A method for synthesizing 4-chlorobutyryl chloride

Abstract

The application relates to the fine chemical field and discloses a synthesis method of 4-chlorobutyryl chloride, which comprises the following steps: taking gamma-butyrolactone as raw material, and reacting with formula I under the catalysis of a catalyst to prepare 4-chlorobutyryl chloride and formula II; the synthesis method of the 4-chlorobutyryl chloride is free of waste gas pollution, has low safety risk, is mild and controllable in reaction, has low production cost, and has high yield, and the problems that the existing production process of the 4-chlorobutyryl chloride on the market is large in three wastes pollution, large in raw material toxicity or difficult to control in reaction, and is not conducive to industrialized green production are solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of fine chemical industry, more particularly, it relates to a synthesis method of 4-chlorobutyryl chloride. BACKGROUND

[0002] 4-chlorobutyryl chloride is an important organic synthesis and pharmaceutical, pesticide intermediate.

[0003] In the pharmaceutical industry, 4-chlorobutyryl chloride is used to produce antipsychotic drugs trifluperidol, trichlormethylpiperidylbenzene, levetiracetam, quinolone antibacterial drugs such as ciprofloxacin, ciprofloxacin, sparfloxacin, etc. In the pesticide industry, it can be used to prepare insecticides such as pyrethrin, isoxazolone, and other plant protection agents, and is also an important intermediate of herbicide glufosinate.

[0004] Currently, there are three methods for preparing 4-chlorobutyryl chloride in the industry: thionyl chloride system, phosgene system, and triphosgene system.

[0005] 1) Thionyl chloride system: using γ-butyrolactone as raw material and thionyl chloride as ring-opening reagent, ring-opening chlorination is carried out under the catalysis of zinc chloride. The reaction process is as follows (Cat is the abbreviation of catalyst):

[0006]

[0007] This process has simple process operation and easy-to-obtain raw materials, and is a suitable synthesis route for industrial production; the disadvantage is that it produces acidic mixed waste gas such as sulfur dioxide and hydrogen chloride, which has high treatment cost and does not meet the current green and environmentally friendly process requirements.

[0008] 2) Phosgene system: phosgene is used instead of thionyl chloride as a ring-opening reagent, and γ-butyrolactone is used as a raw material for chlorination. The reaction process is as follows:

[0009]

[0010] This process does not produce sulfur dioxide, and phosgene is cheaper than thionyl chloride, but phosgene itself is a highly toxic chemical with high toxicity, and is not convenient to transport and store.

[0011] 3) Triphosgene system: the application file with patent number CN101624340A / CN108863767A uses triphosgene as a chlorination reagent and a catalyst to catalyze the chlorination of γ-butyrolactone. The reaction process is as follows:

[0012]

[0013] Triphosgene is stable at room temperature and has low toxicity, but when reacting, the temperature is high, triphosgene decomposes quickly and is difficult to control, the reaction is easy to lose control, and the catalyst is difficult to recover, which is not conducive to industrial production.

[0014] As the market demand for 4-chlorobutyryl chloride is increasing, there is an urgent need for a synthesis method with high yield, which can meet the needs of industrial production, and low cost, and meet the requirements of green and environmentally friendly process. SUMMARY

[0015] The present application provides a 4-chlorobutyryl chloride synthesis method without waste gas pollution, low safety risk, mild and controllable reaction, low production cost and high yield, which solves the problem of existing production process of 4-chlorobutyryl chloride on the market, large three wastes pollution, large raw material toxicity or difficult to control reaction, which is not conducive to industrialized green production.

[0016] A synthesis method of 4-chlorobutyryl chloride, comprising: using γ-butyrolactone as a raw material, and reacting with the following formula I under the catalysis of a catalyst to obtain 4-chlorobutyryl chloride and formula II.

[0017]

[0018] Further, the catalyst is selected from one or more of iron trichloride, zinc chloride, aluminum chloride and chromium chloride.

[0019] Further, the compounds of formula I and formula II are substituted by R1 at positions 2 / 3, wherein R1 is hydrogen, halogen.

[0020] Preferably, the compounds of formula I and formula II are substituted by R2 at positions 4 / 5, wherein R2 is hydrogen, halogen.

[0021] Specifically, at room temperature, γ-butyrolactone is added to the reactor, and then p-chlorobenzotrichloride and anhydrous zinc chloride catalyst are added to the reactor, and the acylation reaction is carried out after stirring and heating.

[0022] After the reaction is completed, the product is separated to obtain 4-chlorobutyryl chloride and p-chlorobenzoyl chloride.

[0023] Preferably, in the reaction, the molar ratio of γ-butyrolactone, p-chlorobenzotrichloride and anhydrous zinc chloride catalyst is 1:1:(0.01-0.03), and the catalyst is preferably 0.02-0.03.

[0024] Preferably, the reaction temperature is 90-160℃, and more preferably, the reaction temperature is 110-140℃; the reaction time is 7-14h.

[0025] Preferably, after the reaction is completed, distillation is carried out to separate 4-chlorobutyryl chloride and p-chlorobenzoyl chloride. The front fraction is 4-chlorobutyryl chloride, and the rear fraction is p-chlorobenzoyl chloride product.

[0026] The reaction of the present application generates two products from two raw materials, i.e. A+B→C+D, without the generation of acidic mixed waste gas such as sulfur dioxide and hydrogen chloride, and the utilization rate of raw materials reaches 100% in theory, which completely meets the green process without pollution.

[0027] The ring-opening reagent compound of formula I of γ-butyrolactone is much safer than thionyl chloride and phosgene, and the reaction is mild, and the reaction speed can be controlled by controlling the temperature and the amount of catalyst, and the production operation is relatively safe.

