A kind of synthesis and separation method of 4-chlorobutyryl chloride

Abstract

The invention provides a synthesis and separation method of 4-chlorobutyryl chloride, comprising the steps of: gamma-butyrolactone reacts with thionyl chloride under the catalysis of a catalyst (9% boron trichloride in dichloromethane solution) to obtain 4-chlorobutyryl chloride, after the reaction is completed, activated carbon is added to adsorb a small amount of polymerized impurities, filtered, and then the catalyst and excess thionyl chloride are removed by distillation to obtain a 4-chlorobutyryl chloride finished product. The reaction conditions of the present invention are relatively mild, high in yield, low in energy consumption, and few in waste, and the molar yield is more than 96%, and the purity of the produced 4-chlorobutyryl chloride is more than 99.0%, and the quality of the product is good, which is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic intermediate synthesis and separation, and relates to a synthesis and separation method of 4-chlorobutyryl chloride. Background Art

[0002] 4-Chlorobutyryl chloride is an important intermediate for organic synthesis, medicine and pesticides. In the pharmaceutical industry, 4-chlorobutyryl chloride is used to produce antipsychotic drugs such as trifluoperidol and trifluoperidol benzene, quinolone antibacterial drugs such as ciprofloxacin, ciprofloxacin, sparfloxacin, and anti-epileptic drugs such as levetiracetam. In the pesticide industry, it can be used to prepare insecticides such as pyrethroids and other plant protection agents. It is also an important intermediate for glufosinate ammonium, and can also be used to prepare isoxachlor, isoxathiapiprolin, etc.

[0003] At present, the existing industrial production method of 4-chlorobutyryl chloride is mainly to obtain it by chlorinating γ-butyrolactone with thionyl chloride under the catalysis of zinc chloride, with a yield of about 82%. However, the process has a low yield and high cost.

[0004] In CN104592001A, it is proposed to use γ-butyrolactone and thionyl chloride to react in the presence of a mixed catalyst. The obtained product has a high purity, but the yield is still unsatisfactory.

[0005] In addition, in patents US2778852 and EP0413264, it is also proposed to use phosgene as a raw material to replace thionyl chloride as a chlorination reagent to synthesize 4-chlorobutyryl chloride from γ-butyrolactone, with a yield of 95%. This method has a high yield, but the chlorination reagent phosgene itself is a highly toxic chemical, and it is inconvenient to transport and store, and has high operating requirements.

[0006] CN104086402 A discloses a method of adding γ-butyrolactone, an amine catalyst and a phase transfer catalyst to an organic solvent, then adding solid phosgene, i.e., bis(trichloromethyl) carbonate, under stirring conditions, to carry out a chlorination reaction to obtain 4-chlorobutyryl chloride. The yield of this method is above 90%, but the organic solvents used are mostly toxic substances, and more by-products are produced, so the purity of the product cannot be guaranteed. At the same time, the organic matter is not easy to handle and pollutes the surrounding environment.

[0007] The separation processes involved in the above methods all use the method of distilling 4-chlorobutyryl chloride. Since the boiling point of 4-chlorobutyryl chloride is 174.35°C, the distillation process is a high-energy consumption process. In addition, in addition to the main fraction of 4-chlorobutyryl chloride, front fractions and kettle residues will inevitably be produced. Although most manufacturers will recycle and reuse them, the problem of large amounts of waste cannot be avoided.

[0008] In summary, the current synthesis and separation methods of 4-chlorobutyryl chloride generally have the disadvantages of high reaction temperature, low yield, high energy consumption and much waste. Domestic research on the synthesis and separation technology of 4-chlorobutyryl chloride has not yet achieved satisfactory results. Summary of the invention

[0009] The main technical problem solved by the invention is to provide a method for synthesizing and separating 4-chlorobutyryl chloride, which has relatively mild reaction conditions, high yield, low energy consumption, less waste and is suitable for industrial production.

[0010] In order to solve the above technical problems, a technical solution adopted by the present invention is: providing a synthesis and separation method of 4-chlorobutyryl chloride, comprising the following steps:

[0011] Step (a): γ-butyrolactone reacts with thionyl chloride at 10-12° C. in the presence of a catalyst (9% boron trichloride in dichloromethane solution) to obtain 4-chlorobutyryl chloride. The reaction equation is:

[0012]

[0013] Step (b): After the reaction is completed, activated carbon is added to stir and adsorb impurities, filtered, and then the dichloromethane solution of the catalyst boron trichloride and excess thionyl chloride are removed by distillation to obtain the finished 4-chlorobutyryl chloride.

