CN107935960A - The preparation method of 2 chlorine, 5 5-chloromethyl thiazole - Google Patents
The preparation method of 2 chlorine, 5 5-chloromethyl thiazole Download PDFInfo
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- CN107935960A CN107935960A CN201711465848.1A CN201711465848A CN107935960A CN 107935960 A CN107935960 A CN 107935960A CN 201711465848 A CN201711465848 A CN 201711465848A CN 107935960 A CN107935960 A CN 107935960A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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 kind of preparation method of 2 chlorine, 5 5-chloromethyl thiazole, comprise the following steps:In microreactor, under condition of no solvent, chlorine and 1 isothiocyanic acid base, 2 chlorine, 2 propylene carry out chlorination reaction under the action of composite initiator, and 2 chlorine, 5 5-chloromethyl thiazole is prepared.This method has the advantages that without solvent, of low cost, reaction condition is gentle, reaction speed is fast, the three wastes are less, technique is simple and target product yield, purity are higher.
Description
Technical field
The invention belongs to the preparing technical field of pesticide intermediate, more particularly to a kind of system of 2- chloro-5-chloromethyl thiazoles
Preparation Method.
Background technology
2- chloro-5-chloromethyl thiazoles(Abbreviation CCMT)It is second generation nicotinic insecticide thiazoles pesticide Diacloden, thiophene worm
Amine key intermediate, can be also condensed by the N-H of alkylated reaction and heterocycle and prepare a series of insecticidal/acaricidal agent, and for resisting
The synthesis of the intermediate 5-Hydroxymethylthiazole of AIDS medicine Ritonavirs.
Thiazoles pesticide simulates the mechanism of action of nicotiana alkaloids, by acting on nAChR, to routine
Pyrethroid, organophosphorus compounds, carbamate insecticides no interactions resistance, while also have degraded it is rapid,
Half-life short in the soil, to bio-safety the advantages of, can controlling sucking insects and all kinds of beetles and Lepidoptera evil extensively
Worm etc..Diacloden, clothianidin molecular structure in introduce chlorine thiazole structure, compared to first generation nicotinic insecticide imidacloprid
Deng having widened insecticidal spectrum, improved bioactivity, be known as the Representative Cultivars of second generation nicotine compound.As Syngenta
Grand strategy kind, Diacloden global marketing in 2015 reaches 1,100,000,000 dollars, ranks insecticide global marketing seniority among brothers and sisters second;Thiophene
Worm piperazine is as insecticide and seed treatment, in more than 50, whole world country, more than 115 in be registered use in crop.Together
The important kind for the novel nicotinamide insecticide that chemical weapons field/Bayer is developed jointly is lived by sample Japan, and clothianidin was in whole world pin in 2015
Sell and reach 3.5 hundred million dollars, rank insecticide global marketing seniority among brothers and sisters the tenth.
The preparation method for the 2- chloro-5-chloromethyl thiazoles reported both at home and abroad at present is more, mainly there is following seven kinds:
(1)1- isothiocyanic acids base -2- propylene reacts at a reflux temperature with substantial amounts of chlorine, and the chloro- 5- of 2- are obtained through distillation, rectifying
5-chloromethyl thiazole(US4748432).
(2)The chloro- 1- propylene of 1- isothiocyanic acid bases -3- is with chlorine or chlorosulfuric acid in catalyst(Iodine or Lewis acid)Effect
Under, 2- chloro-5-chloromethyl thiazoles are prepared in reaction(US5705652).
(3)1- isothiocyanic acids base -2- chloro-2-propenes are reacted with chlorine or chlorosulfuric acid, are obtained through post-processing operations such as precipitations
2- chloro-5-chloromethyl thiazoles(US6214998).
(4)Using methacrylaldehyde as raw material, -5 hydroxymethylthiazole of 2- amino is prepared, through diazo-reaction, then a large amount of
Hydrochloric acid in hydrolysis, heating 2- chloro-5-chloromethyl thiazoles are prepared(US6566530).
(5)2- amino -5- methylthiazols hydrolyze, heating obtains the chloro- 5- first of 2- through diazo-reaction in substantial amounts of hydrochloric acid
Base thiazole, is then prepared 2- chloro-5-chloromethyl thiazoles with the reaction of N- chlorinated succinimides.
