Method for preparing lidocaine intermediate alpha-chloroacetyl-2, 6-dimethylaniline and lidocaine without adding extra alkali

Abstract

The invention relates to a method for preparing lidocaine intermediate alpha-chloroacetyl-2, 6-dimethylaniline and lidocaine without adding extra alkali, which belong to the technical field of organicsynthesis. The invention discloses the method for preparing alpha-chloroacetyl-2, 6-dimethylaniline, which comprises the following steps: in the process of generating alpha-chloroacetyl-2, 6-dimethylaniline by carrying out a chloroacetylation reaction on 2, 6-dimethylaniline and chloroacetyl chloride, taking one or a mixed solution of more than two of an alkane solvent, an ether solvent and an ester solvent as an organic solvent. No extra alkali is added, so that the separation process can be reduced; the method can be applied to one-pot reaction to directly prepare lidocaine, namely, 2, 6-dimethylaniline, chloroacetyl chloride and diethylamine directly react to obtain lidocaine, the method is simple, no extra alkali is added, the separation process is simplified, the used solvents are three types of solvents, operation is safer, and the obtained product is high in purity, high in yield, low in cost and environmentally friendly.

Description

technical field [0001] The invention relates to a method for preparing lidocaine intermediate α-chloroacetyl-2,6-dimethylaniline and lidocaine without adding additional alkali, and belongs to the technical field of organic synthesis. Background technique [0002] The structural formula of Lidocaine (English: Lidocaine) is shown in formula (1). Lidocaine is an anesthetic and antiarrhythmic drug that has been clinically used for many years. It was synthesized by Lofgren in 1934 and used as a local anesthetic. It is A derivative of cocaine, but without the hallucinating and addictive components of cocaine, the local anesthetic effect is strong and long-lasting, with good surface penetration, can be injected or used as topical anesthesia, and it usually takes effect after one to three minutes of application , the effect lasts for one to three hours. In the 1950s, it was used to treat ventricular arrhythmia that occurred during the operation. It was used to treat arrhythmia in 1...

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Problems solved by technology

[0004] Although lidocaine has high application value, its synthetic method still continues the traditional process method, as, U.S. Patent US2441498 discloses a kind of preparation method of lidocaine, uses sodium acid in the synthetic process, has waste liquid and waste residues; the amount of solvent benzene used in the preparation process is large (1mol / L), and benzene belongs to a class of solvents, and the requirements for drug solvent residues are high and will cause adverse effects on the environment; intermediates need to be acid-washed and then alkali-washed , the steps are cumbersome

Chinese patent CN105294477 discloses a preparation method of lidocaine hydrochloride, which uses 2,6-xylenol as a raw material to obtain 2,6-xylenol under Pd / C catalysis, and then reacts with sodium methoxide, N, Methyl N-diethylaminoacetate is reacted to obtain lidocaine hydrochloride, but the method N, N-methylaminoacetate is commercially unavailable, and the cost of raw materials is high

Chinese patent CN102070483 discloses a kind of preparation method of lidocaine, all needs to use carbonate in the two-step reaction of this method, and the consumption of carbonate is large (2.5-3.5 equivalent), there is a large amount of waste residue and waste gas to produce, add Increase the separation and purification process of the product and cause environmental pollution; the solvent acetone used in the two-step reaction is a precursor reagent, and the purchase channel is limited

In summary, in the existing method for preparing lidocaine, 1) use alkalis such as sodium bicarbonate or carbonate, and the consumption is large, and produce a large amount of waste gas (hydrogen chloride or carbon dioxide), waste residue (hydrochloride) and the like The large-scale use of alkali will bring difficulties in product separation, increase separation costs, and environmental and resource issues; 2) The solvents used are Class I solvents or easy-to-toxic solvents, which have adverse effects on the environment and purchase channels; 3) Raw materials Not commercially available, high cost

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