41 8
THOMAS C. BRUICEAND STEPHEN J. BENKOVIC
position of the band is less sensitive to the amount of 1,2-dimethoxyethane when there is a substantial amount present. I t is concluded t h a t local environmental factors play an important role in determining the energy of the visible transition of the ketyl ion pairs. Solvent Polarity.---It is possible that the ketyl spectral shifts reflect solvent properties to a greater extent than solute properties or properties which depend on both solvent and solute (such as the degree of solutesolvent steric interaction). If this should be the case, these spectral variations might have value as mzasures of the “polarity” of ethereal solvents toward ionic or ionoid species. particularly organometallic compounds. In order to be empirically useful and possibly theoretically significant, such a measure of polarity would have to be shown to correlate, qualitatively or quantitatively, with other chemical phenomena dependent on the same kind of “polarity.” The fact that spectral shifts in another solvent dependent system have been successful in correlating spectra and reaction parameters ethereal solvents We have not attemptt-d the extraction of quantitative information on this point
[CONTRIRITION FROM
THE
Vol. 86
in a wide range of solvents is justification for seeking a siniilar application of the present results v, Moreover, it is possible that deviations from otherwise consistent correlational behavior may be significant in establishing the details of theories related to ionic aggregation and ethereal solvent effects in organometallic systems Data against which to make quantitative tests of correlations are not plentiful, but those which are available are, for the most part, consistent, and will be discussed in detail later. Acknowledgments. -This work was supported by Office of Ordnance Research Contract DA-0-2-195ORD-lt542 and Army Research Office (Durham) Grant D.I-XRO(D)-31-124. A portion of the work was s u p ported by National Science Foundation Grant GP-90. The authors wish to thank the staff of the Biometrical Laboratory, University of California, Riverside, for making available the computer facilities and for assisting us with computational operations. We are also indebted to tnany of our colleagues for helpful discussions, notably Professors s. I. Chan and J. F. Hornig. ( 5 5 ) Se? papers cited in footnote 43
DEPARTMENT OF CHEMISTRY, CORKELL UNIVERSITY, ITHACA, S . U.]
The Compensation in AH’ and A S * Accompanying the Conversion of Lower Order Nucleophilic Displacement Reactions to Higher Order Catalytic Processes. The Temperature Dependence of the Hydrazinolysis and Imidazole-Catalyzed Hydrolysis of Substituted Phenyl Acetates BY THOMAS C. BRUICEA N D STEPHEN J. BENKOVIC’ RECEIVED JIJLY 22, 1963 The hydrazinolysis and imidazole-catalyzed hydrolysis of a series of substituted phenyl acetates were found to be dependent on the concentration of t h e conjugate acid and base species of the nitrogen bases in the following manner: -d(ester)/dt = [ ~ , ( H z S K H * ) kgb(H?”H2)2 k,,(H?NNHz)(H?~c’”3~)](ester)and -d(ester)/& = [kn(C3H1N2) kgh(C3Hl?i*)21(ester),respectively. The terms k, are second-order rate constants for nucleophilic displacement a t the ester bond, and the krrb and k,, terms are third-order rate constants for general-base and general-acid assisted nucleophilic displacement reactions a t the ester bond. The k , - p value for hydrazine is considerably greater than t h a t for amnlonia, so t h a t the a-effect is greatest with the best leaving group. Also, the a-effect is of greater importance in k a b and in k,, than in k,. The p-values for the k g h and k,, terms are very much smaller than those for the k, terms, as previously found for general base-catalyzed ammonolysis reactions. The consistent finding t h a t the p-values for the third-order, generally assisted reactions are always much less than the p-values for the simple unassisted bimolecular reactions has the result t h a t the assisted reactions are always of much greater importance for nucleophilic displacement reactions on esters with poorer leaving groups. The k g h term for hydrazine, as previously found for ammonia, exhibits no deuterium solvent kinetic isotope effect; however, the k,b term for imidazole does. Gnlike the kgt, term, the k,, term for hydrazine does exhibit a deuterium solvent isotope effect. The AH* for the k , term does not appear t o be simply related t o the nature of the nucleophile nor the substituent on the phenyl ester. With change in the electronic nature of substituent groups on the ester, the TAS* term may follow a consistent pattern of decrease, of increase, or a random variation. The electronic effects on TAS* may be considered to be secondary perturbations of t h a t value determined by the nucleophile and the kinetic order of the reaction. By averaging the TA.Y* values for the series of esters for a particular term ( i , e . ,k,, k a h , or k K a )with a particular nucleophile, the electronic effects of substituent groups may be compensated for. The kinetic order of the reaction when multiplied by 5 i 1 kcal. mole-1 provides in each case (eleven reactions) the value of TASF,,. This result is discussed on the basis of the arbitrary division of T A S f into a component (TAS*L, ) determined by the number of species which must he brought to a position of close approach in order t o enter the transition state and a component (TAS *+.) which relates to the kinetic energy terms in taking the reactants from a position of close approach to the transition state. The expected lowering of AH and TAS+ accompanying the conversion of a lower order displacement reaction to a higher order catalytic process has been examined. The values of AH+ and TAS* for k , , k,,,, and k,, for the hydrazinolysis reactions are found t o behave in a compensatory manner so t h a t 4 F * becomes only slightly more negative for the catalytic reactions.
