Synthesis Of Sulfonamides Research Articles

Direct sulfonylamidation of unfunctionalized arenes in C[sbnd]H activation manner: A simple protocol to access primary sulfonamides

Among all biologically active sulfonamides, primary sulfonamides possessing terminal SO2NH2 group occupy special place due to their high zinc binding capability which has been successfully exploited for discovery of several different medicinally active primary sulfonamides. However, majority of the primary sulfonamide synthesis involve traditional method of treating ammonia with sulfonyl chloride, which in turn is typically obtained either from thiols by harsh oxidation conditions or chlorination of sulfonic acids. We herein report a simple and convenient protocol to access primary sulfonamides by direct sulfonylamidation of unfunctionalized arenes [direct CH activation to C-SO2NH2]. Usefulness of the protocol has been further demonstrated successfully by extending the application to formal syntheses of known drugs, acetazolamide (2), methazolamide (3), ethoxzolamide (4), and a pharmacologically active benzolamide (6).

Synthesis of Novel Sulfonamide Incorporated Azo Compounds as a PotentSolvatochromic and Antimycobacterial Agents

AbstractIn search of potent solvatochromic and biological agents, here we reported the synthesis of four azo dyes (S1–S4) owing sulfonamide functionality by diazo coupling reaction and their spectroscopic properties were investigated through UV, DRS, IR, NMR and mass spectrometry. Quantum chemical parameters of the synthesised colourants were assessed through DFT studies. The solvatochromic behaviour of sulfonamide incorporated azo compounds was investigated in ten different solvents owing different polarity and proticity and they exhibited remarkable positive solvatochromic behaviour and they exhibited λmax in the range 395–464 nm. Antituberculosis efficacy was evaluated using MABA assay against M. Tuberculosis,among the synthesised colourants compound S3furnished good activity viz MIC=3.85 μM and the remaining compounds showed moderate activity with the MIC values in the range 14.84–32.38 μM.

An Update on Synthesis of Coumarin Sulfonamides as Enzyme Inhibitors and Anticancer Agents.

Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.

Synthesis and characterization of novel sulfonamide functionalized maleimide polymers: Conventional kinetic analysis, antimicrobial activity and dielectric properties

In this study, novel maleimide monomers, N-sulfamethoxazole maleimide(SMM), and N-sulfanilamide maleimide(SAM) were synthesized. Homopolymers of SMM and SAM were obtained by free radical polymerization method in 1,4-dioxane solvent at 65 °C. The structural characterizations of monomers and their homopolymers were carried out via FTIR, 1H- and 13C-NMR techniques. The glass transition temperature (Tg) of the polymers was determined using differential scanning calorimetry (DSC). Using the thermogravimetric analysis (TGA) method determined the thermal stability of the polymers. The thermal degradation activation energies (Ea) of the polymers were calculated by Kissinger, Flynn Wall Ozawa (FWO), and Kissinger-Akahira-Sunose (KAS) methods. The biological activities of compounds have been also studied on various bacteria and fungi. The weight average (Mw) and number average (Mn) molecular weights of the polymers were determined by gel permeation chromatography (GPC). Photochemical properties of polymers were investigated with ultraviolet (UV) and fourier transform infrared (FTIR) spectra. In addition, some physical constants of polymers such as density, solubility parameter, and viscosity were determined. Finally, the dielectric constant, dielectric loss factor and ac conductivity values ​​of the polymers were estimated in the frequency range of 100 Hz–20 kHz.

Synthesis of sulfonamide based chemosensor for sensing of toxic Hg2+ ions in soil extract

Schiff base (3) was synthesized through single step condensation of sulfanilamide and isatin and characterized with 1H NMR, 13C NMR, FT-IR and mass spectrometry analysis. The probe (3) was evaluated as the fluorometric and colorimetric sensor for toxic Hg2+ ions in semi aqueous medium. The LOD and LOQ were found to be 110 and 368 nM, respectively for Hg2+ ions. Binding stoichiometry of the (3):[Hg2+] was establised to be 1:1 (with B-H and Job’s plot), which was also supported by mass spectrometry. Computational studies (TD-DFT) further confirmed the complexation of the (3) and Hg2+ ions with UPBEPBE/6-311G (d.p) level of theory. Finally recuperation studies of probe (3) were carried out with the help of EDTA and showed reusability of (3) upto 6 cycles. Also these studies assist to develp a INHIBIT molecular logic gate. The probe (3) was practically used against spiked soil extract samples and resulted good amount of recovery.

