AT283363B - Process for the production of new cinnamic acid amides - Google Patents
Process for the production of new cinnamic acid amidesInfo
- Publication number
- AT283363B AT283363B AT837569A AT837569A AT283363B AT 283363 B AT283363 B AT 283363B AT 837569 A AT837569 A AT 837569A AT 837569 A AT837569 A AT 837569A AT 283363 B AT283363 B AT 283363B
- Authority
- AT
- Austria
- Prior art keywords
- cinnamic acid
- general formula
- acid amides
- production
- new
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- APEJMQOBVMLION-UHFFFAOYSA-N cinnamamide Chemical class NC(=O)C=CC1=CC=CC=C1 APEJMQOBVMLION-UHFFFAOYSA-N 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 12
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- CPEONABTMRSIKA-UHFFFAOYSA-N 1,4$l^{2}-oxazinane Chemical compound C1COCC[N]1 CPEONABTMRSIKA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229940046892 lead acetate Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 2
- KRTMKXWOJHDSHE-UHFFFAOYSA-N 3-(3-bromophenyl)-1-piperidin-1-ylprop-2-en-1-one Chemical compound BrC1=CC=CC(C=CC(=O)N2CCCCC2)=C1 KRTMKXWOJHDSHE-UHFFFAOYSA-N 0.000 description 1
- QWQHHPOXLXYYOF-UHFFFAOYSA-N 3-(4-bromophenyl)-1-morpholin-4-ylprop-2-en-1-one Chemical compound C1=CC(Br)=CC=C1C=CC(=O)N1CCOCC1 QWQHHPOXLXYYOF-UHFFFAOYSA-N 0.000 description 1
- ZROGHFJYTNYOOQ-UHFFFAOYSA-N 3-(4-bromophenyl)-1-piperidin-1-ylprop-2-en-1-one Chemical compound C1=CC(Br)=CC=C1C=CC(=O)N1CCCCC1 ZROGHFJYTNYOOQ-UHFFFAOYSA-N 0.000 description 1
- GZFOMZGALYVQDX-UHFFFAOYSA-N 3-(4-bromophenyl)prop-2-ynoic acid Chemical compound OC(=O)C#CC1=CC=C(Br)C=C1 GZFOMZGALYVQDX-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- HSAAUAQFSSQOAO-UHFFFAOYSA-N BrC1=CC=C(C=C1)C#CC(=O)N1CCCCC1 Chemical compound BrC1=CC=C(C=C1)C#CC(=O)N1CCCCC1 HSAAUAQFSSQOAO-UHFFFAOYSA-N 0.000 description 1
- AIVADWFYVZADGZ-UHFFFAOYSA-N C=1C=C(Br)C=CC=1C(C)C(=O)N1CCCCC1 Chemical compound C=1C=C(Br)C=CC=1C(C)C(=O)N1CCCCC1 AIVADWFYVZADGZ-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- HCJTYESURSHXNB-UHFFFAOYSA-N propynamide Chemical compound NC(=O)C#C HCJTYESURSHXNB-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
<Desc/Clms Page number 1>
Verfahren zur Herstellung neuer Zimtsäureamide
Die Erfindung betrifft ein Verfahren zur Herstellung neuer Zimtsäureamide der allgemeinen Formel
EMI1.1
in der
EMI1.2
R2 einen Piperidino- oder Morpholinorest bedeuten.
Die neuen Verbindungen werden erfindungsgemäss nach folgendem Verfahren hergestellt : Partielle Hydrierung einer Verbindung der allgemeinen Formel
EMI1.3
in der RundR wie eingangs definiert sind.
Die partielle Hydrierung wird zweckmässigerweise mit katalytisch erregtem Wasserstoff bei partiell vergiftetem Katalysator, beispielsweise mit Palladium - Calciumcarbonat in Gegenwart von Bleiacetat, in einem Lösungsmittel, z. B. Essigester oder Methanol, vorzugsweise bei Raumtemperatur und Normaldruck durchgeführt.
Eine so erhaltene cis-Verbindung der allgemeinen Formel I kann anschliessend gewünschtenfalls in die entsprechende trans- Verbindung umgelagert werden, beispielsweise durch UV-Bestrahlung in einem geeigneten Lösungsmittel, z. B. Benzol.
Ein als Ausgangsstoff verwendetes Propiolsäureamid der Formel II lässt sich beispielsweise durch Abspaltung von 2 Mol Bromwasserstoff aus einer entsprechenden ct, ss-Dibrorn-ss-phenylpropionsäure und anschliessende Überführung der entsprechenden Propiolsäure in ein Amid der Formel II herstellen.
Bei dem erfindungsgemässen Verfahren erhält man in überwiegendem Masse cis- Verbindungen der allgemeinen Formel I, welche gewünschtenfalls nach üblichen Methoden in die entsprechenden transVerbindungen umgelagert werden können.
<Desc/Clms Page number 2>
Die erfindungsgemäss hergestellten neuen Zimtsäureamide der allgemeinen Formel I besitzen wertvolle pharmakologische Eigenschaften, insbesondere eine antiphlogistische und antipyretische Wirkung.
Im Kaolin- und Carrageenin-Ödemtest an der Ratte sind die Verbindungen der Formel I dem Phenylbutazon bezüglich der therapeutischen Breite überlegen.
