ABSTRACT2-[[(2-pyridinyl) methyl] sulfinyl]-1H-benzimidazoles are the prominent motif's that belong to the class of prazoles. These are used in the treatment of gastroesophageal reflux disease (GERD) ulcers and other gastric acid related diseases. The present article describes the modified synthesis of 2-chloromethyl-4-methanesulfonyl-3-methyl pyridine (an intermediate utilized in the synthesis of Dexlansoprazole). The advantages of this modification involves (i) N-oxidation of 2,3-lutidine with catalytic quantity of RuCl 3 in presence of oxygen (ii) One pot synthesis of 2,3-dimethyl-4-(methylthio) pyridine-N-oxide using 30% NaSH, methyl iodide and tetra butyl ammonium hydroxide (iii) Oxidation of methythio pyridine-N-oxide with 30% H 2 O 2 followed by N-deoxygenation with RuCl 3 .H 2 O to produce 2,3-dimethyl-4-(methylsulfonyl)pyridine (iv) Chlorination of the penultimate step using trichloroisocyanuric acid to obtain the desired 2-chloromethyl-4-methanesulfonyl-3-methyl pyridine. Furthermore, green metrics assessment was calculated for the above modified scheme based on the parameters viz., atom economy (AE), reaction mass efficiency (RME) and E-factor. It was observed that, in case of step 4 (oxidation of thiomethyl pyridine-N-oxide), the E-factor value is very less 3.2 which is indicative of less waste generation, when compared to the various steps that are involved in the synthesis.
A modified synthesis of methyl 3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyrazole-4-carboxylate (halosulphuron) is described. The merits of the synthesis are (i) one pot chlorination of methyl 1-methyl-1H-pyrazole-4-carboxylate (1) in presence of sulphuryl chloride resulting in methyl 3,5-dichloro-1-methyl-1H-pyrazole-4-carboxylate (2) (ii) conversion of 3-chloro-5-mercapto-1-methyl-1H-pyrazole-4-carboxylate (3) to 3-chloro-1-methyl-5-sulfamoyl pyrazole-4-carboxylate (4) under mild reaction conditions utilizing tetrabutyl ammonium chloride, N-chlorosuccinimide and ammonium carbonate (iii) condensation of sulphonamide (4) with carbamate (6) by microwave irradiation. Efforts were made to calculate, atom economy, reaction mass efficiency and E-factor for all the reaction steps involved in the synthesis of halosulfuron. The E-factor values in step 2 and step 4 reaction is lower, indicating that these reactions are greener (generation of less waste) when compared to the remaining steps in the synthesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.