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3516 J ourna l

l inkage at C-9 in the real substrate (3) .

(16) (a) G. A. Berchtold and G. F. Uh lig, J. Org. Chem., 28, 1459 (1963); (b) K.

C. Brannock. R . D. Burpitt, and

J.

G. Thwe att, ibid., 28, 1462 (1963); (c)

C. F. Huebner,

L.

Dorfmann, M. M. Robinson, E. Donog hue, W. G. Pierson,

and P. Strachan , hid., 28, 3134 (1963); (d) K. C. Brannoc k,

R.

D. Burpitt,

V.

W .

Goodiett, and J. G. Thweatt, ibid., 29, 8 18 (1964).

(17)

R.

Ratcliffe and R . Rodehorst, J.

Org.

Chem., 35, 4000 (1970) .

(18) The trans-fused symmetrical ketone analogous to 32 has a C-2 axis.

Therefore, the m ethyl groups are equivalent and the trans ketone would

only exhibit seven signals. The cis-fused diketone

32,

on the other hand,

has no

C-2

axis and thus the methyl groups are diastereotopic.

(19)

The methyl peaks of

32

also overlapped in the 'H NMR. The Eu(fod)3

spectrum shifted them from 6

1

.O

o

two singlets at 6 3 .0 and 3.05.

(20) H. C. Brown and

S.

Krishnamurthy, J. Am. Chem. SOC., 94, 7159

(1972) .

(21)

G. Hofle and

W.

Steglich, Synthesis,

619 (1972),

and references cited

therein.

(22) N.

S.

hacca,J. E. Gurst, and D.

H.

Wil l iams, J. Am.

Chem. SOC.

7, 302

(1965) .

(23) if one assumes that isom ers 17 and 19 are normal , then the characteristic

shift for H in CDC13 should be (4.30+ 4.15) /2

6

4.22. The deshieldin

caused by the carbony l group is therefore 6 -

.53

for isomer

16

and

- .58 for isomer 18. In CsDs he n ormal position for Ha is at (4.45 +

4 .85 ) /2

6

4.65. The deshielding or isomer 16

is

therefore

6

- . 4 and

0.2 for isomer 18. The positive s olvent shift is thereby seen, in that the

deshielding of Ha caused by the carbo nyl group is less in C& than in CDC13

for each isom er. The gross CsD, deshielding of all isom ers is probably a

consequence of the polar benzenesulfonatesubstituen t. See D. H. W illiams

and N.S. Bhacca, Tetrahedron, 21, 2021 (1965)) or an extended discussion

of benzene solvent shifts with carbonyl compounds.

(24)

Dienone

49

could be isolated from s everal of the

17

.

5 1

reaction mix-

tures, but the major com ponent was alwa ys dimer 51.

(25) L. M. Jackm an and S. Sternhell, Applications of Nuclear Magnetic Res-

onance Spectrosco py in Organic Chem istry, Pergamon Press, Oxford,

1969, p 185.

(26) (a) See ref 25, p 225; (b) H. B. Kagan, Ed., Determ ination of Configurations

by Spectrom etric Methods, Vol. I.Georg Thieme Verlag, Stuttgart, 1977,

p 59.

of the American Chemical Socie ty / 101:13 / J u n e 20, 1979

(27) Hoffmann has done a m olecular orbital analysis of fragmentation reactions

[R.

Gleiter. W.

D.

Stohrer, and R . Hoffmann, Helv. Chim. Acta, 55, 893

(1972)] and finds that, for thos e cases where th e dihedral angle $J = Oo

cyclobutane formation can be preferred. The cases in point (41-fold,

53-fold) have J 60° , but the Hoffm ann calculations do not give results

other than for 4

0,

90, 180 .

(28) Technical assistance for some of the 360-MHz NMR experiments by

R.

E. Santini, J. Dallas, and N. Nowicki is greatly appreciated.

(29)

International Flavors and Fragrances, sold as transdecahydro-p-na-

phthol.

(30) W. G. Dauben,

R .

C. Tweit. and C. Mannersk antz,J. Am. Chem.

SOC.

76,

(31) H. C. Brow n, C. P. GarQ,and K. T. Liu,

J.

O r a Chem., 36, 387 (1971).

4420 (1954).

(32) A. Kandiah, J. Chem. Soc., 922 (1931).

(33) (a) K. Taguchi and F. H. Westheimer, J.

Org.

Chem., 36, 1571 (1971); (b)

-

H.

Weingarten and W. A. W hite,

bid.,

32, 213 (1967);

(c)

I.

Moretti and G.

Torre. Synthesis, 141 (1970).

(34) (a) H. Weingarten and W. A. W hite,

J.

Org. Chem., 32, 213 (1967); (b) I.

Moretti and G. Torre, Synthesis,

141 (1970).

(35) (a) A.

K.

Bose, G. Mina, M.

S.

Manhas, and E. Rzucidlo. Tetrahedron Lett.,

1467 (1963); (b) K. L. Brannock,

R. D.

Burpitt, U. W. G oodlett, and J. G.

Thweatt, J. Org. Chem.

29,81 8 (1964);

(c) C. F. Huebner, L. Dorfman. M.

M. Robison, E. Donoghue, W. G. Pierso n, and P. Strachan , ibid., 28 ,3134

(1963); (d) J. A. Hirs ch and F. J. Cross, ibid., 36,95 5 (1971); (e) A. J. Birch

and E. G. Hutchins on, J. Chem. SOC.

C 671 (1971);

(f)

E.

Yoshi and S.

Kimoto, Chem. Pharm.Bull., 17, 629 (1969) : (9) G. A. Berch told and G. F.

Uhlig,

J .

Org. Chem., 28, 1459 (1963); (h) D. W. Bo erth and F. A. Van-

Catledge,

ibid., 40,

3319 (1975).

(36)

R. Mozing, Organic Syntheses , Collect. Vol. Ill, Wiley, New York,

1955,

p 181.

(37) E. J. Corey and M. Chaykovsky,

J.

Am. Chem.

Soc.

87, 1345, 1353

(1965).

(38) (a)

H.

C. Brown, Organic Synthesis via Boranes , Wiley-lnterscienc e, New

York, 1975, (b) H. C. Brow n, A. K. M andai. and

S.

U.Kulkarni, J. Org. Chem.,

42, 1392 (1977); (c)

H.

C. Brown and N. Ravindran, ibid., 42, 2533

(1977) .

(39) L.

F.

Fieser and M. Fieser, Reagents for Organic Synthesis , Vol. 1, Wiley.

New York,

1967,

p

1180.

Mechanism of the Cannizzaro R e a ~ t i o r r l - ~

C.

Gardner Swain, Arnet L. P o ~ e l l , ~illiam A. Sheppard, and Charles

R .

Morgan

Contribution fr o m the Department o f Chem istry and the Laboratory f o r Nuclear Science,

Massachusetts Insti tute of Technology, Cambridge, Massachusetts

02139.

Receiced Nocember

13, 1978

.Abstract: A n ultimate technique for disqualifying compounds suspected of being intermediates is illustrated by the use of iso-

tope dilution to prove that benzyl benzoate is not an intermediate i n the Canniz zaro reaction of

0.5

M benzaldehyde-p-t (tri-

tium labeled) with 0.25

M

sodium hydroxide in

74%

methanolL26% water at 100 OC. Th e adduct from hydroxide ion and two

molecules of benzaldehyde th at was though t to rearrange to benzyl benzoate could alternatively rearrang e directly to the prod-

ucts. benzoate ion and benzyl alcohol. Houever, this mechanism also is disproved because methoxide

ion

acting instead

of

hy-

droxide ion should lead to benzyl methyl e the r, but less than 1 is found. Two other mechanisms involving a proton transfer

concerted Mith the hydride transfer a re disproved by the k ~ ~ ~ / k ~ ~ osotope effect of 1.9 . The rate-determining steps can be

rcprcsented by tivo hydride transfer reactions to C~ H S C H O .rom the adduct from HO- + ChHsC HO and from the adduct

from CH30-

+

ChHsCHO, or. equivalently. by t w o termolecular reactions. H O - + 2ChHsCHO and CH3O- +

2

c >ti

J C

H

0

T h e C a n n iz za r o r eac t io n b is t h e d i sp ro p o r t ion a t io n o f an

a ld ch y d c to an eq u im o la r m ix tu re o f p r im ary a l co h o l an d

ca rb o x y l ic sa l t . I t i s ch a rac t e r i s t i c o f a ld eh y d es th a t h av e n o

1

hydrogens, and therefo re canno t undergo aldo l condensat ion .

T h e r cac t io n i s u su a l ly b ro u g h t ab o u t i n a h o m o g en eo u s ,

s t rong ly basic so lu t ion o r in a heterogeneous sys tem consis t ing

o f an o rg an ic p h ase an d a s t ro n g ly b as i c aq u eo u s p h ase .

A

typ ical example is react ion o f benzaldehyde I) i t h co n cen -

t r a t ed so d iu m h y d ro x id e

i n

h o t aq u eo u s m e th an o l t o y i e ld

bcn7yl a lcohol (I I ) an d so d iu m b en zo a te ( I I ) . F o rm ald eh y d e

d i sp ro p o r t io n a tes i n ac id so lu tio n a lso .' T h e C an n izz a ro r e-

ac t io n w as co n s id e red o n e o f t h e m o s t im p o r t an t sy n th e t i c

reactio ns of organic chem istry prior to the discovery of LiAIH4

i n 1946, but has now been totally supplanted by metal hydrides

fo r l ab o ra to r y sy n th eses .

0002-7863/19/1501-3576$01

OO / O

C H 3 0 H

2 C b H 5 C H 0

+

N a O H

-

6 H 5 C H 2 0 H

I

I 1

+

C ~ H S C O ~ N ~

I I I

B en zy l b en zo a te (V I ) w as i so l a ted f ro m t h e r eac t io n o f I

w i t h N a O H

i n

w a t e r

or

i n h o m o g en eo u s aq u eo u s m e th an o l

solution w h en h ea t in g an d ex cess N a O H w ere av o id ed. 8 In

h eav y w a te r (DzO), t h e a l co h ol p ro d u ced f ro m th e r eac t io n

of

I

or fo rm ald eh y d e co n ta in s n o ca rb o n -b o u n d

D;9

th is ex -

c lu d es all mechan isms invo lv ing a hydride t ransfer f rom or to

o x y g en a to m s , for ex am p le , eq

A

or B.

T h e k in e t i c o rd e r w i th

I

and several der ivat ives

i n

w a t e r ,

m e t h a n o l , a q u e o u s m e t h a n o l , o r aq u eo u s d io x an e i s t h i rd :

979

America n Chemical Society

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S w a i n e t

al.

/ M e c h a n i s m of t h e C a n n i z z a r o R e a c t i o n

3517

R 0-

J

o=c

H

Q-0-C-R - RCH20-

+

HOCOR (A)

Ll

H

91

-

O r )

R

H-C=O QR

AJ

HO-H

I

OH

HO- + RCHZOH + RCOiH (B)

k 3

[

J 2 [ b a s e ] . o W i t h f u r f u r a l ' l a , b a n d f o r m a l d e h y d e ' t h e

orde r var ies f rom f i rs t to second in base, hence th i rd to four th

o v era l l d ep en d in g

on

t h e co n d i t i on s ; so d iu m m -fo rm y l -

b en zen es u l fo n a te a l so g ives a fo u r th -o rd e r r eac t io n , k4-

[R C H O J2 . [b ase l2 , u n d er ce r t a in co n d i t io n s . l I f T h e H am m e t t

r eac t io n co n s t an t fo r sev en a ro m at i c a ld eh y d es w i th so d iu m

h y d ro x id e

in

50 m e t h a n o l a t 100 "C is +3 .7 6 (correlat ion

coeff ic ien t 0.998). Ioc~12

Under typ ical Cann izzaro react ion cond i t ions, 0 .6 M I a n d

0.25

M

N a O H in 74% C H 3 0 H - 2 6 % w a te r a t 100 " C , t h e

reac t an t s ex i s t p red o m in an t ly a s f r ee

I

( n o t h y d r a t e or h em i -

ace t a l ) , N a+ , an d H O - , t h e r eac t io n is c lo se to seco n d o rd e r

i n I and f i rs t o rder in

HO-,

a n d t h e p r i nc i p al p r o d uc t s a r e I1

an d T h e p u rpo se of th is work was to invest igate the main

ro u te b y w h ich I 1 i s form ed u n d er t h ese co n d i t i o ns in o rd e r t o

ex c lu d e r ig o ro u s ly f iv e o f t h e s ix m ech an i sm s (1-6) pro-

posed .

Proposed

Mechanisms.

R a d i c a l - c h a i n m e c h a n i s m s h a v e

b een p ro p o sed , I3 b u t a r e ex c lu d ed u n d er h o m o g en eo u s co n -

ditions because radical initiators (benzoyl or sodium peroxide)

or i n h ib i to r s (h y d ro q u in o n e or d ip h en y lam in e) h av e no effect

on t h e r a t e . '

l a , 1 4

U n d e r h e t e ro g en eo u s co n d i t i o ns co n s i s t i n g

of a benzaldehyde phase and a s t rong ly alkal ine aqueous phase,

the react ion is a compos i te

of

two homogeneous react ions; the

reac t io n in t h e o rg an ic p h ase is ca t a ly zed b y I 1 produced by

the s lower react ion in the aqueous phase, bu t in bo th phases

th e r eac t io n ap p ea r s t o b e p 0 1 ar . I ~

S ev era l m ech an i sm s s t il l co n s i s t ent w i th t h e d a t a so f a r

p resen ted have been p roposed fo r the homogeneous Can n izza ro

reac t ion . T h e f i r ~ t ~ ~ , ~ . ~ ~ . ~ ~ ~ , ~ ~a s e q I as i t s r a t e -d e t e rm in in g

s t e p ( R

=

pheny l) .

0

0-

II fast

I

H-C + HO- -C-OH

R

I

R

I IV

0- 0- OH

I fast I I

I

0

II

I

R-C + H-C-OH - -C-0-C-R

H

I

H

~~

I IV V

0 H

slow

II

R-c-O-C-R -C-0-C-R

+

HO- (1)

1-4

H H

I

H

V VI

fast

R C H , O C O R H O -

-

C H , O H + R C 0 , -

VI I1 I11

T h is m ech an i sm in vo lves fo rm at io n o f VI as an in t e rm ed i -

a t e . S i n c e 18Q ex ch an g e b e tw een w a te r an d

I

is m u c h f a s t e r

t h a n t h e C a n n i z z a r o r e ac t i on , " t h e r a t e - d e t e r m i n i ng s t e p

can n o t b e fo rm at io n o f ad d u c t IV

or

t h e m ech an i s t i ca l ly

s im i l a r fo rm at io n o f ad d u c t

V,

b u t i t m ig h t b e th e r ea r r an g e-

m e n t ( e q 1) of V t o VI. E s te r h y d ro ly s is i s k n ow n t o b e f a s t

u n d e r C a n n i z z a r o

condition^.'^

A

seco nd m ech an i sm I8 i s eq

2

with a p r io r equ i l ib r ium fo r

I V a s i n m e c h a n i s m 1. T h is m ech an i sm in vo lves a r a t e -d e t e r -

H 0-1

H

0

1

n

slow

I

II

R-C H-C-R

-

-C-H + C-R

(2 )

I

OH

I + IV

I

OH

I

0-

VI1 vn1

fast

VI1 + VI11

-

C H , O H R C 0 , -

m in in g in t e rm o lecu la r h y d r id e sh i f t , f ol low ed b y f a s t p ro to n

t r an s fe r .

R e a r r a n g e m e n t s of

V

t h a t d o n o t l ead to fo rm a t io n o f V I

h av e a l so b een p ro p o sed, a s d esc r ib ed b y m ec h an i s m 319 or

m ech an i sm 4.20 In (3) , t h e s t a b l e p r o d u c t s (I1 a n d 111) a r e

I1 I11

ro-

OH

0

OH

Y

I

slow II I

R-C-0-C-R

-

-(2-0- + H-C-H

3 )

l

I

A H

I

R

V

I11 I1

0-

OH

0-

OH

I I slow I

I

R-C-0-C-R - -C-H + O=C-R(4)

I

H

I

H

V VI1 VI11

formed directly in the rate-de termin ing st ep, while in (4) a fast

p r o t on t r a n s f e r o c c u r s a f t e r t h e r e a r r a n g e m e n t t o f o r m t h e

s t ab l e p ro d u c ts .

A n o th e r r ea r r an g em en t o f V, m ech an i sm 5, involves a

pro ton t ransfer in the s low step to p roduce the s tab l e p roducts .

0

I L I

H H

I

H

V I1 I11

S im i l a r ly , t h e l a s t tw o s t ep s o f m ech an i sm

2

might be te le-

scoped to ( 6 ) .

OH

0

R-C

(p

0-C-R T -C-H

I

+

-0-C-R

II

(6)

H

b - I

H H

I + IV I1 I11

I n any so lu t ion o f IV a n d I , ther e wil l be some

V

a t eq u i l i b -

r iu m . I n m ech an i sm s

I ,

3 , 4 , a n d

5,

i t is conside red tha t

V,

in

sp i te of i t s low concen trat ion , reacts a t a fas ter ra te tha n more

a b u n d a n t r e a c t a n t s ( I a n d IV) because V h o ld s t h e m ig ra t in g

hydroge n in a favorab le posit ion fo r an in t r amo lecu lar rear-

r an g em en t . In m ech an i sm 2 or 6 the necessary in termolecu lar

hydride t ransfer canno t occur un less I an d

1V

happen to collide

w i th p rec i se ly co r rec t o r i en t a t io n s .

M e c h a n i s m s t h a t a r e s t il l s i m p l e r

i n

the sens e o f bypassing

IV can b e p ro p o sed . M ech an i sm 7 is a n e x a m p l e . H e r e IV is

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3578

Journal of t he Amer ican Chemical Soc ie t y

/ 101.13

/ June

20,

1979

0 0 0- 0

II

I1

slow

H-C

+

H-C +

HO--

R-C-H + C-OH i )

I

R R

I I

R

R

VI1 VI11

a r ev e r s ibly fo rm ed b y p ro d u c t i n eq u i l i b r iu m w i th th e r eac -

t an t s , b u t n o t an in t e rm ed ia t e a l o n g th e m a in r eac t io n p a th .

G en era l a rg u m en t s ag a in s t t e rm o lecu la r m ech an i sm s a re n ot

v a l id a t t h e h ig h co n cen t r a t io n s o rd in a r i l y u sed in t h e C an -

n izza ro r eac t io n . 2 ' T e rm o lecu la r m ech an i sm s h av e b een

dem onstra ted in var ious systems exper imental ly .22 Mec han is m

7 c o u l d h a v e t h e s a m e t r a n si t i on s t a t e a s m e c h a n i s m 2.

I so to pe e f f ec t s u s in g b en za ld eh y d e-a - t (1 . 2 4 -

I

.41)2a13a-23

a nd b e n ~ a l d e h y d e - c u - d ~ ~ , ~ ~ave been mea sured , and a re in the

n o rm al d i r ec t io n fo r p r im ary e f f ec t s ( t h o u g h sm al l e r t h a n

usual) . However , they do no t d is t ingu ish between mechan isms

1-7,

which al l invo lve a hydri de

or

h y d ro g en a to m t r an s fe r i n

t h e r a t e - d e t e r m i n i n g s t e p .

Isotope Dilution Applied

to

the Cannizzaro Reaction of

Benzaldehyde-p-t

in

74% Methanol-26% W ater at 1 0C.

Disproof of Mechanism 1 .

