Synthesis of 2,4-Disubstituted 5-Aminoimidazoles Using Microwave Irradiation

Abstract

A microwave-assisted parallel synthesis of 2,4-disubstituted 5-aminoimidazoles has been developed. Significant rate enhancement was observed for all steps in the three-step protocol. The overall reaction time was shortened to 25 min, as compared to 53 h for the conventional procedures. A representative set of 2,4-disubstituted 5-aminoimidazoles was prepared using commercially available parallel reactors.

Heterocycles from α‐Aminonitriles

“…When a-substituted aminonitriles were used as the substrates, the products 135 react with another equivalent of the iminoester to furnish the corresponding amidines (Scheme 27, B). [71] Another efficient route to 4-substituted 5-aminoimidazoles 140 from a-aminonitriles involves their condensation with trialkyl orthoformates to O-methylimidates. Ring enlargement by Stevens rearrangement of nitrile-stabilized ammonium ylides by Liu and Liang.…”

“…The required thioiminoethers were in turn conveniently obtained from thioamides and benzyl bromide under microwave irradiation. [71] Another efficient route to 4-substituted 5-aminoimidazoles 140 from a-aminonitriles involves their condensation with trialkyl orthoformates to O-methylimidates. The latter can be cocyclized with primary amines to yield imidazoles in high yields (Scheme 27, D).…”

“…This method furnishes the desired products in shorter reaction times and high yields. The required thioiminoethers were in turn conveniently obtained from thioamides and benzyl bromide under microwave irradiation 71…”

Parallel Processing of Microwave-Assisted Organic Transformations

“…The synthetic strategy was based on the reaction between thioamides and benzyl bromide to form the intermediate thioiminoether hydrobromides which in turn did undergo condensation withaminonitriles to give the respective 2,4-disubstituted 5-aminoimidazoles in high yield. The overall reaction time for the three step synthesis was 25 min (Scheme 7) [20].…”

Hydrazine-Hydroquinone Complex as an Efficient Solid Phase Hydrazine Donor: High Yield Synthesis of Luminol and Isoluminol

“…[1][2][3][4][5] The importance of 1-alkyl-5aminoimidazole-4-carboxamide as AICA(aminoimidazolecar boxamide) antagonist also attracted our attention. [6][7][8] In continuation of our synthetic studies on heterocycles, 9 we envisaged combining the above two structural features in a single compound and attempted to explore the synthesis of phthalhydrazido-aminoimidazolecarboxamide as a possible substrate exhibiting chemiluminescence. For this purpose, we required a considerable amount of 1a and 1b.…”