+
+
+
*
The displacement of a leaving group (--X) by a nucleophile ( : N H ) may be assisted by general-acid (AH) and by general-base (RH) I t is anticipated that the conversion of a bimolecular nucleophilic attack by : N H into one of the higher order catalytic processes (i.?., general acid or general base) should be accompanied by a compensatory change in potential and kinetic energy terms. Ahsumingt h a t (1) Predoctornl Fellow o f t h e Sational Tn-titute+ of Health (1960 l!l6,’3) A portion o f the Ph.1) Ihrqis nf S J R. ( 2 ) ‘F C Rroice. R m i i k h o i , r n Sy?nfiortn in Rznlopy, No. 15, 5 2 (1HG2). ( 3 ) M I , . RPnder. C h r m Rrv , 6 0 , R? ilR6O)
P
H-A
:N-H-
v
:B
AH* and TAS+ reflect simply potential energy and kinetic energy parameters, respectively, it is reasonable to suppose t h a t the necessity of incorporating extra species into the transition state should decrease TAS*.
PH
Hf (MI
7.40 7.40 7.40 7.40 7.40
0.000595 0.00119 0.00119 0.00179 0.00248
0.140 0.288 0.271 0.405 0.564
o c = 18 7.20 7.20 7.20 7.20
0.000694 0.00129 0.00178 0.00248
0.219 0.408 0.599 0.810
oc = 25 6.93 6.94 6.95 6.95
.000757 .00141 .00195 .00270
0.331 0.594 0.797 01.16
0.000218 0.000328 0.000437 0.000546
0.133 0.216 0.284 0.353
m-NOZC6H40COCH3 o c = 10 8.57 8.57 8.58 8.59 8.59
0.00297 0.00297 0.00593 0.00900 0.0124
8.49 8.30 8.30 8.30 8.30
0.167 0.0349 0.0598 0.0896 0.125
0.263 0.0165 0.0434 0.0932 0.179
OC = 10 8.60 8.60 8.61 8.60 8.60 8.41 8.42 8.43 8.43 8.20 8.20 8.21 8.21
0.060 0.120 0.180 0.250 0.250 0.115 0.143 0.199 0.199 0.0821 0.103 0.143 0.143
0.0437 0.156 0.361 0.721 0.701 0.154 0.240 0.499 0.479 0.0955 0.144 0.285 0.286
OC = 18
oc = 34 7.13 1.13 7.13 7.13
0.0652 0.0642 0.141 0,229 0.337
8.72 8.72 8.73 8.74 8.39 8.39 8.39 8.39 8.20 8.21 8.21 8.21 8.00
0.0614 0.123 0.184 0.256 0.0600 0.120 0.180 0.250 0.0470 0.0941 0.141 0.196 0.0342 0.0684 0.103 0.143
0.0624 0.204 0,464 0.874 0.0631 0.212 0.481 0.925 0.0438 0.153 0.340 0.615 0,0292 0.0958 0.201 0.391
0.0401 0.0802 0,120 0.167 0.0436 0.0872 0.131 0.182 0.0467 0.0801 0,120 0.167 0.167 0.0347 0.0694 0.104 0.145
0.0461 0.153 0.277 0.524 0.0504 0.165 0.339 0.621 0.0628 0.155 0.345 0.616 0.600 0,0385 0.188 0.258 0.468
8.00 8.00 8.00
OC = 18
OC = 25 8.37 8.37 8.39 8.39 8.39
0.00342 0.00586 0.00878 0.0122 0.0122
.128 .245 .342 .so2 .SO3
OC = 25 8.19 8.19 8.21 8.20
0.0060 0.0120 0.0180 0.0250
0.352 0.736 1.02 1.51
oc = 34 6.76 0.00318 6.77 0.00441 6.77 0.00612
0.326 0.443 0.621
C6HSOCOCH3
oc = 4 8.88 8.88 8.89 8.89 8.89 8.49 8.49 8.50 8.48 8.48 8.48 8.48
0.0777 0,133 0.200 0.200 0.278 0.0474 0.0814 0.122 0.170 0.0468 0.0802 0.120
419
HYDRAZINOLYSIS AND HYDROLYSIS OF PHENYL ACETATES
Feb. 5 , 1964
0.0553 0.165 0.306 0.281 0.661 0.0257 0.0648 0.145 0.274 0.0257 0.0669 0.142
8.29 8.29 8.30 8.30 8.11 8.12 8.12 8.12 7.90 7.90 7.90 7.90 7.90 7.80 7.81 7.81 7.81
OC = 34 8.13 8.13 8.13 8.13 7.76 7.76 7.75 7.74 7.63 7.62 7.61 7.61
0.0423 0.0845 0.127 0.176 0.0445 0.0890 0.134 0.186 0.0365 0.0730 0.109 0.152
0.0654 0.195 0.383 0.682 0.0761 0.231 0.466 0.835 0.0549 0.166 0.334 0.600
It then follows that the change in AF* would depend on whether AH* or T A S exhibited the greater sensitivity to the conversion of the lower order reaction to a higher order catalytic process. It is both of organic and biochemical interest t o determine how much of the cost of incorporating an extra species is returned via the catalytic process. Thus, most proposals for enzymatic catalysis envisage
7.96 7.96 7.94 7.96 7.54 7.54 7.52 7.53 7.30 7.30 7.30 7.33 7.30 7.29 7.30 7.29
0.0420 0.0719 0.108 0.150 0.0348 0.0596 0.0894 0.124 0.0349 0.0599 0.0901 0.125 0.0336 0.0577 0.0864 0.120
0.0981 0.217 0.416 0.687 0.0717 0.152 0.289 0.514 0.0758 0.169 0.337 0.568 0,0768 0.180 0.346 0,598
8.13 8.13 8.13 8.13 8.13 7.76 7.76 7.75 7.74 7.63 7.62 7.61 7.61
oc
8.60 8.60 8.61 8.61 8.42 8.43 8.43 8.44 8.20 8.21 8.22 8.22
0.0603 0.120 0.180 0.250 0.116 0.145 0.181 0,202 0.0832 0.104 0.121 0.145
0.0295 0.109 0.231 0.449 0.111 0.165 0.251 0.320 0.0694 0.107 0.141 0.205
