CN102295605B - Method for preparing benzimidazolone derivative - Google Patents
Method for preparing benzimidazolone derivative Download PDFInfo
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- CN102295605B CN102295605B CN201110168687.6A CN201110168687A CN102295605B CN 102295605 B CN102295605 B CN 102295605B CN 201110168687 A CN201110168687 A CN 201110168687A CN 102295605 B CN102295605 B CN 102295605B
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- FBBCWAOKBAJULM-UHFFFAOYSA-N [O-][N+](c(c(I)c1)cc(N2)c1NC2=O)=O Chemical compound [O-][N+](c(c(I)c1)cc(N2)c1NC2=O)=O FBBCWAOKBAJULM-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention relates to a preparation method of 5-nitro benzimidazolone or/and its derivatives (5-nitro-6-substituted benzimidazolone). The preparation method comprises the following main steps: (1) allowing o-phenylenediamine or its derivatives to react with urea to obtain benzimidazolone or its derivatives; (2) performing a nitration reaction of the benzimidazolone or its derivatives obtained in step (1) to obtain a target compound. The invention is characterized in that both step (1) and step (2) are performed in chlorobenzene by a one-pot method. The invention has the advantages of short preparation period, high yield, environmental friendship, and the like.
Description
Technical field
The present invention relates to a kind of preparation method of benzimidazolone derivatives, specifically, relate to a kind of 5-Nitro-2-benzimidazolinone or/and the preparation method of its derivative (benzimidazolone that 5-nitro-6-replaces).
Background technology
Benzoglyoxaline ketone pigment dyestuff is a class high performance pigment, and their color and luster is very strong, is applicable to most industrial fields.C.I. pigment orange 64 is one of them kind, has very high heat-resistant stability, solvent resistance and fastness to weathering, is mainly used in modulation to the sun-resistant and heat-resisting industrial paint having higher requirements and painted to engineering plastics.Producing this pigment needs crucial intermediate-5-amino-6-methyl benzimidazolone, and it can be made through reduction by 5-nitro-6-methyl benzimidazolone.About the bibliographical information that 5-nitro-6-methyl benzimidazolone is synthetic little, most of bibliographical informations be the synthetic of 5-Nitro-2-benzimidazolinone.At present synthetic 5-Nitro-2-benzimidazolinone is mainly taking O-Phenylene Diamine as starting raw material, makes by series reaction.
The people such as Robert report a kind of method by O-Phenylene Diamine photoreactive gas synthesizing benzimidazole ketone, and the method is passed into phosgene in the hydrochloride solution of O-Phenylene Diamine reacts, and obtains benzimidazolone, yield more than 75% (J.Am.Chem.Soc, 1958,80,1657-1662).Use the very large phosgene of toxicity because reaction relates to, so this author uses O-Phenylene Diamine instead and urea reacts under molten state, obtained equally benzimidazolone.Although but their method is easy and simple to handle, available product yield only has 40%～75%.
US Patent No. 4,269,989 disclose a kind of method, with O-Phenylene Diamine with urea carries out condensation in dilute sulphuric acid and ring-closure reaction has obtained benzimidazolone, yield is 96%, and the needed reaction times of the method is very long, and operation also comparatively bothers, need in reaction process, monitor constantly the pH of reactant, and it is stable to maintain pH constantly to add sulfuric acid.
US Patent No. 4,138,568 also disclose a kind of method, and O-Phenylene Diamine and urea are carried out to condensation and ring-closure reaction in orthodichlorobenzene under comparatively high temps, have obtained benzimidazolone, although yield is higher, reclaims solvent and will consume larger energy.
The people such as Yue Fu by O-Phenylene Diamine and methylcarbonate at Pb (NO
3)
2under existence, also obtained benzimidazolone in 230 DEG C of reactions, yield is 81.2%; But the selectivity of methylcarbonate is bad, and by product is more, product separation difficulty (Journal of Catalysis.2001,197 (1): 91-97).
Benzimidazolone can generate 5-Nitro-2-benzimidazolinone through nitration reaction.Poland Patent (PL 154621) discloses a kind of method, by benzimidazolone in sulfuric acid with nitric acid effect, obtained 5-Nitro-2-benzimidazolinone, yield is about 97%, but this reaction needed is reacted at low temperatures, otherwise easily generates dinitride, it is difficult to remove.
