CN104119291A - Method for preparing 2-chlorine-5 chloromethyl thiazole - Google Patents
Method for preparing 2-chlorine-5 chloromethyl thiazole Download PDFInfo
- Publication number
- CN104119291A CN104119291A CN201410308830.0A CN201410308830A CN104119291A CN 104119291 A CN104119291 A CN 104119291A CN 201410308830 A CN201410308830 A CN 201410308830A CN 104119291 A CN104119291 A CN 104119291A
- Authority
- CN
- China
- Prior art keywords
- preparation
- chloro
- solvent
- chloromethyl
- temperature
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention relates to a method for preparing 2-chlorine-5 chloromethyl thiazole. The method comprises the following steps of: preparing 2-chlorine-5 chloromethyl thiazole by taking 2,3-dichloropropene, sodium sulfocyanate, sulfuryl chloride sulfuryl chloride and the like as main raw materials and changing a reaction solvent, reaction temperature and the like; purifying the product. An experimental result indicates that the method in which 2-chlorine-5 chloromethyl thiazole with the purity of 99% is prepared from 2,3-dichloropropene and sodium sulfocyanate through a one-pot process sequentially including substitution reaction, isomerization reaction and chlorination-cyclization reaction by taking methylbenzene as a solvent has the advantages of simple operation, few side reactions and high efficiency.
Description
Technical field:
The present invention relates to a kind of preparation method of 2-chloro-5-chloromethyl thiazole, belong to chemical intermediate Technology field.
Background technology:
In the middle of up-to-date chemical pesticide research, heterocyclic compound has occupied main status.It in pesticide patent, more than 90% is all heterogeneous ring compound.Especially the thiazole compound taking Diacloden, imidaclothiz etc. as representative, owing to having, consumption is low, wide spectrum, efficient, with other sterilant without features such as cross resistances, become one of focus of domestic and international novel pesticide exploitation.2-chloro-5-chloromethyl thiazole, be called for short CCMT, for white or micro-yellow crystals, temperature is colourless to light yellow liquid during higher than 25 DEG C, it is the key intermediate of synthetic chloro thiazoles agricultural chemicals, the nicotinoids Pesticidal compound of a new generations such as Diacloden, clothianidin, AKD-1022, imidaclothiz can be synthesized, synthetic a series of insecticidal/acaricidal agent can also be reacted by alkylated reaction with the N-H on heterocycle.Therefore, 2-chloro-5-chloromethyl thiazole has broad application prospects and researching value.
Have much for the synthetic method of 2-chloro-5-chloromethyl thiazole both at home and abroad at present, according to the difference of starting raw material, chlorizating agent and operational path, be mainly divided into following several:
(1) the acrylonitrile-chlorinated method of 1-isothiocyanic acid base-2-: the chloroformic solution of chlorine (maybe can produce the compound of chlorine, as sulfuryl chloride) and 1-isothiocyanic acid base-2-propylene is injected in the chloroform of backflow simultaneously and reacts.The a large amount of excessive chlorine of this reaction needed, side reaction is more, and crude product purity is 41.1%, and the purity after simple distillation is only also 47.8%, yield 50.4%.Need just can obtain sterling by rectifying.Although this synthetic method process is simple, pass into a large amount of chlorine and easily pollute, the waste of cost, and also the yield of product is very low, and by product is more.
(2) 1-isothiocyanic acid base-2-chloro-2-propene chlorination process: cooling lower to passing into chlorine (or dripping sulfuryl chloride) in the chloroformic solution of 1-isothiocyanic acid base-2-chloro-2-propene at ice bath (or water-bath), then 40 DEG C of following reactions of temperature control, until heat release stops.The advantage of this method is that the consumption of chlorine (maybe can produce the compound of chlorine, as sulfuryl chloride) greatly reduces, and side reaction is relatively less, through distillation after more than purity to 90%, yield 82%.But synthetic 1-isothiocyanic acid base-2-chloro-2-propene need be used 2 of costliness, and the chloro-1-propylene of 3-bis-is raw material, and production cost is larger, and reaction is very high to the requirement of temperature, and it is also more difficult in industrial production, to control.
