Facile and efficient synthesis of 4'-thioxo-1',3,3',4,4',6' -hexahydro-1H,2'H-spiro[naphthalene-2,5'-pyrimidin]-1-ones in a three-component Mannich-type reaction

Abstract

Spirohexahydropyrimidines were obtained in the one-pot three-component reaction of the tetralone-derived thioamides, amines and formaldehyde with alcoholic hydrogen chloride as the catalyst.

Synthesis of sulfanylidene-diazaspirocycloalkanones in a three-component Mannich-type reaction catalyzed with lactic acid

“…16 The one-pot, three-component reaction (MCRs) of the tetralone-derived thioamides with primary aliphatic amines and formaldehyde was carried out with alcoholic hydrogen chloride as the catalyst. Continuing our studies on the application of thioamides to the synthesis of heterocyclic compounds, [16][17][18] we report now on an easy and efficient synthesis of spirohexapyrimidine derivatives from the thioamidefunction-containing cyclic ketones, primary amines and formaldehyde in DMSO in a Mannich-type reaction with lactic acid used as the catalyst. As shown in Scheme 1, the starting thioamides 2a-f were obtained in moderate yields in the reaction of cyclic ketones 1a-d with sodium hydride and aryl isothiocyanates in a DMF solution.…”

“…However, presumably owing to steric hindrance, no such reactions were observed with tetralone-derived thioamides. 16 The advantages offered by lactic-acid catalysis prompted us to make some preliminary experiments of its use with compounds other than thioamides, and, thus, to find out if it has a more universal applicability to the Mannich-type MCRs. Cyclohexanone was selected as the model reagent since its reactions with aromatic amines and formaldehyde have been studied earlier by numerous authors [9][10][11][12]20 in investigations using both typical and unusual catalysts.…”