CN101597246B - Preparation method of 2-(3, 3, 3-trifluoro propyl) benzsulfamide (I) and midbody thereof - Google Patents
Preparation method of 2-(3, 3, 3-trifluoro propyl) benzsulfamide (I) and midbody thereof Download PDFInfo
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- CN101597246B CN101597246B CN 200810110468 CN200810110468A CN101597246B CN 101597246 B CN101597246 B CN 101597246B CN 200810110468 CN200810110468 CN 200810110468 CN 200810110468 A CN200810110468 A CN 200810110468A CN 101597246 B CN101597246 B CN 101597246B
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Abstract
The invention relates to a preparation method of 2-(3, 3, 3-trifluoro propyl) benzsulfamide (I), in particular to hydrogenation dechlorination reaction of 4, 5 - dichloro -2-(3, 3, 3- trifluoro propyl) benzsulfamide (II). The 4, 5 - dichloro -2-(3, 3, 3- trifluoro propyl) benzsulfamide (II) is prepared by the reaction of 1,2- dichloro-4-(3,3,3- trifluoro propyl) benzene and chlorosulfonic acid, ammonia or ammonia gas.
Description
Technical field
The invention belongs to a kind of preparation method of 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I); This compound is the intermediate of a kind of biologically active substance of preparation.Its structural formula is:
Background technology
Preparation method's step of known 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) is as follows:
A) ORTHO AMINO PHENOL SULPHONIC and Sodium Nitrite under acidic conditions diazotization reaction and 3,3,3-, three fluoro-1-propylene at homogeneous catalyst pd (dba)
2Effect reaction down obtains 1-(3,3,3-trifluoro-propenyl) benzene sulfonic acid sodium salt.
B) product that obtains and 5-10% palladium carbon hydrogenation compressive reaction in water or organic solvent obtain 1-(3,3,3-trifluoro propyl) benzene sulfonic acid sodium salt.
C) 1-(3,3,3-trifluoro-propenyl) benzsulfamide and phosgene, dimethyl formamide and ammonia carry out amidate action and obtain 1-(3,3,3-trifluoro propyl) benzsulfamide.(patent No. EP120814, EP0584043; Open day on November 3rd, 1984).
Reaction formula is as follows:
Have 4 stages altogether.
The shortcoming of present method is to use expensive catalyst P d (dba)
2, raw material 3,3,3-three fluoro-1-propylene are gas boiling point-18 ℃, and adopt the high toxicity phosgene in amidation, the higher and industrialization operation of synthetic cost is difficulty relatively.
Summary of the invention
The present invention adopts new route to synthesize 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) fully; Route of the present invention can be got rid of above shortcoming fully, and adopts economically feasible and method production easy and simple to handle, and cost is lower, and the industrialization operation is very simple.
Content of the present invention: one is the preparation of 4,5-, two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).By 1,2-, two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene and chlorsulfonic acid reaction, the product that obtains reacts at organic solvent and aqueous phase with ammoniacal liquor or ammonia, and reaction finishes, and separates obtaining with currently known methods.The preparation of the 2nd, 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I).By 4,5-, two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) and alkaline earth metal hydroxides solution; 5-10% palladium-carbon catalyst hydrogenation in organic solvent is isolated product with currently known methods then.
Reaction formula is as follows:
The chemical reaction units of the routine that the present invention adopts is carried out, and divides 2 stages; Fs: be to adopt the phenyl ring sulfonation method to generate SULPHURYL CHLORIDE, carry out the neutralization of ammonia solution with ammoniacal liquor or ammonia then.Reacting balance is operated well.Subordinate phase: the catalysis dechlorination method of employing, under the condition that alkali lye, catalyzer exist, logical hydrogen reacts reaction conditions gentleness, safety in the 100atm scope at normal pressure.
Technical scheme of the present invention is in a word:
The synthetic method of 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I)
Comprise with the next stage:
A) 1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene and chlorsulfonic acid are at organic solvent or both direct reaction, and the product that obtains reacts at organic solvent and aqueous phase with ammoniacal liquor or ammonia, and reaction finishes, obtain 4 with the currently known methods separation, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).
B) 4,5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) and alkaline earth metal hydroxides solution; Palladium-carbon catalyst reacts in organic solvent, isolates product 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) with currently known methods then.
