Indian Journal of Chemistry Vol. 50B, June 2011, pp. 872-875 Note Lithium hydroxide catalyzed Michael addition – An easy handling and non-toxic protocol Kumari Sukanya & Dibakar Chandra Deka* Department of Chemistry, Gauhati University, Guwahati 781 014, India E-mail: dcdeka@rediffmail.com Received 7 September 2009; accepted (revised) 31 March 2011 Michael addition of dimethyl malonate to α,β-unsaturated ketones are reported in the presence of lithium hydroxide as an efficient catalyst of low toxicity. Moderate to high yield at room temperature is an added advantage of the reaction. Keywords: Michael addition, lithium hydroxide, dimethyl malonate The Michael addition, defined as the nucleophilic addition of a carbanion to the carbon at β-position of an α,β-unsaturated ketone, aldehyde, nitrile, or carboxylic acid derivatives, is a reaction of wide interest in synthetic organic chemistry. Both acids and bases do catalyze Michael addition, and a wide variety of them have been reported 1-8 . A few lithium salts and complexes 9-12 , either alone or in combination with others, have also been reported as successful catalysts in Michael addition but use of lithium hydroxide as a catalyst could not be traced. Malonate carbanion as a nucleophile in Michael addition is known for long 13,14 but the same in the presence of lithium hydroxide as the catalyst has never been reported. Herein are reported a few examples of such Michael additions with lithium hydroxide as the catalyst. Results and Discussion Reaction of dimethyl malonate with α,β-unsaturated ketones shown in Table I proceeded smoothly under the catalytic effect of lithium hydroxide in methanol at RT giving moderate to high yields. Both steric and electronic factors appear to influence the outcome of reactions. Low yields in entry 2 to 10 as compared to that in entry 1 can be attributed to combined effects of steric and electronic factors of the substituents in the benzene ring. Efforts were made to improve yields and also, to reduce reaction time by refluxing the reaction mixture. Although yields virtually remained unchanged, substantial decrease in reaction time was achieved by carrying out the reaction at refluxing temperature (Table II). No product formation could be observed without lithium hydroxide even after several hours of refluxing. Efforts were also made to improve yields and reduce reaction time by changing solvent and quantity of catalyst. As shown in Table III methanol appears a much better solvent as compared to the other three viz. acetonitrile, toluene and THF. THF with low polarity and high volatility (low b.p.) is the least suited for these reactions. Efforts to improve yield with shorter reaction time by adding more catalyst were met with limited success. Increase in catalyst from 0.025 to 0.3 molar equivalent enhanced yields from about 49 to 92% (Table IV). However, doubling the catalyst from 0.1 to 0.2 molar equivalent had only marginal effect on the yield. Likewise, increase in the catalyst load from 0.2 to 0.3 molar equivalent had no countable benefit. Therefore, 0.1 molar equivalent of catalyst is considered as optimal. Finally, higher catalytic efficiency of LiOH, as compared to a few other commonly used catalysts in Table I — Michael addition of dimethyl malonate (DMM) at RT R O X R O CO 2 Me MeO 2 C X DMM LiOH / MeOH, RT Entry X R Time (hr) Yield (mol%) 1 H Me 40 88 2 o-OMe Me 40 68 3 m-OMe Me 40 70 4 p-OMe Me 40 76 5 p-Cl Me 40 75 6 H Ph 60 76 7 o-OMe Ph 60 64 8 m-OMe Ph 60 65 9 p-OMe Ph 60 71 10 p-Cl Ph 60 72