阅读说明：本技术 一种二氯乙腈的合成方法 (Synthesis method of dichloroacetonitrile ) 是由 李琦斌 梁永江 何泽骁 刘清雷 程贺 于 2020-12-01 设计创作，主要内容包括：本发明公开了一种二氯乙腈的合成方法,以二氯乙酰胺为反应原料,加入定量的二氯甲烷,加入定量的二氯亚砜,在一定温度下,即可反应制得二氯乙腈。本发明利用二氯亚砜作为脱水剂,与传统的五氧化二磷脱水工艺相比,无难处理的含磷废水产生,避免了三废的产生；且收率较高,无溴元素引入,具有很好的工业化前景。(The invention discloses a synthesis method of dichloroacetonitrile, which takes dichloroacetamide as a reaction raw material, adds quantitative dichloromethane and quantitative thionyl chloride, and can react at a certain temperature to prepare the dichloroacetonitrile. Compared with the traditional phosphorus pentoxide dehydration process, the method has the advantages that thionyl chloride is used as a dehydrating agent, no refractory phosphorus-containing wastewater is generated, and the generation of three wastes is avoided; and the yield is high, no bromine is introduced, and the method has good industrialization prospect.)

1. The synthesis method of dichloroacetonitrile is characterized by comprising the following steps:

a. taking dichloroacetamide, adding dichloromethane with the mass of 4-6 times of that of dichloroacetamide, fully dissolving, and then cooling;

b. slowly dropwise adding thionyl chloride while stirring at the reaction temperature of 0-40 ℃, wherein the molar ratio of the thionyl chloride to the dichloroacetamide is 1.0-1.15: 1, and after dropwise adding, keeping the temperature and stirring for 1-2 hours;

c. and after the stirring reaction is finished, adding water with the mass of 0.01-0.03 time that of dichloroacetamide, then adding alkali liquor for defoaming, distilling the reaction liquid after defoaming, and collecting fractions at the temperature of 110-120 ℃ to obtain a finished dichloroacetonitrile product.

2. The method for synthesizing dichloroacetonitrile according to claim 1, wherein: the mass ratio of the dichloroacetamide to the dichloromethane in the step a is 1: 5.

3. The method for synthesizing dichloroacetonitrile according to claim 1, wherein: in the step b, the reaction temperature is 0-10 ℃, the molar ratio of thionyl chloride to dichloroacetamide is 1.05-1.15: 1, and the stirring time is 1.5-2 hours.

4. The method for synthesizing dichloroacetonitrile of claim 3, wherein: in the step b, the reaction temperature is 5 ℃, the molar ratio of thionyl chloride to dichloroacetamide is 1.05:1, and the stirring time is 2 hours.

5. The method for synthesizing dichloroacetonitrile according to claim 1, wherein: the stirring speed in the step b is changed along with the change of the dropping speed.

6. The method for synthesizing dichloroacetonitrile according to claim 1, wherein: the mass ratio of the water added in the step c to the dichloroacetamide is 0.13: 1.

7. The method for synthesizing dichloroacetonitrile according to claim 1, wherein: and c, using an alkali liquor in the step c as a sodium hydroxide solution, wherein the sodium hydroxide solution is a 20% sodium hydroxide solution.

Technical Field

The invention belongs to the technical field of organic chemical industry, also belongs to the technical field of synthesis of veterinary drugs and pharmaceutical raw materials, and particularly relates to a synthetic method of dichloroacetonitrile.

Background

The dichloroacetonitrile is a raw material required by the production of a national second-class novel veterinary drug florfenicol, and has good market prospect. Florfenicol is a new broad-spectrum antibacterial drug successfully developed in the late eighties. Florfenicol is mainly used for preventing animal diseases, is used for treating systemic infection of livestock, poultry and aquatic animals, has obvious treatment effect on respiratory system infection and intestinal infection, and is especially suitable for food animals. The florfenicol is used as a feed additive for pigs to prevent and treat bacterial diseases of the pigs, respiratory diseases are treated by the same dosage, the cure rate of the florfenicol is obviously higher than that of spiramycin, the florfenicol replaces chloramphenicol, and the florfenicol has wide application in veterinary medicine clinic. The molecular structural formula is as follows:

at present, the dichloroacetonitrile preparation at home and abroad mainly comprises the following two synthetic methods:

the catalyst is prepared by taking dichloroacetic acid (production waste of the chloroacetic acid, chlorination product of the chloroacetic acid) as an initial raw material, performing methyl esterification after reaction with methanol, performing amidation after reaction with ammonia water, and dehydrating under the action of a phosphorus-containing catalyst (phosphorus pentoxide). The industrial production mode is simple, the raw materials are cheap, but the phosphorus-containing wastewater is difficult to solve, and the environmental protection pressure is extremely high.