(6)5-Hydroxymethylthiazole is with N- chlorinated succinimides in catalyst(Iodine)Under the action of, reaction prepares the chloro- 5- of 2-
5-chloromethyl thiazole(CN106749086A).
(7)Using 1- isothiocyanic acids base -2- chloro-2-propenes and chlorine as raw material, hydrogen chloride gas are passed through after reaction or add dense salt
2- chloro-5-chloromethyl thiazole hydrochlorides are prepared in acid, and the chloro- 5- chlorine of 2- is obtained by post-processing operations such as filtering, precipitation, washings
Methylthiazol(CN105949145A).
Above-mentioned(1)There is the problems such as amount of chlorine needed is larger, and side reaction is more in kind method.Purity and yield are equal at the same time
It is relatively low.The(2)The suitable inverse proportion of the chloro- 1- propylene of raw material 1- isothiocyanic acid bases -3- has a great influence reaction yield in kind method, together
When catalyst post processing it is more complicated, be not suitable for industrialized production.The(3)Kind method reaction condition is gentle, easy to operate, compares
Suitable industrialized production, but its there are the problems such as the reaction time is longer, product purity is not high.The(4)Kind and the(5)Kind method is equal
There are reaction yield is low, diazo-reaction condition is harsh, hydrochloric acid dosage is big and the problems such as can not recycling, is not suitable for large-scale industry
Metaplasia is produced.The(6)Kind of method 5 kinds of methods earlier above, solve the problems, such as that yield and purity is not high, but its there are the reaction time compared with
It is long, operate the problems such as complex, temperature requirement is harsh;Iodine is employed as catalyst, N- chlorinated succinimides at the same time
It is also higher as chlorination reagent, production cost.The(7)Kind method is longer there are the reaction time, and washes amount is larger and can not
The problems such as recycling, be not suitable for green cleaned industry metaplasia production.
The content of the invention
The technical problem to be solved in the present invention is overcome the deficiencies of the prior art and provide it is a kind of without solvent, it is of low cost,
The 2- chloro-5-chloromethyl thiazoles that reaction condition is gentle, reaction speed is fast, the three wastes are less, technique is simple and yield, purity are higher
Preparation method.
In order to solve the above technical problems, the present invention uses following technical scheme:
A kind of preparation method of 2- chloro-5-chloromethyl thiazoles, comprises the following steps:
In microreactor, under condition of no solvent, the work of chlorine and 1- isothiocyanic acids base -2- chloro-2-propenes in composite initiator
Chlorination reaction is carried out under, 2- chloro-5-chloromethyl thiazoles are prepared.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the composite initiator includes component A and B groups
Point, the component A is benzoyl peroxide, and the B component is one kind in n,N-Dimethylaniline and N, N- diethylaniline.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the composite initiator includes component A and B groups
Point, the component A is tert-butyl hydroperoxide, and the B component is sodium pyrosulfite.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that in the composite initiator, component A and B groups
The mass ratio divided is 1: 0.5~1.5.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the dosage of the composite initiator is the different sulphur of 1-
The 2%~5% of cyanic acid base -2- chloro-2-propene quality.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the chlorine and 1- isothiocyanic acid bases -2- are chloro-
The molar ratio of 2- propylene is 0.9~1.1: 1.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the chlorine enters the charging in microreactor
Speed is 0.64~1.4g/min.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the composite initiator is dissolved in 1- isothiocyanic acids
Mixed liquor is formed in base -2- chloro-2-propenes, the charging rate that the mixed liquor enters in microreactor is 1.3~2.6g/
min。
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the microreactor is sequentially connected in series including polylith
Plate, every block of plate is equipped with microchannel, and the microchannel on each plate is sequentially connected the passage for forming and flowing for liquid;The mixed liquor
Enter from the microchannel of first block of plate in microreactor, chlorine is entered in microreactor by second block of plate;Remaining plate be for
The mixed plate reacted.