The people such as James adopt greatly excessive concentrated nitric acid to carry out nitration reaction to benzimidazolone, can obtain 5-Nitro-2-benzimidazolinone, but produce a large amount of spent acid, to environment unfriendly (J Chem Soc 1950:1515-19).
Chinese patent (CN 101863840) discloses a kind of method of the 5-of preparation nitro-6-methyl benzimidazolone, by 3,4-diaminotoluene first obtains 5-methyl benzimidazolone with urea generation condensation and ring-closure reaction in orthodichlorobenzene, in rare nitric acid medium, carry out again nitration reaction, make 5-nitro-6-methyl benzimidazolone.
In sum, the method of at present synthetic 5-nitro-benzimidazolone or 5-nitro-6-methyl benzimidazolone is all with " two-step approach ", that is: O-Phenylene Diamine (or 3,4-diaminotoluene) in orthodichlorobenzene, first there is condensation and ring-closure reaction with phosgene (or urea), the product obtaining generates 5-nitro-benzimidazolone or 5-nitro-6-methyl benzimidazolone (two-step reaction carries out in different media) from nitric acid effect or direct and rare nitric acid effect again in sulfuric acid.Not only complex operation, and environmental pollution is larger.
Summary of the invention
The object of the invention is to, provide a kind of " single stage method " to prepare 5-Nitro-2-benzimidazolinone or/and the method for its derivative (benzimidazolone that 5-nitro-6-replaces), method provided by the present invention is not only easy and simple to handle but also environmentally friendly.
5-Nitro-2-benzimidazolinone of the present invention is (benzimidazolone that 5-nitro-6-replaces) or/and its derivative, and its structure is suc as formula shown in I:
In formula I, R
1for H or C
1～C
6straight or branched alkyl.
A method for compound shown in preparation formula I, it comprises the steps:
(1) made the step of compound shown in formula III by compound shown in formula II and urea reaction; With
(2) compound shown in formula III is through the nitrated step that makes target compound (compound shown in formula I);
It is characterized in that, step (1) and step (2) are all carried out in chlorobenzene, and compound shown in formula III is without separation and purification, directly implementation step (2);
In formula II and III, R
1for H or C
1～C
6straight or branched alkyl.
The method of compound shown in preparation formula I provided by the present invention, its two-step reaction carries out in identical medium, and intermediate (compound shown in formula III) is without separation and purification, can directly carry out next step reaction.So, not only can shorten preparation cycle, and can reduce process cost.In addition, the present invention also has the advantages such as the high and close friend to environment of yield.
Embodiment
In preferred technical scheme of the present invention, compound shown in formula II and urea reaction temperature are 100 DEG C～135 DEG C, and more preferably 120 DEG C～130 DEG C, the reaction times is 5 hours～10 hours, more preferably 6 hours～8 hours.
In another preferred technical scheme of the present invention, the weight ratio of compound and chlorobenzene shown in formula II is 1: (5～15), more preferably 1: (8～12).
In a further preferred technical solution of the present invention, shown in formula II, the mol ratio of compound and urea is 1: (1～4), more preferably 1: (1.5～2.0).
In a further preferred technical solution of the present invention, in the nitration reaction of compound shown in formula III, shown in formula III, the mol ratio of compound and nitric acid is 1: (1～5), more preferably 1: (1.2～1.8); The temperature of reaction of described nitration reaction is 40 DEG C～120 DEG C, 60 DEG C～90 DEG C of preferred temperature of reaction.
In a further preferred technical solution of the present invention, concentration of nitric acid used is 20wt%～80wt%, and preferred concentration of nitric acid is 30wt%～40wt%.
In a further preferred technical solution of the present invention, R
1for C
1～C
3straight or branched alkyl; Best R
1for methyl.
The method that " single stage method " provided by the present invention prepares 5-Nitro-2-benzimidazolinone or/and its derivative (benzimidazolone that 5-nitro-6-replaces) not only can Reaction time shorten, and can improve yield.In addition,, because reaction medium-chlorobenzene can be recycled (chlorobenzene can reclaim by the method for steam distillation), reduce the pollution to environment.
