CN103724275B - 4-nitroimidazole and preparation method thereof - Google Patents
4-nitroimidazole and preparation method thereof Download PDFInfo
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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Abstract
The present invention discloses a kind of 4-nitroimidazole and preparation method thereof.The preparation method of described 4-nitroimidazole, comprises the following steps: preparation reaction solution step: preparation reaction solution I: mixed according to mass ratio 1:1-1:10 with the vitriol oil by imidazoles; Preparation reaction solution II: using concentrated nitric acid as reaction solution II, or concentrated nitric acid is mixed obtained reaction solution II with the vitriol oil according to mass ratio 1:19-9:1; Preparation 4-nitroimidazole step: use the pump I that flow velocity is 1-200ml/min that reaction solution I is added microreactor, use pump II that reaction solution II is added microreactor, the flow velocity of pump II is that the 1.0-3.0 equivalent of the imidazoles added is advisable to make the concentrated nitric acid joined in microreactor, be heated to 50-150 DEG C, reaction, cooling, separation and purification, obtains 4-nitroimidazole step.Preparation method's concentrated nitric acid usage quantity of the present invention is little and utilization ratio is high, and reaction process does not have the generation of toxic gas, and reaction yield is high.
Description
Technical field
The present invention relates to organic compound field, particularly, relate to a kind of 4-nitroimidazole and preparation method thereof.
Background technology
As everyone knows, imidazole structure unit is extensively present in the chemical structure of medicine, such as: disclose the primary structure fragment that 4-nitroimidazole is Hepatoma therapy and breast cancer medicines in WO2012166778; The primary structure fragment that 4-amido imidazoles is enhancing development medicine is disclosed in US6828331.Therefore, synthesize imidazole derivative is a focus in pharmaceutical chemistry and organic chemistry always.
In one section of document (Khim.Geterotski.Soedin., 1970, No.4,503-507), report the synthetic method of 4-nitroimidazole, at 30-40 DEG C, concentrated nitric acid is added in imidazoles, then, under the condition of ice bath, drips the vitriol oil in this solution.Gained reaction system is heated to 75 DEG C, and insulation reaction 1 hour.Again reaction system is cooled, and add the mixing solutions of concentrated nitric acid and the vitriol oil.Gained reaction system reheats to 75 DEG C, and insulation reaction 1 hour, reaction solution is poured in frozen water, and solid is separated out, and filters, and washing, drying obtains 4-nitroimidazole, productive rate 73%.
In another section of document (J.Phys.Chem.1995,99,5009-5015), report, is dissolved in imidazoles in concentrated nitric acid, and is cooled to 0-5 DEG C, drips the vitriol oil.Dropwise, gained reaction system refluxes 2 hours, is cooled to room temperature and pours in frozen water, filters, and washing, drying obtains 4-nitroimidazole, productive rate 60%.
These two kinds of methods above, concentrated nitric acid amount used is comparatively large, is generally the 3-4 equivalent of imidazoles.When reaction is heated to more than 75 DEG C, reaction can acutely be caused, and releases a large amount of heat, the spontaneous rising of temperature of reaction system, after temperature of reaction system is more than 100 DEG C, start to produce brown gas (nitrogen protoxide, nitrogen peroxide), and usually have the phenomenon of punching material to occur.Therefore, reaction is difficult to be controlled, and easily causes security incident.
One section of world patent report (WO2010021409), be dissolved in by imidazoles in the vitriol oil, gained reaction heat is heated to 70 DEG C, and then instills concentrated nitric acid.After dripping off, reaction solution is warming up to 100 DEG C again, insulation reaction 5 hours.Pour in frozen water after reaction solution cooling, and use ammonia neutralization.Solid precipitation, filtration, washing, drying obtain 4-nitroimidazole, productive rate 78%.
This section of world patent above, concentrated nitric acid amount used is comparatively large, is generally the 3-4 equivalent of imidazoles, and long reaction time.When we repeat this operation in pilot plant test, find that reaction is at 70 DEG C, reaction is comparatively slow, and when temperature rises to 100 DEG C, reaction is accelerated, the rising that temperature is spontaneous, and has brown gas (nitrogen protoxide, nitrogen peroxide) to release.Although, the method drips concentrated nitric acid after reaction system heats up, control temperature of reaction preferably, avoid punching material phenomenon, but it is long to drip the concentrated nitric acid time, and in reaction process, still have part concentrated nitric acid to decompose generation toxic gas, therefore, the method is not suitable for scale operation 4-nitroimidazole.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of safety and the preparation method of the less 4-nitroimidazole of concentrated nitric acid consumption.
