x y g e n m i x t u r e u s e d i n these reac­ tions w a s o b t a i n e d f r o m either a W e l s b a c h T - 2 3 or T-408 L a b o r a t o r y O z o n a t o r . W h e n p u r e o x y g e n w a s f e d i n t o t h e o z o n a t o r at t h e rate of 0.6 l i t e r / m i n . , t h e effluent w a s ca. 5% ozone as d e t e r m i n e d b y i o d o m e t r i c t i t r a t i o n . A s m a l l f r a c t i o n of this stream g i v i n g 0 . 5 - 1 m g . of o z o n e p e r m i n u t e w a s b u b b l e d t h r o u g h 2 - 1 0 m l . of h y d r o c a r b o n solvent c o n t a i n e d i n a s m a l l flask fitted w i t h a c o l d finger condenser ( t o m i n i m i z e solvent e v a p o r a t i o n ) . M o s t of o u r results w e r e o b t a i n e d f r o m c o m p e t i t i o n e x p e r i ­ ments either w i t h k n o w n mixtures of solvents o r w i t h c o m p o u n d s w h i c h c a n react t o give several p r o d u c t s . I n a f e w experiments the t o t a l y i e l d o f c y c l o h e x a n o l a n d c y c l o h e x a n o n e o b t a i n e d f r o m t h e o x i d a t i o n of c y c l o ­ hexane at r o o m t e m p e r a t u r e w a s estimated to b e 0.2 t o 0.3 m g . / m i n . I n cases w h e r e the r e a c t i o n solutions w e r e r e d u c e d f o l l o w i n g o x i d a ­ t i o n , t h e s o l u t i o n w a s d i l u t e d w i t h ca. 50 m l . ether, a n excess (0.15 g r a m ) of l i t h i u m a l u m i n u m h y d r i d e w a s a d d e d , t h e m i x t u r e r e f l u x e d f o r 2 h o u r s a n d t h e n c o o l e d , 0.4 m l . saturated s o l u t i o n of s o d i u m sulfate w a s a d d e d , the r e s u l t i n g suspension w a s filtered, t h e ether w a s d i s t i l l e d off u n t i l 5 - 1 0 m l . r e m a i n e d , a n d this s o l u t i o n w a s injected i n t o t h e gas c h r o m a t o g r a p h

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

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60.

HAMILTON

E TA L .

Alkane

17

Oxidation

for analysis. I n controls w h e r e k n o w n amounts of p r o d u c t s w e r e present, essentially a l l t h e c a r b o n y l c o m p o u n d s w e r e r e d u c e d to alcohols, a n d over 9 5 % of t h e alcohols w e r e r e c o v e r e d b y this p r o c e d u r e . Analyses. T h e oxidation products were determined using a PerkinE l m e r m o d e l 800 gas c h r o m a t o g r a p h e q u i p p e d w i t h flame i o n i z a t i o n detectors. I n t h e c o m p e t i t i o n experiments t h e r e l a t i v e amounts of mate­ r i a l w e r e c a l c u l a t e d b y m u l t i p l y i n g either t h e p e a k heights or p e a k areas b y c o n v e r s i o n factors d e t e r m i n e d u s i n g k n o w n amounts of t h e p r o d u c t s . P r e l i m i n a r y experiments i n d i c a t e d that p e a k heights or p e a k areas gave the same amounts of materials w h e n m u l t i p l i e d b y t h e a p p r o p r i a t e c o n ­ v e r s i o n factors. P e r k i n - E l m e r 12-foot c o l u m n s p a c k e d w i t h C h r o m o s o r b W a n d c o n t a i n i n g t h e l i q u i d phases p o l y p r o p y l e n e g l y c o l ( P e r k i n - E l m e r d e s i g n a t i o n R ) a n d fluorinated silicone o i l ( P e r k i n - E l m e r d e s i g n a t i o n F S - 1 2 6 5 ) gave c o n v e n i e n t separations. T h e last l i q u i d phase w a s u s e d for t h e d e c a l o l d e t e r m i n a t i o n s , a n d the first w a s u s e d f o r a l l others. U s u a l l y a s m a l l s a m p l e ( 1 - 2 /Jiters) of t h e r e a c t i o n s o l u t i o n w a s i n j e c t e d d i r e c t l y i n t o t h e gas c h r o m a t o g r a p h f o r analysis. H o w e v e r , to ensure that other p r o d u c t s w e r e n o t affecting the stereospecificity experiments, representative samples of t h e v a r i o u s systems s t u d i e d w e r e r e d u c e d w i t h l i t h i u m a l u m i n u m h y d r i d e b e f o r e analysis. T h e ratios of t e r t i a r y alcohols o b t a i n e d f o l l o w i n g r e d u c t i o n w e r e a l t e r e d o n l y s l i g h t l y i n a f e w cases, a p p a r e n t l y because some k e t o n i c p r o d u c t s w e r e e l u t e d f r o m t h e c o l u m n at t h e same t i m e as t h e t e r t i a r y alcohols. I n s u c h cases t h e results q u o t e d are those o b t a i n e d after r e d u c t i o n .

