Synthesis process of cyclopropanecarbonyl chloride

Abstract

The invention relates to the technical field of organic synthesis, in particular to a synthesis process of cyclopropanecarbonyl chloride. Reaction materials are replaced, phosgene is adopted to replace thionyl chloride, the yield of cyclopropanecarbonyl chloride products is guaranteed, introduction of sulfur elements is avoided, existence of sulfur dioxide, sulfur trioxide and other substances in by-products is avoided, the yield of the cyclopropanecarbonyl chloride products is increased, and the yield of the cyclopropanecarbonyl chloride products is increased. According to the method, thionyl chloride is adopted as a raw material, the difficulty of three-waste treatment is reduced, the cost of three-waste treatment is reduced, and the technical problems that thionyl chloride is adopted as a raw material in a cyclopropanecarbonyl chloride synthesis process in the prior art, and tail gas treatment is relatively complex due to introduction of sulfur elements can be effectively solved.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a synthesis process of cyclopropanecarbonyl chloride. Background Art

[0002] The uses of cyclopropanecarbonyl chloride mainly include being an intermediate of the plant growth regulator trinexapac-ethyl, a pharmaceutical and pesticide intermediate, and a fine chemical intermediate. It can be used to prepare quinolone antibiotics such as ciprofloxacin, ciprofloxacin, and sparfloxacin. In the prior art, the synthesis process of cyclopropanecarbonyl chloride is as follows: using γ-butyrolactone, isopropanol, thionyl chloride, etc. as raw materials, through the processes of ring opening esterification, ring closing, hydrolysis, etc. to obtain cyclopropanecarboxylic acid, and then reacting with thionyl chloride to obtain the cyclopropanecarbonyl chloride product by acylation.

[0003] However, the prior art synthesis process of cyclopropanecarbonyl chloride uses thionyl chloride as a raw material, and the introduction of sulfur element makes the tail gas treatment more complicated. Summary of the invention

[0004] The invention aims to provide a synthesis process of cyclopropanecarbonyl chloride, aiming to solve the technical problem that the synthesis process of cyclopropanecarbonyl chloride in the prior art adopts thionyl chloride as a raw material, and the introduction of sulfur element leads to complicated tail gas treatment.

[0005] To achieve the above object, a synthesis process of cyclopropanecarbonyl chloride adopted in the present invention comprises the following steps:

[0006] Step 1, adding γ-butyrolactone, isopropanol, the first catalyst and phosgene in proportion to a first 500ml four-necked bottle, heating the reaction, sampling and central control analysis after the reaction is completed, the γ-butyrolactone content is 0% to 2%, and then desolventizing and recovering isopropanol until the isopropanol content is 0% to 2%, stopping distillation, and obtaining 4-chlorobutyric acid isopropyl ester product;

[0007] Step 2, adding the solvent, the second catalyst and sodium hydroxide into a second 500ml four-necked bottle, dropping the 4-chlorobutyric acid isopropyl ester product into the second 500ml four-necked bottle, heating the reaction, sampling and central control analysis after the reaction is completed, and the 4-chlorobutyric acid isopropyl ester content is 0% to 2%, then desolventizing the dichloromethane, and cooling to obtain the reactant;

[0008] Step 3: Add reactants, process water and caustic soda to a 1000mL four-necked bottle with a distillation tower, and heat the reaction. After the reaction is completed, when the isopropanol content at the top of the tower is detected to be 0% to 2%, add 30% hydrochloric acid to the 1000mL four-necked bottle, maintain pH 1 to 3, and stand for stratification to obtain a crude cyclopropanecarboxylic acid product. Distill the crude cyclopropanecarboxylic acid product, collect the fractions, and obtain a cyclopropanecarboxylic acid product.

[0009] Step 4: Add cyclopropanecarboxylic acid product, third catalyst and phosgene into a third 500ml four-necked bottle, and heat to 80-100°C for reaction. After sampling and central control analysis, the acidity is 0%-2%, and then distillation can be carried out to receive the main fraction, sample the top of the tower to detect the phosgene content of 0%-2%, stop distillation, and obtain cyclopropanecarboxylic acid chloride.

