Method for preparing diphenyl carbinol and derivatives thereof

Abstract

The invention discloses a method for preparing diphenyl carbinol and derivatives thereof. In an alkali and solvent environment, diphenyl ketone and derivatives thereof are subjected to a hydrogenation reaction in the presence of a transition metal complex serving as a catalyst to form the diphenyl carbinol and derivatives thereof, wherein the general formula of the transition metal complex is MLnL'XY and is a transitional metal pnictide formed by a ligand having a NH2-N(SP2) or NH2-NH2 structural characteristic and a transition metal. When the method for preparing the diphenyl carbinol and derivatives thereof is used, a small amount of catalyst is used, the reaction process is stable, the conversion rate is over 98 percent, the very few by-products are produced in the reaction, the treatment after reaction is simple, the whole process period is short, the cost is low, and the large-scale production can be realized easily.

Description

technical field [0001] The invention relates to a preparation method of benzhydryl alcohol and derivatives thereof. Background technique [0002] Diphenylmethanol and its derivatives can be used as important pharmaceutical intermediates, for example, diphenylmethanol can be used in the synthesis of benzotropine, diphenhydramine, cephalosporin antibiotics and other drugs; 4,4'-difluorobenzhydrin It can be used in the synthesis of the calcium channel blocker furnarizine and the antihistamine fluterizine. [0003] Benzyl alcohol and 4,4'-difluorobenzyl alcohol are mainly obtained by reducing the corresponding ketones. The traditional reduction processes mainly include: [0004] 1. Zinc powder or aluminum powder-alkali reduction method, but this method requires the use of a large amount of zinc powder or aluminum powder, resulting in cumbersome post-treatment and the generation of environmentally unfriendly metal waste liquid. [0005] 2. Sodium borohydride or potassium borohy...

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Problems solved by technology

[0004] 1. Zinc powder or aluminum powder-alkali reduction method, but this method requires the use of a large amount of zinc powder or aluminum powder, resulting in cumbersome post-treatment and the generation of environmentally unfriendly metal waste liquid

[0005] 2. Sodium borohydride or potassium borohydride reduction method, but this method also needs to use a large amount of sodium borohydride or potassium borohydride, the reaction process often has the occurrence of by-product borate, and the yield is low

For example, benzhydryl alcohol can be prepared by palladium carbon, palladium carbon-ethylenediamine, Raney nickel, etc. catalytic hydrogenation reduction of benzophenone, but at the same time, there is often an over-reduced by-product diphenylmethane [Hironao Sajiki, Kazuyuki Hattori, and Kosaku Hirota, Tetrahedron, 57 (2001), 4817-4824]

Noyori group prepared a structure as trans-[RuCl 2 (phosphane)(1,2-diamine)] transition metal complexes can efficiently catalyze the hydrogenation reduction reaction of diaryl ketones, they use trans-[RuCl 2 {P(C 6 h 4 -4-CH 3 ) 3 } 2 {NH 2 CH 2 CH 2 NH 2 }] Catalytic hydrogenation reduction of benzophenone can achieve 100% conversion rate, but the reaction time is long, up to 48 hours [T.Ohkuma, M.Koizumi, H.Ikehira, T.Yokozawa, R. Noyori, Org. Lett. 2000, 2, 659-662]

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