Preparation of N -( α , β -unsaturated acyl)-sulfonamides

N -( α , β -Unsaturated acyl)sulfonamides are prepared (i) by the N -acylation of sulfonamides with N -( α , β -unsaturated acyl)benzotriazoles in the presence of potassium tert -butoxide or sodium hydride and (ii) by reactions of appropriate α , β -unsaturated carboxamides with sulfonylbenzotriazoles in the presence of sodium hydride.


Results and Discussion
The acylating agents (1a-g) were prepared in 74-95 % yield from the corresponding carboxylic acids and benzotriazole with thionyl chloride. 14Sulfonamides (2c-e) were prepared by the reaction of the corresponding sulfonyl chloride with ammonia (28 % solution). 15-Acylation of p-toluene sulfonamide (2a) with cinnamoyl benzotriazole (1a) in the presence of sodium hydride failed at 0 o C but occurred at higher temperature. 16When, n-butyl lithium was used in acylation of 2a with 1a, at -78 o C to r.t. for 12 h, a mixture of products was obtained one of which was the conjugate addition product as detected by 1 H NMR. This reaction was repeated in the presence potassium tert-butoxide at 0 o C to room temperature (Method A), which gave the desired α,β-unsaturated acyl sulfonamide 3a in 80 % yield.A similar result was obtained when sodium hydride was used as base at room temperature (Method B) or by refluxing (Method B 2 ) (Scheme 1).Under the optimized conditions (Method A, B 1 or B 2 ), N-(α,β-unsaturated acyl)sulfonamides (3) were obtained in good yields from the reaction of a range of acylating agents (1) and sulfonamides (2) (Table 1).β-Heteroarylacroyl benzotriazoles also react readily with sulfonamides (Table 1, entries 2-5).Methyl substituents at both the ortho positions of sulfonamide group did not hinder the reaction (Table 1, entry 5).Electronic variation in the sulfonamide derivatives also affected relatively little efficiency of the reaction (Table 1, entry 7 and 8).Methyl or phenyl groups at the α-position to the carbonyl group of the acylating agent did not prevent the formation of the corresponding substituted sulfonamide (Table 1, entry 9 and 10).Alkenyl acylating agent (1g) also reacted with sulfonamide (2e) ( An alternative route to 3 involves reaction of α,β-unsaturated carboxamide (4) with sulfonyl benzotriazoles (5) in the presence of a base.The reaction of cinnamamide (4a), with ptoluenesulfonylbenzotriazole (5a) in the presence of potassium tert-butoxide at room temperature, failed to give product in 24 h.However, reaction of 4a with 5a in the presence of sodium hydride at room temperature for 1 h, gave the expected N-(α,β-unsaturated acyl)sulfonamide (3a) in 71 % yield.Similarly, carboxamides (4a-c) reacted with sulfonylbenzotriazoles (5a-c) as shown in the Table 2, to provide the products 3k, 3f, 3m and 3n in 25-30 % yields.

Conclusions
A general method for the preparation of N-(α,β-unsaturated acyl)sulfonamides from the corresponding sulfonamides by N-acylation with N-(α,β-unsaturated acyl)benzotriazoles has been developed.An alternative route involves reaction of an unsaturated carboxamide with the sulfonylbenzotriazoles.This method involves readily available starting materials, stable and crystalline benzotriazole derivatives and short reaction times.

Experimental Section
General Procedures.All reactions were carried out under nitrogen atmosphere and solvents were dried according to standard procedures.Carboxylic acids, sulfonamides, sulfonyl chlorides, benzotriazoles and potassium tert-butoxide were purchased and used without further purification.The strength of n-BuLi used was 1.6 M. Purification by column chromatography was carried out using silica gel.Melting points are uncorrected. 1H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were recorded in CDCl 3 (with TMS for 1 H and chloroform-d for 13 C as the internal standard).Elemental analyses were carried out by the Analytical Laboratory in the Center for Heterocyclic Compounds, Department of Chemistry, University of Florida.

General procedure for preparation of sulfonamides 2c-e
To a solution of a sulfonyl chloride (40 mmol) in CHCl 3 was added NH 3 (200 mmol, 28 % solution.After stirring vigorously at room temperature for 2 h, the reaction mixture was extracted with CHCl 3 .The organic layer was dried over anhydrous MgSO 4 and concentrated under reduced pressure to give the corresponding sulfonamide (2c-e ).

General procedure for preparation N-(α,β-unsaturated acyl)sulfonamides 3a-l
To a suspension of potassium t-butoxide (0.08 g, 0.72 mmol) in THF (3 mL) at 0 o C was added a solution of sulfonamide (0.6 mmol) in THF (5 mL).The resulting mixture was stirred at room temperature for 1 h.It was again cooled to 0 o C and a solution of unsaturated Nacylbenzotriazole (0.6 mmol) in THF (7 mL) was added and stirred at room temperature for 3 h.The reaction was quenched with addition of saturated solution of ammonium chloride (5 mL), ethyl acetate (15 mL) was added and the organic layer was separated.The aqueous layer was extracted with ethyl acetate (15 mL).The combined organic layer was dried over anhydrous Na 2 SO 4 .After filtration the solvent was evaporated to get the crude product which was purified by column chromatography (silica gel) eluting ethyl acetate/hexanes (1:3) to get the corresponding N-(α,β-unsaturated acyl)sulfonamides 3a-l (Table 1).

General procedure for preparation of sulfonylbenzotriazoles (5a-c)
To a solution of benzotriazole was added SOCl 2 at rt with stirring.After half an hour, α,βunsaturated acid was added in one portion and stirring was continued for 3 h.The precipitate was filtered off and washed with CH 2 Cl 2 .The filtrate was washed with NaHCO 3 solution, brine and dried over anhydrous MgSO 4 .The solvent was removed under reduced pressure to obtain the corresponding sulfonylbenzotriazoles (5a-c).p-Tolylsulfonylbenzotriazole (5a).Yield 54 %; cream prisms (from ethyl ether); mp 128.0-129.0o C (lit. 21