[0014] The synthesis and separation method of 4-chlorobutyryl chloride comprises the following steps: in step (a), the weight of 9% boron trichloride dichloromethane solution is 4% to 6% of gamma-butyrolactone.

[0015] In step (a), the molar ratio of γ-butyrolactone to thionyl chloride is 1:1.05-1.15.

[0016] In step (a), the time for dropping thionyl chloride is 4 to 6 hours, the time for keeping warm after dropping is 2 to 3 hours, and the temperature for dropping and keeping warm is both 10 to 12°C.

[0017] In step (b), the weight of activated carbon added is 0.5-1.5% of γ-butyrolactone, the stirring time is 10-20 minutes, and the temperature is 10-12°C.

[0018] In step (b), the filtration step uses a precision filter with a filter element of 0.45 μm.

[0019] In step (b), the distillation step is to first perform reduced pressure distillation at 10-12°C (vacuum degree is -0.08 to -0.09 MPa), then gradually increase the temperature from 10-12°C to 45°C, and after no liquid flows out, continue to degas at 45°C (vacuum degree is -0.08 to -0.09 MPa) for 15 minutes.

[0020] Beneficial effects:

[0021] The present invention finds that in the prior art, when preparing 4-chlorobutyryl chloride, most of the Lewis acid catalysts such as anhydrous magnesium chloride and zinc chloride are used, and they all have a common feature, all belong to metal salt catalysts, heterogeneous reaction occurs, and the post-reaction treatment is more troublesome. Based on these shortcomings, the present invention selects to use boron trichloride as a catalyst, and boron trichloride is liquid, and the catalyst dissolves in the reaction solution, thereby carrying out a homogeneous reaction, and the reaction has good compatibility, and a desirable yield can be obtained. And the post-treatment of the catalyst reaction is easily removed in the desolventizing step. Due to the catalysis of boron trichloride, the reaction is carried out more completely, and the product purity is high, and it is not necessary to distill out 4-chlorobutyryl chloride for purification. The present invention develops a synthesis and separation method of 4-chlorobutyryl chloride with relatively mild reaction conditions, high yield, low energy consumption, few wastes, and suitable for industrial production, which is very suitable for industrial production. DETAILED DESCRIPTION

[0022] The present invention is further explained or illustrated by the following examples, but the examples provided should not be construed as limiting the scope of protection of the present invention.

[0023] Example 1

[0024] A 5000L clean and dry reactor was protected by nitrogen (first evacuate, then break the air with nitrogen, repeat 3 times), then γ-butyrolactone (1500kg) was added, the temperature was lowered to 10-12°C, and then a 9% dichloromethane solution of boron trichloride (75kg) was added. After stirring and mixing, thionyl chloride (2280kg) was added dropwise for about 5 hours. During the addition, the reaction temperature was controlled between 10 and 12°C. After the addition was completed, the temperature was continued to be controlled between 10 and 12°C, and the reaction was kept warm for 2.5 hours. The GC detected that the residual γ-butyrolactone was less than 0.2%, and the reaction was completed.

[0025] Open the manhole of the reactor, add activated carbon (15 kg), stir at 10-12°C for 15 minutes, and then filter the material into the desolventizing kettle using nitrogen through a precision filter with a filter element of 0.45 μm.

[0026] First, distill under reduced pressure at 10-12°C (vacuum degree is -0.08-0.09MPa), then gradually increase the temperature from 10-12°C to 45°C, and after no liquid flows out, continue to degas at 45°C (vacuum degree is -0.08-0.09MPa) for 15 minutes. GC analysis: 4-chlorobutyryl chloride purity is 99.23% (greater than 99.0%), the maximum single impurity is 0.16% (less than 0.2%), discharge, weigh, the weight is 2369.5kg, and the molar yield is 96.45%.