2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) synthetic method is characterized in that alkaline earth metal hydroxides solution, palladium-carbon catalyst (hydrogenation dechlorination) with by 1,2-, two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene, chlorsulfonic acid, the material reaction that ammoniacal liquor or ammonia gas react obtain; Separate with currently known methods then and obtain product 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I).
2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) synthetic method, the catalyzer that adds when it is characterized in that reacting is palladium-carbon catalyst.
2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) synthetic method, the alkaline earth metal hydroxides solution that adds when it is characterized in that reacting is sodium hydroxide, any in the potassium hydroxide, concentration 0-30%.
The intermediate 4 of a kind of production 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I), the synthetic method of 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) is characterized in that
1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene and chlorsulfonic acid are at organic solvent or both direct reaction, and the product that obtains reacts at organic solvent and aqueous phase with ammoniacal liquor or ammonia, and reaction finishes, obtain 4 with the currently known methods separation, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).
Describe in detail further below in conjunction with the present invention of embodiment.
Embodiment
The several embodiment of various details further specify the present invention, but content of the present invention is not limited to therewith fully
Embodiment 14, the synthetic method of 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).
Add the 5.7ml chlorsulfonic acid in flask, cryosel is cooled to 0 ℃; Dropwise 5 .0g (0.029mol) 1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene, temperature control added less than 50 ℃ in about 1 hour; 0-5 ℃ of reaction 4 hours, reaction solution became yellowish brown thickness oily matter; With 20g ice and 5ml frozen water, place ice bath; Reaction solution is slowly poured in the frozen water, and temperature control is less than 10-15 ℃ while stirring; Separate out white solid, cooling 15min, suction filtration gets product (MS:340); Add the 10ml ethylene dichloride, be cooled to 0 ℃ after the stirring and dissolving, drip excessive ammonia, reaction solution heats up less than 40 ℃; Drip and finish, to room temperature, pH=8-9; Suction filtration, washing obtains white solid product 4, and benzsulfamide (II) is (MS:321) for 5-two chloro-2-(3,3,3-trifluoropropyl alkyl); Yield is 81%.Product is 93.4% through liquid-phase chromatographic analysis content.
Embodiment 24, the synthetic method of 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).
Add the 5.7ml chlorsulfonic acid in flask, cryosel is cooled to 0 ℃; Dropwise 5 .0g (0.029mol) 1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene, temperature control added less than 10 ℃ in about 1 hour; Be warming up to room temperature, reaction solution becomes yellowish brown thickness oily matter; Stirring reaction 5 hours with 20g ice and 5ml frozen water, places ice bath; Reaction solution is slowly poured in the frozen water, and temperature control is less than 10-15 ℃ while stirring; Separate out white solid, cooling 15min, suction filtration gets product (MS:340); Add the 10ml ethylene dichloride, be cooled to 0 ℃ after the stirring and dissolving, drip excessive ammonia, reaction solution heats up less than 40 ℃; Drip and finish, to room temperature, pH=8-9; Suction filtration, washing obtains white solid product 4, and benzsulfamide (II) is (MS:321) for 5-two chloro-2-(3,3,3-trifluoropropyl alkyl); Yield is 83%.Product is 94.5% through liquid-phase chromatographic analysis content.
Embodiment 34, the synthetic method of 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II).
Add the 5.7ml chlorsulfonic acid in flask, cryosel is cooled to 0 ℃; Dropwise 5 .0g (0.029mol) 1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene, temperature control added less than 10 ℃ in about 1 hour; Be warming up to room temperature, heating in water bath is 4 hours for 55 ℃, and reaction solution becomes yellowish brown thickness oily matter; With 20g ice and 5ml frozen water, place ice bath; Reaction solution is slowly poured in the frozen water, and temperature control is less than 10-15 ℃ while stirring; Separate out white solid, cooling 15min, suction filtration gets product (MS:340); Add the 10ml ethylene dichloride, be cooled to 0 ℃ after the stirring and dissolving, the throughput ammonia, reaction solution heats up less than 40 ℃; Drip and finish, to room temperature, pH=8-9; Concentrate, washing, filter and obtain white solid product 4, benzsulfamide (II) (MS:321) for 5-two chloro-2-(3,3,3-trifluoropropyl alkyl); Yield is 87%.Product is 98% through liquid-phase chromatographic analysis content.
The synthetic method of embodiment 4 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I).
