Synthesis of 6-chloro(dichloro-, trichloro-)-methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]- quinazolin-2-ones and their modification in reactions with nucleophilic and non-nucleophilic bases

Abstract

The synthesis of 6-chloro-(dichloro-, trichloro)methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones and their modification under the action of nucleophilic and/or basic reagents are described in this article. It was shown that 6-chloro-(dichloro-, trichloro)methyl-3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones can be prepared by cyclocondensation of 3-(aminophenyl)-6-R-1,2;4-triazine-5(2Н)-ones with chloro-(dichloro-)acetaldehyde or chloral hydrate. The reactivity of the synthesized compounds toward nucleophilic base morpholine and non-nucleophilic base diisopropylethylamine (DIPEA) under different conditions was studied. It was shown that the prepared compounds under the action of morpholine and/or DIPEA can be converted into the products of substitution, elimination or elimination followed by isomerization and substitution. Refluxing of 6-(chloromethyl)-3-R-6,7-dihydro-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones with equimolar quantity of morpholine and 10% excess of DIPEA in ethylene glycol monoethyl ether (EGEE) yielded the products on N-alkylation. 6-(Morpholinomethyl)-3-R-2H-[1,2,4]triazino[2,3-с]quinazoline-2-ones were obtained by heating of 6-dichloromethyl-3-R-6,7-dihydro-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones with five-fold excess of morpholine in EGEE. Reaction of 3-R-6-(trichloromethyl)-6,7-dihydro-2H-[1,2,4]triazino[2,3-с]quinazolin-2-ones with three-fold excess of DIPEA in EGEE yielded 3-R-2Н-[1,2,4]triazino[2,3-с]quinazoline-2-ones. The physicochemical and spectral characteristics of the prepared compounds were determined and discussed.