OC = 18 8.72 8.72 8.73 8.74 8.39 8.40 8.40 8.40 8.41 8.41 8.20 8.21 8.21 8.21 8-00 8-00 8.00 8.00
0.0614 0.123 0.185 0.256 0.0600 0.120 0,180 0.180 0.250 0.250 0.0471 0.0941 0.141 0.196 0.0342 0.0684 0.103 0.143
0.0408 0.141 0.320 0.613 0.0442 0.152 0.315 0.328 0,666 0.637 0.0304 0.105 0.239 0.452 0.0201 0.0705 0.142 0.286
0.0401 0,0802 0,120 0.167 0.0425 0.0850 0.128 0.177 0.177 0.0331 0.0662 0.0992 0.138 0.0347 0.0695 0.104 0.104 0.145
0.0285 0.0805 0.177 0.322 0.0301 0.111 0.227 0.383 0.373 0.0230 0.0710 0.148 0.276 0.0273 0.0879 0.168 0.177 0.341
OC = 25 8.29 8.29 8.30 g.30 8.10 8.10 8.10 8.10 8.10 7.92 7.92 7.92 7.91 7.81 7.81 7.80 7.80 7.80
0.0429 0.118 0.128 0.255 0.488 0.0472 0.146 0.331 0.590 0.0389 0.123 0.247 0.445
P-CH30C6H40COCH3
PCH3C6H40COCH3
OC = 10
-
0.0423 0.0845 0.0845 0.127 0.176 0.0445 0.0890 0.134 0.186 0.0365 0.0730 0.109 0.152
10
8.60 8.60 8.61 8.61 8.42 8.43 8.43 8.44 8.20 8.21 8.22 8.22 8.22
0.060 0.120 0.180 0.250 0.116 0.145 0,181 0.202 0.0832 0.104 0.121 0.145 0.145
0,0299 0.117 0.257 0.493 0.115 0.186 0.300 0.383 0.0728 0.113 0.152 0.221 0.229
oc = 18 8.72 8.72 8.73 8.74 8.40 8.40 8.41 8.41 8.20 8.21 8.21 8.21 8.02 8.02 8.02 8.02 OC
-
8.26 8.26 8.26 8.26 8.26 8.10 8.10 8.10 8.10 7.92 7.92 7.92 7.92 7.91 7.81 7.81 7.80 7.80 7.80
0.0614 0.123 0.185 0.256 0.0600 0.120 0.180 0.250 0.0471 0.0941 0.141 0.196 0.0353 0.0705 0.106 0.147
0.0409 0.142 0.321 0.589 0.0430 0.160 0.357 0.665 0.0290 0.103 0.228 0.452 0.0193 0.0676 0.148 0.286
0.160 0.187 0.213 0.240 0.267 0.0425 0.0850 0.128 0.177 0.0331 0.0662 0.0993 0.0993 0.138 0.0347 0.0694 0.104 0.145 0.145
0.314 0.427 0,552 0.726 0.842 0.0287 0.100 0.217 0.411 0.0206 0.0658 0.149 0.143 0.265 0.0236 0.081 1 0.178 0.354
25
0.336
a polyfunctional "active site" for the enzyme. The active site would then have the advantage of a prior restriction of the nucleophilic and catalytic functional groups resulting in a lowering of AF+ by an amount ( n - 1)y over the same reaction in aqueous solution, (where n is the number of nucleophilic and catalytic groups, and y the kinetic energy cost in AF+ in bringing each species into the transition state).
THOMAS C. BRUICEAND STEPHEN J. BENKOVIC
32U
Vol. 86
The p H of solutions were determined prior to and a t the completion of the reactions a t the reaction temperature. p H measurements were made with a Radiometer EK 2021 B combined glass calomel electrode and a Radiometer Model 22 p H meter with a Radiometer Model PH.i 630 Pa scale expander. T h e electrode was kept a t the temperature of the reaction being investigated, and reaction solutions were prepared to a tolerance of 1 0 . 0 1 p H unit. In the calculation of the rate constants the heats of ionization of hydrazine and imidazole were taken into account. The pK2 value for hydrazine and pK, value for imidazole (both a t p = 1.0 M with KCl) were determined by the method of half neutralization. pKz'
8.60 8.40 8.20 7.98
T e m p . , OC.
pKi'
10 18 25 34
Temp
7.54 7.36 7.20 7.02
'C
10 18 26 34
From the pK2' values a A H i of 10.4 kcal. mole-' was calculated for hydrazine. The predicted pK2' value a t 30" is 8.08 in good agreement with a previously determined value of 8.07 a t this t e m p e r a t ~ r e . From ~ the pK1' values a A H i of 8 . 4 kcal./mole was calculated for imidazole and was found t o compare favorably t o those previously recorded for imidazole and imidazole compound~.*,~ Deuterium Solvent Isotope Effects.-For hydrazine reactions carried out in D20 a t 18' the p D values were taken as the pH, meter readings Dlus the DroDer electrode correction.1° The D K ~ (18') value for Lydrazine in'D20 was determined t o he 9.11 ( p = 1.0 M w i t h KCI). For imidazole reactions carried out in D20 at 34' the p D values were also taken as the p H meter readings plus the proper electrode correction. The pK,' value at 34" for imidazole in DzO was determined t o be 7.38 ( p = 1 . 0 M with KC1). For experiments at 10 and 25' half-neutralized imidazole was employed, thus obviating the determination of pK1' and electrode corrections.
