CN107935960B - Preparation method of 2-chloro-5-chloromethyl thiazole - Google Patents
Preparation method of 2-chloro-5-chloromethyl thiazole Download PDFInfo
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a preparation method of 2-chloro-5-chloromethyl thiazole, which comprises the following steps: in a microreactor, under the condition of no solvent, chlorine and 1-isothiocyanato-2-chloro-2-propylene are subjected to chlorination reaction under the action of a composite initiator to prepare the 2-chloro-5-chloromethylthiazole. The method has the advantages of no need of solvent, low cost, mild reaction conditions, high reaction speed, less three wastes, simple process, high yield and purity of the target product and the like.
Description
Technical Field
The invention belongs to the technical field of preparation of pesticide intermediates, and particularly relates to a preparation method of 2-chloro-5-chloromethyl thiazole.
Background
2-chloro-5-chloromethyl thiazole (CCMT for short) is a key intermediate of thiamethoxam and clothianidin of a second-generation thiazole pesticide, can also be condensed with heterocyclic N-H through alkylation reaction to prepare a series of insecticidal and acaricidal agents and is used for synthesizing an intermediate 5-hydroxymethylthiazole of anti-AIDS drug ritonavir.
The thiazole pesticide simulates the action mechanism of tobacco alkaloid, has no cross resistance to conventional pyrethroid insecticides, organophosphate insecticides and carbamate insecticides by acting on a nicotine acetylcholine receptor, has the advantages of rapid degradation, short half-life period in soil and biological safety, and can be widely used for preventing and treating piercing-sucking pests, various beetles, lepidoptera pests and the like. The molecular structures of thiamethoxam and clothianidin are introduced with a chlorothiazole structure, so that compared with first-generation nicotine pesticide imidacloprid and the like, the insecticidal spectrum is widened, the biological activity is improved, and the thiamethoxam and clothianidin are known as a representative variety of second-generation nicotine compounds. As an important strategic species of first-hit, thiamethoxam reaches $ 11 billion in global sales in 2015, and the pesticide is listed as the second in global sales; thiamethoxam has been registered for use in crops in over 115 countries around the world as an insecticide and seed treatment. Also, thiamethoxam, an important variety of a novel nicotinic insecticide developed in association with the martial arts/bayer process in japan, reached $ 3.5 billion in global sales in 2015, and ranked as the global sales of insecticides ranked tenth.
At present, the preparation methods of 2-chloro-5-chloromethyl thiazole reported at home and abroad are more, and the preparation methods mainly comprise the following seven methods:
(1) 1-isothiocyanato-2-propene reacts with a large amount of chlorine gas at a reflux temperature, and 2-chloro-5-chloromethylthiazole (US 4748432) is obtained by distillation and rectification.
(2) 1-isothiocyanato-3-chloro-1-propene reacts with chlorine or sulfuryl chloride under the action of a catalyst (iodine or Lewis acid) to prepare 2-chloro-5-chloromethylthiazole (U.S. Pat. No. 5,5705652).
(3) Reacting 1-isothiocyanato-2-chloro-2-propene with chlorine or sulfuryl chloride, and performing post-treatment such as desolventizing to obtain 2-chloro-5-chloromethylthiazole (U.S. Pat. No. 2,989,98).
(4) Acrolein is used as a raw material to prepare 2-amino-5-hydroxymethyl thiazole, and the 2-chloro-5-chloromethyl thiazole (US 6566530) is prepared by diazotization, hydrolysis in a large amount of hydrochloric acid and heating.
(5) Diazotizing 2-amino-5-methylthiazole, hydrolyzing in a large amount of hydrochloric acid, heating to obtain 2-chloro-5-methylthiazole, and then reacting with N-chlorosuccinimide to prepare the 2-chloro-5-chloromethyl thiazole.
(6) The 2-chloro-5-chloromethyl thiazole (CN 106749086A) is prepared by the reaction of 5-hydroxymethyl thiazole and N-chlorosuccinimide under the action of a catalyst (iodine).
(7) 1-isothiocyanato-2-chloro-2-propene and chlorine are used as raw materials, hydrochloric acid gas is introduced or concentrated hydrochloric acid is added after reaction to prepare 2-chloro-5-chloromethylthiazole hydrochloride, and the 2-chloro-5-chloromethylthiazole (CN 105949145A) is obtained through post-treatment operations such as filtration, desolventization, washing and the like.
The above method (1) has problems such as a large amount of chlorine gas required and a large number of side reactions. Meanwhile, the purity and the yield are low. In the method (2), the cis-trans ratio of the raw material 1-isothiocyanato-3-chloro-1-propene has a large influence on the reaction yield, and the post-treatment of the catalyst is complicated and is not suitable for industrial production. The method (3) has mild reaction conditions, convenient operation and relatively suitable industrial production, but has the problems of longer reaction time, low product purity and the like. The methods (4) and (5) both have the problems of low reaction yield, harsh diazotization reaction conditions, large hydrochloric acid consumption, incapability of recycling and the like, and are not suitable for large-scale industrial production. Compared with the first 5 methods, the method (6) solves the problems of low yield and purity, but has the problems of long reaction time, complex operation, strict temperature requirement and the like; meanwhile, iodine is used as a catalyst, N-chlorosuccinimide is used as a chlorination reagent, and the production cost is higher. The method (7) has the problems of long reaction time, large amount of washing wastewater, incapability of recycling and the like, and is not suitable for green clean industrial production.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a preparation method of 2-chloro-5-chloromethyl thiazole, which does not need a solvent, has low cost, mild reaction conditions, high reaction speed, less three wastes, simple process and higher yield and purity.
In order to solve the technical problems, the invention adopts the following technical scheme:
a preparation method of 2-chloro-5-chloromethyl thiazole comprises the following steps:
in a microreactor, under the condition of no solvent, chlorine and 1-isothiocyanato-2-chloro-2-propylene are subjected to chlorination reaction under the action of a composite initiator to prepare the 2-chloro-5-chloromethylthiazole.
In the above preparation method of 2-chloro-5-chloromethylthiazole, preferably, the composite initiator includes a component a and a component B, wherein the component a is benzoyl peroxide, and the component B is one of N, N-dimethylaniline and N, N-diethylaniline.
In the above preparation method of 2-chloro-5-chloromethylthiazole, preferably, the composite initiator comprises a component a and a component B, wherein the component a is tert-butyl hydroperoxide and the component B is sodium metabisulfite.
In the preparation method of the 2-chloro-5-chloromethylthiazole, preferably, in the composite initiator, the mass ratio of the component A to the component B is 1: 0.5-1.5.
In the above preparation method of 2-chloro-5-chloromethylthiazole, preferably, the amount of the composite initiator is 2 to 5 percent of the mass of 1-isothiocyanato-2-chloro-2-propene.
In the above preparation method of 2-chloro-5-chloromethylthiazole, the molar ratio of the chlorine gas to the 1-isothiocyanato-2-chloro-2-propene is preferably 0.9-1.1: 1.
In the preparation method of the 2-chloro-5-chloromethylthiazole, preferably, the feeding speed of the chlorine gas into the microreactor is 0.64-1.4 g/min.
In the above preparation method of 2-chloro-5-chloromethylthiazole, preferably, the composite initiator is dissolved in 1-isothiocyanato-2-chloro-2-propene to form a mixed solution, and the feeding speed of the mixed solution into the microreactor is 1.3-2.6 g/min.
In the above preparation method of 2-chloro-5-chloromethylthiazole, preferably, the microreactor comprises a plurality of plates connected in series in sequence, each plate is provided with a microchannel, and the microchannels on the plates are connected in sequence to form a channel for liquid to flow; the mixed solution enters the microreactor from the microchannel of the first plate, and chlorine enters the microreactor through the second plate; the remaining plates are the mixing plates used to carry out the reaction.
In the preparation method of the 2-chloro-5-chloromethylthiazole, the temperature of the chlorination reaction is preferably 10-50 ℃.
Compared with the prior art, the invention has the advantages that:
1. in the invention, under the condition of no solvent, 1-isothiocyanato-2-chloro-2-propylene and chlorine react under the action of a composite initiator in a microreactor to prepare the 2-chloro-5-chloromethyl thiazole. Compared with the common initiator, the composite initiator adopted by the method can be dissolved in the raw material 1-isothiocyanato-2-chloro-2-propene, so that the normal-temperature solvent-free reaction can be realized, the reaction condition is mild, the process controllability is strong, and the safety coefficient is high; and has the advantages of high reaction rate, less side reaction and the like, so that the obtained target product has high yield and purity. The reported processes all need the existence of a solvent, a solvent recovery process is inevitably needed, common organic solvents such as toluene, 1, 2-dichloroethane, methanol and the like are flammable, explosive, toxic and harmful dangerous chemicals, most of the recovery processes have the characteristics of high temperature and high pressure, complex operation and the like, and have considerable potential safety hazards, thereby forming very adverse factors for safe production. In contrast, with the increasing importance of the country on environmental protection and safety and the demand of the market on the second-generation nicotinoid insecticide thiazole pesticides, the method meets the urgent requirements of the new process of the new era, such as simple process, high safety coefficient, less pollution, high efficiency, green and environmental protection of 2-chloro-5-chloromethyl thiazole.
2. The applicant has tried to prepare 2-chloro-5-chloromethylthiazole in a microreactor by using various initiators, and found that a single initiator such as azobisisobutyronitrile and benzoyl peroxide has problems of low reaction yield and low content. The organic and inorganic mixed initiators comprise a combination of benzoyl peroxide and phosphorus chloride-free, a combination of azodiisobutyronitrile and phosphorus chloride-free and a combination of benzoyl peroxide and ferrous pyrophosphate, and the reactions of the three initiators all have the problems of low target content, low yield, high reaction temperature, reaction solvent requirement and the like. After a large number of initiator attempts, the preparation of 2-chloro-5-chloromethylthiazole at normal temperature and without solvent in a microreactor was finally determined by using chlorine gas and 1-isothiocyanato-2-chloro-2-propene as raw materials and using one of the group consisting of benzoyl peroxide (a) and N, N-dimethylaniline (B), benzoyl peroxide (a) and N, N-diethylaniline (B), and sodium metabisulfite (B) as a composite initiator for the reaction.
3. As for the amount of the composite initiator used in the present invention, the applicant found through a large number of experiments that when the amount of the composite initiator is less than 2% by mass of 1-isothiocyanato-2-chloro-2-propene, a large amount of raw materials in the reaction cannot be reacted completely, and when the amount of the composite initiator is more than 5% by mass of 1-isothiocyanato-2-chloro-2-propene, the reaction effect is equivalent to that when the amount is 5% by mass of 1-isothiocyanato-2-chloro-2-propene, and thus the amount of the composite initiator is preferably 2% to 5% by mass of 1-isothiocyanato-2-chloro-2-propene.
4. As for the selection of the mass ratio of the composite initiator component A to B in the invention, the applicant finds through a large number of experiments that when the mass ratio of A to B is lower than 1: 0.5, the raw material reaction is incomplete and byproducts are generated, and when the mass ratio of A to B is higher than 1: 1.5, the reaction effect is equivalent to 1: 1.5, so that the mass ratio of the composite initiator component A to B is preferably 1: 0.5-1.5.
5. In the invention, the chlorination reaction temperature is preferably 10-50 ℃, because when the chlorination reaction temperature is lower than 10 ℃, a large amount of raw materials cannot be completely reacted in the reaction, and when the chlorination reaction temperature is higher than 50 ℃, a large amount of polychlorinated substitutes are generated.
