CN103288737A - Synthesis method of iminostilbene - Google Patents
Synthesis method of iminostilbene Download PDFInfo
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- CN103288737A CN103288737A CN2013102160975A CN201310216097A CN103288737A CN 103288737 A CN103288737 A CN 103288737A CN 2013102160975 A CN2013102160975 A CN 2013102160975A CN 201310216097 A CN201310216097 A CN 201310216097A CN 103288737 A CN103288737 A CN 103288737A
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- iminostilbene
- synthetic method
- alkali
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- diphenylamine compound
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Abstract
The invention discloses a synthesis method of iminostilbene, belonging to the field of drug synthesis. The method comprises the following steps of: in the presence of a phase transfer catalyst and alkali, heating a compound for coupling in an organic solvent to obtain iminostilbene. The invention provides a novel method for synthesizing iminostilbene, and the reaction conditions are optimized so that the reaction can be performed at a low temperature; and moreover, the reaction steps are greatly reduced, the yield can exceed 80%, and the method has certain application value.
Description
Technical field
What the present invention relates to is a kind of synthetic method of medicine intermediate iminostilbene, belongs to the synthetic field of medicine.
Background technology
Iminostilbene (1), iminostilbene, chemistry 5H-dibenzo [b by name, f] azepine, it has very high physiologically active, and its effect is very extensive, and at first itself can prevent and treat hepatitis C, secondly iminostilbene can be used for synthetic antiepileptic drug Carbamzepine, oxcarbazepine and thymoleptic imipramine as medicine intermediate.Moreover iminostilbene can be stablized the negatively charged ion mixture of rhodium catalyst, for the synthesis of rhodium catalyst (main application is auto-exhaust catalyst).At last, iminostilbene also is the important synthesis material of genetically engineered and materialogy aspect, can be used as the synthesis material of porphyrins such as it.The synthetic of iminostilbene mainly is to be starting raw material with the Ortho Nitro Toluene at present, makes (its reaction scheme is as shown in the formula shown in 1) through seven steps reaction such as condensation, reduction, cyclization.This route is not only complicated, and step is tediously long, and the cost height, pollute heavy, productive rate is low.Therefore, how to obtain this intermediate by easy steps, determined the synthetic cost of synthetic derived product.
The synthetic route of reaction formula 1 iminostilbene
Summary of the invention
For addressing the above problem, namely step is grown, is polluted problems such as heavy, that yield is low, the invention provides the simple method of a kind of high yield, low-cost synthetic compound iminostilbene.
The synthetic method of a kind of iminostilbene of the present invention, carry out according to following step: in the presence of phase-transfer catalyst and alkali, in organic solvent, coupling takes place in the diphenylamine compound heating shown in the formula I, obtains iminostilbene;
The diphenylamine compound structure of wherein said formula I is as follows:
X is Cl, Br, I in the formula.
Wherein said phase-transfer catalyst is tetraethylammonium bromide, Tetrabutyl amonium bromide, benzyltriethylammoinium chloride, L-proline(Pro) etc., and wherein preferable is the L-proline(Pro).
Wherein said solvent is anhydrous methanol, dehydrated alcohol, DMSO, DMF, preferred dehydrated alcohol and DMSO.
Wherein said alkali is KOH, NaOH, K
2CO
3, Na
2CO
3, NaOCH
3, NaNH
2, CS
2CO
3, t-BuOK, t-BuONa, K
3PO
4What wherein alkali was preferable is: KOH, K
2CO
3
Wherein said alkali and diphenylamine compound mol ratio are 2.0:1.0-5.0:1.0.
The mol ratio of wherein said phase-transfer catalyst and diphenylamine compound is 0.05:1.0-0.20:1.0.
Wherein said linked reaction temperature is: 20-120 ℃, the reaction times is 5-96 hour.
The volume mol ratio of wherein said solvent adding amount and diphenylamine compound is: 1500-2500mL/1mol.
Agents useful for same of the present invention and raw material be commercially available getting all.
Positive progressive effect of the present invention is: the method that the present invention proposes the synthetic iminostilbene of comparison novelty, and optimized reaction conditions, and make reaction to carry out at a lower temperature, reactions steps shortens greatly, productive rate can reach more than 80%, has certain application value.