Fig. 1.-The
observed rates of disappearance of ( 0 )p-methyl-, ((I) unsubstituted ) phenyl acetate as a functi8-,11 of hydrazine concentration. ;Oj 1,-methoxy-, and
Fcir the purpose of determining the anticipated compciisatory relationship in AH+ and T A S , we have determiried these parameters for the nucleophilic, general-acid and general-base catalyzed nucleophilic 1; vtlrazinolysis of substituted phenyl acetates. We have also determined the activation parameters for the catalysis of the hydrolysis of a series of substituted phenyl acetates by imidazole and for one case of general-base catalyzed nucleophilic catalysis of the hydrolysis of a substituted phenyl acetate by imidazole. These studies have been carried out in aqueous solution a t a calculated ionic strength of 1.0 M (with KC1). Experimental Materials.-p-Sitro-, m-nitro-, p-chloro-, p-methylphenyl ;!retate as well as phenyl acetate itself were samples employed in a reccnt study.l p-Methoxyphenyl acetate was prepared by a ronventional method.& Kinetics.-The hydrazine and imidazole solutions were prepared in water, and KCI was added t o give a constant (calculated) ionic strength of 1 .0 A f , Aliquots of the desired solution (3 ml.) w t introduced ~ ~ into two matched (1-cm. path) silica cuvettes. TI1e cuvettes were then thermally equilibrated a t the desired temperature before adding 1 drop of the desired ester as an ethereal solution. The resultant solutions were rapidly mixed iind placed in a thermostated ( 1 0 . 1 ' ) brass block in the cell compartment of a Zeiss P M Q I1 spectrophotometer. After a fcir minutes of re-equilibration the appearance of phenoxide i o n was followed spectrophotometrically. The following wave lengths were employed t o follow the reactions: p-NOz, 400 mp; n i - S 0 2 , 350 mp: p-CI, 285 mp; p-H, 275 mp; p-CH3, 280 mp; : i i ~ d p-CH:,O, 288 n i p . . \I1 first-order rate constants were determined by the method of Guggenheim.e This procedure was foutiti to provide more reproducible results than the employrliviit o f tile integrated form of thr first-order rate equation which tic.pcnds o n an accurate knowledge of the absorbance at t m . ~.
)
~~~
'r. C
Bruice and S J Benkovic, J A m . Chem. Soc.. 85, 1 (196'0 F Walker, i b i d . , '76, 4470 (1954) E. A Guggenheim Phil M a g . , 2 , ,538 (19263
) C, Cilento and \T. )
Results l1 Hydrazinolysis.12-The hydrazine reactions were carried out under conditions in which hydrazine was in great excess over ester so that pseudo-first-order kine ics were obtained (solvent H 2 0 ; = 1.0 M with KCl). In Table I are recorded the determined first-order rate constants. For p-nitrophenyl acetate the reaction was found to be first order in hydrazine from the linear dependence of kobsd on the hydrazine concentration. However, for m-nitro-, p-methoxy-, p-methylphenyl acetate and phenyl acetate itself the reactions were found to be dependent on a higher than the first power of the hydrazine concentration. In the case of the m-nitro ester the higher order dependency on the hydrazine concentration was only observed a t the lowest temperature employed for this ester (10'). In Fig. 1 the pseudo-first-order rate constants for Pmethyl-, p-methoxy-, and phenyl acetate have been plotted vs, the concentration of free hydrazine base in the reaction solutions (18'). The decided upward curvature of the plots of Fig. 1 suggests that the disappearance of these esters contains a contribution proportional to Hr.2 At constant pH
+
(1)
+ k"
(2)
-d(ester)ldl = kn(ester)(Hr)* k,(ester)(Hr) kohsd = kA(Hf)' kn(Hf)
+
kabsd/(HI)
=
kdHf)
(7) R. Hinman, J . Org. Chem., as, 1587 (1958). (8) E J . Cohn and J . T. Edsall, "Proteins, Amino Acids and Peptides," Reinhold Publ. Corp., New Y o r k , N. Y., 1943. p. 89 (9) (a) J. T. Edsall, G . Felsenfeld, D. S . Goodman, and F. R. N. G u r d , J . A m . Chem. Soc., 76, 3054 (19.54), ib) Y. Nozaki. F. K . N G u r d , R . F C h e n , and J . T. Edsall. i b i d . , '79, 2123 ( 1 9 5 7 ) . (10) T H . Fife a n d T C. Bruice, J P h y s . Chem , 65, 1079 (1961) ( I 1) Abbreviations employed are H i = concentration of H2NNHz: H h @ = concentration of H ? N N H a @ ; I M f = concentration of imidazole free base; I M H @ = concentration of imidazolium ion; an = hydrogen ion activity as determined hy t h e glass electrode. T h e r a t e constants are a b breviated a s ' k. = t h e apparent third-order rate constant determined a t a particular p H ; k, = t h e second-order rate constant for t h e reaction of nitrogen base with e s t e r , kgb = t h e third-order rate constant f o r t h e general-base catalyzed reaction of a nitrogen base with ester; ken = the third-order rate constant for the general-acid catalyzed reaction of a nitrogen base with ester. (12) W P. Jencks and J . Carriuolo, J . A m . Chem. Soc., m, 1778 (1960).
HYDRAZINOLYSIS AND HYDROLYSIS OF PHENYL ACETATES
Feb. 5 , 1964
I
I
1
0
I
.2
.I
HF
421
.3
(MI,
Fig.%.-Plots of eq. 2 for (0) p-methyl-, ( 0 )p-methoxy-, and (C)) unsubstituted phenyl acetate.
The data of Fig. 1 have been plotted in the form of eq. 2 in Fig. 2 (pH 8.73). The values of k3 are obtained as the slope and the value of k, as the intercept of plots such as Fig. 2. %Then the experiments were extended t o various pH values it was found that kS was dependent on pH and k, independent of pH. The dependence of k2 on aH was determined to be ka
=
kgdaa/&')
$-
(3)
kgb
Fig. 3.-Plots
of eq. 3 for ( 0 ) p-methyl-, (0)p-methoxy-, and phenyl acetate.
((I)unsubstituted )
In Fig. 4 are plotted the log k,, log k g b , and log k g a values vs. 1/T for the hydrazinolysis of p-cresol acetate and phenyl acetate. The AH* and TAS* values calculated from this plot along with those for the other esters of the series are presented in Table 111.
In Fig. 3 the values of k3 have been plotted vs. ~ H / K ~ ' , TABLEI1 where a H is the hydrogen ion activity as measured by RATECONSTANTS FOR THE REACTION OF HYDRAZINE WITH the glass electrode and K2' the dissociation constant of p = 1 0 Jf WITH KC1, SUBSTITUTED PHENYL ACETATES(H20; the conjugate acid of hydrazine. The general acid 180) rate constant kga is obtained as the slope and the Subkn, kga, kgbl stituent 1. mole-1 min.-l 1.2 mole-%m k - 1 1.2 mole-2 m h - 1 general base rate constant k g b as the intercept a t U H / K ~= ' 0. Thus, the over-all kinetic expression P-NO2 327 for the reaction of p-methyl-, p-methoxy-, and phenyl m-XOz 39.7 0') with hydraacetate (and m-nitrophenyl acetate a t 1 H 0.245 2.62 10.75 zine is given by (4).l 3 P-CH, ,130 1.98 7.86 -d(ester)/dt
=
[k,(Hf)
+ kgb(Hf)' $-
P-OCHI
k g d HI)(&@)I (ester) ( 4 ) The values of k n , kgp, and k g a a t 18' are provided in Table 11. The relative proportion of product arising from kn and the third-order terms is of course dependent on the hydrazine concentration and the pH of the experiment. Also included in Table I1 are the deuterium solvent isotope effects determined for the reaction of phenyl acetate with hydrazine. (13) Kinetically equivalent expressions for t h e hydrazine reaction ( i , e , , k b , ( H r ) % ~ )representing the actually reacting species rather t h a n k,,(Hf) ( H h @ ) may be ruled o u t since the constants would exceed those for diffusion controlled process For example k,.(Hi)(Hh@)(ester) = kb,aa(Hf)2(ester) where kgalK2' = kba Since K 2 ' for hydrazine is ca. 1 0 - and kga N 2 , kba 2 X 109. A kinetic process for the specific acid-general base catalyzed t e r m such as
-
-
Ka
ester
+ H 3 0 @z-'ester-H@
f H20 kr(Hr)
ester-H@ -tHf--+
prod.
E,
yields kbs as k , / % Assuming a reasonable value of t o be lo6, k , would have t o be 10'5, a value 106 greater t h a n t h a t observed for a diffusion controlled process.
,097
H
1.82
ka/kn in k, 1.1
8.20
ka/kn in k,, 2.3
kE/kn in 1.2
kgb
TABLE I11 A~CTIVATIOS PARAMETERS' FOR THE
REACTION OF HYDRAZINE
WITH SUBSTITUTED PHENYL ACETATES Substituent
__-
---k,--
-k,b--
-k
AH* TAS* kcal. mole-'
AHT TAS* kcal. mole-'
AH* TAS* kcal. mole-'
ga
p-SOz 6.8 -9.7 rn-h-Oi 1 0 . 9 -6.5 H 11.3 -9.0 4.1 -14.2 ca. 0 . 9 -18 4 p C H 3 12.0 -8.6 5.8 -12.7 c a . 0 . 3 -19.1 9-OCHa 5.0 -13.4 1 . 5 -17 9 a Calculated from AH* = E, - R T , - TAS* = AF* - A H = , andAF* = RT2.303 l o g ( K T / h k , ) ( A . A . F r o s t a n d R . G . Pearson, "Kinetics and Mechanism," John N'iley and Sons, Inc., S e w York, i T Y., 1953, pp. 95-97), standard states of 1 M and 1 .If?; T = 25" and time in sec. Slopes of linear plots were determined by method of least squares.
For k, the activation enthalpy does not appear t o be as constant as previously noted in the bir. olwular and intramolecular nucleophilic displacement reaction a t
THOMAS C. BRUICEAND STEPHENJ . BENKOVIC
422
=
VOl. 86
1' .I
Fig. B.-The observed rates of disappearance of (111) pchloro-, ( 1 1 7 ) unsubstituted, ( V ) P-methyl phenyl acetate as a function of imidazole concentration.
t
favorable enthalpy term than that associated with other esters in the series. The activation enthalpy associated with both general base and general acid Fig. 4.-Plots of log k,, log k g b , and log k,, v s . 1 / T for t h e recatalysis is significantly less than that associated with unsubstituted and ( 0 ) p-methylphenyl acetate actions of (:) simple nucleophilic attack. General-acid catalysis with hydrazine. appears to be the most efficient form of catalysis in terms of lowering the activation enthalpy. The small values of AH* found for p-methyl-, p-methoxy-, and phenyl acetate reflect essentially a temperature independent general-acid constant. The general-acid and general-base mechanisms indicate catalytic processes which are somewhat more favorable in terms of free energy than the uncatalyzed reaction. Since the catalytic processes represent the higher order reactions, i t would be anticipated that they would be less probable. On the other hand, the assistance to nucleophilic attack by the general-base and general-acid species should bring about a lowering of the potential energy barrier. These two opposing effects on A F + should result in compensation in the AH* and TAS* for the k,, kgb, and k g a terms of Table 111. Examination of Fig. 5 reveals a good linear relationship between the two activation parameters, and the slope of the line indicates that a decrease of 1 kcal. mole-' in TAS* is accompanied by a decrease in A H * of 1.15 kcal. mole-'. From this result it follows that the decrease in AF+- brought about by the catalytic processes is almost completely lost in the gain in AF* necessitated by the loss in the entropy of activation associated with the higher order reactions. Imidazole. l5-The reactions of imidazole with sub-TAS,* stituted phenyl acetates were studied under the same Fig. 5.--Plot of AH 21s. - TAS* for the reaction of hydrazine pseudo-first-order conditions employed for hydrazine unsubstituted I)) (solv. H 2 0 ; p = 1.0 M with KCl). For p-nitro-, with (0)p-methyl-, (0) p-methoxy-, and (( phenyl acetate depicting compensation. m-nitro-, p-chloro-, and unsubstituted phenyl acetate the reactions were found to be first order in imidazole. phenyl ester bond^.^,^^ Instead, AH* increases as the However, for p-methyl- and p-methoxy-substituted substituent becomes less electron attracting. In addiphenyl acetates the hydrolytic reactions were found to tion there is no regular trend observable in the TAS+ (1.5) For pertinent references on the catalysis of the hydrolysis of phenyl term. However, the high reactivity of p-nitrophenyl acetate by imidazoles, see. (a) M I.. Bender and B. W. Turnquest, ibid , acetate with hydrazine seems to be due to a more 79, 1652. 1656 ( 1 9 5 7 ) , (b) T. C Bruice and G. L Schmir. ibid , 7 9 , 166X
f x IO?