Das nachstehende Beispiel dient zur näheren Erläuterung der Erfindung :
Beispiel : 4-Brom-zimtsäurepiperidid
3,5g (0,012 Mol) 4-Bromphenyl-propiolsäurepiperidid (Fp. 200 bis 202 C, hergestellt aus 4-Brom- phenyl-propiolsäure, Thionylchlorid und Piperidin) werden in 35 ml Essigester in Gegenwart von 0,3 g 5 %igem Palladium-Calciumcarbonat-Katalysator und 0,35 ml liger Bleiacetatlösung bei Raumtemperatur und Normaldruck hydriert. Nach 2 h wird die Hydrierung abgebrochen, da die theoretische Menge Wasserstoff aufgenommen worden ist. Das nach Filtrieren und Eindampfen des Filtrats erhaltene Rohprodukt enthält neben der gewünschten Verbindung etwas Ausgangsprodukt und ss (4-Bromphe- nyl)-propionsäurepiperidid, das Produkt der vollständigen Hydrierung.
Durch Säulenchromatographie an Kieselgel (Benzol/Aceton = 9 : 1) lassen sich 1, 4g (40 d. Th.) cis-4-Brom-zimtsäurepiperidid als farbloses Öl isolieren.
Durch 10stündige UV-Bestrahlung in Benzol wird die eis-Verbindung indas trans-Derivat umgewandelt. Fp. 134 C (aus Methanol).
Analog wurden folgende Verbindungen hergestellt :
3-Brom-zimtsäurepiperidid, Fp. 95 - 990C
4-Brom-zimtsäuremorpholid, Fp. 142 - 1440C
EMI2.1
Die erfindungsgemäss hergestellten Verbindungen der Formel I lassen sich nach an sich bekannten Methoden in übliche pharmazeutische Anwendungsformen, gegebenenfalls in Kombination mit andern Wirksubstanzen, einarbeiten. Die Einzeldosis beträgt bei Erwachsenen 200,00 bis 600,00 mg, bevorzugt 300,00 bis 400,00 mg und die Tagesdosis 400,00 bis 1200,00 mg, bevorzugt 600,00 bis 800,00 mg.
**WARNUNG** Ende DESC Feld kannt Anfang CLMS uberlappen**.
<Desc / Clms Page number 1>
Process for the production of new cinnamic acid amides
The invention relates to a process for the preparation of new cinnamic acid amides of the general formula
EMI1.1
in the
EMI1.2
R2 is a piperidino or morpholino radical.
According to the invention, the new compounds are prepared by the following process: Partial hydrogenation of a compound of the general formula
EMI1.3
are defined in the RundR as at the beginning.
The partial hydrogenation is expediently carried out with catalytically excited hydrogen in the case of a partially poisoned catalyst, for example with palladium-calcium carbonate in the presence of lead acetate, in a solvent, e.g. B. ethyl acetate or methanol, preferably carried out at room temperature and normal pressure.
A cis compound of the general formula I obtained in this way can then, if desired, be rearranged into the corresponding trans compound, for example by UV irradiation in a suitable solvent, e.g. B. benzene.
A propiolic acid amide of the formula II used as a starting material can be produced, for example, by splitting off 2 mol of hydrogen bromide from a corresponding ct, ß-dibrorno-ß-phenylpropionic acid and then converting the corresponding propiolic acid into an amide of the formula II.
The process according to the invention gives predominantly cis compounds of the general formula I which, if desired, can be rearranged into the corresponding trans compounds by customary methods.
<Desc / Clms Page number 2>
The new cinnamamides of the general formula I prepared according to the invention have valuable pharmacological properties, in particular an anti-inflammatory and anti-pyretic effect.
In the kaolin and carrageenin edema test on rats, the compounds of the formula I are superior to phenylbutazone with regard to the therapeutic range.
The following example serves to explain the invention in more detail:
Example: 4-bromo-cinnamic acid piperidide
3.5 g (0.012 mol) of 4-bromophenyl-propiolic acid piperidide (melting point 200 to 202 ° C., prepared from 4-bromophenyl-propiolic acid, thionyl chloride and piperidine) are dissolved in 35 ml of ethyl acetate in the presence of 0.3 g of 5% palladium -Calcium carbonate catalyst and 0.35 ml lead acetate solution hydrogenated at room temperature and normal pressure. The hydrogenation is stopped after 2 hours, since the theoretical amount of hydrogen has been absorbed. The crude product obtained after filtering and evaporating the filtrate contains, in addition to the desired compound, some starting product and ss (4-bromophenyl) propionic acid piperidide, the product of the complete hydrogenation.
Column chromatography on silica gel (benzene / acetone = 9: 1) allows 1.4 g (40 d. Th.) Of cis-4-bromocinnamic acid piperidide to be isolated as a colorless oil.
The cis compound is converted to the trans derivative by UV irradiation in benzene for 10 hours. M.p. 134 C (from methanol).
The following connections were made in the same way:
3-Bromo-cinnamic acid piperidide, m.p. 95-990C
4-Bromo-cinnamic acid morpholide, m.p. 142-1440C
EMI2.1
The compounds of the formula I prepared according to the invention can be incorporated into customary pharmaceutical application forms by methods known per se, if appropriate in combination with other active substances. The single dose for adults is 200.00 to 600.00 mg, preferably 300.00 to 400.00 mg, and the daily dose is 400.00 to 1200.00 mg, preferably 600.00 to 800.00 mg.
** WARNING ** End of DESC field may overlap beginning of CLMS **.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT837569A AT283363B (en) | 1968-11-05 | 1968-11-05 | Process for the production of new cinnamic acid amides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT837569A AT283363B (en) | 1968-11-05 | 1968-11-05 | Process for the production of new cinnamic acid amides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT283363B true AT283363B (en) | 1970-08-10 |
Family
ID=3604919
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT837569A AT283363B (en) | 1968-11-05 | 1968-11-05 | Process for the production of new cinnamic acid amides |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT283363B (en) |
-
1968
- 1968-11-05 AT AT837569A patent/AT283363B/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ELJ | Ceased due to non-payment of the annual fee |