CN101863847B - Preparation method of sulfonanilide compound - Google Patents
Preparation method of sulfonanilide compound Download PDFInfo
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- CN101863847B CN101863847B CN2010102159688A CN201010215968A CN101863847B CN 101863847 B CN101863847 B CN 101863847B CN 2010102159688 A CN2010102159688 A CN 2010102159688A CN 201010215968 A CN201010215968 A CN 201010215968A CN 101863847 B CN101863847 B CN 101863847B
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- toluidrin
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Abstract
The invention discloses a preparation method for a sulfonanilide compound, which comprises the following steps: adding 1-10 parts by mol of an aprotic dipolar solvent into a reactor, raising the temperature of the reactor to 90-136 DEG C while stirring, adding 0.001-0.1 part by mol of a catalyst, stirring the mixture, dropping 1-10 parts by mol of a sulfonated agent and carrying out a sulfonylation reaction for 10-25h at 90-136 DEG C, and cooling, filtering, washing and baking the reaction product, then obtaining the sulfonanilide compound. The catalyst adopted by the invention is triphenylphosphine, polyethylene glycol or crown ether instead of the former expensive catalysts including tetrabutyl amonium bromide and DMF, while the reaction conversion rate is above 99%, the reaction effect is better, the side reactions are less, and high-purity products are obtained in high yield. With simple technique, low cost of catalyst and few side reactions, the invention is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to the fine chemical technology field, specifically a kind of preparation method of sulfonanilide compound.
Background technology
As everyone knows, the certain substituted sulfonanilide has weeding activity, and has produced some thus and be used to prepare the useful compound of weedicide.For example, USP [US 4818275] discloses sulfentrazone (N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2,4-triazol-1-yl) phenyl) Toluidrin) as herbicide applications.In this piece patent, and sulfentrazone (N-(2,4-two chloro-5-(4-difluoromethyls-4; 5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl) preparation method Toluidrin phenyl)) is following: (5-amino-2 for 1-; The 4-dichlorophenyl)-and 4-difluoromethyl-3-methyl isophthalic acid hydrogen-1,2,4-triazole-5 (4 hydrogen) ketone and methylsulfonyl chloride are solvent with the halogenated alkane; With the triethylamine is that alkali generates two Toluidrins earlier, under the effect of sodium hydroxide, sloughs a part methylsulfonyl then and obtains product.Consequent problem is exactly: one of which; In this reaction process; Triethylamine or pyridine as acid binding agent must be excessive in to accomplish reaction; Can produce a lot of triethylamine hydrochlorides or pyridine hydrochloride and great amount of wastewater thus, high material cost and Environmental costs cause this method to be not suitable for industrialized production; Its two, each molecule product needed consumes the methylsulfonyl chloride of a part more, the result also is both uneconomical also not environmental protection; Its three, the yield that obtains the product sulfentrazone with the two methylsulfonyl compounds of sodium-hydroxide treatment is lower.USP [US 5990315] discloses quaternary ammonium salt, the catalytic direct sulfonylation of solubility salts such as quaternary alkylphosphonium salt, though this method has solved the problem of direct sulfonylation, the catalyzer of using is more expensive, and the yield of reaction is not high yet simultaneously.USP [US 7169952] has been reported the direct sulfonylation of high boiling point acid amides such as DMF and tertiary amine catalytic; The cheap catalyzer of this method utilization has solved the problem of direct sulfonylation; But can produce the higher impurity of content simultaneously, influence product quality.Therefore, need a kind of more perfect direct Sulphonylation method of exploitation, to address the above problem.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, a kind of preparation method of sulfonanilide compound is provided.
The preparation method of the sulfonanilide compound among the present invention is the substituted aniline with 1 molar part, and the aprotic dipole solvent of 1～10 molar part adds reactor drum, is warming up to 90～136 ℃ under stirring; The catalyzer that adds 0.001～0.1 molar part stirs, and drips the sulfonylation agent of 1～10 molar part; Sulfonylation 10～25 hours, sulfonylation temperature are 90～136 ℃, cooling; Suction filtration, washing, oven dry; Obtain sulfonanilide compound, the molecular structure of sulfonanilide compound is:
Wherein: X and Y respectively do for oneself: hydrogen, halogen, alkoxyl group, R
1Group is: alkyl C
1～C
4, haloalkyl, R
2Group is: hydrogen, alkyl C
1～C
4
Said sulfonanilide compound is: and N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2; The 4-triazol-1-yl) phenyl) Toluidrin, N-(2,4-two chloro-5-(3,4-dimethyl--4,5-dihydro-5-oxo-1H-1; 2,4-triazol-1-yl) phenyl) Toluidrin, N-(2,4-two chloro-5-(4-difluoromethyls-4; 5-dihydro-5-oxo-1 hydrogen-1,2,4-triazol-1-yl) phenyl) Toluidrin, N-(2-chloro-5-(4-difluoromethyl-4; 5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2,4-triazol-1-yl) phenyl) Toluidrin, N-(4-chloro-5-(4-difluoromethyl-4; 5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2, the 4-triazol-1-yl) phenyl) Toluidrin and N-(2-fluoro-4-chloro-5-(4-difluoromethyl-4; 5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2, the 4-triazol-1-yl) phenyl) Toluidrin.
The molecular structure of said substituted aniline is:
Wherein: X and Y respectively do for oneself: hydrogen, halogen, alkoxyl group, R
1Group is: alkyl C
1～C
4, haloalkyl, R
2Group is: hydrogen, alkyl C
1～C
4
Described aprotic dipole solvent is toluene, YLENE or diethylbenzene.The mol ratio of described substituted aniline and aprotic dipole solvent 1: 1～1: 4.Described catalyzer is organic phosphine compounds PR
1R
2R
3, crown ether compound or polyoxyethylene glycol PEG compounds.Described organic phosphine compounds is PR
1R
2R
3, R wherein
1, R
2, R
3The group C that respectively does for oneself
1～C
4Aliphatic hydrocarbon, alkoxyl group, cyclohexyl, phenyl or substituted-phenyl.Described crown ether compound is a hexaoxacyclooctadecane-6-6.Described polyethylene glycols Compound P EG, the number-average molecular weight scope is 600～2000.The mol ratio of described catalyzer and substrate substituted aniline is 0.005～0.03.Described sulfonylation agent is a methylsulfonyl chloride.The mol ratio of described substituted aniline and sulfonylation agent is 1: 1～1: 3.Described temperature of reaction is 90～136 ℃.
The beneficial effect that the present invention compared with prior art has:
1. the catalyzer that sulfonylation adopted is a triphenylphosphine, polyoxyethylene glycol or crown ether, and the expensive catalyzer such as Tetrabutyl amonium bromide that used before having replaced, reaction conversion ratio reaches more than 99%.
2. the catalyzer that sulfonylation adopted is a triphenylphosphine, polyoxyethylene glycol or crown ether, and the catalyzer such as DMF that used before having replaced, reaction effect is better, and side reaction is few, has obtained the product of higher degree with higher yields.
3. present method technology is simple, and catalyst system therefor is cheap, and side reaction is few, is fit to large-scale industrial production.
Embodiment
The further for example clear characteristics more of the present invention of following instance, but the present invention applies for the content of protection and the restriction that scope does not receive following embodiment.
Embodiment 1
1-(5-amino-2,4 dichloro benzene the base)-4-difluoromethyl-3-methyl isophthalic acid hydrogen-1,2 that in three-necked flask, adds 0.1 mole, 4-triazole-5 (4 hydrogen) ketone, 0.1 mole toluene; Be warming up to 100 ℃ under stirring, add 0.01 mole triphenylphosphine, drip 0.12 mole methylsulfonyl chloride then, after dropwising, keep 100 ℃ of system temperatures; React stopped reaction after 12 hours, cooling, suction filtration, washing; The oven dry, obtain N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 87%, content 93%.N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl) phenyl) Toluidrin
1HNMR (500MHz, (CD
3)
2SO, TMS) 69.81 (1H, s), 7.98 (1H, s), 7.70 (1H, s), 7.52 (1H, t, J=57Hz), 3.13 (3H, s), 2.41 (3H, s); MS ([M-H]
-): 384.8.
