CN101397293B - Green nitration method based on ion liquid catalysis - Google Patents
Green nitration method based on ion liquid catalysis Download PDFInfo
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- CN101397293B CN101397293B CN2008101219792A CN200810121979A CN101397293B CN 101397293 B CN101397293 B CN 101397293B CN 2008101219792 A CN2008101219792 A CN 2008101219792A CN 200810121979 A CN200810121979 A CN 200810121979A CN 101397293 B CN101397293 B CN 101397293B
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
The invention discloses a green nitration method based on ionic liquid catalysis. The method adopts acetyl nitrate as a nitration agent and the ionic liquid as a catalyst; a prazole intermediate is added while stirring at room temperature; the molar ratio between the acetyl nitrate and the prazole intermediate is 1 to 3 : 1; the mass ratio between the ionic liquid and the prazole intermediate is 0.1 to 0.4 : 1; reaction is carried out for 0.5 to 5 hours at the temperature of 0 to 100 DEG C; the filtrate of the reaction is poured into iced water and then the alkali solution is added to regulate the pH value; an organic solution is adopted for extraction; the water phase is adopted to recycle the ionic liquid for repeated recycling; the oil phase is dried; the solution is pumped out so as to obtain the nitration product of the invention. The operation of the invention is simple; the reaction time is short; the temperature is low and the product can be easily extracted; the method is suitable for industrial production and is a novel high-effective, energy-conserving, environment-friendly method which is suitable for the application of green chemical industry.
Description
(1) technical field: the invention belongs to organic cpds manufacturing technology field, be specially a kind of based on ionic liquid-catalyzed green nitration method.
(2) background technology: omeprazole (omeprazole) chemistry 5-methoxyl group-2-{ [(4-methoxyl group-3 by name; 5-dimethyl--2-pyridyl)-methylene radical]-sulfoxide }-the 1H-benzoglyoxaline; Be the first-generation benzimidazoles hydrochloric acid in gastric juice proton pump inhibitor that Sweden Astra company develops, be used to treat diseases such as peptic gastric ulcer and anti-feeding habits gastritis.Since Initial Public Offering in 1988, the omeprazole sales volume increases rapidly, only just breaks through 4,600,000,000 dollars in 2000, in all medicines, ranks preceding lance.The synthetic of Omprazole compound is made up of multistep, and wherein nitration reaction is maximum to the pollution of environment.What nitration reaction was the most frequently used is mixed acid process, provides proton to make HNO by sulfuric acid
3Produce nitro positive ion (NO
2 +), and then NO
2 +Generate corresponding nitro-compound with substrate generation aromatic hydrocarbon electrophilic substitution reaction.Reacted spent acid dealing with complicated needs therefore, to cause a large amount of waste water and contaminate environment with the neutralization of bases such as sodium hydroxide.Along with the rise of Green Chemistry, novel nitrifying method research has obtained paying attention to widely and research.Research to nitrifying method at present mainly concentrates on following two aspects.
First: the selection of nitrating agent.Nitrating agent commonly used has nitric acid, oxynitride, organic nitrates, nitric acid and sulfonic acid ion exchange resin etc. in producing at present.
The most frequently used nitrating agent is a nitric acid, and its maximum characteristics are exactly low price, are suitable for industrialized production.But nitric acid is exactly to use a large amount of vitriol oils as the maximum problem of nitrating agent, and is big for environment pollution, has a large amount of unreacted spent acid to handle after the reaction, needs to cause a large amount of waste water and contaminate environment simultaneously with a large amount of alkali neutralizations.Along with the reinforcement of national environmental protection dynamics, its use more and more is restricted.
Oxynitride is meant oxynitride vaporphase nitration on the zeolites catalyzer as nitrating agent, because low in raw material cost and good selective are external very active to the theory and the technical study of this nitrifying method in recent years.But because employing is vaporphase nitration, make operation difficult, residual gas is difficult to handle, and is big to topsoil, also has certain danger, not suitable for mass production.
Organic nitrates carries out nitrated as nitrating agent, as catalyzer, only needing to be characterized in the nitric ether of adding equimolar amount with the H-Beta zeolite, just can obtain the nitration product near quantitative yield of highly selective.Catalyzer can recycle, and need not use solvent, does not therefore have the problem of wastewater treatment.The H-Beta zeolite that shortcoming is to use costs an arm and a leg, and activity receives the influence of activation temperature bigger.And catalyzer is a pulverulent solids, and recycling has certain degree of difficulty.
And the method for nitric acid and sulfonic acid ion exchange resin can obtain the purity high product, but its cost is too high, is unfavorable for large-scale production.
Second: selection of catalysts, catalyzer commonly used at present has the vitriol oil, acetate, zeolite, solid super-strong acid, ionic liquid etc.
The most frequently used catalyzer is the vitriol oil in the industry, and it both as the medium of reaction, made catalyst for reaction again.Its excellent catalytic effect, but big to the pollution of environment, producing a large amount of spent acid after the nitration reaction will handle.With solid super-strong acid (like Fe
2O
3/ SO
4 2, ZrO
2/ SO
4 2-, HZSM-5 etc.), though preparation is convenient, low price, its catalytic effect are compared with the vitriol oil, and certain gap is still arranged.And zeolite molecular sieve costs an arm and a leg, and is unfavorable for reclaiming, and the application in industry has received significant limitation.
In recent years, the organic chemistry expert nitration reaction of having studied aromatic compound in multiple comparatively eco-friendly the catalytic nitration method, particularly ionic liquid has received very big concern.Ionic-liquid catalyst is used to draw the nitration reaction of azole midbody not appear in the newspapers as yet.Utilize the stronger polarity of ionic liquid and dissolving power and adjustable Bronsted/Lewis are acid widely to organism, inorganics; With the ionic liquid is that solvent and catalyzer carry out nitration reaction, may become a kind of to more eco-friendly green nitration method.Traditional glyoxaline ion liquid toxicity is high, costs an arm and a leg, and is unsuitable for extensive use.And based on lactan, the ionic liquid of hexanolactam (CapI) especially, raw material is easy to get, and toxicity is low, is fit to green industrialized requirement.And the compound method based on the Brosted acidic ion liquid of hexanolactam is simple, can accomplish through the acid-base neutralisation reaction.And the introducing aromatic group can increase the dissolving power of ionic liquid to aromatic compound in ionic liquid molecules, so the present invention uses tosic acid root (pTSO
-) and Phenylsulfonic acid root (BSO
-) form conjugation, synthesized new ionic liquid [Cap I] pTSO and [Cap I] BSO.
(3) summary of the invention: it is the green nitration method that draws the azole midbody of catalyzer that task of the present invention provides a kind of ionic liquid that is easy to get with the valency of holding concurrently.
The present invention takes following technical scheme to realize:
The inventive method is a nitrating agent with the acetyl nitric ether; Ionic liquid is a catalyzer, under stirring at room, adds and draws the azole midbody, and the acetyl nitric ether is 1～3: 1 with drawing the mol ratio of azole midbody; Ionic liquid is 0.1～0.4: 1 (g/g) with drawing the mass ratio of azole midbody; 0～100 ℃ of down reaction 0.5～5 hour, the reaction times is long does not have helps to reaction, by product generation in addition; After reaction finished, filtrating was poured in the frozen water, and add alkaline solution and regulate the pH value, the extraction after drying, aqueous phase reclaims ionic liquid and reuses, and oil phase is drained solvent and is obtained product; Described ionic-liquid catalyst is to contain hexanolactam positively charged ion and tosic acid root or Phenylsulfonic acid root conjugation to form.
Ionic liquid and the preferred mass of drawing the azole midbody are than 0.1～0.3: 1 (g/g); The acetyl nitric ether is 1～2: 1 with drawing the preferred molar ratio of azole midbody.
The azole midbody that draws of the present invention is 2,3,5-trimethylpyridine-N-oxide compound.
Ionic-liquid catalyst of the present invention is [Cap I] pTSO or [Cap I] BSO, and wherein [Cap I] pTSO is based on the conjugated material of hexanolactam positively charged ion and tosic acid root reaction formation; [Cap I] BSO is based on the conjugated material of hexanolactam positively charged ion and Phenylsulfonic acid root reaction formation.
The present invention follows the tracks of nitration reaction with conventional HPLC (HPLC) and to the analysis of reaction conversion ratio and nitration product, its moving phase is CH
3CN, CH
3OH, H
2O prepares according to a certain percentage, adds a certain amount of trifluoroacetic acid again.
The present invention will pour into rapidly after nitration reaction finishes and blow out reaction in the frozen water, regulates pH with alkali lye such as sodium hydroxide solution, makes the pH value greater than 7.