The present invention is described in detail by the following examples, and its object is only better to understand content of the present invention but not limits the scope of the invention.
Embodiment 1
Be equipped with in the 1000ml four-hole boiling flask of mechanical stirring, reflux condensing tube, thermometer, heating unit one, add 25g 3,4-diaminotoluene and 18g urea, 200ml chlorobenzene, finishes, in 1h by heating material to 130 DEG C, insulation reaction 7h.After reaction finishes, be under agitation cooled to 80 DEG C.Subsequently, in 0.5h, drip 30g 65wt% nitric acid, finish, between 80-90 DEG C, maintain reaction 1h, add 300ml 10%NaOH solution, install water trap additional in reflux condensing tube bottom, after separating about 180ml chlorobenzene (recoverable), stop heating, add 200ml water, filter, extremely neutral with hcl acidifying under the cooling rear stirring of filtrate, now separate out a large amount of solids, filter, filter cake is washed to neutrality, dry, obtain 5-nitro-6-methyl benzimidazolone 35.5g, outward appearance is faint yellow, purity 97.8% (HPLC), and yield is 89.8%.Mass(z/m)：193；
1H?NMR?δ(ppm)：11.25(s，1H，N-H)，11.00(s，1H，N-H)，7.59(s，1H，H-ph)，6.96(s，1H，H-ph)，2.55(s，3H，CH
3).
Embodiment 2
The condensation of 3,4-diaminotoluene and urea and ring-closure reaction step are with embodiment 1, after having reacted, be cooled to 60 DEG C, in 0.5h, drip 30g 68wt% nitric acid, finish, maintain reaction 1h 60 DEG C of left and right, stopped reaction, aftertreatment is identical with embodiment 1, makes 5-nitro-6-methyl benzimidazolone 35.0g, and outward appearance is faint yellow, purity 97.5% (HPLC), yield is 88.5%.
Embodiment 3
The condensation of 3,4-diaminotoluene and urea and ring-closure reaction step are with embodiment 1, after having reacted, cooling approximately to 80 DEG C, in 45min, drip 55g 35wt% nitric acid, finish, maintain reaction 1h 80 DEG C of left and right, stopped reaction, aftertreatment is identical with embodiment 1, makes 5-nitro-6-methyl benzimidazolone 35.2g, and outward appearance is faint yellow, purity 97.8% (HPLC), yield is 89%.
Embodiment 4
Be equipped with in the 1000ml four-hole boiling flask of mechanical stirring, reflux condensing tube, thermometer, heating unit one, add 25g 3,4-diaminotoluene and 24g urea, 250ml chlorobenzene, finishes, in 1h by heating material to 130 DEG C, insulation reaction 6h.Stop subsequently heating, under agitation be cooled to 80 DEG C, in 45min, drip 50g40wt% nitric acid, finish, between 80-90 DEG C, react 1h, stopped reaction, aftertreatment, with embodiment 1, obtains 5-nitro-6-methyl benzimidazolone 35.7g, and outward appearance is faint yellow, purity 98% (HPLC), yield is 90.3%.
Embodiment 5
With embodiment 4,25g 3,4-diaminotoluene and 24g urea in 128-132 DEG C of reaction 8h, are under agitation cooled to 80 DEG C at 250ml chlorobenzene subsequently, in 0.5h, drip 40g 40wt% nitric acid, finish, between 80-90 DEG C, react 1h, aftertreatment is with embodiment 1, obtain 5-nitro-6-methyl benzimidazolone 34.2g, outward appearance is faint yellow, and purity is 97% (HPLC), and yield is 86.5%.
Embodiment 6
One, mechanical stirring is housed, reflux condensing tube, thermometer, in the 500ml four-hole boiling flask of heating unit, add 13g 3, 4-diaminotoluene and 9g urea, 100ml chlorobenzene, under argon shield, material is heated in 1h to 130 DEG C, insulation reaction 6h, under agitation be cooled to subsequently 80 DEG C, in 0.5h, drip 15g 68wt% nitric acid, finish, between 80-90 DEG C, react 1h, add 150ml 10%NaOH, install water trap additional in reflux condensing tube bottom, after separating about 90ml chlorobenzene (recoverable), stop heating, add 200ml water, filter, extremely neutral with hcl acidifying under the cooling rear stirring of filtrate, now separate out a large amount of solids, filter, filter cake is washed to neutrality, dry, obtain 5-nitro-6-methyl benzimidazolone 18.6g, outward appearance is faint yellow, purity 98.3% (HPLC), yield is 90.5%.
Claims (3)
1. a method for compound shown in preparation formula I, it comprises the steps:
(1) made the step of compound shown in formula III by compound shown in formula II and urea reaction; With
(2) compound shown in formula III is through the nitrated step that makes target compound;
It is characterized in that, step (1) and step (2) are all carried out in chlorobenzene, and compound shown in formula III is without separation and purification, directly implementation step (2);
Wherein, R
1for H or C
1～C
6straight or branched alkyl;
Compound shown in formula II and urea reaction temperature are 100 DEG C～135 DEG C, and the reaction times is 5 hours～10 hours;
The mol ratio of compound shown in formula II and urea is 1: (1～4);
Compound shown in formula III refers to compound and nitric acid reaction shown in formula III through nitrated, and temperature of reaction is 40 DEG C～120 DEG C;
Shown in formula III, the mol ratio of compound and nitric acid is 1: (1～5);
The concentration of nitric acid used is 20wt%～80wt%;
The weight ratio of compound shown in formula II and chlorobenzene is 1: (5～15).
2. the method for claim 1, is characterized in that, wherein R
1for C
1～C
3straight or branched alkyl.
3. method as claimed in claim 2, is characterized in that, wherein R
1for methyl.
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|---|---|---|---|
| CN201110168687.6A CN102295605B (en) | 2011-06-22 | 2011-06-22 | Method for preparing benzimidazolone derivative |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232397B (en) * | 2013-04-28 | 2016-04-20 | 江苏双乐化工颜料有限公司 | The synthetic method of 5-amino-N-substituted benzimidazole ketone |
| CN106336381B (en) * | 2016-07-29 | 2017-10-13 | 东营市天正化工有限公司 | The preparation method of the dinitro benzimidazolone of one pot process 5,6 |
| CN107365273B (en) * | 2017-08-11 | 2020-01-24 | 东营市天正化工有限公司 | Production method for synthesizing 5-nitrobenzimidazole ketone by one-pot method |
| CN107739342B (en) * | 2017-11-29 | 2020-01-10 | 华南理工大学 | Method for synthesizing 5-diarylaminobenzimidazole ketone derivative in one step |
| CN112094237B (en) * | 2020-11-06 | 2023-01-20 | 江苏宝众宝达药业股份有限公司 | Synthesis method of fluorobenzene imidazole |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101307023A (en) * | 2008-05-23 | 2008-11-19 | 东营市天正化工有限公司 | Production process of 5-acetyl acetamino benzimidazolone |
| CN101863840A (en) * | 2010-06-18 | 2010-10-20 | 淄博圣马化工厂 | Preparation method of 5-amino-6-methyl benzimidazolone |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101307023A (en) * | 2008-05-23 | 2008-11-19 | 东营市天正化工有限公司 | Production process of 5-acetyl acetamino benzimidazolone |
| CN101863840A (en) * | 2010-06-18 | 2010-10-20 | 淄博圣马化工厂 | Preparation method of 5-amino-6-methyl benzimidazolone |
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Owner name: NANTONG HENGSHENG FINE CHEMICAL CO., LTD. Free format text: FORMER OWNER: ZHEJIANG KESHENG DYESTUFF CHEMICAL CO., LTD. Effective date: 20141021 |
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Effective date of registration: 20141021 Address after: 200237 Meilong Road, Shanghai, No. 130, No. Patentee after: East China University of Science and Technology Patentee after: NANTONG HENGSHENG FINE CHEMICAL CO., LTD. Address before: 200237 Meilong Road, Shanghai, No. 130, No. Patentee before: East China University of Science and Technology Patentee before: Zhejiang Kesheng Dyestuff Chemical Co., Ltd. |