*
(11) E Gartjens and H hlorawetz. J A m Chem. SOC., 8 1 , 5328 (1960)
(1957); ( c ) ibid , 8 0 , 118 (19.58).
HYDRAZINOLYSIS AND HYDROLYSIS OF PHENYL ACETATES
Feb. 5 , 1964
423
-
1,800
-
1.400
1.0000.600
-
kN. 0.2001 0 Fig. ;.---Plot
I
I
I
1
1
I
0.20 0.40 0.60 0.80 1.00 1.20 IMF (MI.
I
1.401
of eq. 7 for the reaction of ( 1 7 ) p-methylphenyl acetate in H20 and D20 with imidazole.
0 -0.200
- 0.600 -
'
0
'
0
-1.000-
be dependent on a higher than the first power of imidazole concentration. These conclusions may be verified by inspection of Fig. 6. In Fig. 6 the pseudofirst-order rate constants for the disappearance of the unsubstituted and the p-chloro- and p-methylphenyl acetates have been plotted vs. the concentration of free imidazole base in the reaction solutions (34'). Inspection of Fig. 6 reveals that for p-chloro- and unsubstituted phenyl acetate the values of kobsd are linearly dependent on the concentration of the free base. However, in the case of p-cresol acetate there is a decided upward curvature in the plot of kobsd vs. I-1.I;. For p-nitro- and m-nitrophenyl acetates kobsd was found to be linearly dependent on the concentrat,ion of I J t as in the case of the p-chloro ester of Fig. 6. I n the case of $-methoxyphenyl acetate the plot of ,bobsd ZU. 1.lf; is virtually superimposable on that of p-cresol acetate. The plots of kobsd for p-cresol acetate and p-methoxyphenyl acetate suggest t h a t the catalysis of ester hydrolysis for these esters might contain a contribution proportional to 131f2. -d(ester),.'dt
=
k,t,(ester)(ZMf)*
kutsd = kgtfliWt)2
+ k,(ester)(ZMr)
kobJd/zilff E
(6)
+
(7)
hgt,(l+%fr)
kn
In Fig. 7 are plotted the values of k o b s d / l M f vs. IMf a t several pH values for p-cresol acetate in HzO and DzO. The third-order rate constant k g b is obtained as the slope and the second-order rate constant k , as the intercept a t 1.11;= 0. The observed isotope effect in k g b is consistent with general base catalysis ( k ~ / = k ~2.2). The values of k n and k g b a t 34' are provided in Table IV, the proportion of hydrolytic products arising from the third-order terms being ca. 30yoa t 1.0Mimidazole. TABLE IV KATE COXSTANTS FOR
THE
REACTION OF IMIDAZOLE WITH H20; j I = 1.0 hf KC1, 34')
SUBSTITUTED P H E N Y L ACETATES (SOLVENT WITH
kat,,
kn,
Substituent
P-XO2
m-Ii02
p-c1
H P-CHI p OCH:
1 mole-' min
47 17 1 0
4 2 60 960 333 .323
--?
1 2 mole-' min
0,105 0.095
I
1
1
I
1
1
3.40 350 3.60 3.70 x IO?
Fig. 8 -Plot of log k , us, 1 / T for the reactions of ( I ) p-nitro-, (11) rn-nitro-, (111)p-chloro-, (11.) unsubstituted, ( V ) p-methoxy-, (VI]p-rnethplphenyl acetate with imidazole.
(5)
-tk n ( l L V f )
and
-I.40031.10 3.20 3.30
P
-8
I
2.90
Fig 9.-Plots
I
300
I
1
I
310
320
330
+
1
1
3.40 3.50
3 io
x 103.
