3-Cyano-4,6-dimethyl-5-R-pyridine-2-sulfonyl chlorides and N-substituted sulfonylamides based on them

Abstract

chloride eliminates a SO 2 molecule at the isolation stage. N-Substituted sulfonylamides based on the latter were obtained by the reaction of the crude sulfonyl chloride with amines in an aqueous medium.Aryl-and heterylsulfonylamides have various types of biological activity, including pharmacological [1, 2], herbicidal [3], and fungicidal [4]. In order to extend the range of biologically active substances we made an attempt at the synthesis of new pyridyl-2-sulfonyl chlorides and N-substituted sulfonylamides based on them. One of the widely used methods for the production of aromatic sulfonyl chlorides is oxidative chlorination of the corresponding mercapto derivatives [5]. As starting compounds we used 3-cyanopyridine-2(1H)-thiones 1a,b, the synthesis of which was described in [6].Oxidative chlorination was realized in a 2 N solution of HCl in the range between -3 and 0°C. Here 5-chloro-4,6-dimethyl-2(1H)-pyridinethione (1a) gives the corresponding pyridine-2-sulfonyl chloride 2a smoothly and with a good yield (85% theor.). 4,6-Dimethyl-2(1H)-pyridinethione (1b) also forms the required sulfonyl chloride 2b in the reaction process. However, its subsequent behavior is unusual; at the drying stage (room temperature, atmospheric pressure or 5-10 mm Hg; distillation of the solvent from the dried extract of the product) the latter eliminates a molecule of SO 2 , just as if it were "boiling". As a result 2-chloro-4,6-dimethylnicotinonitrile (3) is formed.In order to avoid decomposition of the sulfonyl chloride 2b the crude product was used straight away in the reactions with the amines. For this purpose a solution of the corresponding amine in acetone was added dropwise to an aqueous suspension of 2b at 8-10°C, and after stirring for 2-4 h the sulfonylamides 4h-l were isolated with fairly high yields (64-74%). The sulfonyl chloride 2b was consequently unable to be hydrolyzed under the given conditions.