Results F o l l o w i n g o z o n a t i o n of c y c l o h e x a n e f o r short p e r i o d s at r o o m t e m ­ perature, o n l y t w o o x i d a t i o n p r o d u c t s — c y c l o h e x a n o l a n d c y c l o h e x a n o n e — w e r e o b s e r v e d i n significant amounts o n gas c h r o m a t o g r a p h i c analysis. P o s s i b l y some m u c h less v o l a t i l e p r o d u c t s (e.g., r i n g f r a g m e n t a t i o n p r o d ­ ucts, vide infra)

w e r e also f o r m e d b u t n o t d e t e c t e d b y t h e gas c h r o m a t o ­

g r a p h i c p r o c e d u r e . A f t e r 5 m i n u t e s of o z o n a t i o n t h e ratio of c y c l o h e x a ­ none to c y c l o h e x a n o l w a s 0.3 to 0.35, b u t t h e r a t i o r a p i d l y i n c r e a s e d to 1.5 to 2 after 1 h o u r . T h e result indicates that even after v e r y l o w c o n ­ version the i n i t i a l l y f o r m e d c y c l o h e x a n o l is o x i d i z e d f u r t h e r b y ozone (2).

C o n f i r m a t i o n of this w a s o b t a i n e d w h e n a s m a l l a m o u n t ( 2 0 m g . )

of c y c l o h e x a n o l was a d d e d to 10 m l . of c y c l o p e n t a n e a n d t h e s o l u t i o n w a s ozonized under the usual conditions.

Some

cyclopentanol a n d cyclo-

pentanone w e r e f o r m e d , b u t i n a d d i t i o n , over 8 0 % of t h e c y c l o h e x a n o l was o x i d i z e d to c y c l o h e x a n o n e after 1 h o u r . H o w e v e r , n o t a l l t h e c y c l o ­ hexanone

obtained i n the cyclohexane

o x i d a t i o n of c y c l o h e x a n o l .

o z o n a t i o n arises

from

further

If t h e o b s e r v e d ratio of c y c l o h e x a n o n e t o

c y c l o h e x a n o l is p l o t t e d vs. time, a n d the c u r v e is e x t r a p o l a t e d to zero t i m e , one obtains a ratio at t i m e zero of 0.25 to 0.3. T h i s indicates that some of t h e c y c l o h e x a n o n e

is f o r m e d d i r e c t l y f r o m a n i n t e r m e d i a t e i n t h e

ozonation.

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

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C y c l o h e x a n o n e is o x i d i z e d f u r t h e r o n l y s l o w l y u n d e r o u r o z o n a t i o n c o n d i t i o n s . O z o n a t i o n of 30 m g . of c y c l o h e x a n o n e i n 7 m l . of c y c l o p e n tane for 1 h o u r l e d to the o x i d a t i o n of o n l y 1 0 % T h e o x i d a t i o n of c y c l o h e x a n e

of the

cyclohexanone.

requires the presence of o z o n e ;

control

experiments, w h e r e u n o z o n i z e d o x y g e n was passed t h r o u g h the c y c l o ­ hexane w i t h a l l other c o n d i t i o n s the same, gave no detectable amounts of o x i d a t i o n p r o d u c t s . T h e k i n e t i c d e u t e r i u m isotope effect for the r e a c t i o n of c y c l o h e x a n e w i t h ozone was o b t a i n e d f r o m the c o m p e t i t i o n experiments s u m m a r i z e d

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i n T a b l e I. Since the solvent is i n large excess, the ratio fcn/fcp w a s c a l c u Table I.