The present invention's adopted technical scheme that solves the problem is: a kind of preparation method of 4-nitroimidazole, comprises the following steps:
Preparation reaction solution step: prepare following reaction solution I and reaction solution II respectively,
Preparation reaction solution I: be that 1:1-1:10 mixes with the vitriol oil according to mass ratio by imidazoles, obtains reaction solution I;
Preparation reaction solution II: using concentrated nitric acid as reaction solution II, or be that 1:19-9:1 mixes and obtains reaction solution II by concentrated nitric acid and the vitriol oil according to mass ratio;
Preparation 4-nitroimidazole step: use the pump I that flow velocity is 1-200ml/min to add in microreactor by reaction solution I, pump II is used to add in microreactor by reaction solution II, the flow velocity of described pump II controls according to the flow velocity of pump I, the concentrated nitric acid in microreactor is made to be the 1.0-3.0 equivalent of imidazoles, be heated to 50-150 DEG C, after reacting completely, cooling reaction solution, through purification procedures, obtain 4-nitroimidazole step.
As nothing particularly points out, the equivalent described in the present invention refers to the ratio of the mole number of concentrated nitric acid and the mole number of imidazoles.
Wherein, described purification procedures comprises: the pH extremely alkalescence regulating reaction solution, through precipitation, filtration, washing, drying, i.e. and obtained 4-nitroimidazole.
Wherein, in described preparation reaction solution step, the mass concentration of the described vitriol oil is 95wt%-98wt%.
Wherein, in described preparation reaction solution step, the imidazoles in reaction solution I and the preferred 1:2-1:5 of the mass ratio of the vitriol oil, more preferably 1:3.
Wherein, in described preparation reaction solution step, the mass concentration of described concentrated nitric acid is 50wt%-70wt%, is more preferably 68wt%.
Wherein, in described preparation reaction solution step, the concentrated nitric acid in reaction solution II and the preferred 1:1-1:10 of the mass ratio of the vitriol oil, further preferred 1:1-1:5, more preferably 1:2.3.
Wherein, in described preparation reaction solution step, when the imidazoles in reaction solution I and the mass ratio of the vitriol oil are 1:1-1:10, all available concentrated nitric acid mixes with the vitriol oil as reaction solution II; And when the mass ratio of the imidazoles in reaction solution I and the vitriol oil is 1:6-1:10, except available concentrated nitric acid mixes as reaction solution II with the vitriol oil, can also directly use concentrated nitric acid as reaction solution II.
Wherein, in described preparation reaction solution step, reaction solution I and reaction solution II are all prepared under the temperature condition of 0-20 DEG C.
Wherein, in described preparation reaction solution step, preparation reaction solution I and preparation reaction solution II sequencing, that is, prepare reaction solution II after first can preparing reaction solution I, prepare reaction solution I after also first can preparing reaction solution II.
Wherein, in described preparation 4-nitroimidazole step, described pump comprises: ram pump, surge pump, syringe pump, peristaltic pump.
Wherein, in described preparation 4-nitroimidazole step, the preferred 20-100ml/min of flow velocity of described pump I, further preferred 70-80ml/min, more preferably 70ml/min.
Wherein, in described preparation 4-nitroimidazole step, during the flow velocity of control pump II, the concentrated nitric acid in preferred microreactor is the 1.2-2.0 equivalent of imidazoles, further preferred 1.3 equivalents.
Wherein, in described purification procedures, will be stored in container for storing liquid for the reaction solution in reactor, maintenance temperature is 0-20 DEG C, and the pH regulating reaction solution with ammoniacal liquor is 8-9.
Wherein, described microreactor is continous way microreactor.
A kind of 4-nitroimidazole obtained by above-mentioned preparation method.
Wherein, the reaction yield of described 4-nitroimidazole is 84%-92%, and purity is 99.3% ~ 99.8%, and production capacity is 0.45kg/h ~ 1.57kg/h.