of log k , and log kgt, ZIS. 1 / T for the reaction of (1.1) p-rnethylphenyl acetate with imidazole
In Fig. 8 are plotted the log k n values vs. 1, T for the temperature range of 10 to 34'. I t should be noted that linear relationships exist for the log kn values of all esters with one exception. For p-methoxyphenyl acetate a sharp curvature is encountered. The plotted value a t 34' represents the separately determined value of kn, while the values a t all lower temperatures where k g b could not be experimentally distinguished must represent composite constants of k, and kgb, The value of k , a t 10' should reflect little or no contribution from k g b , a supposition that is justified by the negligible contribution of kgb to kobsd for p-cresol acetate a t 10' as illustrated in Fig 9. The activation
424
THOMAS
c. BRUICEAND S T E P H E N J . BENKOVIC
parameters for p-methoxyphenyl acetate were then calculated employing the determined values of k, a t 34 and IOo only. In Table V are recorded the values of AH* and Z'AS* for k, and k g b as calculated from Fig. S and 9. Inspection of the values of Table V reveals t h a t the electronic influence of the substituent group on kn is characterized by shifts of AH* and T A P in the same direction. The incursion of general base catalysis does not result in a significant lowering of hF* as was noted in general-base catalyzed reactions with hydrazine. Thus simple nucleophilic attack is more favored in terms of free energy when imidazole serves as the iiucleophile. Also included in Table V are the observed deuterium solvent isotope effects associated with k n . For nucleophilic attack no solvent isotope effect is anticipated. However, the reaction of phenyl acetate was found to exhibit a deuterium solvent isotope effect that appears to depend on ionic strength. The values of k H / k I ) for k, at various ionic strengths and temperatures are included in Table V. TABLE \.' ACTIVATION PARAMETERS A N D DEUTERIUM SOLVENT ISOTOPE EFFECTSFOR THE REACTION O F IMIDAZOLE XVITH SUBSTITUTED (SOLVENT HzO; p = 1.0 M ; T = 10-34') PHENYL ACETATES ,--
Substituent
p-SO? m-NOs p-CI H
p-CH,
-nk
Vol. 86
TABLE VI P-VALUES F O R REACTIOXS O F V A R I O U S NUCLEOPHILES 1VITH SERIES OF SUBSTITWED PHETYI XCFTATES Sucleophile
Catalyst
NHzNHZ 1;Ha Irnidazole NH:NHZ CH1Oe
NHsNHZ SHs Imidazole SH~SH~@
Kinetic order
P
R tf
3
U 55
d
3 3 3
0 55 5 0O 65
2
0 64
h
2
0.71
h
2
0.8
2
0.98
1
1.5
1
1.3
f
2 2 2
1.8 2.1 2.6
d
1
2 6
1
2.6
I
2 6
,"
, HOCH~CSHZ I
A
CHZOH (as oxyanion) CHjOH I
H 0C H 2 C S H 2
I CHiOH (as amine) OH CHnOH
I HOCH2CCHZO3
I
b
CHzOH
kgb-
7-
AH*
TAS+
7.0 6.0 5.4 8.4
-10 7 -12.3 -14 4 -11.6
a
AH*
TAS*
k A / k D for k n
1.0" 1.P 1.5-1.8," 1.3,f 1 070 1.2h
6.2 -14.4 5.5 -15.8 p-OCH, 4.9 -15 7b Calculated from Jffk = E , - R T , -TA.S* = JF* A$€*, and 3 F ' f = RT2.303 log ( K T l h k , ) (.\. A . Frost and K . G. Pearson, "Kinetics and Mechanism," John Wiley and Sons, Inc., S e w York, S . U.,1953, pp. 95-97) standard state used was 1 -M; T = 25"; with time in sec. Least squares method employed. Calculated from the determined value of k , a t 34" and the assumption t h a t k, a t 10" does not contain any significant conM. L. Bender, E. J . Pollock, and M . C . tribution from k j b , Seveu, J . .4m. Chem. Snr., 84, 596 (1962); 5% dioxane-HyO, 25'. ri At 34', 1.1 = 1 0 ; this study. 1.6 a t 34", 1.5 a t 25O, 1.8 a t lo", 1.1 = 1 . 0 ; this s t u d y 1 . 3 a t 25O, p = 0.50; this study. (' B. hl. Anderson, E. H. Cordes, and S.P. Jencks, J . At 3 4 O , p = R i d . Chew?., 236, 455 (1961): 1.1 = 0.35 a t 25'. 1 . O ; this study.
Discussion AH* and the pKa of the Nucleophile.--At present the dependence of AH* on the nature of the nucleophile and on the electronic effects of ester substituents is not understood. The previously suggestedt4 linear relationship between AH* and pK, of the nucleophile has been proved unsound on the basis of this study. The reactions upon which the correlation was based exhibited AH* values independent of the electronic nature of the substituent groups but dependent upon the pKa o f the nucleophile. In the present study the values of AH* are riot only dependent on the nucleophile, but also on the nature of the electronic substituents. Nevertheless. it is obvious that the determined AH* values deviate widely from those anticipated from the suggested correlation. For example, a AH* of c(z. l(i kcal. inole- I for the bimolecular reaction of iniitlazole with substituted phenyl acetates is predicted on the basis of the previously determined linear dependence of A H * on pK,', whereas a value of 7 to 5 kcal. iriole ' is observed. Hammett p-Values and the "c~-Effect."--Recause of the very high reactivity of hydrazine with esters (the a-efTecti6)),it is of interest t o compare the Hammett
c0@3& L H 3 ,
c:y
0
1 3 2.9 HJSNH? " Kef. 19 of paper. Kef. 17 of paper. Ref. 14 of paper. This s t u d y e .?I' C Bruice and U. E(. Pandit, J . A m , Chem. T. C. Bruice and J . hl. St.urterant, zbid., S o c . , 82, 3386 (1960). 81, 2860 (1959), Kef. 15 of this paper.
