Patent / 1989
Rhodium-containing hydrogenation catalysts for the conversion of methacycline to doxycycline
(.mu.-Hydrazine-N1:N2)-bis[bis(triphenylphosphine)chlororhodium (I)] (I) and di(.mu.-hydrazine-N1:N2)-bis[bis(triphenylphosphine)rhodium (I)]dichloride (II), useful as stereospecific hydrogenation catalysts for the conversion of 6-demethyl-6-deoxy-6-methylene-5-hydroxytetracycline (methacycline) (III) to .alpha.-6-deoxy-5-hydroxytetracycline (doxycycline) (IV), are prepd. by reacting tris(triphenylphosphine)chlororhodium (V) with hydrazine hydrate in MeOH under an inert atm. in the absence of O using degassed MeOH. I is produced when each mol of V is reacted with .ltoreq.1 mol of hydrazine, and II is formed when the reaction is conducted with .gtoreq.1 mol of hydrazine. The reaction mixt. is stirred at room temp. or refluxed, followed by standing at room temp. for .gtoreq.12 h, forming crystals of the resp. complex catalyst. V (15.0 mg) and 124 mL of a 0.4 M methanolic hydrazine soln. were added to 60 mL MeOH under N, and 7.38 g III hydrochloride added. The mixt. was charged into a reactor and hydrogenated at 88.degree. and 8 kg/cm2. p-Toluenesulfonic acid (3.3 g) was added and the mixt. stirred at 0.degree. for 2 h, producing 8.84 g of 98.9% pure IV p-toluenesulfonate.