One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, α-Substituted Methylamines and Sodium Nitrite through α-Nitrosation of Enaminones

Abstract

An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)het(aroyl)-2,5(4)-het(aryl)/alkylimidazoles from readily available 1,3-bishet(aryl)monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with α-substituted methylamines, followed by their α-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting α-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het(aroyl)-5(4)-het(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-N-methy-2,5-bishet(aryl)-4-het(aroyl)imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested.

Novel Sources of Drug Components in Plants

“…It remains as an enormous asset for medicating advancement, novel chemotypes and pharmacophores, and systems for intensi ication into feasible medicinal drugs for a large wide variety of ailment signs and symptoms and other vital bioactive specialists. Since days of yore, regular gadgets were the inspiration of conventional association of getting better during the globe, and feature moreover been an important piece of history and way of life [12]. Despite the reality that the usage of everyday bioactive objects as natural medication arrangements is going again masses, even thousands, of years previous, their application as separated and portrayed mixes to present-day medication revelation and development started uniquely within the nineteenth century [13].…”

Applications of Sodium Nitrite in Organic Synthesis

“…A one‐pot three step transformation of 1,3‐monothioketones 97 to 2,4,5‐trisubstituted imidazoles 98 using NaNO 2 as the nitrosating agent was disclosed by Ila and co‐workers (Scheme ) . Initially reaction of monothio‐1,3‐diketone 97 with α ‐substituted methylamine LXXXIV results into in situ generation of enaminones LXXXV (Scheme ).…”

δ-Keto Aminoacrylonitriles and δ-Keto Aminoenones from 1-Pyrrolines, Cyanoacetylenes, and Acetylenic Ketones

“…3 Generally, enamines are valuable therapeutic pharmacophores, the fragments of which are ubiquitous in antibacterial, 4 anticonvulsant, 5 and nonsteroidal anti-inflammatory agents. 6 Conjugated aminoacrylonitriles and aminoenones are employed for the synthesis of azirines, 7 pyrroles, 8 indoles, 9 pyrazoles, 10 imidazoles, 11 oxazoles, 1a pyridines, 12 dihydropyridines, 13 pyrimidines, 14 pyridazines, 15 quinolines, 16 and diverse condensed heterocyclic systems. 17 δ-Keto amine structural units are contained in neuroleptics Benperidol, 18a Bromperidol, 18b Melperone, 18c antispasmodic Buflomedil, 18d and antipsychotic Moperone.…”

“…15 N NMR:  = -273.2 (NH). IR (film): 3418 (vw, NH), 1714 (s, CO), 1604 (s, CO), 1566 (vs, C=C) cm -1 .MS (EI): m/z (%) = 245 (27) [M] + , 202(16) [M -MeCO] + , 77(11) [Ph] + , 43 (100) [MeCO] + . HRMS (ESI-TOF): m/z calcd for [C 15 H 19 NO 2 + H] + : 246.1494; found: 246…”