The preparation method of above-mentioned 2- chloro-5-chloromethyl thiazoles, it is preferred that the temperature of the chlorination reaction is 10~50
℃。
Compared with prior art, the advantage of the invention is that:
1st, the present invention is under solvent-free state, and in microreactor, 1- isothiocyanic acid base -2- chloro-2-propenes are with chlorine compound
2- chloro-5-chloromethyl thiazoles have been prepared in reaction under the action of initiator.It is anti-that chlorination is carried out as a result of composite initiator
Should, compared to common initiator, the composite initiator that this method uses can be dissolved in the chloro- 2- third of raw material 1- isothiocyanic acid bases -2-
In alkene, it is possible to achieve room temperature, solvent-free reaction, reaction condition is gentle, and process controllability is strong and safety coefficient is high;And with reaction
The advantages that speed is fast, side reaction is few, thus the target product yield of gained, purity are high.And the technique reported is required to solvent
In the presence of inevitably needing solvent recovery process, common organic solvent, as toluene, 1,2- dichloroethanes, methanol etc. are all
Inflammable and explosive, poisonous and hazardous hazardous chemical, its removal process have the characteristics that high temperature and pressure, complicated, exist mostly
Sizable security risk, very unfavorable factor is constituted to safety in production.In contrast, as country is to environmental protection, safety
Pay attention to day by day and market to the demand of second generation nicotinic insecticide thiazoles pesticide, this method meets new era requirement
Technique is simple, safety coefficient is high, pollutes less, an urgent demand of the 2- chloro-5-chloromethyl thiazole new processes of high effective green environmentally friendly.
2nd, applicant attempted a variety of initiators and 2- chloro-5-chloromethyl thiazoles is prepared in microreactor, it turns out that, it is single
One initiator such as azodiisobutyronitrile and benzoyl peroxide, both there are reaction yield, content is relatively low the problem of.It is organic and
Inorganic mixed initiator has benzoyl peroxide and combination without phosphorus chloride, azodiisobutyronitrile and combination without phosphorus chloride, mistake
The combination of Benzoyl Oxide and ferrous pyrophosphate, the reaction that above-mentioned three kinds of initiators participate in there are object content, yield compared with
Low, reaction temperature is higher, and the problems such as need reaction dissolvent.After the trial of a large amount of initiators, finally determine with chlorine
It is raw material with 1- isothiocyanic acid base -2- chloro-2-propenes, using benzoyl peroxide(A)And n,N-Dimethylaniline(B)Group
Close, benzoyl peroxide(A)And N, N- diethylaniline(B)Combination, tert-butyl hydroperoxide(A)And sodium pyrosulfite(B)
Combination composite initiator of the one of which as the reaction, may be implemented in microreactor under room temperature, condition of no solvent
Prepare 2- chloro-5-chloromethyl thiazoles.
3rd, found for the dosage of composite initiator in the present invention, applicant by abundant experimental results, when compound initiation
When the dosage of agent is less than the 2% of 1- isothiocyanic acid base -2- chloro-2-propene quality, there is substantial amounts of raw material not reacted in reaction also
Entirely, when the dosage of composite initiator is higher than the 5% of 1- isothiocyanic acid base -2- chloro-2-propene quality, its reaction effect and dosage
For 1- isothiocyanic acid base -2- chloro-2-propene quality 5% when suitable, therefore preferred 1- isothiocyanic acids of dosage of composite initiator
The 2%~5% of base -2- chloro-2-propene quality.
4th, sent out for the selection of A: B mass ratio of composite initiator component in the present invention, applicant by abundant experimental results
Existing, when A: B mass ratio is less than 1: 0.5, raw material reaction not exclusively and has accessory substance generation, works as A: B mass ratio and is higher than
For 1: 1.5 when, quite, therefore A: B mass ratio of composite initiator component is preferably 1: 0.5~1.5 to its reaction effect and 1: 1.5.
5th, in the present invention, the temperature of chlorination reaction is preferably 10~50 DEG C, this is because, chlorination reaction temperature is less than 10 DEG C
When, have that substantial amounts of raw material can not the reaction was complete in reaction, when reaction temperature is more than 50 DEG C, then there are substantial amounts of more chlorine substitution produce
It is raw.
6th, in addition, the tank reactor used compared to former technique, the present invention is abundant with gas-liquid contact, mass-and heat-transfer effect
It is good;The advantages that reaction condition is gentle, and process controllability is strong, and safety coefficient is high.In addition the addition of composite initiator, also further adds
Fast reaction rate, shortens the reaction time.It is relatively low that both combination overcomes product purity and yield in original technique,
The problems such as side reaction is more, and the reaction time is longer, complicated, severe reaction conditions and larger quantity of three wastes, while this method is adopted
With solvent-free reaction, energy consumption and production cost reduce further.This method has that process conditions are gentle, reaction speed is fast, peace
Overall coefficient is high, and easy to operate, raw material is easy to get, and the three wastes are few, and production cost is relatively low, superior product quality, the advantages that content is high, is adapted to efficient
Green industrialized production.