A

p ro m is in g t ech n iq u e fo r e l im i -

n a t in g a s a n i n t e r m e d i a t e a n y s u g g e s t e d c o m p o u n d C t h a t is

s t ab l e w h en i n p u re fo rm i s t o sh o w th a t i t s ac tu a l co n cen t r a -

tion i n the react ing system is less than would be requ ired i f i t

w e r e a n i n t e r m e d i a t e . T h i s r e q u i re s ( a ) m e a s u r i n g t h e r a t e o f

co n su m p t io n o f t h e su sp ec t ed in t e rm ed ia t e C u n d er r eac t io n

co n d i t i o n s s t a r t i n g w i th i t a s a r eac t an t . (b ) ca l cu l a t in g f ro m

t h i s t h e c o n c e n t r a t i o n s o f C t h a t s h o u l d be p r e s e n t a t v a r i o u s

t im es w h en n o n e i s ad d ed b u t o n th e a s su m p t io n th a t i t i s

fo rm ed as an e s sen t i a l i n t e rm ed ia t e a lo n g th e m a in r eac t io n

p a t h , a n d ( c ) s h ow i n g t h a t t h e m e a s u r e d c o n c e n t r a t i o n s o f C

ar e l e ss t h an th ese ca l cu la t ed v a lu es . S in ce l i k ely r eac t io n i n -

termedia tes a re o f ten very unstab le under react ion cond i t ions,

th i s u su a l ly r eq u i r es a n e x t r em ely sen s i t i ve an a lyt i ca l m e th o d

fo r m easu r in g th e co n cen t r a t io n o f C , e sp ec ia l ly w h en i t

o r ig in a t e s f rom th e u su a l r eac t an t s a lo n e ( a s i n p a r t c ) . T h e

m o s t sen s i t i v e g en era l an a ly t i ca l m e th o d k n o w n fo r h y d ro -

gen-con tain ing C compounds invo lves the use o f p r io r t r i t ium

lab e l in g of C ( in p a r t a ) o r r eac t a n t ( i n p a r t c ) , co u p led w i th

iso tope d i lu t ion by a larger measured amount o f un labeled C,

purification a nd analys is for radioactivity. Th e low cost of pure

t r i t i u m ( T l ) g a s ( c a .

$2

per cur ie) and the h igh sensi t iv i ty o f

r ad io ac t iv e co u n te r s m ak e it p rac t i ca l to m e a s u r e a c c u r a t e l y

concen trat ions o f t r i tia ted m ater ia l as low as M.24.25 h e

fo l lowing i l lust rates the use o f th is techn ique fo r p rov ing that

benzy l benzoate (VI) i s no t an in terme diate i n t h e C a n n i z z a r o

react ion o f I .

I n simul taneous base-catalyzed hydro lysis and m ethano lysis ,

m e th o x id e io n is a b o u t t h r e e t i m e s m o r e r e a c t i v e t h a n h y -

drox ide ion toward acety l L-pheny lalan ine methy l es ter in

80%

m e t h a n o l - 2 0 % w a t e r 2 6 dan d 4 5 t im es m o re r eac t iv e to w ard

p-n i t ropheny l acetate in dilute solutions of alcohol i n w'ater.2"b

W h e n t h e r a t e o f d i s a p p e a r a n c e o f 0.0625 M V I , p a r t i a ll y l a -

b e l ed w i th t r i t i u m i n t h e p a ra p o s i ti o n s of t h e r i n g s , w as d e -

t e r m i n e d u n d e r C a n n i z z a r o c o nd i ti o n s (0. 2 5 M to tal base

( m e t h o x i d e + h y d ro x id e ) , 7 4 % m eth an o l -2 6 % w ate r a t

IO0

"C) by isotope dilution for unchanged VI , i t was found tha t VI

disappears by two pdralk l f i rs t -order react ions, wi th methox ide

ion and with hydrox ide ion , wi th the combi ned f i rs t -o rd er ra te

constan t of 0 .37 s - l . F ro m th ese d a t a an d th e th i rd -o rde r r a t e

c o n s t a n t

k 3

= I . 8 6 X M-? S - I f o r t h e C a n n i r z a r o r e-

ac t io n o f

I ,

t h e co n cen t r a t io n o f VI t h a t s h o u l d b e f o r m e d a t

v a r io u s t im es

in

t h e C a n n i z z a r o r e a c t i o n , a s s u m i n g t h a t i t is

an es sen t i a l i n t e rm ed ia t e a s r eq u i r ed b y m ech an i sm I , w as

ca lcu la t ed b y ap p l i ca t io n o f t h e s t ead y - s t a t e ap p ro x im at io n .

Of co u r se , so m e

VI

m u st fo rm ev en i f m e c h a n i s m

2

o p e r a t e s ,

b ecau se th e ad d u c t o f p ro d u c t b en zy lo x id e io n

V I

I t o b en za l -

d eh y d e I sh o u ld b e ab o u t a s e f f ec t iv e a s IV as a h y d r id e d o n o r .

H o w ev er , IV i s no t fo rm ed in i t ia l ly if mec han is m 2 i s co rrect ,

w h ereas i t

is

a n e c e s s a r y i n t e r m e d i a t e f r o m t h e b e g i n n i n g

i n

m e c h a n i s m 1 T h ere fo re , i so to p e -di lu t io n m easu re m en t s w ere

rest r ic ted to the ear ly par t (6-19%) of the Cann izzaro react ion

of benzaldehyde-p-f . Th e calcu lated concen trat ions o f

VI

were

a t l e a s t 10-17.5 t i m e s t h e c o n c e n t r a t i o n s f o u n d . T h i s s h o w s

t h a t

VI

i s no t an essen t ial in terme diate a long the main reac t ion

p a t h a n d e x c l u d es m e c h a n i s m 1 .

Product Analysis. Disproof of Mechanisms 3 and 4. S i n c e

m eth o x id e io n i s m o re r eac t iv e th an h y d ro x id e ion to w ard es -

t e r s in m e th an o l - w a te r so lu t io n s ,2 6 h e re sh o u ld b e

a

consid -

e rab le am o u n t o f r eac t io n o f

I

w i t h C H 3 O - i n C a n n i z z a r o

reac t io n s ca r r i ed o u t in a lk a l in e m e th a n o l -w a te r so lu tio n s .

M e c h a n i s m s 1 an d 2 w o u ld y ie ld t h e sa m e p ro d u c t s w i th

C H 3 O - as w i th HO- since esters ar e rap id ly hydro lyzed under

t h e c o n d it i o ns . H o w e v e r , s u b s t i t u ti o n o f C H 3 0 - f o r

HO-

i n

m e c h a n i s m 3 requ ires fo rmat ion o f benzy l methy l e ther

( I X ) ,

w h i c h s h o u l d a c c u m u l a t e a s a s t a b l e p r o d u ct . IX ad d ed to a

Cann izza ro react ion m ix tu re in i t ia l ly (0.25 M) was still present

a t t h e e n d ( 0 . 2 4

M ) .

sh o w in g th a t t h i s e th e r i s no t d es t ro y ed

u n d er C an n izza ro co n d i ti o n s . Wh en n o n e w as ad d ed in it i a ll y ,

less than 1 was found a t t h e en d b y g as - l i qu id p a r t i t i o n

c h r o m a t o g r a p h y . T h is e x c l u d e s m e c h a n i s m 3.

M ec h an i s m 4 is fo rbid d en as a co n ce r t ed

or

o n e- s t ep r eac -

t ion by conservat ion o f o rb i ta l symmetry ru les . An equ ivalen t

two-step rearrangement v ia homolysis

to

a d i r ad i ca l

or

triplet

ca rb en e in t e rm ed ia t e h as b een p ro p o sed ?" b u t seem s ex c lu ded

b ecau se th e rm al en e rg y a lo n e i n the absence o f l igh t or f ree

rad ica l s sh o u ld n o t b reak th ese s t ro n g b o n d s th i s r ap id ly , an d

p ro d u c t s or rate shou ld be affected by rad ical inh ib i to rs

i f

rad icals were invo lved .

,4lso.

(4 ) p rov ides no exp lanat ion fo r

base catalysis s ince the homoly t ic re arran geme nt i n (4 ) shou ld

p ro ceed ab o u t a s w e ll w i th t h e n eu t r a l co n ju g a t e ac id o f

V

a s

w i th th e m o n o an io n .

Sovent Isotope Effect. Disproof of Mechanisms 5 and 6.

M e c h a n i s m s 5 a n d 6 a re ex c lu d ed b y

o u r

"solvation rule" ,

which s ta tes that a p ro ton being t ransferred between oxygens

(or o t h e r a t o m s w i th u n s h a r e d p a i r s ) i n t h e r a t e - d e t e r m i n i n g

s t ep o f an o rg an ic r eac t io n (o n e w i th b o n d ch an g e s o n ca rb o n

i n

the rate-determin ing s tep) shou ld l ie a t a po ten t ia l min im um

(ra th e r t h an m ax im u m ) a t t h e t r an s i t io n s t a t e . T h i s m ean s th a t

n o p r im ary k in e t i c i so to p e e f f ec t sh o u ld b e o bse rv ed fo r an y

such hydrogen because i t does no t lose zero -po in t v ib rat ional

e n e r g y f r om g r o u n d s t a t e to t r an s i t i o n s t a t e . S in ce i t s m o t io n

is not a c r i t i ca l p a r t o f t h e d eco m p o s i t i o n m o d e w e sh o u ld n o t

include an arrow or arrows for

its

t ransfer

in

this step. This docs

no t exclude the possib i l i ty o f a favorab le cycl ic or h q d ro g en -

bonded conformat ion fo r the t ransi t ion s ta te bu t does el iminate

th e m o re co n ce r t ed m ech an i sm s 5 a n d 6 .

E x p er im en ta l d a t a o n th e C a n n i rza ro r eac t ion , accu m u la ted

b e fo re t hi s ru le ~ l a sormulated and tes ted by o ther react ions,

l ead s to t h e s a m e c o n c l us i o n. T h e r e a c t a n t s o f m e c h a n i s m 2

i n

heavy water

D20)

r c

DO-

an d

two

molecules of aldehyde.

A t t h e t r an s i t i on s t a t e t h e DO- bond has been replaced bq a

DO bond (uncharged ) . Th is equ i l ib r ium is more favorab le u i th

DO-

i n D 2 0 t h a n w i t h H O -

i n

H 2 0 by a f a c t o r of a b o u t

2.0 .27 .2x n t h e o th e r h an d , i n m e c h a n i s m 5 or

6

th is shou ld

be more than o ffset by

a

prima ry iso tope effect

in

the opposi te

d i r ec t io n f ro m t r an s fe r

of

D r a t h e r t h a n H

i n

t h e r a t e - d e t e r -

m in in g s t ep . r e su l t i n g i n a n e q u a l or f a s t e r r a t e i n H 2 0 . T h e

observcd

k

[,?o/k i 2 s I

.90.