Add 5g 4 in flask, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) adds the 100ml5% sodium hydroxide solution respectively, the 50ml trimethyl carbinol, 0.2gPd-℃ again; Emptying gas, logical hydrogen under palladium-carbon catalyst.And intensification 50-60 ℃; Normal-temperature reaction needs 20 hours approximately, controls among the TLC; Reaction finishes, and after concentrating, adds 10ml water, and cooling is transferred pH1-2 with 2N hydrochloric acid, separates out white solid 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) (HPLC-MS:253), filters oven dry.Yield 95%, product is 88% through liquid-phase chromatographic analysis content.
The synthetic method of embodiment 5 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I)
Add 5g 4 in autoclave pressure, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) adds the 100ml5% sodium hydroxide solution respectively, 50ml water, 0.2gPd-C again; Emptying gas, logical hydrogen under palladium-carbon catalyst.Normal-temperature reaction needs 16 hours approximately under the 3atm pressure, and reaction finishes, and after concentrating, adds 10ml water, and cooling is transferred pH1-2 with 2N hydrochloric acid, separates out white solid 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) (HPLC-MS:253), filters oven dry.Yield 96%, product is 91% through liquid-phase chromatographic analysis content.
The synthetic method of embodiment 6 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I)
Add 5g 4 in autoclave pressure, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) adds the 100ml5% sodium hydroxide solution respectively, 50ml acetone, 0.2gPd-C again; Emptying gas, logical hydrogen under palladium-carbon catalyst.Normal-temperature reaction needs 12 hours approximately under the 10atm pressure, and reaction finishes, and after concentrating, adds 10ml water, and cooling is transferred pH1-2 with 2N hydrochloric acid, separates out white solid 2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (I) (HPLC-MS:253), filters oven dry.Yield 94%, product is 90% through liquid-phase chromatographic analysis content.
Claims (2)
1.2-(3,3,3-trifluoropropyl alkyl) and the synthetic method of benzsulfamide (I),
Comprise with the next stage:
A) 1,2-two chloro-4-(3,3,3-trifluoropropyl alkyl) benzene and chlorsulfonic acid are at organic solvent or both direct reaction, and the product that obtains reacts at organic solvent and aqueous phase with ammoniacal liquor or ammonia, and reaction finishes, obtain 4 with the currently known methods separation, 5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II);
B) 4,5-two chloro-2-(3,3,3-trifluoropropyl alkyl) benzsulfamide (II) and alkaline earth metal hydroxides solution; The 5-10% palladium-carbon catalyst reacts in organic solvent, isolates product 2-(3 with currently known methods then, 3,3-trifluoropropyl alkyl) benzsulfamide (I).
2. according to the 2-(3 of claim 1,3,3-trifluoropropyl alkyl) benzsulfamide (I) synthetic method, the catalyzer that adds when it is characterized in that reacting is the 5-10% palladium-carbon catalyst.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0120814A2 (en) * | 1983-03-28 | 1984-10-03 | Ciba-Geigy Ag | N-phenylsulfonyl-N'-pyrimidinyl- and -triazinyl urea |
| CN1083480A (en) * | 1992-08-18 | 1994-03-09 | 希巴-盖吉股份公司 | The preparation method of substituted benzene or Phenylsulfonic acid and derivative thereof and N, the preparation method of N '-replacement urea |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0120814A2 (en) * | 1983-03-28 | 1984-10-03 | Ciba-Geigy Ag | N-phenylsulfonyl-N'-pyrimidinyl- and -triazinyl urea |
| CN1083480A (en) * | 1992-08-18 | 1994-03-09 | 希巴-盖吉股份公司 | The preparation method of substituted benzene or Phenylsulfonic acid and derivative thereof and N, the preparation method of N '-replacement urea |
Non-Patent Citations (1)
| Title |
|---|
| CHRISTOPHE MENNITI et al.Soil Transformation of Prosulfuron.《J. Agric. Food Chem.》.2003,第51卷(第12期),3525-3527. * |
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Address after: 213022 No. 98 Minjiang Road, Xinbei District, Jiangsu, Changzhou Patentee after: Jiangsu Agricultural Hormone Engineering Technology Research Centre Co., Ltd. Patentee after: Jiangsu Institute of Ecomones Co.,Ltd. Address before: 213022 No. 98 Minjiang Road, Xinbei District, Jiangsu, Changzhou Patentee before: Jiangsu Agricultural Hormone Engineering Technology Research Centre Co., Ltd. Patentee before: Jiangsu Prov. Hormone Inst., Co., Ltd. |