Ozonation Time, min.

Deuterium Isotope Effect for the Ozonation of Cyclohexane at 2 2 ° C .

20

Cyclohexane (50 % ) Cyclopentane (50%)

20

Cyclohexane-d Cyclopentane

50 50

Molar Ratio of Cyclohexane to Cyclopentane Products

Solvent Composition, mole %

Cyclohexane Cyclopentane

12

0.94 4.5

(50%) (50%)

0.21

(50%) (50%)

1.10 4.1

Cyclohexane-d > (50%) Cyclopentane (50 % ) 1L

0.27

l a t e d b y s i m p l y d i v i d i n g the m o l a r ratio of c y c l o h e x a n e to c y c l o p e n t a n e o x i d a t i o n p r o d u c t s o b t a i n e d w i t h c y c l o h e x a n e present b y that w i t h cyclohexane-di » L

after the same o z o n a t i o n t i m e .

obtained

It is not k n o w n

w h y the ratio of p r o d u c t s increases s l i g h t l y or w h y the a p p a r e n t isotope effect decreases s l i g h t l y w i t h time. P e r h a p s it is c a u s e d b y different rates for the f u r t h e r o x i d a t i o n of the i n i t i a l o x i d a t i o n p r o d u c t s .

Nevertheless,

it is clear that there is a sizeable isotope effect for the o z o n a t i o n reaction, a n d k /k H

})

is p r o b a b l y b e t w e e n 4.5 a n d 5 for v e r y l o w conversions w h e n

f u r t h e r o x i d a t i o n of the p r o d u c t s w o u l d have a m i n i m a l effect. The

r e a c t i v i t y of ozone t o w a r d p r i m a r y , secondary,

and

tertiary

h y d r o g e n s was d e t e r m i n e d f r o m experiments w h e r e 2 - m e t h y l b u t a n e

was

o z o n i z e d . T h e s e experiments w e r e p e r f o r m e d at 0 ° C . to decrease solvent loss b y e v a p o r a t i o n d u r i n g o z o n a t i o n .

T o s i m p l i f y the analysis of

p r o d u c t s , the r e a c t i o n m i x t u r e f o l l o w i n g o z o n a t i o n was r e d u c e d

the with

l i t h i u m a l u m i n u m h y d r i d e . T h e relative r e a c t i v i t y per h y d r o g e n , c a l c u ­ l a t e d f r o m the o b s e r v e d quantities of the f o u r isomeric C , alcohols, i s : r

p r i m a r y , 1; secondary,

13; tertiary, 110.

T h e s e values are t i m e i n d e ­

p e n d e n t for u p to 1 h o u r o z o n a t i o n . H o w e v e r , t h e y m a y not be a c o m -

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

60.

HAMILTON

Alkane

E T AL.

19

Oxidation

p l e t e l y accurate measure of t h e r e a c t i v i t y of t h e various h y d r o g e n s b e ­ cause some f r a g m e n t a t i o n p r o d u c t s , i n c l u d i n g ethanol, 2 - p r o p a n o l , a n d other m i n o r p r o d u c t s , w e r e also o b s e r v e d . T h e s e f r a g m e n t a t i o n p r o d u c t s w e r e f o r m e d i n smaller quantities t h a n t h e C , alcohols, a n d they c o u l d r

not alter t h e r e l a t i v e reactivities q u o t e d b y m o r e t h a n 2 5 % . relative y i e l d s of t h e C , alcohols r

Thus, the

(following reduction with

a l u m i n u m h y d r i d e ) s h o u l d b e a f a i r l y g o o d measure

lithium

of t h e relative

reactivities of the v a r i o u s h y d r o g e n s . T h e stereospecificity of t h e h y d r o c a r b o n o z o n a t i o n w a s i n v e s t i g a t e d

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b y m e a s u r i n g t h e isomer d i s t r i b u t i o n of tertiary alcohols f o r m e d o n o z o n a t i n g cis- a n d £rans-l,2-dimethylcyclohexane a n d cis- a n d lin.

trans-Deca-

O t h e r o x i d a t i o n p r o d u c t s are f o r m e d i n these ozonations, b u t t h e

t e r t i a r y alcohols a r e easily separated f r o m these b y gas c h r o m a t o g r a p h y . Some results are s h o w n i n T a b l e I I . T h e o b s e r v e d isomer d i s t r i b u t i o n s of t e r t i a r y alcohols are i n d e p e n d e n t of t i m e f o r u p to 3 hours o z o n a t i o n Table II.

