CN1244530C

CN1244530C - Green synthesis process for carvacrol for fodder antibacterial agent

Info

Publication number: CN1244530C
Application number: CN 03156708
Authority: CN
Inventors: 石波; 梁平; 李秀波; 刘一峰; 赵炳超
Original assignee: Feed Research Institute of Chinese Academy of Agricultural Sciences
Current assignee: Feed Research Institute of Chinese Academy of Agricultural Sciences
Priority date: 2003-09-08
Filing date: 2003-09-08
Publication date: 2006-03-08
Anticipated expiration: 2023-09-08
Also published as: CN1488615A

Abstract

The present invention relates to a chemosynthesis process of carvacrol as an animal antibacterial agent, which comprises: selecting O-cresol as raw material, using methylene chloride, n-hexane, etc. with tiny harm to the human body and environment as a reaction solvent, and preparing carvacrol for a fodder antibacterial agent by alkylation reaction, liquid-liquid extraction, reduced pressure concentration and reduced pressure distillation. The preparation method has the characteristics of simple process, high yield, superior product quality, easy industrial production, etc.

Description

Green synthesis process of carvacrol as feed antibacterial agent

The invention relates to a chemical synthesis process of carvacrol as an antibacterial agent for animals.

Carvacrol is a phenol compound with a bactericidal effect and mainly exists in thymus plant essential oil in nature. One of the main antibacterial components in natural feed antibacterial agents such as origanum oil and mountain pepper oil is carvacrol. Because of broad antibacterial spectrum, safety and extremely low residual quantity in animal bodies, the antibacterial composition is applied to the aspects of treating diarrhea, coccidiosis and the like of animals such as chickens, piglets and the like.

U.S. Patent No. 2064885 discloses a method for preparing carvacrol by condensation reaction of o-cresol as raw material and anhydrous aluminium trichloride as catalyst with 2-chloropropane. Although the method can obtain carvacrol with higher yield, the solvent used in the method is dichloroethane which has high toxicity, is a highly toxic compound and a carcinogenic substance, is harmful to the working environment, and can bring certain toxic residues to the product, so that the synthesized product can be applied only by strictly refining.

The invention aims to protect the environment, eliminate toxic residual substances in the chemical synthesis of the antibacterial agent carvacrol and improve the safety of products.

The invention is mainly characterized in that: anhydrous aluminum trichloride or ferric trichloride is adopted as a catalyst, green compounds with little harm to human bodies and the environment, such as dichloromethane or n-hexane and the like are adopted as reaction solvents, alkylation condensation reaction is carried out on o-cresol and 2-chloropropane, and after extraction by the solvents, such as dichloromethane or n-hexane and the like, reduced pressure concentration is carried out, so that the carvacrol product with high content and direct use is prepared.

Detailed description of the invention:

adding dichloromethane or n-hexane which is a solvent required by a reaction system into a reaction kettle with a stirring device, adding catalyst anhydrous aluminum trichloride or anhydrous ferric trichloride, stirring and cooling to minus 15 ℃ plus or minus 5 ℃, slowly adding o-cresol, dropwise adding 2-chloropropane when the temperature of the reaction system reaches minus 15 ℃ plus or minus 5 ℃, reacting for 4 hours plus or minus 1 hour at minus 15 ℃ plus or minus 5 ℃, and finishing the reaction. At room temperature, crushed ice was slowly added to the reaction product, and stirred until the ice was completely melted. Standing, separating oil layer, washing water layer with dichloromethane or n-hexane twice, mixing separated oil layers, concentrating at 35 deg.C under vacuum degree of 200Pa until no dichloromethane or n-hexane solvent is evaporated to obtain carvacrol crude product. The carvacrol content is determined to be more than or equal to 70 percent by HPLC. Vacuum distilling at 40Pa, and collecting the distillate at 95 + -1 deg.C under 4mm to obtain light yellow carvacrol refined product.

The specific process conditions of the invention are as follows:

(1) alkylation reaction:

the material weight ratio of o-cresol and 2-chloropropane is 1.25: 1, the weight ratio of the catalyst to the o-cresol is 1.9 +/-0.1: 1, the volume and weight ratio of the dichloromethane or n-hexane to the o-cresol is 4.9 +/-0.6: 1, the reaction temperature is minus or plus 15 ℃ to minus 5 ℃, and the reaction time is 4h +/-1 h.

(2) Liquid-liquid extraction: crushed ice was added to the reaction product at room temperature, and stirred until the ice was completely melted. The dosage of the crushed ice is 2-3 times of the dosage of the solvent, and an oil layer is separated. Washing the water layer with fresh reaction solvent for 2-3 times, and combining the separated oil layers. The amount of the washing solvent is 1/4-1/5 of the amount of the crushed ice.

(3) And (3) concentrating under reduced pressure: concentrating at 35 deg.C under vacuum of 200Pa until no solvent flows out.

(4) And (3) reduced pressure distillation: vacuum degree of 40Pa, and collecting the fraction at 95 +/-1 ℃ and 4 mm.

The catalyst in the invention is anhydrous aluminum trichloride or anhydrous ferric trichloride, and the aqueous phase after liquid-liquid extraction is an aluminum salt or iron salt solution which can be recovered by a concentration dehydration mode. By adopting the method, the yield of carvacrol is more than 60 percent and the content is more than 65 percent without reduced pressure distillation.

FIG. 1 is a process flow diagram of the antibacterial agent carvacrol of the present invention.

The invention has the advantages that: the solvent used in the traditional process is a highly toxic compound dichloroethane and a carcinogenic substance, which not only harms the working environment, but also brings certain toxic residues to the product, so that the synthetic product can be applied only by strictly refining. The reactant used in the whole process of the invention has little harm to human body and environment, and the process is simple.

