Synthesis of (E)-5-Arylvinyl-7-methyltetrazolo[1,5-a]pyrimidines

A three-component reaction of 5-aminotetrazole with aromatic aldehydes and acetylacetone under solvent- and catalyst-free conditions at a temperature of 150–160°С proceeds with the formation of (E)-5-arylvinyl-7-methyltetrazolo[1,5-a]pyrimidines. 5,7-Dimethyltetrazolo[1,5-a]pyrimidine is formed as a side-product of the reaction.

Earlier, various 7-aryl-substituted 4,7-dihydrotetrazolo[1,5-a]pyrimidine-6(5)-carboxylates were obtained using the three-component reaction of tetrazol-5-amine with aromatic aldehydes and 1,3-dicarbonyl compound, namely aroyl(hetaryl)pyruvic or acetoacetic acid esters [12,13]. The reaction was carried out by heating a mixture of starting reagents to 160°C in the absence of a solvent and a catalyst. Under these conditions, the reaction proceeded regioselectively to form the title compounds with high yields.
Compounds 2a-2e are yellow crystalline substances, poorly soluble in ethanol, dioxane, acetonitrile, readily soluble in acetic acid when heated, and insoluble in water and hexane.
The IR spectra of compounds 2а-2е and 3 contain absorption bands of medium intensity in the range of 1616-1624 cm -1 , which are characteristic of stretching vibrations of the С=С and С=N bonds. The 1 Н NMR spectra of compounds 2а-2e exhibit characteristic signals of the protons of the methyl group as a singlet at 2.91-2.94 ppm, the proton of the methine group of the heterocycle as a singlet at 7.69-7.75 ppm, and two olefi nic protons as doublets at 7.30-7.57 and 8.02-8. Compound 3 is a white crystalline substance, readily soluble in acetic acid, chloroform, acetone, poorly soluble in ethanol and insoluble in water. The 1 H NMR spectrum contains singlet signals of the protons of two methyl groups at 2.68 and 2.87 ppm, as well as multiplet signal of the methine proton at 7.36 ppm.
To confi rm the proposed structure and establish the spatial structure of compounds 2a-2e, attempts were made to obtain a single crystal by slow crystallization, but crystals suitable for X-ray diffraction analysis were not obtained. Crystallization from acetic acid yielded a single crystal of compound 3 ( Fig. 1).
Compound 3 crystallizes in the centrosymmetric space group of the monoclinic system. The bicyclic system of tetrazolopyrimidine is fl at within 0.02 Å. The bond lengths and bond angles in the molecule have the typical values, with the exception of the slightly distorted C 3 C 2 C 6 angle, 127.9(2)°. A similar deviation of the bond angle from 120°, leading to a shift of the methyl group C 6 H 3 towards the tetrazole ring, is also typical for other alkylsubstituted tetrazolopyrimidines [14,15].
Only 5,6-dimethyltetrazolo[1,5-a]pyrimidine 3 was obtained, when carrying out a three-component reaction under milder conditions in the presence of sodium hydrogen sulfate in methanol according to the previously described method [16]. Tetrazolo[1,5-a]pyrimidine 3 was also formed by direct fusion of 5-aminoterazole with acetylacetone (Scheme 2).
Probably, in the reaction between acetylacetone, aromatic aldehyde, and tetrazole-5amine, at the fi rst stage, the addition of terazol-5-amine to acetylacetone occurs, followed by cyclization and the formation of intermediate 3 (Scheme 3). Compound 3 has a reactive methyl group, and when it reacts with an aromatic  aldehyde, condensation occurs with the formation of (E)-5-(2-arylethenyl)-7-methyltetrazolo[1,5-a]pyrimidines 2а-2e. The reaction stereoselectivity is due to the greater stability of the E-isomers in comparison with the Z-isomers. The low yield (5-22%) of compounds 2 is probably associated with the occurrence of side reactions under these conditions.
EXPERIMENTAL IR spectra were recorded on a FSM 1202 FT-IR spectrometer from mineral oil. 1 H NMR spectra were recorded on a Bruker AVANCE III HD 400 spectrometer from DMSO-d 6 solutions relative to internal TMS. Mass spectra were recorded on a Waters ACQUITY UPLC I-Class instrument by ultra-HPLC-MS method (Acquity UPLC BEH C18 1.7 μm column, acetonitrilewater mobile phases, fl ow rate 0.6 mL/min, Xevo TQD mass detector). Elemental analysis was performed on a PerkinElmer 2400 apparatus. Melting points were measured on a Melting Point M-565 instrument.