Preparation method of amide or ester compound

Abstract

The invention discloses a preparation method of an amide or ester compound, which comprises the steps of under the protection of inert gas, taking substituted carboxylic acid, an amine compound or an alcohol compound as a raw material, and reacting in an organic solvent in the presence of a phosphine oxide compound, an acyl chloride compound and organic alkali to generate the amide or ester compound. According to the preparation method, the phosphine oxide compound and the acyl chloride compound are used as condensing agents, the organic base is used as an acid-binding agent, substituted carboxylic acid and amine or alcohol react in the organic solvent to generate the amide or ester compound, the raw materials are cheap, easy to obtain, green and non-toxic, the green and environment-friendly requirements are met, the reaction rate is high, the yield is high, racemization is not prone to occurring, the atom economic utilization rate is high, the separation and post-treatment processes are simple and easy to operate, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a preparation method of amides or esters. Background technique [0002] Amides and esters are the two most common functional groups in organic chemistry. Amides or esters play an extremely important role in biochemistry, medicinal chemistry, pesticide chemistry and organic polymer materials [1] , and these two types of compounds are also important intermediates in organic synthesis [2] , so the research on the efficient construction of amide bonds and ester bonds has been receiving much attention. [0003] The traditional synthesis methods of amides and esters mostly form C-N bonds or C-O bonds through condensation amidation or condensation esterification of carboxylic acids or derivatives with amines or alcohols [3-5] , including acid chloride method, mixed anhydride method, condensing agent as a medium, etc. The acid chloride method usually reacts carboxylic acid w...

AI Technical Summary

Problems solved by technology

Carbodiimide condensing agents have low solubility in most organic solvents and are difficult to remove

Organophosphorus condensing agents can better solve the problem of racemization of chiral products. A variety of phosphate and phosphoramide condensing agents are widely used in the condensation of amides and esters, with good yield and chirality retention. [8-9] , but its disadvantage is that when the reactivity of amines and alcohols is low, amide and ester products are often not obtained, and an equivalent amount of organophosphorus condensing agent is required, resulting in equivalent by-products, which does not conform to the principle of atom economy

In recent years, several new highly active condensation reagents have emerged, such as the new condensation agent Ynamide [10] , Nitromethyl imidazolium salt [11] , silane [12] etc., the product racemization of amides or lipid compounds synthesized by these new condensing agents is relatively small; but equivalent condensing agents are also required, resulting in equivalent by-products, which do not conform to the principle of atom economy

[0005] In summary, the existing methods for the preparation of amides or esters often have problems such as many operating steps, low yields, easy racemization, expensive condensation agents or catalysts, and do not conform to the principle of atom economy. It is still a great challenge to develop preparation methods that have mild reaction conditions, are environmentally friendly, are not easy to racemize, have fast reaction rates, and are suitable for large-scale production of amides and lipids.

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