(3) 5-methylene radical-1,3-thiazolidine-2-thio-ketone chlorination process: U.Kraatz and A.C.OSulliva philosophy have been reported with chlorine or sulfuryl chloride 5-methylene radical-1,3-thiazolidine-2-thio-ketone carries out chlorination, can obtain CCT with good yield and purity (yield 72%).And 5-methylene radical-1,3-thiazoles alkane-2-thioketones can be reacted by 1-propargylamine synthetic (yield 90%) with dithiocarbonic anhydride.
In above-mentioned reaction, all come with some shortcomings more or less, for example: the acrylonitrile-chlorinated method of 1-isothiocyanic acid base-2-, in reaction process side reaction more, starting material chlorine etc. wastes is serious, and can cause topsoil, the product yield obtaining is not high; 1-isothiocyanic acid base-2-chloro-2-propene chlorination process, the process of reaction requires too highly to temperature, and in actual mechanical process, difficulty is larger.
Summary of the invention:
The present invention is directed to above shortcoming, provide a kind of reaction distance short, simple to operate, the preparation method of the 2-chloro-5-chloromethyl thiazole that efficiency is high.
The invention provides a kind of preparation method of 2-chloro-5-chloromethyl thiazole, comprise Sodium Thiocyanate 99,2,3-dichloropropylene mixes generation 1-thiocyanogen-2-propenyl chloride, high temp isomerizing and sulfuryl chloride mixing and carries out chlorination, and the step such as the purification of chloro-5 5-chloromethyl thiazoles of final product 2-, it is characterized in that adopting the response strategy of " one kettle way ", shorten reaction distance, simplified experimental implementation, reduce the generation of side reaction, reached the object of raising the efficiency.
The preparation method of above-mentioned 2-chloro-5-chloromethyl thiazole, comprises the following steps:
(a) by Sodium Thiocyanate 99,2,3-dichloropropylene is mixed in solvent, obtains 1-thiocyanogen-2-propenyl chloride.
(b) the 1-thiocyanogen-2-propenyl chloride obtaining in above-mentioned (a) is carried out to high temp isomerizing.
(c) mixture obtaining in above-mentioned (b) and sulfuryl chloride are mixed in solvent, obtain compound 2-chloro-5-chloromethyl thiazole.
(d) the 2-chloro-5-chloromethyl thiazole generating in above-mentioned (c) is purified purification process.
Described preparation method, in step (a), taking Tetrabutyl amonium bromide as phase-transfer catalyst; The temperature of mixing is 0 DEG C to 100 DEG C, preferably 60 DEG C to 100 DEG C, and most preferably 80 DEG C.
Further, in step (a), the solvent of mixing mainly contains water, toluene, preferably toluene.
Further, in step (b), isomerisation temperature is 100 DEG C to 120 DEG C, preferably 120 DEG C.
Further, in step (b), the solvent that reacts required is equal to (a).
Further, in step (c), the temperature of mixing is 60 DEG C.
Further, in step (c), the preferred acetonitrile of solvent of mixing.
Further, in step (d), directly pass into hydrogen chloride gas to the reaction system of step (c) and generate 2-chloro-5-chloromethyl thiazole hydrochloride.
Further, in step (d), 2-chloro-5-chloromethyl thiazole hydrochloride is dissolved in water, in then carrying out with the solution of 5% sodium carbonate and crystallization.
Further, in step (d), the temperature of crystallization is 0 DEG C.
The preparation method of the 2-chloro-5-chloromethyl thiazole that the inventive method provides, the feature having is as follows:
(1) response strategy of employing " one kettle way ", has shortened reaction distance, has simplified experimental implementation.
(2) in experimentation, do not extract, the step such as purify intermediates, reduced the loss of product in preparation process.
(3) this technique can be carried out large-scale production, and feasibility is strong.
Embodiment:
Contriver has developed a technological line for the production of 2-chloro-5-chloromethyl thiazole (1).
The preparation method who the invention provides 2-chloro-5-chloromethyl thiazole, comprises the following steps:
(a) by Sodium Thiocyanate 99,2,3-dichloropropylene is mixed in solvent, obtains 1-thiocyanogen-2-propenyl chloride (2).
(b) (2) that in above-mentioned (a), obtain are carried out to high temp isomerizing and generate 1-isothiocyano-2-propenyl chloride (3).
(c) (3) that in above-mentioned (b), obtain and sulfuryl chloride are mixed in solvent, obtain chloro-5 5-chloromethyl thiazoles of compound 2-.
(d) chloro-5 5-chloromethyl thiazoles of 2-that generate in above-mentioned (c) are purified purification process.