T h is ex c lu d es m ech an i sm s 5 a n d

6 a n d S ~ O W Sh a t t h e p ro to n i s t r an s fe r r ed a f t e r , r a th e r t h an

during , the rate-determin ing s tep . ' ' . ' "

Mechanisms

2

and 7. T h ese m ech an i sm s a r e b o th s t il l al -

lowed . We knovv th at the two molecu les o f rea cta n t

l

a re p re -

d o m in an t ly u n so lv a t ed an d u n asso c ia t ed w i th h y d ro x id e

or

m cth o x id e i n

our

so lu tio n s ,' w h ereas t h e b o n d in g o f t h c h q -

d ro x id c o x y g en to ca rb o n is c o m p l e t e o r n ear ly

so

a t t h e t r a n -

si t ion s ta te ( f rom the observed larg e values o f

k l ) ? ~ / k t i ~ ~

n d

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S w a i n

et

al . / Mechani sm of the Cannizzaro React ion

t h e H a m m e t t r eac t io n con s t an t

p .

W e c a n n o t s ay m u c h a b o u t

th e seq u en ce o f ev en ts b e tw een r e ac t an t s an d t r an s i t i on s t a t e ,

w h e th e r t h e r a t e -d e t e rm i n in g r eac t io n m o re u su a l ly in v olv es

two successive doub le co l l is ions o r on e t r ip le co l l is ion , because

t h e s a m e r a t e i s c a l c u l a t e d f o r t h e s a m e t r a n si t i on s t a t e w i th

e i th e r (2)

or 7 ) .

W e know of no operat ional way , exper imental

or

t h eo re t i ca l , t o d i s t i n g u i sh b e tw een (2) a n d

7 ) ,

a n d w e

th e re fo r e co n s ide r t h e m a s equ iv a l en t .

A r easo n ab le s t ru c tu re fo r t h e t r an s i t i o n s t a t e is i l lust rated

by

X .

T h e C - - H - - C b o n d m a y b e b e n t . 3 ' T h e c a r b o n y l

n 6 -

3579

X

o x y g en s of o n e or b o th a ld eh y d es a re l i ke ly to b e p o la r i zed b y

h y d ro g en b o n d in g to w a te r o r a l co h o l solv en t m o lecu les , an d

reasons have been g iven2 ' fo r bel ieving tha t such p ro tons have

n o rm al b o n d s w i th n o rm al ze ro -p o in t en e rg y a t t h e t r an s i t i o n

s t a t e .

T h e f o u r t h - o r d e r t e r m o b s e r v e d w i t h f o r m a l d e h y d e a n d

cer tain o ther a ldehydes may re presen t a t ransi t ion s ta te s imilar

to X excep t that the hydroxy l ic p ro ton has been t ransferred to

a seco n d h y d ro x id e

ion

t o f o r m a s e p a r a t e w a t e r m o l e cu l e .

Experimental

Section3

Toluene-p-t.

A Grignard reagent was prepared from 260

g

(1 .52

mol) ofp-brom otoluene and 40 g

( I

.65

mol) of

M g i n 370 mL of dry

ether. Tritium chloride,33 prepared from a heated m ixture (25 "C to

boiling point) of 1.0 g (0.1 1 equiv, 2.5 Ci) of tritiated water (see

"Inorganic Chemicals"), 5.0

g

(0.55 equiv) of HzO , and 250 gof re-

agent grade C,jH5COCI, was passed into the vigorously stirred Gri-

gnard mixture by a stream of purified N2. After th e ether had been

removed from the resulting mixture, the pressure was reduced to

I O

mm and the crude toluene-p-1 was collected in a dry ice-acetone

cooled flask. Distillation in a Vigreux column ( 1 6.5 cm X 2.5 cm 0.d.)

with a Claisen head gave 59

g

(97%) of partially tritium-labeled tol-

uene, bp 108-109 "C (lit.34 for toluene, bp l l l "C).

Benzaldehyde-p-t (I-p- t). This toluene (59 g, 0.64 mol) was pho-

tochlorinated by a Sylvania

RS

sunlamp

15

cm from the flask. Hy-

d r ~ l y s i s ~ ~f the resulting benzylidene chloride gave partially tri-

tium-labeled

I,

which was purified through the bisulfite addition

product35 and distilled under purified Nz in a semimicro column,36

bp 176- 177 "C, n z 5 ~.5424 (lit. for I, bp 179 0C,35 Z 0 ~.544637),

26.4

g

(39%).

Benzoic-p-t Acid and Benzyl-p-t Alcohol.

A Cannizz aro reaction

on this benzaldehyde (14 g, 0.13 mol)38gave 3.8 g (47% ) of partially

tritium-labeled V l l l after recrystallization from water, mp 121-122

"C (lit.39 for ChH5C 02H, 122.38 "C ), and 3.9 g (55%) of partially

tritium-labeled I 1 after distillation under z in a semim icro column,3h

bp 109-1

10 c

15 mm), f125D 1.5366 (/it ,4\ ' fo r 11, bp 104-105 c

(20 mm) , 1,5340).

Benzyl-p-t Benzoate-p-t

( V I - p , p - 12 ) was prepared by a Tis-

c ht sc he nk o r e a ~ t i o n . ~ 'he partially labeled I

(8.1

g, 0.076

mol)

was

treated with VI1 prepared from 0.033 g (0.001 4 mol) of N a and 0.70

g (0.0065 m ol) of the partially labeled

I I .

Th e pasty. gelatinous

mass

resulting was treated with 40 mL of H2O and 20 mL of ether

to

give

three layers (H 20 , ether, and an oil) which were separated. The H2O

and oil layers were each washed with 20 mL of ether. Th e combined

ether layers were dried over anhydrous NazSO4. After the ether had

been removed, the VI was distilled under K n a semimicro c0lumn.3~

5.1 g (63%), bp 133-134 " C (0.7 mm ), t i Z 5 ~.5664 (lit.I4 for V I . bp

133-1 35 "C (0.5 mm ), n 2 4 ~.5672).

Benzaldehyde-a-i I-a-t) . he Reissert compound, 1 -benzoyl-

I

2-dihydroquinaldonitrile as prepared from ChHsCO CI, quinoline,

and aqueous KCN and recrystallized twice from 95% ethanol as white

needles, mp 154- 154.8 "C (lit.42154- I55 "C) . Th is was hydrolyzed

i n 2.5 M H2S 04 by refluxing I2 g

i n 108 g

of

a

solution of 25.6 g of

96.5% H2S04 (0.25 mol of H2S04

+

0 .05 mol of H2 O) in 84 .6 g of

tritiated water (4.70 mol) of 1.37 mCi/mol activity for 2 h under N2.

Th e solid crystals disappea red within 30 min. The product was steam

distilled, extracted with ether, dried by azeotropic distillation with

15 mL of adde d C6H6, and distilled t hrough

a

semimicro column,36

3.0 g, bp 74.0-74.4 " C (20-2 I

mm.

The 2 4-dinitrophenylhydrazone

recrystallized twice from ethyl a ceta te, mp 241 .O-242.2 *C (l it j3 237

"C), had an activity

of 0.1 16

mCi/mol; the dimethone derivative,

recrystallized twice from CH 30 H, mp 196.5-197.7 "C (lit.44 194-195

C),had 0.120 mCi/m oJ; the semicarbazone, recrystallized twice from

50% ethanol, mp 220.2-221.1 "C (lit.43222

"C) ,

had

0.1

16 mCi/m ol

and changed less than 2% when it was dissolved in the minimum

amou nt of 50% ethanol, refluxed for I h, and recrystallized t o see i f

it exchanged with solvent; and V ll l from KM n0 4 oxidation45 of the

compd recrystallized twice from water, mp 122.8-1 23.5 "C, had no

significant tritium content (4.7

X

mCi/mol). I xchanges with

tritiated H zS 04 ess than I nder these conditions: 5.0 mL of I re-

fluxed with 52. 2 g of a solution of 12.6 g of 96.5% H2S0 4

in

42.3 g of

tritiated w ater of 3.54 mCi/m ol for 3 h under

N2

and worked up as

above gave 3.86 g, bp 66.8 " C

( I

5

mm,

pecific activity of semicar-

bazone 9.39

X

mCi/m ol, of

VI11

5.44

X

mCi/mol. These

tritium analyses reported for water and organic compounds were done

by the Mg46 and

Zn4'

reduction methods, respectively.

The isotope effect in this Reissert aldehyde synthesis is therefore

k H k T

= (1.37

X

4.70 mCi)/O.l16 mCi/mol

X

10.0 equiv of H in

Hz S04 solution = 5.6.

A

second synthesis with nine times t he activity

of the first gave 5.3.4s This isotope effect does not prove that the proton

transfe r occurs in the rate-determining step, because t here would be

a selective competition between proton a nd triton dono rs even in a fast

step unless it were diffusion controlled.

For the Cannizzaro reaction, the benzaldehyde-0-1 was converted

to semicarbazone, recrystallized, hydrolyzed back

to

aldehyde. and

freshly distilled under N 2 before use, bp 69.0-69.7 "C (17-18

mm).

Methanol-d (C H3 0D ) was prepared by decomposition of

Mg(OCH3)2 with DI O. ~'All the glasswa re was baked at 350 OC for

several hours, assembled rapidly while hot, and immediately a ttached

to Ascarite a nd Drierite towers to prevent introduction of CO2 and

moisture. AC S reagent grade CH 30 H was dried by the Mg method.50

Mg

(150

g) was added in small portions to 3.5 L of dry CH30H

without exposing the system to the atmosphere. After the Mg had all

dissolved and the solution had refluxed for 3 h, most of the CH30H

was distilled and the residue was heated at 150-200 "C ( I mm) for

24 h . Th e system was allowed to cool to 25 "C a nd then dr y, COz-free

air admitted. DzO (100 mL, >99.5%, degassed by bubbling purified

N2 through i t for 30 min) was added an d the resulting mixture was

refluxed. with frequent shaking, for 4 days. The flask containing t he

reaction mixture was equipped for trap-to-trap distillation. Dry,

COz-free air was admitted to the system while the distillation flask

was cooled by liquid

N2.

The system was then evacuated to 0.5 mm

and t he liquid

N 1

bath was moved from the distillation flask to the

receiver. After 24

h ,

dry, COz-free air was introduced and the distillate

was allowed to warm to 25 "C. Mg (2

g)

was added to the CH3 0D .

After the Mg had all dissolved. the solution was refluxed for 3 h and

the CH 30 D was distilled, bp 65 "C. 200 mL, GL C at 25 "C wi t h two

different columns (30% (by weight) 3-methyl-3-nitropimelonitrile

on 60- 100 mesh firebrick and 30% Carbowax 600 on SO- IO0 mesh

firebrick i n 8-m ni Pyrex tubes 190 cm long) indicated total im purities

of less than 0. . A determination of the D content by the falling-drop

method" gave 24.65 atom %exces s D (98.6% CH 3O D) .

Methanol was prepared i n the same manner as CH3O D for com-

parison of rates in light and heavy 74% methanol, bp 63.5-64.0 "C.

GL C indicated total impurities

o f

less than 0.1 CHj OH for all the

other

r u n s

was AC S reagent grade dried over Drierite.

Benzaldehyde

I ) ,

Eastman white label, was washed with 10%

a qu eo us N a ~ C 0 3 , ried over anhydrous N a2S 04 and freshly distilled

under N2

i n

a semim icro column3h before use, bp 176-177 "C,

t i Z 5 D

1.5432.

Benzyl benzoate (VI) and methyl benzoate XII ) , Eastman white

label, were redistilled under N2

i n

a Semimicro column:36 V I , bp

121-122 "C ( 0 . 5 mm), n 2 5 ~.5653; XI I , bp 7 5 "C ( I O mm,

n 2 5 0

1 . 5 1 2 2 ( l i t. 5 2 b p 8 3 C ( 1 2 m m ) , n 2 5 D . 51 55 ).

Benzyl benzoate

( V I )

used as the diluent for isotope dilution was

rccrystallized Eastm an white label grade . A CH 30 H solution of

V I

was cooled in an ice-salt water bath; water was added to th e cloud

point and a seed crystal was introduce d. Th e crystallized

V I

was col-

lected on an ice-jacketed fritted-glass funnel, washed with a sma ll

amount of ice-cold C H 30 H , and air dried. After three such recrys-

tallizations, it was recrystallized from a minimum of pure CH30H

7/26/2019 Mechanism of Cannizzaro Reaction

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3580

Journal o f th e Amer ican Chemical Soc iet y /

101:13

/ June

20, 1979

Table

1 Reaction'of 0.5752 M I with 0.2875

M

Na OD in 74%

C H ?O D -D , O a t 9 9. 8

f

.1 "C in Teflon Tubes

Table IV. Kinetics of the Alkaline Hydrolysis of

0.1

84 M VI with

0. I77 M Na OH in 78% CH3OH at 99.4 "C

k3

X I O 4

time,

s [DO-1, M

reaction

M-2 s - I

k z a X I O 2 .

t ime,

s

[HO-1,

M

reaction

'

M-'

s - I

0 0.2872 0

3600 0.2 I64 24.7 3.21

7200 0. I779 38.1 3.38

I O 800

0.1599 44.9 3.12

1 8 000

0.1284 55.3 3.37

57 600 0.07 53 73.8 3.57

mean 3.33

320 0.0577 67.4 3.4

600 0.0246 86.1 5.0

900

0.0

145 91.8 5.6

I200

0.0109 93.9 5.5

I500

0.0092 94.8 5.0

1810

0.0089 94.9 4.2

mean 5

Table 11. Rate Constants for the Cannizzaro Reaction of I in Light

and Heavv 74% Methanol-26% Wa ter in Teflon Tubes

k3

X I O 4

temp, "C [NaOLIo, M

[ l ] ~ ,

M water,

L 2 0

M-*

S - I

-

99.4 0.2850

0.5702

DzO 3.76 f .07

99.4 0.2609

0.5216

H 2 0 1.79

f

0.10

99.8 0.2685

0.5370 H2O 1.86

0. I 1

99.8 0.2875

0.5752

D2O 3.33 0.13

Table

H I .

Cannizzaro Reaction of

1

in

Glass Tubes

solvent . C H IO H te m a " C k l X

IO4.

M-2 s-'

50

67

74

74

100

2.33 f .09O

IO0

2.22

f

.10b

98.3 3.31 f 1.03'

98.6 2.45 f .33d

E.

L. Molt;loa Tommilal°C reported a frequency factor of 4.66 X

I

O4

and a n activation ene rgy of 13.85 kcal for the Cannizza ro reaction

o r I

i n 50% CH3O H. Thes e gave a calculated k3 of 3.47 X M-*

5 - l at 100

"C.

K. B. Wiberg.23 W . A. Sheppard.2a

I-p-t; I

gave

2.36

f

.16

X

at 98.4 "C.

and dried over Anhydrone (MgC104) in a desiccator at

I O

"C, mp

19.3-20.0 "C (lit.s3 mp 19.4 "C),

n 2 5 ~

.5672.

Benzyl methyl ether

IX) , Eastman white label, was redistilled under

N2 in a s e m i m i c r o c ~ l u m n , ~ ~p 169-170 "C (lit.54bp 170.5 "C).

Inorganic Chemicals.

Purified nitrogen was prepurified N2 reed

of

CO2

and H20 by passage through a series of towers containing

Ascarite (NnOH on asbestos) and Drierite (Ca S04 ). Tritiated water

~ i i srepared from T I gas (AEC , Oa k Ridge) as described previous-

l y . H 2 0 was laboratory distilled water which was redistilled from

N aO H -K M n O a i n an all-Pyrex apparatus.

N a O D was prepared by the dropwise addition of 100 mL of de-

gassed D2O ( > 9 9 . 5 %) to 2.3 g (0. mol) of freshly cut reagent grade

N a under

a n

atmosphere of purified N2 and then standardized.

Analbsisil of the solvent of the K aO D solution gave 99.14% DzO.

NnOH was prepared i n the 5ame manner as NaOD for the runs

comparing rates in light and heavy 74% methanol . For the other runs,

i t

was prepared either bj the concentrated NaOH methodSSor by

diluting

I

M Acculute and standardizing. COz-free HzO was used

i n

a11

these preparations.

Kinetic Procedures.

The kinetics of the Canniz zaro reaction of I

i n 74% methanol was measured essentially by the method of Moltlod

and A l c ~ a n d c r . ' ~he procedure was the same in light and heavy

methanol. I (about 3 m L ) was transferred by means of a 5- mL syringe

and under a n atm osphere of purified N2 to a weighed 50-mL volu-

metric flask. The flask was reweighed a nd placed in a dryb ox, which

was

then tlushed with purified

Nz

or 20-30 min. Methanol

(25

mL)

was

added to the flask, and 12.87

mL

of

1 M

NaO H was added f rom

a buret with mixing by swirling. Th e volume was brought to the m ark

by addition of methanol. Af ter the solution had been thoroughly

mixed. i t was drawn into a 50-m L syringe and seven aliquots of ca.

6

mL each were injected into Teflon tubes of ca . 7 mL capacity pre-

viously fitted s nugly inside 18 X I50 mm Pyrex test tubes which had

been constricted about 2.5 cm above the top of the Teflon to 4-5 mm.

a Based on total base consumed

The tubes were protected from t he atmosphere by tight-fitting rubber

stoppers, removed from the drybox, cooled in an ice-water bath, sealed

at the constriction, and placed in the constant tempe rature ba th. After

the tubes had been in the bath for

10

min, one was withdra wn, cooled

in an ice-water bath, allowed to com e to 25 C, and opened.

A 5-mL

aliquot was pipetted into a known excess of 0.1 M sta ndar d HC I and

back-titra ted under purified N Z o the phenolphthalein end point with

0.1 M

Na OH . The constant was calculated from k3

=

x ( 2 a - x)/

8ta2 a- ) ~ , here

a

is the initial concentration of base a t I O min

( t = 0) and

x is

the concentration reacted

in

t ime t . Data for a typical

run a re given in Table I , and th e results for various runs in light and

heavy 74% CH 30 H in Table

11

Teflon tubes were used

in

the later phases of this work because rapid

attack of alkali on Pyrex tubes complicated the kinetics and gave

poorer reproducibility in the earlier runs. Teflon tubes a re convenient

to use as described above an d the solvent shows

no

tendency to distill

out of the Teflon tube into the small spa ce outside or under this tube

(between the Teflon liner and the outer Pyrex tube) because the

electrolyte (N aO H)

is

nonvolatile and keeps the vapor pressure below

tha t of salt-free solvent. A difference

in

height of liquid inside and

outside of over 30

m

would be required for gravity t o compensate this

osmotic difference. Without these inert reaction vessels about one-

quart er of the base was consumed by reaction with Pyrex under our

conditions. Kinetic results of investigations i n glass ar e reported i n

Table

1 1 1 .

I n 74% CH 30H -26 % H:O solutions at 100 "C CH3O- should

attack

V I

to form methyl benzoate

(XII)

more rapidly than HO-

attacks

V I

or

XI1

to form

1 1 1 . 2 6 . 2 7

Therefore the second-order rate

k.

C,H,COOCH,C,H, + CH,O- C,H,COO CH, C,H,CH,O-

k

HO

C , H , C O O H

+

C , H , C H , O -

k 1

HO

C , H , C O O H C H , O -

C , H , C O O - C , H , C H , O H

C , H , C O O -

+

CH,OH

k , > k , and

k ,

consta nt for hydrolysis of V I measured by the usual acid-base titration

procedure should be nearly the sam e as that for

XII.

Since these esters

hydrolyze rapidly even at 25 "C, the involved procedure for trans-

ferring samples under Nz, which was necessary for the Canniz zaro

rcaction runs, could not be used. Inst ead, as soon a s the reaction so-

lutions were prepared, samples were transferre d a s quickly as possible

by means of a syringe to 7-mL a mpules

( 1

5 X 125 mm Pyrex test tubes

constricted i n the middle to 4-6 mm ) which were cooled i n ice watcr

and which had been previously flushed with purified N l . The tubes

were sealed quickly and placed in the constant temper ature bath. A t

suitable intervals. one was withdrawn, cooled

in

ice water, and opened

and then a 5 - m L aliquot was pipetted into a known excess of 0. M

standard HCI and back-titrated with 0.1 M Na OH . The second-order

rate consta nt was calculated from t he equation

2.303 b ( a

- X )

k ? = -

log ~

a ( b

- x)

a - b )

where

a

and

h

are initial V I and NaOH conccntrations. respectively.

and .Y is the amount

of

reactant consumed in time

t .

