395-01-7

Usage

Uses

Used in Pharmaceutical Industry:
2,2-Difluoroacetophenone is used as a key intermediate in the synthesis of various pharmaceuticals. Its unique chemical structure allows for the creation of a wide range of compounds with potential therapeutic applications. The presence of fluorine atoms in the molecule can significantly influence the pharmacokinetic and pharmacodynamic properties of the resulting drugs, potentially enhancing their efficacy and safety.
Used in One-Pot Synthesis:
2,2-Difluoroacetophenone is utilized in the one-pot synthesis of difluoromethylated arenes from aryl chlorides and bromides. This method offers a convenient and efficient route to produce a variety of difluoromethylated aromatic compounds, which are important building blocks in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Reduction Reactions:
2,2-Difluoroacetophenone undergoes reduction with (-)-diisopinocampheylchloroborane chloride to obtain R-alcohols with a purity of 85% ee. This selective reduction process is valuable in the synthesis of enantiomerically pure compounds, which are often required for the development of chiral drugs with improved efficacy and reduced side effects.

Synthesis Reference(s)

Tetrahedron, 52, p. 15, 1996 DOI: 10.1016/0040-4020(95)00884-B

InChI:InChI=1/C8H6F2O/c9-8(10)7(11)6-4-2-1-3-5-6/h1-5,8H

Upstream product

• 98-86-2 acetophenone 
• 381-72-6 difluoroacetyl chloride 
• 71-43-2 benzene 
• 677-67-8 fluorosulfonyldifluoroacetyl fluoride 
• 2206-94-2 1-acetoxy-1-phenylethene 
• 150542-06-6 α,α,α-iodinefluoroacetophenone 
• 140-88-5 ethyl acrylate 
• 592-76-7 1-Heptene 
• 111-66-0 oct-1-ene 
• 2680-03-7 N,N-Dimethylacrylamide 
• 1663-39-4 tert-Butyl acrylate 
• 141-32-2 acrylic acid n-butyl ester 
• 86340-78-5 2,2-difluoro-1-phenyl-1-trimethylsiloxyethene 
• 78-94-4 methyl vinyl ketone 

Downstream Products

• 82255-42-3 2,2-difluoro-1-phenyl-ethanol 
• 383-16-4 (1,1-dichloro-2,2-difluoro-ethyl)-benzene 
• 114829-09-3 4-[2,2-Difluoro-1-phenyl-eth-(Z)-ylidene]-2-phenyl-4H-oxazol-5-one 
• 149597-15-9 (2,2-Dibromo-1-difluoromethyl-vinyl)-benzene 
• 50562-23-7 2.2-Difluor-1-phenylethanol-1-d1 
• 16839-91-1 Phenyldifluoracetat 
• 115818-55-8 2,2-difluoro-3-hydroxy-1,3-diphenylpropan-1-one 
• 1415315-21-7 C₁₂H₁₄F₂ 
• 1415314-94-1 C₁₀H₁₀F₂O 
• 1577232-99-5 2,2-difluoro-2-(isoquinolin-7-yl)-1-phenylethanone 
• 1204298-71-4 C₁₀H₇F₂N 
• 1577233-00-1 2,2-difluoro-2-(quinolin-5-yl)-1-phenylethanone 
• 1261738-94-6 C₁₀H₇F₂N 

Relevant academic research and scientific papers

Solvent dependence of the synthesis and reactions of acetyl hypofluorite

Acetyl hypofluorite (AcOF) has been previously prepared using CFCl3 (CFC-11) as a solvent.It was found that acetonitrile can replace trichlorofluoromethane without sacrificing the efficiency and the regio- and stereo-selectivity of the addition of AcOF to olefins.Most other solvents tested proved to be inadequqte for the synthesis of AcOF, despite the fact that fluorine does react with the dispersed sodium acetate present in the solvent.

