Novel One Pot Synthesis of Substituted 1, 2, 4-Triazines

Abstract

Substituted-1, 2, 4-triazines were conveniently prepared in one pot by the condensation of amides and 1,2-diketones in presence of base, followed by cyclisation with hydrazine hydrate. Introduction1, 2, 4-triazines and their derivatives have been widely studied in terms of their synthetic methodologies and reactivity since some of these derivatives were reported to have promising biological activities (la-g). The synthesis of 1, 2, 4-triazines and their derivatives are well documented and their methods of preparations are manifold and varied. A survey of the literature revealed that 1, 2-dicarbonyl compounds (aliphatic, aromatic and aromatic-aliphatic) are the most common reagents used for the synthesis of I, 2, 4-triazines and their derivatives (2, 3). Laakso and coworkers (4), as well as other groups (5) reported the condensation of acylhydrazides with benzil in acetic acid containing ammonium acetate to give 5, 6-diphenyl-l, 2, 4-triazines with various aromatic and heterocyclic groups attached at position 3. A similar method was also applied by Metze and his group (6) and also Hasselquist (7) using a variety of aliphatic and aromatic 1, 2-diketones and aliphatic, aromatic, and heterocyclic acid hydrazides but with preliminary isolation of the 1, 2diketones monoacylhydrazones followed by ring closure with alcoholic ammonia under pressure to give substituted 1, 2, 4-triazines. Results and DiscussionsRecently, we have reported the synthesis of trisubstituted pyridazine by the condensation of 1, 2diketone with acetophenone in the presence of base, followed by cyclisation with hydrazine hydrate (8). We wish to report here the synthesis of 1, 2, 4-triazine starting from amides and 1, 2-dicarbonyl compounds and hydrazine hydrate in the presence of base.

Molecular Construction Using Formamide as a C1 Feedstock

“…In 2006, Nongklaw and Myrboh [27c] synthesized triazines by a different method. Formamide and 1‐phenyl‐1,2‐propanedione were added to tert ‐butoxide in benzene.…”

1,2,4‐Triazines and Calcium Carbide in the Catalyst‐Free Synthesis of 2,3,6‐Trisubstituted Pyridines and Their D‐, 13C‐, and Doubly D2‐13C2‐Labeled Analogues

“…The authors have cited additional references within the Supporting Information (Ref. [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]).…”

Bicyclization of 4-Cyano-1,2-diketones with Amidines: Synthesis of Tetrahydroimidazo[4,5-b]-5-pyridinones

“…1,2-Diketones frequently appear in biologically active compounds . They are also broadly used as versatile building blocks in the preparation of a variety of heterocyclic compounds, for example, the synthesis of functionalized imidazoles via the multicomponent reaction of 1,2-diketones with aldehydes and amines, triazines via the condensation reaction of 1,2-diketones with hydrazides and ammonium acetate, and polyheterocyclic indolocarbazoles via the reaction of 1,2-diketones with indoles. In this field, functionalized 1,2-diketones in particular have found important applications due to their versatile reactivity; for example, ynediones are used in the preparation of useful pyrazoles and furanones .…”