Preparation method's sluggish below 70 DEG C of 4-nitroimidazole of the present invention, when temperature rises to 100 DEG C, reaction is violent to be caused, and release a large amount of heat, the temperature of reaction is made to increase further, again because the volume of the reaction solution in microreactor in the unit time is 64ml, avoid the accumulation of a large amount of nitration mixture in reaction system, reduce the danger of reaction, microreactor has better mass-and heat-transfer effect than traditional reactor again, reaction liberated heat is taken away by heat exchanger in time, and the temperature therefore in reaction process is almost invariable.In the present invention, the usage quantity of concentrated nitric acid has reduced to 1-3 equivalent even less by the 3-4 equivalent of imidazoles, and the yield of reaction has brought up to 84%-92% from 50%-78%.Preparation method of the present invention improves the utilization ratio of concentrated nitric acid, does not have the generation of toxic gas (nitrogen protoxide, nitrous oxide), produce environmental protection more in reaction process.
To sum up, the invention has the beneficial effects as follows:
1, the preparation method of 4-nitroimidazole of the present invention uses the concentrated nitric acid of imidazoles 1.0-3.0 equivalent to react, and prepare 4-nitroimidazole, reaction yield is high, and safety, easy temperature control system in production process.
2, the yield of reaction improves.
3, the utilization ratio of concentrated nitric acid improves, and reaction process does not have the generation of toxic gas, more environmental protection.
Embodiment
Below in conjunction with embodiment, to the detailed description further of the present invention's do, but embodiments of the present invention are not limited thereto.
4-nitroimidazole of the present invention is tested in accordance with the following methods:
HPLC tests: HPLC model: Shimadzu LC-20AT; Detector: SPD-20A; Chromatographic column: GeminiC18,4.0x250mm; Moving phase: 0.1TFA/H2O:MeCN=70:30; Column temperature: 25 DEG C; Flow velocity: 1ml/min; Product retention time: 2.98min.
Production capacity: the ratio of the product weight prepared and reaction solution I pump complete time.
Reaction yield: the product weight of real income and the ratio of theoretical yield.
Embodiment 1:
The preparation of reaction solution:
Preparation reaction solution I: get the vitriol oil (2760g, 1500ml, concentration is 98wt%) put into plastic beaker, and be cooled to 0 DEG C, add imidazoles (500g, 7.34mol), maintain the temperature in 0-20 DEG C in the process, the volume having prepared rear reaction solution I is 1925ml, the volumetric molar concentration 3.81mol/L of imidazoles in reaction solution I.
Preparation reaction solution II: get concentrated nitric acid (1000g, 704ml, 10.13mol, concentration is 68wt%) and put into plastic beaker, and be cooled to 0 DEG C, slowly drip the vitriol oil (3000g, 1630ml, 29.9mol, concentration is 98wt%), maintain the temperature in the process in 0-20 DEG C.Having prepared rear reaction solution II volume is 2252ml, and the volumetric molar concentration of the concentrated nitric acid in reaction solution II is 4.49mol/L.
Preparation 4-nitroimidazole: microreactor temperature is risen to 70 DEG C; With 2 ram pumps, reaction solution I and reaction solution II are pumped into microreactor respectively, the flow velocity of reaction solution I is 20ml/min, the flow velocity of reaction solution II is 21ml/min, now, the concentrated nitric acid added is 1.2 equivalents of imidazoles, after 1.56 minutes (microreactor cumulative volume is 64ml), flow out microreactor after reaction solution cooling, be collected in container for storing liquid.1.6h is operated more than continuing, complete to all reaction solution I pumps.
Separation and purification: the reaction solution in container for storing liquid is cooled to 0 DEG C, slowly drips strong aqua, regulates pH to 8-9.Product is separated out from reaction system, and filtration, washing, drying obtain 4-nitroimidazole 720.8 grams, and reaction yield is 87%, HPLC purity is 99.8%, and production capacity is 0.45kg/h.
Test mass spectrum and the nucleus magnetic resonance of above-mentioned 4-nitroimidazole: MS (M+H
+):
m/z113.7;
1hNMR:7.85 (S, 1H), 8.33 (S, 1H), 13.20-13.25 (bro., 1H).
Embodiment 2:
The preparation of reaction solution:
Preparation reaction solution I: get the vitriol oil (1500g, 815ml, concentration is 98wt%) put into plastic beaker, and be cooled to 0 DEG C, add imidazoles (500g, 7.34mol), maintain the temperature in 0-20 DEG C in the process, the volume having prepared rear reaction solution I is 1046ml, and in reaction solution I, the volumetric molar concentration of imidazoles is 6.8mol/L.
