An Extremely Efficient Three-Component Reaction of Aldehydes/Ketones, Amines, and Phosphites (Kabachnik−Fields Reaction) for the Synthesis of α-Aminophosphonates Catalyzed by Magnesium Perchlorate

• Published in: Journal of organic chemistry Vol. 72; no. 4; pp. 1263 - 1270
• Main Authors: Bhagat, Srikant, Chakraborti, Asit K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.02.2007; Amer Chemical Soc
• Subjects: Catalysis; Catalysts: preparations and properties; Chemistry; Chemistry, Organic; Exact sciences and technology; General and physical chemistry; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; LANTHANIDE TRIFLATE; PHOSPHONATES; SOLVENT-FREE CONDITIONS; ONE-POT SYNTHESIS; STATE ANALOG INHIBITORS; CARBONYL-COMPOUNDS; ACYLATION CATALYST; IONIC LIQUIDS; MICROWAVE-ASSISTED SYNTHESIS; LEUCINE AMINOPEPTIDASE; Nitro compound; Metal; Phosphorus Organic compounds; Amine; Magnesium perchlorates; Aromatic compound; Chemical synthesis; Arylamine; Solvent; Organic phosphite; Catalytic reaction; Aniline derivatives; Organic phosphonate; Imine; Aldehyde; Perchlorates; Reaction rate; Ketone; Cyclic compound; Acetophenone derivatives; Transition state; Benzenic compound; Counter ion; Catalyst activity; Magnesium compound; Catalyst
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo062140i

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the synthesis of α-aminophosphonates. A three-component reaction (3-CR) of an amine, an aldehyde or a ketone, and a di-/trialkyl phosphite (Kabachnik−Fields reaction) took place in one pot under solvent-free conditions to afford the corresponding α-aminophosphonates in high yields and short times. The use of solvent retards the rate of the reaction and requires a much longer reaction time than that for neat conditions. The reactions involving an aldehyde, an aromatic amine without any electron-withdrawing substituent, and a phosphite are carried out at rt. The reactions involving cyclic ketones, aromatic amines with an electron-withdrawing substituent, and aryl alkyl ketone (e.g., acetophenone) require longer reaction times at rt or heating. Magnesium perchlorate was found to be superior to other metal perchlorates and metal triflates during the reaction of 4-methoxybenzaldehyde, 2,4-dinitroaniline, and dimethyl phosphite. The catalytic activity of various magnesium compounds was influenced by the counteranion, and magnesium perchlorate was found to be the most effective. The reaction was found to be general with di-/trialkyl phosphites and diaryl phosphite. The Mg(ClO4)2-catalyzed α-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or α-hydroxy phosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine, and the phosphite in the transition state.