Method for synthesizing 5-bromine-4-chlorine-1-acetyl-3-indoxyl

Abstract

The invention discloses a 5-bromine-4-chlorine-1-acetyl-3-indoxyl synthesis process method. According to the method, 3-chlorine-2-methylaniline which is very easy to obtain is adopted as an initial raw material, and 5-bromine-4-chlorine-1-acetyl-3-indoxyl is prepared through seven steps of acetylation of acetic anhydride, bromine addition, oxidation of hydrogen peroxide, hydrolysis under an acidiccondition, a nucleophilic reaction of chloroacetic acid, cyclization of acetic anhydride, selective hydrolysis of sodium sulfite, and the like. The 5-bromine-4-chlorine-1-acetyl-3-indoxyl is furtheradopted as indoxyl for producing chromogen and is indirectly condensed with an enzyme substrate to prepare an indole developing substrate. The method is simple and practical in process, reaction conditions of the method are very mild, the raw materials are easy to obtain, the process is safe and environment-friendly, and industrialization is easy.

Description

Background technique [0001] Indoxyl is easy to self-polymerize into dimers in the air to form indigo, which is insoluble in water, has high thermal stability and forms stable color rendering. It is widely used in the detection of various enzymes, especially the condensation between indoxyl as a chromogen or its substituent and an enzyme substrate. After synthesizing the 5-bromo-4-chloro-1-acetyl-3-indoxyl, the corresponding compounds are formed with derivatives of enzyme substrates such as sugars, amino acids, peptides, esters, and nucleotide halides , the corresponding chromogenic substances of the corresponding microbial enzyme hydrolyzate do not need to be observed by ultraviolet radiation, and most of them have no diffusion phenomenon in solid medium. [0002] Holt et al. (Proc.R.Soc.B, 1958, 148.481-494) disclosed that using anthranilic acid and haloaniline as starting materials, a series of different substituted 1-acetyl-3 -The synthetic method of indole ethyl ester, b...

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Problems solved by technology

[0006] Chinese patent CN106986809A "a kind of synthetic method of 5-bromo-6-chloro-3-indole octyl ester" is that 4-chloro-2-aminobenzoic acid and N-bromosuccinimide are synthesized through bromoreaction Obtain 5-bromo-4-chloro-2-aminobenzoic acid, and then undergo cyclodecarboxylation to obtain 5-bromo-6-chloro-3-bromoindole ethyl ester, and then perform transesterification to obtain 5-bromo-6- Chloro-3-indooctyl ester, there are similar steps, but this key intermediate cannot be obtained

This method uses precious metals such as platinum, palladium, etc. as a catalyst, and hydrogenation reaction occurs with hydrogen under a pressurized condition of 20-80 bar. The total yield is very low, and the reaction process is complicated, and dangerous or uncontrollable conditions are used. And the obtained product is not suitable for synthesizing derivatives of enzyme substrates such as sugars, amino acids, peptides, esters, and halogenated nucleotides to form corresponding compounds

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