6. In addition, compared with the kettle type reactor adopted by the prior art, the invention has the advantages of full gas-liquid contact and good mass and heat transfer effects; mild reaction conditions, strong process controllability, high safety factor and the like. In addition, the addition of the composite initiator further accelerates the reaction rate and shortens the reaction time. The organic combination of the two overcomes the problems of low product purity and yield, more side reactions, longer reaction time, complex operation, harsh reaction conditions, large amount of three wastes and the like in the prior art, and simultaneously, the method adopts a solvent-free reaction, thereby further reducing the energy consumption and the production cost. The method has the advantages of mild process conditions, high reaction speed, high safety coefficient, easy operation, easily available raw materials, less three wastes, lower production cost, good product quality, high content and the like, and is suitable for high-efficiency green industrial production.
Detailed Description
The invention is further described below with reference to specific preferred embodiments, without thereby limiting the scope of protection of the invention.
The micro-reactor adopted in embodiments 1 to 10 is a Corning LFR, and comprises 10 plates connected in series in sequence, each plate is provided with a micro-channel, and the micro-channels on the plates are connected in sequence to form a channel for liquid to flow; (the temperature range of each plate is-60-200 ℃, the maximum value of the bearing pressure is 18bar, and the effective volume is 0.45 mL) liquid raw materials enter the microreactor from the microchannel of the first plate, and gas raw materials enter the microreactor through the second plate; the remaining plates are the mixing plates used to carry out the reaction.
Example 1
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 10 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 30.2g of 2-chloro-5-chloromethylthiazole with the content of 97.5 percent and the yield of 87.6 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Comparative example 1
0.8g of an initiator (benzoyl peroxide) was dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene with stirring to obtain a mixture. Keeping the temperature in the microreactor at 10 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 27.2g of 2-chloro-5-chloromethylthiazole with the content of 80.5% and the yield of 65% (based on 1-isothiocyanato-2-chloro-2-propene).
Comparative example 2
A dichloroethane solution containing 0.8g of an initiator (benzoyl peroxide/phosphorus chloride-free, mass ratio of the two is 1: 1) was dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene with stirring to obtain a mixed solution. Keeping the temperature in the microreactor at 10 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and sequentially carrying out hydrogen chloride removal, desolventization and distillation to obtain 29.2g of 2-chloro-5-chloromethylthiazole with the content of 88.5 percent and the yield of 77 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 2
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and then carrying out hydrogen chloride driving and distillation to obtain 30.8g of 2-chloro-5-chloromethylthiazole with the content of 99.5 percent and the yield of 91.2 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 3
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 50 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 30.3g of 2-chloro-5-chloromethylthiazole with the content of 94% and the yield of 84.8% (based on 1-isothiocyanato-2-chloro-2-propene).
Example 4
0.5g of a composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 0.5) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 30.1g of 2-chloro-5-chloromethylthiazole with the content of 99 percent and the yield of 88.7 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 5
1.3g of a composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 0.7g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 30.8g of 2-chloro-5-chloromethylthiazole with the content of 99 percent and the yield of 90.7 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 6
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1.5) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, introducing 12.8g (0.18 moL) of chlorine into a second plate of the microreactor at a speed of 0.64g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 28.8g of 2-chloro-5-chloromethylthiazole with the content of 98.5% and the yield of 84.4% (based on 1-isothiocyanato-2-chloro-2-propene).
Example 7
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.3g/min by a plunger pump, introducing 15.6g (0.22 moL) of chlorine into a second plate of the microreactor at a speed of 0.78g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride driving and distillation to obtain 30.7g of 2-chloro-5-chloromethylthiazole with the content of 97.5 percent and the yield of 89.1 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 8
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 2.6g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 1.4g/min by a mass flow meter, mixing the materials in the mixing plates, continuously feeding and discharging, collecting the reaction solution, and then carrying out hydrogen chloride driving and distillation to obtain 29g of 2-chloro-5-chloromethylthiazole with the content of 99.5 percent and the yield of 85.9 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 9
0.8g of composite initiator (a mixture of benzoyl peroxide and N, N-dimethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.9g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 1.0g/min by a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and then carrying out hydrogen chloride driving and distillation to obtain 31.5g of 2-chloro-5-chloromethylthiazole with the content of 99.5 percent and the yield of 93.3 percent (based on 1-isothiocyanato-2-chloro-2-propene).
