- Catalytic, Kinetic, and Mechanistic Insights into the Fixation of CO2 with Epoxides Catalyzed by Phenol-Functionalized Phosphonium Salts
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A series of hydroxy-functionalized phosphonium salts were studied as bifunctional catalysts for the conversion of CO2 with epoxides under mild and solvent-free conditions. The reaction in the presence of a phenol-based phosphonium iodide proceeded via a first order rection kinetic with respect to the substrate. Notably, in contrast to the aliphatic analogue, the phenol-based catalyst showed no product inhibition. The temperature dependence of the reaction rate was investigated, and the activation energy for the model reaction was determined from an Arrhenius-plot (Ea=39.6 kJ mol?1). The substrate scope was also evaluated. Under the optimized reaction conditions, 20 terminal epoxides were converted at room temperature to the corresponding cyclic carbonates, which were isolated in yields up to 99 %. The reaction is easily scalable and was performed on a scale up to 50 g substrate. Moreover, this method was applied in the synthesis of the antitussive agent dropropizine starting from epichlorohydrin and phenylpiperazine. Furthermore, DFT calculations were performed to rationalize the mechanism and the high efficiency of the phenol-based phosphonium iodide catalyst. The calculation confirmed the activation of the epoxide via hydrogen bonding for the iodide salt, which facilitates the ring-opening step. Notably, the effective Gibbs energy barrier regarding this step is 97 kJ mol?1 for the bromide and 72 kJ mol?1 for the iodide salt, which explains the difference in activity.
- Hu, Yuya,Wei, Zhihong,Frey, Anna,Kubis, Christoph,Ren, Chang-Yue,Spannenberg, Anke,Jiao, Haijun,Werner, Thomas
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p. 363 - 372
(2020/11/30)
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- Production process of levodropropizine
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The invention belongs to the technical field of chemical synthesis and in particular relates to a production process of levodropropizine. The production process of levodropropizine comprises the following steps: with water as a medium, reacting N-phenylpiperazine and R-(-)-3-chloro-1,2-propanediol in the presence of a catalyst sodium hydroxide to obtain a crude product of levodropropizine, thereby obtaining a refined product of levodropropizine after refining the crude product. The production process has the advantages of low production cost, high yield, high product quality and environment friendliness.
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Paragraph 0022
(2016/12/07)
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- 1,3-dioxolanes with antitussive activity
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(S)-3-(4-Phenyl-1-piperazinyl)-1,2-propanediol cyclic acetals useful as antitussive agents and as intermediates for the preparation of levodropropizine and the salts thereof, as well as a process for the preparation of said acetals, are disclosed.
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- Chemo-enzymatic synthesis of levodropropizine
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Levodropropizine, an antitussive drug, was prepared in high enantiomeric excess in three steps, starting from dichloroacetone (2). Monosubstitution of 2 with sodium benzoate and subsequent baker's yeast reduction stereoselectively afforded the corresponding chlorohydrin in 73% ee, which was converted to levodropropizine and enantiomerically enriched up to 95% ee by fractional crystallisation.
- Caselli, Emilia,Tosi, Giovanni,Forni, Arrigo,Bucciarelli, Maria,Prati, Fabio
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p. 1029 - 1032
(2007/10/03)
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- 2,2-disubstituted 1,3-dioxolanes as antitussive agents
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(±) 3-(4-Phenyl-1-piperazinyl)-1,2-propanediol cyclic acetals, a process for the optical resolution thereof and their use as intermediates for the preparation of (?) 3-(4-phenyl-1-piperazinyl)-1,2-propanediol (levodropropizine) and salts thereof.
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- Process for the optical resolution of dropopizine
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A process for the optical resolution of racemic dropropizine, carried out using L(+)tartaric acid as the optical resolution agent in aqueous medium, is described.
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- Enzymatic resolution of 1,2-diols: Preparation of optically pure dropropizine
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Kinetic resolution of (R,S)-3-(4-phenyl-1-piperazinyl)-1,2-propranediol diacetate (2) by alcoholysis with n-propanol was carried out under lipase Amano PS catalysis in various organic solvents. Pure enantiomers of the corresponding diol (1) are useful as antitussive and central sedative therapeutic agents.
- Bianchi,Bosetti,Cesti,Golini
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p. 3231 - 3234
(2007/10/02)
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- A process for the optical resolution of dropropizine
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A process for the optical resolution of racemic dropropizine, carried out using L(+)tartaric acid as the optical resolution agent in aqueous medium, is described.
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- Preparation of enantiomers of dropropizine
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The invention relates to a process for the preparation of enantiomers of dropropizine by coupling 1-phenylpiperazine with a gly-cidol containing an excess of one of the enantiomers and purifying the dropropizine by recrystallization.
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- Synthesis and pharmacological screening of new phenylpiperazinepropane derivatives and their enantiomers
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Enantiomers of phenylpiperazine-1,2-diol derivatives were synthesized with the purpose to obtain a better antitussive activity/sedative effect ratio. (S)-isomers showed better pharmacological profiles than (R)-isomers and corresponding racemates. Among the (S)-isomers, the unsubstituted compound, levodropropizine (S(-)-3-(4-phenylpiperazin-1-yl)propane-1,2-diol, DF 526), has the most favourable antitussive activity/sedative effect ratio and was selected for pharmacotoxicological evaluation.
- Giani,Marinone,Melillo,Borsa,Tonon
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p. 1139 - 1141
(2007/10/02)
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- Levo and dextro dropropizine having antitussive activity
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The optical isomers of 3-(4-phenyl-1-piperazinyl)-1,2-propanediol, a process for the stereo-selective preparation and pharmaceutical composition containing the same as active principles are described.
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