[0010] Among them, in step one:

[0011] The first catalyst comprises any one or a combination of metal halides and metal oxides, the metal halide comprises one of zinc chloride, copper chloride, silver chloride and zinc bromide, and the metal oxide comprises one of zinc oxide, copper oxide and silver oxide;

[0012] γ-butyrolactone, isopropanol, the first catalyst and phosgene were added into a first 500 ml four-necked bottle according to a certain proportion, and the specific method of heating the reaction was as follows:

[0013] In a 500mL four-necked bottle, add 110g of γ-butyrolactone, 150g of isopropanol and 8g of zinc chloride, raise the temperature to 30-40°C, then introduce 148g of phosgene for 5h; after the introduction is complete, raise the temperature to 50-60°C and react for 2h.

[0014] Among them, in step 1, before desolventizing and recovering isopropanol, it is necessary to deacidify at -0.01 MPa for 2 hours and then heat to 80°C.

[0015] Among them, in step 2:

[0016] The solvent includes any one or more of halogenated alkanes, toluenes, and nitriles, and the halogenated alkanes include any one or more of monochloroethane, dichloroethane, dichloromethane, and dichloropropane;

[0017] The second catalyst includes any one or more of polyethylene glycol, quaternary ammonium salts, and crown ethers. The quaternary ammonium salts include one or more of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, and dodecyltrimethylammonium chloride.

[0018] The solvent, the second catalyst and sodium hydroxide are added into a second 500 ml four-necked bottle, and the 4-chlorobutyric acid isopropyl ester product is added dropwise into the second 500 ml four-necked bottle. The specific method of the temperature-raising reaction is as follows:

[0019] Add 210 g of dichloromethane, 2.5 g of benzyltriethylammonium chloride, and 37 g of sodium hydroxide into a 500 mL four-necked bottle, raise the temperature to 30-40°C, add 103 g of isopropyl 4-chlorobutyrate dropwise for 5-6 hours, raise the temperature to 40-50°C and keep warm for 6 hours.

[0020] Wherein, in step 2, dichloromethane is removed and the reactant is obtained after cooling by 20-30°C.

[0021] Among them, in step three:

[0022] The specific method of adding reactants, process water and caustic soda to a 1000mL four-necked bottle with a distillation tower and conducting a temperature reaction is as follows: adding reactants, 100g process water and 24g caustic soda to a 1000mL four-necked bottle with a distillation tower, heating to 50-75°C, controlling the tower top temperature at 38-42°C, reacting for 4h, and producing dichloromethane as a fraction; then heating to 80-100°C, controlling the tower top temperature at 45-78°C, collecting transition fraction A for about 1h; heating to 110°C, controlling the tower top temperature at 78-82°C, collecting isopropanol for about 4h; with vacuum at -0.03-0.05MPa, producing transition fraction B.

[0023] Before adding 30% hydrochloric acid into a 1000mL four-necked bottle with a distillation tower, it is necessary to detect that the isopropanol content at the top of the tower is 0% to 2%, perform dehydration to obtain a reaction solution, and then acidify the reaction solution and cool it to 20-30°C.

[0024] Wherein, in step 3, the crude cyclopropanecarboxylic acid product is obtained by standing and stratifying, and the crude cyclopropanecarboxylic acid product is distilled and the fractions are collected to obtain the cyclopropanecarboxylic acid product in the following specific manner:

[0025] The mixture was allowed to stand for 1 hour and the layers were separated. The upper layer was the organic layer of crude cyclopropanecarboxylic acid and the lower layer was hydrochloric acid water. The mixture was extracted three times with dichloromethane. The organic phases were combined and the oil layer obtained by desolventizing and the acidified oil layer were combined for distillation.

[0026] 68g of crude cyclopropanecarboxylic acid was distilled at 85-100°C and -0.1-0.001Mpa, and the 92-96°C fraction was collected to obtain 10g of the front fraction, 46.7g of the main fraction, and 11.3g of the still residue; the yield of cyclization, hydrolysis, acidification and distillation was 91%.

[0027] Among them, in step 4:

[0028] The third catalyst includes any one or a combination of amines and pyridine;

[0029] Add cyclopropanecarboxylic acid product, the third catalyst and phosgene into a third 500ml four-necked bottle, and heat to 80-100°C. The specific method of the reaction is: add 137.5g cyclopropanecarboxylic acid and 1g triethylamine into the third 500ml four-necked bottle, heat to 70-75°C, then introduce 174g phosgene for 7h, then heat to 90-93°C and keep warm for 3h.

[0030] The invention discloses a synthesis process of cyclopropanecarbonyl chloride. Firstly, gamma-butyrolactone, isopropanol, a first catalyst and phosgene are added into a first 500ml four-necked bottle in proportion, and the temperature is raised for reaction. After the reaction is completed, sampling is performed to analyze the gamma-butyrolactone content to be 0% to 2%, and then isopropanol is desolventized and recovered until the isopropanol content is 0% to 2%. Then, distillation is stopped to obtain a 4-chlorobutyric acid isopropyl ester product for standby use. Then, a solvent, a second catalyst and sodium hydroxide are added into a second 500ml four-necked bottle. The 4-chlorobutyric acid isopropyl ester product is added dropwise into the second 500ml four-necked bottle, and the temperature is raised for reaction. After the reaction is completed, sampling is performed to analyze the 4-chlorobutyric acid isopropyl ester content to be 0% to 2%, and then dichloromethane is desolventized. After cooling, a reactant is obtained. Then, the reactant, process water and caustic soda are added into a 1000ml four-necked bottle with a rectifying tower, and the temperature is raised for reaction. After the reaction is completed, when the isopropanol content at the top of the tower is detected to be 0% to 2%, 30% hydrochloric acid is added to the bottle. The method comprises the following steps: keeping the pH value of the reaction mixture in a 1000 ml four-necked bottle at 1-3, allowing the mixture to stand for stratification to obtain a crude cyclopropanecarboxylic acid product, rectifying the crude cyclopropanecarboxylic acid product, collecting fractions to obtain a cyclopropanecarboxylic acid product, adding the cyclopropanecarboxylic acid product, a third catalyst and phosgene into a third 500 ml four-necked bottle, heating the mixture to 80-100 DEG C for reaction, and then rectifying the reaction mixture after the acidity of the reaction mixture is 0%-2% by sampling and central control analysis, receiving a main fraction, sampling the tower top to detect the phosgene content of 0%-2%, stopping the rectification, and obtaining cyclopropanecarbonyl chloride. The method replaces the reaction materials, ensures the yield of the cyclopropanecarbonyl chloride product, avoids the introduction of sulfur, and further avoids the presence of sulfur dioxide, sulfur trioxide and other substances in the by-products, reduces the difficulty of three waste treatment, and reduces the cost of three waste treatment. The method can effectively solve the technical problem that the cyclopropanecarbonyl chloride synthesis process in the prior art uses thionyl chloride as a raw material, and the introduction of sulfur will lead to complicated tail gas treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 It is a process flow chart of the synthesis process of cyclopropanecarbonyl chloride of the present invention.

[0033] Figure 2 The invention is a schematic diagram of the synthesis of 4-chlorobutyric acid isopropyl ester and cyclopropanecarbonyl chloride in the prior art.

[0034] Figure 3 The present invention is a schematic diagram of the synthesis of 4-chlorobutyric acid isopropyl ester and cyclopropanecarbonyl chloride. DETAILED DESCRIPTION

[0035] Embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0036] See also Figure 1 and Figure 3 ,in Figure 1 It is a process flow chart of the synthesis technique of cyclopropanecarbonyl chloride of the present invention, Figure 2 It is a schematic diagram of the synthesis of 4-chlorobutyric acid isopropyl ester and cyclopropanecarbonyl chloride in the prior art. Figure 3 The present invention is a schematic diagram of the synthesis of 4-chlorobutyric acid isopropyl ester and cyclopropanecarbonyl chloride.