Embodiment 2
The 1-(5-amino-2,4 dichloro benzene base)-3 that in three-necked flask, adds 0.1 mole, 4-dimethyl--1 hydrogen-1,2,4-triazole-5 (4 hydrogen) ketone; 1 mole toluene is warming up to 90 ℃ under stirring, and adds 0.001 mole tributyl phosphorus, drips 1 mole methylsulfonyl chloride then, after dropwising; Keep 90 ℃ of system temperatures, react stopped reaction after 25 hours, cooling, suction filtration, washing; The oven dry, obtain N-(2,4-two chloro-5-(3,4-dimethyl--4,5-dihydro-5-oxo-1H-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 79%, content 94%.
Embodiment 3
1-(5-amino-2,4 dichloro benzene base)-4-difluoromethyl-1 hydrogen-1,2 that in three-necked flask, adds 0.1 mole, 4-triazole-5 (4 hydrogen) ketone, 0.3 mole YLENE; Be warming up to 136 ℃ under stirring, add the triethyl-phosphite of 0.1 mmole, drip 0.1 mole methylsulfonyl chloride then, after dropwising, keep 136 ℃ of system temperatures; React stopped reaction after 20 hours, cooling, suction filtration, washing; The oven dry, obtain N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-5-oxo-1 hydrogen-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 83%, content 92%.
Embodiment 4
1-(5-amino-2-the chloro-phenyl-)-4-difluoromethyl-3-methyl isophthalic acid hydrogen-1,2 that in three-necked flask, adds 0.1 mole, 4-triazole-5 (4 hydrogen) ketone, 0.5 mole toluene; Be warming up to 110 ℃ under stirring, add 0.03 mole PEG 600, drip 0.15 mole methylsulfonyl chloride, after dropwising; Keep 110 ℃ of system temperatures, react stopped reaction after 15 hours, cooling, suction filtration; Washing, oven dry obtains N-(2-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 85%, content 93%.
Embodiment 5
1-(5-amino-4-the chloro-phenyl-)-4-difluoromethyl-3-methyl isophthalic acid hydrogen-1,2 that in three-necked flask, adds 0.1 mole, 4-triazole-5 (4 hydrogen) ketone, 0.6 mole toluene; Be warming up to 112 ℃ under stirring, add 0.05 mole PEG2000, drip 0.6 mole methylsulfonyl chloride, after dropwising; Keep 112 ℃ of system temperatures, react stopped reaction after 13 hours, cooling, suction filtration; Washing, oven dry obtains N-(4-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 84%, content 93%.
Embodiment 6
1-(5-amino-2-fluoro-4-the chloro-phenyl-)-4-difluoromethyl-3-methyl isophthalic acid hydrogen-1,2 that in three-necked flask, adds 0.1 mole, 4-triazole-5 (4 hydrogen) ketone, 0.6 mole toluene; Be warming up to 110 ℃ under stirring, add 0.02 mole hexaoxacyclooctadecane-6-6, drip 0.3 mole methylsulfonyl chloride, after dropwising; Keep 110 ℃ of system temperatures, react stopped reaction after 16 hours, cooling, suction filtration; Washing, oven dry obtains N-(2-fluoro-4-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1; 2, the 4-triazol-1-yl) phenyl) Toluidrin, yield 82%, content 92%.
