3447-50-5

Basic information

• Product Name: Benzene, 1-[(difluoromethyl)thio]-4-methyl-
• Synonyms: Difluormethyl-p-tolyl-sulfid;1-Difluoromethylsulfanyl-4-methyl-benzene;4-methyl(difluorothiomethoxy)benzene;4-methyl-1-(difluoro-methylthio)benzene;(difluoromethyl)(p-tolyl)sulfane
• CAS NO: 3447-50-5
• Molecular Formula: C8H8F2S
• Molecular Weight: 174.214
• Mol File: 3447-50-5.mol
• Article Data: 12

Chemical Properties

• CAS DataBase Reference: Benzene, 1-[(difluoromethyl)thio]-4-methyl-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzene, 1-[(difluoromethyl)thio]-4-methyl-(3447-50-5)
• EPA Substance Registry System: Benzene, 1-[(difluoromethyl)thio]-4-methyl-(3447-50-5)

Safety Data

• Hazardous Substances Data: 3447-50-5(Hazardous Substances Data)

Upstream product

• 58310-28-4 (Difluoromethyl)triphenylphosphonium bromide 
• 106-45-6 para-thiocresol 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 100-52-7 benzaldehyde 
• 1895-39-2 sodium chlorodifluoroacetate 
• 75-46-7 trifluoromethan 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 1097192-99-8 N-toluylsulfonyl S-difluoromethyl S-phenyl sulfoximine 
• 623-13-2 4-methylphenyl methylsulfide 
• 75-45-6 Chlorodifluoromethane 
• 354-08-5 bromodifluoroacetic acid 

Downstream Products

• 3447-51-6 1-Bromomethyl-4-difluoromethylsulfanyl-benzene 
• 4837-22-3 4-((difluoromethyl)sulfonyl)benzoic acid 
• 126300-86-5 2-(4-Difluoromethylsulfanyl-benzyl)-2-formylamino-malonic acid diethyl ester 
• 126300-90-1 2-Amino-3-(4-difluoromethylsulfanyl-phenyl)-propionic acid 

Relevant articles and documents

Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide

A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a SRN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH2, amide, ester).

Difluoromethyl bioisostere: Examining the lipophilic hydrogen bond donor concept

There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085-0.126) were determined using Abraham's solute 1H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water-octanol) values (log P(XCF2H) - log P(XCH3)) spanned from -0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.

A Route to α-Fluoroalkyl Sulfides from α-Fluorodiaroylmethanes

α,α-Difluorodiaroylmethane can be used as a nucleophilic difluoromethylation reagent for generating α-thioaryl-α,α-difluoroacetophenones (Ar1COCF2SAr) and difluoromethylthiolated arenes (ArSCF2H) under transition-metal-free conditions. The reaction selectivity is mainly dependent on temperature. The method has also been extended to the synthesis of α-thioaryl-α-monofluoroacetophenones using α-monofluorodibenzoylmethane. Moreover, the benzoyl cation derived from α,α-difluorodibenzoylmethane can react with nucleophiles to afford the desired products in a one-pot process.