Verfahren zur Herstellung von Thyroxin und seinen Derivaten

Compounds of the formula in which R is or where X is hydrogen or a methyl or ethyl group and Y is hydrogen or a formyl, acetyl or b -carboxy propionyl group, are prepared by reacting a compound of the formula with iodine in the presence of a suitable solvent and a suitable organic base. Such solvents are water, dioxan, or a lower aliphatic alcohol, e.g. methanol or ethanol, and such bases are primary or secondary aliphatic amines which may contain a cyclohexyl or alkylcyclohexyl group and may also contain one or two hydroxy groups, piperidine, a C-alkylpiperidine or morpholine. Preferred bases are methylamine, ethylamine, butylamine, ethylene diamine, dibutylamine or mono- or di-ethanolamine. by performing the reaction in the presence of hydrogen peroxide which oxidizes hydrogen iodide produced the iodine employed is reduced by half. If R is the Group optically active products are obtained from optically active starting materials. Examples describe the iodination of (1), (2), (9) 3 : 5-diiodothyronine to form thyroxine; (3) 5-(31 : 51-diiodo - 41 - p - hydroxyphenoxybenzyl)-hydantoin to form thyroxine hydantoin; (4) 3 : 5-diiodo-N-acetylthyronine to give N-acetylthyroxine; (5) 3 : 5-diiodo-N-b -carboxypropionylthyronine to give N-b -carboxypropionyl thyroxine; (6) N-formyl-3 : 5-diiodothyronine to form N-formyl thyroxine; (7) 3 : 5-diiodo-L-thyronine to form L-thyroxine; (8) 3 : 5-diiodo-DL-thyronine methyl ester to give thyroxine methyl ester. As starting materials are prepared: (4) 3 : 5-diiodo-N-acetyl thyronine, by reacting 3 : 5-diiodo thyronine methyl ester with acetyl chloride in anisole solution, followed by saponification; (5) 3 : 5-diiodo-N-b -carboxypropionylthyronine by reacting 3 : 5-diiodothyronine methyl ester in anisole solution with b -carbethoxy-propionyl chloride, followed by saponification.