A kind of synthetic preparation method of berberine hydrochloride

A technology of berberine hydrochloride and a synthesis method, applied in the field of organic chemistry, can solve the problems of increased treatment cost of copper-containing wastewater, cumbersome synthesis steps, complicated operation, etc., and achieves reduction of labor protection cost, high chemical yield, and mild reaction conditions. Effect

Active Publication Date: 2022-06-07
SICHUAN UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The above method has the following defects: 1, highly toxic sodium cyanide is used in the process of preparing piperonyl ethylamine; 2, a copper catalyst is used in the ring closure process, resulting in the production of a large amount of copper-containing wastewater, which increases the treatment cost and pollutes the environment; 3 1. The synthesis steps are relatively cumbersome and the operation is complicated; 4. The preparation of o-veratraldehyde needs to use o-vanillin as a raw material, but o-vanillin itself is a drug intermediate that can be used to synthesize various drugs and spices. It is mainly derived from the by-products of the production of vanillin and ethyl vanillin, so the production capacity is low and the price is expensive

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  • A kind of synthetic preparation method of berberine hydrochloride
  • A kind of synthetic preparation method of berberine hydrochloride
  • A kind of synthetic preparation method of berberine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0165] Example 1 Preparation of 4-bromoguaiacol

[0166] Under argon protection, guaiacol (25 g, 201 mmol) was uniformly dispersed in 125 mL of chloroform, and then the reaction solution was pre-cooled at -5 °C for 10 minutes, and bromine (10.3 ml, 201 mmol) was slowly added dropwise thereto. chloroform (75mL) solution, try to keep the system colorless. After the dripping was completed, the reaction was moved to room temperature for 1 hour, and the reaction was detected by TLC dot plate. With 150mL Sat.NaHSO 3 (aq) Quenching the reaction, separating the liquids in a separating funnel, extracting the aqueous layer three times with chloroform, combining the organic phases, backwashing once with saturated brine, drying over anhydrous sodium sulfate and spin-dried to obtain pale yellow crystals Crude. Under reduced pressure distillation (97-100°C / 2mmHg, Lit. 119-120°C / 5mmHg), 4-bromoguaiacol (40g, 94%, mp=31-32°C) was obtained.

[0167] 1 H NMR (400MHz, Chloroform-d) δ 6.99 (...

Embodiment 2

[0168] Example 2 Preparation of 2-hydroxy-3-methoxy-5-bromomandelic acid

[0169] Under ice bath, 4-bromoguaiacol (2 g, 9.8 mmol) was gradually added dropwise to a solution of sodium hydroxide (692 mg, 17.3 mmol) in water (12 mL), and then alumina powder (441.3 mmol) was gradually added thereto. mg, 4.33 mmol). After stirring for 5 minutes in an ice bath, an aqueous solution of glyoxylic acid (50% wt in H 2 O, 1.54g, 10.4mmol), the pH value of the reaction solution is 9-10. The reaction was then moved to a 60°C oil bath for 6 hours, and the reaction was monitored by TLC. After the reaction solution was cooled to room temperature, the alumina powder was removed by suction filtration and the filter cake was washed with a small amount of 20% sodium hydroxide. The filtrate was collected, and the pH value of the filtrate was adjusted to 3-4 with concentrated hydrochloric acid, and the aqueous layer was extracted with toluene 4 times. 63%). The aqueous layer was then adjusted t...

Embodiment 3

[0171] Example 3 Preparation of 2-hydroxy-3-methoxy-5-bromobenzaldehyde

[0172] At room temperature, 25 mL aqueous solution of crude 2-hydroxy-3-methoxy-5-bromomandelic acid (5 g, 18 mmol) was fully mixed with 100 mL of toluene, then moved to 90 °C oil bath for heating, and then slowly added 20 mL of water to the reaction system. % Aqueous solution of ferric chloride (22 mL, 27 mmol), after the dripping was completed, the reaction was continued by heating in an oil bath at 90° C. for 4 hours, and the reaction was monitored by TLC. After the reaction solution was cooled to room temperature, an appropriate amount of toluene was added to the reaction system to dilute, and the reaction solution was extracted with toluene in a separating funnel for 4 times, and the organic phases were combined. 2 SO 4 After drying, spin-dried to obtain 2-hydroxy-3-methoxy-5-bromobenzaldehyde (2.4 g, 85%, mp=115-116° C.) as a pale yellow solid. The aqueous layer was further adjusted to pH 1 with ...

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Abstract

The invention belongs to the field of organic chemistry, and relates to a synthetic method of berberine hydrochloride, comprising: S1: N-[2-(3,4-dioxygen phenyl-5-yl)ethyl]-1-(5-halo-2,3-dimethoxybenzyl)methimine; S2: preparation of 2-(3,4-dioxy Phenyl)-N-(5-bromo-2,3-dimethoxybenzyl) ethylamine; S3: 2-(3,4-dioxyphenyl)-N-(5-bromo ‑2,3‑dimethoxybenzyl) ethylamine hydrochloride; S4: preparation of 12‑halogenated berberine derivatives; S5: preparation of berberine. The present invention gets rid of the constraints of using the by-product o-vanillin to synthesize o-veratraldehyde as a raw material, synthesizes 5-substituting o-veratraldehyde and piperonyl ethylamine, and uses the two to prepare berberine hydrochloride, which has the advantages of easy-to-obtain raw materials and mild reaction conditions , easy operation, high chemical yield, low cost and other advantages.

Description

technical field [0001] The invention belongs to the field of organic chemistry and relates to a preparation method of natural products, in particular to a synthetic preparation method of berberine hydrochloride. Background technique [0002] Berberine hydrochloride (berberine, berberine) is an isoquinoline alkaloid with numerous pharmacological activities extracted from the rhizomes of Coptis chinensis, Phellodendron chinensis, and three needles. It is widely used in traditional Chinese medicine, and has the functions of clearing away heat, detoxification, and purging fire. Initially clinically, berberine hydrochloride mainly played an antibacterial effect and was used to treat bacterial gastrointestinal inflammation and bacillary dysentery and other indications. At the same time, it also showed good curative effect on diarrhea caused by irritable bowel syndrome. In recent years, it has been found that berberine hydrochloride also has the activities of regulating blood sug...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D455/03C07D317/58C07C45/64C07C47/575
CPCC07D455/03C07D317/58C07C45/64C07C45/54C07C51/353C07C51/367C07C47/575C07C59/64Y02P20/55
Inventor 陈芬儿唐培李伟剑蒋龙
Owner SICHUAN UNIV
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