CN102746254A - Preparation method of thifluzamide - Google Patents
Preparation method of thifluzamide Download PDFInfo
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- CN102746254A CN102746254A CN2012102629926A CN201210262992A CN102746254A CN 102746254 A CN102746254 A CN 102746254A CN 2012102629926 A CN2012102629926 A CN 2012102629926A CN 201210262992 A CN201210262992 A CN 201210262992A CN 102746254 A CN102746254 A CN 102746254A
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- thifluzamide
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Abstract
The invention relates to a preparation method of a bactericide, in particular to a preparation method of thifluzamide, and belongs to the chemical technical field. The invention discloses a synthetic method of the thifluzamide through an intermediate without purification. 2-methyl-4-trifluoromethyl-5-thiazole formic acid serves as a raw material, thionyl chloride serves as a chlorinating reagent for chlorination, 2, 6-dibromo-4-trifluoroanisidine, a solvent, an acid-binding agent and a catalyst are added after a chlorinating solvent is recovered, and a target product thifluzamide is obtained after backflow. The method has the advantages that side products are few, the yield is high, the product has a high purity and stable quality, and the method is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of sterilant, especially the preparation method of thiazole amide sterilant belongs to technical field of chemistry.
Background technology
Thifluzamide belongs to the thiazole amide sterilant, and its chemistry is by name: 2 ', 6 '-two bromo-2-methyl-4 '-trifluoromethoxy-4-Trifluoromethyl-1s, and 3-thiazole-5-methane amide, structural formula is:
Thifluzamide all has activity to pathomycetes such as Rhizoctonia, Puccinia, Ustilago, Tilletia, corticium, nuclear cavity Pseudomonas, especially the fungus-caused disease of Basidiomycetes such as hypochnus, damping-off etc. is had special efficacy.The preparation method of relevant thifluzamide, prior art EP0371950A2 (28,11; 1989) disclose a kind ofly, made solvent with DMF, with the thioacetamide effect from trifluoroacetic ethyl acetoacetate; Obtain 2-methyl-4-trifluoromethyl-5-thiazol formic-acid through hydrolysis, behind the THIONYL CHLORIDE 97 chloro, obtain the midbody acyl chlorides through the high vacuum underpressure distillation; Again with acyl chlorides in xylene solvent with 2,6-two bromo-4-trifluoro-methoxyaniline effects obtain thifluzamide.And the reactions step of this method is more, makes by product many, and productive rate only has 32.3%, the incompatibility market requirement.
Summary of the invention
The technical problem that the present invention will solve is: to the defective that above prior art exists, propose a kind of preparation method of thifluzamide, improve productive rate.
The present invention is through following technical scheme technical solution problem: a kind of preparation method of thifluzamide may further comprise the steps:
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid is mixed with sulfur oxychloride, add the chlorination reaction solvent and carry out chlorination reaction;
Step 2: with the reaction product in the step 1 and 2,6-two bromo-4-trifluoro-methoxyanilines, acid binding agent, catalyzer and acylation reaction solvent are cooled to and separate out solid after carrying out 4～12h acylation reaction under 60～180 ℃ of conditions;
Step 3:, promptly get title product, thifluzamide with using the weak acid scrubbing of concentration behind the said solid filtering as 5-10%.
In step 1, the temperature of said chlorination reaction is room temperature～65 ℃, reacts and reclaims the chlorination reaction solvent after 12～24 hours.
Further, the temperature of said chlorination reaction is 55-65 ℃.
Again further, said chlorination reaction solvent is chloroform or sulfur oxychloride.
In step 2, said acylation reaction solvent is N, dinethylformamide, methyl-sulphoxide, toluene, YLENE, dioxane, MIBK, di-tert-butyl ether or MTBE.
Reaction equation of the present invention is following:
Said reactant is pressed following molar ratio computing, 2-methyl-4-trifluoromethyl-5-thiazol formic-acid: sulfur oxychloride: acid binding agent: catalyzer: 2, and 6-two bromo-4-trifluoro-methoxyanilines are 1.0:1.05-15:0.9-1.5:0.02-0.2:0.9-1.5.
In the above-mentioned reaction, said acid binding agent is triethylamine, tripropyl amine, Tributylamine, N, a kind of in accelerine, the pyridine.
Said catalyzer be benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, 18-hat-6,
A kind of in 15-hat-5, Polyethylene Glycol-600, PEG 400, triphenyl butyl bromide phosphine, the triphenyl ethyl bromide phosphine.
