CN110172039A - A kind of method of solid acid catalysis synthesis metronidazole - Google Patents
A kind of method of solid acid catalysis synthesis metronidazole Download PDFInfo
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- CN110172039A CN110172039A CN201810446093.9A CN201810446093A CN110172039A CN 110172039 A CN110172039 A CN 110172039A CN 201810446093 A CN201810446093 A CN 201810446093A CN 110172039 A CN110172039 A CN 110172039A
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- solid acid
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- nitro imidazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/94—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to other ring members
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Abstract
This application discloses a kind of methods of solid acid catalysis synthesis metronidazole, and this method comprises the following steps: obtaining metronidazole by raw material, solid acid as catalyst and reacting ethylene oxide of 2- 5-nitro imidazole.Reaction system filtering, recycles solid acid;Filtrate concentration adjusts pH value to 2~3 with alkali after adding water to mix, 2- 5-nitro imidazole is recovered by filtration, filtrate, which adjusts pH value with alkali again, can be obtained metronidazole to 10.The invention synthesis route is easy, and production cost is low, and solid acid catalyst is environmentally friendly, reproducible utilization.
Description
Technical field
The present invention relates to a kind of methods of solid acid catalysis synthesis metronidazole, belong to chemical pharmacy technology field.
Background technique
Metronidazole, white to slightly yellow crystalline powder, entitled 1- (2- the ethoxy) -2- 5-nitro imidazole of chemistry.First
Nitre azoles often individually or with other antibiotic is combined treatment pelvic infection, bacterial vaginitis as antibiotic and antiprotozoan agent.It is right
Anti- drachunculiasis, Giardiasis disease, Trichomonas vaginalis and amcbiasis.Metronidazole is the light moderate fusiform of First episode
Bacillus colitis disease's first choice medication, the drug is also effective to septicemia, endocarditis, infection of meninges, is also used for treating
Oral cavity anaerobium infection.The drug ranks in standard essential medicines list of WHO, even more indispensable on basic medical treatment
Drug.
In existing metronidazole API synthesis technology, formic acid and sulfuric acid mixed acid process are mainly used, which needs
The a large amount of concentrated sulfuric acid is used, sulfuric acid can not recycle.It needs to adjust pH value with liquid alkaline in postprocessing working procedures, to obtain required product.
N-process liquid alkaline dosage brine waste produced greatly is more, and post processing cost is high, and environmental hazard is big.
Summary of the invention
It is environmentally friendly the purpose of the present invention is to propose to a kind of low cost, the metronidazole with fine prospects for commercial application
Synthetic method.
Specifically, the present invention provides a kind of method for synthesizing metronidazole, this method with 2- 5-nitro imidazole and
Ethylene oxide is raw material, using solid acid as catalyst.
The shortcomings that present invention can overcome liquid acid to be not easily recycled using solid acid as catalyst holds after solid acid reaction
It is easily separated with liquid-phase reaction system, to reduce liquid alkaline amount needed for post-processing neutralizes, and then reaches and reduce salt content in waste water
Purpose, also, solid acid catalyst is i.e. reusable after simple regeneration is handled.
Solid acid of the present invention, the solid acid are SO4 2-/MxOyType solid catalyst, wherein M is selected from Ti, Zr
Or Fe;X, y is each independently selected from 1~3.
Preferably, the solid acid is selected from SO4 2-/TiO2、SO4 2-/ZrO2、SO4 2-/Fe2O3One of or it is a variety of;Especially
Its preferred SO4 2-/ZrO2Solid acid.The synthesis that metronidazole is carried out using the solid acid of the above-mentioned type, can be improved the receipts of metronidazole
Rate.
Solid acid of the present invention is known product, can be bought by commercial sources
In order to further ensure that the quality of synthetic route, the present invention also optimize the ideal amount ratio of each material,
It specifically includes:
The ideal feed weight ratio of the 2- 5-nitro imidazole and the solid acid is 1:0.02~0.06 (recycling
Regenerated solids acid dosage is identical with fresh solid acid dosage), preferred 1:0.04~0.05.Within the scope of above-mentioned feed ratio, help
In the yield for improving metronidazole.
The feed weight ratio of the 2- 5-nitro imidazole and the ethylene oxide is 1:0.4~0.7, preferably 1:0.5
~0.6.Within the scope of above-mentioned feed ratio, the yield of metronidazole and the utilization rate of ethylene oxide are helped to improve.It is of the present invention
Method, preferably using formic acid as reaction dissolvent.
More specifically, synthetic method of the present invention includes the following steps:
(1) 2- 5-nitro imidazole (referred to as itrated compound) is added in formic acid, solid acid is added after stirring and dissolving;
(2) it is passed through ethylene oxide into system obtained by step (1), controls reaction temperature within the scope of 40~75 DEG C, has led to
The reaction was continued after ethylene oxide 30~60 minutes;Separate reaction product to get.
Preferably, the separation reaction product specifically:
Reaction solution obtained by step (2) is filtered to remove solid acid, and (obtained solid acid can be used as reclaiming solid acid circulation
Using), be dissolved in water (preferably the dosage of water is 1~2 times of -5 nitroimidazole of 2- methyl) after filtrate concentration, uses sodium hydroxide solution
(preferably 30% concentration) filters after adjusting pH2~3, and filtrate continues to be adjusted pH value with sodium hydroxide solution to 10~12, and separation is solid
Body is to get (such as filtering obtained filter cake is metronidazole).
Preferably, will filter out the reaction solution after solid acid in vacuum degree is 0.085~0.095MPa, 65~90 DEG C of items of temperature
Concentration and recovery formic acid under part.
Preferably, synthetic method of the present invention includes the following steps:
(1) 2- 5-nitro imidazole is added in formic acid, SO is added after stirring and dissolving4 2-/ZrO2Solid acid, wherein
2- 5-nitro imidazole and SO4 2-/ZrO2The feed ratio of solid acid is 1:0.035~0.05;
(2) it is passed through ethylene oxide into system obtained by step (1), 2- 5-nitro imidazole and ethylene oxide feed intake
Than for 1:0.5~0.6;Reaction temperature is controlled within the scope of 50~65 DEG C, has led to after ethylene oxide that the reaction was continued 30~45 minutes;
(3) reaction solution obtained by step (2) is filtered to remove solid acid, be dissolved in water after filtrate concentration, it is molten with sodium hydroxide
Liquid filters after adjusting pH2~3, and filtrate continues to be adjusted pH value with sodium hydroxide solution to 10~12, filters to obtain metronidazole.
The solid acid catalyst that the present invention uses can recycle after regeneration treatment is dry, and what the present invention used consolidates
Body acid catalysis synthesizes metronidazole, and not only catalytic effect is significant, and environmentally friendly, recovery and reusing and recycling, appointing can guarantee high activity, should
Cost of material can be greatly reduced in method, while new process is easy to operate, can generate very high economic and social benefit.
Detailed description of the invention
Fig. 1 is metronidazole crude product HPLC map in embodiment 1.
Fig. 2 is metronidazole finished product HPLC map in embodiment 8.
Fig. 3 is metronidazole finished product HPLC map in embodiment 15.
Fig. 4 is metronidazole finished product HPLC map in comparative example 1.
Specific embodiment
The application is described in detail below with reference to embodiment, but the application is not limited to these embodiments.
Embodiment 1
- 5 nitroimidazole of 2- methyl is added in the reaction vessel, and is equivalent to the formic acid of 3 times of -5 nitroimidazole of 2- methyl,
And put into the SO42-/ZrO2 type solid acid for being equivalent to 0.035 times of -5 nitroimidazole of 2- methyl.Reaction system is warming up to 50 DEG C
It is uniformly mixed, then starts that the ethylene oxide that total amount is 0.6 times of -5 nitroimidazole of 2- methyl is added portionwise, control temperature exists
50~60 DEG C.Ethylene oxide add after in 55 DEG C insulation reaction 30 minutes, reaction system is then removed by filtration solid acid.It will filter
Except the reaction solution after solid acid is 0.085~0.095MPa, concentration and recovery formic acid under the conditions of 65~90 DEG C of temperature in vacuum degree.It returns
The water for being equivalent to 1.15 times of -5 nitroimidazole of 2- methyl is added after receipts in concentrate, stirring keeps reaction product mixing equal
It is even, then filtered after adjusting pH to 3 with 30% sodium hydroxide solution, filter cake recycles to obtain itrated compound.Filtrate is continued with 30% hydrogen-oxygen
Change sodium solution and be neutralized to pH 10 or so, metronidazole solid can be obtained in filtering (HPLC map is shown in Fig. 1).
Metronidazole crude yield is 73.4% in the present embodiment, content 98.56%.
The solid acid of reaction recycling, i.e. reusable after simple regeneration is handled, dosage and fresh solid acid amount
It is identical.
Embodiment 2-7
Compared with Example 1, the difference of embodiment 2-7 is only that: the amount ratio of itrated compound and ethylene oxide is 1:
0.6, reaction temperature is at 50~60 DEG C, and solid acid and its dosage are different, and see Table 1 for details.
