CH332664A - Process for preparing N-benzhydryl-N'-benzylpiperazines - Google Patents
Process for preparing N-benzhydryl-N'-benzylpiperazinesInfo
- Publication number
- CH332664A CH332664A CH332664DA CH332664A CH 332664 A CH332664 A CH 332664A CH 332664D A CH332664D A CH 332664DA CH 332664 A CH332664 A CH 332664A
- Authority
- CH
- Switzerland
- Prior art keywords
- benzhydryl
- benzylpiperazines
- preparing
- ether
- mole
- Prior art date
Links
- KUAJKNGLESWEFE-UHFFFAOYSA-N 1-benzhydryl-4-benzylpiperazine Chemical class C=1C=CC=CC=1CN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 KUAJKNGLESWEFE-UHFFFAOYSA-N 0.000 title claims description 3
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 238000000034 method Methods 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- -1 phenylmagnesium halide Chemical class 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VTEOTZPEMDQENX-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]piperazine Chemical compound CC1=CC=CC(CN2CCNCC2)=C1 VTEOTZPEMDQENX-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940095564 anhydrous calcium sulfate Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- ULKGULQGPBMIJU-UHFFFAOYSA-N benzene;hydron;bromide Chemical compound Br.C1=CC=CC=C1 ULKGULQGPBMIJU-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/092—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings with aromatic radicals attached to the chain
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
<Desc/Clms Page number 1>
Procédé de préparation de N-üenzhydryl-N'-benzylpipérazines La présente invention a pour objet un procédé de préparation de N-benzhydryl-N'-benzyl- pipérazines, substances possédant des propriétés pharmaceutiques, par action d'un halogénure de phénylmagnésium sur un éther-oxyde aminé de formule
EMI1.6
où Y représente un groupe alcoyle contenant de 1 à 4 atomes de carbone.
L'éther-oxyde s'obtient, par exemple, par la méthode de Stewart et Hausser / J. Ain. chem. Soc. 77, (1955), 1098-1103 /. La réaction s'effectue habituellement par chauffage au point d'ébullition de l'éther. Le rendement obtenu est de l'ordre de 70 - 75 Exemple 1 On agite pendant 48 heures, à la température ambiante, un mélange de 0,22 mole de 1-p-(t-butyl)-benzylpipérazine (Pt Ebull. 128 - 130o C / 0,1 mm Hg) préparée selon la technique décrite par Morren / Bull. Soc. chim. Belg. 60, (1951), 282-95 /, 0,20 mole de p-chlorbenzaldéhyde, 0,01 mole de chlorure mercurique, 1 mole de butanol-1, 0,75 mole de sulfate de calcium anhydre.
On ajoute ensuite une solution méthylique fraîche de méthylate de sodium jusqu'à réaction fortement alcaline. On filtre. On distille le solvant. On dissout le résidu dans le toluène ; puis on distille sous vide poussé pour chasser complètement le butanol.
L'éther-oxyde aminé ainsi obtenu est dissout ensuite dans l'éther-anhydre et on ajoute cette solution refroidie à 50 C à une solution éthérée de bromure de phénylmagnésium (préparée à partir de 0,27 atome de magnésium et de 0,25 mole de bromure de benzène). Après addition, on chauffe progressivement et l'on maintient le mélange réactionnel à l'ébullition pendant. deux heures.
On refroidit, on verse la suspension sur un mélange de glace et de chlorure d'ammonium pour décomposer le magnésium qui n'a pas réagi. On décante et on sépare la solution éthérée que l'on sèche, que l'on évapore et dont on distille le résidu sous vide. La 1-p-cNor- benzhydryl-4-p-(t-butyl)-benzylpipérazine (Pt
<Desc/Clms Page number 2>
Ebull. = 230 - 2400 C/0,001 mm Hg) est ob-' tenue avec un rendement de 75 %. Le dichlor- hydrate (Pt Fusion = 265 - 2660 C)
se prépare en faisant passer de l'acide chlorhydrique dans la solution éthanolique de la base.
