DE1025868B - Process for the preparation of tetracycline nitrile - Google Patents
Process for the preparation of tetracycline nitrileInfo
- Publication number
- DE1025868B DE1025868B DEA24288A DEA0024288A DE1025868B DE 1025868 B DE1025868 B DE 1025868B DE A24288 A DEA24288 A DE A24288A DE A0024288 A DEA0024288 A DE A0024288A DE 1025868 B DE1025868 B DE 1025868B
- Authority
- DE
- Germany
- Prior art keywords
- nitrile
- tetracycline
- preparation
- parts
- catalyst
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 tetracycline nitrile Chemical class 0.000 title claims description 10
- 239000004098 Tetracycline Substances 0.000 title claims description 9
- 229960002180 tetracycline Drugs 0.000 title claims description 9
- 229930101283 tetracycline Natural products 0.000 title claims description 9
- 235000019364 tetracycline Nutrition 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 239000004099 Chlortetracycline Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003522 tetracyclines Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von Tetracyclinnitril Die vorliegende Erfindung betrifft die Herstellung von Tetracyclinnitril.Process for the preparation of tetracycline nitrile The present invention relates to the manufacture of tetracycline nitrile.
Die erfindungsgemäß erhaltene neue Verbindung entspricht der allgemeinen Formel R-C N, in der R den Tetracyclinrest bedeutet, der durch eine einfache Kohlenstoff-Kohlenstoff-Bindung in 2-Stellung an die C N-Gruppe gebunden ist. Diese neue Verbindung stellt ein wertvolles Zwischenprodukt bei der Herstellung von tertiären Butylderivaten des Anhydrotetracyclins dar, die neue Verbindungen mit breitem Wirkungsspektrum sind. Diese Verbindungen sind in der Patentanmeldung A 24289 IV b / 12 o beschrieben.The new compound obtained according to the invention corresponds to the general one Formula R-C N, in which R denotes the tetracycline residue created by a simple carbon-carbon bond is bonded in the 2-position to the C N group. This new connection represents a valuable one Intermediate product in the manufacture of tertiary butyl derivatives of anhydrotetracycline which are new compounds with a broad spectrum of activity. These connections are described in patent application A 24289 IV b / 12 o.
Gemäß der Erfindung kann Tetracyclinnitril durch Hydrieren eines Halogentetracyclinnitrils in Gegenwart eines Palladium-Aktivkohle-Katalvsators hergestellt werden. Bei dieser Arbeitsweise kann Chlortetracyclinnitril oder Bromtetracyclinnitril mit einem inerten organischen Lösungsmittel, wie 2-Methoxväthanol, aufgeschlämmt werden. Vorzugsweise wird außerdem ein geeignetes tertiäres Amin, wie Triäthylamin oder Pyridin, zum Alkalischmachen des Reaktionsgemisches verwendet. Es werden etwa 2 Mol Amin je Mol Chlortetracyclinnitril oder Bromtetraevclinnitril verwendet. Dann wird das Reaktionsgemi.sch in Gegenwart des Katalysators bis zum End.@ der Wasserstoffaufnahme hydriert. Nach dem Abfiltrieren des Katalysators wird äthanolische Salzsäure zugesetzt, bis der pH-Wert auf etwa 3,0 bis 3,5 abgesunken ist. Zu diesem Zeitpunkt scheidet sich eine kristalline feste Substanz, das Tetracyclinnitril. aus.According to the invention, tetracycline nitrile can be prepared by hydrogenating a halo-tetracycline nitrile in the presence of a palladium-activated carbon catalyst. At this Working method can chlortetracycline nitrile or bromotetracycline nitrile with an inert organic solvents, such as 2-methoxy ethanol, are slurried. Preferably is also a suitable tertiary amine, such as triethylamine or pyridine, for Making the reaction mixture alkaline is used. There are about 2 moles of amine per mole Chlortetracyclinenitril or Bromtetraevclinnitril used. Then the reaction mixture is hydrogenated in the presence of the catalyst until the end of hydrogen uptake. To the filtration of the catalyst, ethanolic hydrochloric acid is added until the pH has dropped to around 3.0 to 3.5. At this point, one divorces crystalline solid substance, tetracycline nitrile. the end.
Das folgende Beispiel erläutert die Erfindung. ohne sie zu beschränken. Alle Teile sind Gewichtsteile, trenn nichts anderes angegeben ist. Beispiel 4,61 Teile Chlortetracyclinnitril werden in 75 Volumteilen 2-i@lethoxyäthanol aufgeschlämmt und mit 2,8 Volumteilen Triäthylamin versetzt. Die Mischung wurde 15 bis 20 Minuten mechanisch geschüttelt, bis nahezu die gesamten Feststoffe in Lösung gegangen waren. Die Lösung wurde filtriert und das Filtrat mit 0,5 Teilen eines 10%igen Palladium-Aktivkohle-Kata-1vsators versetzt. Die Lösung wurde in einer Hydriervorrichtung bei 20c' C und Atmosphärendruck ge-.,chüttelt; in 25 Minuten wurden 2-15 Volumteile Was.,erstoff aufgenommen. dann hörte die Aufnahme nahezu auf. -Nach dem Abfiltrieren des Katalvsatorz wurden 1,3 Volumteile 7,7 normaler äthanolischer Salzsäure zugegeben, wodurch ein p11-Wert von etwa 5 bis 6 erreicht wurde. Einige weitere Tropfen brachten den pH-Wert auf 3,0 bis 3,5, und eine kristalline feste Substanz fiel aus. Nach dem Abkühlen in Eis wurde das Produkt abfiltriert und durch erneutes Aufschlämmen in Wasser gut gewaschen. Das getrocknete Tetracyclinnitril wog 3,5 g. Die Elementaranalyse des Produktes ergab 60,3°/o Kohlenstoff, 5,8% Wasserstoff und 6,33% Stickstoff.The following example illustrates the invention. without restricting them. All parts are parts by weight unless otherwise indicated. Example 4.61 parts of chlorotetracycline nitrile are slurried in 75 parts by volume of 2-i @ lethoxyethanol, and 2.8 parts by volume of triethylamine are added. The mixture was mechanically shaken for 15 to 20 minutes until nearly all of the solids had gone into solution. The solution was filtered and 0.5 part of a 10% palladium-activated carbon catalyst was added to the filtrate. The solution was shaken in a hydrogenation device at 20 ° C. and atmospheric pressure; 2-15 parts by volume of water were absorbed in 25 minutes. then the recording almost stopped. After filtering off the catalyst, 1.3 parts by volume of 7.7 normal ethanolic hydrochloric acid were added, resulting in a p11 value of about 5 to 6. Some more drop brought the pH to 3.0 to 3.5, and a crystalline solid substance precipitated. After cooling in ice, the product was filtered off and washed well by reslurrying in water. The dried tetracycline nitrile weighed 3.5 g. Elemental analysis of the product showed 60.3% carbon, 5.8% hydrogen and 6.33% nitrogen.
Das Produkt zeigte, wie derartige Verbindungen allgemein, keinen scharfen Schmelzpunkt. Bei der Schmelzpunktsbestimmung wurde die Substanz bei Temperaturen von 240 bis 280° C langsam dunkel.The product, like such compounds in general, showed no sharpness Melting point. When determining the melting point, the substance was at temperatures slowly darkens from 240 to 280 ° C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1025868XA | 1955-02-14 | 1955-02-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1025868B true DE1025868B (en) | 1958-03-13 |
Family
ID=22290607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEA24288A Pending DE1025868B (en) | 1955-02-14 | 1956-02-09 | Process for the preparation of tetracycline nitrile |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1025868B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3030377A (en) * | 1959-08-27 | 1962-04-17 | Hoechst Ag | Process for the manufacture of nitriles of tetracyclines |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2699054A (en) * | 1953-10-09 | 1955-01-11 | Lloyd H Conover | Tetracycline |
-
1956
- 1956-02-09 DE DEA24288A patent/DE1025868B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2699054A (en) * | 1953-10-09 | 1955-01-11 | Lloyd H Conover | Tetracycline |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3030377A (en) * | 1959-08-27 | 1962-04-17 | Hoechst Ag | Process for the manufacture of nitriles of tetracyclines |
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