HFIP-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes

Hexafluoroisopropanol (HFIP)-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes is developed. This procedure enables the synthesis of a broad range of α,α-difluoroketones, a class of highly valuable intermediates and building blocks in medicinal and organic chemistry. Here, we have demonstrated for the first time that HFIP could act as a powerful catalyst for fluorinated carbon-carbon bond formation. The application of this protocol in late-stage dehydroxydifluoroalkylation of potentially bioactive drugs and natural products has also been carried out.

Palladium-catalyzed one-pot construction of difluorinated 1,3-enynes from α,α,α-iododifluoroacetones and alkynes

A palladium-catalyzed one-pot difunctionalization of alkynes with α,α,α-iododifluoroacetones is introduced for the synthesis of difluorinated 1,3-enynes. The reaction proceeds through the radical addition of RCOCF2 radical to alkynes and subseq

Addition of trifluoromethyltrimethylsilane to acyl phosphonates: Synthesis of TMS-protected 1-alkyl-1-trifluoromethyl-1-hydroxy phosphonates and 1-aryldifluoroethenyl phosphates

(Chemical Equation Presented) Addition reactions of nucleophilic CF 3TMS to acyl phosphonates were investigated. Various acyl phosphonates reacted readily with CF3TMS in the presence of K 2CO3 in DMF at rt to gi

Single electron transfer approaches to the practical synthesis of aromatic and heterocyclic-CF2H derivatives

Single electron transfer (SET) approaches with organic reductants such as sodium hydroxymethanesulfinate (Rongalite), sodium dithionite (regarded as precursors of sulfoxylate radical anion) and tetrakis(dimethylamino)ethylene (TDAE) were employed for the reductive dehalogenation of a series of halogeno-difluoromethylated aromatics and heterocycles, and for the practical synthesis of the corresponding difluoromethylated derivatives.

Difluoromethylation reactions of ethyl pyruvate with the TDAE - A mild approach to the synthesis of 3,3-difluoro-2-hydroxy-2-methyl-4-oxo-butyric ethyl esters derivatives

New 3,3-difluoro-2-hydroxy-2-methyl-4-oxo-butyric ethyl esters derivatives are easily obtained in moderate to good yields from the tetrakis(dimethylamino)ethylene (TDAE) mediated reduction of a series of RCF2X (X = Cl or Br) starting materials in the presence of ethyl pyruvate.

Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions

A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed.

Direct electrochemical hydrodefluorination of trifluoromethylketones enabled by non-protic conditions

CF2H groups are unique due to the combination of their lipophilic and hydrogen bonding properties. The strength of H-bonding is determined by the group to which it is appended. Several functional groups have been explored in this context includ

Trifluoromethylthiolation, Trifluoromethylation, and Arylation Reactions of Difluoro Enol Silyl Ethers

This study reports a new application area of difluoro enol silyl ethers, which can be easily obtained from trifluoromethyl ketones. The main focus has been directed to the electrophilic fluoroalkylation and arylation methods. The trifluoromethylthiolation of difluoro enol silyl ethers can be used for the construction of a novel trifluoromethylthio-α,α-difluoroketone (-COCF2SCF3) functionality. The -CF2SCF3 moiety has interesting properties due to the electron-withdrawing, albeit lipophilic, character of the SCF3 group, which can be combined with the high electrophilicity of the difluoroketone motif. The methodology could also be extended to difluoro homologation of the trifluoromethyl ketones using the Togni reagent. In addition, we presented a method for transition-metal-free arylation of difluoro enol silyl ethers based on hypervalent iodines.

Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines

Transition metal-catalysed C–H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the past 30 years. Here, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C–H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway that involves an uncommon Pd-catalysed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements ‘C–H activation’ strategies that convert inert C–H bonds into C–metal bonds prior to C–C bond formation. Instead, this reaction exploits an inverted sequence and promotes C–C bond formation prior to deprotonation. These studies provide an opportunity to develop general para-selective C–H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of the reaction conditions. [Figure not available: see fulltext.].