A method for one-step synthesis of carboxylic acids with two extended carbon chains from olefins

Abstract

The invention relates to a method for one-step synthesis of carboxylic acid with two extended carbon chains from olefin, which comprises the following steps: under the protection of inert gas, sequentially adding an olefin substrate, a photocatalyst, a hydrogen atom transfer reagent, alpha-haloacetic acid, a reducing agent, a solvent and protonic acid into a reactor, and reacting at normal temperature under the irradiation of 25W blue light to obtain a reaction product; diluting, alkalizing, washing, acidifying and extracting the reaction product to obtain an organic phase; and finally, carrying out reduced pressure distillation and column chromatography on the organic phase to obtain a carboxylic acid product with two extended carbon chains; or carrying out reduced pressure distillation and column chromatography on the reaction product to obtain a carboxylic acid product with two extended carbon chains. The invention is simple to operate, direct synthesis conditions are mild, mutual conversion among various functional groups in the traditional carboxylic acid compound synthesis process is avoided, and the atom and step economy of the reaction is improved. Meanwhile, the method disclosed by the invention can also be applied to the simplified synthesis of the medicines cinacarbazide and tirofiban.

Description

technical field [0001] The invention relates to the technical field of synthesis of carboxylic acid compounds, in particular to a method for one-step synthesis of carboxylic acids extending two carbon chains from alkenes. Background technique [0002] Carboxylic acid compounds widely exist in nature and daily life, and are a very important class of chemicals. Whether it is complex natural products, drug molecules for treating diseases or simple surfactants, a large part of them are carboxylic acid compounds . In addition, carboxylic acid compounds can also be used to make industrial raw materials such as plastics, rubber, dyes, etc., which are closely related to our daily life. Indeed, some organizations predict that by 2023, the global market share of carboxylic acid compounds will reach about 20 billion US dollars, and from 2017 to 2023, the market share will grow at an annual growth rate of about 5%, so the synthesis of carboxylic acid compounds, In particular, a clean,...

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Problems solved by technology

The necessary condition for the implementation of this type of method is to introduce pre-functional groups in the molecule; secondly, the reaction conditions are relatively harsh. In the oxidation reaction of alcohols and aldehydes, the oxidizing agent is generally a metal Mn and Cr compound with high valence and strong oxidizing properties. The post-processing of this process is relatively difficult and will cause great environmental pollution; while the hydrolysis reactions of compounds such as cyano groups and ester groups generally need to be carried out under strong acid or strong alkaline conditions, and heating is required in most cases

These methods play a very important role in the synthesis of carboxylic acid compounds, but due to the harsh reaction conditions, they are not suitable for complex molecules with more functional groups, especially for the modification of complex molecules in the later stage of synthesis.

[0005] Although the method of synthesizing carboxylic acids extended by two carbon atoms from substrates is of great significance in organic synthesis, especially in the synthesis of drugs, there is no literature report on the direct synthesis of carboxylic acids extended by two carbon atoms from alkenes. Synthetic method, from the current development method, malonic acid or malonic acid ester is an important raw material for the synthesis of carboxylic acid extended by two carbon atoms from the substrate, these synthetic processes include condensation reaction, conjugate addition, hydrogenation reaction , the generated intermediate product containing malonic acid or malonate still needs to be further hydrolyzed and decarboxylated under acidic and heating conditions to obtain a carboxylic acid product with two carbon atoms extended (WO2007005633A2, CN104478736, CN107963965, CN104447509 , Tetrahedron 1993, 49 , 5767-5776; Bioorg. Med. Chem. Lett. 2012, 22 , 2287-2290; J. Med. Chem. 2012, 55 , 9817−9830)

This kind of synthesis method not only has cumbersome steps, poor atom economy, but also relatively harsh reaction conditions, which makes this method have certain limitations in the synthesis and application of complex molecules containing multifunctional groups.

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