Reactions of 1,2,4‐triazines with nitromethide ion. A convenient method of preparation of 1,2,4‐triazin‐5‐ylcarbaldehyde oximes and their synthetic applications

Abstract

An efficient procedure for the preparation of 1,2,4‐triazin‐5‐ylcarbaldehyde oximes 2a‐f from 1,2,4‐triazines 1a‐f and nitromethide ion is described. The oximes 2c‐d were converted into corresponding 5‐cyano‐1,2,4‐triazines 6c‐d. The latter compounds react easily with various nucleophiles to afford 5‐substituted 1,2,4‐triazines 7a‐i and with 1‐pyrrolidino‐1‐cyclohexene to form cyano derivative of 5,6,7,8‐tetrahydroisoquinoline 9.

Synthesis and Structure of (E)-1-(3-Methylsulfanyl-1,2,4-triazin-5-yl)-ethanone O-Acryloyl Oxime.DAGGER.

“…Yield, 81%; m.p., 99 -100˚C. 1 The title compound, C9H10N4O2S, crystallizes in the triclinic system, space group P1, with cell constants a = 7.5330 (2) …”

“…1 The latter may serve as common intermediates in the construction of pyrazolo [4,3-e][1,2,4]triazines, 2 2-acylpyridines and 3-acyl-5,6,7,8-tetrahydroisoquinolines, valuable precursors for the synthesis of sempervirine, and its analogues, 3 possessing interesting pharmacological activity. In view of the wide application of the 1,2,4-triazine oximes in organic synthesis, unequivocal assignments of their stereochemistry became indispensable.…”

“…Yield, 81%; m.p., 99 -100˚C. 1 Yellowish prism crystals suitable for X-ray diffraction analysis were grown by the slow evaporation of an ethanol solution. X-ray data were collected by graphite-monochromatized Mo Kα radiation at 293 K, ω scans.…”

The synthesis of 1,2,4-triazines bearing the residues of higher alcohols in the 5-position via the ipso-substitution of cyano group under the solvent-free conditions

“…The ipso-substitution of a cyanogroup deserves a special attention because 5-cyano-1,2,4-triazines are highly affordable compounds due to previously developed convenient method of obtaining them by using the direct nucleophilic substitution of hydrogen in the series of 1,2,4-triazine-4-oxides [13]. The different variations of the ipso-substitution of a cyanogroup are reported in a literature [14][15][16][17][18][19][20][21]. Typically, mineral or organic bases (potassium hydroxide, sodium alcoholate, sodium hydride, triethylamine) were used in this reaction.…”

“…Отдельного внимания за-служивает ипсо-замещение циано-группы, поскольку 5-циано-1,2,4-три-азины являются весьма доступными соединениями ввиду разработанного ранее удобного метода их получения с использованием методологии нук-леофильного замещения водорода в ряду 1,2,4-триазин-4-оксидов [13]. В публикациях [14][15][16][17][18][19][20][21] представле-ны различные варианты такого ипсо-замещения. Обычно в ходе реакции используются основания (гидроксид калия, алкоголят натрия, гидрид на-трия, триэтиламин), помимо этого имеются примеры нагревания исход-ного 5-циано-1,2,4-триазина в избытке спирта без дополнительной активации (в частности, использование подобной процедуры предложено в случае введе-ния остатков метанола, этиленгликоля и глицерина).…”