The present invention adopts ionic liquid to make catalyzer for fear of using a large amount of vitriol oils, and environment protection is had positive effect.Ionic-liquid catalyst can recycling use, because mass loss, effect just can descend to some extent, does not need the frequent change catalyzer, has practiced thrift production cost greatly after using 4 to 5 times.
The present invention has realized ion liquid catalytic nitration, has avoided the use of a large amount of vitriol oils, and ionic-liquid catalyst can recycling use, and reclaims simply, can practice thrift cost in a large number, raises labour productivity.Use the acetyl nitric ether to substitute the nitric acid use again, avoided unreacted nitric acid second environmental pollution.Use rational experimental technique and ingredient proportion, this reaction conversion ratio is high, and transformation efficiency reaches 95%, aborning widespread use.In reaction, do not use any solvent, the consumption of having practiced thrift solvent had both reduced cost, had avoided the pollution of solvent to environment again.Therefore, we can say that reaction of the present invention is a kind of efficient, energy-conservation, free of contamination novel method that is applicable to the Green Chemistry industrial application.
(4) specific embodiments:
The present invention can be further understood through embodiment, but content of the present invention can not be limited.
Embodiment 1: the preparation of [CapI] pTSO ionic-liquid catalyst
In 100 milliliters reaction flask, take by weighing the 11.32g hexanolactam and add in the bottle, add the 10ml deionized water again, stir and make it dissolving, ice-water bath is cooled to 0 ℃; Slowly add the 19.52g tosic acid then, return to room temperature, continue reaction 4 hours; Underpressure distillation removes and desolvates, and with toluene and ether repetitive scrubbing twice, removes the raw material of unionization, and further dry 5 hours (65 ℃), promptly obtains product white solid 27.4g.
Embodiment 2: the preparation of [Cap I] BSO ionic-liquid catalyst
In 100 milliliters reaction flask, take by weighing the 11.32g hexanolactam and add in the bottle, add the 10ml deionized water again, stir and make it dissolving, ice-water bath is cooled to 0 ℃; Slowly add the 15.82g Phenylsulfonic acid, return to room temperature, stirred overnight.Underpressure distillation removes and desolvates, and uses the ether washed twice, and further dry, promptly obtains product yellow oily liquid 26.1g.
Embodiment 3: the preparation of nitrating agent acetyl nitric ether
In 100 milliliters reaction flask, (18.9ml, 0.2mmol), (7g, 4.8ml 0.1mmol), stirred 0.5 hour, generated the acetyl nitric ether, about 0.1mmol under the ice-water bath condition, to stir the adding nitrosonitric acid to add diacetyl oxide.
Embodiment 4:
Preparation nitration product: get 0.01mmol nitrating agent acetyl nitric ether, add in the reaction flask, add 0.3g ionic liquid [Cap I] pTSO again; Under stirring at room, add 2,3,5-trimethylpyridine-N-oxide compound (1.37g; 0.01mmol); Reaction is violent, and a large amount of heat releases are arranged, and the reaction times was controlled at 0.5 hour; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 87%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 85%.
Embodiment 5
Preparation nitration product: get 0.02mmol nitrating agent acetyl nitric ether and add in the reaction flask, add 0.29g ionic liquid [Cap I] BSO again, under stirring at room, add 2; 3; 5-trimethylpyridine-N-oxide compound (0.91g, 0.0067mmol), reaction is violent; A large amount of heat releases are arranged, and the reaction times was controlled at 5 hours; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 83%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 82%.
Embodiment 6
The preparation nitration product: get 0.012mmol nitrating agent acetyl nitric ether and add in the reaction flask, under stirring at room, add 2,3,5-trimethylpyridine-N-oxide compound (1.37g, 0.01mmol), reacting phase has exothermic phenomenon to steadily, and the reaction times was controlled at 2 hours; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 52%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 52%.
Do not use the ionic-liquid catalyst that the present invention relates in the present embodiment, in order to embody meliority of the present invention.
Embodiment 7
Preparation nitration product: get 0.015mmol nitrating agent acetyl nitric ether and add in the reaction flask, add 0.55g ionic liquid [Cap I] pTSO again, under stirring at room, add 2; 3; 5-trimethylpyridine-N-oxide compound (1.37g, 0.01mmol), reaction is violent; A large amount of heat releases are arranged, and the reaction times was controlled at 2 hours; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 95%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 93%.
