• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:

    公开号:SU931104A3
    申请号:SU792719854
    申请日:1979-02-08
    公开日:1982-05-23
    发明作者:Кибурц Эмилио；Ашванден Вернер
    申请人:Ф.Хоффманн-Ля Рош Унд Ко Аг. (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to new derivatives of 2-pyrrolidinone, which can be used in medicine: in the treatment or prevention of cerebral insufficiency. B
    Known acylation reaction of nitrogen-containing compounds, in particular, using acid halides And
    The aim of the invention is to develop on the basis of the well-known method of the method for producing new compounds * with high biological activity.
    This goal is achieved by 1B by the method of producing 1 - (p-methoxybenzoyl) -2-pyrrolidinone, namely, that 2-pyrrolidinone or its salt of a 1-alkali metal or 1-trialkylsilyl derivative is acylated with a functional derivative of I-methoxybenzoic acid.
    As the functional product of p-methoxybenzoic acid, η-methoxybenzoyl chloride or p-methoxybenzoic acid pentachlorophenyl ester is used.
    When acylating 2-pyrrolidinone with P-methoxybenzoyl chloride, it is advisable to work in the presence of an inert organic solvent and base. Moreover, ethers such as diethyl ether, tetrahydrofuran, dioxane are primarily suitable as a solvent; aromatic hydrocarbons such as toluene; as bases, tertiary amines such as triethylamine. Acylation can also be carried out in pyridine, which is used simultaneously as a solvent and a base. However, the presence of a solvent and a base is not necessary. It is possible to heat the components together for about 1 hour to 80-90 ° C or for several hours to heat under reflux in the appropriate
    931 solvent ', for example, ether, aromatic hydrocarbon. Moreover,. 2-pyrrolidinone can first be treated with a base capable of abstracting the hydrogen atom at the nitrogen atom in position 1, and then allowed to interact with P-methoxybenzoyl chloride. In this case, for example, an alkali metal hydride such as sodium can be used as a base, and an aromatic hydrocarbon such as benzene, dimethylformamide as a solvent. It is also possible to work with 2-pyrrolidinone as a reactive derivative in which, at the nitrogen atom in position 1, there is an easily leaving group, for example an organometallic, in particular trialkylsilyl. Preferred derivatives of this kind include 1-trimethylsilyl-2-pyrrolidinone.
    I
    Example 1. To 40.0 g of p-methoxybenzoyl chloride, 25.0 g of 2-pyrrolidinone and 110 ml of absolute diethyl ether with stirring at 0-10 ° C., 52.5 ml of triethylamine are added. Then, stirring was continued for another 30 minutes at room temperature and 3 hours under reflux, cooled, and cold water was added at 2 ° C. Insoluble components are sucked off and washed with water and diethyl ether. The solid product thus obtained, after drying of the phosphorus pentoxide, was recrystallized from alcohol to obtain 1- (P ~ methoxybenzoyl) -2-pyrrolidinone with a melting point of 121-122 ° C.
    Example 2. To a solution of 37.0 g of P-methoxybenzoyl chloride in 50 ml of dimethylformamide at -10 ° C was added 20.2 g of sodium salt of 2-pyrrolidinone obtained in 270 ml of dimethylformamide suspended in 270 ml in 4 portions. Then it is stirred for 1 hour at room temperature, and then for 4 hours at 40 ° C. The solvent was evaporated, diethyl ether and a cold sodium bicarbonate solution were added to the residue. The insoluble crystalline part is filtered off, washed with water and diethyl ether, and dried under vacuum of phosphorus pentoxide. Get 1- (C * methoct sibenzoyl) -2-pyrrolidinones so pl. 120121 ° C.
    C 4
    Example 3-20 hP-methoxy. benzoyl chloride and 20 g of 2-pyrrolidinone for 16 hours are refluxed in 20 ml of diethyl ether for 16 hours, after which diethyl ether, ice and 2N are added to the reaction mixture. aqueous ammonia. The insoluble portion is filtered off and washed with diethyl ether and water until no ions are present. The cake is dried, obtaining 1 - (p-methoxybenzoyl) -2-pyrrolidinone with so pl. 119.5 120.5 ° C.
    Example 4. Proceed analogously to example 3, however, the components are heated not in diethyl ether, but in 20 ml of toluene. Mp obtained 1 - (P-methoxybenzoyl) -2-pyrrolidinone 117118 ° C.
    Example 5. The south of 2-pyrrolidi) none and 10 gp-methoxybenzoyl chloride without a solvent is heated to 80 ~ 90 ° С (internal temperature) for 1 h, after which it is allowed to cool, proceeding analogously to example 3. By recrystallization from alcohol, 1- (p -methoxybenzoyl) -2-pyrrolidinone with mp 120-121 ° C.
    Example 6. 24.4 g of tl-methoxybenzoyl chloride and 22.5 g of 1-trimethylsilyl-2-pyrrolidinone were mixed, after which the mixture was stirred for 10 minutes at room temperature. After that, in an oil bath at 80 ° C, the obtained trimethylchlorosilane is distilled off under reduced pressure. The residue was mixed with 100 ml of diethyl ether, filtered off and recrystallized from 40 ethyl alcohol to give 1- (P _ methoxybenzoyl) -2-pyrrolidinone, so pl. 120-121 ° C.
    Example 7. To a solution of 20.0 g of pentachlorophenyl ether of I-methoxy, · 5 benzoic acid in 100 ml of dimethylformamide at -10 ° C was added 7.0 g of sodium salt of 2-pyrrolidinone obtained using 120 ml of dimethylformamide. 50 Then it is stirred for 1 hour at room temperature and for 8 hours at 55 ° C. The solvent was evaporated, a cold aqueous solution of acetic acid was added to the residue, after which it was extracted with ethyl acetate. The organic phase is washed with cold sodium bicarbonate and water, dried ! sodium sulfate, filtered and evaporated5. The residue was dissolved in ethanol and stirred in an ice bath; the precipitated crystals are filtered off, obtaining 1- (p-methoxybenzoyl) -2-pyrrolidinone with a mp of 119120 ° C.