Below in conjunction with specific embodiment, further set forth the present invention.These embodiment only, for the present invention is described, limit the scope of the invention and be not used in.As non-definition separately, the familiar same meaning of all specialties used and scientific words and one skilled in the art in literary composition.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The effect that only presents a demonstration of better implementation method described in literary composition and material.
Embodiment 1
Step 1, replacement-isomerization reaction
In 500mL three-necked bottle, add 100g Sodium Thiocyanate 99 (1.23mol), 2.5g Tetrabutyl amonium bromide, 200mL toluene, under agitation slowly drips 2 of accurate measurement, 3-dichloropropylene 108g (0.97mol).Connect prolong condensing reflux in 80 DEG C of oil baths and after 4 hours, be directly warming up to 120 DEG C of reactions 3 hours (experimental phenomena: be transformed into the liquid of chocolate by original yellow liquid and white solid, be transformed into the liquid of black non transparent after high temperature isomery).Question response finishes cooling, on Rotary Evaporators, steams and desolventizes toluene, obtains the product 117.5g of black non transparent.Product and the toluene being steamed out are carried out to gas chromatographic analysis (gas phase condition: 55 DEG C of lasting 2min, are elevated to 250 DEG C with the speed of 20 DEG C of per minutes), and product purity is 93%, and yield is 81.3%.The product that contains 9% left and right in the toluene steaming.
Step 2, chlorination-ring-closure reaction
In 500mL three-necked bottle, add above-mentioned product 1-isothiocyano-2-propenyl chloride 117.5g (purity 93%), acetonitrile 450mL, under agitation slowly drip the sulfuryl chloride 184g (1.35mol) of accurate measurement, drip rear stirring hour, then condensing reflux 3 hours (experimental phenomena: become grey black liquid by black liquor) in the oil bath of 60 DEG C, reaction finishes directly to carry out next step afterwards.
Step 3,
Taking 400g sodium-chlor joins in the middle of filter flask, the vitriol oil that measures 50mL is added to constant pressure funnel, slowly be added drop-wise to and filter in the middle of bottle, by produce hydrogen chloride gas to be passed into the liquid level of three-necked bottle by conduit following and constantly stir, allow it react in the middle of three-necked bottle is placed in to ice-water bath.Observing response is found, precipitates and substantially separated out completely when reaction proceeds to 4 hours, and the 2-chloro-5-chloromethyl thiazole hydrochloride of separating out is filtered.
The product filtering out is proceeded in beaker, under the condition of heating, slowly toward dripping 5% aqueous sodium carbonate in beaker until weakly alkaline, and constantly stir with glass stick, in the process of product dissolving, constantly have bubble to emerge, gradually product dissolves completely, occurs the liquid of oily.Subsequently beaker is placed in to ice-water bath, has gradually tawny solid to separate out, after treating that product is separated out completely, filter, and constantly wash product with water, dry, finally obtain jonquilleous crystal 108g, liquid-phase chromatographic analysis product purity reaches more than 99%, and overall yield is 67%.
Claims (10)
1. a preparation method for chloro-5 5-chloromethyl thiazoles of structure 2-as shown in Equation 1,
It is characterized in that, said method comprising the steps of:
(a) by Sodium Thiocyanate 99,2,3-dichloropropylene is mixed in solvent, obtains 1-thiocyanogen-2-propenyl chloride.
(b) the 1-thiocyanogen-2-propenyl chloride obtaining in above-mentioned (a) is carried out to high temp isomerizing.
(c) mixture obtaining in above-mentioned (b) and sulfuryl chloride are mixed in solvent, obtain chloro-5 5-chloromethyl thiazoles of compound 2-.
(d) chloro-5 5-chloromethyl thiazoles of 2-that generate in above-mentioned (c) are purified purification process.
2. preparation method as claimed in claim 1, is characterized in that, in step (a), taking Tetrabutyl amonium bromide as phase-transfer catalyst.
3. preparation method as claimed in claim 1, is characterized in that, in step (a), the temperature of mixing is 0 DEG C-100 DEG C.
4. preparation method as claimed in claim 3, is characterized in that, in step (a), the temperature of mixing is 80 DEG C.
5. preparation method as claimed in claim 1, is characterized in that, in step (a) and step (c), solvent phase is same, is water or toluene.
6. preparation method as claimed in claim 5, is characterized in that, in step (a) and step (c), solvent is toluene.
