CN103387546B - One prepares the method for 2-(2,4 dichloro benzene amido)-6-trifluoromethyl pyrimidine phenol - Google Patents
One prepares the method for 2-(2,4 dichloro benzene amido)-6-trifluoromethyl pyrimidine phenol Download PDFInfo
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Abstract
One prepares 2-(2,4-dichloroanilino) method of-6-trifluoromethyl pyrimidine phenol, with 2,4-dichlorphenamide bulk powder is starting raw material, through two-step reaction, and obtained 2-(2,4-dichloroanilino)-6-trifluoromethyl pyrimidine phenol, total yield of products more than 90%, content more than 97%.The 2-(2 that this method is obtained, 4-dichloroanilino)-6-trifluoromethyl pyrimidine phenol yield and content all higher, reduce cost simultaneously, alleviate the impact on surrounding environment, be applicable to suitability for industrialized production.
Description
Technical field
The present invention relates to a kind of miticide phonetic mite amine intermediate 2-(2,4-dichloroanilino) preparation method of-6-trifluoromethyl pyrimidine phenol.
Background technology
Phonetic mite amine (Compound I) is the compound disclosed in Chinese patent CN101906075A with acaricidal activity.This compound biological activity is excellent, not only to one-tenth mite, and if all have good biological activity to full, mite ovum, there are wide market outlook.
Structural formula II (chemical name 2-(2,4-dichloroanilino)-6-trifluoromethyl pyrimidine phenol, hereinafter referred to as substituted pyrimidines phenol) be an important intermediate in phonetic mite amine preparation process, Chinese patent CN101906075A reports the preparation method of this intermediate:
The first step: 2,4 dichloro aniline and cyanamide react prepares corresponding replacement guanidinesalt
Second step: replacement guanidinesalt and trifluoroacetic ethyl acetoacetate react obtained intermediate substituted pyrimidines phenol
Although Chinese patent CN101906075A reports the preparation method of this intermediate, but there is obvious shortcoming in the synthetic method reported in document: reaction yield is low, foreign matter content is many, product purity is low, long reaction time, energy consumption large, is not suitable for suitability for industrialized production.
Summary of the invention
In order to meet the needs of suitability for industrialized production, the present invention is devoted to develop a kind of product yield and purity preparation 2-(2 higher, easy and simple to handle, 4-dichloroanilino) method of-6-trifluoromethyl pyrimidine phenol.
Technical scheme of the present invention is as follows:
One prepares 2-(2,4-dichloroanilino) method of-6-trifluoromethyl pyrimidine phenol, reaction formula is as follows:
Reaction comprises the following steps:
1) at room temperature by 2, the mixing of 4-dichlorphenamide bulk powder, mineral acid rises to 50 DEG C-100 DEG C, drip cyanamide at this temperature, dropwising the insulation reaction time is 2-20 hour, be cooled to about 40 DEG C after completion of the reaction, add the aqueous sodium carbonate of 20%, stir, continue to be cooled to 10 DEG C after separate out solid, suction filtration, dryly must replace guanidinesalt; The mol ratio of 2,4 dichloro aniline and cyanamide is 1:1.5-4; The mol ratio of 2,4 dichloro aniline and sodium carbonate is 1:0.5-0.8, and the mol ratio of 2,4 dichloro aniline and mineral acid is 1:1-1.2;
2) the replacement guanidinesalt of drying and trifluoroacetic ethyl acetoacetate are joined in reaction solvent, are warming up to 65 DEG C-145 DEG C reactions, add water after completion of the reaction, filter, dry intermediate substituted pyrimidines phenol; The mol ratio replacing guanidinesalt and reaction solvent is 1:10-30, and the mol ratio replacing guanidinesalt and trifluoroacetic ethyl acetoacetate is 1:1-3.
1st) mineral acid that step is reacted used is hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid etc., preferred hydrochloric acid or nitric acid; Preferred processing condition are: temperature of reaction 50 DEG C-80 DEG C, insulation reaction time 4-8 hour; Preferred feed molar ratio is the mol ratio of 2,4 dichloro aniline and cyanamide is further 1:1.5-2; The mol ratio of 2,4 dichloro aniline and sodium carbonate is 1:0.6-0.8.
Dropping cyanamide and aqueous sodium carbonate should be suitably slow, reacted in fierceness to prevent..
2nd) reaction solvent that step is reacted used is the aromatic hydrocarbon solvent such as benzene,toluene,xylene or chlorobenzene, preferred benzene, toluene or dimethylbenzene etc.; Preferred temperature of reaction for react under solvent reflux temperature; The mol ratio preferably replacing guanidinesalt and reaction solvent is further 1:15-20; The mol ratio replacing guanidinesalt and trifluoroacetic ethyl acetoacetate is 1:1.05-1.2.
Each step reaction end is monitored with liquid chromatography, and product content adopts liquid chromatography external standard method.
Contriver finds in the preparation process of further investigation substituted pyrimidines phenol, because prior art drips trifluoroacetic ethyl acetoacetate under reflux dewatering state, the water that reaction generates is by fast eliminating reaction system, the substituted pyrimidines phenol solubleness in reaction solvent generated is very little, reaction starts namely there is a large amount of precipitation soon, the substituted pyrimidines phenol solid of separating out sweeps along part to replace guanidinesalt, causes prior art to there is the drawbacks such as product reaction yield is lower, product purity is lower, the reaction times is longer thus.In order to address this problem, applicant is by have unexpectedly discovered that a kind of effective operating method after the test of a large amount of condition optimizing: first replacement guanidinesalt and trifluoroacetic ethyl acetoacetate and solvent are added reaction system simultaneously, be warming up to back flow reaction again, in reaction process, do not remove the water of generation; This operating method makes the solvability of substituted pyrimidines phenol in reaction system greatly increase, thus the process of accelerated reaction, not only shorten the reaction times, and improve reaction yield and product purity.In addition, in prior art, under reflux dewatering state, drip trifluoroacetic ethyl acetoacetate, be easy to cause unreacted trifluoroacetic ethyl acetoacetate to deviate from from reaction system together with water, cause wastage of material; Method of the present invention both can avoid wastage of material, made again operation more simplify.
Preparation method provided by the invention is easy and simple to handle, and reaction conditions is gentle, and total yield of products more than 90%, content more than 97%, suitability for industrialized is applied.
Embodiment
Following examples, for further describing the present invention, react raw materials used and reagent all has commercially available.
Embodiment 1
16.2 grams of 2,4 dichloro anilines are joined (with stirring and prolong) in 500ml reaction flask, add the aqueous hydrochloric acid of 26 gram 15%, intensification stirring reaction, when temperature rises to 75 DEG C, starts the cyanamide aqueous solution dripping 28 gram 30%, within 1 hour, add, dropwise, HPLC follows the tracks of.React complete, add 32g 20 ﹪ aqueous sodium carbonate, separate out solid after stirring, suction filtration.Dry product 22.5 grams.Yield 95.7%, content 99%.
22.5 grams replace guanidinesalt and join (with stirring, prolong and division box) in 500ml reaction flask, and add 22 grams of trifluoroacetic ethyl acetoacetates, 200ml toluene successively, temperature rising reflux reacts 6 hours.HPLC follows the tracks of, and reacts complete.Add 50 grams of water, be cooled to 30 DEG C, suction filtration, dry solid phase prod 30.6 grams, content 97%, yield 95.8%.
Embodiment 2 replaces the preparation of guanidinesalt
16.2 grams of 2,4 dichloro anilines are joined (with stirring and prolong) in 500ml reaction flask, add the aqueous nitric acid of 31.5 gram 20%, intensification stirring reaction, when temperature rises to 75 DEG C, starts the cyanamide aqueous solution dripping 26 gram 30%, within 1 hour, add, dropwise, HPLC follows the tracks of.React complete, be cooled to 40 DEG C, add 32g 20 ﹪ aqueous sodium carbonate.Solid is separated out, suction filtration after stirring.Dry product 22.1 grams.Yield 94.1%, content 99%.
22.1 grams replace guanidinesalt and join (with stirring, prolong and division box) in 500ml reaction flask, and add 21 grams of trifluoroacetic ethyl acetoacetates, 200ml dimethylbenzene successively, temperature rising reflux reacts 6 hours.HPLC follows the tracks of, and reacts complete.Add 50 grams of water, be cooled to 30 DEG C, suction filtration, dry solid phase prod 30.2 grams, content 97.6%, yield 95.2%.