Utilization of transition metal fluoride-based solid support catalysts for the synthesis of sulfonamides: carbonic anhydrase inhibitory activity and in silico study.

The applications of solid support catalysts in catalyzing organic reactions are well-evident. In the present study, we explored a transition metal fluoride (FeF3) adsorbed on molecular sieves (4 Å) as a solid support catalyst for the preparation of sulfonamides 3a–3o. The solid support catalyst was characterized via X-ray diffraction and AFM analysis. The catalyst was further explored for the synthesis of indoles 6a–h, 1H-tetrazoles and 1,4-dihydropyridines. The sulfonamides prepared herein were investigated for their potential to inhibit carbonic anhydrase (hCA II, hCA IX and hCA XII). All compounds were found to be active inhibitors with IC50 values in the low micromolar range. Some compounds were even found to be highly selective inhibitors. Compound 3i only inhibited hCA II (IC50 = 2.76 ± 1.1 μM) and had <27% inhibition against hCA IX and hCA XII. Similarly, 3e (IC50 = 0.63 ± 0.14 μM) only inhibited hCA XII and showed <31% inhibition against hCA II and hCA IX. Molecular docking studies were carried out to rationalize the ligand-binding site interactions. Given the lack of selective CA inhibitors, compounds 3e and 3i can provide significant leads for the further development of highly selective CA inhibitors.

Synthesis of Sulfinamides, Sulfonimidamides, and Sulfonamides: A One-Pot Procedure to Rule them All

Key words boroxines - nickel catalysis - sulfinylamines - sulfonimidamides - trichloroisocyanuric acid

Direct C–H-sulfonylation of 6-membered nitrogen-heteroaromatics

Heterocyclic sulfones and sulfonamides represent important structural motives in medicinal chemistry and drug development. Therefore, efficient and reliable methods for their construction from simple building blocks are in high demand. Herein we report a novel approach for the direct C–H-sulfonylation of N-heteroaromatics via N-activation with triflic anhydride (Tf2O), base-mediated addition of a sulfinate salt and subsequent rearomatization through trifluoromethanesulfinate elimination. This operationally simple one-pot protocol enables direct access to various sulfonylated 6-ring N-heterocycles. It is applicable to the late-stage functionalization of complex, drug-like molecules. The direct incorporation of sulfur dioxide with organometallic reagents as well as the utilization of a rongalite-based sulfonylation reagent provide opportunities for a highly modular synthesis of N-heterocyclic sulfones and sulfonamides from three different building blocks.

Synthesis, Characterization and Antidiabetic Evaluation of Sulfonamide in Corporated with 1,3,4-Oxadiazole Derivatives

Synthesis, Characterization and Antidiabetic Evaluation of Sulfonamide in Corporated with 1,3,4-Oxadiazole Derivatives

Expeditious Asymmetric Synthesis of Polypropionates Relying on Sulfur Dioxide-Induced C–C Bond Forming Reactions

For a long time, the organic chemistry of sulfur dioxide (SO2) consisted of sulfinates that react with carbon electrophiles to generate sulfones. With alkenes and other unsaturated compounds, SO2 generates polymeric materials such as polysulfones. More recently, H-ene, sila-ene and hetero-Diels–Alder reactions of SO2 have been realized under conditions that avoid polymer formation. Sultines resulting from the hetero-Diels–Alder reactions of conjugated dienes and SO2 are formed more rapidly than the corresponding more stable sulfolenes resulting from the cheletropic additions. In the presence of a protic or Lewis acid catalyst, the sultines derived from 1-alkoxydienes are ionized into zwitterionic intermediates bearing 1-alkoxyallylic cation moieties which react with electro-rich alkenes such as enol silyl ethers and allylsilanes with high stereoselectivity. (C–C-bond formation through Umpolung induced by SO2). This produces silyl sulfinates that react with carbon electrophiles to give sulfones (one-pot four component asymmetric synthesis of sulfones), or with Cl2, generating the corresponding sulfonamides that can be reacted in situ with primary and secondary amines (one-pot four component asymmetric synthesis of sulfonamides). Alternatively, Pd-catalyzed desulfinylation generates enantiomerically pure polypropionate stereotriads in one-pot operations. The chirons so obtained are flanked by an ethyl ketone moiety on one side and by a prop-1-en-1-yl carboxylate group on the other. They are ready for two-directional chain elongations, realizing expeditious synthesis of long-chain polypropionates and polyketides. The stereotriads have also been converted into simpler polypropionates such as the cyclohexanone moiety of baconipyrone A and B, Kishi’s stereoheptad unit of rifamycin S, Nicolaou’s C1–C11-fragment and Koert’s C16–CI fragment of apoptolidin A. This has also permitted the first total synthesis of (-)-dolabriferol.

Functionalized GO@ZIF-90-supported sulfuric acid and its application in the catalytic synthesis of sulfonamides

Functionalized GO@ZIF-90-supported sulfuric acid and its application in the catalytic synthesis of sulfonamides

Nickel(II)-Catalyzed Addition of Aryl and Heteroaryl Boroxines to the Sulfinylamine Reagent TrNSO: The Catalytic Synthesis of Sulfinamides, Sulfonimidamides, and Primary Sulfonamides.

We report a redox-neutral Ni(II)-catalyzed addition of (hetero)aryl boroxines to N-sulfinyltritylamine (TrNSO). The reactions use a catalyst generated from the combination of commercial, air-stable NiCl2·(glyme) and a commercially available bipyridine ligand, and deliver sulfinamide products. The scope of the reaction is established using a sulfonimidamide synthesis, in which the initially formed sulfinamides undergo oxidative chlorination with the inexpensive and safe chlorinating agent, trichloroisocyanuric acid (TCCA), to produce sulfonimidoyl chlorides as key intermediates. These are combined in situ with a range of amines to deliver sulfonimidamides. The sulfonimidoyl chlorides can also be elaborated into primary sulfonamides via hydrolysis, and sulfonimidoyl fluorides via treatment with fluoride. These transformations are all achieved using one-pot procedures. Unprotected, primary sulfinamides are also available. For larger-scale reactions, the catalyst loading can be reduced to 1 mol %.

Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides.

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.

PEG-Supported Hypervalent Iodine Reagent for Sulfonamide Synthesis

AbstractA reusable and recoverable PEG-supported hypervalent iodine reagent is reported. This hypervalent iodine reagent, immobilized in a soluble polymer support, was easily prepared in six steps from PEG-OH 2000. This reagent was successfully applied in a mild sulfonamide synthesis using a sulfinate salt and an amine in up to 95% yield. The use of the soluble polymer allowed a facile workup procedure and reaction monitoring, by simple precipitation and filtration of the reagent, with an easy recovery and subsequent re-oxidation and reuse. This approach greatly improves the sustainability of this sulfonamide synthesis method, avoiding frequent preparation of reagents and generation of waste during the purification steps.

Yevheniia Markushyna.

"My biggest inspiration is the diversity and beauty of the world … My favorite thing about my lab group is the level of independency, responsibility, and trust given to each member …" Find out more about Yevheniia Markushyna in her Introducing … Profile.

Chromoselektive Synthese von Sulfonylchloriden und Sulfonamiden mit Kalium‐Poly(heptazinimid)‐Photokatalysator

AbstractUnter den zur Förderung einer chemischen Reaktion verwendeten externen Reizen, besitzt die Photokatalyse einen einzigartigen – Licht. Photonen sind spurlose Reagenzien, die eine exklusive Möglichkeit bieten, die Chemoselektivität der photokatalytischen Reaktion durch Variation der Farbe des einfallenden Lichts zu verändern. Durch die Verwendung eines Sensibilisators, welcher in der Lage ist einen spezifischen Reaktionsweg in Abhängigkeit des Anregungslichts zu aktivieren, kann diese Strategie implementiert werden. Hier verwenden wir Kalium‐Poly(heptazinimid) (K‐PHI), eine Art der Kohlenstoffnitride, um selektiv drei verschiedene Produkte aus S‐Arylthioacetaten zu erzeugen, indem wir, unter ansonsten identischen Bedingungen, einfach die Wellenlänge des Anregungslichts variieren. Dabei werden Arylchloride unter UV/violettem, Sulfonylchloride mit blau/weißem und Diaryldisulfide bei grünem bis rotem Licht erzeugt. Es wird gezeigt, dass eine Kombination aus dem negativ geladenen Polyanion, dem hochpositiven Potential des Valenzbandes, dem Vorhandensein von Intraband‐Zuständen, der Fähigkeit, Singulett‐Sauerstoff zu sensibilisieren, und dem Multi‐Elektronentransfer diese chromoselektive Umwandlung von Thioacetaten ermöglicht.

Chromoselective Synthesis of Sulfonyl Chlorides and Sulfonamides with Potassium Poly(heptazine imide) Photocatalyst.

Among external stimuli used to promote a chemical reaction, photocatalysis possesses a unique one—light. Photons are traceless reagents that provide an exclusive opportunity to alter chemoselectivity of the photocatalytic reaction varying the color of incident light. This strategy may be implemented by using a sensitizer capable to activate a specific reaction pathway depending on the excitation light. Herein, we use potassium poly(heptazine imide) (K‐PHI), a type of carbon nitride, to generate selectively three different products from S‐arylthioacetates simply varying the excitation light and otherwise identical conditions. Namely, arylchlorides are produced under UV/purple, sulfonyl chlorides with blue/white, and diaryldisulfides at green to red light. A combination of the negatively charged polyanion, highly positive potential of the valence band, presence of intraband states, ability to sensitize singlet oxygen, and multi‐electron transfer is shown to enable this chromoselective conversion of thioacetates.

Visible Light as the Key for the Formation of Carbon–Sulfur Bonds in Sulfones, Thioethers, and Sulfonamides: An Update

AbstractThis review summarizes the most relevant advancements made in the photocatalyzed synthesis of sulfones, thioethers, and sulfonamides from 2017 to the beginning of 2021. Synthetic strategies towards the construction of sulfur–carbon bonds are discussed together with the proposed reaction mechanisms. Interestingly, sulfur-based functional groups, which are of fundamental importance for the pharmaceutical field, can be assembled by photocatalysis in an easy and straightforward way under milder reaction conditions employing less toxic and expensive sulfur sources in comparison with common strategies.1 Introduction2 Sulfones2.1 Sodium Sulfinates and Sulfinic Acids2.2 Sulfonyl Halides2.3 Sulfonyl Hydrazones2.4 Sulfur Dioxide Surrogates2.5 Miscellaneous3 Thioethers4 Sulfonamides5 Conclusions

Synthesis and reactions of ω-CF3O-substituted aliphatic sulfonyl chlorides

• Aliphatic ω-CF 3 O-substituted sulfonyl chlorides were synthesized on 10–20 g scale. • Among a number of synthetic approaches studied, alkylation of thiourea – oxidative chlorination was optimal. • β-CF 3 O-ethanesulfonyl chloride was prone to β-elimination upon reaction with N -nucleophiles. • Meanwhile, the higher homologue – γ-CF 3 O-propanesulfonyl chloride – worked well in the sulfonamide synthesis. A two-step approach to the synthesis of ω-CF 3 O-substituted aliphatic sulfonyl chlorides is reported. The method is based on the reaction of alkylating agents bearing a ω-CF 3 O substituent with thiourea and subsequent oxidative chlorination of the obtained isothiuronium salt. In this way, β-(trifluoromethoxy)ethane and γ-(trifluoromethoxy)propane sulfonyl chlorides were obtained and assessed as the reagents in the sulfonylation reaction with amines. The former one participated the reaction affording the corresponding vinylsulfonamides because of β-elimination of trifluoromethanol, while the latter one allowed for the preparation of desired γ-(trifluoromethoxy)propane sulfonamides.

Frontispiece: Metal‐Free Electrochemical Synthesis of Sulfonamides Directly from (Hetero)arenes, SO2, and Amines

Electrochemical Synthesis In their Communication on page 5056, Siegfried R. Waldvogel et al. report the metal-free electrochemical synthesis of sulfonamides directly from (hetero)arenes, SO2, and amines.