Example 10
0.8g of a composite initiator (a mixture of benzoyl peroxide and N, N-diethylaniline, the mass ratio of the two is 1: 1) is stirred and dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.9g/min by a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 1.0g/min by a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and performing hydrogen chloride removal and distillation to obtain 30.5g of 2-chloro-5-chloromethylthiazole with the content of 99.5% and the yield of 90.3% (based on 1-isothiocyanato-2-chloro-2-propene).
Example 11
0.8g of a composite initiator (a mixture of tert-butyl hydroperoxide and sodium metabisulfite in a mass ratio of 1: 1) was dissolved in 26.6g (0.2moL) of 1-isothiocyanato-2-chloro-2-propene with stirring to obtain a mixed solution. Keeping the temperature in the microreactor at 20 ℃, pumping the mixed solution into a first plate of the microreactor at a speed of 1.9g/min through a plunger pump, simultaneously introducing 14.2g (0.2moL) of chlorine gas into a second plate of the microreactor at a speed of 1.0g/min through a mass flow meter, mixing the materials in the mixing plate, continuously feeding and discharging, collecting the reaction solution, and then carrying out hydrogen chloride removal and distillation to obtain 30g of 2-chloro-5-chloromethylthiazole with the content of 99 percent and the yield of 88.4 percent (based on 1-isothiocyanato-2-chloro-2-propene).
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above-described embodiments. All technical schemes belonging to the idea of the invention belong to the protection scope of the invention. It should be noted that modifications and embellishments within the scope of the invention may be made by those skilled in the art without departing from the principle of the invention, and such modifications and embellishments should also be considered as within the scope of the invention.
Claims (8)
1. A preparation method of 2-chloro-5-chloromethyl thiazole comprises the following steps:
in a microreactor, under the condition of no solvent, carrying out chlorination reaction on chlorine and 1-isothiocyanato-2-chloro-2-propylene under the action of a composite initiator to prepare 2-chloro-5-chloromethylthiazole;
the composite initiator comprises a component A and a component B, wherein the component A is benzoyl peroxide, and the component B is one of N, N-dimethylaniline and N, N-diethylaniline;
or the composite initiator comprises a component A and a component B, wherein the component A is tert-butyl hydroperoxide, and the component B is sodium metabisulfite.
2. The method for preparing 2-chloro-5-chloromethylthiazole according to claim 1, wherein the mass ratio of the component A to the component B in the composite initiator is 1: 0.5-1.5.
3. The method for preparing 2-chloro-5-chloromethylthiazole as claimed in claim 2, wherein the amount of the composite initiator is 2 to 5% by mass based on the 1-isothiocyanato-2-chloro-2-propene.
4. The method for preparing 2-chloro-5-chloromethylthiazole according to claim 3, wherein the molar ratio of chlorine to 1-isothiocyanato-2-chloro-2-propene is 0.9 to 1.1: 1.
5. The method for preparing 2-chloro-5-chloromethylthiazole according to claim 4, wherein the feeding speed of the chlorine gas into the microreactor is 0.64 to 1.4 g/min.
6. The method for preparing 2-chloro-5-chloromethylthiazole according to claim 5, wherein the composite initiator is dissolved in 1-isothiocyanato-2-chloro-2-propene to form a mixed solution, and the feeding speed of the mixed solution into the microreactor is 1.3 to 2.6 g/min.
7. The process for preparing 2-chloro-5-chloromethylthiazole according to claim 5 or 6, wherein the microreactor comprises a plurality of plates connected in series in sequence, each plate having microchannels, the microchannels of the plates being connected in sequence to form channels for the flow of a liquid; the mixed solution enters the microreactor from the microchannel of the first plate, and chlorine enters the microreactor through the second plate; the remaining plates are the mixing plates used to carry out the reaction.
8. The method for preparing 2-chloro-5-chloromethylthiazole according to claim 7, wherein the temperature of the chlorination reaction is 10 to 50 ℃.
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| CN1654460A (en) * | 2000-08-23 | 2005-08-17 | 辛根塔参与股份公司 | Continuous process for the preparation of pesticidal chlorothiazoles |
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