Preparation reaction solution II: get concentrated nitric acid (1100g, 774ml, 11.14mol, concentration is 68wt%) and put into plastic beaker, and be cooled to 0 DEG C, slowly drip the vitriol oil (4400g, 2390ml, 43.89mol, concentration is 98wt%), maintain the temperature in the process in 0-20 DEG C.The volume having prepared rear reaction solution II is 3093ml, and in reaction solution II, the volumetric molar concentration of concentrated nitric acid is 3.6mol/L.
Preparation 4-nitroimidazole: microreactor temperature is risen to 100 DEG C; With 2 ram pumps, reaction solution I and reaction solution II are pumped into microreactor respectively, the flow velocity of reaction solution I is 30ml/min, the flow velocity of reaction solution II is 85ml/min, now, the concentrated nitric acid added is 1.5 equivalents of imidazoles, after 0.55 minute (microreactor cumulative volume is 64ml), flow out microreactor after reaction solution cooling, be collected in container for storing liquid.0.58h is operated more than continuing, complete to all reaction solution I pumps.
Separation and purification: the reaction solution in container for storing liquid is cooled to 0 DEG C, slowly drips strong aqua, regulates pH to 8-9.Product is separated out from reaction system, and filtration, washing, drying obtain 4-nitroimidazole 711.8 grams, and reaction yield is 85.8%, HPLC purity 99.3%, and production capacity is 1.57kg/h.
Test mass spectrum and the nucleus magnetic resonance of above-mentioned 4-nitroimidazole: MS (M+H
+):
m/z113.7,
1hNMR:7.88 (S, 1H), 8.31 (S, 1H), 13.23-13.27 (bro., 1H).
Embodiment 3
The preparation of reaction solution:
Preparation reaction solution I: get the vitriol oil (1000g, 545ml, concentration is 98wt%) put into plastic beaker, and be cooled to 0 DEG C, add imidazoles (500g, 7.34mol) in batches, maintain the temperature in 0-20 DEG C in the process, the volume having prepared rear reaction solution I is 699ml, and in reaction solution I, the volumetric molar concentration of imidazoles is 10.5mol/L.
Preparation reaction solution II: get concentrated nitric acid (2000g, 1408ml, 20.26mol, concentration is 68wt%) and put into plastic beaker, and be cooled to 0 DEG C, slowly drip the vitriol oil (2000g, 1086ml, 20mol, concentration is 98wt%), maintain the temperature in the process in 0-20 DEG C.The volume having prepared rear reaction solution II is 2360ml, and in reaction solution II, the volumetric molar concentration of concentrated nitric acid is 8.58mol/L.
Preparation 4-nitroimidazole: first, microreactor temperature is risen to 130 DEG C; With 2 ram pumps, reaction solution I and reaction solution II are pumped into microreactor simultaneously respectively, the flow velocity of reaction solution I is 20ml/min, the flow velocity of reaction solution II is 48ml/min, now, the concentrated nitric acid added is 2 equivalents of imidazoles, after 0.94 minute (microreactor cumulative volume is 64ml), flow out microreactor after reaction solution cooling, be collected in container for storing liquid.0.58h is operated more than continuing, complete to all reaction solution I pumps.
Separation and purification: the reaction solution in container for storing liquid is cooled to 0 DEG C, slowly drips strong aqua, regulates pH to 8-9.Product is separated out from reaction system, and filtration, washing, drying obtain 4-nitroimidazole 709.1 grams, and reaction yield is 85.5%, HPLC purity 99.5%, and production capacity is 1.22kg/h.
Test mass spectrum and the nucleus magnetic resonance of above-mentioned 4-nitroimidazole: MS (M+H
+):
m/z113.7,
1hNMR:7.89 (S, 1H), 8.32 (S, 1H), 13.19-13.23 (bro., 1H).
Embodiment 4
The preparation of reaction solution:
Preparation reaction solution I: get the vitriol oil (5000g, 2717ml, concentration is 98wt%) put into plastic beaker, and be cooled to 0 DEG C, add imidazoles (500g, 7.34mol) in batches, maintain the temperature in 0-20 DEG C in the process, the volume having prepared rear reaction solution I is 3486ml, the volumetric molar concentration 2.1mol/L of reaction solution I imidazoles.