The present invention obtains the thifluzamide of purifying with the thifluzamide bullion of step 3 through ETHYLE ACETATE-sherwood oil recrystallization method, can be used as standard reference material and uses.
The present invention adopts aforesaid method, and the chlorination reaction product is purified without aftertreatment, directly will become the reaction mass of acid amides to add wherein; Originally the efficient purification step saves; Obviously improve productive rate, the thifluzamide bullion purity of gained reaches 97%, and content reaches more than 99% behind the purifying; Yield 65-80% is far above prior art.Its beneficial effect is: by product is few, and productive rate is high, and the good and steady quality of product purity is suitable for suitability for industrialized production.
Embodiment
Various reactants that adopted in following examples and reagent are commercially available, repeat no more.
Embodiment one
Present embodiment prepares thifluzamide according to the following steps:
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid of 0.25mol, 53g is mixed with the 200ml sulfur oxychloride, and 80 ℃ were refluxed 12 hours, obtained midbody 2-methyl-4-trifluoromethyl-5-thiazole formyl chloride, reclaimed excessive sulfur oxychloride; The consumption of above sulfur oxychloride comprises reactant and reaction solvent.
Step 2: YLENE, 0.25mol, the pyridine of 20g and the Polyethylene Glycol-600 of 5mL of 150ml are added in the acyl chlorides; Splash into 2 under stirring; The xylene solution (84g 0.25mol/300mL) of 6-two bromo-4-trifluoro-methoxyanilines refluxed 8 hours, was cooled to and separated out solid;
Step 3: solid is carried out behind the suction filtration Hydrogen chloride washing with 5%, obtains pale solid 95g, i.e. thifluzamide finished product, detect purity: 97.5%, yield: 72%.
Embodiment two
Present embodiment prepares thifluzamide according to the following steps:
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid of 0.25mol, 53g is mixed with the chloroform of 30ml sulfur oxychloride and 150ml, and 62 ℃ were refluxed 24 hours, obtained midbody 2-methyl-4-trifluoromethyl-5-thiazole formyl chloride, reclaimed chloroform;
Step 2: YLENE, 0.25mol, the pyridine of 20g and the benzyltriethylammoinium chloride of 2g of 150ml are added in the acyl chlorides; Splash into 2 under stirring; The xylene solution (84g 0.25mol/300mL) of 6-two bromo-4-trifluoro-methoxyanilines refluxed 8 hours, was cooled to and separated out solid;
Step 3: solid is carried out behind the suction filtration Hydrogen chloride washing with 10%, obtains pale solid 89g, i.e. thifluzamide finished product, detect purity: 97%, yield: 68%.
Embodiment three
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid of 0.25mol, 53g is mixed with the 200ml sulfur oxychloride, and 40 ℃ were refluxed 12 hours, obtained midbody 2-methyl-4-trifluoromethyl-5-thiazole formyl chloride,, reclaim excessive sulfur oxychloride;
Step 2: with the N of 150ml; The triethylamine of dinethylformamide, 0.25mol, 25g and the 18-of 1g hat-6 add in the acyl chlorides; Splash into 2, the N of 6-two bromo-4-trifluoro-methoxyanilines, dinethylformamide solution (84g 0.25mol/300mL) under stirring; Refluxed 8 hours, and be cooled to and separate out solid;
Step 3: solid is carried out behind the suction filtration dilute sulphuric acid washing with 5%, obtains pale solid 102g, i.e. thifluzamide finished product, detect purity: 97.4%, yield: 77%.
Embodiment four
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid of 0.25mol, 53g is mixed with the 200ml sulfur oxychloride, and 60 ℃ were refluxed 12 hours, obtained midbody 2-methyl-4-trifluoromethyl-5-thiazole formyl chloride,, reclaim excessive sulfur oxychloride;
Step 2: with the N of the toluene of 150ml, 0.25mol, 31g; The Tetrabutyl amonium bromide of accelerine and 2g adds in the acyl chlorides, splashes into 2, the toluene solution (84g 0.25mol/300mL) of 6-two bromo-4-trifluoro-methoxyanilines under stirring; Refluxed 8 hours, and be cooled to and separate out solid;
Step 3: solid is carried out behind the suction filtration dilute sulphuric acid washing with 8%, obtains pale solid 105g, i.e. thifluzamide finished product, detect purity: 97.3%, yield: 79%.
With 10g thifluzamide finished product with ETHYLE ACETATE-sherwood oil (1:1) heating for dissolving, cooling crystallization, 6.8g thifluzamide highly finished product, detect purity: 99.7%, use as the standard reference material of the foregoing description.