'
p-value of this nucleophile to values tleteririitied for other nucleophiles with the same series of estkrs. .i re-evaluation of Hammett plots for nucleophilic displacement reactions on phenyl esters has shown that much better plots are obtained when a r-value of 1.i) is eniployed for the p - X 0 2 group. For certain nuclec~p1iile.s the conventional values of 1.27 and 0.78 are quite satisfactory. However, all the data collected to date appear to correlate with the value of 1 .O, and we prefer to employ a single o-constant for comparative purpiises. The use of 1.0 as the v for the p-NOz group removes the cases of curvature previously encouiitered for tain nucleophiles (i.e., pentaerythritoi and l T i 5 ( l a ) J. 0 E d w a r d s a n d R G Pearson, J . A m Chem
HYDRAZINOLYSIS AND HYDROLYSIS OF PHENYL ACETATES
Feb. 5, 1964
droxymethyl) -amhomethane).l7 Justification for the use of a U-value of 1.0 for the P-NOZ group stems from the consideration that the displacement reactions considered are two-step mechanisms. I n the first step the nucleophile attacks the ester carbonyl group (requiring the nonconjugative u of 0.78) and in the second step the phenoxide ion leaves the tetrahedral intermediate (requiring a u of 1.27). The accumulated data are presented in Fig. 10 and Table VI along with the related p-constants using n = 1.0 for p-nitrophenyl acetate. The p-value for kn for hydrazine is the largest (+)value yet obtained for nucleophilic displacement reactions a t the phenyl ester bonds. A comparison of the kn values for hydrazine and ammonia is provided in Table VII. TABLE VI1 OF THE RATECONSTANTS FOR THE SECOND-ORDER COMPARISOK OF HYDRAZINE A N D AMMONIA WITH SUBSTITUTED REACTION PHENYL ACETATES (30"; Solvent H20; 7
Substituent
p
= 1.0
M with KCl)
kn
H2NNH2 "P 1. mole-1 rnim-1
kHzNNHi/kNH8
534 29.2 18.2 pN02 m-NOz 82.2 10.5 7.82 H 0.65 0.245 2.65 p-CH3 0.36 0.13 2.77 a Data of T. C. Bruice and M . F. Mayahi; see ref. 19 of paper
Inspection of the values of kHs"Hl/kNHa of Table VI1 reveals that the a-effect decreases with decreasing electron withdrawal by the substituent groups and thus the p-value reflects this sensitivity t o the a-effect. The slope of the Bronsted plots for the reaction of nitrogen bases with 9-nitrophenyl acetate is ca. 0.81a and the pKa of hydrazine and ammonia a t 30' have been determined to be 8.11 and 9.5, respectively. If no special effect were in operation it would be anticipated that the ratio of kH1"H2/kxHs would be 0.077 so that hydrazine can be seen to react with 9-nitrophenyl acetate some 236 times more rapidly than expected. For the general-base catalyzed ammonolysis and hydrazinolysis of phenyl acetate and p-cresol acetate the ratio of kH2"Hi/kNHs = 21.0 and 21.6, so that the a-effect is approximately ten times as important in the general base term ( k g b ) as in the nucleophilic term (kn).
The small p-value obtained for the k g b terms with hydrazine and imidazole is identical with that obtained for the same term with a r n m ~ n i a . ' ~Like most other general-base assisted aminolysis reactions, the hydrazine general-base reaction exhibits no deuterium solvent isotope effect.2o However, the general-base catalyzed reaction of imidazole with p-cresol acetate exhibits a deuterium solvent isotope effect of 2.2. This finding is similar to that reported for the imidazole catalysis of the hydrolysis of a series of m- and p-substituted p-nitrophenyl benzoates in 27% acetonitrile-water solution where there is, in addition to the second-order nucleophilic catalysis term, a third-order term which is first order in ester and second order in imidazole.21 The latter general-base term was associated with a deuterium solvent isotope effect of 1.81. AS* and the Kinetic Order.-Possibly more can be said about the entropy of activation than about the enthalpy of activation. This is so since AH* possesses both potential and kinetic energy terms, whereas AS* (17) T . C. Bruice and J . L. York, J. A m . Chem. Soc., 89, 1382 (1961). (18) T. C . Bruice and R.Lapinski, i b i d . , 80, 2265 (1958). (19) T . C Bruice and h l . F. Mayahi, ibid., 82, 3067 (1960). (20) W. P. Jencks and J , Carriuolo, ibid., 82, 675 (1960). (21) M. Caplow and W .P. Jencks, Biochcm.,1, 883 (1962).
I
I
425
I
I
I
U.
Fig. lO.-Hamrnett type plots for the reactions of substituted phenyl acetates with the various nucleophiles of Table V I I I , utilizing u p - ~ o z= 1.0. The plots refer to the nucleophiles in Table VI11 as: a-7, b-2, c-6, d-5, e-8, f-13, g-14, h-17, i-9, j-11.
is composed of only kinetic energy terms.22 Values of AH* and TAS* have now been amassed for eleven different nucleophilic displacement reactions each on series of phenyl ester bonds. These reactions share in common the fact that the same series of bonds are being broken but differ in the nucleophiles involved and also in the kinetic order and mechanism of the reactions. Thus, with various nucleophiles we have collected activation parameters for simple intramolecular displacement reactions which are kinetically first order, simple bimolecular nucleophilic displacement reactions, and third-order general-acid and generalbase assisted nucleophilic displacement reactions. Though electronic effects may produce erratic (as with H ~ N N H zor ) systematic (as with N(CH3)3)l 4 alterations in TAS* these may be considered as secondary perturbations on a value which is that of the average entropy of activation (TAS*av)for the series of phenyl ester bonds investigated with a particular nucleophilic displacement reaction. We may conveniently divide the T A . S a V term into two parts: (1) the first part may be considered t o be that involved with the translation of the nucleophile and catalytic species (if any) to a position of very close approach to the ester bond, (As*,,,,) and (2) the second part of the entropy term (AS*,) may be considered t o be that involved in the bond breaking and making processes. TAs*..
= T(AS*t,,,
+ AS*,)
(8)
The term A S * t , r , should be due t o translational and in part rotational entropy factors while AS*, should be determined by those kinetic energy terms involved in the formation of the transition state when the ground state of the reactants is that of very close approach. We may include entropy terms associated with solvent striction or solvent reacting, and electronic effects in AS'*e. First-order spontaneous processe; shou'd
