Benzoxazolyl-and benzothiazolyl-guanidines in three-component reactions

Abstract

The previously unknown three component condensation of hetarylguanidines, orthoesters, and active methylene carbonyl compounds has been studied. Depending on the nature of the latter products of both linear combination and subsequent cyclizationl leading to pyrimidine or tetrahydroquinazoline structures were obtained.Three component condensations with the participation of C-H acids, aldehydes or orthoesters, and Ncontaining mono-or binucleophiles lead to a variety of derivatives, which possess a wide spectrum of biological activity [1]. For example, interaction of aromatic aldehydes, (thio)urea, and β-diketones in Biginelli conditions gave dihydro(thia)pyrimidones, which are calcium channel activators, antagonists of adrenoreceptors, etc. [2][3][4].At present there are no reports connected to the use in such reactions of guanidines, despite the great synthetic potential of the latter [5].In this work the three component condensation of benzoxa(thia)zolyl-2-guanidines 1a,b with orthoesters (RC)OEt 3 2a,b (a R = H, b R = Me) and active methylene compounds containing a carbonyl function has been studied. In this case one can expect formation of products of linear combination [6] and products of subsequent cyclization. X N N H NH N H 2 1 a,b 1 a X = O, b X = S It has been established that boiling an equimolar mixture of guanidines 1a,b with linear β-diketones 3a-c and an excess of the corresponding orthoester 2 for 20-40 min gave the acylpyrimidine 5. Cyclization, evidently occurs via formation of a linear intermediate 4 with subsequent intramolecular condensation.__________________________________________________________________________________________

Divalent N(I) Character in 2-(Thiazol-2-yl)guanidine: An Electronic Structure Analysis

“…27b 6 and 7 are reported to be calcium channel blockers. 28 1 also found extensive applications in the synthesis of heterocyclic compounds, 29 especially in three-component synthesis reactions. 30 In the medicinal chemistry literature, most often, the (thiazol-2-yl)guanidine derivatives are represented as derivatives of 1-(thiazol-2-yl)guanidine as in VI (Figure 2).…”