Method for synthesizing 1,3-diphenyl-1-propanol compound

Abstract

The invention relates to a method for synthesizing a 1,3-diphenyl-1-propanol compound, belonging to a method for synthesizing a compound. P-substituted 1-phenyl ethanol and p-substituted benzyl alcohol are used as raw materials, wherein R and R' are hydrogen atoms, halogen atoms Cl, Br, alkyl and alkoxy, and the adding ratio of the substituted 1-phenyl ethanol to the substituted benzyl alcohol is 1: (1-2). The method comprises the following steps of: sequentially adding a dry catalyst, alkali, substituted1-phenyl ethanol and substituted benzyl alcohol into an anhydrous solvent under the condition of nitrogen, placing a reactor into an oil bath of 125 to 135 DEG C, and stirring for 8 to 24 hours; cooling, neutralizing the reaction solution, performing extraction by using ethyl acetate, and concentrating the extract in vacuum till no ethyl acetate smell; and performing chromatographic purification by using a positive silica gel column of 100 to 200 meshes. The invention has the advantages of simple, convenient and feasible method, low production cost, reduced difficulty of purification and post treatment and weakened influence on the environment.

Description

technical field [0001] The invention belongs to a compound synthesis method, specifically refers to the cross-coupling reaction of secondary alcohols and primary alcohols. Background technique [0002] 1,3-diphenyl-1-propanol compounds are as follows formula A, wherein Ar 1 , Ar 2 Respectively substituted phenyl, and its derivative B, are important pharmaceutical and chemical raw materials, which are used in immunosuppression (J.Am.Chem.SOC.1993, 115, 9925-9938), prevention and treatment of neuropathy. Degenerative diseases (WO03048142A1), anticoagulation (WO9810763A1), anti-abnormal proliferation (US20030191279), inhibition of β-secretase (US2005119329A1), antibacterial (WO2007014885A1), inhibition of HIV-1 protease (Journal of Medicinal Chemistry, 1997 , Vol.40, No.23, 3707-3711) and other fields are widely used in the synthesis of drugs and intermediates. Therefore, the development of its convenient, economical and environmentally friendly synthetic methods has attract...

AI Technical Summary

Problems solved by technology

But despite this, there are still the following problems that limit the application of this method in the industrial production of 1,3-diphenyl-1-propanol compounds:

[0007] 1) At present, all such reactions use ruthenium (Ru), iridium (Ir), palladium (Pd) and silver (Ag) metals as catalysts, which are expensive and increase the reaction cost;

[0008] 2) Some reactions need to add hydrogen acceptors (such as 1-dodecene) to promote the reaction, which reduces the atomic efficiency of the reaction and brings great difficulties to the subsequent separation and purification of the reaction;

[0009] 3) Some catalysts (such as RuCl2(DMSO)4, etc.) are not commercialized and require special preparation, which is not suitable for industrial production;

[0010] 4) Most reactions need to add special ligands (such as azacarbene ligands, etc.) to enable the reaction to proceed smoothly and achieve better selectivity, and these ligands are often not suitable for obtaining, and the production cost is quite high;

[0011] 5) For some reactions, it is necessary to add an excessive amount of primary alcohol to ensure better product selectivity, resulting in waste and loss of raw materials;

[0012] 6) Most reactions must add stoichiometric alkali to receive better results, which not only causes great environmental problems, but also produces a large amount of alkaline waste liquid that also increases the cost of post-treatment

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