    权利要求:
    Claims (3)
    [1]
    39 solvent, for example, ether, aromatic hydrocarbon. In addition, 2-pyrrolidinone can first be treated with a base capable of abstracting a hydrogen atom at the nitrogen atom at the t position, and then allowed to react with P-methoxy-benzoyl chloride. In this case, as a base, an alkali metal hydride such as sodium can be used, for example, and an aromatic hydrocarbon such as benzene, dimethylformamide can be used as a solvent. It is also possible to work with 2-pyrrolidinone as a reactive derivative in which at the nitrogen atom in position 1 there is an easily eliminating group, for example, an organometallic, in particular, trialkylsilyl. The preferred derivatives of this type include 1-trimethylsilyl-2-pyrrolidinone. Example 1. Or p-methoxybenzoyl chloride, 25.0 g of 2-pyrrolidione and 110 ml of absolute diethyl ether with stirring, 52.5 ml of triethylamine are added. Then they continue to stir for another 30 minutes at room temperature and 3 hours with a reverse fridge, cool, and cold water is added at 2 ° C. The insoluble components are filtered off with suction and washed with water and diethyl ether. The solid product thus obtained is recrystallized from alcohol with phosphorus pentoxide to give 1- (C-methoxybenzoyl) -2-pyrrlidinone, m.p. 121-122 C. Example
    [2]
    2. To a solution of 37.0 g of P-methoxybenzoyl chloride in 50 ml of dimethylformamide was added 20.2 g of sodium salt of sodium hydride 2-pyrrolidinone obtained in sodium hydride and suspended in 270 ml of dimethyl form and in 4 portions. Then, 1 h is stirred at room temperature, and then C h at. The solvent is evaporated, diethyl ether and cold sodium bicarbonate solution are added to the residue. The insoluble crystalline portion is filtered off, washed with water and diethyl ether and dried under vacuum with phosphorus oxide. Get 1 - (P-labels sibenzoyl) -2-pyrrolidinones so pl. 120 Example 3. 20 gp-methoxy-. benzoyl chloride and 20 g of 2-pyrrolidinone are boiled under reflux in 20 ml of diethyl ether for 16 hours for 16 hours, after which diethyl ether, ice and 2N are added to the reaction mixture. ammonia water. The insoluble part is filtered and washed with diethyl ether and water until no ions are present. The cake is dried to obtain 1- (p-methoxybenzoyl) -2-pyrrolidinone with m.p. 119.5120.5 ° C. Example t. Proceed analogously to example 3, however, the components are heated not in diethyl ether, but in 20 ml of toluene. M.p. obtained 1 - (P-methoxybenzoyl) -2-pyrrolidinone I7-118 ° C. Example 5. South of 2-pyrrolidi) non and 10 g of p-methoxybenzoyl chloride without solvent is heated to 80-90 ° C (internal temperature) for 1 h, ° C cooled down, proceeding analogously to the example
    [3]
    3. By recrystallization from alcohol, 1- {p-methoxybenzoyl) -2-pyrrolidinone is obtained with m.p. 120-121 ° C. Example 6. 2, Cg of h-methoxybenzoyl chloride and 22.5 g of 1-trimethylsilyl-2-pyrrolidinone are mixed, after which the mixture is stirred at room temperature for 10 minutes. Thereafter, in the oil bath, the resulting trimethylchlorosilane is distilled off under reduced pressure. The residue is mixed with 100 ml of diethyl ether, filtered and recrystallized from ethyl alcohol to give 1- (p-methoxybenzoyl) -2-pyrrolidinone, m.p. 120-121C. Example 7- To a solution of 20.0 g of P-methoxybenzoic acid pentachlorophenyl ester) in 100 ml of dimethylformamide at -10 ° C was added 7.0 g of 2-pyrrolidinone sodium salt prepared using sodium hydride suspended in 120 ml of dimethylformamide. Then it is stirred at room temperature for 1 hour and at room temperature for 8 hours. The solvent is evaporated, a cold aqueous solution of acetic acid is added to the residue, and then extracted with ethyl acetate. The organic phase is washed with cold sodium bicarbonate solution and water, dried over sodium sulfate, filtered and evaporated. The residue is dissolved in ethyl alcohol and stirred in an ice bath; the precipitated crystals are filtered off to give 1- (p-methox benzoyl) -2-pyrrolidinone with m.p.119. Claim 1. A method for producing 1- (p-methoxy benzoyl) -2-pyrrolidinone, characterized in that 2-pyrrolidinone or its 1-alkali metal salt or 1-trialkylsilyl derivative is acylated by a functional L-methoxybenzoic acid derivative. 2, the method according to claim 1, and with the fact that α-methoxybenzoyl chloride or pentachlorophenyl ether h-methoxybenzo (acidic acid) is used as the functional derivative P-me 6 of toxibenzoic acid. The priority is as follows: 10.02.78 - functional the derivative of p-methoxybenzoic acid is reacted with 2-pyrrolidinone or with its 1-alkali metal salt; 22.I.78 is a functional derivative of p-methoxybenzoic acid and is reacted with the 1-trialkylsilyl derivative of 2-pyrrolidinone. Maintenance for the examination 1. Weigand-Hilgetag. Methods of experiment in organic chemistry. M., Chemistry, 1968, p. IFBL.
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    法律状态:
    优先权:
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    CH140378|1978-02-10|
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