Example 1

Weighing 50L of dichloromethane, adding into a 100L reaction kettle, adding 20.0kg of catalyst anhydrous aluminum trichloride, stirring, cooling to-10 ℃, slowly adding 10.92kg of o-cresol, dropwise adding 8.76kg of 2-chloropropane when the temperature of a reaction system reaches-10 ℃, and reacting for 4.0h at-10 ℃ to finish the reaction. At room temperature, 100.0kg of crushed ice was slowly added to the reaction product, and stirred until the ice was completely melted. Standing, separating oil layer, washing water layer with 20L dichloromethane twice, mixing separated oil layers, concentrating at 35 deg.C under vacuum degree of 200Pa until no dichloromethane solvent is evaporated to obtain 11.2L carvacrol crude product. The carvacrol content is more than or equal to 70 percent (measured by HPLC). Vacuum distilling to obtain light yellow carvacrol 7.6L (vacuum degree of 40Pa, collecting 94-96 deg.C, and 4mm fraction).

Example 2

Weighing 50L of n-hexane, adding into a 100L reaction kettle, adding 20.0kg of catalyst anhydrous aluminum trichloride, stirring, cooling to-15 ℃, slowly adding 10.92kg of o-cresol, dropwise adding 8.76kg of 2-chloropropane when the temperature of a reaction system reaches-15 ℃, reacting for 4.0h at-15 ℃ and finishing the reaction. At room temperature, 100.0kg of crushed ice was slowly added to the reaction product, and stirred until the ice was completely melted. Standing, separatingoil layer, washing water layer with 20L n-hexane twice, mixing separated oil layers, vacuum concentrating at 35 deg.C under 200Pa until no n-hexane solvent is evaporated to obtain 12.0L carvacrol crude product. The carvacrol content is more than or equal to 65 percent (measured by HPLC).

Example 3

Weighing 50L of dichloromethane, adding into a 100L reaction kettle, adding 20.0kg of catalyst anhydrous ferric chloride, stirring, cooling to-10 ℃, slowly adding 10.92kg of o-cresol, dropwise adding 8.76kg of 2-chloropropane when the temperature of a reaction system reaches-10 ℃, reacting for 4.0h at-10 ℃ to finish the reaction. At room temperature, 100.0kg of crushed ice was slowly added to the reaction product, and stirred until the ice was completely melted. Standing, separating oil layer, washing water layer with 20L dichloromethane twice, mixing separated oil layers, concentrating at 35 deg.C under vacuum degree of 200Pa until no dichloromethane solvent is evaporated to obtain 10.8L carvacrol crude product. The carvacrol content is more than or equal to 70 percent (measured by HPLC).

Example 4

Weighing 50L of n-hexane, adding into a 100L reaction kettle, adding 20.0kg of catalyst anhydrous ferric chloride, stirring, cooling to-15 ℃, slowly adding 10.92kg of o-cresol, dropwise adding 8.76kg of 2-chloropropane when the temperature of a reaction system reaches-15 ℃, reacting for 4.0h at-15 ℃ and finishing the reaction. At room temperature, 100.0kg of crushed ice was slowly added to the reaction product, and stirred until the ice was completely melted. Standing, separating oil layer, washing water layer with 20L n-hexane twice, mixing separated oil layers, concentrating at 35 deg.C under vacuum degree of 200Pa until no n-hexane solvent is evaporated to obtain 11.6L carvacrol crude product. The carvacrol content is more than or equal to 65 percent (measured by HPLC).

Note: the green synthesis process provided by the invention means that the solvents in the reaction system are dichloromethane and n-hexane which have low toxicity to animals and human beings and are environment-friendly, and three wastes are not discharged in the production process.

Claims

1. A preparation method of carvacrol as a feed antibacterial agent is characterized by comprising the following steps:

(1) adding dichloromethane serving as a solvent required by a reaction system into a reaction kettle with a stirring device, adding anhydrous aluminum trichloride serving as a catalyst, stirring and cooling to minus 15 ℃ plus or minus 5 ℃, slowly adding o-cresol, dropwise adding 2-chloropropane after the temperature of the reaction system reaches minus 15 ℃ plus or minus 5 ℃, reacting for 4h plus or minus 1h at minus 15 ℃ plus or minus 5 ℃, and finishing the reaction, wherein in the reaction, the weight ratio of the o-cresol to the 2-chloropropane is 1.25: 1, the weight ratio of the anhydrous aluminum trichloride to the o-cresol is 1.9 plus or minus 0.1: 1, and the volume to weight ratio of the dichloromethane to the o-cresol is 4.9 plus or minus 0.6: 1;

(2) slowly adding crushed ice into a reaction product at room temperature, stirring until the ice is completely melted, keeping stand, separating an oil layer, washing an aqueous layer for 2-3 times by using a fresh reaction solvent with the crushed ice amount of 1/4-1/5, combining the separated oil layers, concentrating under reduced pressure at 35 ℃ under the vacuum degree of 200Pa until no solvent is evaporated out to obtain a carvacrol crude product, and measuring the carvacrol content by using HPLC (high performance liquid chromatography) to be more than or equal to 70%;

(3) vacuum distilling, and collecting distillate at 95 + -1 deg.C under vacuum degree of 40Pa and under vacuum degree of 4mm to obtain light yellow carvacrol refined product.

2. The preparation method of carvacrol as a feed antibacterial agent according to claim 1, wherein n-hexane is used as a solvent for the reaction system instead of dichloromethane.

3. The method for preparing carvacrol as a feed antibacterial agent according to claim 1, wherein anhydrous ferric trichloride is used as a catalyst instead of anhydrous aluminum trichloride.