[0037] The present invention provides a synthesis process of cyclopropanecarbonyl chloride, comprising the following steps:

[0038] S101, add 110g of γ-butyrolactone, 150g of isopropanol and 8g of the first catalyst to the first 500mL four-necked bottle, heat to 30-40°C, then introduce 148g of phosgene for 5h; after the introduction, heat to 50-60°C for reaction for 2h, take a sample for central control analysis after the reaction is completed and the γ-butyrolactone content is less than 1%, deacidify at -0.01MPa for 2h, then heat to 80°C, then desolventize and recover isopropanol until the isopropanol content is less than 1%, stop distillation, and obtain 4-chlorobutyric acid isopropyl ester product;

[0039] According to this specific embodiment, the first catalyst includes any one or a combination of metal halides and metal oxides, the metal halide includes one of zinc chloride, copper chloride, silver chloride and zinc bromide, and the metal oxide includes one of zinc oxide, copper oxide and silver oxide;

[0040] In this embodiment, the first catalyst is preferably zinc chloride.

[0041] S102, add 210g of solvent, 2.5g of the second catalyst, and 37g of sodium hydroxide to a second 500mL four-necked bottle, raise the temperature to 30-40°C, add 103g of 4-chlorobutyric acid isopropyl dropwise, complete the addition for 6 hours, raise the temperature to 40-50°C and keep warm for 6 hours, then take a sample and analyze the 4-chlorobutyric acid isopropyl content to be less than 1%, then desolventize the dichloromethane, cool to 20-30°C, and transfer the material to hydrolysis to obtain the reactant;

[0042] According to this specific embodiment, the solvent includes any one or more of halogenated alkanes, toluenes, and nitriles, and the halogenated alkanes include any one or more of monochloroethane, dichloroethane, dichloromethane, and dichloropropane;

[0043] The second catalyst includes any one or more of polyethylene glycol, quaternary ammonium salts, and crown ethers. The quaternary ammonium salts include one or more of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, and dodecyltrimethylammonium chloride.

[0044] S103. Add reactants, 100 g of process water and 24 g of caustic soda to a 1000 mL four-necked bottle with a distillation tower, heat to 50-75 ° C, control the tower top temperature at 38-42 ° C, react for 4 h, and extract dichloromethane; then heat to 80-100 ° C, control the tower top temperature at 45-78 ° C, collect transition fraction A for about 1 h; heat to 110 ° C, control the tower top temperature at 78-82 ° C, collect isopropanol for about 4 h; Vacuum -0.03-0.05MPa, extract transition fraction B, then detect the isopropanol content of the top of the tower and when it is less than 2%, add 113g of 30% hydrochloric acid to a 1000mL four-necked bottle, maintain pH 1-3, stand for 1h to separate, the upper layer is the organic layer of crude cyclopropanecarboxylic acid, the lower layer is hydrochloric acid water, extract three times with dichloromethane; combine the organic phases, desolventize the oil layer and the acidified oil layer, combine and rectify, collect the fractions, and obtain the cyclopropanecarboxylic acid product;

[0045] According to the present specific implementation mode, the specific method of distillation is as follows: 68 g of crude cyclopropanecarboxylic acid is distilled at a temperature of 85 to 100 ° C and a pressure of -0.1 to -0.001 MPa, and a 92-96 ° C fraction is collected to obtain 10 g of a front fraction, 46.7 g of a main fraction, and 11.3 g of a kettle residue; the yield of cyclization, hydrolysis, acidification, and distillation is 91%.

[0046] S104, add 137.5g cyclopropanecarboxylic acid and 1g third catalyst to the third four-necked bottle, and heat to 70-75°C. Pass 174g phosgene for 7h, heat to 90-93°C, keep warm for 3h, take a sample to detect the acidity is less than 0.5%, the atmospheric pressure belt distillation tower receives the fraction before 110°C (apply to the next batch of acyl chloride synthesis), keep for 30min, take a sample at the top of the tower to detect the phosgene content is less than 0.15%, receive the main fraction, (the kettle residue is barreled, several batches are combined and fed, and the acylation reaction is carried out again, and the secondary kettle residue is used as solid waste), and 155.3g cyclopropanecarboxylic acid chloride is obtained, and the yield is 93%.

[0047] According to this specific embodiment, the third catalyst includes any one of amines and pyridine or a combination of two of them.

[0048] The invention discloses a synthesis process of cyclopropanecarbonyl chloride. The invention replaces the reaction materials, ensures the yield of the cyclopropanecarbonyl chloride product, avoids the introduction of sulfur, and further avoids the presence of sulfur dioxide, sulfur trioxide and other substances in the by-products, reduces the difficulty of three waste treatment, and reduces the cost of three waste treatment. The method can effectively solve the technical problem that the synthesis process of cyclopropanecarbonyl chloride in the prior art uses thionyl chloride as a raw material, and the introduction of sulfur will lead to more complicated tail gas treatment.

[0049] What is disclosed above is only a preferred embodiment of the present invention, and it certainly cannot be used to limit the scope of rights of the present invention. Ordinary technicians in this field can understand that all or part of the processes of the above embodiment and equivalent changes made according to the claims of the present invention still fall within the scope of the invention.

Claims

1. A synthesis process for cyclopropanecarbonyl chloride, characterized in that, The steps include: Step 1, adding γ-butyrolactone, isopropanol, the first catalyst and phosgene in proportion to a first 500ml four-necked bottle, heating the reaction, sampling and central control analysis after the reaction is completed, the γ-butyrolactone content is 0% to 2%, and then desolventizing and recovering isopropanol until the isopropanol content is 0% to 2%, stopping distillation, and obtaining 4-chlorobutyric acid isopropyl ester product; Step 2, adding the solvent, the second catalyst and sodium hydroxide into a second 500ml four-necked bottle, dropping the 4-chlorobutyric acid isopropyl ester product into the second 500ml four-necked bottle, heating the reaction, sampling and central control analysis after the reaction is completed, and the 4-chlorobutyric acid isopropyl ester content is 0% to 2%, then desolventizing the dichloromethane, and cooling to obtain the reactant; Step 3: Add reactants, process water and caustic soda to a 1000mL four-necked bottle with a distillation tower, and heat the reaction. After the reaction is completed, when the isopropanol content at the top of the tower is detected to be 0% to 2%, add 30% hydrochloric acid to the 1000mL four-necked bottle, maintain pH 1 to 3, and stand for stratification to obtain a crude cyclopropanecarboxylic acid product. Distill the crude cyclopropanecarboxylic acid product, collect the fractions, and obtain a cyclopropanecarboxylic acid product. Step 4: Add cyclopropanecarboxylic acid product, third catalyst and phosgene into a third 500ml four-necked bottle, and heat to 80-100°C for reaction. After sampling and central control analysis, the acidity is 0%-2%, and then distillation can be carried out to receive the main fraction, sample the top of the tower to detect the phosgene content of 0%-2%, stop distillation, and obtain cyclopropanecarboxylic acid chloride.

2. The synthesis technique of cyclopropanecarbonyl chloride as claimed in claim 1, characterized in that, In step one: The first catalyst comprises any one or a combination of metal halides and metal oxides, the metal halide comprises one of zinc chloride, copper chloride, silver chloride and zinc bromide, and the metal oxide comprises one of zinc oxide, copper oxide and silver oxide; γ-butyrolactone, isopropanol, the first catalyst and phosgene were added into a first 500 ml four-necked bottle according to a certain proportion, and the specific method of heating the reaction was as follows: In a 500mL four-necked bottle, add 110g of γ-butyrolactone, 150g of isopropanol and 8g of zinc chloride, raise the temperature to 30-40°C, then introduce 148g of phosgene for 5h; after the introduction is complete, raise the temperature to 50-60°C and react for 2h.

3. The synthesis technique of cyclopropanecarbonyl chloride as claimed in claim 2, characterized in that, In step 1, before desolventizing and recovering isopropanol, it is necessary to deacidify at -0.01 MPa for 2 h and then heat to 80°C.

4. The synthesis technique of cyclopropanecarbonyl chloride as claimed in claim 3, characterized in that, In step 2: The solvent includes any one or more of halogenated alkanes, toluenes, and nitriles, and the halogenated alkanes include any one or more of monochloroethane, dichloroethane, dichloromethane, and dichloropropane; The second catalyst includes any one or more of polyethylene glycol, quaternary ammonium salts, and crown ethers. The quaternary ammonium salts include one or more of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, and dodecyltrimethylammonium chloride. The solvent, the second catalyst and sodium hydroxide are added into a second 500 ml four-necked bottle, and the 4-chlorobutyric acid isopropyl ester product is added dropwise into the second 500 ml four-necked bottle. The specific method of the temperature-raising reaction is as follows: Add 210 g of dichloromethane, 2.5 g of benzyltriethylammonium chloride, and 37 g of sodium hydroxide into a 500 mL four-necked bottle, raise the temperature to 30-40°C, add 103 g of isopropyl 4-chlorobutyrate dropwise for 5-6 hours, raise the temperature to 40-50°C and keep warm for 6 hours.

5. The synthesis process of cyclopropanecarbonyl chloride as claimed in claim 4, characterized in that, In step 2, dichloromethane is removed and the temperature is reduced by 20-30° C. to obtain the reactant.

6. The synthesis process of cyclopropanecarbonyl chloride as claimed in claim 5, characterized in that, In step three: The specific method of adding reactants, process water and caustic soda to a 1000mL four-necked bottle with a distillation tower and conducting a temperature reaction is as follows: adding reactants, 100g process water and 24g caustic soda to a 1000mL four-necked bottle with a distillation tower, heating to 50-75°C, controlling the tower top temperature at 38-42°C, reacting for 4h, and producing dichloromethane as a fraction; then heating to 80-100°C, controlling the tower top temperature at 45-78°C, collecting transition fraction A for about 1h; heating to 110°C, controlling the tower top temperature at 78-82°C, collecting isopropanol for about 4h; with vacuum at -0.03-0.05MPa, producing transition fraction B.

7. The synthesis process of cyclopropanecarbonyl chloride as claimed in claim 6, characterized in that, Before adding 30% hydrochloric acid into a 1000mL four-necked bottle with a distillation tower, it is necessary to perform dehydration treatment to obtain a reaction solution after detecting that the isopropanol content at the top of the tower is 0% to 2%, and then acidify the reaction solution and cool it to 20-30°C.

8. The synthesis process of cyclopropanecarbonyl chloride as claimed in claim 7, characterized in that, In step 3, the crude cyclopropanecarboxylic acid product is obtained by standing and stratifying, and the crude cyclopropanecarboxylic acid product is distilled and the fractions are collected to obtain the cyclopropanecarboxylic acid product in the following specific manner: The mixture was allowed to stand for 1 hour and the layers were separated. The upper layer was the organic layer of crude cyclopropanecarboxylic acid and the lower layer was hydrochloric acid water. The mixture was extracted three times with dichloromethane. The organic phases were combined and the oil layer obtained by desolventizing and the acidified oil layer were combined for distillation. 68g of crude cyclopropanecarboxylic acid was distilled at 85-100°C and -0.1-0.001Mpa, and the 92-96°C fraction was collected to obtain 10g of the front fraction, 46.7g of the main fraction, and 11.3g of the kettle residue.

9. The synthesis process of cyclopropanecarbonyl chloride as claimed in claim 8, characterized in that, In step four: The third catalyst includes any one or a combination of amines and pyridine; Add cyclopropanecarboxylic acid product, the third catalyst and phosgene into a third 500ml four-necked bottle, and heat to 80-100°C. The specific method of the reaction is: add 137.5g cyclopropanecarboxylic acid and 1g triethylamine into the third 500ml four-necked bottle, heat to 70-75°C, then introduce 174g phosgene for 7h, then heat to 90-93°C and keep warm for 3h.

Images