Embodiment 8
Preparation nitration product: get 0.015mmol nitrating agent acetyl nitric ether and add in the reaction flask, add 0.137g ionic liquid [Cap I] BSO again, under stirring at room, add 2; 3; 5-trimethylpyridine-N-oxide compound (1.37g, 0.01mmol), reaction is violent; A large amount of heat releases are arranged, and the reaction times was controlled at 2 hours; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 89%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 88%.
Embodiment 9
Preparation nitration product: under the ice-water bath condition, get 0.015mmol nitrating agent acetyl nitric ether and add in the reaction flask, add 0.3g ionic liquid [Cap I] pTSO again; Under the ice-water bath cooling, stir and add 2,3,5-trimethylpyridine-N-oxide compound (1.37g; 0.01mmol); Anyway reaction has slight exotherm, and the reaction times was controlled at 2 hours; Get sample with its transformation efficiency of high effective liquid chromatography for measuring, transformation efficiency is 61.3%; Reaction solution directly is poured in the frozen water, regulates pH value to 8 with 30% aqueous sodium hydroxide solution; Use ethyl acetate extraction, revolve dried solvent after the drying and obtain product, transformation efficiency is 60%.
Present embodiment is in order to explain that temperature of reaction is the influence of transformation efficiency to the nitration reaction result.
Claims (2)
1. one kind based on ionic liquid-catalyzed green nitration method; It is characterized in that this method steps is following: with the acetyl nitric ether is nitrating agent; Ionic liquid is a catalyzer; Under stirring at room, add and draw the azole midbody, ionic liquid and the mass ratio 0.1～0.4: 1 that draws the azole midbody reacted 0.5～5 hour down at 0～100 ℃; After reaction finished, filtrating joined in the frozen water, and add alkaline solution and regulate the pH value, the extraction after drying, aqueous phase reclaims ionic liquid, and oil phase is drained solvent and is obtained nitration product; Described ionic-liquid catalyst is to contain the conjugated material that hexanolactam positively charged ion and tosic acid root or Phenylsulfonic acid root conjugation form, and promptly ionic-liquid catalyst is [CapI] pTSO or [CapI] BSO; The described azole midbody that draws is 2,3,5-trimethylpyridine-N-oxide compound.
2. green nitration method according to claim 1 is characterized in that employed acetyl nitric ether is 1～3: 1 with drawing the mol ratio of azole midbody.
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| CN102408339B (en) * | 2011-08-22 | 2014-05-07 | 盐城师范学院 | Clean nitration reaction of aromatic hydrocarbon of heteropolyacid pyridinium ionic liquid catalyst |
| CN102659537B (en) * | 2012-05-18 | 2014-10-29 | 常州大学 | Method for preparing polyformaldehyde dimethyl ether under catalysis of caprolactam ionic liquid |
| CN114805078B (en) * | 2022-02-11 | 2023-09-29 | 上海农帆生物科技有限公司 | Method for preparing 2,3, 4-trichloronitrobenzene through microchannel nitration |
| CN115353458B (en) * | 2022-07-08 | 2023-09-29 | 上海农帆生物科技有限公司 | Method for preparing aclonifen |
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| CN1469859A (en) * | 2000-10-10 | 2004-01-21 | ������˹��Ů����ѧ | Aromatic nitration reactions |
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Non-Patent Citations (4)
| Title |
|---|
| 戴桂元等.2-氯甲基-4-甲氧基-3 5-二甲基吡啶盐酸盐的制备.《中国医药工业杂志》.2004 |
| 戴桂元等.2-氯甲基-4-甲氧基-3,5-二甲基吡啶盐酸盐的制备.《中国医药工业杂志》.2004,(第05期),261-262. * |
| 戴立言等.奥美拉唑的合成新工艺研究.《浙江大学学报(工学版)》.2004,第38卷(第03期),333-336. * |
| 齐秀芳等.甲苯在基于己内酰胺的离子液体-硝酸/乙酐体系中的区域选择性硝化反应.《应用化学》.2008,第25卷(第02期),147-151. * |
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Address after: 322002 Zhejiang city in Yiwu Province, the temple town of Shuangfeng Road No. 15 Patentee after: Hangzhou Huadong Pharmaceutical Group Zhejiang Huayi Pharmaceutical Co., Ltd. Address before: 322002 Yiwu City, Zhejiang Province, South Industrial District Patentee before: Zhejiang Huayi Medicine Co., Ltd. |
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