Embodiment 2-7 products therefrom yield and purity information are shown in Table 1.
Table 1: the influence of solid acid classification and dosage to reaction result
Solid acid type | Solid acid dosage (w/w) | Yield | Content |
SO4 2-/TiO2 | 1:0.05 | 69.5% | 97.1% |
SO4 2-/Fe2O3 | 1:0.05 | 68.3% | 97.2% |
SO4 2-/ZrO2 | 1:0.02 | 72.8% | 97.9% |
SO4 2-/ZrO2 | 1:0.05 | 74.9% | 98.2% |
SO4 2-/ZrO2 | 1:0.07 | 74.6% | 98.0% |
Recycle SO4 2-/ZrO2 | 1:0.05 | 74.2% | 97.8% |
It is optimal by SO42-/ZrO2 type catalyst effect known to above data, when catalyst amount is 1:0.04~0.05
To optimize dosage, catalytic amount is more than not significantly improve yield after 1:0.05.Used catalyst passes through regeneration treatment aftereffect
Fruit and fresh catalyst effect indifference.
Embodiment 8
- 5 nitroimidazole of 2- methyl is added in the reaction vessel, and is equivalent to the formic acid of 3 times of -5 nitroimidazole of 2- methyl,
And put into the SO42-/ZrO2 solid acid for being equivalent to 0.04 times of -5 nitroimidazole of 2- methyl.Reaction system is warming up to 50~60 DEG C
It is uniformly mixed, then starts that the ethylene oxide that total amount is equivalent to 0.55 times of -5 nitroimidazole of 2- methyl, epoxy is added portionwise
Ethane add after in 55 DEG C insulation reaction 30 minutes, reaction system is then removed by filtration solid acid.Filtering out will be anti-after solid acid
Answering liquid in vacuum degree is 0.085~0.095MPa, concentration and recovery formic acid under the conditions of 65~90 DEG C of temperature.It is being concentrated after recycling
In object plus it is equivalent to the water of 1.15 times of -5 nitroimidazole of 2- methyl, stirring is uniformly mixed reaction product, then with 30% hydroxide
Sodium solution filters after adjusting pH to 3, and filter cake recycles to obtain itrated compound.Filtrate, which continues to be neutralized to pH with 30% sodium hydroxide solution, to be existed
10 or so, metronidazole solid can be obtained in filtering (HPLC map is shown in Fig. 2).
In the present embodiment, metronidazole crude yield is 74.5%, content 98.58%.
Embodiment 9-14
Compared with Example 8, the difference of embodiment 9-14 is only that: itrated compound and solid acid amount ratio are 1:0.04,
Hydroxylation reaction temperature is at 50~60 DEG C, and ethylene oxide dosage is different, and see Table 2 for details.
Embodiment 9-14 products therefrom yield and purity information are shown in Table 2.
Influence of the 2 ethylene oxide dosage of table to metronidazole yield and purity
Solid acid type | Amount of ethylene oxide (w/w) | Yield | Content |
SO4 2-/TiO2 | 1:0.5 | 68.7% | 97.2% |
SO4 2-/TiO2 | 1:0.6 | 69.9% | 97.5% |
SO4 2-/Fe2O3 | 1:0.5 | 68.5% | 97.0% |
SO4 2-/ZrO2 | 1:0.4 | 72.3% | 98.1% |
SO4 2-/ZrO2 | 1:0.5 | 74.1% | 98.2% |
SO4 2-/ZrO2 | 1:0.7 | 73.0% | 98.3% |
Metronidazole yield quality is most when by itrated compound known to 2 data of table and ethylene oxide amount ratio being 1:0.5~0.6
It is high.
Embodiment 15
- 5 nitroimidazole of 2- methyl is added in the reaction vessel, and is equivalent to the formic acid of 3 times of -5 nitroimidazole of 2- methyl,
And put into the SO42-/ZrO2 type solid acid for being equivalent to 0.4 times of -5 nitroimidazole of 2- methyl.Reaction system is warming up to 40~55
It DEG C is uniformly mixed.Then start that the ethylene oxide that total amount is equivalent to 0.6 times of -5 nitroimidazole of 2- methyl, epoxy is added portionwise
Ethane add after in 55 DEG C insulation reaction 30 minutes, reaction system is then removed by filtration solid acid.The anti-of solid acid will be filtered out
Answering liquid in vacuum degree is 0.085~0.095MPa, concentration and recovery formic acid under the conditions of 65~90 DEG C of temperature.It is being concentrated after recycling
It is added in object and is equivalent to the water of 1.15 times of -5 nitroimidazole of 2- methyl, stirring is uniformly mixed reaction product, then with 30% hydrogen-oxygen
Change after sodium solution adjusts pH to 3 and filter, filter cake recycles to obtain itrated compound.Filtrate continues to be neutralized to pH with 30% sodium hydroxide solution
10 or so, metronidazole solid is can be obtained in filtering (HPLC map is shown in Fig. 3).
