A method for preparing dichloroacetonitrile

Abstract

The invention discloses a method for preparing dichloroacetonitrile, comprising the following steps: esterifying methyl chloroacetate with hydroxylamine under methanol conditions to obtain 2,2-dichloro-N-hydroxyacetamide; using a dehydrating agent such as thionyl chloride to produce dichloroacetonitrile, and the product is distilled to obtain a colorless liquid with a purity greater than 99%. Compared with the traditional method for preparing dichloroacetonitrile using phosphorus pentoxide, the present invention has simple reaction, mild conditions, simple post-processing, and is more environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a new method for preparing dichloroacetonitrile. Background Art

[0002] Dichloroacetonitrile is a colorless liquid with strong irritation and tear-inducing effects. It is soluble in hydrocarbons and ethanol, insoluble in water, and toxic by inhalation, oral administration, or contact with the skin. Dichloroacetonitrile is the raw material required for the production of the national second-class new veterinary drug florfenicol, and has a good market prospect. Florfenicol is a new broad-spectrum antibacterial drug successfully developed in the late 1980s. Florfenicol is mainly used in animal disease prevention and treatment of systemic infections in livestock, poultry and aquatic animals. It has significant therapeutic effects on respiratory and intestinal infections, especially in food animals. It is used as a feed additive for pigs to prevent and control bacterial diseases in pigs. With the same dose for the treatment of respiratory diseases, the cure rate of florfenicol is significantly higher than that of spiramycin. Florfenicol will replace chloramphenicol and has a wide range of clinical applications in veterinary medicine.

[0003] Existing preparation methods include:

[0004] 1) Phosphorus pentoxide dehydration method: This method is currently a large-scale production method, which uses methyl dichloroacetate (or ethyl ester) to react with ammonia water to generate dichloroacetamide. The dried dichloroacetamide uses phosphorus pentoxide as a dehydrating agent, and dichloroacetonitrile is distilled out while heating. Finally, the dichloroacetonitrile is completely distilled out by reduced pressure distillation. The resulting crude product is distilled to obtain a high-purity finished product. This production method is relatively complicated, and phosphorus-containing wastewater is difficult to deal with. It is very unfriendly to the environment and has high costs;

[0005] 2) N-chlorosuccinimide method: In the literature {Organic Syntheses, Col 1.Vo 1.4, p.254 (1963); Vo 1.38, p1.6 (1958)}, it is reported that dibromoacetonitrile is obtained by reacting N-bromosuccinimide with cyanoacetic acid and dichloroacetonitrile is obtained by reacting N-chlorosuccinimide with cyanoacetic acid. The yield of this route is 75% to 87%. The by-product is succinimide, which is difficult to recover and has troublesome post-processing problems. It has high environmental protection requirements and high pressure.

[0006] 3) Photoirradiation method: Patent CN114105819A discloses a method for synthesizing various substituted chloroacetonitriles by photochlorination reaction, using acetonitrile and chlorine as raw materials, azo compounds as catalysts, and reacting under 300-400nm ultraviolet light to obtain a mixture of chloroacetonitrile and polychloroacetonitrile, and then distilling and separating and purifying to obtain a very small amount of dichloroacetonitrile, and the reaction time is 10-16h. The raw materials of this method are easy to obtain and there is no phosphorus-containing wastewater. However, there are efficiency problems, and the equipment requirements for light irradiation in industrialization are high, and the generated polychloroacetonitrile is difficult to separate.

[0007] 4) Sulfonyl chloride method: Patent CN112521308A reports a method for preparing dichloroacetonitrile using dichloroacetamide as raw material and thionyl chloride as dehydrating agent. This method did not react after our test. Only traditional phosphorus pentoxide is feasible.

[0008] In view of the above-mentioned defects of the prior art, it is of great significance to develop a method for synthesizing dichloroacetonitrile with easy-to-obtain raw materials, simple equipment requirements, less waste and low cost. N-hydroxyacetamide is milder than amide, and its preparation method is simple, and cyano can be prepared under mild dehydrating agent conditions. Summary of the invention

[0009] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is how to prepare chloroacetonitrile practically and efficiently.

[0010] To achieve the above object, the technical solution adopted by the present invention is:

[0011] A method for preparing dichloroacetonitrile comprises the following steps: step 1: methyl dichloroacetate and hydroxylamine hydrochloride are reacted under the action of a base to generate 2,2-dichloro-N-hydroxyacetamide; step 2: 2,2-dichloro-N-hydroxyacetamide is reacted under the action of a dehydrating agent to generate dichloroacetonitrile, and the dichloroacetonitrile is neutralized, filtered and distilled.

[0012] Step 1

[0013] Step 2

[0014] As a preferred technical solution, the solvent used in the chemical reaction is a group consisting of methanol, ethanol, water, dichloromethane, dichloroethane, toluene, ethyl acetate, tetrahydrofuran, DMF and 1,4-dioxane.

[0015] As a preferred technical solution, the base is a group consisting of sodium acetate, sodium bicarbonate, sodium carbonate, potassium carbonate, triethylamine, DBU and DIPEA.

[0016] As a preferred technical solution, in step 1, the molar ratio of methyl dichloroacetate, hydroxylamine hydrochloride and base is 1:1-1.5:1-1.5; and the reaction temperature is 0-50°C.

[0017] As a preferred technical solution, the dehydrating agent is a group consisting of thionyl chloride, phosphorus pentoxide, phosphorus oxychloride, phosphorus tribromide, titanium tetrachloride, and methylsulfonyl chloride.

[0018] As a preferred technical solution, in step 2, the molar ratio of the 2,2-dichloro-N-hydroxyacetamide to the dehydrating agent is 1:1-2; and the reaction temperature is 50-80°C.

[0019] The present invention has the advantages that:

[0020] Compared with the traditional method of preparing dichloroacetonitrile by using phosphorus pentoxide, the present invention has simple reaction, mild conditions, simple post-treatment, and is more environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Attached Figure 1 It is a schematic diagram of the main chemical formula of a method for preparing dichloroacetonitrile of the present invention. DETAILED DESCRIPTION

[0022] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0023] Embodiment 1:

[0024] Please see attached Figure 1 , attached Figure 1 This is a schematic diagram of the main chemical formula of a method for preparing dichloroacetonitrile of the present invention. At room temperature, methyl dichloroacetate (100g, 0.699mol), water (200ml) and sodium acetate (68.9g, 0.839mol) were added to a 500ml three-necked flask, the internal temperature was controlled to be less than 5°C, and hydroxylamine hydrochloride (53.47g, 0.769mol) was slowly added in batches. The temperature was slowly raised to room temperature and stirred for 4 hours, and the GC monitored the disappearance of the methyl dichloroacetate raw material. The temperature was lowered again by about 5°C, and the filtered white solid was vacuum dried to obtain 91.6g of the intermediate 2,2-dichloro-N-hydroxyacetamide with a yield of 91%. 1 HNMR(d6-DMSO):7.10(brs,2H,),6.21(s,1H).

[0025] Add the above-obtained 2,2-dichloro-N-hydroxyacetamide (91.6 g, 0.636 mol) and dichloroethane (250 ml) to a 500 ml three-necked flask, heat to 80 ° C, slowly drop thionyl chloride (83.3 g, 0.70 mol), control the temperature in the range of 75-83 ° C, and stir for 4 hours after the addition. After the GC detection reaction is completed, about 100 ml of the front fraction is distilled out at normal pressure, and after cooling to room temperature, the pH is adjusted to neutral with soda ash, filtered, and the filtrate is distilled at normal pressure to obtain 61.6 g of anhydrous liquid with a yield of 88%. The GC purity is 99.5%, 1 HNMR (CDCl3): 6.13 (s, 1H).

[0026] Embodiment 2:

[0027] At room temperature, add methyl dichloroacetate (100g, 0.699mol), water (200ml) and sodium bicarbonate (70.5g, 1.11mol) to a 500ml three-necked flask, control the internal temperature to less than 5°C, and slowly add hydroxylamine hydrochloride (53.5g, 0.77mol) in batches. Slowly heat to room temperature and stir for 4 hours. GC monitors the disappearance of methyl chloroacetate raw material. Cool down again by about 5°C, and vacuum dry the filtered white solid to obtain 86.6g of intermediate 2,2-dichloro-N-hydroxyacetamide with a yield of 86%. 1 HNMR(d6-DMSO):7.10(brs,2H,),6.21(s,1H).

[0028] To a 500ml three-necked flask (with mechanical stirring), add the above-obtained 2,2-dichloro-N-hydroxyacetamide (86.6g, 0.60mol), add phosphorus pentoxide (93.9g, 0.66mol), slowly raise the temperature to about 100°C, and liquid reflux begins, and refluxes for about half an hour. Change the reflux to atmospheric distillation and start collecting the liquid. At the same time, set the oil bath temperature to 150 degrees, and the gas phase temperature of the system does not exceed 120°C. The whole process lasts about 3 hours. After the flow rate begins to decrease, use a water pump to pump at negative pressure until there are no droplets. The crude product is adjusted to a neutral pH with soda ash, filtered, and the filtrate is distilled at atmospheric pressure to obtain 55.6g of anhydrous liquid with a yield of 84%. The GC purity is 99.5%, 1 HNMR (CDCl3): 6.13 (s, 1H). 200 g of water was slowly added to the remaining reaction system and stirred into a uniform liquid, which was the by-product phosphoric acid.

[0029] The preferred specific embodiments of the present invention are described in detail above. It should be understood that ordinary technicians in the field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. A method for preparing dichloroacetonitrile, characterized in that: The method comprises the following steps: Step 1: reacting methyl dichloroacetate with hydroxylamine hydrochloride in the presence of a base to generate 2,2-dichloro-N-hydroxyacetamide; The solvents used in the chemical reaction are from the group consisting of methanol, ethanol, water, dichloromethane, dichloroethane, toluene, ethyl acetate, tetrahydrofuran, DMF and 1,4-dioxane; Step 2: 2,2-dichloro-N-hydroxyacetamide is reacted with a dehydrating agent to generate dichloroacetonitrile, which is then neutralized, filtered and distilled; The solvents used in the chemical reaction are from the group consisting of methanol, ethanol, dichloromethane, dichloroethane, toluene, ethyl acetate, tetrahydrofuran, DMF and 1,4-dioxane; In the step 1, the molar ratio of methyl dichloroacetate, hydroxylamine hydrochloride and base is 1:1-1.5:1-1.5; the reaction temperature is 0-50°C; In the step 2, the molar ratio of the 2,2-dichloro-N-hydroxyacetamide to the dehydrating agent is 1:1-2; the reaction temperature is 50-80°C; The dehydrating agent is thionyl chloride or phosphorus pentoxide.

2. The method according to claim 1, characterized in that In step 1, the base is a group consisting of sodium acetate, sodium bicarbonate, sodium carbonate, potassium carbonate, triethylamine, DBU and DIPEA.

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