The kinetic results

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Swa in et al.

/

Mechanism

of

the C annizzaro React ion

Table V. Kinetics of the Alkaline Hydrolysis of 0.244 M

XI1

with

0 .235 M NaOH i n 74% Methanol-26% Wat er a t 99.4 OC

k l a

X

IO 2 ,

[HO-1,

M

reactiona M-1 s - I

time, s

300

0.042 82.1 5.7

600

0.0121 94.8 9.4

900

0.0084 96.4 8 . 3

1200

0.0067 97.1

1 . 3

I500

0.0051 97.8 7.2

I800

0.0049 97.9 6.0

mean 7

358

1

Based

on

total base consumed

for the hydrolysis of V I and XI1 as determin ed by acid-base titration

are reported i n Tables

IV

and

V.

Despite the large errors inherent i n measuring the rates of these very

fast reactions, the close agreem ent of the second-order rate constant

for VI

( 5

X I O - ? M-I s - I ) with that for

XI1

(7 X

IO-*

M-' S - I ) in-

dicates that what is really being measured i n the ca se of V I by the ti-

tration method

is

the attack of base

on X I I .

The ra te of disappearance

of

VI is

very much faste r, as reported below under "Isotope Dilution

Technique".

The ra te of disappeara nce of

V I - p . p - t ?

under Cannizzaro condi-

tions was measured by determ ining the amou nt of unchanged ester

at various times

using

isotope dilution. All trans fers were m ade under

purified

I \r l

to glassware that had been flushed with purified

N2.

To

a 50-m L volumetric flask containing 1.3256

g

(0.006 25 mol) of V I

(with tracer-level p,p -r2 labeling) was added 25 mL of CH3OH.

COz-free water ( 1 2.50 mL ) was added from a buret. The temperature

rose I0 "C a nd some ester separated as fine droplets. After the mixture

had cooled to 25 O C . thevolum e was brought almost t o the mark with

CH IO H, and the flask was swirled gently

u n t i l

the ester had dissolved.

The volume wab brought to the m ark, and the resulting solution was

thoroughly mixed by shak ing. To a separat e 50 -mL volumetric flask

containing 25 mL of CH3OH was added

12.50

mL of 1.002

M

N aO H

from a b ure t. After t he solution had cooled to 25 OC, th e volume was

brought to the mark with C H 30 H . The resulting solution was thor-

oughly mixed by shaking. A constant-delivery automatic syringe was

used to deliver 3-mL aliquots of the 0.1250 M ester solution to one ar m

of inverted-Y-shaped Pyrex tubes. The tubes were stoppered with

rubber stoppers. Th e syringe was cleaned by repeated rinsing with

C H 30 H , dried, and then used to deliver

3 - m L

aliquots of the 0.2500

M Na OH solution to the other arm of the tubes. Eight tubes were

loaded in this manner. cooled

i n

ice water, and sealed

so

that the re-

sul t ing

third arm had about the same capacity

as

the other two.

(Measurement, after the run.

of

the total capacity of each

of

seven of

the tubes gave

17. 0.4

mL.) Some of the ester separ ated as fine

droplets when the solutions were cooled. One of the tube s, the zero

point, was opened and treated as described below u nder "Isotope

Dilution Technique". T o obtain each of the other points. a tube

was

placed in the constant temp erature bath, held upright for 4-5 min to

allow it to reach bath temperature, inverted (measurements

on

blanks

showed that there was no rise i n temperature when a 74% CH jO H

solution was mixed with an equal volume of 0.250

M

K a O H i n 74%

CH3OH), and shaken vigorously. At a suitable time, the tube was

removed from the bath and plunged into ice water. The time was

measured by means

of

a stopwatch from th e instant the tube was in-

verted to the moment it was immersed in ice water. After the tube had

been cooled, the sample was treated as described

i n

the next sec-

tion.

Isotope Dilution Technique. The 6- mL aliquots from the reaction

of tritium-labeled V I with base under C annizza ro conditions were

washed with C H 30 H solutions containing known am ounts of unla-

beled

VI.

The solution was thoroughly mixed and the ester was puri-

fied by recrystallization five times. For the first three recrystalliza-

tions, the CH 3 0 H solutions were cooled in an ice-salt-water bat h,

water was adde d to the cloud point. and a seed crystal was introduced.

The crystals were collected on an ice-jacketed fritted-glass funnel and

washed twice with ice-cold CH 30 H . Th e fourth and fifth recrystal-

lizations were from pure C H3O H: filtration was used to remove the

mother liquid and washings a fter the fourth. and decantation was used

aft er the fifth. After the ester had been dried over .Anhydrone i n a

desiccator kept at 10

"C,

melting points were ta ken. The ester was

liquefied and kept dr y by allowing the desiccator to wa rm to 25 OC.

Aliquots of the recovered ester were transferred to heighed counting

bottles. After the amount of ester had been determined, 20 ml. of

scintillation solution

( 1

5 mg of diphenylhexatriene and 4

g

of 2 , s -

diphenyloxazole/L of toluene) was added and the material & a s

counted

in

a Packard Tri-Carb liquid scintillation spectrometer at

I200 v .

The amount of VI (Ao) i n the aliquot of the reaction solution was

found from

A =

AS/So. where S is counts/min .g for recovered ester.

SOs counts/m in.g for undiluted VI . and A is g of untagged VI added

to the aliquot. Self-quenching by t he ester ma de

i t

necessarq to use

differ ent values of

So

for different amounts of ester coun ted. Corrected

So values were obtained from a plot of So vs. g of added

V I .

The ra te of consumption of

VI

under Cannizzaro conditions

is

slow

enough to be measurable,

as

shoun i n Table V I . Although the ratio

of total base (CH3O-

+

HO- ) to ester was

2:l

at 7ero time. the re-

action was treated as first order since

a t

7

s

the concentration of

VI

was 4.73 X M while the total strong base concentration was 6.72

X

IO-'

VI.

Accordingly.

a

plot

\ b a s

nude of the logarithm

of

the

concentration of V I

vs.

time. (Concentr ations used were those after

the fifth recrystallization.) The first-order rate constant

X

of 0.37

s-I obtained from the initial slope. which ~ 4 3 sonstant from 0 io ?0

s (four points), was interpreted as being that for the reaction? of

V I

wi t h HO- and CH 30- . The fractions of the initial V I left after 7.

12.

Table VI.

Reaction of Tritium-Labeled 0.0625

M V I

with 0.1250

M

N a O H i n 7 4% C H 3 0 H

;it

99.8

0.1

OC

sample counted,

S,

counts min-'

time.

s

A , g no. of recrystns mp. "C g sam ple coun ts",h '5-I

[V I ] , [ '

0 5.532 4 19.2- 19.7 0.0 108 278 857 71 7*

3.58 x

107 6 .30 X IO-'

4 6 4

x

10-3

5.490 4 19.0- 19.8 0.1001 I30

910 f 25*

1.31

x

106

3 .73

x

10-318.5-19. I 0.0999 I33 870 f 320* 1.34 X I O h

12 5.484 4 19.0- 19.7 0. I007 17 006 220* 1 .68

x

105 6.0 x lo-'

5 18.0- 18.5 0.1000 176 I67 1473 1.76

X

10'

6 .2

x

10-4

20 5.499 4

18.8- 19.8 0.0997

I3 833 I18 1.34 X I O 4 3 .7 x l o - '

5 18.0- 18.7 0. I000

I2

917 185

1.24

X I O J 4.4 x io-i

40 5.487

4 19.1-19.7 0.1001 9750 f 168 9.22

x

10' 3.8

x 10-5

5

18.0-18.5

0. I000 9465 162

8.99 x 103 3.2 x

l o - '

90 5.490 4 18.7- 19.5

0.1004 5683 58

5 . 1 4

x 103 1.8 x 10-5

5

18.2-18.7 0. I000 5065 64

4.59

x 103

1.6

x

10-5

300 5.487 4 19.0- 19.8 0.0996 1986

51

1.47 X

I O 3

5 . 2 x 10-6

5 18.2- 18.9

0. I002 I550 48

1.07

x

103 3.8

x

1 0 - 6

3630 5.485 4

18.8-19.7 0.0999

2086 f 3

I .-57 X 1 O3 _ .6 x 10-6

5 18.4- 19.0

0.1001 1551 5 3 6

1.07 X

I O 3

3.8

x

10-6

~~

['Astcrisked counts are in I min; ali others are i n 10 r n i n .

Mean value for ten trials wi th avera ge deviation from the iiiciin. .4lt cr subtrLicting

backgrou nd, which was 5 I8

f

2 count s/l 0 min for samples after the fourth recrystallization and 480

f

0 counts/

10

min for \amplea after

thc f i f t h recrystallimtion. (' alculated using So of I .75 X I O 9 counts/mi n.g for 7ero point and

SO

f I .2

I5

X IO' counts/niin.g for all othcr

points.

''

Calcula ted initial concentration was 0.0625 M.

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3 5 8 2

Journal of th e American Chemical Society /

101:13 /

June

20,

1979

Table VI I .

V I Found by Isotope Dilution in the Cannizz aro Re action of Tritium-Labe led 0.485

M I

with 0.217

M

N a O H i n 7 4% C H 3 0 H

at 100.5 "C

so

x 10-9,

no. of sam ple

S d

counts counts min-' [VI], M X

t ime, s reaction A g recr ystm u mp, "C counted , g sampl e countsb ,c min-' g-' g-' 107

0 0

0.5076

1

2

3

4

I800 5.9 0.4949 I

2

3

4

3600 13.4 0.4923

I

2

3

4

5400 18.7 0.4977

1

2

3

4

0.007 76

0.007 67

0.01 6 91

0.007 72

0.008 23

0.01

I

27

0.009 43

0.007 43

18.7-19.1 0.023 21

0.0

12 76

0.008 5 2

0.006 67

0.007 I O

18.7-19.2 0.043 72

18.7-19.1 0.04 8 20

18.7-19.1 0.014 18

2620

f

42

535 19

IO74

f 15

1827

f

129*

2532

f

36

491

f

18

989

f 1

7345

f

4*

2213

f

56

458

f 1

702 f 27

7756 f 125*

1826

f

50

450

f

20

547

f

17

6056 f 17*

29 630

2740

1700

1500

28 640

2020

1360

1810

20 060

I790

I590

I930

17 660

1870

1510

I070

I .77

1.494

1.692

1.767

1.47

1

1.739

1.772

1.645

1.725

1.780

1.715

1.776

7.4

4.

