24933-57-1

Usage

Uses

Used in Organic Synthesis:
4-(Difluoromethylthio)nitrobenzene is used as a chemical intermediate for the synthesis of various organic compounds. Its unique structure and reactivity make it a valuable component in the preparation of complex molecules and pharmaceuticals.
Used in Chemical Research:
In the field of chemical research, 4-(Difluoromethylthio)nitrobenzene is used as a model compound to study the properties and reactions of similar compounds. This helps researchers understand the behavior of related molecules and develop new synthetic strategies and applications.
Used in Laboratory Settings:
4-(Difluoromethylthio)nitrobenzene is used as a reagent in various laboratory experiments, where its properties and reactions are explored and utilized to achieve specific chemical transformations or to produce desired products.
Used in Pharmaceutical Development:
Although not directly used in everyday products, 4-(Difluoromethylthio)nitrobenzene plays a crucial role in the development of new pharmaceuticals. Its involvement in the synthesis of complex molecules and its potential as a chemical intermediate make it an essential component in the drug discovery process.

InChI:InChI=1/C7H5F2NO2S/c8-7(9)13-6-3-1-5(2-4-6)10(11)12/h1-4,7H

Upstream product

• 100-01-6 4-nitro-aniline 
• 1849-36-1 para-nitrobenzenethiol 
• 354-08-5 bromodifluoroacetic acid 
• 24067-17-2 4-nitrophenylboronic acid 
• 636-98-6 p-nitrobenzene iodide 
• 100-32-3 di(p-nitrophenyl) disulfide 
• 365-00-4 2,2-difluoro-1,3-diphenyl-1,3-propanedione 
• 456-27-9 4-nitrobenzenediazonium tetrafluoroborate 
• 2137-92-0 4-nitrophenyl thiocyanate 
• 65864-64-4 trimethyl(difluoromethyl)silane 
• 115262-01-6 [bromo(difluoro)methyl]-trimethyl-silane 
• 75-45-6 Chlorodifluoromethane 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 1097192-99-8 N-toluylsulfonyl S-difluoromethyl S-phenyl sulfoximine 

Downstream Products

• 55384-49-1 2-Amino-5-difluoromethylthiobenzophenone 
• 24906-77-2 4-((difluoromethyl)sulfonyl)aniline 
• 24906-88-5 (4-Amino-phenyl)-difluormethyl-sulfoxid 
• 24906-81-8 Difluormethyl-<4-hydroxy-phenyl>-sulfon 
• 24906-74-9 1-((difluoromethyl)sulfonyl)-4-nitrobenzene 
• 24933-67-3 1-((difluoromethyl)sulfinyl)-4-nitrobenzene 
• 24933-60-6 4-difluoromethylsulfanylaniline 
• 55384-52-6 5-difluoromethylsulfanyl-3-phenyl-benzo[c]isoxazole 

Relevant academic research and scientific papers

Difluoromethylation of Phenols and Thiophenols with the S-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study

A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.

Difluoro methylation reagent, preparation method and application thereof (by machine translation)

The present invention discloses a two-trifluoromethylation of the reagent, preparation method and application thereof. The invention [...] methylation reagent preparation process is simple, high yield; and the reagent can be a more moderate, high-efficiently the sulfonic acid, alcohol, carbonyl and on the α carbon atom of the difluoromethyl. (by machine translation)

Visible-Light Photoredox Difluoromethylation of Phenols and Thiophenols with Commercially Available Difluorobromoacetic Acid

A simple and efficient visible-light photoredox one-pot method for difluoromethylation of phenols and thiophenols has been developed. The protocol uses commercially available, inexpensive, and easy handling difluorobromoacetic acid as the difluoromethylating agent, and the diverse O- and S-difluoromethylated products were prepared in good yields with tolerance of many functional groups.

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.

PhSO2SCF2H: A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation

A new shelf-stable and easily scalable difluoromethylthiolating reagent S-(difluoromethyl) benzenesulfonothioate (PhSO2SCF2H) was developed. PhSO2SCF2H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl-difluoromethylthio difunctionalization of alkenes under mild reaction conditions.

Palladium-catalyzed difluoromethylthiolation of heteroaryl bromides, iodides, triflates and aryl iodides

A palladium-catalyzed difluoromethylthiolation of heteroaryl halides and triflates under mild conditions was described. A vast range of heteroaryl halides such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl and pyazolyl halides could be difluoromethylthiolated efficiently, thus providing medicinal chemists with new tools for their search of new lead compounds for drug discovery. Likewise, aryl iodides were difluoromethylthiolated in high yields under a modified reaction condition.

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.

N-Difluoromethylthiophthalimide: A Shelf-Stable, Electrophilic Reagent for Difluoromethylthiolation

A new, electrophilic difluoromethylthiolating reagent N-difluoromethylthiophthalimide 3 was developed. Reagent 3 can be readily synthesized in four steps from easily available starting materials phthalimide and TMSCF2H. N-difluoromethylthiophthalimide 3 is a powerful electrophilic difluoromethylthiolating reagent that allows the difluoromethylthiolation of a wide range of nucleophiles including aryl/vinyl boronic acids, alkynes, amines, thiols, β-ketoesters, and oxindoles and electron-rich heteroarenes such as indole, pyrrole, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyridine, aminothiazole, isoxazole, and pyrazole under mild conditions.

Copper-promoted sandmeyer difluoromethylthiolation of aryl and heteroaryl diazonium salts

An efficient copper-promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one-pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules. A dose of salt: The title reaction is conducted under mild reaction conditions and various functional groups are compatible. (Hetero)aryl diazonium salts reacted smoothly to afford the medicinally important difluoromethylthiolated (hetero)arenes. A practical one-pot direct diazotization and difluoromethylthiolation protocol was developed for aniline derivatives to generate difluoromethylthiolated arenes.

Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and organothiocyanates generated in situ

A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups - a largely unexplored substituent with highly promising properties - into drug-like molecules. A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts.