T H E JOURNAL OF
Organic Chemistry 0 Copyright 1984 by the American Chemical Society
VOLUME49,NUMBER 19
SEPTEMBER 21, 1984
Intramolecular Nucleophilic Catalysis by the Neighboring Hydroxyl Group in Acid-Catalyzed Benzenesulfonamide Hydrolysis' Anno Wagenaarp Anthony J. Kirby,2band Jan B. F. N. Engberts*2a Department of Organic Chemistry, University of Groningen, Nijenborgh 16, 9747 AG Groningen, The Netherlands, and The University Chemical Laboratory, Lensfield Road, Cambridge CB2 IEW, England Received February 23, 1984
The reactivity toward the neighboring hydroxyl group of two NJV-dialkylbenzenesulfonamidesystems 1 and 2 is extraordinarily sensitive to structure. In the presence of o-CH20H,the SOzNMezgroup is stable almost indefinitely in 1 M HC1, whereas the corresponding compound with o-CMe20Hcyclizes to the sultone under the same conditions with a half-life of around 20 min. When the sulfonamide group is constrained in a fivemembered ring its cleavage must be followed by the stopped-flow technique. These very large variations in reactivity are interpreted primarily in terms of ground-state strain, which is partially relieved in the transition state for cyclization. The hydrolysis of sulfonamides is an extremely slow reaction, generally requiring strong acid and drastic conditions? However, very large rate accelerations are observed in the presence of a neighboring carboxyl gr0up.l7~ The reaction involves intramolecular nucleophilic catalysis and features a pentacovalent sulfur intermediate." We have discussed previously how the effective molarity (EM) of the carboxyl group depends on the subtle interplay of mechanistic and structural factors, and can be as high as 1O'O M in favorable case^.^^^ We present a study of intramolecular catalysis in two Nfl-dialkylbenzenesulfonamide systems (1 and 2) by the neighboring hydroxyl group. This acid-catalyzedreaction R 2 \,/OH
l a , R, = R, = H
R2
Scheme I
3b
2b +
H*
Lb
involves nucleophilic catalysis. It is extraordinarily sensitive to substituents R1and R2. Thus, the 2-hydroxymethyl compound (la) is unchanged after 7 months a t 25 "C in aqueous ethanol containing 1 M HCl, whereas the half-life of lb under similar conditions is about 20 min.
\,/OH
tie ' ~ e
(1) Part 8 in the series on intramolecular-catalyzed sulfonamide hydrolysis. (a) Part 7: Jager, J.; Graafland, T.; Schenk, H.; Kirby, A. J.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1984, 106, 139. (b) Part 6: Graafland, T.;Nieuwpoort,W. C.; Engberts,J. B. F. N. J.Am. Chem. SOC. 1981,103,4490. (2) (a) University of Groningen. (b) university of Cambridge. (3) (a) Searles, S.; Nukina, S. Chem. Rev. 1959, 59, 1077. (b) Carpenter, P. D.; Lennon, M. J. Chem. SOC.,Chem. Commun. 1973, 664. (4) (a) Wagenaar, A.; Kirby, A. J.; Engberta, J. B. F. N. Tetrahedron Lett. 1974,3736. (b) Wagenaar, A.; Kirby, A. J.; Engberta, J. B. F. N. Zbid. 1976,489. (c) Graafland, T.; Engberta, J. B. F. N.; Kirby, A. J. J. Org. C h m . 1977,42,2462. (d) Graatland, T.;Engberts,J. B. F. N.;Kirby, A. J. Zbid. 1981,46, 215. (e) Graafland, T.; Wagenaar, A,; Kirby, A. J.; Engberts, J. B. F. N. J. Am. Chem. SOC.1979,101,6981.
Results and Discussion Sulfonamides l b and 2b, with geminal dimethyl substitution, cyclize irreversibly under acidic conditions to the corresponding sultones (Scheme I). Pseudo-first-order rate constants (kobad) for both reactions in 1:l (v/v) EtOH-H20 a t 25.50 "C are given in Table I. Although 2b is some 4000 times more reactive, the rate constant for the cyclization even of l b is far higher than any reasonable estimate for the rate of hydrolysis of N,N-dimethylbenzenesulfonamide, for which the half-life in 70% (v/v) CF3C02H-H20at 99 "C is 95 h.S Evidently the effective (5) Wagenaar, A.; Kirby, A. J.; Engberta, J. B. F. N., to be published. Compare: Vinnik, M. I.; Ryabova, R. S.;Lazareva, V. T. Zh.Org. Khim. 1970,6, 1434, 1438.
0022-3263/84/1949-3445$01.50/00 1984 American Chemical Society
3446
J. Org. Chem., Vol. 49,No.19,1984
Wagenaar, Kirby, and Engberts Table 11. Pseudo-First-Order Rate Constants for Hydrolysis of 2b in Aqueous Buffer Solutions" at 25.50 "C X [XCO2H1,M [XC02Nal,M pH 104knM,s-' Me 0.050 0.025 4.08 5.86 0.100 0.050 4.10 7.72 0.500 0.250 4.22 22.1 CHzCl 0.050 0.025 2.45 177 0.100 0.050 2.37 180 0.500 0.250 2.37 241
Table 1. Pseudo-First-Order Rate Constants for the Acid-Catalyzed Hydrolysis of lb,c and 2b in 1:l (v/v) EtOH-H90 at 25.50 "C compd [HClI, M 1 0 2 & , ~a-1 , lba 0.1352 0.0054 0.3367 0.0147 1.009 0.0610 0.279 2.159 IC 1.009 0.00026 0.00103 2.159 0.00594 4.138 2bb 0.0107 1.82 0.0216 2.65 0.0320 4.77 0.0424 5.62 10.3 0.0541 24.2 0.1352 68.6 0.3367 111 0.5221 166 0.7120 257 1.009 463 1.327 752 1.850 1070 2.159
a Ionic
"AH*= 68.3 f 1.2 kJ mol-', AS* = -80 f 4 J mol-' K-' (0.0541 M HCI). bAH* = 35.1 f 1.2 kJ mol-', AS* = -121 f 4 J mo1-l K-' (0.0541 M HCl). Scheme I1
a'z-'oH2Me,
Ib
+ Hi
,Me
Me2NH
t
Me2NH2
+
I
/S