5.3

4.3

5.

4.7

4.5

5 .

4.9

4.

3.

5.4

First recrystallization was from CH 30 H -H 20 with filtration; next three were from a minimum of pure CH3O H with decan tation.

Ast-

erisked counts a re for 100 min; all others a re for 10min. C Mean value for ten trials with average deviation from the mean. After subtracting

background, which was 321 f 6 counts in 10 min for samples after the first recrystallization, 325 f 9 count s in

I O

min aft er the second re-

crystallization, 333 16 counts in 10 min after the third recrystallization, and 5300 140 counts in

100

min afte r the fourth recrystalliza-

tion

Table VI I I .

Concentration

of V I

i n the Cannizzaro Reaction of

Tritium-Labeled 0.485 M

I

with 0.2167

M

NaOH in 74% CH30H

at 100.5 "C

~ ~ ~ ~ ~ ~~~~~~

[VI ] calcd, [VI ] found,O

time.

s

%react ion 111 .

M

M

M

0 0 0.4854 7.4 X 4. X

I800 5.9 0.4596

6.6 X 5. X

3600

13.4 0,42 74 5.7 X 5. X

IO-7

5400 18.7 0.4042

5.1

X

3.

X

f 'See Tab le

V I I .

The nonzero values are probably due mostly to

labeled reactant

I

and product I I impurities rather than

V I

because

scavenging by unlabeled

I

and

I I

was not used in this series of mea -

surements.

and 20 s , respectively, were 7 (93% reacte d), I (99% reacted), and

0.07% (99.93% reacted). A falling off of k l after 20

s

(beyond 99.93%

reaction) was attributed to significant back-reaction regenerating VI

by reaction of VI1 with XII.

The amount of VI present at various times in a Cannizz aro reaction

of0.4854 M tritium-labeled

I

with0.2167 M N a O H i n 7 4 % C H 3 0 H

at 100.5 OC was determi ned using isotope dilution. The procedure for

preparing th e reaction solution and taking points has already been

described under "Kinetic Procedure". Bromthymol blue was used as

indicator. The third-order ra te constant k3 was calculated using

26 - Q ) ~ X

a ( a - 2x)

b (a - 2x)

a ( 6

- )

+

In

where

I

is the initial concentration

of

benzaldehyde-p-1 at 10 min ( t

= 0),

b

is the initial concentration of base a t I O min

r

= 0),and

x

is

Ihc amount of base reacted i n time t . The third-order rate constant

obtained , k3 = 1.72 * 0.21 X

M-' s-l ,

does not differ signifi-

cantly from that obtained

i n

the solvent isotope effect runs (see Table

I I ) .

After the 5 -mL aliquots from the run had been titrated, they were

made slightly acidic and a known amount of untagged V I was added.

CH3O H was added until all the V I had dissolved, and the resulting

solutions were then tre ated a s described above. Table

V I 1

gives the

concentrations of

V I

found at various times in this run.

The concentration of V I that should accumulate i n the Cannizzaro

reaction a t any time if it were an interm ediate can be calculated using

the steady-state approximation. The reactions involved ar e

2 C h H sC H O + H O - o r C H 3 0 - k C h H 5 C O O C H 2 C h H 5 (V I)

VI +

H O - o r C H 3 0 - C h H sC OO C H 3

or ChH5COOH)

+

C6HsCH'O-

Application of the steady-state approximation gives

d [ V l ] / d t

=

k3[I l2 [B] - kz[VI][B]

=

0

( 8 )

( 9 )

where [B] is the total base concentration ([CH3O-]

+

[ HO-1) at any

time i n the Canniz zaro reaction, k3 is the third-order rate consta nt

for the Cannizz aro reaction in 74% methanol, and kz is the second-

order rate constant for the reaction

of

VI with HO- or CH3O- in the

sam e solvent.

Equation 9 was used tocalcu late the concentration of VI that should

have formed if it were an intermediate

i n

the Cann izzaro reaction; k3

= I .86 X M-? s-' was used since this value is considered the

most accurate. k? as found above

is

0.37/0.0625 = 5.92

s-'

M-I. The

calculated concentrations of V I . along with those actually found, are

reported in Table

V I I I .

a-Hydro gen Isotope Effects.

Our earliest work on the Canniz zaro

r e i ~ c t i o n ~ ~ ~ ~ ~tilized

I-a-t.

The procedure involved Pyrex ampules

with IO-mL aliquots of 0.48

M

I-a-t and 0.24

M

N a O H i n 74%

CH iO H under Nz at 98.3 "C. After titration of

5

mL of the solution,

the remainder was diluted with 4

m L

of water and a dded to an excess

ol 'xmicarbazide i n a test tube. The mixture was thoroughly shake n,

heated on a ste am bath. and cooled to 5 OC. The white precipitate of

I scmic arbazo ne was filtered and recrystallized twice from 50% eth-

anol. Each sample w'as dried at 130 "C and less than

1

mm. The

melting point (220-221 "C ) and activitydhwereconstant after the first

crystallization.

I-a-t

was shown to exchange 3.5%of its tritium with

Na OH solution in I2 h and 6 .5% in 24 h, by sepa rating the I-a-t re-

maining as the semicarbazone and assaying it. Thus, the rate of ex-

change is slow com pared

to

the Can nizzaro reaction. The plot of log

(activity) vs. log (fraction unreacted) deviated noticeably from a

straight line for large fractions reacted for eight different samples of

scmic arbaz one from 0 to 80% reaction.'" After correction of the ac-

tivities for

loss

of tritium by exchange with the solvent it became linear;

then from the slope of the least-squares lineSh he isotope effect kH /kT

was found to be 1.24.':' Thi s value is even lower than t ha t found by

Miklukhin for kH /kD from a similar competition experiment.?"

Analysis for Benzyl Methyl Ether I X ) . IX was shown to be stable

under C annizza ro conditions. A reaction mixture of

I

and NaOH wi th

added IX i n 74% CH3OH was prepared. Four 6-mL aliquots were

scaled i n Teflon tubes and the tubes were placed in the bath a t 99.5

"C.

At suita ble times, at the beginning and near the end of the reac-

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Swa in e t a l . / Me c han i sm of the Cannizzaro React ion

t i on . tubes we re w i thd rawn , coo led to room tempe ra tu re , a nd opened .

A 5 -mL a l i q u o t w a s p i p e t t e d i n t o a 6 0 - m L s e p a r a t or y f u n n e l a n d

c x t ra c t e d w i t h t w o

IO-mL

p o r t i o n s o f p u r e p e n t a n e. T h e p e n t a n e

laye rs we re comb ined and evapo ra ted

to 2

mL. T h i s s a m p l e w as

w a s he d i n t o a 5 - m L v o l u m e t r i c f l as k a n d d i l u t e d t o t h e m a r k w i t h

p e n ta n e . T h e a m o u n t o f e t h e r w a s d e t e r m i n e d by GLC w i t h 30% (by

w e i g h t ) C a r b o w a x 600 o n

50-100

m e s h f i r e b r i c k a t 130 C. A r e a s

f o r t h r e e 1 5 - p L al i q uo t s of each samp le we re measu red by p l an ime te r

a numb er of t imes and averages used. Va lues for the areas for the thre e

15-pL

a l i quo ts o f a g i v e n s a m p le w e r e g e n e r a l ly w i t h i n 3% o f e a ch

o t h e r . F r o m k n o w n s ol u ti o ns o f 0 . 0 2 6 0 - 0 .2 8 0

M

IX i n p e n t an e , t h e

r a t i o o f a r e a t o c o n c e n t r a t io n f o r t h e c o l u m n w a s d e t e r m i n e d . This

v a l u e w a s t h e n u s e d t o c a l c u l a t e t h e c o n c e n t r at i o n o f IX i n s a m p le s

f r o m t h e C a n n i z r a r o r ea c t i o n. T h e r e w a s no s i g n i f ic a n t c h a n ge i n

c o n c e n t r a t i o n of IX u n d e r C a n n i z r a r o c o n d i t i o n s : c o n c e n t r a t io n s

found i n two samp les taken a f te r I O m i n a t 9 9 . 5 "C were 0 .26 and 0.25

M; a f t e r 3 3 4 a n d 4 9 9 h t h e y w e r e 0 . 2 5 a n d 0 . 2 4 M .

A f t e r t h e f i n al p o i n t f r o m o n e C a n n i r z a r o

run

( 2 6 2 h,

>90%

r e -

ac t i on ) ha d been t i t r a ted , the resu l t i ng so lu t i on was ex t rac ted w i th

t H o 2 5 - m L p o r t i o ns o f p u r e p e nt an e . T h e o r g a n ic l a ye r s u e r e c o m -

b i n e d a n d e v a p o r a te d t o 2 mL. This so lu t i on was washed i n to a 5-mL

v o l u m e t r i c f l a s k a n d d i l u t e d t o t h e m a r k w i t h p e n t a ne . G L C u s i n g

C a r b o w a x 6 0 0 s h o w e d no peak fo r IX. IX i n pen tane (0.0260 M , the

amoun t tha t wou ld have been p resen t i f

IO%

o f h e

I

h a d r e a c te d w i t h

CH30- i o n b y m e c h a n is m 3 ) w a s a c c u r a t e l y m e a s u ra b l e b y t h i s

t e c h n i q u e ( a r e a / c o n c e n tr a t i o n r a t i o w i t h i n I % o f t h a t f o r 0 .2 6 -0 . 28

M) .

The re fo re ce r ta i n l ) less t h a n I %

of

IX

was

present.

References and Notes

(1) Supported in part by the Off ice of Naval Research, the Atomic Energy

Commission, the National Science Foundation, and the National Institutes

of Health, and by a predoctoral NIH fellowship to C.R.M.