Embodiment
Below in conjunction with specific preferred embodiment, the invention will be further described, but not thereby limiting the invention
Protection domain.
The microreactor model Corning LFR used in embodiment 1~10, the microreactor are gone here and there successively including 10 pieces
The plate of connection, every block of plate are equipped with microchannel, and the microchannel on each plate is sequentially connected the passage for forming and flowing for liquid;(Every block of plate
Temperature range -60~200 DEG C, it is 18bar, effective volume 0.45mL to bear Pressure maximum value)Liquid charging stock is from first piece
The microchannel of plate enters in microreactor, and gas raw material is entered in microreactor by second block of plate;Remaining plate is for carrying out
The mixed plate of reaction.
Embodiment 1
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 10 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30.2g, content
97.5%, yield 87.6%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Comparative example 1
By 0.8g initiators(Benzoyl peroxide)Stirring is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)
In, obtain mixed liquor.It is 10 DEG C to keep temperature in microreactor, is squeezed into mixed liquor with the speed of 1.3g/min by plunger pump
First block of plate of microreactor, while by mass flowmenter by chlorine 14.2g(0.2moL)It is passed through with the speed of 0.7g/min
Second block of plate of microreactor, material are mixed in mixed plate, and serialization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and steaming
Evaporate to obtain 2- chloro-5-chloromethyl thiazole 27.2g, content 80.5%, yield 65%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Comparative example 2
Will be dissolved with 0.8g initiators(Benzoyl peroxide/without phosphorus chloride, both mass ratioes 1: 1)Dichloroethane solution, stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 10 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then successively through catching up with hydrogen chloride, precipitation and distillation to obtain 2- chloro-5-chloromethyl thiazoles
29.2g, content 88.5%, yield 77%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 2
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30.8g, content
99.5%, yield 91.2% (1- isothiocyanic acid base -2- chloro-2-propenes meter).
Embodiment 3
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 50 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation obtains 2- chloro-5-chloromethyl thiazole 30.3g, content 94%,
Yield 84.8%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 4
By 0.5g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 0.5)Stir
Mix and be dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.Temperature is in holding microreactor
20 DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while passes through quality stream
Gauge is by chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate,
Serialization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30.1g, content
99%, yield 88.7%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 5
By 1.3g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 0.7g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation obtains 2- chloro-5-chloromethyl thiazole 30.8g, content 99%,
Yield 90.7%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 6
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1.5)Stir
Mix and be dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.Temperature is in holding microreactor
20 DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while passes through quality stream
Gauge is by chlorine 12.8g(0.18moL)Second block of plate of microreactor is passed through with the speed of 0.64g/min, material is mixed in mixed plate
Close, serialization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 28.8g, contain
Amount 98.5%, yield 84.4%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 7
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.3g/min, while pass through mass flow
Count chlorine 15.6g(0.22moL)Second block of plate of microreactor is passed through with the speed of 0.78g/min, material is mixed in mixed plate,
Serialization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30.7g, content
97.5%, yield 89.1%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 8
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 2.6g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 1.4g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation obtains 2- chloro-5-chloromethyl thiazole 29g, content 99.5%,
Yield 85.9%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 9
By 0.8g composite initiators(The mixture of benzoyl peroxide and n,N-Dimethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.9g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 1.0g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 31.5g, content
99.5%, yield 93.3%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 10
By 0.8g composite initiators(The mixture of benzoyl peroxide and N, N- diethylaniline, both mass ratioes 1: 1)Stirring
It is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.9g/min, while pass through mass flow
Chlorine 14.2g (0.2moL) is passed through second block of plate of microreactor by meter with the speed of 1.0g/min, and material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30.5g, content
99.5%, yield 90.3%(1- isothiocyanic acid base -2- chloro-2-propene meters).
