Cleavage of Pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with Thiocarbonohydrazide. Synthesis of Substituted 4-Amino-1,2,4-triazines

Abstract

3-Acylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with thiocarbonohydrazide to give mixtures of 4-amino-6-(acylmethyl)-3-sulfanylidene-3,4-dihydro-1,2,4-triazin-5(2H)-ones and 6-substituted 1,4-benzoxazine-2,3-diones which can be separated by fractional crystallization directly from the reaction mixture. The reaction is likely to involve a sequence of nucleophilic transformations with intermediate formation of spiro[pyrrole-2,6′-[1,2,4]triazines] which undergo cleavage of the C²-N¹ bond in the pyrrole ring. The structure of the products was determined by X-ray analysis, and intermediate products were identified by UPLC/MS. 1,2,4-Triazine derivatives can also be synthesized independently from alkyl 2,4-dioxobutanoates or 2-oxobutanedioic acid and thiocarbonohydrazide. The known procedure for the synthesis of 4-amino-1,2,4-triazines from 4-aryl-2,4-dioxobutanoic acids and thiocarbonohydrazide was improved to meet the “green chemistry” principles. Two new methods for the synthesis of substituted 4-amino-1,2,4-triazines were developed. The obtained compounds attract interest for medicinal chemistry, pharmacology, and fine organic synthesis.