Hydrocarbon Solvent

a

Isomer Distribution of Tertiary Alcohols from the Ozonation of cis- and trans-Hydrocarbons Isomer Distribution of Hydrocarbon Solvent, % cis trans

T,°C.

Isomer Distribution of Tertiary Alcohols, % trans cis

D M C

100 100 0 0 68 26

0 0 100 100 32 74

22 -48 22 -48 22 22

85 91 21 20 78 59

15 9 79 80 22 41

Decalin

100 100 0 0 62 36

0 0 100 100 38 64

22 0 22 0 22 22

85 85 20 29 79 68

15 15 80 71 21 32

1,2-Dimethylcyclohexane.

a n d are r e p r o d u c i b l e to ± 2 % .

C l e a r l y t h e f o r m a t i o n of t e r t i a r y alcohols

occurs w i t h c o n s i d e r a b l e b u t n o t c o m p l e t e

r e t e n t i o n of c o n f i g u r a t i o n

( e a r l i e r results b y others (7, 17) w i t h less sensitive a n a l y t i c a l procedures i n d i c a t e d almost c o m p l e t e r e t e n t i o n of c o n f i g u r a t i o n ) .

T h e observation

that t e m p e r a t u r e has s u c h l i t t l e effect o n the isomer d i s t r i b u t i o n suggests that i t is u n l i k e l y that t h e lack of c o m p l e t e stereospecificity is c a u s e d b y t w o d i s t i n c t l y different m e c h a n i s m s o p e r a t i n g s i m u l t a n e o u s l y . B e c a u s e the cis- a n d f r a n s - h y d r o c a r b o n s g i v e different ratios of tertiary alcohols i t is possible to d e t e r m i n e t h e r e l a t i v e r e a c t i v i t y of t h e t e r t i a r y positions of these h y d r o c a r b o n s b y u s i n g k n o w n mixtures of the h y d r o c a r b o n s . F r o m

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

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COMPOUNDS

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the results i n T a b l e II one calculates that the t e r t i a r y positions o n cis-1,2d i m e t h y l c y c l o h e x a n e are f o u r times m o r e reactive t h a n those of dimethylcyclohexane.

trans-1,2-

A s s u m i n g that the a x i a l t e r t i a r y h y d r o g e n of the

cis c o m p o u n d has the same r e a c t i v i t y as e a c h of the a x i a l t e r t i a r y h y d r o ­ gens of the trans c o m p o u n d ( 8 ) , one calculates that the e q u a t o r i a l tertiary h y d r o g e n is seven times m o r e reactive t h a n a x i a l ones.

S i m i l a r l y , the

t e r t i a r y h y d r o g e n s of ci-s-Decalin are 5.6 times m o r e reactive t h a n those of f r a n s - D e c a l i n . T h e effect of v a r i o u s a d d i t i v e s o n the isomer d i s t r i b u t i o n of tertiary

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alcohols,

obtained

from d$-l,2-dimethylcyclohexane,

was

investigated

to d e t e r m i n e the reason for the l a c k of c o m p l e t e stereospecificity i n the ozonation.

T h e results are s u m m a r i z e d i n T a b l e III.

N o n e of the a d d i -

Table III. Isomer Distribution of Tertiary Alcohols from the Ozonation of cK-l,2-Dimethylcyclohexane at 2 2 ° C . in the Presence of Various Additives Isomer Distribution of Tertiary Alcohols Solvent Composition, mole % from c i s - D M C , % trans cis-DMC cis Additive

Additive None Cumene Chloroform Nitrobenzene Benzophenone E t h y l acetate 2,4-Di-tert-butylphenol Diphenylamine Iodine Bromotrichloromethane

15 15 15 15 18 21 27 30 30 20

85 85 85 85 82 79 73 70 70 80

100 88 38 44 91 43 91 92 93 84

0 12 62 56 9 57 9 8 7 16

tives has a d r a m a t i c effect. Some of the results m a y arise f r o m a g e n e r a l solvent effect w h i c h requires f u r t h e r i n v e s t i g a t i o n . H o w e v e r , since none of the a d d i t i v e s increases the stereospecificity of the o z o n a t i o n , several m e c h a n i s m s w h i c h m i g h t h a v e e x p l a i n e d the p a r t i a l loss of ficity c a n be e l i m i n a t e d (see L o n g (17)

stereospeci­

Discussion).

