CH525206A - Alkyl flavone-7-oxyacetates prepn - Google Patents
Alkyl flavone-7-oxyacetates prepnInfo
- Publication number
- CH525206A CH525206A CH886472A CH886472A CH525206A CH 525206 A CH525206 A CH 525206A CH 886472 A CH886472 A CH 886472A CH 886472 A CH886472 A CH 886472A CH 525206 A CH525206 A CH 525206A
- Authority
- CH
- Switzerland
- Prior art keywords
- flavone
- oxyacetates
- alkyl
- prepn
- preparation
- Prior art date
Links
- -1 Alkyl flavone-7-oxyacetates Chemical class 0.000 title claims description 4
- 238000000034 method Methods 0.000 claims description 7
- MQGPSCMMNJKMHQ-UHFFFAOYSA-N 7-hydroxyflavone Chemical compound C=1C(O)=CC=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 MQGPSCMMNJKMHQ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- ZVXBAHLOGZCFTP-UHFFFAOYSA-N Efloxate Chemical compound C=1C(OCC(=O)OCC)=CC=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 ZVXBAHLOGZCFTP-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 239000003218 coronary vasodilator agent Substances 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- SGCWGDJXEREHOI-UHFFFAOYSA-N 2-(4-oxo-2-phenylchromen-7-yl)oxyacetonitrile Chemical compound O1C2=CC(OCC#N)=CC=C2C(=O)C=C1C1=CC=CC=C1 SGCWGDJXEREHOI-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Abstract
Alkyl flavone-7 oxyacetates prepn. Title cpds. are prepd. by the follg. route:- Compared with prior art, this involves fewer stages and gives better yields of purer material. The Et ester is a known coronary dilator.
Description
Procédé de préparation des flavone-7-oxyacétates d'alcoyle inférieur
Le flavone-7-oxyacétate d'éthyle de formule:
EMI1.1
est un produit déjà connu et employé en thérapie pour sa remarquable activité coronaire dilatatrice. associée à une toxicité très basse.
Le but de la présente invention est un nouveau procédé de préparation des flavone-7-oxyacétates d'alcoyle inférieur et en particulier du flavone-7-oxyacétate d'éthyle. Ce procédé permet d'arriver à un produit qui, grâce à ses caractères de pureté, se prête déjà à l'emploi pharmaceutique.
Le procédé selon l'invention est caractérisé par les stades suivants: (a) l'on fait réagir du chloroacétonitrile avec de la 7-hydroxy-flavone pour obtenir la 7cyanométhoxy-flavone et (b) l'on fait réagir cette dernière avec un alcanol inférieur anhydre en présence d'un acide minéral.
Une mise en oeuvre préférée de ce procédé est représentée dans le schéma suivant:
EMI1.2
Exemple
A. 7-cyanométhoxy-flavone
A une solution de 2,38 g de 7-hydroxy-flavone dans 10 ml de diméthylformamide, on ajoute 1,38 g de carbonate de potassium anhydre et une petite quantité catalytique d'iodure de potassium. Dans le mélange, agité au bain-marie bouillant, on laisse ensuite tomber goutte à goutte 0,83g de chloroacétonitrile.
Après avoir terminé l'addition on agite encore pendant 1 heure au bain-marie bouillant, ensuite on refroidit et on verse dans l'eau (100 mi). On extrait ensuite le solide précipité dans du chlorure de méthylène, on lave l'extrait avec de l'hydroxyde de sodium dilué, puis avec de l'eau, on le sèche (Na2SO4) et on l'évapore: 2,22 g de solide blanc, p.f. 182-1830 C unitaire à la chromatographie sur couche mince. Le produit peut être cristallisé à partir de méthanol.
Analyse pour ClTHttNO3: C o/o Ho/o N ego
calculé: 73,65 4,00 5,05
trouvé : 73,80 4,10 5,06
B. Flavone-7-oxyacétate d'éthyle
Dans une suspension de 2,77 g de 7-cyanométhoxyflavone dans 50 ml d'éthanol absolu on fait passer un courant d'acide chlorhydrique gazeux sec pendant 2 heures, en refroidissant extérieurement avec de l'eau glacée et en protégeant de l'humidité. On laisse ensuite reposer pendant une nuit, puis on traite avec précaution avec de l'eau (100 mi en tout) en maintenant la température au-dessous de 10o C par refroidissement.
