Microwave-Assisted One-Pot Synthesis Of 1-Indanones

1-Indanones are important synthetic intermediates for pharmaceuticals and biologically active compounds, and ligands of olefin polymerization catalysts. There are numerous methods available for the preparation of 1-indanones, the intramolecular Friedel-Crafts acylation of 3-aryl carboxylic acids or the corresponding acyl chlorides catalyzed by Lewis acids and/or protic acids, has been one of the oldest and most widely used approaches due to its efficiency and convenience. Microwave irradiation has been widely applied in organic synthesis recently and achieved a great success for many reactions, including Friedel-Crafts acylations, with high efficiency and yield.A series of 1-indanones were synthesized in good yields via the tandem Friedel-Crafts acylation and alkylation of substituted benzenes andα,β-unsaturated acyl chlorides in the presence of aluminum chloride under microwave irradiation. The current route is a practical and convenient method for these reasons: simple starting materials and catalyst, one-pot reaction, shorter reaction time than conventional thermal heating, good yields, wide applicability.The competitive Friedel-Crafts alkylation and/or acylation of arenes andα,β-unsaturated carboxylic acids usually led to mixtures of 1-indanones,α,β-unsaturated aromatic ketones, and 3-aryl carboxylic acids, the latter as major products in most cases. Furthermore, Friedel-Crafts alkylation of 3-arylα,β-unsaturated carboxylic acids affords 3,3-diaryl carboxylic acids, which will produce different structural isomers during the subsequent cyclization when the two aryl groups are different. Since the acyl chloride predominantly undergoes a Friedel-Crafts acylation rather than a Friedel-Crafts alkylation, in order to avoid competitive intermolecular Friedel-Crafts alkylation at the first step, active acyl chloride should be more suitable reactants instead of the corresponding acids. By determining the ratio of these two isomers of 1-indanones generated from this approach, we did detailed research on the regioselectivity of the first acylation step.The following mechanism for this tandem reaction is proposed: firstly Friedel-Crafts acylation between a substituted benzenes and anα,β-unsaturated acyl chloride occurs, and then an intramolecular Friedel-Crafts alkylation cylization and/or Nazarov cyclization gives rise to 1-indanones.The existence of so-called"microwave effects"has been announced for the observed rate enhancements and sometimes altered product distributions compared to oil-bath experiments. Essentially, one can envisage three different possibilities for rationalizing it: thermal effects (kinetics), specific microwave effects and non-thermal microwave effects. In our tandem reaction, a combination of thermal effects (kinetic) and specific microwave effects may be responsible for the observed phenomena.