CH268051A - Process for preparing 1-methyl-4-piperazine-N, N-diethyl-carboxamide. - Google Patents
Process for preparing 1-methyl-4-piperazine-N, N-diethyl-carboxamide.Info
- Publication number
- CH268051A CH268051A CH268051DA CH268051A CH 268051 A CH268051 A CH 268051A CH 268051D A CH268051D A CH 268051DA CH 268051 A CH268051 A CH 268051A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperazine
- methyl
- diethyl
- carboxamide
- reaction
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims description 9
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OIPVYUVLPGCBMB-UHFFFAOYSA-N ClOCl.CN1CCNCC1 Chemical compound ClOCl.CN1CCNCC1 OIPVYUVLPGCBMB-UHFFFAOYSA-N 0.000 description 1
- 201000006353 Filariasis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 201000009361 ascariasis Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Procédé de préparation de 1-méthyl-4-pipérazine-N,N-diéthyl-earboxamide. La présente invention concerne un procédé de préparation de 1-méthy 1-4-pipérazine-N,N- diéthylcarboxamide, qui est un composé noLi- veau répondant à la formule:
EMI0001.0007
Suivant la présente invention, ce composé est préparé en faisant réagir de la 1-méthyl- pipérazine avec du chlorure de diéthyl-carb- amy le.
Le 1-méthyl-4-pipérazine-N,N-diéthyl-carb- oxamide obtenu par ce procédé est une huile incolore ou jaune pâle, soluble dans la plu part des solvants organiques. Ses sels d'acides sont des solides blancs hygroscopiques solu bles dans l'eau.
La. réaction. est avantageusement réalisée à une température comprise entre 0 et 40 C, de préférence à la température ambiante, dans un solvant tel que le chloroforme, le tétrachlorure de carbone, l'acétate d'éthyle, l'eau, etc.
Lorsqu'on emploie le chloroforme ou un solvant organique similaire pour la mise en aeuvre de l'invention, il est préférable de ré cupérer le produit en saturant tout d'abord le mélange réactionnel avec de l'acide chlor- hydrique, à basse température. Toute frac tion de méthyl-pipérazine non entrée en réac tion est précipitée sous. forme de chlorhy- drate et peut être éliminée par filtration.
Le mélange réactionnel est concentré par élimi nation du solvant, et le dichlorhy drate de 1- méthyl-4-pipérazine-N,N-diéthyl-carboxamide s qui se sépare sous forme solide est traité pour en régénérer la base, éventuellement après recristallisation.
Lorsque la réaction est effectuée cri pré sence d'eau comme solvant (de préférence additionnée d'un alcali), le mode habituel de récupération du produit consiste à, saturer le mélange réactionnel. avec du carbonate de po tassium, du sulfate d'ammonium ou un sel similaire. Le produit est ensuite extrait. par ; un solvant tel que l'éther ou le chloroforme, séché et ensuite distillé.
Le 1-méthyl-4-pipérazine-N,N-diéthyl-earb- oxamide peut être utilisé pour le: traitement de la filariose et en médecine vétérinaire pour le traitement de l'ascaridiose des chiens. <I>Exemple 1:</I> On a préalablement préparé de la 1-mé- thy 1-pipérazine en malaxant intimement<B>81,4g</B> de chaux éteinte avec 43,5 g de dichlorhy- drate de 1-méthyl-pipérazine, puis en distil lant le mélange.
Le distillai: a été séché sur de la potasse caustique solide, additionné d'éther, filtré et séché sur du sulfate de ma- gnésium. L'éther a été éliminé et le résidu distillé. On a obtenu un rendement de 9,0 g en 1-méthyl-pipérazine, distillant entre 127 et 137 C.
Aux 9,0 g de 1-méthyl-pipérazine ainsi obtenus, dissous dans 25 em3 de chloroforme:, on ajoute goutte à goutte, en l'espace d'une heure et demie et en agitant, 6,12 de chlo rure de diéthylcarbamyle dans environ 25 cm' de chloroforme. Le récipient de réaction est refroidi dans un bain de glace. Après l'addi tion de la totalité du réactif, la solution est agitée pendant une demi-heure supplémen taire.
Cette solution contient le 1-méthyl-4- pipérazinef-N,N-diéthyl-carboxamide présen tant les propriétés suivantes: point d'ébulli tion 108,5 à 11111/3 mm, point de fusion 47-49'C, soluble dans le chloroforme, l'éther, Facétone, l'éthanol et partiellement soluble dans l'eau.
<I>Exemple 2:</I> On effectue un deuxième essai dans les mêmes conditions que dans l'exemple 1, sauf que l'on fait réagir 9,0 g de 1-méthyl-pipé- razine avec 12,2 g de chlorure de diéthyl- carbamyle. Le rendement est alors un peu in férieur à celui de l'exemple 1.
