K. Kobayashi, Daiki Fujiwara
2019
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HETEROCYCLES
Abstract
An efficient method for the synthesis of 2-substituted 3-aroyl-2,3dihydro-1,4,2-benzodithiazine 1,1-dioxides has been developed. Thus, 2,Ndilithio compounds of secondary benzenesulfonamides, generated by treating secondary benzenesulfonamides with two equivalents of butyllithium, are allowed to react with elemental sulfur and then phenacyl bromide and its derivatives to give N-substituted o-[(aroylmethyl)sulfanyl]benzenesulfonamides in moderate to good yields. Oxidative coupling of these precursors to the desired products can be achieved in moderate to good yields on successive treatment with sodium hydride and iodine under mild conditions. Compounds with the 2,3-dihydro-1,4,2-benzodithiazine 1,1-dioxide skeleton have been known to be of potential biological interest. Especially, some 3-aroyl derivatives have been reported to exhibit anti-HIV integrase activities. The synthesis of these compounds has used the reduction of 3-aroyl-1,4,2benzodithiazine 1,1-dioxides, obtainable by the two-step sequence starting from the reaction between primary 2-sulfanylbenzenesulfonamides and phenacyl bromides, with benzenesulfonyl hydrazide. Meanwhile, we have been investigating synthetic routes to benzene-fused heterocyclic compounds by means of the reaction of 2,N-dilithio compounds of secondary benzenesulfonamides with isothiocyanates affording the corresponding o-(aminosulfonyl)benzothioamides and recently demonstrated that these precursors could be transformed into (Z)-N-substituted 1,2-benzothiazol-3(2H)-imine 1,1-dioxides, (Z)N-substituted 4H-1,3,2-benzodithiazin-3-imine 1,1-dioxides and 1,2-benzothiazole-3(2H)-thione 1,1dioxides by simple operations utilizing ordinal inexpensive reagents, such as thionyl chloride, iodine and 1,8-diazabicyclo[5.3.0]undec-7-ene (DBU), respectively, under metal-free and mild conditions. So, we were interested in developing a new approach for the preparation of 3-aroyl-2,3-dihydro-1,4,2benzodithiazine 1,1-dioxides utilizing these dilithio compounds. We now wish to report the results of our study, which provide a facile method for the synthesis of 2-substituted 3-aroyl-2,3-dihydro-1,4,2benzodithiazine 1,1-dioxides (3). It has been found that the dilithio compounds generated from secondary benzenesulfonamides (1) afford N-substituted o-[(aroylmethyl)sulfanyl]benzenesulfonamides (2) on successive treatment with elemental sulfur and phenacyl bromide and its derivatives and that intramolecular oxidative coupling of 2 can be successfully conducted with sodium hydride and iodine to give rise to this new type of 2,3-dihydro-1,4,2-benzodithiazine 1,1-dioxides (3).