RU2088569C1 - Method of synthesis of 2,6-di-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone - Google Patents
Method of synthesis of 2,6-di-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone Download PDFInfo
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- RU2088569C1 RU2088569C1 RU94033536A RU94033536A RU2088569C1 RU 2088569 C1 RU2088569 C1 RU 2088569C1 RU 94033536 A RU94033536 A RU 94033536A RU 94033536 A RU94033536 A RU 94033536A RU 2088569 C1 RU2088569 C1 RU 2088569C1
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- Prior art keywords
- hydroxy
- cyclohexanone
- methoxybenzylidene
- synthesis
- yield
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 10
- DHKKONBXGAAFTB-UHFFFAOYSA-N cyclovalone Chemical compound C1=C(O)C(OC)=CC(C=C2C(C(=CC=3C=C(OC)C(O)=CC=3)CCC2)=O)=C1 DHKKONBXGAAFTB-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 230000015572 biosynthetic process Effects 0.000 title abstract description 6
- 238000003786 synthesis reaction Methods 0.000 title abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims abstract description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 5
- DKZBBWMURDFHNE-UHFFFAOYSA-N trans-coniferylaldehyde Natural products COC1=CC(C=CC=O)=CC=C1O DKZBBWMURDFHNE-UHFFFAOYSA-N 0.000 claims abstract description 5
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000009833 condensation Methods 0.000 claims abstract description 4
- 230000005494 condensation Effects 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 150000001299 aldehydes Chemical class 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 4
- 239000007795 chemical reaction product Substances 0.000 abstract 2
- 239000000126 substance Substances 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010008617 Cholecystitis chronic Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Изобретение относится к химико-фармацевтической промышленности, а именно к способам синтеза лекарственных препаратов. The invention relates to the pharmaceutical industry, and in particular to methods for the synthesis of drugs.
2,6-Ди-(4-гидрокси-3-метоксибензилиден)циклогексанон под названием "Циквалон" используется в медицинской практике для стимуляции образования и выделения желчи и применяется при хронических холециститах, холангитах, холецистогепатитах, желчекаменной болезни, а также в качестве противовоспалительного средства [1]
Известен способ получения циквалона, используемый в промышленности, как наиболее удобный из существующих, заключающийся в конденсации 4-гидрокси-3-метоксибензальдегида с циклогексаном при пропускании через их раствор в этаноле тока газообразного хлорводорода и перемешивании в течение 10 12 ч. Выход целевого продукта составляет 74,7% [2]
Данный способ имеет следующие недостатки:
необходимость использования сложного технологического оборудования и аппаратуры для получения, пропускания через реакционную массу, улавливания и утилизации газообразного хлороводорода;
высокая продолжительность технологического процесса.2,6-Di- (4-hydroxy-3-methoxybenzylidene) cyclohexanone called "Cycalvalon" is used in medical practice to stimulate the formation and secretion of bile and is used for chronic cholecystitis, cholangitis, cholecystohepatitis, cholelithiasis, and also as an anti-inflammatory agent [1]
A known method of producing cycvalone, used in industry, as the most convenient of the existing ones, which consists in the condensation of 4-hydroxy-3-methoxybenzaldehyde with cyclohexane by passing a stream of gaseous hydrogen chloride through ethanol solution and stirring for 10 12 hours. The yield of the target product is 74 , 7% [2]
This method has the following disadvantages:
the need to use sophisticated technological equipment and apparatus for receiving, passing through the reaction mass, trapping and disposing of gaseous hydrogen chloride;
high duration of the process.
Целью изобретения является повышение выхода целевого продукта, исключение из процесса технологически неудобного газообразного хлороводорода и сложного оборудования и аппаратуры, сокращение продолжительности синтеза. The aim of the invention is to increase the yield of the target product, the exclusion from the process of technologically inconvenient gaseous hydrogen chloride and complex equipment and apparatus, reducing the duration of the synthesis.
Цель достигается конденсацией 4-гидрокси-3-метокси- бензальдегида с циклогексаноном в этанольном растворе в присутствии серной кислоты и иллюстрируется следующим примером. The goal is achieved by condensation of 4-hydroxy-3-methoxybenzaldehyde with cyclohexanone in an ethanol solution in the presence of sulfuric acid and is illustrated by the following example.
Пример. 2,6-Ди-(4-гидрокси-3-метоксибензилиден)циклогексанон. К 12 мл этанола при перемешивании добавляют 2 мл концентрированной серной кислоты, 3,04 г (0,02 моль) 4-гидрокси-3-метоксибензальдегида и 1,1 г (0,011 моль) циклогексанона. Реакционную смесь перемешивают в течение 1,5 ч и добавляют 6 мл воды. Выделившийся осадок отделяют, промывают водой до нейтральной реакции и сушат. Example. 2,6-Di- (4-hydroxy-3-methoxybenzylidene) cyclohexanone. To 12 ml of ethanol, 2 ml of concentrated sulfuric acid, 3.04 g (0.02 mol) of 4-hydroxy-3-methoxybenzaldehyde and 1.1 g (0.011 mol) of cyclohexanone are added with stirring. The reaction mixture was stirred for 1.5 hours and 6 ml of water was added. The precipitate formed is separated, washed with water until neutral and dried.
Выход C22H22O5 3,4 г (91%). Кристаллизуют из этанола. Т. пл. 180 181oC.Yield C 22 H 22 O 5 3.4 g (91%). Crystallized from ethanol. T. pl. 180 181 o C.
Найдено, C 72,21; H 6,11
Вычислено, C 72,13; H 6,01
Данные спектров, см-1: УФ- 393, (269), 256, 212 нм; ИК 3350, 1645, 1580, 1510, 1310, 1285, 1255, 1050, 990, 945, 850, 800, 715.Found, C, 72.21; H 6.11
Calculated, C 72.13; H 6.01
Spectrum data, cm -1 : UV-393, (269), 256, 212 nm; IR 3350, 1645, 1580, 1510, 1310, 1285, 1255, 1050, 990, 945, 850, 800, 715.
Таким образом, предлагаемый способ получения циквалона, по сравнению с существующим, позволяет существенно повысить выход целевого продукта, значительно сократить продолжительность синтеза и исключить из процесса технологически неудобный газообразный хлороводород и, в связи с этим, сложное оборудование и аппаратуру. Thus, the proposed method for producing cycvalone, compared with the existing one, can significantly increase the yield of the target product, significantly reduce the synthesis time and eliminate technologically uncomfortable gaseous hydrogen chloride from the process and, therefore, complex equipment and apparatus.
По предлагаемому способу циквалон может быть получен на любом химико-фармацевтическом заводе с использованием имеющегося оборудования и аппаратуры. According to the proposed method, cyclonal can be obtained at any chemical-pharmaceutical plant using the available equipment and apparatus.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU94033536A RU2088569C1 (en) | 1994-09-12 | 1994-09-12 | Method of synthesis of 2,6-di-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU94033536A RU2088569C1 (en) | 1994-09-12 | 1994-09-12 | Method of synthesis of 2,6-di-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU94033536A RU94033536A (en) | 1996-07-20 |
| RU2088569C1 true RU2088569C1 (en) | 1997-08-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU94033536A RU2088569C1 (en) | 1994-09-12 | 1994-09-12 | Method of synthesis of 2,6-di-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone |
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| RU (1) | RU2088569C1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0860422A1 (en) * | 1997-02-20 | 1998-08-26 | The University of Gajah Mada | Derivatives of benzylidene cyclohexanone, benzylidene cyclopentanone, and benzylidene acetone and their synthesis. |
-
1994
- 1994-09-12 RU RU94033536A patent/RU2088569C1/en active
Non-Patent Citations (1)
| Title |
|---|
| 1. J.Med. Chem, 1976, 19(3), 433-6. 2. Рубцов М.В., Байчиков А.Г. Синтетические химико-фармацевтические препараты. - М.: Медицина, 1971, с. 36 - 37. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0860422A1 (en) * | 1997-02-20 | 1998-08-26 | The University of Gajah Mada | Derivatives of benzylidene cyclohexanone, benzylidene cyclopentanone, and benzylidene acetone and their synthesis. |
Also Published As
| Publication number | Publication date |
|---|---|
| RU94033536A (en) | 1996-07-20 |
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