408
Solvation of Ions. XVIII.' Protic-Dipolar Aprotic Solvent Effects on the Free Energies, Enthalpies, and Entropies of Activation of an SNAr Reaction B. G . Cox and A. J. Parker*2
Contribution f r o m the Research School of Chemistry, Australian National University, Canberra, A.C.T., Australia. Received April 20, 1972 Abstract: The effects of solvent transfer on free energies, enthalpies, and entropies of activation of an aromatic nucleophilic substitution (SNAr) reaction are examined. Hexamethylphosphoramide is an excellent solvent for SNAr reactions. The enhanced rate of transfer from protic to dipolar aprotic solvents is more a function of decreased enthalpy than that of increased entropy of activation. The transfer of a SNAr transition-state anion from methanol to a dipolar aprotic solvent is usually exothermic by about 5 kcal mol-', and this exerts a strong influence on the rate of reaction. The enthalpy of transfer of reactant anions is also significant in determining a solvent effect on the rate of SNAr reactions.
I
n 1961 we first noted the enormous increase in rate when aromatic nucleophilic substitution reactions (eq 1) of azide ion with 4-fluoronitrobenzene were ArF N3- +ArN3 + F(1)
+
Ar = 4-NOzCeH4
transferred f r o m protic to dipolar aprotic solvents.
This and related observations on solvent effects on rates of the general reaction 2 at 25" have been explained Y-
+ RX e YRX*-
--f
YR
+ X-
(2)
and analyzed as in eq 3 4 in terms of the solvent activity coefficients: 81ys2for transfer from solvent s1 to solvent sz o f reactant anions Y-, reactant molecular species RX, and transition-state anions YRX*-. An alternative to eq 3 is to analyze the solvent effect (AG,,) on log ks'/ks2= log S'y"RX log - log S1yS3yRX*- (3) the free energies of transfer of reactants and transition states at 25" from reference solvent s1 to another solvent s2 as in (4). AGtr* = AGtr(Y-) AG,,(RX) - AGt,(YRX*-) (4) The question of solvent effects on rate at temperatures other than 25" and the effect of solvent transfer on the enthalpy and entropy of activation of reaction 2 have received some attention, 3,5 but we know of no systematic investigation which provides information as detailed as that which is available for solvent effects on free energies of activation at 25 ". The situation has been clouded by uncertainties about heats of solution of salts in methanol and in dimethylformamide, key examples o f protic and dipolar aprotic solvents, respectively. Recent work by K r i s h n a n and Friedman has6 removed these uncertainties.' In this paper we make a detailed study o f the solvent effects on AG*: AH*, and AS* of reaction 1; in a variety
+
+
( I ) Part XVII: B. G. Cox and A. J. Parker, J . Amer. Chem. Soc., 95, 402 (1973). (2) Author to whom enquiries should be addressed. (3) J. Miller and A. J. Parker, J. Amer. Chem. Soc., 83, 117 (1961). (4) A . J . Parker, Chem. Rev., 69, 1 (1969). (5) P. Haberfield, L. Clayman, and J. S. Cooper, J . Amer. Chem. Soc., 91, 787 (1969). (6) C. V. Krishnan and H. L. Friedman, J . Phys. Chem., 75, 3606 (1971).
Journal of the American Chemical Society
95:2
of solvents. The treatment is in terms of the popular extrathermodynamic assumptions738 that AGt,(Ph4As+) = AGt,(Ph4B-), AHt,(Ph4As+) = AHtr(Ph4B-), and ASs(Ph4As+) = AStr(Ph4B-). The reasons for adopting these assumptions are discussed in parts XVI8 and XVII. Experimental Section Reaction Rates. Conventional methods of measuring and treating rate data were used. Reactions 1 were followed either by titration of N3- with standard AgN03 using reactant concentrations of about 4 X 10-2 MNBu4N3and 2 x 10-2 M4-fluoronitrobenzene, or spectrophotometrically by following the increase in absorption at 330 mp with a Gilford 2400 spectrophotometer. AI1 spectrophotometric measurements were carried out under pseudo-firstorder conditions with [NBu4N3]about M , except in water M. where it was 10-1 M , and [4-fluoronitrobenzene]about 1 X It was assumed that at these concentrations, NBu4N8was a strong electrolyte in all solvents used. Rate constants for reaction 1 are in Table I. Table I. Rate Constants k ( A 4 - I sec-') for SNAr Reactions (1) of NBu4Ns(0.01 M ) with 4-Fluoronitrobenzene M ) at the Temperatures Shown in Parentheses 103k M-1 set-1 Solvents
_--___-
DMSO CH3CN TMS PC MeN02 Waterd HMPT
0.57 (27.11:b2c 1.62(34.7); 9.11, 8.90(53.9); 24.8, 24 6 (65.1) 0.54(25.1);*2' 0.61 (26 2); 1.53 (33.8); 5.70 (52.7); 6.30b (53 0); 7.06, 6 97 (53.9); 19.8,'20.7 (65.2) 3.32(32.l), 7.19(41 .O),13.8(50.3),29.7V9.3) 1.06, 1.00 (32.0); 1.59b (36.5); 3.45, 3.79 (44.6); 7.70, 7.61 (53.8); 10.gb (60.0); 14.0, 14.5 (65.0) 0.184 (25.1), 0.415 (33.0), 1.06 (45.4), 2.74 (53.4), 6.64 (64.4) 0.0051 (64.0), 0.028 (79.9), 0.185 (101.1) 39.2 (16.7); 8 5 . 5 (25.8); 181.0 (35.6); 384 (44.3)
a DMSO, dimethyl sulfoxide; PC, propylene carbonate; TMS, Retetramethylene sulfone; HMPT, hexamethylphosphoramide. action followed by titration of N3- with AgN03; others were followed spectrophotometrically. Reference 3. d These reactions were carried out in sealed tubes at an ionic strength of 0.1 M and were analyzed spectrophotometrically.
(7) E. Grunwald, G. Baugham, and G. I
