CN1421438A - Prepn process of thianidazole - Google Patents
Prepn process of thianidazole Download PDFInfo
- Publication number
- CN1421438A CN1421438A CN 01139969 CN01139969A CN1421438A CN 1421438 A CN1421438 A CN 1421438A CN 01139969 CN01139969 CN 01139969 CN 01139969 A CN01139969 A CN 01139969A CN 1421438 A CN1421438 A CN 1421438A
- Authority
- CN
- China
- Prior art keywords
- thianidazole
- formic acid
- methyl
- acid
- neutralized
- 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
- 238000000034 method Methods 0.000 title abstract description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 38
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 19
- 235000019253 formic acid Nutrition 0.000 claims abstract description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 14
- FFYTTYVSDVWNMY-UHFFFAOYSA-N 2-Methyl-5-nitroimidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1 FFYTTYVSDVWNMY-UHFFFAOYSA-N 0.000 claims abstract description 10
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 150000002460 imidazoles Chemical class 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- -1 thiophene nitre azoles Chemical class 0.000 claims description 7
- 238000013019 agitation Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 7
- 238000005516 engineering process Methods 0.000 abstract description 5
- 238000001914 filtration Methods 0.000 abstract description 4
- 238000010790 dilution Methods 0.000 abstract description 3
- 239000012895 dilution Substances 0.000 abstract description 3
- 238000003756 stirring Methods 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 230000003472 neutralizing effect Effects 0.000 abstract 2
- 238000001816 cooling Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- 238000006396 nitration reaction Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to organic chemical technology field. The preparation process of thianidazole includes dissolving 2-methyl-5-nitroimidazole in mixed acid comprising formic acid and sulfuric acid; adding epoxy propane while stirring, at 15-55 deg.c and for 2-6 hr; adding water for dilution; neutralizing with sodium hydroxide to pH 4; filtering to eliminate unreacted 2-methyl-5-nitroimidazole; further neutralizing the filtrate to pH 10; cooling naturally to 25 deg.c; and filtering to obtain thianidazole. The said process has thianidazole yield of 45.2%, 10% higher than that in available technology.
Description
Technical field
The invention belongs to technical field of organic chemistry, particularly relate to a kind of medicine preparation process of thianidazole.
Background technology
Preparation method at present known anaerobe resistant, antiprotozoal drug thiophene nitre azoles has a lot, and FrM3270 (1965) is dissolved in 1000ml with 2-methyl-5-nitroimidazole (II) of 127g, in 85% the formic acid, is cooled to 13 ℃.Add 290g oxyethane, 1.5 hours time, temperature rises to and allows to place liquid (20mm) under 14 ℃ of room temperatures, adds 100ml water, mixes, filters.With 200ml water flushing throw out, to (II) surplus 75.5g.NaOH with 10N filters, flushing, makes pH≤9, makes this mixture cross liquid in the ice, gets the thiophene nitre azoles of 36g, and yield is 35%.
Above-mentioned reaction is to be solvent with formic acid, because formic acid is limit the solubleness of 2-methyl-5-nitro imidazoles (II), its temperature of reaction requires low in addition, needing to add 8 times of formic acid to (II) weight just can make material fully dissolve, because after the existence of a large amount of formic acid causes reaction to be finished, add the alkali neutralization to aftertreatment and caused difficulty again, by underpressure distillation, steam formic acid again, the formic acid that steams can not be applied mechanically because of water content is too high again, cause the formic acid consumption very big, from reaction mechanism, the solvent comprises water amount is few more, acidity is strong more good more, and acid the carrying out that helps main reaction by force, and can suppress the generation of by product isomer, and can improve transformation efficiency and yield.
Summary of the invention
In order to overcome the problem that prior art exists, we with the acidity that strengthens solvent, reduce the moisture in the solvent and strengthen the solubleness of solvent, the raising yield is a purpose, we provide a kind of new preparation process of thianidazole.
