CN103086969B - Synthesis method of iminostilbene carbonyl chloride - Google Patents
Synthesis method of iminostilbene carbonyl chloride Download PDFInfo
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- CN103086969B CN103086969B CN201310029806.9A CN201310029806A CN103086969B CN 103086969 B CN103086969 B CN 103086969B CN 201310029806 A CN201310029806 A CN 201310029806A CN 103086969 B CN103086969 B CN 103086969B
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- carbonyl chloride
- iminodibenzyl
- iminostilbene
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Abstract
The invention discloses a synthesis method of iminostilbene carbonyl chloride. The synthesis method comprises the following steps of: performing bromination reaction on iminodibenzyl carbonyl chloride and a brominating agent at the temperature of 100-120 DEG C for 10-20 hours under the action of an organic solvent and an initiator, then performing heating reflux for 4-5 hours, and performing post-treatment on a reaction solution after the end of reflux. According to the method disclosed by the invention, by selecting different brominating agents, the utilization rate of the brominating agent is improved, and the requirements for labor protection during the production process are reduced so as to be conducive to environmental protection.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of synthetic method of iminostilbene carbonyl chloride.
Background technology
Iminostilbene carbonyl chloride (Iminostilbene carbonyl chloride) is a kind of medicine intermediate, it is hydrolyzed to obtain iminostilbene, iminostilbene carbonyl chloride and iminostilbene are the key intermediates of synthesis Carbamzepine, opipramol, and tool has been widely used.
Iminostilbene carbonyl chloride Carbamzepine opipramol
It take iminodibenzyl as the method for raw material dehydrogenation one-step synthesis iminostilbene under catalyst action that Chinese patent CN200810062839.2 discloses a kind of, this technique has the advantage that production cost is low, synthesis step is short, but because it is high to equipment requirements, temperature of reaction is high, operational condition is harsh, catalyzer price and the facility investment popularization limiting it such as large.
Chinese patent CN 200410066503.5 disclose a kind of iminodibenzyl formyl chloride and bromine are reacted after again high temperature removal hydrogen bromide obtain the method for iminostilbene carbonyl chloride; this technique has the following disadvantages: 1) use bromine in production process; because bromine is intense stimulus material, be unfavorable for labour protection.
2) bromine utilization ratio is low.Can find out from following reaction formula, reaction generates hydrogen bromide, is up to 50%.
3) in reaction process, hydrogen bromide quantity discharged is large, is unfavorable for environmental protection.
Summary of the invention
The object of the invention is to overcome prior art deficiency; a kind of synthetic method of new iminostilbene carbonyl chloride is provided; the method is by selecting different bromizating agents; improve the utilization ratio of bromizating agent; reduce the requirement to labour protection in production process; bromide chloride quantity discharged reduces (half for former technique), is beneficial to environmental protection.
For achieving the above object, the present invention adopts following technical scheme:
A kind of synthetic method of iminostilbene carbonyl chloride, it comprises the steps: under organic solvent and initiator effect, iminodibenzyl formyl chloride (chemical name: 10,11-dihydro-5H-dibenzo [b, f] azatropylidene-5-formyl chloride) with bromizating agent in 100-120 DEG C of bromination reaction 10-20h, then temperature rising reflux 4-5 hour, backflow terminates rear reaction solution through aftertreatment and get final product.
Concrete, described organic solvent is preferably chlorobenzene or dimethylbenzene; Described initiator is preferably benzoyl peroxide or azo-bis-isobutyl cyanide; Described bromizating agent is preferably the mixture of C5H6Br2N2O2, n-bromo-succinimide or bromine water and sodium bromate.
The mol ratio of described iminodibenzyl and bromizating agent (in bromine) is advisable with 1:1-1.2.
In reaction process, the addition of described initiator is preferably 3-6%(and every 100g iminodibenzyl formyl chloride interpolation 3-6g initiator of iminodibenzyl formyl chloride weight).Initiator can disposablely when reacting beginning all add; Also first can add the consumption of about 1/2 when reacting and starting, remaining every reacting space about 6h adds once.The consumption of solvent generally adds 2.5-4ml with 1g iminodibenzyl formyl chloride and is advisable.
