SYNTHETIC POSSIBILITY OF USING IMIDAZOLIUM IONIC LIQUIDS, HYDRAZIDES AND ESTERS OF HALOGENATED CARBOXYLIC ACIDS IN THE ARBUZOV REACTION TO OBTAIN FOSENAZIDE AND ITS
Rubrics: 1. CHEMISTRY
Authors:
1.
KNITU; KNITU
2.
Kazan National Research Technological University
3.
Kazan National Research Technological University
4.
KNITU; KNITU
Type:
Article
Pages:
from 45
to 49
Status:
In work
Language:
Russian
Keywords:
IONIC LIQUID (IL), IMIDAZOLE (IM), 1-METHYLIMIDAZOLE (MIM), ARBUZOV REACTION, PHOSENAZIDE, MONOCHLOROACETIC ACID HYDRAZIDE (MCAAH), MONOBROMOACETIC ACID HYDRAZIDE (MBAAH), ETHYL ESTER OF MONOBROMOACETIC ACID (EEMBAA)
Abstract (English):
Ionic liquids based on imidazoles find various applications in organic synthesis, catalysis, and biochemical processes. In this paper, the possibility of using IL for the synthesis of phosphorylacetic acid hydrazides, which are obtained by the Arbuzov reaction, which in the classical version is the interaction of trialkyl phosphites with alkyl halides, is considered. The ability of ionic liquids to increase the nucleophilicity of trivalent phosphorus esters makes it possible to activate the reaction of Arbuzov with alkyl halides. Phosphorylacetic acid hydrazide - Phosenazide, whose neurotropic activity is not associated with cholinesterase inhibition, was chosen as the object of synthesis. The drug Phosenazide is allowed as a tranquilizer and anti-alcohol agent. The general synthesis algorithm consists of the following stages: the initial diphenyl chlorophosphine interacts with ethyl alcohol in the presence of imidazole (im) or 1-methylimidazole (mim) to form diphenyl(O-ethyl)phosphinite. Hydrogen chloride, which is released during the reaction, interacts with heterocycles to form imidazolium chloride ([Him]+Cl-) or 1-methylimidazolium chloride ([Hmim]+Cl-). Next, alkylating reagents were added to the reaction mixture. The following alkyl halides were studied: monochloroacetic acid hydrazide (MCAAH), monobromacetic acid hydrazide (MBAAH), ethyl ether of monobromacetic acid (EEMBAA). The hydrazides of halocarboxylic acids as haloalkyl in the Arbuzov reaction were studied for the first time. The whole process proceeds without the release of intermediate reaction products. The following variants were used as the medium of the reaction mixture: solvent-free, dimethyl sulfoxide, methylene chloride. It was found that: when conducting a reaction with DMSO or MBAAH without a solvent, regardless of the IL ([Him]+Cl-) or ([Hmim]+Cl-), Phosphenazide hydrochloride is formed as the main reaction product; when conducting a reaction in DMSO with MBAAH as an alkylating reagent and [Hmim]+Cl- as IL, Phosenazide is formed as the main product of the reaction; during the reaction in methylene chloride with MBAAH as an alkylating reagent and [Hmim]+Cl- as IL, Phosenazide is formed as the main reaction product. The synthetic possibility of using imidazolium ions, hydrazides and halocarboxylic acid esters in the Arbuzov reaction to obtain Phosenazide and its hydrochloride is shown.
Ionic liquids based on imidazoles find various applications in organic synthesis, catalysis, and biochemical processes. In this paper, the possibility of using IL for the synthesis of phosphorylacetic acid hydrazides, which are obtained by the Arbuzov reaction, which in the classical version is the interaction of trialkyl phosphites with alkyl halides, is considered. The ability of ionic liquids to increase the nucleophilicity of trivalent phosphorus esters makes it possible to activate the reaction of Arbuzov with alkyl halides. Phosphorylacetic acid hydrazide - Phosenazide, whose neurotropic activity is not associated with cholinesterase inhibition, was chosen as the object of synthesis. The drug Phosenazide is allowed as a tranquilizer and anti-alcohol agent. The general synthesis algorithm consists of the following stages: the initial diphenyl chlorophosphine interacts with ethyl alcohol in the presence of imidazole (im) or 1-methylimidazole (mim) to form diphenyl(O-ethyl)phosphinite. Hydrogen chloride, which is released during the reaction, interacts with heterocycles to form imidazolium chloride ([Him]+Cl-) or 1-methylimidazolium chloride ([Hmim]+Cl-). Next, alkylating reagents were added to the reaction mixture. The following alkyl halides were studied: monochloroacetic acid hydrazide (MCAAH), monobromacetic acid hydrazide (MBAAH), ethyl ether of monobromacetic acid (EEMBAA). The hydrazides of halocarboxylic acids as haloalkyl in the Arbuzov reaction were studied for the first time. The whole process proceeds without the release of intermediate reaction products. The following variants were used as the medium of the reaction mixture: solvent-free, dimethyl sulfoxide, methylene chloride. It was found that: when conducting a reaction with DMSO or MBAAH without a solvent, regardless of the IL ([Him]+Cl-) or ([Hmim]+Cl-), Phosphenazide hydrochloride is formed as the main reaction product; when conducting a reaction in DMSO with MBAAH as an alkylating reagent and [Hmim]+Cl- as IL, Phosenazide is formed as the main product of the reaction; during the reaction in methylene chloride with MBAAH as an alkylating reagent and [Hmim]+Cl- as IL, Phosenazide is formed as the main reaction product. The synthetic possibility of using imidazolium ions, hydrazides and halocarboxylic acid esters in the Arbuzov reaction to obtain Phosenazide and its hydrochloride is shown.
Keywords:
IONIC LIQUID (IL), IMIDAZOLE (IM), 1-METHYLIMIDAZOLE (MIM), ARBUZOV REACTION, PHOSENAZIDE, MONOCHLOROACETIC ACID HYDRAZIDE (MCAAH), MONOBROMOACETIC ACID HYDRAZIDE (MBAAH), ETHYL ESTER OF MONOBROMOACETIC ACID (EEMBAA)
IONIC LIQUID (IL), IMIDAZOLE (IM), 1-METHYLIMIDAZOLE (MIM), ARBUZOV REACTION, PHOSENAZIDE, MONOCHLOROACETIC ACID HYDRAZIDE (MCAAH), MONOBROMOACETIC ACID HYDRAZIDE (MBAAH), ETHYL ESTER OF MONOBROMOACETIC ACID (EEMBAA)