Except that above-mentioned enforcement, this product can also have other embodiments.All employings are equal to the technical scheme of replacement or equivalent transformation formation, all drop on the protection domain of this product invention requirement.
Claims (8)
1. the preparation method of a thifluzamide may further comprise the steps:
Step 1: 2-methyl-4-trifluoromethyl-5-thiazol formic-acid is mixed with sulfur oxychloride, add the chlorination reaction solvent and carry out chlorination reaction;
Step 2: with the reaction product in the step 1 and 2,6-two bromo-4-trifluoro-methoxyanilines, acid binding agent, catalyzer and acylation reaction solvent are cooled to and separate out solid after carrying out 4～12h acylation reaction under 60～180 ℃ of conditions;
Step 3:, promptly get title product, thifluzamide with using the weak acid scrubbing of concentration behind the said solid filtering as 5-10%.
2. according to the preparation method of the said thifluzamide of claim 1, it is characterized in that: the temperature of said chlorination reaction is room temperature～80 ℃, reacts and reclaims the chlorination reaction solvent after 12～24 hours.
3. according to the preparation method of the said thifluzamide of claim 2, it is characterized in that: the temperature of said chlorination reaction is 65～80 ℃.
4. according to the preparation method of the said thifluzamide of claim 1, it is characterized in that: said chlorination reaction solvent is chloroform, N, dinethylformamide or sulfur oxychloride.
5. according to the preparation method of the said thifluzamide of claim 1; It is characterized in that: said acylation reaction solvent is N, dinethylformamide, methyl-sulphoxide, toluene, YLENE, dioxane, MIBK, di-tert-butyl ether or MTBE.
6. according to the preparation method of the said thifluzamide of claim 1; It is characterized in that: said reactant is by following molar ratio computing; 2-methyl-4-trifluoromethyl-5-thiazol formic-acid: sulfur oxychloride: acid binding agent: catalyzer: 2,6-two bromo-4-trifluoro-methoxyanilines are 1.0:1.05-15:0.9-1.5:0.02-0.2:0.9-1.5.
7. according to the preparation method of claim 1 or 6 said thifluzamides, it is characterized in that: said acid binding agent is triethylamine, tripropyl amine, Tributylamine, N, a kind of in accelerine, the pyridine.
8. according to the preparation method of claim 1 or 6 said thifluzamides, it is characterized in that: said catalyzer is a kind of in benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, 18-hat-6,15-hat-5, Polyethylene Glycol-600, PEG 400, triphenyl butyl bromide phosphine, the triphenyl ethyl bromide phosphine.
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| CN2012102629926A CN102746254A (en) | 2012-07-27 | 2012-07-27 | Preparation method of thifluzamide |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837491A (en) * | 2016-04-22 | 2016-08-10 | 山东省联合农药工业有限公司 | Novel carboxamide derivative bactericide, preparation method and application thereof |
| CN108059625A (en) * | 2016-11-09 | 2018-05-22 | 广东广康生化科技股份有限公司 | A kind of novel process that thifluzamide is prepared by thiazole acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1043127A (en) * | 1988-11-29 | 1990-06-20 | 孟山都公司 | Substituted thiazole and mycocide purposes thereof |
| CN1160712A (en) * | 1996-02-28 | 1997-10-01 | 罗姆和哈斯公司 | Thifluzamide with stabilized efficacy |
| CN1214684A (en) * | 1996-02-28 | 1999-04-21 | 日产化学工业株式会社 | Thifluzamide with enhanced potency |
-
2012
- 2012-07-27 CN CN2012102629926A patent/CN102746254A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1043127A (en) * | 1988-11-29 | 1990-06-20 | 孟山都公司 | Substituted thiazole and mycocide purposes thereof |
| CN1160712A (en) * | 1996-02-28 | 1997-10-01 | 罗姆和哈斯公司 | Thifluzamide with stabilized efficacy |
| CN1214684A (en) * | 1996-02-28 | 1999-04-21 | 日产化学工业株式会社 | Thifluzamide with enhanced potency |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837491A (en) * | 2016-04-22 | 2016-08-10 | 山东省联合农药工业有限公司 | Novel carboxamide derivative bactericide, preparation method and application thereof |
| CN105837491B (en) * | 2016-04-22 | 2018-11-06 | 山东省联合农药工业有限公司 | A kind of novel carboxamide derivative fungicide and its preparation method and application |
| CN108059625A (en) * | 2016-11-09 | 2018-05-22 | 广东广康生化科技股份有限公司 | A kind of novel process that thifluzamide is prepared by thiazole acid |
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Application publication date: 20121024 |