Embodiment 11
By 0.8g composite initiators(The mixture of tert-butyl hydroperoxide and sodium pyrosulfite, both mass ratioes 1: 1)Stir molten
In 1- isothiocyanic acid base -2- chloro-2-propenes 26.6g(0.2moL)In, obtain mixed liquor.It is 20 to keep temperature in microreactor
DEG C, mixed liquor is squeezed into first block of plate of microreactor by plunger pump with the speed of 1.9g/min, while pass through mass flow
Count chlorine 14.2g(0.2moL)Second block of plate of microreactor is passed through with the speed of 1.0g/min, material is mixed in mixed plate, even
Continuousization charging discharging, collects reaction solution, then through catching up with hydrogen chloride and distillation to obtain 2- chloro-5-chloromethyl thiazole 30g, content 99%, is received
Rate 88.4%(1- isothiocyanic acid base -2- chloro-2-propene meters).
The above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-mentioned implementation
Example.All technical solutions belonged under thinking of the present invention belong to protection scope of the present invention.It is noted that for the art
Those of ordinary skill for, improvements and modifications without departing from the principle of the present invention, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of 2- chloro-5-chloromethyl thiazoles, comprises the following steps:
In microreactor, under condition of no solvent, the work of chlorine and 1- isothiocyanic acids base -2- chloro-2-propenes in composite initiator
Chlorination reaction is carried out under, 2- chloro-5-chloromethyl thiazoles are prepared.
2. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 1, it is characterised in that the compound initiation
Agent includes component A and B component, and the component A is benzoyl peroxide, and the B component is n,N-Dimethylaniline and N, N- bis-
One kind in ethyl aniline.
3. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 1, it is characterised in that the compound initiation
Agent includes component A and B component, and the component A is tert-butyl hydroperoxide, and the B component is sodium pyrosulfite.
4. the preparation method of the 2- chloro-5-chloromethyl thiazoles according to Claims 2 or 3, it is characterised in that described compound to draw
Send out in agent, the mass ratio of component A and B component is 1: 0.5~1.5.
5. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 4, it is characterised in that the compound initiation
The dosage of agent is the 2%~5% of 1- isothiocyanic acid base -2- chloro-2-propene quality.
6. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 5, it is characterised in that the chlorine and 1-
The molar ratio of isothiocyanic acid base -2- chloro-2-propenes is 0.9~1.1: 1.
7. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 6, it is characterised in that the chlorine enters
Charging rate in microreactor is 0.64~1.4g/min.
8. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 7, it is characterised in that the compound initiation
Agent, which is dissolved in 1- isothiocyanic acid base -2- chloro-2-propenes, forms mixed liquor, and the mixed liquor enters the charging speed in microreactor
Spend for 1.3~2.6g/min.
9. the preparation method of the 2- chloro-5-chloromethyl thiazoles according to claim 7 or 8, it is characterised in that micro- reaction
Device includes the plate that is sequentially connected in series of polylith, and every block of plate is equipped with microchannel, and the microchannel on each plate is sequentially connected to form flows for liquid
Dynamic passage;The mixed liquor enters in microreactor from the microchannel of first block of plate, and chlorine is by second block of plate into anti-in a subtle way
Answer in device;Remaining plate is the mixed plate for being reacted.
10. the preparation method of 2- chloro-5-chloromethyl thiazoles according to claim 9, it is characterised in that the chlorination reaction
Temperature be 10~50 DEG C.
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CN111808043A (en) * | 2020-07-23 | 2020-10-23 | 岳阳景嘉化工有限公司 | Continuous synthesis method of 2-chloro-5-chloromethyl thiazole |
CN116082271A (en) * | 2022-12-05 | 2023-05-09 | 济宁福顺化工有限公司 | Method for preparing 2-chloro-5-chloromethylthiazole by one-step method |
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CN1401646A (en) * | 2001-08-08 | 2003-03-12 | 南通江山农药化工股份有限公司 | Insecticidal compound and production process thereof |
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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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 |
CN1401646A (en) * | 2001-08-08 | 2003-03-12 | 南通江山农药化工股份有限公司 | Insecticidal compound and production process thereof |
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CN111808043A (en) * | 2020-07-23 | 2020-10-23 | 岳阳景嘉化工有限公司 | Continuous synthesis method of 2-chloro-5-chloromethyl thiazole |
CN116082271A (en) * | 2022-12-05 | 2023-05-09 | 济宁福顺化工有限公司 | Method for preparing 2-chloro-5-chloromethylthiazole by one-step method |
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