Difluoromethylation Agents

Difluoromethylation Agents

Introduction

The application and development of difluoromethylation agents is a research hotspot in the field of drug synthesis. With this reagent, a difluoromethyl group can be introduced into organic compounds. Difluoromethyl is an important structural motif, which is commonly found in medicine, pesticides and functional materials. As lipophilic hydrogen bond donors, difluoromethyl groups can improve the lipid solubility, membrane permeability, bioavailability and other pharmacokinetic properties of drug molecules, and play an important role in drug design and development. In recent years, various difluoromethylation agents have been developed, which have important applications and significance in the field of drug synthesis.

Classification

Based on the electrical effect of the compounds, difluoromethylation agents are divided into nucleophilic difluoromethylation agents, electrophilic difluoromethylation agents and free radical difluoromethylation agents.

• Nucleophilic difluoromethylation agents. Nucleophilic difluoromethylation agents mainly include tetramethylsilane (TMS), PhXCF₂H, BrCF₂PO(OEt)₂ and benzenesulfonyl difluoroacetic acid metal salts. Nucleophilic difluoromethylation agents are widely used in fluorination reactions, which can perform difluoromethylation reactions on a series of substrates such as aldehydes, ketones, and imines.
• Electrophilic difluoromethylation agents. Electrophilic difluoromethylation agents mainly include onium salts, phenyl sulfoximine, sulfur ylide and phosphine ylide. Electrophilic difluoromethylation agents can conveniently introduce difluoromethyl groups into the electron-rich sites of molecules, and can also be reduced to participate in the reaction as difluoromethyl radical precursors, which have obvious advantages in the synthesis of fluorine-containing compounds.
• Free radical difluoromethylation agents. The free radical difluoromethylation agents that have been developed so far include difluoromethanesulfonyl chloride, difluoromethyl benzothiazole alum, sodium difluoromethanesulfonyl, brominated difluoromethyl triphenylphosphine and so on. These free radical difluoromethylation agents form CF₂H radicals under light, and then add with C=C to form carbon radical intermediates, which are then captured by intermolecular or intramolecular nucleophiles and aromatic rings to obtain difluoromethyl-containing compounds. These agents can be used to synthesize difluoromethyl compounds that are not easily synthesized by conventional routes.

Alfa Chemistry can offer various difluoromethylation agents, including nucleophilic difluoromethylation agents, electrophilic difluoromethylation agents and free radical difluoromethylation agents. You can click on our product list for a detailed view. If you do not find the product you want, we also offer product customization according to customer's detailed requirements. Please contact us, if you are in need of assistance.