A method for synthesizing methoxymethylpiperidinium

Abstract

The application provides a synthesis method of methylpiperidinium, which comprises the following steps: adding methanol into a closed reaction kettle, then adding piperidine into the reaction kettle, adding chloromethane, passing through a metal cation exchange column, and evaporating the methanol and chloromethane to obtain the final product methylpiperidinium. The synthesis method of methylpiperidinium provided by the application can effectively reduce the amount of by-products generated in the first step of reaction and reduce production consumption by using methanol instead of chloromethane and using copper phosphine catalyst for catalysis.

Description

TECHNICAL FIELD

[0001] The present application relates to a synthesis method of mepiquat chloride, and belongs to the technical field of pesticide production. BACKGROUND

[0002] Mepiquat chloride is a low-toxicity, broad-spectrum quaternary ammonium plant growth regulator, which is mainly used as a plant growth regulator, can be quickly absorbed by the leaves and leaf system or the whole plant, and is similar to auxin in the plant body, and can be applied to various crops.

[0003] At present, the most commonly used industrial production method of mepiquat chloride is to first react piperidine with chloromethane to obtain N-methyl piperidine, and then react N-methyl piperidine with chloromethane under pressure to obtain N,N-dimethyl piperidine chloride salt. In the first step of the production process, the intermediate N-methyl piperidine generates HCL, which needs to be removed by reacting with an acid-binding agent. The reaction is exothermic and intense, and the by-products generated with the acid-binding agent also need to be removed in the subsequent process, which increases the production cost and reduces the economic benefit. SUMMARY

[0004] The purpose of the present application is to provide a synthesis method of mepiquat chloride, which uses methanol instead of chloromethane in the first step of the reaction, and uses copper phosphine catalyst for catalysis, which can effectively reduce the amount of by-products generated in the first step of the reaction and reduce production consumption.

[0005] To achieve the above purpose, the present application provides a synthesis method of mepiquat chloride, comprising the following steps:

[0006] a. Add methanol to a sealed reaction kettle, then add piperidine to the reaction kettle, stir and dissolve, then add copper catalyst and solid sodium hydroxide to the reaction kettle, the copper catalyst is a copper phosphine catalyst with zeolite as a carrier, then heat the reaction kettle to 50-60 DEG C, control the reaction pressure at 0.1-0.2 Mpa, and react for 5-10 hours to obtain a methanol solution of N-methyl piperidine;

[0007] b. Filter the reaction product of step a, and recycle the filtered copper phosphine catalyst;

[0008] c. Add chloromethane to the filtrate obtained in step b, heat and control the reaction temperature at 30-50 DEG C, the reaction pressure at 0.2-0.6 Mpa, and the reaction time at 2-5 hours;

[0009] d. Remove sodium ions in the reaction product of step c by passing through a metal cation exchange column;

[0010] d. Evaporate the eluate obtained in step d to remove methanol and chloromethane, and obtain the final product mepiquat chloride.

[0011] Furthermore, the preparation method of the copper phosphine catalyst with zeolite support includes the following steps:

[0012] Step 1: Add an organic solvent into the reactor, wherein the organic solvent is diethyl ether, toluene, or xylene;

[0013] Step 2: Add triphenylphosphine (PPh3) into the reactor.

[0014] Step 3: Add analytical grade cuprous chloride into the reactor and heat the solvent in the reactor to 35-45 degrees Celsius for 3-5 hours.

[0015] Step 4: Prepare zeolite by heating the zeolite particles to 200°C to 400°C and maintaining the temperature for 20-40 minutes.

[0016] Step 5: Add the zeolite processed in Step 4 to the mother liquor obtained in Step 3, and stir and mix for 3-5 hours.

[0017] Step 6: Centrifuge the mixture obtained in Step 5 to obtain zeolite particles containing copper phosphine. Then, place the separated catalyst sample in an oven and heat it to 60°C to 120°C for 20-60 minutes to remove residual organic solvents, thus obtaining the desired copper phosphine catalyst supported on zeolite.