Claims (3)
1. the preparation method of a sulfonanilide compound is characterized in that the substituted aniline with 1 molar part, and the aprotic dipole solvent of 1～10 molar part adds reactor drum, is warming up to 90～136 ℃ under stirring, and adds the catalyzer of 0.001～0.1 molar part; Stir, drip the sulfonylation agent of 1～10 molar part, sulfonylation 10～25 hours, the sulfonylation temperature is 90～136 ℃; Cooling, suction filtration, washing, oven dry; Obtain sulfonanilide compound, said sulfonanilide compound is: and N-(2,4-two chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1; 2,4-triazol-1-yl) phenyl) Toluidrin, N-(2,4-two chloro-5-(3,4-dimethyl--4; 5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl) phenyl) Toluidrin, N-(2,4-two chloro-5-(4-difluoromethyls-4; 5-dihydro-5-oxo-1 hydrogen-1,2,4-triazol-1-yl) phenyl) Toluidrin, N-(2-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1; 2,4-triazol-1-yl) phenyl) Toluidrin, N-(4-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2; The 4-triazol-1-yl) Toluidrin and N-(2-fluoro-4-chloro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1 hydrogen-1,2,4-triazol-1-yl) phenyl) Toluidrin phenyl); Described sulfonylation agent is a methylsulfonyl chloride; Described catalyzer is: triphenyl phosphorus, hexaoxacyclooctadecane-6-6 or number-average molecular weight scope are 600～2000 polyethylene glycols Compound P EG; The mol ratio of described catalyzer and substrate substituted aniline is 0.005～0.03.
2. the preparation method of a kind of sulfonanilide compound as claimed in claim 1, it is characterized in that: described aprotic dipole solvent is toluene, YLENE or diethylbenzene; The mol ratio of described substituted aniline and aprotic dipole solvent 1: 1～1: 4.
3. the preparation method of a kind of sulfonanilide compound as claimed in claim 1, it is characterized in that: the mol ratio of described substituted aniline and sulfonylation agent is 1: 1～1: 3.
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| CN103951627B (en) * | 2014-05-06 | 2017-04-19 | 泸州东方农化有限公司 | Method for synthesizing sulfentrazone midbody and sulfentrazone |
| CN106478533A (en) * | 2016-08-27 | 2017-03-08 | 江苏瑞邦农药厂有限公司 | A kind of synthetic method of flucarbazone |
| SG11202006811VA (en) * | 2018-01-18 | 2020-08-28 | Fmc Corp | Processes for the synthesis of sulfentrazone |
| CN108424395B (en) * | 2018-04-24 | 2021-07-06 | 山东潍坊润丰化工股份有限公司 | Preparation method of sulfentrazone |
| CN109096152B (en) * | 2018-07-31 | 2021-01-08 | 乐平市赛复乐医药化工有限公司 | Preparation method of m-methanesulfonamido aniline |
| CN111606863A (en) * | 2019-02-22 | 2020-09-01 | 山东润博生物科技有限公司 | Preparation method of aryl sulfonamide |
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| CN85106905A (en) * | 1985-08-08 | 1987-02-04 | Fmc公司 | Contain 1-aryl-Δ 2-1,2,4, weedicide of-triazoline-5-ketone and preparation method thereof |
| JPH0819084B2 (en) * | 1990-02-07 | 1996-02-28 | 日本新薬株式会社 | Sulfonanilide derivatives and drugs |
| US5990315A (en) * | 1998-05-29 | 1999-11-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of sulfentrazone |
| HUP0302238A2 (en) * | 2000-06-05 | 2003-10-28 | Fmc Corporation | Process to prepare sulfonamides |
| CN101260069A (en) * | 2007-03-07 | 2008-09-10 | 天津药物研究院药业有限责任公司 | Method for preparing nimesulide intermediate 2-phenoxymethanesulphonylaniline |
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Effective date of registration: 20160620 Address after: 646300 Luzhou City, Sichuan Province town of Xinle District Patentee after: ORIENTAL (LUZHOU) AGROCHEMICALS. Co.,Ltd. Address before: 310052 No. 603 bin Kang Road, Binjiang hi tech Development Zone, Zhejiang, Hangzhou, China Patentee before: ZHEJIANG ZHUJI UNITED CHEMICALS Co.,Ltd. Patentee before: MAX (RUDONG) CHEMICALS Co.,Ltd. |
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