Claims (1)
1. prepare a method for 2-(2,4 dichloro benzene amido)-6-trifluoromethyl pyrimidine phenol, reaction formula is as follows:
It is characterized in that comprising following reactions steps:
1) at room temperature by 2, the mixing of 4-dichlorphenamide bulk powder, mineral acid rises to 50 DEG C-80 DEG C, drip cyanamide, dropwise insulation reaction 4-8 hour, be cooled to 40 DEG C after completion of the reaction, add the aqueous sodium carbonate of 20%, stir, continue to be cooled to 10 DEG C after separate out solid, filtration, the dry intermediate that obtains replace guanidinesalt, and the mol ratio of 2,4 dichloro aniline and cyanamide is 1:1.5-2,2, the mol ratio of 4-dichlorphenamide bulk powder and sodium carbonate is 1:0.6-0.8, and the mol ratio of 2,4 dichloro aniline and mineral acid is 1:1-1.2;
2) the replacement guanidinesalt of drying and trifluoroacetic ethyl acetoacetate are joined in reaction solvent, are warming up to back flow reaction, add water after completion of the reaction, filter, dry intermediate substituted pyrimidines phenol, the mol ratio replacing guanidinesalt and reaction solvent is 1:15-20; The mol ratio replacing guanidinesalt and trifluoroacetic ethyl acetoacetate is 1:1.05-1.2;
Described the 1st) in step reaction, mineral acid used is selected from hydrochloric acid or nitric acid; Temperature of reaction is 50 DEG C-80 DEG C; The insulation reaction time is 4-8 hour; The mol ratio of 2,4 dichloro aniline and cyanamide is 1:1.5-2; The mol ratio of 2,4 dichloro aniline and sodium carbonate is 1:0.6-0.8;
Described 2nd) step reaction solvent is selected from benzene,toluene,xylene or chlorobenzene;
Described 2nd), in step reaction, first replacement guanidinesalt and trifluoroacetic ethyl acetoacetate and solvent are added reaction system simultaneously, then be warming up to back flow reaction, in reaction process, do not remove the water of generation.
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| CN201210144758.3A CN103387546B (en) | 2012-05-10 | 2012-05-10 | One prepares the method for 2-(2,4 dichloro benzene amido)-6-trifluoromethyl pyrimidine phenol |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1388402A (en) * | 1972-04-18 | 1975-03-26 | Ici Ltd | Phosphorous containing pyrimidine derivatives and pesticidal com- positions thereof |
| US4000138A (en) * | 1966-03-31 | 1976-12-28 | Imperial Chemical Industries Limited | Organic compounds and compositions containing them |
| US5106852A (en) * | 1989-07-13 | 1992-04-21 | Basf Aktiengesellschaft | Pest control with pyrimidines |
| US6114342A (en) * | 1995-05-21 | 2000-09-05 | Basf Aktiengesellschaft | 2-(O-[pyrimidin-4-yl]methylenoxy)phenylacetic acid derivatives and their use for controlling harmful fungi and animal pests |
| CN101906075A (en) * | 2009-06-05 | 2010-12-08 | 中国中化股份有限公司 | E-type phenyl acrylic acid ester compound containing substituted anilino pyrimidine group and applications thereof |
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- 2012-05-10 CN CN201210144758.3A patent/CN103387546B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4000138A (en) * | 1966-03-31 | 1976-12-28 | Imperial Chemical Industries Limited | Organic compounds and compositions containing them |
| GB1388402A (en) * | 1972-04-18 | 1975-03-26 | Ici Ltd | Phosphorous containing pyrimidine derivatives and pesticidal com- positions thereof |
| US5106852A (en) * | 1989-07-13 | 1992-04-21 | Basf Aktiengesellschaft | Pest control with pyrimidines |
| US6114342A (en) * | 1995-05-21 | 2000-09-05 | Basf Aktiengesellschaft | 2-(O-[pyrimidin-4-yl]methylenoxy)phenylacetic acid derivatives and their use for controlling harmful fungi and animal pests |
| CN101906075A (en) * | 2009-06-05 | 2010-12-08 | 中国中化股份有限公司 | E-type phenyl acrylic acid ester compound containing substituted anilino pyrimidine group and applications thereof |
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Effective date of registration: 20160201 Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No. Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD. Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28 Patentee before: Sinochem Corporation Patentee before: Shenyang Research Institute of Chemical Industry |