ChemInform Abstract: A Straightforward and Efficient Catalyst‐Free One‐Pot Synthesis of N‐Acyl‐1,3‐diaryl‐2‐azaphenalene Derivatives via Multicomponent Reactions.

Abstract

A novel, one-pot multicomponent reaction of two molecules of aldehydes with 2,7-naphthalenediol and ammonium carboxylates is described as an efficient and direct procedure for the preparation of N-acyl-1,3-diaryl-2-azaphenalene derivatives in EtOH under reflux conditions. N-Acyl-1,3-diaryl-2-azaphenalene derivatives were obtained in good to high yields without any catalyst or activation. Multicomponent reactions (MCRs), with three or more reactants combining in a one-pot procedure to give a single product, are a promising and vita lfi el do f chemistry because the synthesi so f complicated molecules can be achieved in a very fast, efficient, and time-saving manner without the isolation of any intermediate. 1­4 As a result, it requires minimum effort, which minimizes the environmenta ll oading and is acceptable from a “Green Chemistry” point of view. MCRs are perfectly suited for combinatoria ll ibrary synthesis, and thus are finding increased use in the discovery process for new drugs and agrochemicals. 5,6 Therefore, the design of novel MCRs has attracted great attention from research groups working in medicinal chemistry, drug discovery, and material ss cience. The Biginelli, 7 Ugi, 8 Passerini, 9 and Mannich 10 reactions are some exampl eo f MCRs. Nevertheless, development and discovery of new MCRs i ss till in demand. In this context, recently we have reported 11 the reaction of 2naphthol and aldehydes (2:1) in the presence of p-toluenesulfoni ca ci d( p-TSA) to form dibenzoxanthenes. The reaction proceeds through the i ns itu formation of ortho-quinone methides (o-QMs) and 2-naphthol acts as a nucleophile. To expand this type of tandem process that would permit the condensation of the i ns itu generated o-QMs with nucleophiles other than phenols, we utilized urea, amides, and semicarbazide hydrochloride (to work as nucleophiles) to produce corresponding amidoalkyl and semicarbazonoalkyl naphthols. 12 In the present study, we report our results on a new type of multicomponent reaction where five molecules react to form a piperidine ring. Thus, aromati ca ldehydes, ammonium carboxylates, and 2,7-naphthalenediol are directly transformed into N-acyl-1,3-diaryl-4,9-dihydroxy-2,3-dihydro-2-azaphenalenes (Figure 1).