A method for preparing dichloroacetonitrile

Abstract

Dichloroacetonitrile is an important raw material required for the production of florfenicol, a new Class II veterinary drug in China, and has a promising market prospect. The present invention discloses a method for preparing dichloroacetonitrile, comprising the following steps: using dichloroacetaldehyde as a raw material, in the presence of different nitrogen sources and a copper catalyst, and using air as an oxidant to generate dichloroacetonitrile. The reaction liquid is filtered, extracted, and distilled to obtain a colorless liquid with a purity greater than 99%. Compared with the traditional method of preparing dichloroacetonitrile using phosphorus pentoxide, the present invention has a simple reaction, mild conditions, simple post-processing, and is more environmentally friendly, providing a new approach to the production of dichloroacetonitrile.

Description

Technical Field

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

[0002] Dichloroacetonitrile is a colorless liquid with strong irritant and tear-inducing properties. It is soluble in hydrocarbons and ethanol but insoluble in water. It is toxic upon inhalation, oral administration, or contact with the skin. Dichloroacetonitrile is a raw material required for the production of florfenicol, a new Class II veterinary drug in China, and has a promising market outlook. Florfenicol was successfully developed in the late 1980s as a new broad-spectrum antibacterial drug. It is primarily used in animal disease prevention and treatment of systemic infections in livestock, poultry, and aquatic animals, with significant efficacy in treating respiratory and intestinal infections, particularly in food-producing animals. It is also used as a feed additive in pigs to prevent and control bacterial diseases. At the same dose, florfenicol has a significantly higher cure rate than spiramycin for respiratory diseases. Florfenicol is poised to replace chloramphenicol and has broad clinical applications in veterinary medicine.

[0003] Existing preparation methods include:

[0004] 1) Phosphorus pentoxide dehydration method: This method is currently the most widely used production method. It reacts methyl dichloroacetate (or ethyl dichloroacetate) with aqueous ammonia to produce dichloroacetamide. The dried dichloroacetamide is then heated with phosphorus pentoxide as a dehydrating agent to distill off dichloroacetonitrile. Finally, distillation under reduced pressure is performed to completely remove the dichloroacetonitrile. The resulting crude product is then rectified to produce a high-purity finished product. This production method is relatively complex, and phosphorus-containing wastewater is difficult to dispose of. It is environmentally unfriendly and expensive.

[0005] 2) N-Chlorosuccinimide Method: The literature {Organic Syntheses, Col. 1. Vol. 4, p. 254 (1963); Vol. 1. 38, p. 1. 6 (1958)} reports a method for obtaining dibromoacetonitrile by reacting N-bromosuccinimide with cyanoacetic acid, and a method for obtaining dichloroacetonitrile by reacting N-chlorosuccinimide with cyanoacetic acid. This route has a yield of 75% to 87%, but the byproduct is succinimide, which is difficult to recover and has complex post-processing issues. It also has high environmental protection requirements and high pressure.

[0006] 3) Photoirradiation method: Patent CN 114105819 A discloses a method for synthesizing various substituted chloroacetonitriles via photochlorination. Acetonitrile and chlorine are used as raw materials, and an azo compound is used as a catalyst. Under 300-400 nm ultraviolet light, a mixture of chloroacetonitrile and polychloroacetonitriles is reacted. Distillation and purification yield a very small amount of dichloroacetonitrile. The reaction time is 10-16 hours. This method uses readily available raw materials and eliminates phosphorus-containing wastewater. However, there are efficiency issues. Industrialized photoirradiation requires high equipment requirements, and the resulting polychloroacetonitrile is difficult to separate.

[0007] 4) Thionyl Chloride Method: Patent CN 112521308 A reports a method for preparing dichloroacetonitrile using dichloroacetamide as a raw material and thionyl chloride as a dehydrating agent. This method, in our tests, did not react. Only conventional phosphorus pentoxide is feasible.

[0008] 5) Hydroxylamine hydrochloride method: In our patent application (application number 202310335999.4), methyl chloroacetate (ethyl chloroacetate) and hydroxylamine undergo an esterification reaction in methanol to produce 2,2-dichloro-N-hydroxyacetamide; a dehydrating agent such as thionyl chloride is then used to produce dichloroacetonitrile. This method utilizes milder dehydration conditions than previous methods, but the steps are still relatively lengthy.

[0009] In view of the above-mentioned defects of the prior art, it is of great significance to develop a simpler synthesis method for dichloroacetonitrile with simple equipment requirements, less three wastes and low cost. Summary of the Invention

[0010] 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 dichloroacetonitrile practically and efficiently.

[0011]

[0012] To achieve the above object, the technical solution adopted by the present invention is:

[0013] A method for preparing dichloroacetonitrile comprises the following steps: uniformly mixing dichloroacetaldehyde, a nitrogen source and a copper catalyst in a solvent, reacting in an air atmosphere to generate dichloroacetonitrile, and filtering, extracting and rectifying the reaction solution to obtain a pure product.

[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 dimethyl sulfoxide, and the preferred solvent is dichloroethane.

