Optimization of the enol ether formation reaction of androstenedione

Abstract

The search for suitable protecting groups of carbonyl and hydroxyl functions has beer, of continuous 1^. portance in steroid chemistru~y. Carbonyl groups are protected by formation of cyclic or acyclic ketals and thioketals, hemithioketals, cool ethers and thioenol ethers and are stable in basic medium. They are resistant to reduction with metal hydrides and with sodium and alcohol; Grignard reactions; Oppenauer and chromic anhydride-pyridine oxidations and to treatment with acylating or dehydrating agents in pyridine. However, they are regenerated easily by acids to the corresponding ketone. In this work, the optimization of the carbonyl protection reaction of position 3 of androstendione molecule with enol ether formation has been accomplished using the composite central 2' factorial design. The model was adjusted with a correlation coefficient of 0,9971 and an absolute medium error of 4,18 %. For optimum conditions maintaining as restriction the study limits of each parameter, the conversion was of 99 %. The results were by studying the response surfaces and the isolines curves, showing in all cases the existence of an optimum zone near to center of applied design. Finally, the substitution results of paratoluensulphonic acid by methanosulphonic acid are shown, giving higher yields of this reaction than previously reported, with additional savings on the cost of raw materials.