CN102557994A - Synthesis method of 2-phenoxymethanesulfonyl aniline - Google Patents
Synthesis method of 2-phenoxymethanesulfonyl aniline Download PDFInfo
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- CN102557994A CN102557994A CN2011104197299A CN201110419729A CN102557994A CN 102557994 A CN102557994 A CN 102557994A CN 2011104197299 A CN2011104197299 A CN 2011104197299A CN 201110419729 A CN201110419729 A CN 201110419729A CN 102557994 A CN102557994 A CN 102557994A
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Abstract
The invention relates to a synthesis method of 2-phenoxymethanesulfonyl aniline. O-aminodiphenyl ether and methanesulfonyl chloride are used as raw materials to react in an N,N-dimethylaniline solvent under heating conditions, the reaction liquid precipitates in highly acidic water in an ice water bath, and the precipitate is washed with water. The method comprises the following steps: reacting at 75-90 DEG C for 20-26 hours, slowly pouring the reaction liquid in acid water cooled by the ice water bath to precipitate, filtering, and washing with water; and recrystallizing to obtain the 2-phenoxymethanesulfonyl aniline, carrying out reduced pressure distillation on the filtrate to recycle the N,N-dimethylaniline. The invention has the advantages of mild reaction conditions, simple equipment, high yield and low pollution, and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of compound method of 2-benzene oxygen sulfonyl methane aniline, be specially N, accelerine replaces the method for pyridine Synthetic 2-benzene oxygen sulfonyl methane aniline, belongs to chemical field.
Background technology
2-benzene oxygen sulfonyl methane aniline is the important intermediate of organic synthesis medicine nimesulide, and mainly adopting with the pyridine in the suitability for industrialized production at present is solvent, the method for neighbour-amino-diphenylethers and methane sulfonyl chloride reaction Synthetic 2-benzene oxygen sulfonyl methane aniline.Because aftertreatment need be iced and separated pyridine solution, therefore cause the expensive pyridine solution of price to reclaim, not only improve raw materials cost, and caused environmental pollution.Chinese patent CN 200710056882.3 uses ETHYLE ACETATE or triethylamine solvent to synthesize.And using N, accelerine is that the compound method of solvent is not reported.
Summary of the invention
The purpose of this invention is to provide a kind of simple, gentleness, high yield, oligosaprobic N; Accelerine replaces the method for pyridine Synthetic 2-benzene oxygen sulfonyl methane aniline; Can overcome deficiency of the prior art, technology of the present invention is simple, gentleness, high yield, lowly pollute, suitable suitability for industrialized production.
The method of a kind of Synthetic 2 provided by the invention-benzene oxygen sulfonyl methane aniline; It is to be raw material with neighbour-amino-diphenylethers and methane sulfonyl chloride, reacting by heating in organic solvent, and reaction solution is separated out deposition under ice-water bath He in the highly acid water; Washing, concrete step is:
1) at 75-90 ℃ and N, in the accelerine solvent, the abundant stirring reaction 20-26 of neighbour-amino-diphenylethers and methane sulfonyl chloride hour; Reaction is reduced to room temperature after finishing, in the sour water under slowly the impouring ice-water bath cools off with reaction solution; Separate out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion;
2) bullion is dissolved in the aqueous sodium hydroxide solution under 60 ℃, adds activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter, filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing, drying;
3) filtrating of step 1) is transferred pH=10-12 with sodium hydroxide solution, tells organic layer, anhydrous sodium sulfate drying, and N, accelerine are reclaimed in underpressure distillation.
Described neighbour-amino-diphenylethers and N, the mol ratio of accelerine is 1: 1.5-3.
The invention provides the method for a kind of simple, gentleness, high yield, oligosaprobic Synthetic 2-benzene oxygen sulfonyl methane aniline, overcome deficiency of the prior art, technology is simple, gentleness, high yield, low pollution, suitable suitability for industrialized production.
Embodiment
Following examples are intended to explain the present invention rather than do any restriction to of the present invention.
Embodiment 1
Have stirring, temperature is taken into account in the reaction flask of reflux exchanger, adds neighbour-amino-diphenylethers 300g, N, accelerine 480g opens and stirs; Be warming up to 75 ℃, in 1-2 hour, drip methane sulfonyl chloride 200g, 85 ℃ are incubated 22 hours; Reaction is reduced to room temperature after finishing, and in the 650g concentrated hydrochloric acid and 1200ml water under slowly the impouring ice-water bath cools off with reaction solution, separates out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion 630g.
Refining: the aniline bullion is dissolved in 140g sodium hydroxide and the 4400ml water, and 60 ℃ dissolve clearly, add activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter; Filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing; Drying, heavy 399g, yield 93.44%, mp123-126 ℃.
Embodiment 2
Have stirring, temperature is taken into account in the reaction flask of reflux exchanger, adds neighbour-amino-diphenylethers 300g, N, accelerine 300g opens and stirs; Be warming up to 80 ℃, in 1-2 hour, drip methane sulfonyl chloride 200g, 85 ℃ are incubated 24 hours; Reaction is reduced to room temperature after finishing, and in the 650g concentrated hydrochloric acid and 1200ml water under slowly the impouring ice-water bath cools off with reaction solution, separates out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion 580g.
Refining: the aniline bullion is dissolved in 140g sodium hydroxide and the 4400ml water, and 60 ℃ dissolve clearly, add activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter; Filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing; Drying, heavy 363g, yield 91.1%, mp122-124 ℃.