o b s e r v e d that o z o n a t i o n of n o r b o r n a n e

(bicyclo-2,2,l-hep-

t a n e ) i n C C 1 at 0 ° C . gives o n l y e x o - 2 - n o r b o r n a n o l a n d 2 - n o r b o r n a n o n e . 4

W e have c o n f i r m e d this result u s i n g c y c l o h e x a n e as solvent a n d gas c h r o ­ m a t o g r a p h y f o r analysis; less t h a n 2 % formed.

of a n y other a l c o h o l or ketone is

E n d o - 2 - n o r b o r n a n o l c o u l d not h a v e b e e n f o r m e d i n i t i a l l y a n d

t h e n r a p i d l y o x i d i z e d to 2 - n o r b o r n a n o n e .

I n a control experiment 6 m g .

of e n d o - 2 - n o r b o r n a n o l w e r e a d d e d to 1.7 grams n o r b o r n a n e i n 8 m l . of cyclohexane

a n d o z o n i z e d f o r 95 m i n u t e s .

Then, 75%

of the

endo-2-

n o r b o r n a n o l w a s o x i d i z e d . T h u s , it is o x i d i z e d u n d e r the r e a c t i o n c o n d i -

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

60.

HAMILTON

ET

Alkane

AL.

21

Oxidation

tions, b u t this r e a c t i o n is s l o w e n o u g h that if 2 % of the o x i d a t i o n p r o d u c t s w e r e this c o m p o u n d , it c o u l d h a v e b e e n detected.

B y c o m p a r i n g the

y i e l d s of n o r b o r n a n e o x i d a t i o n p r o d u c t s w i t h those o b t a i n e d f r o m c y c l o ­ hexane, a n d k n o w i n g the i n i t i a l solvent c o m p o s i t i o n , one c a n calculate that p e r h y d r o g e n the exo h y d r o g e n s of n o r b o r n a n e are o n l y 1.3 times m o r e reactive t h a n the h y d r o g e n s of c y c l o h e x a n e . Some peroxides are f o r m e d w h e n saturated h y d r o c a r b o n s are o z o n ­ i z e d at r o o m temperature.

F o r e x a m p l e , w h e n 1.07 m m o l e s of ozone are

b u b b l e d ( d u r i n g 2 h o u r s ) i n t o 8 m l . of d s - l , 2 - d i m e t h y l c y c l o h e x a n e , 0.26

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m m o l e s of ozone passes t h r o u g h the s o l u t i o n , a n d 0.31 m m o l e s p e r o x i d e [determined by iodometric titration (25)]

is f o r m e d i n the h y d r o c a r b o n

solvent. T h e i d e n t i t y of these peroxides has not yet b e e n d e t e r m i n e d .

Discussion T a b l e I V compares some of the characteristics of the o z o n a t i o n re­ a c t i o n w i t h those of some other h y d r o c a r b o n reactions w h o s e nisms h a v e b e e n s t u d i e d extensively. free r a d i c a l reactions, O—C(CH ) 3

3

prim

Ozonation Chromate oxidation Carbene insertions Nitrene insertions H abstraction by •O—C(CH ), Carbene-oxygen oxidation

by

i n its selectivity

C o m p a r i s o n of Some H y d r o c a r b o n R e a c t i o n s Relative Reactivity per H

Reaction

mecha­

resembles

s u c h as the a b s t r a c t i o n of h y d r o g e n atoms

a n d the c a r b e n e - o x y g e n o x i d a t i o n (12),

Table I V .

3

T h e ozonation reaction

Deuterium Isotope Effect(k /k )

Reference

70

4.5

This work

70-100

2.5

16,19,

1.2 (21)

100

1.3 to 2

15

sec

tert

1

13

110

1

110

7,000

1 (1)

1.0 (8)

% Retention of Configuration

H

D

1

10

30

100

1.5

1,

1

12

44

0

3.7

23, 26

1

15

140

0

4.6

12

28

5,18

t o w a r d various h y d r o g e n s a n d i n its d e u t e r i u m isotope effect. It is clear that the t r a n s i t i o n state for the o z o n a t i o n r e a c t i o n i n a l k a n e cannot

have m u c h c a r b o n i u m i o n character;

w o u l d be m u c h greater.

otherwise its

solvents

selectivity

T h e o b s e r v a t i o n that the exo h y d r o g e n s

of

n o r b o r n a n e d o not h a v e a n y s p e c i a l r e a c t i v i t y agrees w i t h this c o n c l u s i o n . A l s o , the t r a n s i t i o n state for the c h r o m a t e o x i d a t i o n of alkanes is b e l i e v e d

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

22

OXIDATION

OF

ORGANIC

to h a v e o n l y p a r t i a l c a r b o n i u m i o n character (22),

COMPOUNDS

III

a n d yet its selectivity

is m u c h greater. T h e h i g h degree of retention of c o n f i g u r a t i o n is different f r o m that u s u a l l y o b s e r v e d for free r a d i c a l reactions. I n the o z o n a t i o n experiments, o x y g e n was present at a p p r o x i m a t e l y 1 a t m . , a n d a l k y l r a d i c a l s react w i t h o x y g e n to g i v e alcohols a n d ketones

(21).

However, only racemized

a l c o h o l is f o r m e d w h e n s u c h r a d i c a l s are generated b y other m e t h o d s i n the presence of a n atmosphere of o x y g e n (3,

12).

T h u s , it is e v i d e n t

that most of the o z o n a t i o n r e a c t i o n cannot p r o c e e d t h r o u g h " f r e e " free

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r a d i c a l intermediates,

a n d the a l c o h o l w i t h r e t e n t i o n of c o n f i g u r a t i o n

m u s t be f o r m e d b y some d i r e c t r e a c t i o n of ozone w i t h the h y d r o c a r b o n . T h e o b s e r v e d r e t e n t i o n of c o n f i g u r a t i o n is s i m i l a r to that o b t a i n e d i n carb e n e a n d n i t r e n e i n s e r t i o n reactions.

Therefore, an insertion reaction

w h o s e t r a n s i t i o n state has c o n s i d e r a b l e r a d i c a l character is the m e c h a n i s m f o r the initial

step of the o z o n a t i o n w h i c h is i n best agreement w i t h the

d a t a . T h e details of the steps l e a d i n g to the f o r m a t i o n of r a c e m i z e d alco­ h o l , ketone, p e r o x i d e , a n d f r a g m e n t a t i o n p r o d u c t s are not c o m p l e t e l y clear at this t i m e . H o w e v e r , some possibilities for the o v e r - a l l m e c h a n i s m are o u t l i n e d i n the r e a c t i o n scheme b e l o w . It is suggested that the a l k a n e a n d

ROH'

( r a c e m i z e d ) + ketone +

per-

oxides + fragmentation p r o d u c t s

ozone react to g i v e a t r a n s i t i o n state ( o r solvent c a g e d i n t e r m e d i a t e ) , I or II, w h i c h has c o n s i d e r a b l e r a d i c a l character. If there is no p a r t i a l b o n d i n g a m o n g the v a r i o u s r a d i c a l s of I a n d II, t h e n t h e r m o d y n a m i c

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

60.

HAMILTON

ET

considerations (4)

AL.

Alkane

23

Oxidation

i n d i c a t e that I is m o r e l i k e l y t h a n I I .

H o w e v e r , if

the R - r a d i c a l is p a r t i a l l y b o n d e d to a n o x y g e n species either I or I I seem possible.

R e t e n t i o n of c o n f i g u r a t i o n i n the a l c o h o l p r o d u c t w o u l d

be e x p e c t e d if I or I I c o l l a p s e d d i r e c t l y to a l c o h o l a n d o x y g e n ( I I p o s s i b l y r e a c t i n g w i t h R O O O H as a n i n t e r m e d i a t e

(27)).

T o a c c o u n t for the

f o r m a t i o n of some r a c e m i z e d a l c o h o l , ketone, peroxides, a n d f r a g m e n t a ­ t i o n p r o d u c t s , it is suggested that I a n d I I c a n also separate i n t o the r a d i c a l s R • a n d H O •. A l k y l r a d i c a l s are k n o w n to react w i t h o x y g e n i n a series of steps to g i v e these other p r o d u c t

(21).

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M e c h a n i s m s f o r the f o r m a t i o n of r a c e m i z e d a l c o h o l , w h i c h i n v o l v e the R O - radical's a b s t r a c t i n g a h y d r o g e n a t o m f r o m the a l k a n e as, f o r example, i n the f o l l o w i n g sequence: R O O O H —» RO* + H O O R O - + R H -> R- + R O H (retention) R- + 0

2

—> R O H (racemized) + ketone + peroxides + fragmentation products

are not consistent w i t h the stereospecificity experiments w i t h v a r i o u s a d d i ­ tives ( T a b l e I I I ) .

M a n y of the a d d i t i v e s w o u l d h a v e t r a p p e d the R O -

r a d i c a l s , a n d thus no R - r a d i c a l s w o u l d b e f o r m e d a n d the p e r c e n t re­ t e n t i o n of c o n f i g u r a t i o n w o u l d h a v e i n c r e a s e d .

T h i s is the o p p o s i t e of

that o b s e r v e d . If some of the a d d i t i v e s c o u l d t r a p the R - r a d i c a l s , t h e n b y either of the above m e c h a n i s m s the p e r c e n t r e t e n t i o n of c o n f i g u r a t i o n s h o u l d increase.

H o w e v e r , o x y g e n w o u l d p r o b a b l y react too

rapidly

w i t h R - f o r it to b e t r a p p e d b y other species. T h e results r e p o r t e d here c o u l d also be e x p l a i n e d if ozone or a n i n t e r m e d i a t e s u c h as I or II c o u l d exist i n a singlet a n d a t r i p l e t f o r m . T h e p r o d u c t s w i t h r e t e n t i o n of c o n f i g u r a t i o n w o u l d t h e n arise f r o m the singlet species a n d the r a c e m i z e d p r o d u c t s f r o m the t r i p l e t . S o m e of the results w i t h a d d i t i v e s are consistent w i t h this h y p o t h e s i s : t h e

decreased

p e r c e n t r e t e n t i o n of c o n f i g u r a t i o n w i t h some a d d i t i v e s c o u l d b e c a u s e d b y catalysis of singlet to t r i p l e t interconversions.

Clearly more experi­

m e n t a l results are necessary to c l a r i f y this p o i n t . Regardless of the nature of the subsequent steps i n the r e a c t i o n , it seems clear f r o m the results here that the i n i t i a l step i n the o x i d a t i o n is a n i n s e r t i o n t y p e r e a c t i o n i n w h i c h the t r a n s i t i o n state has r a d i c a l char­ acter.

B e c a u s e the selectivity of ozone is greater t h a n that of

i n s e r t i o n species

other

( c a r b e n e s a n d n i t r e n e s ) , it is possible to s p e c i f y the

characteristics of intermediates or t r a n s i t i o n states ( s u c h as I or I I ) a greater extent.

to

H o w e v e r , it s h o u l d not be c o n c l u d e d that a l l ozone

reactions necessarily p r o c e e d b y s u c h a m e c h a n i s m . I n other cases w h e r e i o n i c intermediates are m o r e f a v o r e d (e.g., i n m o r e p o l a r solvents or i n cases w h e r e c a r b o n i u m ions are m o r e stable) it is possible that the t r a n ­ sition state for the r e a c t i o n has m o r e p o l a r character (9, 10,

27).

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

24

OXIDATION

O F ORGANIC

COMPOUNDS

III

E n z y m i c h y d r o x y l a t i o n s of saturated h y d r o c a r b o n s , w h i c h a p p a r e n t l y i n v o l v e t h e i n s e r t i o n of a n o x y g e n to g i v e alcohols w i t h r e t e n t i o n of c o n ­ figuration,

c o u l d p r e s u m a b l y o c c u r b y a m e c h a n i s m s i m i l a r to that p r o ­

p o s e d f o r the o z o n a t i o n r e a c t i o n .

I n t h e e n z y m i c reactions o x y g e n is the

oxidant, a n d the o v e r - a l l m e c h a n i s m is c l e a r l y m o r e c o m p l i c a t e d

than

that f o r o z o n a t i o n ( I I ) . H o w e v e r , i n these reactions p o s s i b l y some c o m p l e x e d f o r m of o x y g e n is c a p a b l e of a b s t r a c t i n g h y d r o g e n atoms a n d t h e n d o n a t i n g a h y d r o x y l r a d i c a l b e f o r e the a l k y l r a d i c a l has a n o p p o r t u n i t y to i n v e r t . T h e o v e r - a l l r e a c t i o n w o u l d b e a n i n s e r t i o n r e a c t i o n (11), b u t the

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t r a n s i t i o n state c o u l d h a v e r a d i c a l character, as o b s e r v e d f o r the o z o n a ­ tion reaction.

