COMWNICATIONS TO THE EDITOR
4588
Iiowland, Colin MacKay and Michael Henchman for stimulating and helpful discussions. STERLING CHEMISTRY LABORATORY YALEUNIVERSITY RICHARD WOLFGANG XEW HAVEN,CONNECTICUT AUGUST20, 1962 RECEIVED
Vol. s4 I1
ti
-OH CH3 5H3 I
.
I
.o
-0
I11
CHB CHs
-C-H
---+
1
KINETICS AND MECHANISMS OF T H E RAPID ALKALINE HYDROLYSIS OF DIMETHYL PHOSPHOACETOIN 1
I
,O“-C
HO-C-C-H
+ t
v
OCH3 VI
Sir:
The hydrolysis of dimethyl phosphoacetoin2 Bender and Silver5 explained the fast rate of the (I) in the pH-range 7.7-8.3 gives acetoin (11) hydroxide ion-catalyzed hydrolysis of methyl oand dimethylhydrogen phosphate (111), identified formylbenzoate in terms of aldehyde participation as its barium salt. The reaction is first order with (VII, R = H). respect to the phosphotriester, I, and first order We have interpreted the extremely rapid hywith respect to hydroxide ion. The second-order drolysis of the crystalline cyclic saturated oxyphosrate constant in this pH-range is kS = 360 h 20 phorane,6a VIII, to the cyclic phosphotriester, X, liters-mole-l-sec.-’ a t 25’. The rate was de- in benzene or ether solution, as involving the oxyKC104 $lby titration with 0.02 M phosphorane intermediate,6bIX. termined in 0.07 .. NaOH in the pH-stat3 already described. The R CH3 CH3 initial concentration was 4 X M. I ,OH I / CH3 1
CH3
0-
CH3 CH3
I
EX+
C-C-H I/ I
II
0
I
+ O=P-OCHa
A-L-H
I
I
OCIh
OH
I1
I11
VII, R = C,H, or H
OCHj VIII, Ac=CHBCO
Measurements of the rate of hydrolysis of a 0.05
JI solution of trimethyl phosphate in 0.02 M KC104 with 0.05 M NaOH gave 1.4 X lop4 litersmole-’-sec.-’ a t 2 5 O . The hydroxide ion-catalyzed hydrolysis of the simple a-keto1 phosphotriester, I, is a t least 2 X lo6 times faster than that of trimethyl phosphate. This enormous acceleration could be explained in two ways: (1) A substitution a t phosphorus on the enediol-phosphate, IV, in which the rate enhancement would be due to the unsaturated nature of the leaving group and to hydrogen-bonding assistance. This picture is being considered further. (2) Carbonyl participation, (V), and oxyphosphorane formation, (VI), in the hydrolysis. CH3
CH3
I
I
?
-f
11
+ 111
1v
(’113 I 1 Ac-C-C-Ac I
I
4 /o P
0” ‘OCHs
X
(:Ha
I
-CH
3
Ac-C-C-Ac I
CIls
I
1
0 0 ,>P( HO OCH3 ‘OCH3 IX
I
Formulas VI and IX bring out the structural features which could account for the difference in the direction of the hydrolytic cleavage of the keto1 phosphate (I) and of the oxyphosphorane (VIII). In the former, the ring is not preserved due to facile C-0 bond fission. These observations may have a bearing on the chemistry of naturally occurring a-keto1 phosphomonoesters such as certain sugar phosphates, and, as pointed out by Bender5 for carboxylic esters, on enzymic processes of phosphate esters in general.
Newinan and Hishida4 have suggested that the increased rate of alkaline hydrolysis of certain methyl o-benzoylbenzoates is a consequence of steric factors which promote a mechanism involving attack of hydroxide ion on the ketonic carbonyl (VII, R = C6H?)followed by an intramolecular expulsion of a methoxide ion. Subsequently,
NOTEADDEDIN PROOF.-C. A . Vernon gives kt = 1.3 X at 25’ for the alkaline hydrolysis of trimethyl phosphate in water; cf,. “Phosphoric Esters and Related Compounds,” The Chemlcal Society, London, Special Publication N o . 8, 1957, p. 30. FAUSTO RAMIREZ’ STATEUNIVERSITY OF NEW YORK LONGISLAND CENTER B. HANS EN^ IX.B. DESAI OYSTERBAY,N. Y. RECEIVED AUGCST 23, 1962
(1) These investigations are being supported by t h e Cancer Institute of t h e National Institutes of Health (CY-4769) and t h e Petroleum Research F u n d Administered by t h e American Chemical Society. ( 2 ) F. Ramirez and N. B. Desai, J . A m . Chem. Soc., 82, 2652 (1960). (3) L. 1.arsson and B. Hansen, SDensk K e m . T i d s k r . , 68, 621 (1456). (4) hl. S . Sewman arid S . IIishida, .T, A m . C h e w S n r . , 8 4 , 33688 (l!Ifi?),
(5) hl. L. Bender a n d ?VI.S. Silver, ibid., 84, 4589 (1962). (6) (a) F. Ramirez, S . Ramanatban and N. B. Desai, i b i d . , 84, 1317 (1962); (b) in press. (7) Alfred P. Sloan Fellow 1861-1962. T h e authors appreciate t h e opportunity of examining the manuscripts of Newrnan and IIishida‘ a n d of Render and Silvers before publication. ( 8 ) A R l’harinaria, I i p p w l a , Swrdeii.
10-4 liters-mole-’-sec.-l
