5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines. Message 3. Synthesis of 2-aryl-5-trichloromethyl-5,6-dihydro[1,2,4]triazolo[1,5-с]quinazolines and their reactivity towards n-nucleophiles

Abstract

quinazolines formation as result of [5+1]-cyclocondensation of the corresponding [2-(3-aryl-1H-1,2,4-triazole-5-yl)phenyl]amines with chloral hydrate are described in the article. It has been shown that this transformation is regioselective, occurs by refluxing of the initial compounds in acetic acid with formation of 2-aryl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines. The possible mechanism of 5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines has been proposed and substantiated. It has been shown that the reaction proceeds as step-by-step transformation that includes A N E and A N processes. The 2-phenyl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazoline obtained was studied in reactions with N-nucleophiles. It has been found that regardless of the nature of nucleophile the reaction mentioned above leads to formation of 2-phenyl-5-(dichloromethyl)-[1,2,4]triazolo[1,5-c]qinazoline. The mechanism of the transformation mentioned above is given; it is β-elimination on the Е 1cb-mechanism followed by isomerisation. The structure of the compounds synthesized has been confirmed by the complex of physicochemical methods, including 1 H-, 13 C-NMR-spectrometry, chromato-massspectrometry, mass-spectrometry and X-ray structural study. A detailed analysis of 1 H and 13 C-NMR spectral data of the compounds synthesized has been conducted. It has been found that the signals of the carbon atom in position 5 at 79.25-77.95 ppm were characteristic for 2-aryl-5-trichloromethyl-5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines, whereas aromatization of the molecule leads to significant deshielding of this carbon atom (163.41 ppm). The prospects of further chemical modification of 2-aryl-5-(dichloromethyl)-[1,2,4]triazolo[1,5-c]quinazolines has been discussed.

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

“…Listed above processes have the disadvantages including the usage of toxic reagents and low regioselectivity. Cyclocondensation of NÑÑÑN-nucleophiles with halogen-containing reagents (halogen-substituted aldehydes, halogen-substituted acids and their derivatives) can be considered as a promising alternative approach for the synthesis of heterocyclic compounds with halogen-substituted alkyl fragments [2,3]. These methods have undeniable advantages when possibility of variation of halogen atoms quantity and saturation state of the cycle are required.…”

“…Thus, monohalogenalkyl derivatives react with nucleophiles by the nucleophilic sub stit utio n me chanism. For instance, 6-(chloromethyl)-3-R 1 -2Í- [1,2,4]triazino [2,3ñ]quinazoline-2-ones in reactions with saturated azaheterocycles yielded corresponding 6-heterylmethylsubstituted derivatives [4]. The features of trichloromethyl substituted heterocycles reactivity were studied as well [5][6][7][8].…”

“…Specifics of interaction be twee n ab ovem entioned com poun ds and nucleophiles were revealed and it was shown that the reactions proceed via S NAr -and tele-S Nmechanism and yield corresponding heterocyclic systems [5][6][7][8]. Kholodnyak et al [2] studied the reactivity of 2-phenyl-5-trichloromethyl-5,6dihydro [1,2,4]triazolo [1,5-ñ]quinazoline towards Nnucleophiles and showed that initial compound underwent b-elimination under E 1cb -mechanism what re sult ed in the formation of 2-phe nyl-5-(dichloromethyl)- [1,2,4]triazolo [1,5-c]quinazoline. Nevertheless, the systematic studies of the reactivity of compounds that contain m ono-, di-, trihalogen alkyl substituen t at the partially hydrogenated heterocyclic system were not conducted.…”

“…Therefore, this work was aimed at synthesizing 6-chloro-(dichloro-, trichloro)methyl-3-R-6,7dihydro-2H- [1,2,4]triazino [2,3-c]quinazolin-2-ones and studying their reactivity towards morpholine, non-nucleophilic base diisopropylethylamine (DIPEA) and their mixtures under different conditions.…”

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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[2,3c]quinazolin-2-ones can be prepared by cyclocondensation of 3-(aminophenyl)-6-R-1,2;4triazine-5(2Í)-ones with chloro-(dichloro-)acetaldehyde or chloral hydrate.

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