The aftertreatment of reaction solution is specially: reaction solution is chilled to 0-5 DEG C, adds water washing, stratification, and after organic layer drying, concentrating under reduced pressure steams except organic solvent, and gained solid phase adds ethanol mixed at room temperature stirring to pulp, and filter, namely filter cake obtains product after drying.
The synthetic route of the inventive method is as follows:
In the inventive method, the reaction formula selecting three kinds of different bromizating agents corresponding is as follows:
5 RH+2 Br
2+BrO
3 -+H
+→5 RBr+2H
2O。
The inventive method with iminodibenzyl formyl chloride for raw material
,carry out bromination reaction with the mixture of C5H6Br2N2O2, n-bromo-succinimide or bromine water and sodium bromate as bromizating agent and obtain iminodibenzyl formyl chloride bromide, then reflux dehydrobromination obtains target iminostilbene carbonyl chloride.Compared with the conventional method comparatively, present method has the following advantages: 1) bromizating agent selects C5H6Br2N2O2 or bromo succinyl imido, reduces toxicity, improves the utilization ratio of bromine, can reach 100% in theory.2) select the mixture of bromine and sodium bromate to carry out bromination reaction, the hydrogen bromide produced in bromination can react with sodium bromate and generate simple substance bromine, improves the utilization ratio of bromine equally.3) features such as the method has that facility investment is few, bromine utilization ratio is high, bromide chloride quantity discharged reduces (half for former technique), and product yield is high, labour protection is good in production process, environmental pollution is little, are applicable to suitability for industrialized production.
Embodiment
The present invention is further illustrated by the following examples, but protection scope of the present invention is not limited thereto.
embodiment 1
A kind of synthetic method of iminostilbene carbonyl chloride, it comprises the steps: to add 300ml chlorobenzene, 106g (0.410mol) iminodibenzyl formyl chloride, 77g (0.431mol) N-bromo-succinimide and 2g Diisopropyl azodicarboxylate in the reactor, oil bath is warming up to 120 DEG C and carries out bromination reaction 20 hours (adding 1g Diisopropyl azodicarboxylate at interval of 6h in reaction process), and then temperature rising reflux (about 140 DEG C) 5h is in order to remove hydrogen bromide (to discharging without hydrogen bromide).Backflow terminates rear reaction solution and is chilled to 1 DEG C, add 300ml water washing once, stratification, organic phase Sodium sulfate anhydrous.min(99) is dry, concentrating under reduced pressure steams and adds 200ml ethanol except after chlorobenzene, stirring at room temperature 1 hour, filter, filter cake less than 50 DEG C is dry must about 83g yellow solid imino stilbene formyl chloride, yield about 80%.
embodiment 2
A kind of synthetic method of iminostilbene carbonyl chloride, it comprises the steps: to add 300ml dimethylbenzene, 106g (0.410mol) iminodibenzyl formyl chloride, 67.5g (0.236 mol) C5H6Br2N2O2 and 2g Diisopropyl azodicarboxylate in the reactor, oil bath is warming up to 100 DEG C and carries out bromination reaction 15 hours (adding 1g Diisopropyl azodicarboxylate at interval of 6h in reaction process), and then temperature rising reflux 4h is in order to remove hydrogen bromide.Backflow terminates rear reaction solution and is chilled to 5 DEG C, adds 300ml water washing once, stratification, organic phase Sodium sulfate anhydrous.min(99) is dry, concentrating under reduced pressure steams and adds 200ml ethanol, stirring at room temperature 1 hour except after dimethylbenzene, filters, must about 81g yellow solid imino stilbene formyl chloride after filtration cakes torrefaction, yield about 78%.
embodiment 3
A kind of synthetic method of iminostilbene carbonyl chloride, it comprises the steps: to add 300ml chlorobenzene, 106g (0.410mol) iminodibenzyl formyl chloride, 13g (0.086 mol) sodium bromate and 4g benzoyl peroxide in the reactor, oil bath is warming up to 110 DEG C, 28 g (0.175mol) bromine is dripped in reactor, bromination reaction 10h, then temperature rising reflux 4h is in order to remove hydrogen bromide.Backflow terminates rear reaction solution and is chilled to 3 DEG C, adds 300ml water washing once, stratification, organic phase Sodium sulfate anhydrous.min(99) is dry, concentrating under reduced pressure steams and adds 200ml ethanol, stirring at room temperature 1 hour except after chlorobenzene, filters, must about 81g yellow solid imino stilbene formyl chloride after filtration cakes torrefaction, yield about 78%.