Exemple 2 On opère comme dans l'exemple 1, mais on remplace la 1-p-(t-butyl)-benzylpipérazine par la 1-m-méthylbenzyl-pipérazine (Pt Ebull. 118 - 121 C/2 mm Hg) préparée selon la technique de Morren (loc. cit.). On obtient avec un rendement de 71 % la 1-p-chlorbenz- hydryl-4-m-méthylbenzylpipérazine (Pt Ebull. 2300 C/2 mm Hg).
Le dichlorhydrate correspondant fond à 215o C.
<Desc / Clms Page number 1>
Process for the preparation of N-üenzhydryl-N'-benzylpiperazines The present invention relates to a process for the preparation of N-benzhydryl-N'-benzyl-piperazines, substances having pharmaceutical properties, by the action of a phenylmagnesium halide on a ether-amino oxide of the formula
EMI1.6
where Y represents an alkyl group containing 1 to 4 carbon atoms.
The ether oxide is obtained, for example, by the method of Stewart and Hausser / J. Ain. chem. Soc. 77, (1955), 1098-1103 /. The reaction is usually carried out by heating to the boiling point of ether. The yield obtained is of the order of 70-75. Example 1 A mixture of 0.22 moles of 1-p- (t-butyl) -benzylpiperazine (Pt Ebull. 128 -) is stirred for 48 hours at room temperature. 130o C / 0.1 mm Hg) prepared according to the technique described by Morren / Bull. Soc. chem. Belg. 60, (1951), 282-95 /, 0.20 mole of p-chlorbenzaldehyde, 0.01 mole of mercuric chloride, 1 mole of 1-butanol, 0.75 mole of anhydrous calcium sulfate.
A fresh methyl solution of sodium methoxide is then added until the reaction is strongly alkaline. We filter. The solvent is distilled off. The residue is dissolved in toluene; then distilled under high vacuum to completely remove the butanol.
The ether-amino oxide thus obtained is then dissolved in ether-anhydrous and this solution cooled to 50 C is added to an ethereal solution of phenylmagnesium bromide (prepared from 0.27 atom of magnesium and 0.25 mole of benzene bromide). After addition, the mixture is gradually heated and the reaction mixture is kept at the boil for a period of time. two o'clock.
Cool, pour the suspension onto a mixture of ice and ammonium chloride to decompose unreacted magnesium. The ethereal solution is decanted and separated, dried, evaporated and the residue distilled in vacuo. 1-p-cNor- benzhydryl-4-p- (t-butyl) -benzylpiperazine (Pt
<Desc / Clms Page number 2>
Ebull. = 230 - 2400 C / 0.001 mm Hg) is obtained with a yield of 75%. Dichlorhydrate (Pt Fusion = 265 - 2660 C)
is prepared by passing hydrochloric acid through the ethanolic solution of the base.
Example 2 The procedure is as in Example 1, but the 1-p- (t-butyl) -benzylpiperazine is replaced by 1-m-methylbenzyl-piperazine (Pt Ebull. 118 - 121 C / 2 mm Hg) prepared according to Morren's technique (loc. cit.). 1-p-chlorbenzhydryl-4-m-methylbenzylpiperazine (Pt Ebull. 2300 C / 2 mm Hg) is obtained with a yield of 71%.
The corresponding dihydrochloride melts at 215o C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH332664T | 1955-09-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH332664A true CH332664A (en) | 1958-09-15 |
Family
ID=4502533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH332664D CH332664A (en) | 1955-09-09 | 1955-09-09 | Process for preparing N-benzhydryl-N'-benzylpiperazines |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH332664A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135756A (en) * | 1964-06-02 | Table ii | ||
| US3168522A (en) * | 1963-10-10 | 1965-02-02 | Ciba Geigy Corp | N-aryl-n'-aralkyl-diaza cycloalkanes |
-
1955
- 1955-09-09 CH CH332664D patent/CH332664A/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135756A (en) * | 1964-06-02 | Table ii | ||
| US3168522A (en) * | 1963-10-10 | 1965-02-02 | Ciba Geigy Corp | N-aryl-n'-aralkyl-diaza cycloalkanes |
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