CH259665A - Process for the preparation of a biguanide derivative. - Google Patents
Process for the preparation of a biguanide derivative.Info
- Publication number
- CH259665A CH259665A CH259665DA CH259665A CH 259665 A CH259665 A CH 259665A CH 259665D A CH259665D A CH 259665DA CH 259665 A CH259665 A CH 259665A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- biguanide derivative
- acid
- biguanide
- salts
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims 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
- PLFFHJWXOGYWPR-HEDMGYOXSA-N (4r)-4-[(3r,3as,5ar,5br,7as,11as,11br,13ar,13bs)-5a,5b,8,8,11a,13b-hexamethyl-1,2,3,3a,4,5,6,7,7a,9,10,11,11b,12,13,13a-hexadecahydrocyclopenta[a]chrysen-3-yl]pentan-1-ol Chemical compound C([C@]1(C)[C@H]2CC[C@H]34)CCC(C)(C)[C@@H]1CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@@H]1[C@@H](CCCO)C PLFFHJWXOGYWPR-HEDMGYOXSA-N 0.000 claims 1
- SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 claims 1
- 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
- -1 N'-3 Chemical class 0.000 description 2
- 239000002253 acid Substances 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000002246 antineoplastic 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
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001704 evaporation Methods 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
- DADSZOFTIIETSV-UHFFFAOYSA-N n,n-dichloroaniline Chemical compound ClN(Cl)C1=CC=CC=C1 DADSZOFTIIETSV-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines Biguanidderivates. Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von N'-3,-I-Di- ehlorl>lienyl-N '-n-propylbiguanid,welches ein wertvolles chemotherapeutisches Mittel ist oder als Zwischenprodukt für die Herstellung von ehemotherapeutisehen Mitteln verwendet werden kann. Es ist insbesondere ein wert volles Antimalariamittel.
Erfindungsgemäss wird die besagte neue Verbindung, nämlich N'-3,4-Dichlorphenyl- N'-n-propylbiguanid, dadurch erhalten, dass man N:'-n-Propyldicyandiainid mit. 3,4=Di- chloranilin umsetzt.
Die Umsetzung erfolgt zweckmässig durch Erhitzen eines Salzes des Amins mit dem substituierten Dicyandiamid in Gegenwart eines Lösungsmittels, wie z. B. Wasser oder P-Äthoxyäthanol.
Das N'-3,4-Diclilorphenyl-N'-n-propz-1- biguanid stellt eine starke Base dar, welche mit organischen und anorganischen Säuren beständige Salze ergibt, die in manehen Fällen in Wasser leicht löslieh sind. Die Salze lassen sieh dadurch herstellen, dass die Base in wässrigen Lösungen der Säure gelöst und hierauf das Wasser verdampft wird, doch können sie in trockener Form bequemer dureli Vermischen der Komponenten in einem ornanisehen Lösungsmittel, wie z. B.
Aceton, oder in einem Alkohol, in welchem die Salze spärlich löslich sind, hergestellt werden. Auf diese Weise kann inan beispielsweise die Salze mit Essigsäure, lIilchsättre, Methansulfon- säure, lletliyleiidisalie5-lsäure, Metliylen-bis-P- oxynaphthoesäure und Salzsäure bequem her stellen.
Das folgende Beispiel diene zur Erläute rung der Erfindung. Beispiel: Bin Gemisch von 13,9 Teilen N 1-n-Pr opy 1 dieyandiamid und 19,85 Teilen 3,4-Dichlor- anilin-chlorhydrat in 100 Teilen P-Äthox@-- ät.lianolwird während 3 Stunden unter Rüek- fluss zuin Sieden erhitzt. Hierauf lässt man das Gemisch abkühlen, worauf abfiltriert wird.
Der feste Rückstand wird mit kaltem Äthylacetat gewaschen und aus 'Wasser um kristallisiert. Auf diese Weise erhält man N'-3,4-Dichlorphenyl-N I-n-propylbiguanid in Form seines Monohydrochlorids, welches bei \?37-238" C schmilzt.
Process for the preparation of a biguanide derivative. The present invention relates to a process for the preparation of N'-3, -I-di-ehlorl> lienyl-N'-n-propylbiguanide, which is a valuable chemotherapeutic agent or can be used as an intermediate for the preparation of former therapeutic agents. It is a particularly valuable antimalarial drug.
According to the invention, said new compound, namely N'-3,4-dichlorophenyl-N'-n-propylbiguanide, is obtained by reacting with N: '- n-propyldicyandiainide. 3.4 = dichloroaniline converts.
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 P-ethoxyethanol.
The N'-3,4-diclilorphenyl-N'-n-propz-1-biguanide is a strong base which, with organic and inorganic acids, gives stable salts which in some cases are easily soluble in water. The salts can be produced by dissolving the base in aqueous solutions of the acid and then evaporating the water, but in dry form they can be more conveniently by mixing the components in an organic solvent, such as e.g. 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, lletliyleiidisalic-oleic acid, methylene-bis-oxynaphthoic acid and hydrochloric acid can be conveniently prepared.
The following example serves to explain the invention. Example: A mixture of 13.9 parts of N 1-n-Pr opy 1 dieyandiamid and 19.85 parts of 3,4-dichloro-aniline chlorohydrate in 100 parts of P-ethox @ - ät.lianol is for 3 hours under Rüek- river heated to boiling point. The mixture is then allowed to cool and it is filtered off.
The solid residue is washed with cold ethyl acetate and crystallized from 'water. In this way, N'-3,4-dichlorophenyl-N I-n-propyl biguanide is obtained in the form of its monohydrochloride, which melts at 37-238 "C.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB259665X | 1945-10-08 | ||
| GB170946X | 1946-09-17 | ||
| CH254800T | 1946-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH259665A true CH259665A (en) | 1949-01-31 |
Family
ID=27178021
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH259665D CH259665A (en) | 1945-10-08 | 1946-10-08 | Process for the preparation of a biguanide derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH259665A (en) |
-
1946
- 1946-10-08 CH CH259665D patent/CH259665A/en unknown
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