Claims (4)
1. the synthetic method of an iminostilbene carbonyl chloride, it is characterized in that, comprise the steps: under organic solvent and initiator effect, iminodibenzyl formyl chloride and bromizating agent are in 100-120 DEG C of bromination reaction 10-20h, then temperature rising reflux 4-5 hour, backflow terminates rear reaction solution through aftertreatment and get final product; Described organic solvent is chlorobenzene or dimethylbenzene; Described initiator is benzoyl peroxide or azo-bis-isobutyl cyanide; Described bromizating agent is the mixture of C5H6Br2N2O2, N-bromo-succinimide or bromine water and sodium bromate.
2. the synthetic method of iminostilbene carbonyl chloride as claimed in claim 1, it is characterized in that, the mol ratio of described iminodibenzyl formyl chloride and bromizating agent is 1:1-1.2.
3. the synthetic method of iminostilbene carbonyl chloride as claimed in claim 1, it is characterized in that, the addition of described initiator is the 3-6% of iminodibenzyl formyl chloride weight.
4. the synthetic method of iminostilbene carbonyl chloride as claimed in claim 1, it is characterized in that, the aftertreatment of reaction solution is specially: reaction solution is chilled to 0-5 DEG C, add water washing, stratification, after organic phase drying, concentrating under reduced pressure steams except organic solvent, and gained solid phase adds ethanol mixed at room temperature stirring to pulp, filter, namely filter cake obtains product after drying.
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| CN106467490B (en) * | 2015-08-15 | 2019-05-03 | 浙江华洲药业有限公司 | A kind of synthetic method of carbamazepine intermediate iminostilbene carbonyl chloride |
| CN106946780A (en) * | 2017-02-09 | 2017-07-14 | 上海现代哈森（商丘）药业有限公司 | A kind of synthetic method of Oxcarbazepine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616433A (en) * | 2004-09-20 | 2005-05-18 | 俞锋 | Carbamazepine medicine and its preparing method |
| CN102807528A (en) * | 2012-08-07 | 2012-12-05 | 常州华生精细化工有限公司 | Preparation method of 10-methoxy iminostilbene |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616433A (en) * | 2004-09-20 | 2005-05-18 | 俞锋 | Carbamazepine medicine and its preparing method |
| CN102807528A (en) * | 2012-08-07 | 2012-12-05 | 常州华生精细化工有限公司 | Preparation method of 10-methoxy iminostilbene |
Non-Patent Citations (1)
| Title |
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| 亚氨基芪的合成及氯甲酰基保护基脱除新工艺;戴立言等;《化工学报》;20080930;第59卷(第9期);第2420页实验部分 * |
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Inventor after: Chen Hong Inventor after: Wang Yingli Inventor after: Liu Tongbin Inventor after: Jiang Zhengxiang Inventor after: Liu Li Inventor after: Fu Dongli Inventor after: Bai Mei Inventor after: Wang Zihua Inventor before: Chen Hong Inventor before: Wang Yingli Inventor before: Liu Tongbin Inventor before: Jiang Zhengxiang Inventor before: Tang Qiuling Inventor before: Song Zhenfeng Inventor before: Wang Zihua |
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Free format text: CORRECT: INVENTOR; FROM: CHEN HONG WANG YINGLI LIU TONGBIN JIANG ZHENGXIANG TANG QIULING SONG ZHENFENG WANG ZIHUA TO: CHEN HONG WANG YINGLI LIU TONGBIN JIANG ZHENGXIANG LIU LI FU DONGLI BAI MEI WANG ZIHUA |