Investigations in Heterocycles. XVIII. The Synthesis of 1,2-Disubstituted 5,6,7,8-Tetrahydro-4-quinazolinethiones¹

Heterocyclic diversity: The road to biological activity

“…Dissolution of this substance in refluxing tetrahydrofuran gave rise to the tetrahydroquinazoline. The identical product could be obtained through the condensation of N-phenylbenzimidoyl isothiocyanate with morpholinocyclohexene [38,39]. The N-phenylbenzimidoyl isothiocyanate intermediate was found to be most versatile in that it readily underwent intramolecular ring closure to 2-phenyl-4(3H) quinazolinethione in refluxing benzene ( Figure 34).…”

6,7-Dimethoxy-3,4-dihydroisoquinolin-1(2H)-ylidenoacetonitrile in some fusion reactions

“…They readily react with enamines of diverse structures [8,10,[20][21][22][23][24][25][26][27]. The reaction as a rule is started by the attack of the carbon atom of the iso(thio)cyanate group on the C-nucleophilic site of the enamine (when it is inaccessible, the attack is directed on the N-nucleophilic site [25]) followed by the cyclization of the formed intermediate [25][26][27]. The cyclization character depends on the structure of the initial enamine and the type of isocyanate.…”

“…For instance, after the reaction with acyl iso(thio) cyanates the aliphatic and carbocyclic enamines with a tertiary amino group loose it in the stage of cyclization giving as a result fused oxazinethiones [8,[25][26][27], and in the presence of a source of ammonium group (ammonia, ammonium acetate), substituted and/or fused pyrimidones, pyrimidonethiones [26], pyrimidonethiols [10] of various degree of aromatization. Yet the primary and secondary amino groups as structural elements of aliphatic [10,19,[25][26][27], carbocyclic [25][26][27] and some heterocyclic [20][21][22][23][24][25][26][27] enamines in analogous transformations remain intact in the course of the formation of similar cyclization products, pyrimidone(thione)s of various structures.…”

“…Yet the primary and secondary amino groups as structural elements of aliphatic [10,19,[25][26][27], carbocyclic [25][26][27] and some heterocyclic [20][21][22][23][24][25][26][27] enamines in analogous transformations remain intact in the course of the formation of similar cyclization products, pyrimidone(thione)s of various structures.…”

“…Unlike the acyl derivatives the alkyl isocyanates require severe conditions in the reactions with enamines and basic catalysis in the cyclization stage [25]. Therewith the intermediate products of the reaction between the aliphatic enamines and activated chloroalkyl isocyanates [25][26][27] can suffer more complex transformations loosing a number of functional groups and forming dihydropyridones of various structures.…”