In the present embodiment, metronidazole crude yield is 70.8%, content 98.33%.
Embodiment 16-21
Compared with embodiment 15, the difference of embodiment 9-14 is only that: itrated compound and solid acid amount ratio 1:0.04, nitrification
Object and ethylene oxide amount ratio are 1:0.6, and reaction temperature is different, and see Table 2 for details.
Embodiment 9-14 products therefrom yield and purity information are shown in Table 3.
Influence of 3 reaction temperature of table to metronidazole yield and purity
Solid acid type | Reaction temperature/DEG C | Yield | Content |
SO4 2-/TiO2 | 40~50 | 69.7% | 96.5% |
SO4 2-/TiO2 | 50~60 | 70.2% | 96.9% |
SO4 2-/Fe2O3 | 40~50 | 68.5% | 96.1% |
SO4 2-/Fe2O3 | 60~70 | 67.5% | 96.3% |
SO4 2-/ZrO2 | 55~65 | 74.7% | 98.1% |
SO4 2-/ZrO2 | 65~75 | 74.2% | 98.0% |
Best, the temperature mistake by hydroxylation reaction temperature metronidazole yield quality within the scope of 50~65 DEG C known to 3 data of table
High by-product increases, and yield reduces.
Comparative example 1
- 5 nitroimidazole of 2- methyl is added in the reaction vessel, and is equivalent to the first of 1.2 times of -5 nitroimidazole of 2- methyl
The mixed solution (middle formic acid and the sulfuric acid proportion of mixed solution be 1:0,9) of acid and sulfuric acid, stirring be warming up to 90 DEG C~95 DEG C it is mixed
Close uniformly, be then added portionwise the ethylene oxide for being equivalent to 0.6 times of -5 nitroimidazole of 2- methyl, ethylene oxide add after in 95 DEG C
Insulation reaction 30 minutes, the water for being equivalent to 1.5 times of -5 nitroimidazole of 2- methyl was added in end of reaction, and stirring mixes reaction product
Uniformly, then after adjusting pH to 3 with 30% sodium hydroxide solution it filters, filter cake recycles to obtain itrated compound.Filtrate is continued with 30% hydrogen
Sodium hydroxide solution is neutralized to pH 10 or so, and metronidazole solid can be obtained in filtering (HPLC map is shown in Fig. 4).Metronidazole crude product is received
Rate is 67.8%, content 98.28%.This method formic acid and sulfuric acid can not recycle, and liquid alkaline dosage is big, and technological reaction temperature is high, receive
Rate and purity are all not as good as the application.
The above is only several embodiments of the application, not does any type of limitation to the application, although this Shen
Please disclosed as above with preferred embodiment, however not to limit the application, any person skilled in the art is not taking off
In the range of technical scheme, a little variation or modification are made using the technology contents of the disclosure above and is equal to
Case study on implementation is imitated, is belonged in technical proposal scope.
Claims (10)
1. a kind of method for synthesizing metronidazole, using 2- 5-nitro imidazole and ethylene oxide as raw material, it is characterised in that: with
Solid acid is catalyst.
2. according to the method described in claim 1, it is characterized by: the solid acid is SO4 2-/MxOyType solid catalyst,
Wherein, M is selected from Ti, Zr or Fe;X, y is each independently selected from 1~3.
3. according to the method described in claim 2, it is characterized by: the solid acid is selected from SO4 2-/TiO2、SO4 2-/ZrO2、
SO4 2-/Fe2O3One of or it is a variety of;It is preferred that SO4 2-/ZrO2Solid acid.
4. according to the method described in claim 3, it is characterized by: the 2- 5-nitro imidazole and the solid acid
Feed weight ratio is 1:0.02~0.07;It is preferred that 1:0.04~0.05.
5. according to claim 1 or 3 described in any item methods, it is characterised in that: the 2- 5-nitro imidazole with it is described
The feed weight ratio of ethylene oxide is 1:0.4~0.7;It is preferred that 1:0.5~0.6.
6. according to claim 1,3,5 described in any item methods, it is characterised in that: using formic acid as reaction dissolvent.
7. method according to claim 1-6, it is characterised in that: this method comprises the following steps:
(1) the 2- 5-nitro imidazole is added in the formic acid, the solid acid is added after stirring and dissolving;
(2) it is passed through the ethylene oxide into system obtained by step (1), controls reaction temperature within the scope of 40~75 DEG C, has led to
The subsequent continuous insulation reaction of ethylene oxide 30~60 minutes;Separate reaction product to get.
8. according to the method described in claim 7, it is characterized by: the separation reaction product specifically: will be obtained by step (2)
Reaction solution system is filtered to remove solid acid, and after filtrate concentration plus water mixes, and filters after adjusting pH2~3, filtrate adjusts pH value again
To 10~12, separate solid to get.
9. according to the method described in claim 8, it is characterized by: the drying of filter cake obtained by the suction filtration is former directly as reaction
Material 2- 5-nitro imidazole is recycled.
10. preparation method according to claim 8 or claim 9, characterized by the following steps:
(1) 2- 5-nitro imidazole is added in formic acid, SO is added after stirring and dissolving4 2-/ZrO2Solid acid, wherein 2- first
Base -5- nitroimidazole and SO4 2-/ZrO2The feed ratio of solid acid is 1:0.035~0.05;
(2) it is passed through ethylene oxide into system obtained by step (1), the feed ratio of 2- 5-nitro imidazole and ethylene oxide is
1:0.5~0.6;Reaction temperature is controlled within the scope of 50~65 DEG C, has led to after ethylene oxide that the reaction was continued 30~45 minutes;
(3) reaction solution obtained by step (2) is filtered to remove solid acid, be dissolved in water after filtrate concentration, with sodium hydroxide solution tune
Section filters behind pH2~3, and filtrate continues to be adjusted pH value with sodium hydroxide solution to 10~12, filters to obtain metronidazole.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111848524A (en) * | 2020-07-27 | 2020-10-30 | 南京甘倍加生物科技有限责任公司 | Method for synthesizing metronidazole at low temperature |
CN113896684A (en) * | 2020-07-06 | 2022-01-07 | 复旦大学 | Preparation method of medetomidine |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102321028A (en) * | 2011-06-30 | 2012-01-18 | 湖北省宏源药业有限公司 | Method for synthesizing 2-methyl-5-nitroimidazole-1-ethanol |
CN102911122A (en) * | 2012-11-08 | 2013-02-06 | 兰亚朝 | Metronidazole preparation method |
CN104177297A (en) * | 2013-05-20 | 2014-12-03 | 东港市宏达制药有限公司 | Clean production method for synthesizing metronidazole by using bulk drugs |
CN105348200A (en) * | 2015-12-23 | 2016-02-24 | 武汉武药制药有限公司 | Environment-friendly method for metronidazole synthesis |
-
2018
- 2018-05-11 CN CN201810446093.9A patent/CN110172039A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102321028A (en) * | 2011-06-30 | 2012-01-18 | 湖北省宏源药业有限公司 | Method for synthesizing 2-methyl-5-nitroimidazole-1-ethanol |
CN102911122A (en) * | 2012-11-08 | 2013-02-06 | 兰亚朝 | Metronidazole preparation method |
CN104177297A (en) * | 2013-05-20 | 2014-12-03 | 东港市宏达制药有限公司 | Clean production method for synthesizing metronidazole by using bulk drugs |
CN105348200A (en) * | 2015-12-23 | 2016-02-24 | 武汉武药制药有限公司 | Environment-friendly method for metronidazole synthesis |
Non-Patent Citations (4)
Title |
---|
AKHIL V. NAKHATE等: "Template Assisted Synthesis of Nanocrystalline Sulfated Titania:Active and Robust Catalyst for Regioselective Ring Opening of Epoxide with Aniline and Kinetic Modeling", 《IND. ENG. CHEM. RES》 * |
BISWANATH DAS等: "Efficient synthesis of 3-alkyl indoles through regioselective ring opening of epoxides catalyzed by sulfated zirconia", 《CATALYSIS COMMUNICATIONS》 * |
邱方利等: "甲硝唑合成中羟乙基化工艺的改进", 《中国医药工业杂志》 * |
闵恩泽等: "《绿色化学与化工》", 30 November 2000, 化学工业出版社 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113896684A (en) * | 2020-07-06 | 2022-01-07 | 复旦大学 | Preparation method of medetomidine |
CN111848524A (en) * | 2020-07-27 | 2020-10-30 | 南京甘倍加生物科技有限责任公司 | Method for synthesizing metronidazole at low temperature |
CN111848524B (en) * | 2020-07-27 | 2022-02-18 | 南京甘倍加生物科技有限责任公司 | Method for synthesizing metronidazole at low temperature |
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