Second, dibutyloacetonitrile { organic syntheses, col. Vol.4, p.254 (1963); vol.38, p1.6(1958) } documents mention that dibromoacetonitrile is obtained by reacting N-bromosuccinimide (and other similar substances) with cyanoacetic acid, and dichloroacetonitrile can be obtained by the same principle as N-chlorosuccinimide. The yield of the route is 75-87%, the yield is low, bromide and bromine-containing wastewater can be generated, the problem of post-treatment is troublesome, the requirement on environmental protection is high, and the pressure is high.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: the synthesis method of dichloroacetonitrile overcomes the defects in the prior art, and effectively avoids the generation of impurities and improves the yield by using a process of generating dichloroacetonitrile by reacting dichloroacetamide and thionyl chloride and using dichloromethane as a solvent.

The invention takes dichloroacetamide as a reaction raw material, adds a certain amount of dichloromethane and a certain amount of thionyl chloride, and can react at a certain temperature to prepare dichloroacetonitrile. The reaction formula is as follows:

in order to solve the technical problems, the technical scheme of the invention is as follows:

a synthetic method of dichloroacetonitrile comprises the following steps:

a. taking dichloroacetamide, adding dichloromethane with the mass of 4-6 times of that of dichloroacetamide, fully dissolving, and then cooling;

b. slowly dropwise adding thionyl chloride while stirring at the reaction temperature of 0-40 ℃, wherein the molar ratio of the thionyl chloride to the dichloroacetamide is 1.0-1.15: 1, and after dropwise adding, keeping the temperature and stirring for 1-2 hours;

c. and after the stirring reaction is finished, adding water (bubbles can be generated after water is added) with the mass of 0.01-0.03 time of that of dichloroacetamide, then adding alkali liquor for defoaming, distilling the reaction solution after defoaming, and collecting fractions at the temperature of 110-120 ℃ to obtain a finished dichloroacetonitrile product.

Preferably, the mass ratio of the dichloroacetamide to the dichloromethane in the step a is 1: 5.

Preferably, in the step b, the reaction temperature is 0-10 ℃, the molar ratio of thionyl chloride to dichloroacetamide is 1.05-1.15: 1, and the stirring time is 1.5-2 hours.

Furthermore, in the step b, the reaction temperature is 5 ℃, the molar ratio of thionyl chloride to dichloroacetamide is 1.05:1, and the heat preservation and stirring time is 2 hours.

Preferably, the stirring speed in the step b is changed along with the change of the dropping speed; the stirring speed is usually controlled to be 300 to 500rpm, and the dropping speed is controlled to be 70 to 80 ml/m.

Preferably, the mass ratio of the water added in the step c to the dichloroacetamide is 0.013:1, and the added water is pure water.

Preferably, the alkali solution in step c is a sodium hydroxide solution, and the sodium hydroxide solution is a 20% sodium hydroxide solution.

Due to the adoption of the technical scheme, the invention has the beneficial effects that:

the synthesis method of the invention comprises the following steps: compared with the traditional phosphorus pentoxide dehydration process, the method has the advantages that thionyl chloride is used as a dehydrating agent, no phosphorus-containing wastewater which is difficult to treat is generated, and sulfur dioxide and hydrogen chloride can be recovered by tail gas absorption and sold as byproducts, so that the generation of three wastes is avoided, the pollution problem of the traditional process is improved, and the limiting factors of the traditional process are solved.

Compared with the prior art, the method has the advantages of higher yield, total reaction yield of 92.17%, remarkably improved yield compared with 75-87% in the prior art, no introduction of bromine element, and good industrialization prospect.

Detailed Description

The invention is further illustrated by the following examples.

Example 1

150.12g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.2g of dichloromethane is added, the temperature is reduced to 5 ℃, 146.21g (1.23mol) of thionyl chloride is slowly dripped under stirring, after the dripping is finished, the mixture is stirred for 1.5 hours under heat preservation. And after the stirring reaction is finished, adding 2.03g of water, generating bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 119.08g, the purity of the dichloroacetonitrile is 99.78%, and the yield is 92.17%.

Example 2

150.04g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.11g of dichloromethane is added, the temperature is reduced to 15 ℃, 146.12g (1.23mol) of thionyl chloride is slowly dripped under stirring, after dripping is finished, the mixture is stirred for 1.5 hours under heat preservation. And after the stirring reaction is finished, adding 2.11g of water, generating bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 115.8g, the purity of the dichloroacetonitrile is 99.73%, and the yield is 89.59%.

Example 3

150.08g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.13g of dichloromethane is added, 146.23g (1.23mol) of thionyl chloride is slowly dripped into the flask under the stirring at the temperature of 25 ℃, after the dripping is finished, the mixture is kept warm and stirred for 1.5 h. Adding 2.15g of water, generating bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, and collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 110.2g, the purity of the dichloroacetonitrile is 99.7%, and the yield is 85.23%.

Example 4

150.08g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.02g of dichloromethane is added, refluxing is carried out at 35 ℃, 146.18g (1.23mol) of thionyl chloride is slowly added dropwise under stirring, the dropwise addition is finished, and then stirring is carried out for 1.5 hours under heat preservation. Adding 2.13g of water to generate bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, and collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 107.3g, the purity of the dichloroacetonitrile is 99.66%, and the yield is 82.96%.

Example 5

150.02g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 749.92g of dichloromethane is added, the temperature is reduced to 5 ℃, 139.2g (1.17mol) of thionyl chloride is slowly added dropwise under stirring, the dropwise addition is finished, and then the mixture is stirred for 1.5 hours under heat preservation. And after the stirring reaction is finished, adding 2.03g of water to generate bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 118.12g, the purity of the dichloroacetonitrile is 99.63%, and the yield is 91.44%.

Example 6

149.92g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.02g of dichloromethane is added, the temperature is reduced to 5 ℃, 153.2g (1.29mol) of thionyl chloride is slowly added dropwise under stirring, the dropwise addition is finished, and then the mixture is stirred for 1.5 hours under heat preservation. And after the stirring reaction is finished, 3.1g of water is added, bubbles are generated, the bubbles are absorbed by 20% sodium hydroxide solution, when no bubbles are generated in the reaction liquid, the reaction liquid is distilled to recover dichloroacetonitrile, components at 110-120 ℃ are collected, the weight of the dichloroacetonitrile is 118.03g, the purity of the dichloroacetonitrile is 99.69%, and the yield is 91.43%.

Example 7

150.03g (1.17mol) of dichloroacetamide is taken and added into a 1000ml four-neck flask, 750.1g of dichloromethane is added, the temperature is reduced to 5 ℃, 160.2g (1.35mol) of thionyl chloride is slowly added dropwise under stirring, the dropwise addition is finished, and then the mixture is stirred for 1.5 hours under heat preservation. And after the stirring reaction is finished, adding 4.1g of water, generating bubbles, absorbing the bubbles by using 20% sodium hydroxide solution, distilling the reaction solution to recover dichloroacetonitrile when no bubbles are generated in the reaction solution, collecting components at 110-120 ℃, wherein the weight of the dichloroacetonitrile is 117.86g, the purity of the dichloroacetonitrile is 99.71%, and the yield is 91.31%.

To summarize:

from example 1/2/3/4, it is known that: under the condition that other conditions are not changed, the yield of the chloroacetonitrile is gradually reduced along with the increase of the reaction temperature, so that the reaction temperature of 5 ℃ is more optimal;

from example 1/5/6/7, it is known that: under the condition of keeping other conditions unchanged, the thionyl chloride ratio is 1.05:1, and the yield of dichloroacetonitrile is higher, so that the thionyl chloride ratio is controlled to be 1.05: 1.

It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.