[0018] Furthermore, the molar ratio of methanol to piperidine is 30-50:1, the molar ratio of piperidine to chloromethane is 1:1.2-1.5, the amount of copper phosphine catalyst with zeolite support for piperidine chloromethane is 5-10% of the mass of piperidine, and the amount of sodium hydroxide is 3-5% of the mass of piperidine.

[0019] Furthermore, the metal cation exchange column is a hydrogen-form cation exchange resin.

[0020] Furthermore, the molar ratio of cuprous chloride to triphenylphosphine is 1-2:1, and the weight ratio of zeolite to cuprous chloride is 10-20:1. The beneficial technical features of this invention are: in the first step of the reaction, methanol is used instead of chloromethane, and the reaction byproduct is water, which does not need to be specifically removed in subsequent reactions. Furthermore, in this invention, the solid alkali largely participates in the reaction as a catalyst, significantly reducing the amount of sodium chloride produced compared to existing processes. Sodium ions in the reaction can be efficiently removed using an ion exchange column, reducing the burden on subsequent processes and effectively decreasing the burden of removing byproducts. Chloromethane, compared to methanol, is not only more expensive but also more toxic; therefore, the amount of chloromethane used in production can be reduced by half compared to traditional processes. Attached Figure Description

[0021] Appendix Figure 1 The NMR spectrum of the final product. DETAILED DESCRIPTION

[0022] The production method used in the following examples is a conventional method unless otherwise specified. Example 1

[0023] 1) Preparation of copper phosphine catalyst:

[0024] Step 1, put 200ml of ether into a conical flask, then add 10g of triphenylphosphine;

[0025] Step 2, add 5.67g of analytical pure cuprous chloride into the conical flask, protect it with nitrogen, and heat the conical flask in water bath to 40 degrees Celsius, reaction time is 3 hours;

[0026] Step 3, prepare 100g of zeolite, put the zeolite particles into a muffle furnace and heat to 200°C for 40 minutes;

[0027] Step 4, add the zeolite treated in step 3 into the conical flask in step 2, stir and mix for 3 hours, and protect it with nitrogen in the meantime;

[0028] Step 5, centrifuge the mixture obtained in step 4 to remove the ether, obtain the zeolite particles containing the loaded copper phosphine, then put the separated catalyst sample into an oven, heat to 80°C and keep for 20 minutes to remove the residual organic solvent, thus obtaining the desired copper phosphine catalyst with zeolite as the carrier.

[0029] 2) Preparation of methylpiperidinium N,N-dimethylpiperidinium chloride:

[0030] Put 5g of piperidine and 100ml of methanol into a conical flask, stir and dissolve, then add 0.4g of copper phosphine catalyst with zeolite as the carrier, and then add 0.2g of solid sodium hydroxide, heat the water bath to 50 degrees Celsius, and react under normal pressure for 6 hours to obtain a methanol solution of N-methylpiperidine. Filter the obtained methanol solution of N-methylpiperidine, add it into an autoclave, add 3.85g of chloromethane into the autoclave, heat and control the reaction temperature at 35 degrees Celsius, the reaction pressure at 0.25Mpa, and the reaction time at 5 hours. After the reaction is completed, remove the sodium ions in the reaction mother liquor by passing it through a strong acid styrene cation exchange column. Evaporate the eluent passing through the ion exchange column to remove methanol and chloromethane, thus obtaining the final product methylpiperidinium 8.68g, with a content of 99.3% and a yield of 98.1%.

[0031] Figure 1 Figure 1 Figure 1 is the nuclear magnetic resonance spectrum of the final product, which confirms that the obtained product is the target product methylpiperidinium. Example 2

[0032] 1) Preparation of copper phosphine catalyst:

[0033] Step 1, put 5000ml of toluene into a reaction kettle, then add 280g of triphenylphosphine;

[0034] Step 2, add 148.5g of analytical pure cuprous chloride into the reaction kettle, protect with nitrogen, and heat the reaction kettle to 40°C, reaction time 5 hours;

[0035] Step 3, prepare 2000g of zeolite, put the zeolite particles into a muffle furnace and heat to 300°C for 30 minutes;

[0036] Step 4, add the zeolite treated in step 3 into the reaction kettle in step 2, stir and mix for 4 hours;

[0037] Step 5, centrifuge the mixture obtained in step 4 to remove toluene, obtain zeolite particles loaded with copper phosphine, then put the separated catalyst sample into an oven, heat to 60°C and keep for 50 minutes to remove residual organic solvents, thus obtaining the desired zeolite-supported copper phosphine catalyst.

[0038] 2) Preparation of Mepiprazine N,N-dimethylpiperidine chloride salt:

[0039] Put 4.5kg of piperidine and 76.97kg of methanol into an autoclave, stir and dissolve, then add 270g of zeolite-supported copper phosphine catalyst, and then add 160g of solid sodium hydroxide, protect with nitrogen, heat to 55°C, control the reaction pressure at 0.15Mpa, and react for 5-10 hours to obtain a methanol solution of N-methylpiperidine; filter the obtained methanol solution of N-methylpiperidine, then add chloromethane 3.73kg to the filtrate, heat and control the reaction temperature at 45°C, the reaction pressure at 0.35Mpa, and the reaction time at 4.5 hours; after the reaction is completed, pass the reaction mother liquor through a strong acid styrene-based cation exchange column to remove sodium ions therein; evaporate the eluate passing through the ion exchange column to remove methanol and chloromethane, thus obtaining 7.83kg of mepiprazine with a concentration of 99% and a yield of 98%.

Claims

1. A method of synthesizing metformin, characterized by, The synthesis method comprises the following steps: a, methanol is added into a closed reaction kettle, then piperidine is added into the reaction kettle, after stirring and dissolving, copper catalyst and solid sodium hydroxide are added into the reaction kettle, the copper catalyst is copper phosphine catalyst with zeolite as carrier, then the reaction kettle is heated to 50-60 DEG C, the reaction pressure is controlled to be 0.1-0.2 Mpa, after reaction for 5-10 hours, N-methyl piperidine methanol solution is obtained; b, the reaction product of step a is filtered, and the filtered copper phosphine catalyst is recycled; c, chloromethane is added into the filtrate obtained in step b, heating is conducted and the reaction temperature is controlled to be 30-50 DEG C, the reaction pressure is controlled to be 0.2-0.6 Mpa, and the reaction time is 2-5 hours; d, the reaction product obtained in step c is passed through a metal cation exchange column to remove sodium ions therein; d, the eluate obtained in step d is evaporated to remove methanol and chloromethane, and the final product is obtained, the preparation method of the copper phosphine catalyst with zeolite as carrier comprises the following steps: step 1, an organic solvent is added into a reactor, the organic solvent is diethyl ether, toluene or xylene; Step 2, triphenylphosphine (PPh3) is added into the reactor; Step 3, analytical pure cuprous chloride is added into the reactor, and the temperature of the solvent in the reactor is heated to 35-45 DEG C, and the reaction time is 3-5 hours; Step 4, zeolite is prepared, and the zeolite particles are heated to 200 DEG C to 400 DEG C and kept for 20-40 minutes; Step 5, the zeolite treated in step 4 is added into the mother liquor obtained in step 3, and stirring and mixing are conducted for 3-5 hours; Step 6, the mixture obtained in step 5 is centrifuged to obtain zeolite particles loaded with copper phosphine, then the separated catalyst sample is placed into an oven, heated to 60 DEG C to 120 DEG C and kept for 20-60 minutes to remove residual organic solvent, and the required copper phosphine catalyst with zeolite as carrier is obtained.

2. The method of claim 1, wherein: The molar ratio of methanol to piperidine is 30-50:1, the molar ratio of piperidine to chloromethane is 1:1.2-1.5, the input amount of the copper phosphine catalyst with zeolite as carrier is 5-10% of the mass of piperidine, and the input amount of sodium hydroxide is 3-5% of the mass of piperidine.

3. The method of claim 1, wherein: The metal cation exchange column is hydrogen type cation exchange resin.

4. The method of claim 1, wherein: The molar ratio of the analytical pure cuprous chloride to triphenylphosphine is 1-2:1, and the weight ratio of the zeolite to the analytical pure cuprous chloride is 10-20:1.

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