[0027] Example 2

[0028] A 5000L clean and dry reactor was protected with nitrogen (first evacuate, then break the air with nitrogen, repeat 3 times), then γ-butyrolactone (1500kg) was added, the temperature was lowered to 10-12°C, and then a 9% dichloromethane solution of boron trichloride (60kg) was added. After stirring and mixing, thionyl chloride (2176.5kg) was added dropwise for about 4 hours. During the addition, the reaction temperature was controlled between 10 and 12°C. After the addition was completed, the temperature was continued to be controlled between 10 and 12°C, and the reaction was kept warm for 2 hours. The GC detected that the residual γ-butyrolactone was less than 0.2%, and the reaction was completed.

[0029] Open the manhole of the reactor, add activated carbon (7.5 kg), stir at 10-12°C for 10 minutes, and then filter the material into the desolventizing kettle using nitrogen through a precision filter with a filter element of 0.45 μm.

[0030] First, distill under reduced pressure at 10-12°C (vacuum degree is -0.08-0.09MPa), then gradually increase the temperature from 10-12°C to 45°C, and after no liquid flows out, continue to degas at 45°C (vacuum degree is -0.08-0.09MPa) for 15 minutes. GC analysis: 4-chlorobutyryl chloride purity is 99.02% (greater than 99.0%), the maximum single impurity is 0.18% (less than 0.2%), discharge, weigh, the weight is 2361.4kg, and the molar yield is 96.12%.

[0031] Example 3

[0032] A 5000L clean and dry reactor was protected by nitrogen (first evacuate, then break the air with nitrogen, repeat 3 times), then γ-butyrolactone (1500kg) was added, the temperature was lowered to 10-12°C, and then a 9% dichloromethane solution of boron trichloride (90kg) was added. After stirring and mixing, thionyl chloride (2383.8kg) was added dropwise for about 6 hours. During the addition, the reaction temperature was controlled between 10 and 12°C. After the addition was completed, the temperature was continued to be controlled between 10 and 12°C, and the reaction was kept warm for 3 hours. The GC detected that the residual γ-butyrolactone was less than 0.2%, and the reaction was completed.

[0033] Open the manhole of the reactor, add activated carbon (22.5 kg), stir at 10-12°C for 20 minutes, and then filter the material into the desolventizing kettle using nitrogen through a precision filter with a filter element of 0.45 μm.

[0034] First, distill under reduced pressure at 10-12°C (vacuum degree is -0.08-0.09MPa), then gradually increase the temperature from 10-12°C to 45°C, and after no liquid flows out, continue to degas at 45°C (vacuum degree is -0.08-0.09MPa) for 15 minutes. GC analysis: 4-chlorobutyryl chloride purity is 99.22% (greater than 99.0%), the maximum single impurity is 0.16% (less than 0.2%), discharge, weigh, the weight is 2358.7kg, and the molar yield is 96.01%.

[0035] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing and separating 4-chlorobutyryl chloride, characterized in that The steps include: Step (a): γ-butyrolactone reacts with thionyl chloride at 10-12° C. under the catalysis of a 9% boron trichloride dichloromethane solution to obtain 4-chlorobutyryl chloride, wherein the weight of the 9% boron trichloride dichloromethane solution is 4%-6% of the γ-butyrolactone, and the molar ratio of γ-butyrolactone to thionyl chloride is 1:1.05-1.

15. Step (b): after the reaction is completed, activated carbon is added to stir and adsorb impurities, filtered, and then the dichloromethane solution of the catalyst boron trichloride and excess thionyl chloride are removed by distillation to obtain a finished 4-chlorobutyryl chloride product, wherein the weight of the activated carbon added is 0.5-1.5% of the γ-butyrolactone, the stirring time is 10-20 minutes, and the temperature is 10-12°C.

2. A method for synthesizing and separating 4-chlorobutyryl chloride according to claim 1, characterized in that: In step (a), the time for dropping thionyl chloride is 4 to 6 hours, the time for keeping warm after dropping is 2 to 3 hours, and the temperature for dropping and keeping warm is both 10 to 12°C.

3. A method for synthesizing and separating 4-chlorobutyryl chloride according to claim 1, characterized in that: In step (b), the filtration step uses a precision filter with a filter element of 0.45 μm.

4. A method for synthesizing and separating 4-chlorobutyryl chloride according to claim 1, characterized in that: In step (b), the distillation step is to first perform reduced pressure distillation at 10-12°C with a vacuum degree of -0.08 to -0.09 MPa, then gradually increase the temperature from 10-12°C to 45°C, and after no liquid flows out, continue to degas at 45°C with a vacuum degree of -0.08 to -0.09 MPa for 15 minutes.

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