Method for synthesizing 1-acetyl-halo-indolyl-3-acetate

Abstract

The invention discloses a method for synthesizing 1-acetyl-halo-indolyl-3-acetate. According to the method, ortho-aminobenzoic acid with a general formula (II) and a chloride of ortho-aminobenzoic acid which serve as starting raw materials react with ClCH2COOH, NaOH, Na2CO3 and a catalyst KI (or NaI or the like) to produce N-(2-carboxyl)phenylglycine with a general formula (III) and a chloride of N-(2-carboxyl)phenylglycine, N-(2-carboxyl)phenylglycine bromine of a general formula (IV) and a chloride of N-(2-carboxyl)phenylglycine bromine are produced in a manner that N-(2-carboxyl)phenylglycine and the chloride of N-(2-carboxyl)phenylglycine react with N-bromosuccinimide (NBS), CH3OH, H2O and a catalyst, namely ammonium nitrate (or strong acids and weak-base salts, such as ammonium chloride, ammonium sulfate, hydrochloric acid, p-toluenesulfonic acid (p-TSA) and sulfuric acid, or protonic acid), and N-(2-carboxyl)phenylglycine bromine and the chloride of N-(2-carboxyl)phenylglycine bromine react with Ac2O and anhydrous AcNa to produce 1-acetyl-halo-indolyl-3-acetate. The method has the advantages of being safer, more environment-friendly, more time-saving, more convenient in operation, and the like.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a synthesis method of 1-acetyl-halogenated indolyl-3-acetate. Background technique: [0002] Indoxyl, also known as 3-oxindole, tautomerizes with 3-indolinone and spontaneously dimerizes into indigo in air. Indoxyl chromogenic substrates are a very important class of chromogenic substrates, especially widely used in microbial detection. They are formed by the indirect condensation of chromogenic indoxyl and enzyme substrate. When it is hydrolyzed by the target enzyme, indoxyl will be released and two molecules will be coupled under the oxidation of oxygen in the air to form an insoluble in water, heat High stability, color-developing dimer dye. Different indoxyl chromogens have different color development results, among which 5-bromo-4-chloro-3-indoxyl and 5-bromo-3-indoxyl are widely used. Due to the advantages of high sensitivity, low toxicity, and good color rendering perf...

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Problems solved by technology

For the synthesis of these two intermediates of 1-acetyl-5-bromo-4-chloroindolyl-3-acetate and 1-acetyl-5-bromoindolyl-3-acetate, Holt et al. It is reported that 3-chloroaniline is obtained through a five-step reaction, in which there is no catalyst for the condensation of chloroacetic acid, and the reaction time is long (6-72h); the bromination reaction uses acetic acid as a solvent and liquid bromine as a bromination reagent. , this method has disadvantages such as high risk, strong acid HBr pollutants, high boiling point of acetic acid leading to post-processing troubles such as recovery, and these shortcomings are more obvious when the scale is large; the last step reacts under the conditions of acetic anhydride and sodium acetate (i.e. Heumann After the reaction), the post-treatment adopts vacuum rotary evaporation to obtain the crude product. Due to the high boiling point of acetic anhydride, the operation consumes energy and is relatively inconvenient.

And about their improvement or new synthetic technique, especially 1-acetyl-5-bromo-4 chloroindolyl-3-acetate has not yet seen any report

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