[0015] As a preferred technical solution, the nitrogen source is a group consisting of ammonium acetate, ammonium carbonate, ammonium nitrate, ammonium sulfate, ammonium formate and ammonia water, and ammonium acetate is preferably used as the nitrogen source.

[0016] As a preferred technical solution, the copper catalyst is a group consisting of copper sulfate, copper acetate (anhydrous), copper acetate monohydrate, copper chloride, copper nitrate, ammonium sulfate, copper oxide and cuprous chloride, with copper acetate being preferred as the catalyst.

[0017] As a preferred technical solution, in the above step, the molar ratio of dichloroacetaldehyde, nitrogen source, and copper catalyst is 1:1-2:0.01-0.2, preferably 1:1.5:0.1. The reaction temperature is 0-80°C, preferably 60°C.

[0018] The advantages of the present invention are:

[0019] Compared with the traditional method of preparing dichloroacetonitrile by using phosphorus pentoxide, the present invention has simple reaction, mild conditions, simple post-treatment, is more green and environmentally friendly, and provides a new idea for the production of dichloroacetonitrile. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Attachment Figure 1 The diagram is a schematic diagram of the main chemical formula of a method for preparing dichloroacetonitrile according to the present invention. DETAILED DESCRIPTION

[0021] Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used in limiting the scope of the present invention.In addition, should be understood that after reading the content of the present invention record, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall equally within the scope limited by the application's appended claims.

[0022] Example 1:

[0023] Please see the attached Figure 1 , attached Figure 1 The diagram is a schematic diagram of the main chemical formula of a method for preparing dichloroacetonitrile according to the present invention.

[0024] At room temperature, dichloroacetaldehyde (50g, 0.44mol), ammonium acetate (51.2g, 0.66mol), dichloroethane (250ml) and copper acetate (8.0g, 0.044mmol) were added to a 500ml three-necked flask. The reaction system was connected to the air, the internal temperature of the reaction was controlled at 60°C, and refluxed for 8 hours. The GC monitoring showed that the dichloroacetaldehyde raw material was less than 1%. Cooled to room temperature, the solid was filtered to remove, and the organic phase was washed twice with water. The organic phase was switched to a distillation device, and dichloroethane was recovered at normal pressure and distilled to obtain 41.9g of colorless dichloroacetonitrile with a yield of 86%. The GC purity was 99.4%. 1 H NMR (CDCl3): 6.13 (s, 1H).

[0025] Example 2:

[0026] At room temperature, dichloroacetaldehyde (50 g, 0.44 mol), ammonium carbonate (63.8 g, 0.66 mol), dichloroethane (250 ml), and cupric acetate (8.0 g, 0.044 mmol) were added to a 500 ml three-necked flask. The reaction system was ventilated, the internal temperature was controlled at 60°C, and refluxed for 6 hours. GC monitoring showed that the dichloroacetaldehyde starting material was less than 1%. The mixture was cooled to room temperature, filtered to remove solids, and the organic phase was washed twice with water. The organic phase was switched to a distillation apparatus, and dichloroethane was recovered at atmospheric pressure and distilled to obtain 33.4 g of colorless dichloroacetonitrile (68.6% yield). The GC purity was 99.1%.

[0027] Example 3:

[0028] At room temperature, dichloroacetaldehyde (50 g, 0.44 mol), ammonium carbonate (63.8 g, 0.66 mol), dichloroethane (250 ml), and copper sulfate (7.1 g, 0.044 mmol) were added to a 500 ml three-necked flask. The reaction system was ventilated, the internal temperature was controlled at 60°C, and refluxed for 6 hours. GC monitoring showed that the dichloroacetaldehyde starting material was less than 1%. The mixture was cooled to room temperature, filtered to remove solids, and the organic phase was washed twice with water. The organic phase was switched to a distillation apparatus, and the dichloroethane was recovered at atmospheric pressure and distilled to obtain 26.8 g of colorless dichloroacetonitrile (55.1% yield). The GC purity was 99.6%.

[0029] The preferred embodiments of the present invention have been described in detail above. It should be understood that numerous modifications and variations based on the concepts of the present invention are possible without inventive effort by those skilled in the art. Therefore, any technical solution that can be derived by one skilled in the art through logical analysis, reasoning, or limited experimentation based on the concepts of the present invention and the prior art should be within the scope of protection defined by the claims.

Claims

1. A method for preparing dichloroacetonitrile, characterized in that, The method comprises the following steps: Reaction steps: dichloroacetaldehyde, a nitrogen source and a copper catalyst are uniformly mixed in a solvent, reacted in an air atmosphere to generate dichloroacetonitrile, and the reaction solution is filtered, extracted and distilled to obtain a pure product; The solvent is ethylene dichloride; The nitrogen source is ammonium acetate or ammonium carbonate; The copper catalyst is copper sulfate or copper acetate.

2. The method according to claim 1, characterized in that In the reaction step, the molar ratio of the dichloroacetaldehyde, the nitrogen source, and the copper catalyst is 1:1-2:0.01-0.2; and the reaction temperature is 0-80°C.

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