17692-31-8

Basic information

• Product Name: Dropropizine
• Synonyms: 3-(4-phenyl-1-piperazinyl)-2-propanediol;catabex;dipropizine;ditustat;dopropizin;katril;larylin;ribex
• CAS NO: 17692-31-8
• Molecular Formula: C₁₃H₂₀N₂O₂
• Molecular Weight: 236.31
• EINECS: 241-683-7
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 17692-31-8.mol

Chemical Properties

• Melting Point: 105° (Morren); mp 108° (Bourdais)
• Boiling Point: 412.7 °C at 760 mmHg
• Flash Point: 220.9 °C
• Appearance: white or almost white powder
• Density: 1.168 g/cm³
• Vapor Pressure: 1.5E-07mmHg at 25°C
• Refractive Index: 1.576
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 14.21±0.20(Predicted)
• CAS DataBase Reference: Dropropizine(CAS DataBase Reference)
• NIST Chemistry Reference: Dropropizine(17692-31-8)
• EPA Substance Registry System: Dropropizine(17692-31-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: TZ1074800
• Hazardous Substances Data: 17692-31-8(Hazardous Substances Data)

Usage

Originator

Ribex,Formenti

Uses

Different sources of media describe the Uses of 17692-31-8 differently. You can refer to the following data:
1. antitussive
2. Dropropizine is a cough suppressant and central sedative therapeutic agent.

Manufacturing Process

34 g 1,2-epoxy-3-hydroxypropane (glycide) in 50 ml of water were added to 64.8 g 1-phenylpiperazine in 80 ml of ethanol at the temperature not higher 50°C. The mixture was stood at night, then it was evaporated to dryness in vacuum and the stark product was recrystallized from 100 ml of acetone to give 60 g 1-phenyl-4-(2,3-dihydroxypropyl)piperazine (dropropizine) MP 105°C; BP 205°C/1 mm Hg.

Therapeutic Function

Antitussive

InChI:InChI=1/C13H20N2O2/c16-11-13(17)10-14-6-8-15(9-7-14)12-4-2-1-3-5-12/h1-5,13,16-17H,6-11H2

Upstream product

• 72566-27-9 1-(1-phenyl-4-piperazino)-2,3-epoxypropane 
• 92-54-6 4-phenyl-1-piperazine 
• 142730-57-2 (R,S)-3-(4-phenyl-1-piperazinyl)-1,2-propanediol diacetate 

Downstream Products

• 90331-38-7 Dropropizin-4-methyliodid 
• 142794-17-0 Acetic acid (S)-1-acetoxymethyl-2-(4-phenyl-piperazin-1-yl)-ethyl ester 
• 152237-41-7 C₁₃H₂₀N₂O₄ 
• 142730-59-4 Acetic acid 2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl ester 

Relevant articles and documents

Catalytic, Kinetic, and Mechanistic Insights into the Fixation of CO2 with Epoxides Catalyzed by Phenol-Functionalized Phosphonium Salts

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.

1,3-dioxolanes with antitussive activity

(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.

2,2-disubstituted 1,3-dioxolanes as antitussive agents

(±) 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.

Process for the optical resolution of dropopizine

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.

Enzymatic resolution of 1,2-diols: Preparation of optically pure dropropizine

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.

A process for the optical resolution of dropropizine

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.