Embodiment
Describe the present invention with specific embodiment.Protection scope of the present invention is not limited with embodiment, but is limited by claim.
Example 1
In the 100mL four-hole boiling flask, add the 2-(toluene dichloride successively) pentanoic 6.65g(0.025mol), L-proline(Pro) 0.14g(0.0012mol) and 10mL dehydrated alcohol.Stir, and maintain the temperature at 20-40 ℃, drip the potassium hydroxide ethanol solution in the 1h and (contain 2.80g, 0.05molKOH, 27.50mL CH
3CH
2OH).Reaction 5-12 hour.Filter, use absolute ethanol washing brown solid three times, with the ethyl acetate extraction of heat, cooling, solid is separated out, and obtains golden yellow solid 2.19g with the toluene recrystallization, and productive rate is 45.38%.
Example 2
In the 100mL four-hole boiling flask, add the 2-(dibromomethylbenzene successively) pentanoic 8.87g(0.025mol), L-proline(Pro) 0.58g(0.0050mol) and 20mL dehydrated alcohol.Stir, and maintain the temperature at 20-40 ℃, drip the potassium hydroxide ethanol solution in the 1h and (contain 7.01g, 0.12molKOH, 42.50mL CH
3CH
2OH).Reaction 5-12 hour.Filter, use absolute ethanol washing brown solid three times, with the ethyl acetate extraction of heat, cooling, solid is separated out, and obtains golden yellow solid 2.92g with the toluene recrystallization, and productive rate is 60.51%.
Example 3
In the 100mL four-hole boiling flask, add 2-(two toluene iodides successively) pentanoic 11.22g(0.025mol), L-proline(Pro) 0.44g(0.0038mol) and 20mL dehydrated alcohol.Stir, and maintain the temperature at 20-40 ℃, drip the potassium hydroxide ethanol solution in the 1h and (contain 4.90g, 0.087molKOH, 30mL CH
3CH
2OH).Reaction 5-12 hour.Filter, use absolute ethanol washing brown solid three times, with the ethyl acetate extraction of heat, cooling, solid is separated out, and obtains golden yellow solid 3.90g with the toluene recrystallization, and productive rate is 80.82%.
Example 4
In the 100mL four-hole boiling flask, add the 2-(toluene dichloride successively) pentanoic 6.65g(0.025mol), Tetrabutyl amonium bromide 0.40g(0.0012mol), salt of wormwood 6.91g(0.050mol), DMSO37.50mL, stir, be heated to 90 ℃-120 ℃, reaction 48-96h, TLC follows the tracks of reaction.Reaction is finished, and is cooled to room temperature, pours in the suitable quantity of water, with ethyl acetate extraction (3 * 30mL), merge organic layer, use the saturated common salt water washing, anhydrous sodium sulfate drying filters, the filtrate decompression distillation obtains brown solid, obtains golden yellow solid 1.96g, productive rate 40.62% with the toluene recrystallization.
Example 5
In the 100mL four-hole boiling flask, add the 2-(dibromomethylbenzene successively) pentanoic 8.87g(0.025mol), tetraethylammonium bromide 1.05g(0.0050mol), potassium hydroxide 7.01g(0.12mol), DMF62.5mL, stir, be heated to 90 ℃-120 ℃, reaction 48-96h, TLC follows the tracks of reaction.Reaction is finished, and is cooled to room temperature, pours in the suitable quantity of water, with ethyl acetate extraction (3 * 30mL), merge organic layer, use the saturated common salt water washing, anhydrous sodium sulfate drying filters, the filtrate decompression distillation obtains brown solid, obtains golden yellow solid 3.02g, productive rate 62.59% with the toluene recrystallization.
Example 6
In the 100mL four-hole boiling flask, add 2-(two toluene iodides successively) pentanoic 11.22g(0.025mol), benzyltriethylammoinium chloride 0.86g(0.0038mol), sodium hydroxide 3.50g(0.087mol), DMSO50mL, stir, be heated to 90 ℃-120 ℃, reaction 48-96h, TLC follows the tracks of reaction.Reaction is finished, and is cooled to room temperature, pours in the suitable quantity of water, with ethyl acetate extraction (3 * 30mL), merge organic layer, use the saturated common salt water washing, anhydrous sodium sulfate drying filters, the filtrate decompression distillation obtains brown solid, obtains golden yellow solid 3.80g, productive rate 78.75% with the toluene recrystallization.
Claims (8)
1. the synthetic method of an iminostilbene, carry out according to following step: in the presence of phase-transfer catalyst and alkali, in organic solvent, coupling takes place in the diphenylamine compound heating shown in the formula I, obtains iminostilbene;
The diphenylamine compound structure of wherein said formula I is as follows:
X is Cl, Br, I in the formula.
2. the synthetic method of a kind of iminostilbene according to claim 1 is characterized in that wherein said phase-transfer catalyst is tetraethylammonium bromide, Tetrabutyl amonium bromide, benzyltriethylammoinium chloride, L-proline(Pro) etc., and wherein preferable is the L-proline(Pro).
3. the synthetic method of a kind of iminostilbene according to claim 1 is characterized in that wherein said solvent is anhydrous methanol, dehydrated alcohol, DMSO, DMF, preferred dehydrated alcohol and DMSO.
4. the synthetic method of a kind of iminostilbene according to claim 1 is characterized in that wherein said alkali is KOH, NaOH, K
2CO
3, Na
2CO
3, NaOCH
3, NaNH
2, CS
2CO
3, t-BuOK, t-BuONa, K
3PO
4
What wherein alkali was preferable is: KOH, K
2CO
3
5. the synthetic method of a kind of iminostilbene according to claim 1, the mol ratio that it is characterized in that wherein said alkali and diphenylamine compound is 2.0:1.0-5.0:1.0.
6. the synthetic method of a kind of iminostilbene according to claim 1, the mol ratio that it is characterized in that wherein said phase-transfer catalyst and diphenylamine compound is 0.05:1.0-0.20:1.0.
7. the synthetic method of a kind of iminostilbene according to claim 1, it is characterized in that wherein said linked reaction temperature is: 20-120 ℃, the reaction times is 5-96 hour.
8. the synthetic method of a kind of iminostilbene according to claim 1 is characterized in that the volume mol ratio of wherein said solvent adding amount and diphenylamine compound is: 1500-2500mL/1mol.
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| CN201310216097.5A CN103288737B (en) | 2013-06-03 | 2013-06-03 | A kind of synthetic method of iminostilbene |
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| CN103288737B CN103288737B (en) | 2015-08-26 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115304547A (en) * | 2022-08-16 | 2022-11-08 | 山东金吉利新材料有限公司 | Preparation method of 10-methoxyiminostilbene compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB820476A (en) * | 1956-11-13 | 1959-09-23 | Geigy Ag J R | 5-dibenzo [b.f.] azepines and their preparation |
| CN101307021A (en) * | 2008-07-04 | 2008-11-19 | 浙江工业大学 | Chemical synthesis process for iminostilbene |
-
2013
- 2013-06-03 CN CN201310216097.5A patent/CN103288737B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB820476A (en) * | 1956-11-13 | 1959-09-23 | Geigy Ag J R | 5-dibenzo [b.f.] azepines and their preparation |
| CN101307021A (en) * | 2008-07-04 | 2008-11-19 | 浙江工业大学 | Chemical synthesis process for iminostilbene |
Non-Patent Citations (4)
| Title |
|---|
| MEIGH J. P. K.: "Product subclass 6: benzazepines and their group 15 analogues", 《SCIENCE OF SYNTHESIS》 * |
| PAUL C. B.等: "SYNTHESIS OF NEW DIBENZO[b,f]AZEPINE DERIVATIVES", 《REVUE ROUMAINE DE CHIMIE》 * |
| 宋国强等: "亚氨基芪的合成", 《中国医药工业杂志》 * |
| 戴立言等: "亚氨基芪的合成及氯甲酰基保护基脱除新工艺", 《化工学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115304547A (en) * | 2022-08-16 | 2022-11-08 | 山东金吉利新材料有限公司 | Preparation method of 10-methoxyiminostilbene compound |
| CN115304547B (en) * | 2022-08-16 | 2024-01-16 | 山东金吉利新材料有限公司 | Preparation method of 10-methoxyiminostilbene compound |
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| CN103288737B (en) | 2015-08-26 |
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