Cascade synthesis of pyrimido-[4,3-b][1,3,5] selenadiazine derivatives

Abstract

The interest in the chemistry of selenium heterocycles is largely due to the broad spectrum of their biological activity [1,2]. Derivatives of 1,3,5-selenadiazine form a relatively little studied class of heterocyclic compounds. The methods reported for preparation of the 1,3,5-selenadiazine ring have been based on the reaction of 1,3-dichloro-1,3-bis(dimethylamino)-2-azapropenylium chlorides with selenamides or selenoureas [3,4], the multicomponent reaction of benzylamine, sodium hydroselenide, and formaldehyde with aryl selenoisocyanates in acid media [5], the recyclization of 1,3,5-oxaselenazine [6,7], and the reaction of dialkyl(1-aryl-1-chloro-2-aza-1-propenylidene)immonium perchlorate with N-acylselenoureas [8]. Butler and Fox [9] have described the preparation of a selenadiazine derivative as the result of recyclization of a 1,2,4-selenadiazolium salt. Condensed derivatives of 1,3,5-selenadiazines have not been described in the literature. S N NH 2 Se S Se N N N R R N 1, 3 a R = 4-MeC 6 H 4 , b R = CH 2 Ph RNH 2 (3), HCHO EtOH, ∆ 1 1 3 4 5 6 7 8 9 2 2We have developed a one-pot cascade method for the preparation of derivatives of pyrimido [4,3-b][1,3,5]selenadiazine (1) starting from (2-thienyl)methylidenecyanoselenoacetamide (2) [10,11]. Selenamide 2 readily undergoes the Mannich reaction with primary amines 3 and excess formaldehyde upon brief heating at reflux to give 1a and 1b in 38-50% yield.

Synthesis and alkylation of triethylammonium 3,5,5-tricyano-4,6-di(2-thienyl)-1,4,5,6-tetrahydro-pyridine-2-selenolate

“…In the course of our study of cyanoselenoacetamide derivatives [3][4][5], we have developed a method for the synthesis of a new selenium heterocyclic system, namely, triethylammonium 3,5,5-tri-cyano-4,6-di(2-thienyl)-1,4,5,6-tetrahydropyridine-2-selenolate (1). 2-Cyano-2-(2-thienyl)methylideneselenoacetamide (2) [6,7] was found to react with (2-thienyl)methylidenemalononitrile (3) in the presence of excess triethylamine to give 1,4,5,6-tetrahydropyridine-2-selenolate 1 in 71% yield.…”