(2) For further experime ntal details, c f. (a) W A. Sheppard, Ph.D. Thesis,

Massachusetts nstitute of Technology, 1954; (b) C. R. Morgan, P h D Thesis,

Massachu setts Institute of Technology, 1963.

(3) (a) C. G. Swain and W. A . Sheppard, Abstracts, 127th National Meeting of

the American Chemical Society, Cincinnati, Ohio, April 195 5, p 40N; (b)

C . G. Swain, A. L. Powell, and C. R . Morgan, Abstracts, 144th National

Meeting of the American C hemical Society, Los Angeles, Calif.. April 1 963,

p 18M; (c) A. L. Powe ll, C. G. Swain, and C. R. Morgan in Tritium in the

Physical and Biological Science s , V ol. 1, International Atomic Energy

Agency Sym posium, Vienna, 1962, pp 153-160; C. G. Swain, A. L. Powell,

C.

R .

Morgan, T.

J.

Lynch.

S.

R. Alpha. and R. P. Dunlap, Abstracts, 166th

National Meeting of the American Chemical Society, Chicago, Ill., Aug

1973, No. ORGN -27.

(4)

C.

G. Swain, A. L. Powell, T.

J.

Lynch, S.

R.

Alpha, and

R .

P. Duniap, J. Am.

Chem.

Soc.

ollowing paper in this issue.

(5) Office o f Naval Resea rch, Boston, Mass. Guest of the Institute. 1956-

1979.

(6) (a) F. Wohler and J. Liebig, JUSIUSiebigs Ann. Chem ., 3, 252 (1832): (b)

S.

Cannizzaro,

ibid.

88, 129 (1853). For extensive discussions, see (c)

T. A. Geissm an, Org. React., 2, 94 (1 944); (d) E. R. Alexander, Principles

of Ionic Organic Reactions . Wiley, New York, 1950, p 168; (e)

J.

Hine,

Physical Organic Chemistry , 2nd ed., McGraw-Hill, New York, 1962, p

267.

3583

(7) M. S. Nemtsov and K. M . Trenke, Zh.

Obshch. Khim.,

22,415 (1952); Chem.

Abstr.. 46. 84 85 i (1952 ).

(8) A. Lachman,

J.

Am.

Chem.

SOC. 5, 2356 (1923).

(9) (a) H . Fredenhagen and K. F. Bonhoeffer,

2.

Phys. Chem., Abt. A, 181,379

(1938); (b) C. R. Hauser, P. J. Hamrick, J r., and A. T. S tewart, J. Org. Chem.,

21, 260 (1956).

(10) (a) E. L. Molt , R e d Trav. Chim. Pays-Bas, 56, 233 (1937); (b) A. Eitel and

G. Lock. Monatsh. Chem., 72, 392 (1 939): c) E. Tomm ila, Ann. Acad. Sci.

Fenn., Ser. A. 59 (a) , 3-69 (1942); Chem. Abstr., 38, 6175 (194 4)

(11) (a) K. H. Geib, Z. Phys. Chem., Abt. A, 169, 41 (1934); (b) A. Eitel, Monatsh.

Chem., 74, 124 (1942); (c) H. v. Euler and T. Lovgren,

Z.

Anorg. Chem.,

147, 123 (1925); (d)R. J. L. Martin,

Aus t .

J. Chem., 7, 335 (1954); (e) E.

Pfeil, Chem. Ber., 84, 229 (1951);

(f)

E. A. Shilov and G. I. Kudryavtsev,

Dokl. Akad. Nauk SSSR, 63, 681 (1948 ); Chem. Abstr., 43, 4547

(1949).

(12) H. H. Jaffe, Chem Rev., 53, 209 (1953).

(13) F. Haber and

R.

Willstatter. Ber., 64 , 2851 (1931); J. Weiss, Trans. Faraday

(14) E.

R.

Alexander, J. Am. Chem.

SOC.,

69, 289 (1947).

(15) M.

S.

Kharasch and

R.

H. Snyder, J. Org. Chem., 14, 819 (1949).

(16) L. Claisen,

Chem.

Ber., 20, 646 (1887); H. Meerwein and

R .

Schmidt, Justus

(17) M. Senkus and W. G. Brown,

J.

Org.Chem., 3,5 69 (193 8). Exchange occurs

Soc. 7, 782 (1941).

Liebigs Ann. Chem., 444, 2 21 (1925).

even at 2 5 OC with no base added.

(18) B. Eistert, Tautomerie und Mesom erie , F. Enke, Stuttgart, 1938, p 116;

ref lo b, p 410. L. P. Hamm ett, Physical Organic Chemistry , M cGraw-Hill,

New York, 1940, p 350, proposed this mechanism in slightly modified form

to explain the fourth-order term s; see also E. R. Alexander, J. Am. Chem.

SOC.,70, 259 2 (1948).

(19) A. E. Favorsky,

Zh.

Fiz. Khim., 27, 8 (1895): ref 16, p 230.

(20) G. P. Miklukhin and A. F. R ekasheva, J. Gen. Chem. USSR(€ngl. Trans/.),

25, 1099 (1955);

Zh.

Obshch.

Khim.,

25, 1146 (1955).

(21) K. J. Laidler. Che mica l Kinetics , 1st ed., McGraw -Hill, New York, 1950,

pp 96-101,2nd ed , 1965, pp 137-143

(22) Cf ref 25 in C G Swain and D

R

Crist,

J

Am Chem S o c , 94, 3199

(1972)

(23) K. B. Wiberg,

J.

Am. Chem. SOC., 78, 53 71 (1954): D. Luther and H. Koch.

Ber., 99, 2227 (1966).

(24) H, von Buttlar and W. F. Libby, J. lnorg. Nucl. Chem., 1, 75 (19 55). Tritium

contents of lo - ' ' in ordinary hydrogen can be me asured

to

f 5 % accu-

racy.

(25) C. G. Swain and A. J. Kresge, J. Am. Chem. Soc., 80, 5281 (1958).

(26) (a) M. L. Bender and W. A. Glasson, J. Am . Chem. Soc., 81, 1590 (1959);

(b) W. P. Jencks and M. Gilchrist. ibid., 84, 2 910 (196 2).

(27 ) C . G. Swain, D. A. Kuhn, and R. L. Schowen, J. Am. Chem. SOC. 87, 1553

(1965).

(28) C . G. Swain and E. R. Thornton, J. Am. Chem. SOC.,83, 3890 (1961).

However, exact agreement is not

to

be expected becau se the solvent is

74 % m ethanol-26% water at 100 OC instead of pure water at 25 C .

(29) Likewise J. Hine and H. W. Haworth, J. Am, Chem. SOC., 0, 2274 (1958),

found the rearrangement of benzil to benzilic acid

to

be 1.85 times as fast

in 67 % dioxane-33 % D20 as in 67 dioxane-33 H20 and concluded

that the phenyl migration precedes the proton transfer.

(30) It also excludes a cyclic m echanism for the Cannizzaro reaction in which

hydrogen is transferred between carbons as a proton rather than as a hy-

dride ion or hydrogen atom, an alternative suggested by G. A. Hamilton:

E. T. Ka iser and F. J. Kezdy, fr og . Bioorg. Chem ., 1 148-152 (1971).

(31) M. F. Hawthorne and E.

S.

Lewis, J. Am. Chem. Soc.. 80, 4296 (1958).

(32) Melting points and boiling points are uncorrected.

(33) The procedure used here was essentially that of H. C. Brown and

C.

Groot,

J. Am . Chem. Soc., 64, 2223 (194 2). for preparing deuterium chloride.

(34 ) D . M. Hughes and

J.

C. Reid, J.

Org.

Chem., 14, 524 (1949).

(35) L. Gattermann and H. Wieland, Laboratory Methods of Organic Chemistry ,

Macmillan, New York, 1938, p 209,

(36) C. W. Gould, Jr., G. Holzman, and C. Niemann, Anal. Chem., 20, 361

(1948).

(37) H. B. Haas and M . L. Bender, J. Am. Chem.

SOC.,

71, 17 68 (1949).

(38) Reference 35, p 220.

(39) F. W. Schwab and E. Wichers, J . Res. Natl. Bur. Stand., Sect. A, 34,333

(40) H. Adkins and H. R. Billica, J. Am. Chem. SOC.,70, 696 (1948).

(41)

0.

Kamm and W. F. Kamm, Organic Syntheses . Collect.

Vol.

I,Wiley,

(42) A. Reissert. Ber., 38, 1610 (1905).

(43)

R .

L. Shriner,

R.

C. Fuson, and D. Y. Curtin, Systematic identification of

(44) E. C. Horning and M. G. Horning, J. Org. Chem., 11, 97 (1946).

(45) Reference 43, p 218, procedure A.

(46) C. G. Swain, V. P. Kreiter, and W. A. Sheppard. Anal. Chem., 27, 1157

(1955).

(47) K. E. Wilzbach, L. Kapian, and W. G. Brown, S cience, 118, 522 (1953 ).

(48) These values were reported in 1955.3aDr. Clair J. Collins informed us in

1960 that on repeating this work he obtained a value of 5. 26.

(49)

0.

Redlich and F. Pordes. Monatsh. Chem., 67, 203 (1936).

(50)

H. Lund and J. Bjerrum, Ber., 64, 2 10 (1931); L. F. Fieser, Experiments

in Organic Chemistry , 3rd ed.. D. C. Heath, Boston, Mass., 1955, pp 289,

29.1

(1945).

New York, 1941, p 104.

Organic Com pounds , 4th ed., Wiley. New York, 19 56.

(53)

(54)

These analyses were performed by Mr. Josef Nameth. Urbana, 111

H. Rinderknecht and C. Niemann.

J.

Am. Chem. SOC.,70,26 05 (1948); R.

0.Clinton and

S.

C. Laskowski, ibid., 70, 3135 (1948).

J . Kendall and A. H. Wright, J. Am. Chem.

SOC.

2, 177 8 (1920).

W. T. Olson et al., J. Am. Chem. Soc. 69, 2451 (1947).

(55) H.Diehl and G. F. Smith, Quantitative Analysis, Elementary Principles and

Practices , Wiley, New York, 1952, p 207.

(56) A. M . Downes and G. M. Harris, J. Chem. Phys. 20, 196 (1952).