Ammonium Chloride-Promoted Four-Component Synthesis of Pyrrolo[3,4-b]pyridin-5-one

Abstract

A novel multicomponent synthesis of 5-aminooxazole starting from simple and readily available inputs is described. Thus, simply heating a methanol solution of an aldehyde 3, an amine 4, and an alpha-isocyanoacetamide 5 provided the 5-aminooxazole (1) in good to excellent yield. The reaction of 1 with alpha,beta-unsaturated acyl chloride 13 lead to the formation of pyrrolo[3,4-b]pyridin-5-one (2) in a single operation. A triple domino sequence, acylation/IMDA/retro-Michael cycloreversion, is involved in this new scaffold-generating reaction. After the observation that ammonium chloride can significantly accelerate the oxazole formation in toluene, a one-pot four-component synthesis of 2 is developed.

The domino way to heterocycles

“…57 The further reaction of 142 with a variety of α,β-unsaturated acid chlorides produced DielsAlder substrates 143 that underwent cyclization to give bridged ethers 144. Ring opening with concomitant loss of morpholine afforded 145 that rapidly tautomerized to give 146 in 32 -75% yield.…”

Recent progress of Ammonium chloride as catalyst in organic synthesis

“…Subsequently, treatment of acyl chloride gave the product 40 in good yield (Scheme 13). 21 Ammonium chloride provided a proton source that is able to form hydrogen bond with 38 favoring subsequent nucleophilic attack of isonitrile.…”

A New Method for Synthesis of 2,4,5-Triaryl-1H-Imidazole Derivatives using SiO2-NaHSO4 under Solvent-free Conditions

“…They have the biological roles and also found application as a chromophore with high extinction coefficient, readily tunable absorption wavelength, and fluorophoric properties and was desirable as a large planar synthetic building block in supramolecular chemistry. Recently, several improved methodologies have been developed that use HY/silica gel, acidic Al 2 O 3 , AcOH, ionic liquid, NH 4 OAc, sodium bisulfate among others [5][6][7][8] . Previously, we have synthesized a number of heterocyclic compounds [9][10][11][12][13][14][15][16][17] .…”