Alkylation of Ketones by Use of Solid Koh in Dimethyl Sulf’oxide

A mixture of solid KOH in dimethyl sulfoxide has a strong basicity, but only a low nucleophilicity and is used for Q methylation of ketones. With this simple and inexpensive reagent complete methylation with yields up to 90% can be achieved. Solid KOH in dimethyl sulfoxide (DMSO) is a very strong base with a pKa-value of 27 or even higher. l-3 On the other hand, the nucleophilicity of this reagent is low due to the low solubility of KOH in DMSO which allows only surface reactivity. Therefore, the mixture is especially prone as a base for nucleophilic displacement reactions. This simple and inexpensive reagent has already been used for the alkylation of OH groups in phenols and alcohols 4-5 and of the nitrogens of carboxylic amides6 with high yields. The reaction of ketones with an alkylation reagent in presence of strong bases is an attractive way for the preparation of peralkylated ketones. However, peralkylations are reported to be achieved by stepwise reactions. 7 The use of NaH in THF is an essential improvement. 8 Solid KOH has been applicated in toluene as a solvent, ' but crown ether had to be added. The basicity of the reagent KOH/DMSO is high enough for the direct alkylation of ketones in CL position, and the preparation procedure can be carried out in a very simple manner. 10 All reagents can be used without drying, for the solid KOH binds small amounts of water. l-3 Technical grade KOH can be applicated in pellets without further purification. Pulverization of the pellets will increase the reaction rate, but has only little influence on the yields of alkylation products. The presence of oxygen causes a slow decomposition of DMSO under the reaction conditions, but the exclusion of air is not essential. Methylation is carried out with methyliodide as alkylating reagent. Dimethyl sulfate reacts with DMSO and gives a complex reaction mixture.