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

Features of 5-trichloromethyl-2-aryl-5,6-dihydro-[1,2,4]triazolo[1,5-с]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 ANE and AN 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-phenyl5-(dichloromethyl)-[1,2,4]triazolo[1,5-c]qinazoline. The mechanism of the transformation mentioned above is given; it is β-elimination on the Е1cb-mechanism followed by isomerisation. The structure of the compounds synthesized has been confirmed by the complex of physicochemical methods, including 1H-, 13C-NMR-spectrometry, chromato-massspectrometry, mass-spectrometry and X-ray structural study. A detailed analysis of 1H and 13C-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.

Characteristics of chemical transformations of compounds with the trichloromethyl moiety in heterocyclic fragments were widely discussed in recent publication. The authors described the features of their interaction with N-, О-nucleophiles by S NAr -or tele-S N -mechanisms and formation of the corresponding N-, O-substituted heterocyclic fragments [1][2][3]. In order to expand the synthetic potential of the reaction mentioned above it would be interesting to study the interaction of non-aromatic heterocyclic compounds with trichloromethyl substituent at sp 3 hybridized carbon atom.
The aim of the work is to study the features of the reaction between [2-(3-aryl-1H-1,2,4-triazol-5-yl)phenyl]amines with chloralhydrate and transformations of the non-aromatic heterocyclic compounds obtained with the trichlormethyl moiety at sp 3 -hybridized carbon atom under the action of N-nucleophiles.
The reactions were carried out by refluxing equimolar amounts of diamines 1a-g and chloral hydrate in acetic acid or methanol with an acidic catalyst (Scheme 1). It is worth noting that 1a-g normally exist in two tautomeric forms, which may invoke parallel formation of isomeric [1,2,4]triazolo [1,5-с]-and -[4,3-c] quinazolines. Nevertheless, our experiments have demonstrated that the reaction proceeds regioselectivity through an azomethine intermediate A with the subsequent intramolecular nucleophilic cyclization into tricyles 2a-g (Scheme 1). We attribute such selectivity to a +М-effect (a-effect) of the neighbouring nitrogen atom.
The experiments have shown that the reaction of 2a with different N-nucleophiles ((2,2-dimethoxyethyl) amine, benzylamine, morpholine, piperidine and triethylamine) results in the same product, namely dichloromethylated aromatic heterocycle 3а (Scheme 2). Most likely the reaction proceeds via the step-by-step mechanism with Е 1cb b-elimination followed by iso-merization of the resulting enamine (intermediate B). It starts with elimination of the acidic hydrogen in position 5 in the presence of a base giving a carbanion (intermediate A). Next the negative charge is displaced towards the electron withdrawing trichloromethyl group causing elimination of a chloride anion. At the final stage isomerization into a heterocyclic aromatic system takes place (Scheme 2).

Experimental Part
Melting points were determined in open capillary tubes in a Thiele apparatus and were given uncorrected. The elemental analysis (C, H, N, S) was performed using an ELEMENTAR vario EL cube analyzer (Elementar Analysensysteme GmbH, Hanau, Germany). IR-spectra (4000-600 cm -1 ) were recorded on a Bruker ALPHA FT-IR spectrometer (Bruker Bioscience, Germany) using an ATR eco ZnSe module. 1 H NMRspectra (400 MHz) were recorded on a Varian-Mercury 400 spectrometer (Varian, Palo Alto, CA) in DMSO-d 6 with SiMe 4 as an internal standard. LC-MS were recorded using the chromatography/mass spectrometric system consisting of an "Agilent 1100 Series" (Agilent, Palo Alto, CA) HPLC chromatograph equipped with an "Agilent LC/MSD SL" diode-matrix and massselective detector (atmospheric pressure chemical ionization -APCI). Electron impact mass spectra (EI-MS) were measured on a Varian 1200 L instrument (Varian, USA) at 70 eV.