Its chemical name of thiophene nitre azoles: 1-(hydroxyl-2-propyl group)-2-methyl-5-nitro imidazoles (I) chemical structural formula:
New preparation method is:
2-methyl-5-nitro imidazoles (II) is dissolved in formic acid and sulfuric acid (formic acid: sulfuric acid=1: 0.2～1: 0.6) in Pei Zhi the mixing acid, under agitation added propylene oxide (III) in 15～55 ℃ in 2～6 hours, propylene oxide finishes, thin up, be neutralized to pH4 with 28% sodium hydroxide, filter, leach unconverted (II), filtrate continuation is neutralized to pH10, put and be chilled to 25 ℃, filter, get thiophene nitre azoles (I), yield 45.2%.
The formic acid consumption of this new preparation method-nitration mixture technology is 19% of a known technology consumption, and yield is increased to 45.2% by 35%, and has cut down the technological process of the underpressure distillation formic acid after reaction is finished, and has reduced the investment and the power consumption of equipment.
Embodiment
For further understanding content of the present invention, characteristics and effect, exemplify following examples now:
Embodiment 1:
In the reaction flask of stirring is housed, add 85% formic acid 64g, slowly in formic acid, drip 15.4ml sulfuric acid and be mixed with nitration mixture, temperature must not be crossed 50 ℃.In nitration mixture, add 2-methyl-5-nitro imidazoles 35g, be warming up to 40 ℃ complete molten, in 2 hours, drip propylene oxide 69g in 40～45 ℃, be incubated 30 minutes, add water 50ml dilution, only 25 ℃ drip down 28% sodium hydroxide and be neutralized to pH3, filter, reclaim 2-methyl-5-nitro imidazoles 19.7g, filtrate continuation is neutralized to pH10, be chilled to 15 ℃ of filtrations, obtain thiophene nitre azoles 10.2g (50 ℃ of vacuum-drying), yield 45.2%.
Embodiment 2:
In the reaction flask of stirring is housed, add 85% formic acid 64g, slowly in formic acid, drip 15.4ml sulfuric acid and be mixed with nitration mixture, temperature must not be crossed 50 ℃, take out 22.8ml nitration mixture (making the usefulness of adding in the reaction) and in nitration mixture, add 2-methyl-5-nitro imidazoles 35g, be warming up to 40 ℃ complete molten, in 1 hour, drip propylene oxide 34g in 40～45 ℃, to stay the 22.8ml nitration mixture and add in the reaction solution, and in 1 hour, continue again to drip propylene oxide 35g, be incubated 30 minutes in 40～45 ℃, add water 50ml dilution, only 25 ℃ drip down 28% sodium hydroxide and be neutralized to pH3, filter, reclaim 2-methyl-5-nitro imidazoles 17.2g, filtrate continuation is neutralized to pH10, be chilled to 15 ℃ of filtrations, obtain thiophene nitre azoles 12.6g (50 ℃ of vacuum-drying), yield 48.6%.
Claims (1)
1. the preparation process of thianidazole of formula (I), (formic acid: sulfuric acid=1: 0.2～1: 0.6) in Pei Zhi the mixing acid, under agitation added propylene oxide (III) in 15～55 ℃ in 2～6 hours, propylene oxide finishes to it is characterized in that 2-methyl-5-nitro imidazoles (II) is dissolved in formic acid and sulfuric acid, thin up, be neutralized to pH4 with 28% sodium hydroxide, filter, leach unconverted (II), filtrate continuation is neutralized to pH10, put and be chilled to 25 ℃, filter, get thiophene nitre azoles (I).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01139969 CN1421438A (en) | 2001-11-22 | 2001-11-22 | Prepn process of thianidazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01139969 CN1421438A (en) | 2001-11-22 | 2001-11-22 | Prepn process of thianidazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1421438A true CN1421438A (en) | 2003-06-04 |
Family
ID=4675559
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01139969 Pending CN1421438A (en) | 2001-11-22 | 2001-11-22 | Prepn process of thianidazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1421438A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539745A (en) * | 2013-10-11 | 2014-01-29 | 黄冈赛康药业有限公司 | Preparation method of secnidazole |
| CN110564394A (en) * | 2019-09-20 | 2019-12-13 | 中国石油化工股份有限公司 | Thick oil thermal recovery well sulfide remover and preparation method thereof |
| US11253501B2 (en) | 2015-06-01 | 2022-02-22 | Lupin Inc. | Secnidazole formulations and use in treating bacterial vaginosis |
| CN116813554A (en) * | 2023-07-03 | 2023-09-29 | 爱斯特（成都）生物制药股份有限公司 | Continuous flow synthesis method of secnidazole |
-
2001
- 2001-11-22 CN CN 01139969 patent/CN1421438A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103539745A (en) * | 2013-10-11 | 2014-01-29 | 黄冈赛康药业有限公司 | Preparation method of secnidazole |
| CN103539745B (en) * | 2013-10-11 | 2015-09-02 | 黄冈赛康药业有限公司 | A kind of preparation method of secnidazole |
| US11253501B2 (en) | 2015-06-01 | 2022-02-22 | Lupin Inc. | Secnidazole formulations and use in treating bacterial vaginosis |
| CN110564394A (en) * | 2019-09-20 | 2019-12-13 | 中国石油化工股份有限公司 | Thick oil thermal recovery well sulfide remover and preparation method thereof |
| CN110564394B (en) * | 2019-09-20 | 2022-01-28 | 中国石油化工股份有限公司 | Thick oil thermal recovery well sulfide remover and preparation method thereof |
| CN116813554A (en) * | 2023-07-03 | 2023-09-29 | 爱斯特（成都）生物制药股份有限公司 | Continuous flow synthesis method of secnidazole |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102321028B (en) | Method for synthesizing 2-methyl-5-nitroimidazole-1-ethanol | |
| CN114031551B (en) | Fluopicolide and synthesis method thereof | |
| CN1421438A (en) | Prepn process of thianidazole | |
| CN101508635B (en) | Method of preparing copper acetylacetone | |
| CN111533660A (en) | Preparation method of 2, 4-dichloro-3, 5-dinitrobenzotrifluoride | |
| CN102146022A (en) | Method for preparing 3-chlorine-5-bromophenol | |
| CN118184546B (en) | Preparation method of O-methyl-N-nitroisourea | |
| CN113354623B (en) | Preparation method of ilaprazole key intermediate 5- (1H-pyrrole-1-yl) -2-mercaptobenzimidazole | |
| CN112358404B (en) | Preparation method of 2-chloro-6-methylaniline | |
| CN113979892A (en) | Catalytic synthesis method of hexamidine and hexamidine diisethionate | |
| CN102229625B (en) | Preparation method of ferrocenecarboxylic acid | |
| CN1091442C (en) | Method for preparing phenylpyridyl substituted urea | |
| CN114230456A (en) | Synthesis process of cobalt acetate | |
| CN1194970C (en) | Preparation method of 2-nitroimidazole | |
| CN119039132A (en) | Preparation method of 2- (4-chloro-2, 6-dimethylphenyl) acetic acid | |
| JPS6222752A (en) | Production of guazatine 3-alkylbenzenesulfonic acid salt | |
| EP2349980B1 (en) | Process for preparing 2-amino-6-nitro-benzoic acid | |
| CN119019413A (en) | A method for continuously synthesizing vitamin B6 intermediates by microwave catalysis | |
| CN114634422B (en) | Preparation method of dinitolmide | |
| CN112645824B (en) | Method for biosynthesizing isopropylamine hydrochloride by laccase | |
| CN115925559B (en) | Preparation method of 1-amino-1-cyclopentyl methanol | |
| CN112079894B (en) | Preparation method of Levonorgestrel pharmacopoeia impurity V | |
| CN121021414A (en) | A high-purity cycloazinone cyclization process | |
| CN100378069C (en) | Refining method of ammoximation reaction product of p-hydroxyacetophenone | |
| CN119528806A (en) | Synthesis method of 5-difluoromethoxy-2-pyridinecarboxaldehyde |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |