Aryl Sulfonyl Research Articles

The recycling of sulfur dioxide

Sulfur-containing compounds are commonly found in important fossil fuels, such as coal and petroleum etc. Therefore, in the process of utilizing these energy sources, we will inevitably produce a large amount of sulfur dioxide gas. According to statistics, the annual emission of sulphur dioxide is 1.5 billion tons worldwide. Sulfur dioxide is one of the four core pollutants in air (nitrogen dioxide, ozone and solid particles are other three core pollutants), its content in the air directly affects the ecological environment and human healt. Meanwhile, sulfur dioxide is widely used as food additives, bleaching agents and other chemical raw materials, and this usage accounts is only 1.6% of its emissions. Sulfonyl-containing compounds exist widely in the drug and organic photoelectric material molecules. How to convert harmful sulfur dioxide into useful chemical products has become a scientific problem demanding prompt solution. In 1957, Meerwein et al. developed the synthesis of arylsulfonyl chlorides from aryl diazonium salts and SO2 gas in the presence of a catalytic amount of CuCl. Afterwards, some CuCl-catalyzed strategies were developed and applied to preparations of aryl sulfonyl chlorides from different organometallic reagent and SO2 gas. Sulfur dioxide, as a toxic gas, is not easy to handle and store in the process of its use. Therefore, the development of sulfur dioxide gas surrogates has become an important research direction in organic chemistry. In 2010, the Willis group employed the known complex DABSO DABCO·(SO2)2 (DABCO=1,4-diazabicyclo [2.2.2] octane) to synthesize aryl N -aminosulfonamides via the palladium- catalyzed three-component coupling of aryl iodides, hydrazines and DABSO. Subsequently, the Wu group described a palladium-catalyzed three-component coupling of arylboronic acids, DABSO and hydrazines in the presence of dioxygen. Inorganic sulfites also can be used as the source of sulfur dioxide. In 2012, the Wus group disclosed a palladium-catalyzed coupling of aryl halides, potassium metabisulfite (K2S2O5), and hydrazines for the synthesis of aryl N -aminosulfonamides. The Toste group developed a gold(I)-catalyzed sulfination of aryl boronic acids via the three-component coupling of aryl boronic acids, potassium metabisulfite and alkyl bromides. Shavnya et al. explored the palladium-catalyzed one-step synthesis of (hetero)aryl-alkyl sulfones via the three-component coupling of (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides. In 2017, our group reported a straightforward sulfur dioxide-iodine exchange protocol for the construction of diarylannulated sulfone employing the readily available inorganic sodium metabisulfite as a safe and convenient sulfur dioxide surrogate. Some structural novel π-conjugated molecules, which give great potentials as organic light emitting diodes (OLEDs) materials molecules, were successfully established through our strategy, Despite the great attention of direct introduction of sulfur dioxide into organic frameworks have been paid, there is still necessary to develop more stable, green, cheap and easy to handle sulfur dioxide surrogates.

Synthesis of 3-sulfonyl coumarins through radical sulfonylation with disulfides under catalyst-free conditions

An efficient and convenient aryl sulfonyl introducing strategy for the synthesis of 3-sulfonyl coumarins via ipso-cyclization/1,2-ester migration from substituted phenyl 3-phenylpropiolates with disulfides and potassium persulfate as sulfonylating reagents was developed, halogen and many other electron-withdrawing or -donating functional groups are tolerated. When naphthalen-1-yl 3-phenylpropiolate was used as a starting material, a spiro compound was obtained via ipso-cyclization.

A comparative experimental and theoretical investigation of hydrogen-bond, halogen-bond and π-π interactions in the solid-state supramolecular assembly of 2- and 4-formylphenyl arylsulfonates.

To explore the operational role of noncovalent interactions in supramolecular architectures with designed topologies, a series of solid-state structures of 2- and 4-formylphenyl 4-substituted benzenesulfonates was investigated. The compounds are 2-formylphenyl 4-methylbenzenesulfonate, C14H12O4S, 3a, 2-formylphenyl 4-chlorobenzenesulfonate, C13H9ClO4S, 3b, 2-formylphenyl 4-bromobenzenesulfonate, C13H9BrO4S, 3c, 4-formylphenyl 4-methylbenzenesulfonate, C14H12O4S, 4a, 4-formylphenyl 4-chlorobenzenesulfonate, 4b, C13H9ClO4S, and 4-formylphenyl 4-bromobenzenesulfonate, C13H9BrO4S, 4c. The title compounds were synthesized under basic conditions from salicylaldehyde/4-hydroxybenzaldehydes and various aryl sulfonyl chlorides. Remarkably, halogen-bonding interactions are found to be important to rationalize the solid-state crystal structures. In particular, the formation of O...X (X = Cl and Br) and type I X...X halogen-bonding interactions have been analyzed by means of density functional theory (DFT) calculations and characterized using Bader's theory of `atoms in molecules' and molecular electrostatic potential (MEP) surfaces, confirming the relevance and stabilizing nature of these interactions. They have been compared to antiparallel π-stacking interactions that are formed between the arylsulfonates.

One-pot Synthesis of Pyrazolone Sulfones by Iodine-catalyzed Sulfenylation of Pyrazolones with Aryl Sulfonyl Hydrazides Followed by Oxidation in Water

Aim and Objective: Pyrazolone sulfones have been reported to exhibit herbicidal and antibacterial activities. In spite of their good bioactivities, only a few methods have been developed to prepare pyrazolone sulfones. However, the substrate scope of these methods is limited. Moreover, the direct sulfonylation of pyrazolone by aryl sulfonyl chloride failed to give pyrazolone sulfones. Thus, developing a more efficient method to synthesize pyrazolone sulfones is very important. Materials and Method: Pyrazolone, aryl sulphonyl hydrazide, iodine, p-toluenesulphonic acid and water were mixed in a sealed tube, which was heated to 100°C for 12 hours. The mixture was cooled to 0°C and m-CPBA was added in batches. The mixture was allowed to stir for 30 min at room temperature. The crude product was purified by silica gel column chromatography to afford sulfuryl pyrazolone. Results: In all cases, the sulfenylation products were formed smoothly under the optimized reaction conditions, and were then oxidized to the corresponding sulfones in good yields by 3-chloroperoxybenzoic acid (m-CPBA) in water. Single crystal X-ray analysis of pyrazolone sulfone 4aa showed that the major tautomer of pyrazolone sulfones was the amide form instead of the enol form observed for pyrazolone thioethers. Moreover, the C=N double bond isomerized to form an α,β-unsaturated C=C double bond. Conclusion: An efficient method to synthesize pyrazolone thioethers by iodine-catalyzed sulfenylation of pyrazolones with aryl sulfonyl hydrazides in water was developed. Moreover, this method was employed to synthesize pyrazolone sulfones in one-pot by subsequent sulfenylation and oxidation reactions.

Synthesis, Molecular Docking, Analgesic, and Anti-Inflammatory Activities of New 1,2,4-Oxadiazolo-Sulfonamides

In the present study novel 1,2,4-oxadiazolo sulfonamides 3a–3o are synthesized by an efficient method based on the reaction of 1,2,4-oxadiazole amines with aryl sulfonyl chlorides. Structures of the synthesized compounds are confirmed by IR, NMR and Mass spectra. Molecular interactions of the obtained compounds are studied by Discovery Studio v3.5, molecular docking with COX-2 enzyme. The compounds with high LibDock score are screened for their in vivo analgesic and anti inflammatory activities. The compound 3l demonstrates the highest activity.

Three-component one-pot synthesis of N-arylsulfonyl-2-iminocoumarins

A one-pot, synthesis of N-arylsulfonyl-2-iminocoumarins is developed at ambient temperature by the reaction of 2-hydroxybenzaldehydes, arylacetonitriles, and aryl sulfonyl chlorides using DABCO as a base in a bio-mass-derived green solvent 2-MethylTHF. A simple telescoped process in which 2H-chromen-2-imines are formed in situ by the condensation of 2-hydroxybenzaldehyde and arylacetonitriles. The formed imines are further reacted with arylsulfonyl chlorides in a one-pot approach to obtain the target compounds. This protocol provides access to 3-aryl-N-arylsulfonyl-2-iminocoumarins in a practical and environmentally benign way avoiding cumbersome steps of intermediate syntheses and purifications.

A copper-catalyzed three component reaction of aryl acetylene, sulfonyl azide and enaminone to form iminolactone via 6π electrocyclization.

We developed a copper-catalyzed three component reaction of aryl acetylene, enaminone and sulfonyl azide to construct iminolactone via a cascade process involving copper-catalyzed alkyne-azide cycloaddition (CuAAC), Michael addition of metalated ketenimine followed by elimination and 6π electrocyclization.

Computational Study of Engineered Cytochrome P450-Catalyzed C-H Amination: The Origin of the Regio- and Stereoselectivity.

Cytochrome P450 enzymes were recently engineered to catalyze the C-H amination reaction of aryl sulfonyl azides with excellent regio- and stereoselectivity (Arnold and co-workers J. Am. Chem. Soc. 2014 , 136 , 15505 ). The mechanism of this reaction was studied by quantum mechanical (QM)/molecular mechanical (MM) calculations in this work. The C-H activation is found to be a stepwise process consisting of hydrogen abstraction (H-abstraction) of the reactive C-H bond by an iron nitrenoid cofactor to produce the biradical intermediate and subsequent radical rebinding to form the final product. The rate of rotation of the carbon radical center was estimated to be much faster than that of radical rebinding, which implies that the H-abstraction does not determine the stereoselectivity. For mutant A, the H-abstraction step has a barrier of 16.7 kcal/mol, which is 3.0 kcal/mol higher than that of the following radical rebinding step. The H-abstraction step determines the regioselectivity, but the radical rebinding step determines the stereoselectivity. Barriers of these two steps are 16.1 and 27.5 kcal/mol, respectively, for mutant B. It is different from mutant A in that the radical rebinding step has the higher barrier and determines both the regio- and stereoselectivity. The initial distances between the hydrogens of reactive C-H bonds and the iron nitrenoid were found to not correlate with their reactivities. The calculated barriers are qualitatively consistent with the experimentally observed regio- and stereoselectivity with the exception of the stereoselectivity of mutant B. The lower barriers of mutant A presumably come from the stabilization effect of the H-bond between G265 and the sulfone O. This H-bond does not exist in mutant B. The conformation of the protein backbone, with the exception of the active site, does not change much (RMSD < 0.05) along the reaction pathway.

Hydroxysulfonylation of Quinones with Aryl(alkyl)sulfonyl Hydrazides for the Synthesis of 1,4‐Dihydroxy‐2‐aryl(alkyl)sulfonylbenzenes

β‐Ketoacyl‐ACP‐synthase III (FabH) plays an important role in bacterial fatty‐acid biosynthesis as an important condensing enzyme. 1,4‐Dihydroxy‐2‐tosylnaphthalene and its analogues are potent inhibitors of FabH. Traditional methods for the synthesis of these compounds still suffer from some drawbacks. In this work, an efficient copper‐catalyzed method for the hydroxysulfonylation of quinones with aryl(alkyl)sulfonyl hydrazides was developed for the direct synthesis of 1,4‐dihydroxy‐2‐phenylsufonylbenzenes. A series of biologically useful FabH inhibitors were obtained in good yields under argon. Both aryl and alkyl substituents were well tolerated in the reaction.

