Reserch On α-Alkylation Of Ketones With Alcohols In Water

Carbon-carbon bond-forming reaction, especially the α-alkylation of carbonyl compounds with different electrophiles such as alkyl halides, is one of the most important and frequently used methods in organic systhesis. However, the conventional α-alkylation method suffers from problems with waste salts. Therfore, the metal catalyzed α-alkylation of ketones through borrowing hydrogen mechanism has attraced considerable attention because it is an efficient, clean and atom-economic protocol, and producing water as the only side product. In this paper, the effect of homogeneous catalyst and heterogeneous catalyst were studied in detail, acetophenone and 1-butanol in the water phase system as reaction substrate.In homogeneous catalyst study, we first designed and synthesized six ligands, including IMes.HCl, IPr.HCl, Bis[N,N’-(2,4,6-Trimethylphenyl)imino]acenaphthene, 1,10-phenanthrolines and so on. In combination with RuCl3, RhCl3, IrCl3 or PdCl2 as homogeneous catalyst, the catalytic effect of them was studied, respectively. It was found that all of the homogeneous catalysts were less effective in the α-alkylation of ketones with 1-butanol in water.In the exploration of heterogeneous catalysts, Ru/C, Rh/C, Ir/C and Pd/C were mainly studied. It was found that Pd/C was a promising candidate to catalyze the direct α-alkylation of ketones in water. On this basis,other reaction parameters including temperature, reaction time, base and the heating method were studied. Finally the optimized reaction conditions were determined as follows: acetophenone and 1-butanol were mixed with 5 wt% Pd/C and 1.92 equivalents of K3PO4 in H2 O, then the reaction proceeded well to give the corresponding α-alkylation of ketones in good yield at 180℃ for 90 min though microwave irradiation.When the recovered catalyst was used without any treatment, the catalyst still retained relatively high activity and always good selectivity to the alkylated product. We also found that α-alkylation of ketones with a variety of primary alcohols proceeded well to give the corresponding coupling ketones in good yield.