Preparation reaction solution II: get concentrated nitric acid (2500g, 1760ml, 25.32mol, concentration is 68wt%) and put into plastic beaker, and be cooled to 0 DEG C, slowly drip the vitriol oil (12500g, 6790ml, 83mol, concentration is 98wt%), maintain the temperature in the process in 0-20 DEG C.The volume having prepared rear reaction solution II is 8400ml, and in reaction solution II, the volumetric molar concentration of concentrated nitric acid is 3.01mol/L.
Preparation 4-nitroimidazole: microreactor temperature is risen to 90 DEG C; With 2 ram pumps, reaction solution I and reaction solution II are pumped into microreactor respectively, the flow velocity of reaction solution I is 80ml/min, the flow velocity of reaction solution II is 160ml/min, now, the concentrated nitric acid added is 3 equivalents of imidazoles, after 0.27 minute (microreactor cumulative volume is 64ml), flow out microreactor after reaction solution cooling, be collected in container for storing liquid.0.72h is operated more than continuing, complete to all reaction solution I pumps.
Separation and purification: the reaction solution in container for storing liquid is cooled to 0 DEG C, slowly drips strong aqua, regulates pH to 8-9.Product is separated out from reaction system, and filtration, washing, drying obtain 4-nitroimidazole 700 grams, and separation yield is 84%, HPLC purity 99.6%, and production capacity is 0.97kg/h.
Test mass spectrum and the nucleus magnetic resonance of above-mentioned 4-nitroimidazole: MS (M+H
+):
m/z113.7,
1hNMR:7.84 (S, 1H), 8.33 (S, 1H), 13.20-13.25 (bro., 1H).
Embodiment 5
The preparation of reaction solution:
Preparation reaction solution I: get the vitriol oil (3000g, 1630ml, concentration is 98wt%) put into plastic beaker, and be cooled to 0 DEG C, add imidazoles (500g, 7.34mol) in batches, maintain the temperature in 0-20 DEG C in the process, the volume having prepared rear reaction solution I is 2092ml, and in reaction solution I, the volumetric molar concentration of imidazoles is 3.51mol/L.
Preparation reaction solution II: get concentrated nitric acid (68wt%, 14.4mol/L) as reaction solution II.
Preparation 4-nitroimidazole: microreactor temperature is risen to 110 DEG C; With 2 ram pumps, reaction solution I and reaction solution II are pumped into microreactor respectively, the flow velocity of reaction solution I is 70ml/min, the flow velocity of reaction solution II is 22ml/min, now, the concentrated nitric acid added is 1.3 equivalents of imidazoles, after 0.69 minute (microreactor cumulative volume is 64ml), flow out microreactor after reaction solution cooling, be collected in container for storing liquid.0.49h is operated more than continuing, complete to all reaction solution I pumps.
Separation and purification: the reaction solution in container for storing liquid is cooled to 0 DEG C, slowly drips strong aqua, regulates pH to 8-9.Product is separated out from reaction system, and filtration, washing, drying obtain 4-nitroimidazole 768 grams, and separation yield is 92%, HPLC purity 99.3%, and production capacity is 1.57kg/h.
Test mass spectrum and the nucleus magnetic resonance of above-mentioned 4-nitroimidazole: MS (M+H
+):
m/z113.7,
1hNMR:7.83 (S, 1H), 8.31 (S, 1H), 13.20-13.24 (bro., 1H).
Comparative example 1
The 60ml vitriol oil (concentration is 95wt%) is added in flask, then adds 20 grams of imidazoles, and this reaction solution is heated to 70 DEG C.Instill 60ml concentrated nitric acid (concentration is 69wt%) again, now, concentrated nitric acid is 3.1 equivalents of imidazoles, after adding, the temperature of reaction solution is risen to 100 DEG C, and keeps 5 hours.Reaction solution is poured in 100 grams of frozen water, regulates pH to neutral with ammoniacal liquor.Solid filtering, washing, drying obtain 26 grams of 4-nitroimidazoles, and reaction yield is 78%.
Test the nucleus magnetic resonance of above-mentioned 4-nitroimidazole:
1h-NMR (
d-DMSO) δ ppm:7.83 (s, 1H), 8.30 (s, 1H), 13.1 (br, s, 1H).
Comparative example 2
4ml concentrated nitric acid (concentration 70wt%) is joined 1 gram of imidazoles to dissolve, now, concentrated nitric acid is 4.1 equivalents of imidazoles, stirs to clarify, and is cooled to 0-5 DEG C, drips the 2ml vitriol oil (concentration is 100wt%).Dropwise, gained reaction system refluxes 2 hours, is cooled to room temperature and pours in 40 grams of frozen water, filters, and washing, drying obtains 1 gram of 4-nitroimidazole, and reaction yield is 60%.
Test the nucleus magnetic resonance of above-mentioned 4-nitroimidazole:
1h-NMR (
d-DMSO) δ ppm:7.83 (s, 1H), 8.30 (s, 1H), 13.1 (br, s, 1H).
Contrast from above-described embodiment 1-5 and comparative example 1-2, can find out, when prior art prepares 4-nitroimidazole, the concentrated nitric acid of 3.1-4.1 equivalent is used to react, reaction yield is 60%-78%, and the preparation method of 4-nitroimidazole of the present invention only uses the concentrated nitric acid of the 1.0-3.0 equivalent of imidazoles to react, reaction yield is 84%-92%, and react safer, temperature is more easy to control, there is no the generation of toxic gas (as nitrogen protoxide, nitrous oxide) in reaction process, produce environmental protection more.
As mentioned above, the present invention can be realized preferably.
Claims (8)
1. a preparation method for 4-nitroimidazole, comprises the following steps:
Preparation reaction solution step: prepare following reaction solution I and reaction solution II respectively,
Preparation reaction solution I: be that 1:6-1:10 mixes with the vitriol oil according to mass ratio by imidazoles, obtains reaction solution I,
Preparation reaction solution II: using concentrated nitric acid as reaction solution II;
Preparation 4-nitroimidazole step: use the pump I that flow velocity is 1-200mL/min to add in microreactor by reaction solution I, pump II is used to add in microreactor by reaction solution II, the flow velocity of described pump II controls according to the flow velocity of pump I, the concentrated nitric acid in microreactor is made to be the 1.0-3.0 equivalent of imidazoles, be heated to 90-150 DEG C, after reacting completely, cooling reaction solution, through purification procedures, obtain 4-nitroimidazole step.
2. the preparation method of 4-nitroimidazole according to claim 1, is characterized in that, described purification procedures comprises: the pH extremely alkalescence regulating reaction solution, through precipitation, filtration, washing, drying, i.e. and obtained 4-nitroimidazole.
3. the preparation method of 4-nitroimidazole according to claim 1 and 2, is characterized in that, in described preparation reaction solution step, the mass concentration of the described vitriol oil is 95wt%-98wt%.
4. the preparation method of 4-nitroimidazole according to claim 1 and 2, is characterized in that, in described preparation reaction solution step, the mass concentration of described concentrated nitric acid is 50wt%-70wt%.
5. the preparation method of 4-nitroimidazole according to claim 1 and 2, is characterized in that, described pump comprises: ram pump, surge pump, syringe pump, peristaltic pump.
6. the preparation method of 4-nitroimidazole according to claim 1 and 2, it is characterized in that, in described preparation 4-nitroimidazole step, the flow velocity of described pump II controls according to the flow velocity of pump I, the 1.3-2.0 equivalent being imidazoles to make the concentrated nitric acid in microreactor.
7. the preparation method of 4-nitroimidazole according to claim 2, is characterized in that, in described purification procedures, described ammoniacal liquor regulates the pH of reaction solution to be 8-9.
8. the preparation method of 4-nitroimidazole according to claim 1 and 2, is characterized in that, described microreactor is continous way microreactor.
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| CN101768122A (en) * | 2009-12-25 | 2010-07-07 | 中北大学 | Preparation method of 4,5-dimetridazloe ammonium salt |
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| RU2198877C1 (en) * | 2001-07-16 | 2003-02-20 | Общество с ограниченной ответственностью "Поливит" | Method of synthesis of 2-methyl-4(5)-nitro-imidazole |
| CN101768122A (en) * | 2009-12-25 | 2010-07-07 | 中北大学 | Preparation method of 4,5-dimetridazloe ammonium salt |
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