CH259654A - Process for the preparation of a biguanide derivative. - Google Patents
Process for the preparation of a biguanide derivative.Info
- Publication number
- CH259654A CH259654A CH259654DA CH259654A CH 259654 A CH259654 A CH 259654A CH 259654D A CH259654D A CH 259654DA CH 259654 A CH259654 A CH 259654A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- chloro
- methylphenyl
- biguanide derivative
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 4
- 150000004283 biguanides Chemical class 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000155 melt Substances 0.000 claims description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
- 230000000078 anti-malarial effect Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- SWHSXWLSBBYLGM-UHFFFAOYSA-N 2-[(2-carboxyphenoxy)methoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCOC1=CC=CC=C1C(O)=O SWHSXWLSBBYLGM-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- -1 4-chloro-3-methylaniline chlorohydrate Chemical compound 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung eines Biguanidderivates. Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von Nl-4-Chlor-3- methylphenyl-N'-isopropylbiguanid, welches ein wertvolles chemotherapeutisches Mittel ist oder als Zwischenprodukt für die Herstellung von chemotherapeutischen Mitteln verwendet werden kann. Es ist insbesondere ein wert volles Antimalariamittel.
Erfindungsgemäss wird die besagte neue Verbindung, nämlich Nl-4-Chlor-3-methyl- phenyl-NS-isopropylbiguanid, dadurch erhal ten, dass man NI-Isopropyldicyandiamid mit 9-Chlor-3-niethylaniliri umsetzt.
Die Umsetzung erfolgt zweckmässig durch Erhitzen eines Salzes des Amins mit dem substituierten Dicyandiamid in Gegenwart eines Lösungsmittels, wie z. B. Wasser oder ss-Äthoxyäthanol.
Das Nl-4-Chlor-3-methylphenyl-NS-isopro- pylbiguanid stellt eine starke Base dar, welche mit organischen und anorganischen Säuren beständige Salze ergibt, die in man chen Fällen in Wasser leicht löslich sind. Die Salze lassen sich dadurch herstellen, dass die Base in wässrigen Lösungen der Säure gelöst und hierauf das Wasser verdampft wird, doch können sie in trockener Form bequemer durch Vermischen der Komponenten in einem organischen Lösungsmittel, wie z. B. Aceton, oder in einem Alkohol, in welchem die Salze spärlich löslich sind, hergestellt werden.
Auf diese Weise kann man beispielsweise die Salze mit Essigsäure, Milchsäure, Methansulfon- säure, Methylendisalicylsäure, Methy len-bis-ss- oxynaphthoesäure und Salzsäure bequem her stellen.
Das folgende Beispiel diene zur Erläute rung der Erfindung.
<I>Beispiel:</I> Ein Gemisch von 6,3 Teilen N3-Isopropy 1- dicyandiamid und 8,9 Teilen 4-Chlor-3-me- thylanilin-chlorhydrat in 50 Teilen fl-Äthoxy- äthanol wird während 3 Stunden unter Rückfluss zum Sieden erhitzt. Hierauf lässt man das Gemisch abkühlen, worauf abfil- triert wird. Der feste Rückstand wird mit kaltem Äthylacetat gewaschen und aus Wasser umkristallisiert.
Auf diese Weise er hält man Nl-4-Chlor-3-methylphenyl-NJ-iso- propylbiguanid in Form seines Monohydro- chlorids, welches bei 245 C schmilzt.
Process for the preparation of a biguanide derivative. The present invention relates to a process for the preparation of Nl-4-chloro-3-methylphenyl-N'-isopropyl biguanide, which is a valuable chemotherapeutic agent or which can be used as an intermediate for the preparation of chemotherapeutic agents. It is a particularly valuable antimalarial drug.
According to the invention, said new compound, namely Nl-4-chloro-3-methylphenyl-NS-isopropylbiguanide, is obtained by reacting NI-isopropyldicyandiamide with 9-chloro-3-niethylaniliri.
The reaction is conveniently carried out by heating a salt of the amine with the substituted dicyandiamide in the presence of a solvent, such as. B. water or ss-ethoxyethanol.
The Nl-4-chloro-3-methylphenyl-NS-isopropylbiguanid is a strong base which, with organic and inorganic acids, results in stable salts which in some cases are easily soluble in water. The salts can be prepared in that the base is dissolved in aqueous solutions of the acid and then the water is evaporated, but they can be more conveniently in dry form by mixing the components in an organic solvent, such as. B. acetone, or in an alcohol in which the salts are sparingly soluble.
In this way, for example, the salts with acetic acid, lactic acid, methanesulfonic acid, methylenedisalicylic acid, methylene-bis-s-oxynaphthoic acid and hydrochloric acid can be conveniently prepared.
The following example serves to explain the invention.
<I> Example: </I> A mixture of 6.3 parts of N3-isopropy-1-dicyandiamide and 8.9 parts of 4-chloro-3-methylaniline chlorohydrate in 50 parts of fl-ethoxyethanol is used for 3 hours heated to boiling under reflux. The mixture is then allowed to cool, whereupon it is filtered off. The solid residue is washed with cold ethyl acetate and recrystallized from water.
In this way, Nl-4-chloro-3-methylphenyl-NJ-isopropyl biguanide is obtained in the form of its monohydrochloride, which melts at 245.degree.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB259654X | 1945-10-08 | ||
| GB170946X | 1946-09-17 | ||
| CH254800T | 1946-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH259654A true CH259654A (en) | 1949-01-31 |
Family
ID=27178010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH259654D CH259654A (en) | 1945-10-08 | 1946-10-08 | Process for the preparation of a biguanide derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH259654A (en) |
-
1946
- 1946-10-08 CH CH259654D patent/CH259654A/en unknown
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