Exemple <I>3:</I> A 50 cm@ d'eau, on ajoute 18 g de dichlor- hydrate de 1-méthyl-pipérazine et 8,34 g de soude caustique. Après dissolution, le réci pient de réaction est refroidi à 100C et, tout en agitant, on ajoute simultanément 4,17 g de soude caustique dissous dans 15 cm@ d'eau et 14 g de chlorure de diéthyl-carbamyle. Après cette addition, la solution est soumise trois fois à l'extraction par l'éther, les extraits étant ensuite séchés et filtrés.
La solution éthérée contient le 1-méthyl-4-pipérazine-N,N- diéthyl-carboxamide.
Process for the preparation of 1-methyl-4-piperazine-N, N-diethyl-earboxamide. The present invention relates to a process for the preparation of 1-methyl 1-4-piperazine-N, N-diethylcarboxamide, which is a novel compound having the formula:
EMI0001.0007
According to the present invention, this compound is prepared by reacting 1-methyl-piperazine with diethyl-carb-amyl chloride.
The 1-methyl-4-piperazine-N, N-diethyl-carboxamide obtained by this process is a colorless or pale yellow oil, soluble in most organic solvents. Its acid salts are hygroscopic white solids soluble in water.
The reaction. is advantageously carried out at a temperature of between 0 and 40 C, preferably at room temperature, in a solvent such as chloroform, carbon tetrachloride, ethyl acetate, water, etc.
When using chloroform or a similar organic solvent for the practice of the invention, it is preferable to recover the product by first saturating the reaction mixture with hydrochloric acid at low temperature. . Any non-reactive methyl-piperazine fraction is precipitated under. hydrochloride form and can be removed by filtration.
The reaction mixture is concentrated by removing the solvent, and the 1-methyl-4-piperazine-N, N-diethyl-carboxamide s dichloride which separates out in solid form is treated to regenerate the base, optionally after recrystallization.
When the reaction is carried out in the presence of water as solvent (preferably with the addition of an alkali), the usual method of recovering the product consists in saturating the reaction mixture. with potassium carbonate, ammonium sulphate or the like. The product is then extracted. through ; a solvent such as ether or chloroform, dried and then distilled.
1-Methyl-4-piperazine-N, N-diethyl-earb-oxamide can be used for the treatment of filariasis and in veterinary medicine for the treatment of ascariasis in dogs. <I> Example 1: </I> 1-methy 1-piperazine was prepared beforehand by thoroughly kneading <B> 81.4g </B> of slaked lime with 43.5 g of dichlorhydrate. 1-methyl-piperazine, then distilling the mixture.
The distillate was dried over solid caustic potash, added with ether, filtered and dried over magnesium sulfate. The ether was removed and the residue distilled off. A yield of 9.0 g of 1-methyl-piperazine was obtained, distilling between 127 and 137 ° C.
To the 9.0 g of 1-methyl-piperazine thus obtained, dissolved in 25 em3 of chloroform :, 6.12 of diethylcarbamyl chloride are added dropwise over the course of one and a half hours and with stirring. in about 25 cm 3 of chloroform. The reaction vessel is cooled in an ice bath. After all the reagent has been added, the solution is stirred for an additional half hour.
This solution contains 1-methyl-4-piperazinef-N, N-diethyl-carboxamide with the following properties: boiling point 108.5 to 11111/3 mm, melting point 47-49 ° C, soluble in chloroform, ether, acetone, ethanol and partially soluble in water.
<I> Example 2: </I> A second test is carried out under the same conditions as in Example 1, except that 9.0 g of 1-methyl-piperazine is reacted with 12.2 g of diethylcarbamyl chloride. The yield is then a little lower than that of Example 1.
Example <I> 3: </I> To 50 cm @ of water, 18 g of 1-methyl-piperazine dichlorhydrate and 8.34 g of caustic soda are added. After dissolution, the reaction vessel is cooled to 100C and, while stirring, simultaneously added 4.17 g of caustic soda dissolved in 15 cm @ of water and 14 g of diethyl-carbamyl chloride. After this addition, the solution is subjected to extraction three times with ether, the extracts then being dried and filtered.
The ethereal solution contains 1-methyl-4-piperazine-N, N-diethyl-carboxamide.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US268051XA | 1946-04-12 | 1946-04-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH268051A true CH268051A (en) | 1950-04-30 |
Family
ID=21833877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH268051D CH268051A (en) | 1946-04-12 | 1947-04-10 | Process for preparing 1-methyl-4-piperazine-N, N-diethyl-carboxamide. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH268051A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE923967C (en) * | 1951-06-14 | 1955-02-24 | Bayer Ag | Process for the production of tetra-substituted ureas |
-
1947
- 1947-04-10 CH CH268051D patent/CH268051A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE923967C (en) * | 1951-06-14 | 1955-02-24 | Bayer Ag | Process for the production of tetra-substituted ureas |
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