MECHANISM OF THE HYDROLYSIS OF ORGANIC PHOSPHATES
Aug. 20, 1953
[CONTRIBUTION FROM THE DEPARTMENT OF CHEMISTRY, THE MOUNT
SINAI
4035
HOSPITAL]
The Mechanism of the Hydrolysis of Organic Phosphates. II. o-Carboxynaphthyl Phosphates'
BY J. D. CHANLEY AND E. M. GINDLER RECEIVEDMARCH31, 1953 The rates of the hydrolyses of 2-carboxy-1-naphthyl phosphate (11), 3-carboxy-2-naphthyl phosphate (111) and l-carboxy2-naphthyl phosphate (IV), to the corresponding parent acid and phosphoric acid have been investigated in the pH region of 2-10. These orthocarboxynaphthyl phosphates show the same striking pH dependency on hydrolysis as observed in the case of salicyl phosphate (I).2 They are most unstable a t PH ca. 5-6, are very stable in the extreme acid region and completely stable in strong alkali up t o 75". The ease and unusual PH dependency on hydrolysis, observed with compounds 11, I11 and IV,support the assumption of a mechanism involving the formation of a cyclic transition state as first proposed in the study on the hydrolysis of salicyl phosphate.* The variations in rates of hydrolysis of the aforementioned compounds are discussed and the entropies and heats of activation evaluated.
We have previously reported o n the mechanism of the hydrolysis of salicyl phosphate (I).2 In continuation of this work we have investigated the hydrolysis of three related o-carboxy-aryl phosphates: 2-carboxy-1-naphthyl phosphate (II), 3carboxy-2-naphthyl phosphate (111) and l-carboxy-2-naphthyl phosphate (IV) to the corresponding parent acid and phosphoric acid.
0
2-10 under the mild conditions which effect the complete hydrolysis of the aforementioned carboxy phosphates. pH Dependency.-We have determined the rates of hydrolysis of compounds 11, I11 and IV a t 37" over the fiH range 2-10 in buffered medium of ionic strength p = 0.1 by analysis for liberated phosphoric, acid. In each instance first-order kinetics obtained throughout the course of the reaction. The same analysis, as given for salicyl phosphate,2 was employed in the elucidation of PH dependency for the hydrolysis of compounds 11, I11 and IV. The rate equation deduced to describe the observed rate of hydrolysis a t any pH is kobd.
I
oz-$))2 I11
I1
C6:gH)*
As with salicyl phosphate the three . carboxynaphthyl phosphates exhibit the same striking pH dependency on hydrolysis. They are most rapidly hydrolyzed at that pH (ca. 5-6) where the compound exists mainly in the di-ionic form, are very stable in the extreme acid region and completely stable in strong alkali up to 75'. The half-life periods a t 37' and PH ca. 5.7 for the hydrolysis of the four aforementioned compounds I, 11, I11 and IV are 2.2, 0.5, 4.3 and 84 hours, respectively. This ease of hydrolysis is in marked contrast to the behavior of phenyl phosphate, a-naphthyl phosphate, &naphthyl phosphate18 salicyl aldehyde phosphate4a and m- and p-carboxyphenyl phoshate,^^ which remain virtually unchanged a t PH (1) This work was supported in part by a grant from the National Science Foundation. The material was presented in part at the Annual Meeting of the American Chemical Society, Division of Organic Chemistry, on September 17, 1952. For the first paper in this series see reference (2). (2) J. D. Chanley, E.M. Gindler and H. Sobotka, THIS JOUENAL,74, 4347 (1952). (3) The half-life periods of a-and &naphthyl phosphate over the p H range 2-6 are ca. 4300 and 1200 hours, respectively, the rate of hydrolysis dropping off rapidly above p H E to be reported in a subsequent communication. (4) (a) C. Manaka, 1.Biochcm., 14, 481 (1932); (b) 14, 191 (1931). (Ba) As with salicyl phosphate (cf. ref. 3) we have observed that at p H v b e s above 10 compounds 11.I11 and I V undergo no measurable hydrolysis during 6 hours at 76'.
k2Af2
(1)
where kl and kz are the specific rate constants for the hydrolysis of the mono-ionic form and di-ionic form and M I and M2 are the respective mole fractions for each of the forms at the particular PH XO
IV
= klM1 f
2 0
R-o-pkAH
-COOH -cooMI MI R = naphthyl (1,2-, 2,3-, or 2,l-substituted)
The specific rate constants k1and kz were obtained in exactly the same manner as already described.2 The determination of the three ionization constants KI, K2, Ka {at fi = 0.1) (see Table 11) of compounds 11, I11 and IV makes possible the calculation of Ml and M Za t any pH. From the observed rate constants a t PH ca. 5.7, ks was evaluated; and a t pH 2.3 kl was obtained. These particular PH's were chosen since the only reactive species present a t pH 5.7, the di-ionic form, is almost a t a maximum; a t PH 2.3 the monoionic form to the over-all rate is small and may be accounted for. The evaluation of kl, kz, MI and Ma enabled us to compute from equation (1) the theoretical values for the rate constants a t various PH's (see Table I). The agreement between observed and calculated values for the rate constants is satisfactory. In general the greatest deviations occur a t the high PH's, since slight changes in pH effect a considerable percentage change in the mole fraction of the di-ionic group. This point is discussed in detail in the first paper of this series2 The particular shape of the PH DS. hydrolysis rate curves (see Fig. 1) will be governed (1) by the
TABLE I
HYDROLYSIS OF U-CARBOXYNAPEITHYL hOSPHATE8‘ 3-Carboxy-2-phosphate (111)
2-Carboxy-1-phosphate (11) kobad.
Ma
.$f L
9H
konled.
h r . 7 X 1000
.u
M I
kobad. 2
0 03 166 (166) 0.85 0.04 0 91 2 34 86 13 257 2 94 286 83 . 14 071 *;in 3 71 54 46 756 .50 1200 07 92 1300 4 82 .08 .91 1300 (1300) 82 01 99 5 67 1300 99 1300 5 94 6 22 6 57 .37 1280 .. .95 1300 6 69 1120 .. .86 1280 .13 7.22 711 .. .56 814 .03 7 90 .. .24 297 313 .. 8 50 .006 Computations based on figures in parentheses; t is 37.2‘
three ionization constants for the particular phosphate since these constants determine the mole fractions of MI and M 2 , (2) by the relative values of kl and kz. However, since the first ionization constants all fall around pK = 1.2 and ko is larger than k l , the contours of the curves will be governed principally by pKz and PK3, in the region of p H 2-10, The further apart the latter are, the flatter and wider the maximum region, conversely the closer these PK’s, the sharper will be the maximum region. This is indeed the case. Figure 1 shows the log of the experimental rate constants as plotted against the p H . The curves for compounds I, I11 and IV are nearly identical in shape, since the difference between f i K ~and $K3 is almost a constant value (see Table 11). In contrast, 2carboxy-1-naphthyl phosphate (11), which has an
I
II:
3.00
2.00
f P M
c
I
1.oo
0.00
1
I
I
I
I
2
3
4
5
6
7
1
J
8
9
PH . Fig. 1.-Logs of observed rates of hydrolysis in hours“ a t 37.2’ for compounds I, 11, I11 and IV at various pH values. The solid curve is derived from the values of kt and kl obtained a t pH 2.34 and 5.67, respectively.
I-Carboxy-2-phosphate (IV)
kaalcd.
hr.” X 1000
22.3 42 2 I12 188 169
(22.3) 41 112 188 (169)
90.0
77.0
30.5 8.7 1.9
26.3 6.8 1.2
‘1fI
0.84 6