Embodiment 3
Have stirring, temperature is taken into account in the reaction flask of reflux exchanger, adds neighbour-amino-diphenylethers 300g, N, accelerine 470g opens and stirs; Be warming up to 80 ℃, in 1-2 hour, drip methane sulfonyl chloride 200g, 85 ℃ are incubated 24 hours; Reaction is reduced to room temperature after finishing, and in the 650g concentrated hydrochloric acid and 1200ml mixed aqueous solution under slowly the impouring ice-water bath cools off with reaction solution, separates out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion 640g.
Refining: the aniline bullion is dissolved in 140g sodium hydroxide and the 4400ml water, and 60 ℃ dissolve clearly, add activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter; Filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing; Drying, heavy 405g, yield 94.8%, mp124-126 ℃.
Embodiment 4
The reaction filtrating 2400ml of above-mentioned instance adds the neutralization of 30% sodium hydroxide solution, transfers pH=10-11, divides oil-yielding stratum, anhydrous sodium sulfate drying, and N is reclaimed in underpressure distillation, and accelerine 342g surveys refractive power and meets the requirements, and the recovery 70% can directly be used for reaction.
Have stirring, temperature is taken into account in the reaction flask of reflux exchanger, adds neighbour-amino-diphenylethers 300g, above-mentioned recovery N, accelerine 470g opens and stirs; Be warming up to 90 ℃, in 1-2 hour, drip methane sulfonyl chloride 200g, 90 ℃ are incubated 24 hours; Reaction is reduced to room temperature after finishing, and in the 650g concentrated hydrochloric acid and 1200ml water under slowly the impouring ice-water bath cools off with reaction solution, separates out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion 600g.
Refining: the aniline bullion is dissolved in 140g sodium hydroxide and the 4400ml water, and 60 ℃ dissolve clearly, add activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter; Filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing; Drying, heavy 380g, yield 93.3%, mp123-125 ℃.
Advantage of the present invention is reaction conditions gentleness, simple, the high yield of equipment, the low pollution.2-benzene oxygen sulfonyl methane aniline is suitable for the suitability for industrialized production nimesulide as midbody.
Claims (2)
1. the method for Synthetic 2-benzene oxygen sulfonyl methane aniline; It is to be raw material with neighbour-amino-diphenylethers and methane sulfonyl chloride, reacting by heating in organic solvent, and reaction solution is separated out deposition under ice-water bath He in the highly acid water; Washing is characterized in that concrete step is:
1) at 75-90 ℃ and N, in the accelerine solvent, the abundant stirring reaction 20-26 of neighbour-amino-diphenylethers and methane sulfonyl chloride hour; Reaction is reduced to room temperature after finishing, in the sour water under slowly the impouring ice-water bath cools off with reaction solution; Separate out deposition; Filter, washing gets 2-benzene oxygen sulfonyl methane aniline bullion;
2) bullion is dissolved in the aqueous sodium hydroxide solution under 60 ℃, adds activated carbon decolorizing, continue to be heated to 85 ℃, the heat filter, filtrating is reduced to 45 ℃, adds concentrated hydrochloric acid and transfers pH=1-2, separates out deposition, filters washing, drying;
3) filtrating of step 1) is transferred pH=10-12 with sodium hydroxide solution, tells organic layer, anhydrous sodium sulfate drying, and N, accelerine are reclaimed in underpressure distillation.
2. method according to claim 1 is characterized in that described neighbour-amino-diphenylethers and N, and the mol ratio of accelerine is 1: 1.5-3.
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| CN2011104197299A CN102557994A (en) | 2011-12-15 | 2011-12-15 | Synthesis method of 2-phenoxymethanesulfonyl aniline |
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| CN2011104197299A CN102557994A (en) | 2011-12-15 | 2011-12-15 | Synthesis method of 2-phenoxymethanesulfonyl aniline |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3840597A (en) * | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
| US3856859A (en) * | 1973-06-08 | 1974-12-24 | Riker Laboratories Inc | Selective nitration process |
| US4664673A (en) * | 1983-12-16 | 1987-05-12 | Ciba-Geigy Corporation | Process for protecting keratinous material from attack by insects that feed on keratin and novel phenoxytrifluoromethanesulfonanilides |
| CN1511828A (en) * | 2002-12-31 | 2004-07-14 | �й������ž�����ҽѧ��ѧԺ����ҽ | Sufonic aniline derivatives and their medicinal use |
| WO2007110876A2 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Novel sulfonanilide derivatives, pharmaceutical compositions comprising the same and process thereof |
| 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 |
-
2011
- 2011-12-15 CN CN2011104197299A patent/CN102557994A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3840597A (en) * | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
| US3856859A (en) * | 1973-06-08 | 1974-12-24 | Riker Laboratories Inc | Selective nitration process |
| US4664673A (en) * | 1983-12-16 | 1987-05-12 | Ciba-Geigy Corporation | Process for protecting keratinous material from attack by insects that feed on keratin and novel phenoxytrifluoromethanesulfonanilides |
| CN1511828A (en) * | 2002-12-31 | 2004-07-14 | �й������ž�����ҽѧ��ѧԺ����ҽ | Sufonic aniline derivatives and their medicinal use |
| WO2007110876A2 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Novel sulfonanilide derivatives, pharmaceutical compositions comprising the same and process thereof |
| 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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Application publication date: 20120711 |