[0028] Since the utilization rate of raw materials is 100%, the other product besides 4-chlorobutyryl chloride also has great market value, and since no waste gas is generated, no additional waste gas treatment cost is needed, so compared with other processes, the production cost of the process of the present application is low and the benefit is high. DETAILED DESCRIPTION

[0029] The present application will be further illustrated by the following examples, in which the compound of formula I is taken as p-chlorobenzotrichloride. It should be understood that the preparation method of the examples of the present application is only used to illustrate the present application, but is not a limitation of the present application, and simple improvement, equivalent replacement or equivalent transformation of the preparation method of the present application under the concept of the present application form a technical solution within the scope of the present application.

[0030] Example 1

[0031] In a 500 mL four-necked flask, 100 g (1.16 mol) of γ-butyrolactone (content 99.5%), 267.44 g (1.16 mol) of p-chlorobenzotrichloride (content 98.1%), and 5.68 g (0.035 mol) of anhydrous ferric chloride catalyst were added, and stirred to be heated to 120-130°C, and kept for 11 hours. Distillation was performed to obtain 148.02 g of the front fraction as 4-chlorobutyryl chloride product with a purity of 99.1% and a molar yield of 90.28%; and 190.11 g of the rear fraction as p-chlorobenzotrichloride product with a purity of 99.2% and a molar yield of 93.43%.

[0032] Example 2

[0033] In a 500 mL four-necked flask, 100 g (1.16 mol) of γ-butyrolactone (content 99.5%), 267.44 g (1.16 mol) of p-chlorobenzotrichloride (content 98.1%), 3.64 g (0.023 mol) of anhydrous chromium chloride catalyst were added, and the temperature was raised to 110-120°C under stirring, and the reaction was kept for 7 hours. Distillation was performed to obtain 151.98 g of the front fraction as 4-chlorobutyryl chloride product with a purity of 99.4% and a molar yield of 92.70%, and 189.07 g of the rear fraction as p-chlorobenzoyl chloride product with a purity of 99.1% and a molar yield of 92.91%.

[0034] Example 3

[0035] In a 500 mL four-necked flask, 100 g (1.16 mol) of γ-butyrolactone (content 99.5%), 267.44 g (1.16 mol) of p-chlorobenzotrichloride (content 98.1%), 4.77 g (0.035 mol) of anhydrous zinc chloride catalyst were added, and the temperature was raised to 130-140°C under stirring, and the reaction was kept for 11 hours. Distillation was performed to obtain 149.07 g of the front fraction as 4-chlorobutyryl chloride product with a purity of 99.2% and a molar yield of 90.92%, and 188.60 g of the rear fraction as p-chlorobenzoyl chloride product with a purity of 99.2% and a molar yield of 92.69%.

[0036] Example 4

[0037] In a 500 mL four-necked flask, 100 g (1.16 mol) of γ-butyrolactone (content 99.5%), 267.44 g (1.16 mol) of p-chlorobenzotrichloride (content 98.1%), 4.67 g (0.035 mol) of anhydrous aluminum chloride catalyst were added, and the temperature was raised to 120-130°C under stirring, and the reaction was kept for 12 hours. Distillation was performed to obtain 149.19 g of the front fraction as 4-chlorobutyryl chloride product with a purity of 99.3% and a molar yield of 90.99%, and 187.67 g of the rear fraction as p-chlorobenzoyl chloride product with a purity of 99.1% and a molar yield of 92.23%.

[0038] The above embodiment is not limited to the specific embodiments described above, and the specific embodiments described above are merely illustrative, rather than limiting, and a person of ordinary skill in the art can make many forms under the inspiration of the above embodiment without departing from the purpose of the above embodiment and the scope protected by the claims, and all of them belong to the protection of the above embodiment.

Claims

1. A method for synthesizing 4-chlorobutyryl chloride, characterized in that, include: Using γ-butyrolactone as a raw material, 4-chlorobutyryl chloride and formula II were prepared by reacting with formula I under the catalysis of a catalyst; ； The catalyst is selected from one or more of ferric chloride, zinc chloride, aluminum chloride, and chromium chloride; In compounds of formula I and formula II, R1 is substituted at the 2 / 3 position, where R1 is hydrogen or halogen. In compounds of formula I and formula II, R2 is substituted at the 4 / 5 position, where R2 is hydrogen or halogen.

2. The method for synthesizing 4-chlorobutyryl chloride according to claim 1, characterized in that, At room temperature, γ-butyrolactone was added to the reactor, followed by the addition of p-chlorotrichlorotoluene and anhydrous zinc chloride catalyst. The mixture was stirred and heated to carry out the acylation reaction. After the reaction is complete, the products are separated to obtain 4-chlorobutyryl chloride and p-chlorobenzoyl chloride.

3. The method for synthesizing 4-chlorobutyryl chloride according to claim 2, characterized in that, In the reaction, the molar ratio of γ-butyrolactone, p-chlorotrichlorotoluene and anhydrous zinc chloride catalyst is 1:1:(0.01-0.03).

4. The method for synthesizing 4-chlorobutyryl chloride according to claim 2, characterized in that, The reaction temperature is 90-160℃.

5. The method for synthesizing 4-chlorobutyryl chloride according to claim 4, characterized in that, The reaction temperature is 110-140℃; the reaction time is 7-14h.

6. The method for synthesizing 4-chlorobutyryl chloride according to claim 2, characterized in that, After the reaction was completed, 4-chlorobutyryl chloride and p-chlorobenzoyl chloride were separated by distillation.

7. The method for synthesizing 4-chlorobutyryl chloride according to claim 3, characterized in that, The molar ratio of γ-butyrolactone, p-chlorotrichlorotoluene and anhydrous zinc chloride catalyst is 1:1:(0.02-0.03).

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