A cknowledgments S e v e r a l h e l p f u l discussions at t h e O x i d a t i o n S y m p o s i u m , especially w i t h P . S. B a i l e y , C . W a l l i n g , M . C . W h i t i n g , a n d S. W . B e n s o n are gratefully

acknowledged.

This

research

was supported

by

research

grants G M - 0 9 5 8 5 a n d G M - 1 4 9 8 5 f r o m t h e Institute of G e n e r a l M e d i c a l Sciences, P u b l i c H e a l t h Service, a n d i n part b y a grant to B . S. R . f r o m the

N a t i o n a l Science

Foundation

Undergraduate

Research

Program,

P r i n c e t o n U n i v e r s i t y . G . A . H . is a n A l f r e d P . S l o a n R e s e a r c h

Fellow

(1967-69).

Literature Cited

(1) Anastassiou, A. G., Simmons, H. E., J. Am. Chem. Soc. 89, 3177 (1967). (2) Bailey, P. S., Chem. Rev. 58, 925 (1958). (3) Bartlett, P. D., Pincock, R. E., Rolston, J. H., Schindel, W. G., Singer, L. A., J. Am. Chem. Soc. 87, 2590 (1965). (4) Benson, S. W., J. Am. Chem. Soc. 86, 3922 (1964). (5) Breslow, D. S., Prosser, T. J., Marcantonio, A. F., Genge, C. A., J. Am. Chem. Soc. 89, 2384 (1967). (6) Chiurdoglu, G., Bull. Soc. Chim. Beiges. 47, 241 (1938). (7) Durland, J. R., Adkins, H., J. Am. Chem. Soc. 61, 429 (1939). (8) Eliel, E. L., "Stereochemistry of Carbon Compounds," p. 211, McGrawHill, New York, 1962. (9) Erickson, R. E., Bakalik, D., Richards, C., Scanlon, M., Huddleston, G., J. Org. Chem. 31, 461 (1966). (10) Erickson, R. E., Myszkiewicz, T. M., J. Org. Chem. 30, 4326 (1965). (11) Hamilton, G. A., J. Am. Chem. Soc. 86, 3391 (1964). (12) Hamilton, G. A., Giacin, J. R., J. Am. Chem. Soc. 88, 1584 (1966). (13) Hamilton, G. A., Workman, R. J., Woo, L., J. Am. Chem. Soc. 86, 3390 (1964). (14) Jones, R., Linstead, R., J. Chem. Soc. 1936, 616. (15) Kirmse, W., "Carbene Chemistry," Academic Press, New York, 1964. (16) Lehr, R., Senior Thesis, Princeton University, Princeton, May, 1965. (17) Long, Jr., W. P., Ph.D. Thesis, Harvard University, 1955. (18) Lwowski, W., Maricich, T. J., J. Am. Chem. Soc. 87, 3630 (1965). (19) Mareš, F., Roček, J., Collection Czech. Chem. Commun. 26, 2370 (1961).

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ET

AL.

Alkane

Oxidation

(20) (21) (22) (23) (24) (25)

25

Nevitt, T., Hammond, G., J. Am. Chem. Soc. 76, 4124 (1954). Pryor, W. A., "Free Radicals," McGraw-Hill, New York, 1966. Rocek, J., Tetrahedron Letters 1962, 135. Russell, G. A., J. Am. Chem. Soc. 79, 3871 (1957). Schubert, C. C., Pease, R. N., J. Am. Chem. Soc. 78, 2044 (1956). Wagner, C. D., Smith, R. H., Peters, E. D., J. Anal. Chem. 19, 976 (1947). (26) Walling, C., Thaler, W., J. Am. Chem. Soc. 83, 3877 (1961). (27) White, H. M., Bailey, P. S., J. Org. Chem. 30, 3037 (1965). (28) Wiberg, K. B., Foster, G., J. Am. Chem. Soc. 83, 423 (1961). October 9, 1967.

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RECEIVED

In Oxidation of Organic Compounds; Mayo, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1968.