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Patent / Jan 01, 1989

Homogeneous catalytic system for hydrogenation of methylenetetracyclines and a process for the preparation of same

  • Philip Page
US 4743699

A process for the prepn. of a homogeneous stereospecific Rh complex hydrogenation catalyst for methylenetetracyclines, of a uniform and well defined compn., contg. Rh, a hydrazine and PPh3, as well as an anion, comprising reacting a Rh salt with R1R2NNR3R4 (I; R1, R2, R3, R4 = lower alkyl, H) or a salt thereof in the presence of PPh3, or by reacting a complex of Rh and PPh3 with I or salt thereof, if necessary in the presence of excess PPh3, was characterized by the fact that the reaction is carried out in a mixt. of a degassed org. solvent, miscible in the reaction, and possibly H2O, at a temp. between and reflux of the reaction medium for between 20 min and 5 h, under an inert atm., and the isolation of the catalyst is carried out by cooling when the complex so formed is little sol. in the cold reaction mixt., or by slow addn. of a degassed inert non-solvent and by cooling when the complex prepd. is sol. in the reaction mixt., followed by filtration and drying under an inert atom. (PPh3)3RhCl and N2H4.H2O in 95% EtOH were refluxed 25 min to give an orange product contg. 16.95% Rh and 4.25% N. This in MeOH was stirred with 6-methylene-5-hydroxytetracycline-HCl and PPh3 in MeOH under 8 kg/cm2 H2 6 h 30 min and the product treated with 4-MeC6H4SO3H to give an .alpha.-6-deoxyoxytetracycline p-tofluenesulfonate in 98.4% yield and 99.8% purity.