CH259710A - Process for the preparation of a biguanide derivative. - Google Patents
Process for the preparation of a biguanide derivative.Info
- Publication number
- CH259710A CH259710A CH259710DA CH259710A CH 259710 A CH259710 A CH 259710A CH 259710D A CH259710D A CH 259710DA CH 259710 A CH259710 A CH 259710A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- chloro
- methyl
- iodophenyl
- biguanide derivative
- 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 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 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
- 229940123208 Biguanide Drugs 0.000 claims 2
- 230000000078 anti-malarial effect Effects 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 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
- -1 3-chloro-4-iodaniline chlorohydrate Chemical compound 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 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
- 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
- ONZHMGRKWJMTDE-UHFFFAOYSA-N 3-chloro-4-iodoaniline Chemical compound NC1=CC=C(I)C(Cl)=C1 ONZHMGRKWJMTDE-UHFFFAOYSA-N 0.000 description 1
- 101100202589 Drosophila melanogaster scrib gene Proteins 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
- 238000001704 evaporation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000006303 iodophenyl group Chemical group 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
- 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)
- 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 N1-3-Chlor-4- ,jodphenyl - N 5 - nietliyl - N:-, - isopropylbiguanid, -%aelches ein wertvolles chemotherapeutisehes Mittel ist oder als Zwischenprodukt für die Herstellung von chemotherapeutischen Mit teln verwendet werden kann. Es ist insbeson dere ein wertvolles Antimalariamittel.
Erfindungsgemäss wird die besagte neue Verbindung, e-, nämlich N 1-3-Chlor-4-jodpheny 1- NI-methyl-N",-isopropyIbig-ianid, dadurch er halten, dass man N3-hlethyl-N3-isopropyl- dicyaudiamid mit 3-Chlor-4-jodanilin um setzt.
Die Umsetzung erfolgt zweckmässig durch Erhitzen eines Salzes des Amins mit dem sub stituierten Dicyandiamid in fTegen-%vart eines Lösungsmittels, -vie z. B. Wasser oder ss- @1thor-väthanol.
Das N1-3-Clilor-4-jodphenyl-N -methyl-N5- isopropylbiguanid 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 sieh dadurch herstellen, dass die Base in wässrigen Lös-uigen der Säure ge löst 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, Methylendisalicylsäu re, 111ethylen-bis-p- oxynapht.hoesäure und Salzsäure bequem her stellen.
Das folgende Beispiel diene zur Erläute rung der Erfindung. <I>Beispiel:</I> Ein Gemisch von 14 Teilen N3-lslethyl-N3- isoprop@-ldieyandiamid und 29 Teilen 3-Chlor- 4-jodanilin-ehlorhydrat in 120 Teilen Athoxyäthanol wird während 3 Stunden -unter Rüekfluss zum Sieden erhitzt. Hierauf lässt man das Gemisch abkühlen, worauf abfiltriert wird. Der feste Rückstand wird mit kaltem Athylacetat gewaschen und aus Wasser um kristallisiert.
Auf diese Weise erhält. man N1 3 - Chlor-4-j odphenyl -N' -methyl-N '-isopropyl- biguanid in Form seines Monohy drochlorids, welches bei 231 C schmilzt.
Process for the preparation of a biguanide derivative. The present invention relates to a process for the preparation of N1-3-chloro-4-, iodophenyl - N 5 - nietliyl - N: -, - isopropylbiguanide, -% which is a valuable chemotherapeutic agent or as an intermediate for the preparation of chemotherapeutic agents can be used. It is especially a valuable antimalarial agent.
According to the invention, the said new compound, e-, namely N 1-3-chloro-4-iodopheny 1- NI-methyl-N ", - isopropyIbig-ianid, is obtained by using N3-methyl-N3-isopropyl-dicyaudiamide with 3-chloro-4-iodaniline.
The reaction is conveniently carried out by heating a salt of the amine with the sub-substituted dicyandiamide in fTegen-% vart of a solvent, -vie z. B. water or ss- @ 1thor-väthanol.
The N1-3-Clilor-4-iodophenyl-N -methyl-N5-isopropylbiguanid is a strong base, which with organic. and inorganic acids results in stable salts, which in some cases easily in water. are soluble. The salts can be prepared by dissolving the base in aqueous solutions of the acid and then evaporating the water, but they can be more conveniently prepared in dry form 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, methylenedisalicylic acid, 111ethylene-bis-p-oxynaphthoic acid and hydrochloric acid can be conveniently prepared.
The following example serves to explain the invention. <I> Example: </I> A mixture of 14 parts of N3-islethyl-N3-isoprop®-ldieyandiamide and 29 parts of 3-chloro-4-iodaniline chlorohydrate in 120 parts of ethoxyethanol is heated to boiling for 3 hours under reflux . The mixture is then allowed to cool and it is filtered off. The solid residue is washed with cold ethyl acetate and recrystallized from water.
That way it gets. one N1 3 - chloro-4-iodophenyl -N '-methyl-N' -isopropyl biguanid in the form of its Monohy drochlorids, which melts at 231C.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB259710X | 1945-10-08 | ||
| GB170946X | 1946-09-17 | ||
| CH254800T | 1946-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH259710A true CH259710A (en) | 1949-01-31 |
Family
ID=27178066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH259710D CH259710A (en) | 1945-10-08 | 1946-10-08 | Process for the preparation of a biguanide derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH259710A (en) |
-
1946
- 1946-10-08 CH CH259710D patent/CH259710A/en unknown
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