CN1053229A - Synthetic process for " metholazine " - Google Patents
Synthetic process for " metholazine " Download PDFInfo
- Publication number
- CN1053229A CN1053229A CN 91100481 CN91100481A CN1053229A CN 1053229 A CN1053229 A CN 1053229A CN 91100481 CN91100481 CN 91100481 CN 91100481 A CN91100481 A CN 91100481A CN 1053229 A CN1053229 A CN 1053229A
- Authority
- CN
- China
- Prior art keywords
- acid
- reaction
- masalazine
- synthetic process
- metholazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Synthetic process for " metholazine ".
Masalazine is a new treatment ulcerative colitis medicine, and the present invention is starting raw material with the Whitfield's ointment, prepares Masalazine through reactions steps such as nitrated and reduction.
Description
The invention belongs to meticulous organic chemical industry (medicine is synthetic) field.
H.Well et al. is at " Berlchte de Deutschen Chemlschen Gesellschaft " 1922, the disclosed relevant Masalazines (5-aminosalicylic acid) of 55B 2664 synthetic is to be starting raw material with the 5-nitrosalicylic acid, is that solvent avoided thermal response to make with zinc powder and concentrated hydrochloric acid with alkali lye.Its reaction formula is:
The present invention is starting raw material with the Whitfield's ointment through nitrated generation compound (I), and (I) generates Masalazine under acidic conditions and metallic reducing agent and acid row reduction reaction between 60-100 ℃.Its reaction formula is:
The new synthesis process of Masalazine is compared with preceding technology, and difference is the starting raw material difference, reaction reagent, and the processing mode after condition and reaction are finished is also different.Novel process is a starting raw material with the Whitfield's ointment, has increased nitration reaction technology; Former technology is starting raw material with the nitrosalicylic acid, and the domestic market does not have this raw material and sells.Novel process reaction conditions in reduction process be acid and between 60-100 ℃ the prepared in reaction Masalazine; Avoid overheated and react and former technology is solvent with alkali lye.Novel process can use metallic iron as going back original reagent; And former technology is to use zinc powder to make reductive agent, and cost is higher.Novel process uses molten acid folding of alkali or sour molten alkali to analyse after reduction reaction is finished and the method for adding antioxidant obtains Masalazine; And former technology obtains Masalazine with salt by salting-out process.In a word, the invention provides and a kind ofly prepare the novel process of Masalazine by Whitfield's ointment, its cost value is cheap, the processing condition gentleness.
Embodiment:
Whitfield's ointment 69g is suspended among the water 70ml, drips 70% nitric acid 87.5ml, insulation reaction 1 hour about 70 ℃, in the impouring 700ml frozen water, place 1 hour after-filtration, filter residue adds 650ml water and is heated to and boils, heat filtering, washing filter residue secondary gets light yellow solid (I) 30.4g, mp227-230 ℃.
Water 250ml is warming up to more than 60 ℃, adds the iron powder 14g of hydrochloric acid 17ml and full dose 1/3, is heated to boiling, iron powder and (I) of surplus are alternately dropped into, insulation reaction 1 hour is cooled to 80 ℃, adds caustic lye of soda and regulates PH to alkalescence, discard after filtration, the filter residue washing, the powder 5.6g that takes a policy filters, and adds 40% sulfuric acid after the cooling to slightly acidic, filter dry light grey Masalazine crude product 24.7g.
Above-mentioned crude product 48g is dissolved in 800ml water and hydrochloric acid 36ml, adds gac, is heated to filtrations of boiling, and cooling is stirred and dripped solution of ammonium hydroxide down to PH2-3, filters, and washing, dryly gets Masalazine 43.2g, mp274 ℃ (decomposition).
Claims (4)
1, a kind of employing Whitfield's ointment is a starting raw material, through the certain reaction step, makes the new synthetic process of the ulcerative colitis medicine Masalazine that obtains medical treatment, and it is characterized in that making Whitfield's ointment and nitric acid effect to carry out nitration reaction and generates compound (1).(1) reaction in acidic solution generates Masalazine with metallic reducing agent and acid.Its reaction formula is:
2, according to the said synthetic process for " metholazine " of claim 1, when carrying out nitration reaction generation compound (I) by Whitfield's ointment and nitric acid effect, its feature is being a reaction medium with water or acetic acid, and concentration of nitric acid is more than 25%, and reaction is 1-2 hour between 20-95 ℃.
3, according to the said synthetic process for " metholazine " of claim 1, when reacting the generation Masalazine by (I) with metallic reducing agent and acid in acid liquid, its feature is being solvent with dilute hydrochloric acid, and metallic reducing agent is an iron, acid is hydrochloric acid, and reaction is 1-2 hour between 60-100 ℃.
4,, it is characterized in that reacting the method for using alkali-soluble acid analysis or sour molten alkali to analyse after finishing and obtain Masalazine, and in this process, use antioxidant according to claim 1 or 3 said synthetic process for " metholazine ".
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 91100481 CN1053229A (en) | 1991-01-23 | 1991-01-23 | Synthetic process for " metholazine " |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 91100481 CN1053229A (en) | 1991-01-23 | 1991-01-23 | Synthetic process for " metholazine " |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1053229A true CN1053229A (en) | 1991-07-24 |
Family
ID=4904652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 91100481 Pending CN1053229A (en) | 1991-01-23 | 1991-01-23 | Synthetic process for " metholazine " |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1053229A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999040060A1 (en) * | 1998-02-06 | 1999-08-12 | Rhodia Chimie | Method for hydrogenating 5-nitrosalicylic acids |
| CN1850334B (en) * | 2006-05-26 | 2012-03-28 | 中国科学院上海有机化学研究所 | Use of Zr compound in catalyzing clean nitration of salicylic-acids compounds |
| CN103201255A (en) * | 2010-12-25 | 2013-07-10 | 浙江华海药业股份有限公司 | Preparation of 5-aminosalicylic acid by gas phase catalytic carboxylation |
| CN106831460A (en) * | 2017-02-24 | 2017-06-13 | 青铜峡市嘉华化工有限公司 | The preparation method of the aminobenzoic acid of 3 methyl 4 |
| US11249150B2 (en) | 2019-11-14 | 2022-02-15 | Institute Of Semiconductors, Chinese Academy Of Sciences | Spin valve and spintronic device comprising the same |
| CN114605277A (en) * | 2022-04-18 | 2022-06-10 | 宁波怡和医药科技有限公司 | Synthesis method of mesalazine |
-
1991
- 1991-01-23 CN CN 91100481 patent/CN1053229A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999040060A1 (en) * | 1998-02-06 | 1999-08-12 | Rhodia Chimie | Method for hydrogenating 5-nitrosalicylic acids |
| FR2774685A1 (en) * | 1998-02-06 | 1999-08-13 | Rhodia Chimie Sa | PROCESS FOR HYDROGENATION OF NITROSALICYLIC ACIDS |
| CN1850334B (en) * | 2006-05-26 | 2012-03-28 | 中国科学院上海有机化学研究所 | Use of Zr compound in catalyzing clean nitration of salicylic-acids compounds |
| CN103201255A (en) * | 2010-12-25 | 2013-07-10 | 浙江华海药业股份有限公司 | Preparation of 5-aminosalicylic acid by gas phase catalytic carboxylation |
| CN103201255B (en) * | 2010-12-25 | 2014-11-19 | 浙江华海药业股份有限公司 | Preparation of 5-aminosalicylic acid by gas phase catalytic carboxylation |
| US9067867B2 (en) | 2010-12-25 | 2015-06-30 | Zhejiang Huahai Pharmaceutical Co., Ltd. | Preparation of 5-aminosalicylic acid by gas phase catalytic carboxylation |
| CN106831460A (en) * | 2017-02-24 | 2017-06-13 | 青铜峡市嘉华化工有限公司 | The preparation method of the aminobenzoic acid of 3 methyl 4 |
| US11249150B2 (en) | 2019-11-14 | 2022-02-15 | Institute Of Semiconductors, Chinese Academy Of Sciences | Spin valve and spintronic device comprising the same |
| CN114605277A (en) * | 2022-04-18 | 2022-06-10 | 宁波怡和医药科技有限公司 | Synthesis method of mesalazine |
| CN114605277B (en) * | 2022-04-18 | 2022-10-11 | 宁波怡和医药科技有限公司 | Synthesis method of mesalazine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111646881B (en) | Synthetic method of m-trifluoromethyl phenol | |
| JPS5850775B2 (en) | Production method of copper-iron-aluminum catalyst | |
| CN1053229A (en) | Synthetic process for " metholazine " | |
| Hawthorne et al. | A Study of the Reaction of Hydroxide Ion with B20H18-2 | |
| CN114213205A (en) | Preparation method of deuterium-substituted benzene | |
| CN101638353B (en) | Method for removing residual metal in organic compounds by using EDTA calcium disodium salts as chelons in liquid phase | |
| US4299965A (en) | Preparation of benzotriazole | |
| JPH0393750A (en) | Fluorobenzene derivative and method of its preparation | |
| US2022889A (en) | Method of desulphonating diaminodiphenylamine-2-sulphonic acid compounds | |
| US2946822A (en) | Purification of m-phenylenediamine | |
| CN106167471A (en) | A kind of preparation method of chlorzoxazone | |
| DE2053715A1 (en) | Production of 2-alk> oil-substituted thiazoles and selenazoles | |
| CN101830831B (en) | Method for preparing ortho-diazanyl benzonitrile | |
| CN106518747A (en) | New method for preparing gliclazide intermediate | |
| JPS59190984A (en) | Production of furfuryl alcohol | |
| US3190886A (en) | 2, 5-diaryl-1, 2, 3, 4, 5, 6-hexaazapentalenes | |
| DE4018245A1 (en) | METHOD FOR PRODUCING SULFONATED ANTHRANILE ACIDS | |
| DE10297840B3 (en) | Process for the preparation of metal acetylacetonates | |
| DE2911176C2 (en) | ||
| CN113979892A (en) | Catalytic synthesis method of hexamidine and hexamidine diisethionate | |
| CN117645574A (en) | Preparation method of 2, 4-dichloro-6- (4-methoxyphenyl) -1,3, 5-triazine | |
| JP2522823B2 (en) | Novel mercapto compound and method for producing the same | |
| CN104592137B (en) | 2,2 ', 2 "-[1,3,5-triazine-2,4,6-tri-thiol] three propanoic acid and synthetic method thereof | |
| CN86100379A (en) | 2,4-DfBP new synthetic process | |
| CN116375705A (en) | Preparation method of ruthenium compound for protein fluorescent staining |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |