Vicarious Nucleophilic Chloromethylation of Nitroaromatics

Abstract

Nitroaromatics substituted with electron-acceptor or electron-donor groups undergo vicarious nucleophilic substitution with the lithium salt of dichloromethane to provide chloromethyl-substituted nitroaromatics in good to high yields. The methodology represents a new strategy for the synthesis of benzyl chlorides.

Alkylation of Nitropyridines via Vicarious Nucleophilic Substitution

“…Only recently a few attempts to extend the methodology have been reported in the literature . Mąkosza and Loska and then Beier reported introduction of alkyl groups that can partially stabilize the negative charge (i.e., act as an EWG), such as benzyl, chlorobenzyl, and chloromethyl. In turn, Kim and co-workers demonstrated alkylation of quinoline N -oxides and pyrazinones with sulfonium and sulfoxonium salts at elevated temperatures .…”

Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium

“…In fact, other (halomethyl)lithium reagents have already been successfully generated and utilized in continuous flow mode, namely the more stable (dibromomethyl)­lithium, (chloromethyl)­lithium, and (dichloromethyl)­lithium . Generation of (dichloromethyl)­lithium and (fluoroiodomethyl)­lithium has been recently reported in batch mode. Notably, LiCHCl 2 showed relatively high stability in solution at low temperatures. , …”

“…Generation of (dichloromethyl)­lithium and (fluoroiodomethyl)­lithium has been recently reported in batch mode. Notably, LiCHCl 2 showed relatively high stability in solution at low temperatures. , …”

Introduction of Carbon Substituents into Nitroarenes via Nucleophilic Substitution of Hydrogen: New Developments

“…In 2019, the direct nucleophilic chloromethylation of nitroarenes was achieved via VNS reaction of excess lithiated methylene chloride with nitroarenes at low temperature (Scheme 10). 34 Products of the substitution of hydrogen with a chloromethyl group were obtained with a variety of nitrobenzenes, 2-nitrothiophene, and 2-nitrofuran.…”