395-46-0

Upstream product

• 1885-29-6 anthranilic acid nitrile 
• 55165-45-2 2-cyano-benzenediazonium tetrafluoroborate 
• 119072-55-8 tert-butylisonitrile 
• 88284-48-4 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 
• 69360-26-5 2-cyanobenzenesulfonyl chloride 

Downstream Products

• 114772-53-1 2-Cyano-4'-methylbiphenyl 
• 394-47-8 2-fluorobenzonitrile 

Relevant academic research and scientific papers

Metal-Free Visible-Light Synthesis of Arylsulfonyl Fluorides: Scope and Mechanism

The first metal-free procedure for the synthesis of arylsulfonyl fluorides is reported. Under organo-photoredox conditions, aryl diazonium salts react with a readily available SO2 source (DABSO) to afford the desired product through simple nucleophilic fluorination. The reaction tolerates the presence of both electron-rich and -poor aryls and demonstrated a broad functional group tolerance. To shed the light on the reaction mechanism, several experimental techniques were combined, including fluorescence, NMR, and EPR spectroscopy as well as DFT calculations.

Desulfonative Suzuki–Miyaura Coupling of Sulfonyl Fluorides

Sulfonyl fluorides have emerged as powerful “click” electrophiles to access sulfonylated derivatives. Yet, they are relatively inert towards C?C bond forming transformations, notably under transition-metal catalysis. Here, we describe conditions under which aryl sulfonyl fluorides act as electrophiles for the Pd-catalyzed Suzuki–Miyaura cross-coupling. This desulfonative cross-coupling occurs selectively in the absence of base and, unusually, even in the presence of strong acids. Divergent one-step syntheses of two analogues of bioactive compounds showcase the expanded reactivity of sulfonyl fluorides to encompass both S?Nu and C?C bond formation. Mechanistic experiments and DFT calculations suggest oxidative addition occurs at the C?S bond followed by desulfonation to form a Pd-F intermediate that facilitates transmetalation.

Synthesis of Arenesulfonyl Fluorides via Sulfuryl Fluoride Incorporation from Arynes

Transition-metal-free multicomponent reactions involving aryne precursors, secondary amines, and sulfuryl fluoride are reported herein. Zwitterionic intermediates formed from the reaction of arynes with amine nucleophiles can capture SO2F2 under mild conditions, offering a novel and practical protocol for the synthesis of 2-dialkyl-, 2-alkylaryl-, or 2-diarylamino-substituted arenesulfonyl fluoride derivatives in good to excellent yields.

SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase

Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form.

Sulfur(VI) fluoride compounds and methods for the preparation thereof

This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

A study of the reactivity of S(VI)-F containing warheads with nucleophilic amino-acid side chains under physiological conditions

Sulfonyl fluorides (SFs) have recently emerged as a promising warhead for the targeted covalent modification of proteins. Despite numerous examples of the successful deployment of SFs as covalent probe compounds, a detailed exploration of the factors influencing the stability and reactivity of SFs has not yet appeared. In this work we present an extensive study on the influence of steric and electronic factors on the reactivity and stability of the SF and related SVI-F groups. While SFs react rapidly with N-acetylcysteine, the resulting adducts were found to be unstable, rendering SFs inappropriate for the durable covalent inhibition of cysteine residues. In contrast, SFs afforded stable adducts with both N-acetyltyrosine and N-acetyllysine; furthermore, we show that the reactivity of arylsulfonyl fluorides towards these nucleophilic amino acids can be predictably modulated by adjusting the electronic properties of the warhead. These trends were largely conserved when the covalent reaction occurred within a protein binding pocket. We have also obtained a crystal structure depicting covalent modification of the catalytic lysine of a tyrosine kinase (FGFR1) by the ATP analog 5′-O-3-((fluorosulfonyl)benzoyl)adenosine (m-FSBA). Highly reactive warheads were demonstrated to be unstable with respect to hydrolysis in buffered aqueous solutions, indicating that warhead reactivity must be carefully tuned to provide optimal rates of protein modification. Our results demonstrate that the reactivity of SFs complements that of more commonly studied acrylamides, and we hope that this work spurs the rational design of novel SF-containing covalent probe compounds and inhibitors, particularly in cases where a suitably positioned cysteine residue is not present.

NOVEL COMPOUNDS

The present invention relates to novel indole derivatives such as compounds of the formula (I): which possess antagonist potency at the 5-HT6 receptor and the use of such compounds or pharmaceutically acceptable salts or solvates thereof in the treatment of Alzheimer's disease and other CNS disorders.

Process for the preparation of 2-fluorobenzonitrile from saccharin

The present invention relates to a process for the preparation of 2-fluorobenzonitrile. The process comprises the steps of: (a) heating saccharin and phosphorus pentachloride under conditions and for a time sufficient to provide 2-cyanobenzenesulfonyl chloride; and (b) reacting the 2-cyanobenzenesulfonyl chloride with alkali metal fluoride in solvent for said 2-cyanobenzenesulfonyl chloride under conditions and for a time sufficient to provide 2-fluorobenzonitrile. The present invention provides a process for the preparation of 2-fluorobenzonitrile which is a versatile intermediate for a variety of 2-fluoro substituted benzenes. For example, hydrolysis of 2-fluorobenzonitrile leads to 2-fluorobenzoic acid or 2-fluorobenzamide while reduction of 2-fluorobenzonitrile leads to 2-fluorobenzylamine. Also, the reaction of 2-fluorobenzonitrile with organometallic reagents results in various 2-fluorophenyl ketones.