CN102311391A - Method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole - Google Patents
Method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole Download PDFInfo
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- CN102311391A CN102311391A CN201110171994A CN201110171994A CN102311391A CN 102311391 A CN102311391 A CN 102311391A CN 201110171994 A CN201110171994 A CN 201110171994A CN 201110171994 A CN201110171994 A CN 201110171994A CN 102311391 A CN102311391 A CN 102311391A
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- benzoglyoxaline
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Abstract
The invention provides a method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole. The method is characterized in that hydrazine hydrate is taken as a reductant, 2-nitryl-4-(difluoromethoxy) aniline is reduced under the catalysis of Raney-Ni, and the obtained reduction products are used for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole through one-pot reaction without separation; and the total yield of the 2-mercapto-5-difluoromethoxy-1H-benzimidazole is over 95%. The method provided by the invention is simple and safe in operation, and more suitable for industrial production.
Description
Technical field
The present invention relates to the preparation method of a kind of 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline, belong to medicine and make the field.
Background technology
2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline is the important intermediate of synthetic new drug pantoprazole, and the method for existing preparation 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline is for being that carrier, precious metal palladium are catalyzer with the gac, with hydrogen reducing 2-nitro-4-difluoro-methoxy-aniline; Product 4-difluoro-methoxy O-Phenylene Diamine comes out with the isolated in form of its hydrochloride, is dissolved in ethanol-aqueous solution again, hydro-oxidation sodium solid and oxyethyl group sulphur ortho acid potassium; Backflow 15h; Handle then 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline, this method cost is higher, complex process; The aftertreatment trouble, and total recovery is less than 70%.
Summary of the invention
In order to overcome the shortcoming that prior art exists, the invention provides the preparation method of a kind of 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline, it is characterized in that: this preparing method's step is: in 95% ethanolic soln of 2-nitro-4-difluoro-methoxy-aniline, add catalyzer Raney-Ni and reductive agent Hydrazine Hydrate 80; 50-70 ℃ of insulation 1-2h; Reduce 2-amino-4-difluoro-methoxy-aniline, add the Raney-Ni of equivalent, backflow 2-6h; The elimination catalyzer; In filtrating, add oxyethyl group sulphur ortho acid potassium,, leave standstill cooling at 70-90 ℃ of following reflux 3-6h; Reaction solution is poured in the water of 200ml, adding Hydrogen chloride, to be adjusted to PH be 3, changes white solid into, refilters, and washing to filtrating is neutral, and filter cake is dissolved in an amount of sodium hydroxide solution, activated carbon decolorizing, 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline.
The mol ratio of said 2-nitro-4-difluoro-methoxy-aniline, Hydrazine Hydrate 80 and oxyethyl group sulphur ortho acid potassium is: (1-1.5): 2: (1.1-1.6).The employing one kettle way that responds among this preparation method.
Beneficial effect: this invention is made reductive agent with Hydrazine Hydrate 80; Reductase 12-nitro under Raney-Ni catalysis-4-difluoro-methoxy-aniline; Reduzate is without separating the preparation that one kettle way is used for 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline; Total recovery reaches more than 95%, and easy and simple to handle, safety is more suitable in suitability for industrialized production.
Embodiment
Below be to further specify technical scheme of the present invention through embodiment.
Embodiment 1
(the 2.52g massfraction is 80% solution, and 0.04mol), 60 ℃ are incubated 2h in 95% ethanol (50ml) solution of the 2-of 4g, 0.02mol nitro-4-difluoro-methoxy-aniline, to add catalyzer Raney-Ni (0.2g) and reductive agent Hydrazine Hydrate 80; Reduce 2-amino-4-difluoro-methoxy-aniline, add 0.2gRaney-Ni, backflow 4h; The elimination catalyzer, and adding oxyethyl group sulphur ortho acid potassium in filtrating (4.2g, 0.026mol); At 80 ℃ of following reflux 5h, leave standstill cooling; Reaction solution is poured in the water of 200ml, adding Hydrogen chloride, to be adjusted to PH be 3, changes white solid into; Refilter, washing to filtrating is neutral, and filter cake is dissolved in the 20ml sodium hydroxide solution; Activated carbon decolorizing gets 4.07g white powder 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline.Total recovery: 96% (mp:251-253 ℃).
Embodiment 2
(the 3.52g massfraction is 80% solution, and 0.03mol), 70 ℃ are incubated 1.5h in 95% ethanol (50ml) solution of the 2-of 6g, 0.015mol nitro-4-difluoro-methoxy-aniline, to add catalyzer Raney-Ni (0.3g) and reductive agent Hydrazine Hydrate 80; Reduce 2-amino-4-difluoro-methoxy-aniline, add 0.3gRaney-Ni, backflow 5h; The elimination catalyzer, and adding oxyethyl group sulphur ortho acid potassium in filtrating (5.2g, 0.018mol); At 90 ℃ of following reflux 4h, leave standstill cooling; Reaction solution is poured in the water of 200ml, adding Hydrogen chloride, to be adjusted to PH be 3, changes white solid into; Refilter, washing to filtrating is neutral, and filter cake is dissolved in the 20ml sodium hydroxide solution; Activated carbon decolorizing gets 5.36g white powder 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline.Total recovery: 97% (mp:251-253 ℃)
Claims (3)
1. the preparation method of 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline; It is characterized in that: this preparing method's step is: in 95% ethanolic soln of 2-nitro-4-difluoro-methoxy-aniline, add catalyzer Raney-Ni and reductive agent Hydrazine Hydrate 80,50-70 ℃ is incubated 1-2h, reduce 2-amino-4-difluoro-methoxy-aniline; Add the Raney-Ni of equivalent; Backflow 2-6h, the elimination catalyzer adds oxyethyl group sulphur ortho acid potassium in filtrating; At 70-90 ℃ of following reflux 3-6h, leave standstill cooling; Reaction solution is poured in the water of 200ml, adding Hydrogen chloride, to be adjusted to PH be 3, changes white solid into, refilters, and washing to filtrating is neutral, and filter cake is dissolved in an amount of sodium hydroxide solution, activated carbon decolorizing, 2-sulfydryl-5-difluoro-methoxy-1H-benzoglyoxaline.
2. preparation method according to claim 1 is characterized in that: the mol ratio of said 2-nitro-4-difluoro-methoxy-aniline, Hydrazine Hydrate 80 and oxyethyl group sulphur ortho acid potassium is: (1-1.5): 2: (1.1-1.6).
3. preparation method according to claim 1 is characterized in that: the employing one kettle way that responds among this preparation method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110171994A CN102311391A (en) | 2011-06-24 | 2011-06-24 | Method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110171994A CN102311391A (en) | 2011-06-24 | 2011-06-24 | Method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole |
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| CN102311391A true CN102311391A (en) | 2012-01-11 |
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| CN201110171994A Pending CN102311391A (en) | 2011-06-24 | 2011-06-24 | Method for preparing 2-mercapto-5-difluoromethoxy-1H-benzimidazole |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539746A (en) * | 2013-09-09 | 2014-01-29 | 浙江科技学院 | Method for synthesizing 5-difluoromethoxy-2-mercapto-1H-benzimidazole |
-
2011
- 2011-06-24 CN CN201110171994A patent/CN102311391A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 刘德龙等: "以水合肼作还原剂制备2-巯基-5-二氟甲氧基-1H-苯并咪唑", 《徐州师范大学学报(自然科学版)》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539746A (en) * | 2013-09-09 | 2014-01-29 | 浙江科技学院 | Method for synthesizing 5-difluoromethoxy-2-mercapto-1H-benzimidazole |
| CN103539746B (en) * | 2013-09-09 | 2016-01-27 | 浙江科技学院 | A kind of synthetic method of 5-difluoro-methoxy-2-sulfydryl-1H-benzoglyoxaline |
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Application publication date: 20120111 |