From 3-chloromethyl-1,2,4-triazine 4-oxides to various substituted pyridines and 1,2,4-triazines

Abstract

An efficient strategy for the synthesis of new pyridine and 1,2,4 triazine derivatives starting from available 6 aryl 3 chloromethyl 1,2,4 triazine 4 oxides was proposed. The deoxygenative nucleophilic hydrogen substitution in the triazine oxide ring, nucleophilic substitution of the chlorine atom in the side chain, and transformations of the 1,2,4 triazine ring into the pyridine ring via the inverse electron demand Diels-Alder reactions, being used in different orders, are a rather flexible tool for the functionalization of the titled heterocycles. The cyanide anion, indoles, thiophenols, amines, and triphenylphosphine were used as nucleophiles. The direct introduction of indole residues into the 1,2,4 triazine ring followed by the substitution of the chlorine atom by a residue of the primary or secondary aliphatic amine was found to be the most convenient method for the library synthesis.

A PASE Approach towards (Adamantyl‐1)‐, Alkyl‐ and (Het)Aryl‐Substituted [1, 2,4]triazolo[1, 5‐d][1, 2,4]triazines: A Sequence of Two Solvent‐Free Reactions Bearing Lower E‐Factors

“…5‐Cyano‐1,2,4‐triazines ( 1 ) are easily accessible and could be obtained using previously reported approaches via S N H reactions of 1,2,4‐triazine‐4‐oxides, and the starting 1,2,4‐triazines 1 and their derivatives could be prepared as described earlier . The ipso ‐substitution of the 5‐cyano group in 1,2,4‐triazines is widely reported for various nucleophiles, for instance amines, alcohols ,[18][13] lithium carboranes, etc. Recently, we also reported a solvent‐free method for the substitution of 5‐cyano‐group in 1,2,4‐triazines by the reaction between aromatic amines and carboxylic acids hydrazides …”

Was methionine the molecular trigger of life on early earth?

“…Thus, in 1977, Minato et al reported the Salkylation of an aromatic thiolester to give a sulfonium 16 which was sufficiently stable to be detected by NMR spectroscopy and in 2005 the isolation of a stable solid acyl sulfonium was described by Kozhevnikov et al 17 . Some 3-and 4-membered cyclic acyl sulfoniums have also been described by Lebedev et al 18 , and the intermediacy of a 5-membered cyclic acyl sulfonium has been postulated by Truce and Abraham to explain the formation of a thiolactone when 4- 19 .…”

Combinatorial approach to the synthesis of substituted 1,2,4-triazines

“…Amines [1][2][3][4], alcohols [3] and CH-active compounds [5] can act as nucleophiles. In principle, anilines also enter into this reac-tion, but do so very reluctantly only aft er prolonged heating [6].…”

“…Нуклеофилами могут выступать амины [1][2][3][4], спирты [3] и СН-активные соединения [5]. В принципе, анилины также вступают в данную реакцию, но делают это весьма неохотно, лишь после длительного нагрева [6].…”