403-50-9

Upstream product

• 62-23-7 4-nitro-benzoic acid 
• 110-86-1 pyridine 
• 122-04-3 4-nitro-benzoyl chloride 
• 555-16-8 4-nitrobenzaldehdye 
• 98-88-4 benzoyl chloride 
• 636-98-6 p-nitrobenzene iodide 
• 243656-25-9 2,2-difluoro-2-(4-nitrophenyl)acetic acid ethyl ester 
• 206360-56-7 2,2-difluoro-2-(4-nitrophenyl)acetic acid 
• 619-73-8 4-nitrobenzyl chloride 

Downstream Products

• 86448-86-4 1-(4-nitrobenzoyl)indoline 
• 76339-62-3 p-Nitro-benzoesaeure-fluorsulfonsaeureanhydrid 
• 62-23-7 4-nitro-benzoic acid 
• 85237-02-1 (3S,4R)-2-Ethylsulfanyl-1-(4-nitro-benzoyl)-pyrrolidine-3,4-dicarboxylic acid dimethyl ester 
• 14786-27-7 benzyl 4-nitrobenzoate 
• 6629-65-8 S-2-naphthyl 4-nitrobenzenecarbothioate 
• 1144-74-7 4-nitrobenzophenone 
• 619-50-1 4-nitrobenzoic acid methyl ester 
• 619-72-7 4-nitrobenzonitrile 
• 80986-41-0 4-nitrophenyl(2',3',4',5',6'-pentafluorophenyl)ketone 
• 5323-47-7 N,N-diethyl-4-nitrobenzamide 
• 5397-76-2 1-morpholin-4-yl-1-(4-nitro-phenyl)-methanone 

Relevant academic research and scientific papers

Rapid and column-free syntheses of acyl fluorides and peptides usingex situgenerated thionyl fluoride

Thionyl fluoride (SOF2) was first isolated in 1896, but there have been less than 10 subsequent reports of its use as a reagent for organic synthesis. This is partly due to a lack of facile, lab-scale methods for its generation. Herein we report a novel protocol for theex situgeneration of SOF2and subsequent demonstration of its ability to access both aliphatic and aromatic acyl fluorides in 55-98% isolated yields under mild conditions and short reaction times. We further demonstrate its aptitude in amino acid couplings, with a one-pot, column-free strategy that affords the corresponding dipeptides in 65-97% isolated yields with minimal to no epimerization. The broad scope allows for a wide range of protecting groups and both natural and unnatural amino acids. Finally, we demonstrated that this new method can be used in sequential liquid phase peptide synthesis (LPPS) to afford tri-, tetra-, penta-, and decapeptides in 14-88% yields without the need for column chromatography. We also demonstrated that this new method is amenable to solid phase peptide synthesis (SPPS), affording di- and pentapeptides in 80-98% yields.

METHOD AND REAGENT FOR DEOXYFLUORINATION

A safe, simple, and selective method and reagent for deoxyfluorination is disclosed. With the method and reagent disclosed herein, organic compounds such as carboxylic acids, carboxylates, carboxylic acid anhydrides, aldehydes, and alcohols can be fluorinated by using the most common nucleophilic fluorinating reagents and electron deficient fluoroarenes as mediators under mild conditions, giving corresponding fluoroorganic compounds in excellent yield with a wide range of functional group compatibility and easy product purification. For example, directly utilizing KF for deoxyfluorination of carboxylic acids provides the most economical and the safest pathway to access acyl fluorides, key intermediates for syntheses of peptide, amide, ester, and dry fluoride salts.

Acyl fluorides from carboxylic acids, aldehydes, or alcohols under oxidative fluorination

We describe a novel reagent system to obtain acyl fluorides directly from three different functional group precursors: carboxylic acids, aldehydes, or alcohols. The transformation is achieved via a combination of trichloroisocyanuric acid and cesium fluoride, which facilitates the synthesis of various acyl fluorides in high yield (up to 99%). It can be applied to the late-stage functionalization of natural products and drug molecules that contain a carboxylic acid, an aldehyde, or an alcohol group.

Deoxyfluorination of Carboxylic Acids with CpFluor: Access to Acyl Fluorides and Amides

3,3-Difluoro-1,2-diphenylcyclopropene (CpFluor), a bench-stable fluorination reagent, has been developed in the deoxyfluorination of carboxylic acids to afford various acyl fluorides. This all-carbon-based fluorination reagent enabled the efficient transformation of (hetero)aryl, alkyl, alkenyl, and alkynyl carboxylic acids to the corresponding acyl fluorides under the neutral conditions. This deoxyfluorination method was featured by the synthesis of acyl fluorides with in-situ formed CpFluor, as well as the one-pot amidation reaction of carboxylic acids via in-situ formed acyl fluorides.

Deoxyfluorination of Carboxylic Acids with KF and Highly Electron-Deficient Fluoroarenes

A deoxyfluorination reaction of carboxylic acids using potassium fluoride (KF) and highly electron-deficient fluoroarenes is reported here, giving acyl fluorides in moderate to excellent yield (57-92% based on NMR integration and 34-95% for isolated examples).

Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions

Acyl fluorides are subjected to methoxylation with tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to afford the corresponding methyl esters in good to excellent yields. This transformation is featured by C(sp2)-OMe bond cleavage under metal-free conditions. Unprecedented utilization of TMPP as a methoxylating agent realized the installation of an OMe group into the desired products.

C-F Bond Activation of a Perfluorinated Ligand Leading to Nucleophilic Fluorination of an Organic Electrophile

We report a fluorine transfer reaction in which fluorine from a perfluorinated ligand undergoes C-F bond activation and transfers to an electrophile, resulting in the formation of a new fluorinated product and dimerization of the monodefluorinated complex. Treatment of [(η5,κ2C-C5Me4CH2C6F5CH2NC3H2NMe)-RhCl] with the organic electrophile, toluoyl chloride, resulted in the formation of a rhodium(III) metallocycle via C-F bond activation assisted defluorinative coupling. Fission of the C-F bond liberated nucleophilic fluoride, which converted acyl chloride to acyl fluoride. The overall reaction was monitored using a multivariate analysis approach in real time.

Tertiary-Amine-Initiated Synthesis of Acyl Fluorides from Carboxylic Acids and CF3SO2OCF3

A convenient method for deoxyfluorination of aromatic and aliphatic carboxylic acids with CF3SO2OCF3 in the presence of a suitable base at room temperature has been developed. The reaction allows a straightforward access to a variety of acyl fluorides and proves that CF3SO2OCF3 is an effective deoxyfluorination reagent for carboxylic acids. The method features simplicity, expeditiousness, high efficiency, ease of handling, good functional group tolerance, a wide range of substrates, excellent yields of products, compatibility of many amine initiators, use of environmentally friendly reagents, and effortless removal of byproducts. This reaction represents the first utilization of trifluoromethyl trifluoromethanesulfonate as a fluorination reagent.

Synthesis of Acyl Fluorides from Carboxylic Acids Using NaF-Assisted Deoxofluorination with XtalFluor-E

The synthesis of acyl fluorides using the deoxofluorination reaction of carboxylic acids using XtalFluor-E is described. This transformation, assisted by a catalytic amount of NaF, occurs at room temperature in EtOAc, where XtalFluor-E behaves as the activating agent and the fluoride source. A wide range of acyl fluorides were obtained in moderate to excellent yields (36-99%) after a simple filtration on a pad of silica gel. We also demonstrated that sequential deoxofluorination/amidation was possible.

Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride

Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30-80percent yields, and esters, amides, and thioesters in 72-96percent yields without reoptimization for each nucleophile.