Synthetic method of iron-catalyzed biaromatic hydrocarbon and derivatives thereof

Abstract

The invention relates to a synthetic method of an iron-catalyzed biaromatic hydrocarbon and derivatives thereof. According to the synthetic method, under concerted catalysis of a catalysis system composed of an iron salt, a ligand, titanate, phenols or phenolate, aryl halides or halogenoid and an aryl grignard reagent are subjected to mixed heating and coupling in a solvent to obtain the biaromatic hydrocarbon and the derivatives thereof. The synthetic method has the advantages that (1) expensive palladium or high-toxicity nickel does not need to be adopted as a catalytic metal, meanwhile, a zinc reagent, a tin reagent, a boron reagent, a copper reagent, a silicon reagent and the like do not need to be used, the low-toxicity, rich and cheap iron salt and titanate are only needed for use, thus the cost is low, and the environmental-friendly effect is achieved; (2) the application range is wide, the yield is high, and chemical selectivity is high; and (3) operation is easy and convenient, the conditions are mild, enlargement is easy, and the synthetic method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of organic compound preparation and catalytic synthesis, in particular to an iron-catalyzed synthesis method of biaryl compounds. Background technique [0002] Biaryl compounds are widely used in medicine, natural products, functional materials, pesticides and other fields. For example, as shown in the following structural formula: [0003] [0004] Losartan is a commonly used clinical antihypertensive drug; Nantenine is an important natural product of aporphine; and NCB 807 is an important liquid crystal material. [0005] It is precisely because of the importance of the biaryl hydrocarbon structural unit that researchers have made unremitting efforts in the synthesis of such compounds, and the transition metal coupling reaction that emerged in the 1970s has now become the main synthetic method for synthesizing such compounds [Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds....

AI Technical Summary

Problems solved by technology

First of all, the main catalytic metals currently used are Pd or Ni, among which Pd is a noble metal, which is expensive, and most of the catalysts are homogeneous catalysts, which are difficult to recycle, which has become an important bottleneck restricting the industrialization of Pd catalytic reactions; and Ni Although the price is low, the toxicity is high, and the toxicity problem caused by Ni residue after use also severely limits the use of Ni-catalyzed reactions in the large-scale preparation of drugs.

Secondly, in this type of coupling, aryl metal reagents generally use boron reagents, zinc reagents, tin reagents, etc., and it is difficult to directly use easily available and cheap Grignard reagents because Grignard reagents are more active and sensitive. Functional groups such as ester group, amide group, cyano group, ketone group, etc. are easily destroyed in the reaction [Johansson Seechurn, C.C.C.; Kitching, M.O.; Colacot, T.J.; Snieckus, V.Angew.Chem., Int.Ed.2012, 51 , 5062]; and boron reagent, zinc reagent, tin reagent, copper reagent etc. often need to be prepared by Grignard reagent as shown in reaction formula (2), and this not only makes these coupling reactions have no difference in atomic yield and reaction steps. Economical, but also brings a lot of toxic waste due to the use of salts such as zinc, tin, copper, etc., causing serious environmental problems

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