Sulfonamides and carbamates of 3-fluoro-4-morpholinoaniline (linezolid intermediate): synthesis, antimicrobial activity and molecular docking study

The precursor compound 3-fluoro-4-morpholinoaniline (7) is an important intermediate of the antibiotic drug linezolid and was synthesized initially by the substitution of morpholine (5) on 1,2-difluoro-4-nitrobenzene (4) under neat conditions, resulting in 4-(2-fluoro-4-nitrophenyl)morpholine (6) followed by its nitro group reduction with Fe/NH4Cl. A series of new sulfonamides (9a–e) and carbamates (11a–e) have been synthesized in good yields (75–89%) by the reaction of substituted aryl sulfonyl chlorides (8a–e) and substituted aryl/acyclic chloroformates (10a–e) with precursor compound 7, respectively, for biological interest. Structures of the title products were elucidated by spectroscopic data such as IR, NMR (1H and 13C NMR) and mass and elemental analyses. The antimicrobial potency of title products was examined by the screening of growth of zone of inhibition against four bacteria and four fungi, and minimum inhibitory concentration (MIC) was also determined. Most of the compounds showed good to potent antimicrobial activity, whereas the title products, 9d and 9e against bacterial strains, and 9a, 9b, 9d and 11a against fungi, exhibited promising activity in the MIC range of 6.25–25.0 µg/mL. The whole biological activity results revealed that the sulfonamide derivatives behaved as potent antifungal agents as compared to the carbamate derivatives. Molecular docking studies of the crystal structure of topoisomerase II gyrase A complexed with natural inhibitor, clorobiocin (1kzn), using the molecular operating environment (MOE) programme were performed in order to predict the affinity and orientation of the synthesized compounds at the active enzyme site. The test compounds showed good binding affinities and formed hydrogen bonds with a surrounding of amino acids at the active sight, whereas compounds 9d (−189.0 kcal/mol) and 11a (−280.3 kcal/mol) exhibited high binding affinities and good agreement with in vitro antimicrobial screening.

Coumarin sulfonates: New alkaline phosphatase inhibitors; in vitro and in silico studies

A library of coumarin derived sulfonyl esters (1–38) was synthesized by reacting various hydroxy coumarins with different alkyl and aryl sulfonyl chlorides. All compounds were evaluated for their potential to inhibit alkaline phosphatases (hTNAP and hIAP). Most of the compounds were found to be inhibitors of APs. Compound 20 was found to be the most active hIAP inhibitor (IC50 = 1.11 ± 0.15 μM), whereas, compound 13 was found to be the most active hTNAP inhibitor (IC50 = 0.58 ± 0.17 μM). Detailed structure activity relationship studies (SAR), and molecular docking studies were carried out to identify structural elements necessary for AP inhibition, in addition to rationalize most probable binding site interaction of the inhibitors with the AP enzymes.

Pd-Catalyzed Conversion of Aryl Iodides to Sulfonyl Fluorides Using SO2 Surrogate DABSO and Selectfluor.

A one-pot Pd-catalyzed conversion of aryl iodide to aryl sulfonyl fluorides using DABSO and Selectfluor has been developed generating aryl sulfonyl fluorides in good to excellent yields. The reaction results in the generation of electronically and sterically diverse sulfonyl fluorides. Additionally, sulfonyl fluorides can be converted to aryl sulfonamides and sulfonic esters using Cs2CO3 under mild conditions.

Synthesis and bioactivity of several new hetaryl sulfonamides

1-(4-Methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles were synthesized from different tetrahydropyrimidinethiones and aryl sulfonyl chloride. These compunds were tested for metal chelating effects and to determine the phrase in which inhibition occured between two physiologically pertinent compunds and carbonic anhydrase (CA) isozymes I and II (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). AChE was detected in high concentrations in the brain and red blood cells. BChE is another enzymes that is abundant available in the liver and released into the blood in a soluble form. Newly synthesized hetaryl sulfonamides exhibited impressive inhibition profiles with Ki values in the range of 1.42–6.58 nM against hCA I, 1.72–7.41 nM against hCA II, 0.20–1.14 nM against AChE and 1.55–5.92 nM against BChE. Moreover, acetazolamide showed Ki values of 43.69 ± 6.44 nM against hCA I and 31.67 ± 8.39 nM against hCA II. Additionally, tacrine showed Ki values of 25.75 ± 3.39 nM and 37.82 ± 2.08 against AChE and BChE, respectively.

Recent advances in reactions of aryl sulfonyl isocyanates.

Aryl sulfonyl isocyanates are important intermediates in organic synthesis. They are used as electrophilic reagents and easily react with nucleophiles to form amides, sulfonyl ureas, pyrrolidine derivatives, lactams, oxazolidinones, and so on. Although there are some reviews on the applications of isocyanates in chemistry, few are concerned about aryl sulfonyl isocyanates. This review focuses on recent advances related to aryl sulfonyl isocyanates in organic synthesis, mainly including three special characteristics. The mechanisms of the typical reactions are also discussed.

ChemInform Abstract: Catalyst‐Controlled Selectivity in the Synthesis of C2‐ and C3‐Sulfonate Esters from Quinoline N‐Oxides and Aryl Sulfonyl Chlorides.

AbstractC2‐ and C3‐Sulfonate esters [(III) and (IV)] are selectively synthesized starting from quinoline N‐oxides (I) and aryl sulfonyl chlorides (II).

ChemInform Abstract: Synthesis of Substituted Pyrroles via Copper‐Catalyzed Cyclization of Ethyl Allenoates with Activated Isocyanides.

A new method for the synthesis of di- and trisubstituted pyrroles via copper-catalyzed cyclization of ethyl allenoates with activated isocyanides has been developed. In contrast to related annulation reactions previously reported, this new process features a skeletal rearrangement in which the aryl sulfonyl moiety, which functions as the electron-withdrawing group in the α-carbon of the isocyanide, was found to migrate to the γ-carbon of the starting allenoate in the final product for the first time.

Potassium iodide promoted thiolation of pyrazolones and benzofurans using aryl sulfonyl chlorides as sulfenylation reagents

An efficient, transition-metal-free method to synthesize pyrazolone thioethers as well as 2-aryl and 3-aryl benzofuran thioethers by employing aryl sulfonyl chlorides as sulfenylation reagents in the presence of triphenylphosphine was developed. Potassium iodide was found to facilitate the transformation for the first time by generating more reactive sulfenyl iodide in situ from sulfenyl chloride.

Chemoselective Preparation of Clickable Aryl Sulfonyl Fluoride Monomers: A Toolbox of Highly Functionalized Intermediates for Chemical Biology Probe Synthesis.

Sulfonyl fluoride (SF)-based activity probes have become important tools in chemical biology. Herein, exploiting the relative chemical stability of SF to carry out a number of unprecedented SF-sparing functional group manipulations, we report the chemoselective synthesis of a toolbox of highly functionalized aryl SF monomers that we used to quickly prepare SF chemical biology probes. In addition to SF, the monomers bear an embedded click handle (a terminal alkyne that can perform copper(I)-mediated azide-alkyne cycloaddition). The monomers can be used either as fragments to prepare clickable SF analogues of drugs (biologically active compounds) bearing an aryl ring or, alternatively, attached to drugs as minimalist clickable aryl SF substituents.

Inside Cover: Catalyst‐Controlled Selectivity in the Synthesis of C2‐ and C3‐Sulfonate Esters from Quinoline N‐Oxides and Aryl Sulfonyl Chlorides (ChemCatChem 16/2016)

Inside Cover: Catalyst‐Controlled Selectivity in the Synthesis of C2‐ and C3‐Sulfonate Esters from Quinoline <i>N</i>‐Oxides and Aryl Sulfonyl Chlorides (ChemCatChem 16/2016)

Catalyst‐Controlled Selectivity in the Synthesis of C2‐ and C3‐Sulfonate Esters from Quinoline N‐Oxides and Aryl Sulfonyl Chlorides

AbstractThe first example of the catalyst‐controlled selective synthesis of C2‐ and C3‐sulfonate‐ester‐substituted quinolines was developed by employing LaCl3 and chitosan@CuI catalysts, respectively. This protocol provides an expeditious route to an important class of quinoline derivatives frequently found in many biologically active compounds and features good practicality, high efficiency, and environmental friendliness. In addition, the easily recoverable chitosan@copper catalysts can be recycled five times without significant loss of catalytic performance.