7. preparation method as claimed in claim 1, is characterized in that, in step (b), isomerisation temperature is 100 DEG C-120 DEG C.
8. preparation method as claimed in claim 1, is characterized in that, in step (c), the temperature of mixing is 60 DEG C.
9. preparation method as claimed in claim 1, is characterized in that, in step (c), the solvent of mixing is acetonitrile.
10. preparation method as claimed in claim 1, is characterized in that, the method for step (d) purifying comprises the following steps: directly pass into hydrogen chloride gas to the reaction system of step (c) and generate the chloro-5 5-chloromethyl thiazole hydrochlorides of 2-; Chloro-2-5 5-chloromethyl thiazole hydrochlorides are dissolved in water, and in then carrying out with the solution of 5% sodium carbonate and crystallization, the temperature of crystallization is 0 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410308830.0A CN104119291A (en) | 2014-06-30 | 2014-06-30 | Method for preparing 2-chlorine-5 chloromethyl thiazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410308830.0A CN104119291A (en) | 2014-06-30 | 2014-06-30 | Method for preparing 2-chlorine-5 chloromethyl thiazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104119291A true CN104119291A (en) | 2014-10-29 |
Family
ID=51764957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410308830.0A Pending CN104119291A (en) | 2014-06-30 | 2014-06-30 | Method for preparing 2-chlorine-5 chloromethyl thiazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104119291A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105254584A (en) * | 2015-11-20 | 2016-01-20 | 河北德瑞化工有限公司 | Preparation method of 2-chloro-5-chloromethyl thiazole |
| CN109776446A (en) * | 2019-01-31 | 2019-05-21 | 河北科技大学 | A kind of synthetic method of 2- chloro-5-chloromethyl thiazole |
| CN110240555A (en) * | 2019-06-24 | 2019-09-17 | 宁夏贝利特生物科技有限公司 | A kind of synthetic method of 1- isothiocyanic acid base -2- chloro-2-propene |
| CN110252211A (en) * | 2019-07-15 | 2019-09-20 | 宁夏贝利特生物科技有限公司 | The method of 2- chloro-5-chloromethyl thiazole is continuously synthesized in a kind of tube type falling-film reactor |
| CN113004218A (en) * | 2020-12-10 | 2021-06-22 | 怀仁市普惠生物科技有限公司 | Preparation method of dichloro pentachloromethyl thiazole |
| CN113121465A (en) * | 2021-05-28 | 2021-07-16 | 安徽海顺化工有限公司 | Synthesis process of 2-chloro-5-chloromethyl thiazole |
| CN113603527A (en) * | 2021-08-05 | 2021-11-05 | 安徽省司尔特肥业股份有限公司 | High-yield and high-efficiency special fertilizer for cotton and preparation method thereof |
| CN115109008A (en) * | 2022-07-05 | 2022-09-27 | 山西玉龙化工有限公司 | Method for prolonging reuse of toluene solvent in preparation of 2-chloro-5-chloromethyl thiazole |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5180833A (en) * | 1990-03-16 | 1993-01-19 | Takeda Chemical Industries, Ltd. | Process for the preparation of chlorothiazole derivatives |
| JP2000143649A (en) * | 1998-11-16 | 2000-05-26 | Kuraray Co Ltd | Production of 2-chloro-5-chloromethyl-1,3-thiazole |
| 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 |
| CN1483320A (en) * | 2003-07-31 | 2004-03-24 | 南开大学 | Heterocyclic ring contained methylamine cyanoacrylate compound and weeding activity |
-
2014
- 2014-06-30 CN CN201410308830.0A patent/CN104119291A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5180833A (en) * | 1990-03-16 | 1993-01-19 | Takeda Chemical Industries, Ltd. | Process for the preparation of chlorothiazole derivatives |
| JP2000143649A (en) * | 1998-11-16 | 2000-05-26 | Kuraray Co Ltd | Production of 2-chloro-5-chloromethyl-1,3-thiazole |
| 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 |
| CN1483320A (en) * | 2003-07-31 | 2004-03-24 | 南开大学 | Heterocyclic ring contained methylamine cyanoacrylate compound and weeding activity |
Non-Patent Citations (2)
| Title |
|---|
| 吴建 等: "2-氯-5-氯甲基噻唑合成改进", 《浙江化工》, vol. 37, no. 10, 31 October 2006 (2006-10-31), pages 1 - 3 * |
| 张海滨 等: "2-氯-5-氯甲基-1,3-噻唑提纯新方法", 《精细化工中间体》, vol. 36, no. 5, 31 October 2006 (2006-10-31), pages 50 - 51 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105254584A (en) * | 2015-11-20 | 2016-01-20 | 河北德瑞化工有限公司 | Preparation method of 2-chloro-5-chloromethyl thiazole |
| CN105254584B (en) * | 2015-11-20 | 2018-01-02 | 河北德瑞化工有限公司 | The preparation method of the 5-chloromethyl thiazole of 2 chlorine 5 |
| CN109776446A (en) * | 2019-01-31 | 2019-05-21 | 河北科技大学 | A kind of synthetic method of 2- chloro-5-chloromethyl thiazole |
| CN110240555A (en) * | 2019-06-24 | 2019-09-17 | 宁夏贝利特生物科技有限公司 | A kind of synthetic method of 1- isothiocyanic acid base -2- chloro-2-propene |
| CN110252211A (en) * | 2019-07-15 | 2019-09-20 | 宁夏贝利特生物科技有限公司 | The method of 2- chloro-5-chloromethyl thiazole is continuously synthesized in a kind of tube type falling-film reactor |
| CN113004218A (en) * | 2020-12-10 | 2021-06-22 | 怀仁市普惠生物科技有限公司 | Preparation method of dichloro pentachloromethyl thiazole |
| CN113121465A (en) * | 2021-05-28 | 2021-07-16 | 安徽海顺化工有限公司 | Synthesis process of 2-chloro-5-chloromethyl thiazole |
| CN113603527A (en) * | 2021-08-05 | 2021-11-05 | 安徽省司尔特肥业股份有限公司 | High-yield and high-efficiency special fertilizer for cotton and preparation method thereof |
| CN115109008A (en) * | 2022-07-05 | 2022-09-27 | 山西玉龙化工有限公司 | Method for prolonging reuse of toluene solvent in preparation of 2-chloro-5-chloromethyl thiazole |
| CN115109008B (en) * | 2022-07-05 | 2024-02-06 | 山西玉龙化工有限公司 | Method for prolonging toluene solvent application in preparation of 2-chloro-5-chloromethylthiazole |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104119291A (en) | Method for preparing 2-chlorine-5 chloromethyl thiazole | |
| CN110002989B (en) | Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid | |
| CN101863858A (en) | Synthetic method of bentazone | |
| CN106699831A (en) | Method of preparing liquid crystal cholesterol by using wool fat by virtue of complexing method | |
| CN101830866A (en) | Method for preparing bentazone | |
| CN105481735B (en) | A kind of method for preparing orthanilic acid | |
| CN104557720A (en) | Preparation method of cimetidine | |
| CN103980120B (en) | A kind of synthetic method of DL danshensu isopropyl ester | |
| CN102167716A (en) | Synthesis method of clofarabine, midbody thereof and preparation method of midbody | |
| CN106608858A (en) | Production technology of 4-methyl-5-beta-hydroxyethyl thiazole | |
| CN104529935A (en) | Method for synthesizing high-purity ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate | |
| CN106608843A (en) | WT-02 manufacturing process | |
| CN106518840B (en) | A kind of synthetic method of 2- chlorothiophene -5- formic acid | |
| CN100494187C (en) | Method for synthesizing Ranolazine | |
| CN100516025C (en) | Method for synthesizing D-norvaline using n-pentanoic acid | |
| CN107381912B (en) | Comprehensive treatment method of 1, 4-diamino-2-sulfonic acid wastewater | |
| CN104496801A (en) | Preparation method of 2,4-difluorobenzoic acid | |
| CN106810546A (en) | A kind of umeclidinium compound | |
| CN104497048A (en) | Preparation method of minodronic acid | |
| CN104649947B (en) | A kind of preparation method of 2,2 '-dibenzamido diphenyl disulfide zinc salt | |
| CN108164423A (en) | A kind of preparation method of naftifine hydrochloride | |
| CN107445813A (en) | The method that Malania Oleifera Oil prepares cyclopentadecanone | |
| CN103922892B (en) | A kind of preparation method of 3,4-dichloro-bromobenzene | |
| CN100436444C (en) | New technology of synthesizing lipoamide | |
| CN106496031A (en) | A kind of method for improving dimethyl malenate yield |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20141029 |