On obtient une solution légèrement trouble de laquelle commence à se séparer un solide floconneux après quelques minutes. On laisse reposer pendant 15 minutes, puis on extrait à l'éther. On lave la solution éthérée avec du bicarbonate de sodium et ensuite avec de l'eau, on la sèche (Na2SO4) et on l'évapore: 2,90 g de solide blanc, p.f. 123-1240 C. On obtient 2,60 g à partir d'éthanol à 500/op.f. 123,5-124,50 C.
Analyse pour C1QH1605 : C 0/o H < )/o
calculé: 70,36 4,97
trouvé : 70,22 5,15
Process for the preparation of lower alkyl flavone-7-oxyacetates
Ethyl flavone-7-oxyacetate of the formula:
EMI1.1
is a product already known and used in therapy for its remarkable coronary dilating activity. associated with very low toxicity.
The object of the present invention is a new process for preparing lower alkyl flavone-7-oxyacetates and in particular ethyl flavone-7-oxyacetate. This process makes it possible to obtain a product which, thanks to its characteristics of purity, is already suitable for pharmaceutical use.
The process according to the invention is characterized by the following stages: (a) reacting chloroacetonitrile with 7-hydroxy-flavone to obtain 7cyanomethoxy-flavone and (b) reacting the latter with a anhydrous lower alkanol in the presence of a mineral acid.
A preferred implementation of this method is shown in the following diagram:
EMI1.2
Example
A. 7-cyanomethoxy-flavone
To a solution of 2.38 g of 7-hydroxy-flavone in 10 ml of dimethylformamide, 1.38 g of anhydrous potassium carbonate and a small catalytic amount of potassium iodide are added. In the mixture, stirred in a boiling water bath, 0.83 g of chloroacetonitrile is then allowed to drop dropwise.
After completing the addition, stir for a further 1 hour in a boiling water bath, then cool and pour into water (100 ml). The solid precipitated is then extracted with methylene chloride, the extract is washed with dilute sodium hydroxide, then with water, dried (Na2SO4) and evaporated: 2.22 g of white solid, pf 182-1830 C unit by thin layer chromatography. The product can be crystallized from methanol.
Analysis for ClTHttNO3: C o / o Ho / o N ego
calculated: 73.65 4.00 5.05
found: 73.80 4.10 5.06
B. Ethyl Flavone-7-oxyacetate
In a suspension of 2.77 g of 7-cyanomethoxyflavone in 50 ml of absolute ethanol is passed a stream of dry hydrochloric acid gas for 2 hours, cooling externally with ice water and protecting from humidity. . It is then left to stand overnight, then treated carefully with water (100 ml in all) while maintaining the temperature below 10 ° C. by cooling.
A slightly cloudy solution is obtained from which a fluffy solid begins to separate after a few minutes. Allowed to stand for 15 minutes, then extracted with ether. The ethereal solution is washed with sodium bicarbonate and then with water, dried (Na2SO4) and evaporated: 2.90 g of white solid, m.p. 123-1240 C. 2.60 g is obtained from ethanol at 500 / m.p. 123.5-124.50 C.
Analysis for C1QH1605: C 0 / o H <) / o
calculated: 70.36 4.97
found: 70.22 5.15
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT275571 | 1971-02-19 | ||
| CH769771A CH525205A (en) | 1971-02-19 | 1971-05-26 | Process for the preparation of lower alkyl flavone-7-oxyacetates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH525206A true CH525206A (en) | 1972-07-15 |
Family
ID=25701947
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH886472A CH525206A (en) | 1971-02-19 | 1971-05-26 | Alkyl flavone-7-oxyacetates prepn |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH525206A (en) |
-
1971
- 1971-05-26 CH CH886472A patent/CH525206A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |