Sulfonyl Hydrazides Research Articles

Lewis Acid‐Promoted C−H Chalcogenation of Arenes and Heteroarenes

AbstractAn efficient catalytic system employing TMS•OTf for the regioselective thiolation of electron‐rich arenes with sulfonyl hydrazides has been developed. The reaction occurs in a solvent mixture of dichloroethane and trifluoroethanol under mild conditions, with the addition of water. This method furnishes a range of para‐thio‐substituted arenes and 3‐sulfenyl‐indoles in good to excellent yields, marking a significant advancement in organic synthesis.

One‐Pot Synthesis of Pyrazoles from Sulfonyl Hydrazides and Alkynyl Ketones Using Environmentally Benign Sulfonium Iodate (I) Reagent

AbstractPyrazole is an omnipresent moiety in many natural products and pharmaceutically active compounds. Here, we have developed a simple and dynamic method for one‐pot synthesis of substituted pyrazoles through the intramolecular cyclization of hydrazides and alkynyl ketones, using a novel sulfonium saltbased iodate (І) reagent system. This method has the advantage that it proceeds in a one‐pot, without isolating a less stable hydrazone intermediate. Hypervalent iodine‐based reagents are an environmentally benign and greener option to toxic metal oxidants; they have an extensive application in metal‐catalyst‐free reactions, and this reaction proceeds in less time with high yields.

Design, Synthesis, Anticholinesterase and Antidiabetic Inhibitory Activities, and Molecular Docking of Novel Fluorinated Sulfonyl Hydrazones.

In this study, it was aimed to synthesize (E)-N'-(2-hydroxybenzylidene)-substituted benzenesulfonohydrazide (1-7) from the 2-hydroxybenzaldehyde reaction of different substituted fluorinated sulfonyl hydrazides. The structures of the synthesized molecules were characterized by elemental analysis, FTIR, 1H NMR, 13C NMR, 19F NMR, and 2D NMR (HMBC, correlation spectroscopy, and HQSC). The anticholinesterase (AChE and BChE) and antidiabetic (α-glucosidase, α-amylase) inhibition activities of the synthesized compounds were evaluated. According to biological activity test results, (E)-N'-(2-hydroxybenzylidene)-4-(trifluoromethoxy)benzenesulfonohydrazide (compound 7 among hydrazone derivatives 1-7) demonstrated better BChE inhibitor activity than galantamine in anticholinesterase inhibition; and in the α-glucosidase and α-amylase assay, it exhibited more antidiabetic inhibition activity than the reference standard.

Synthesis of N-Acyl-N′-Sulfonyl Hydrazides from Sulfonyl Hydrazides and Activated Amides

AbstractA methodology was developed for synthesizing N-acyl-N'-sulfonyl hydrazides through acyl substitution reactions between activated amides and arylsulfonyl hydrazides. Optimization of the reaction conditions revealed that using Cs₂CO₃ as a base and 1,4-dioxane as a solvent at 25 °C for 12 hours produced the highest yields. Among various amides tested, N-benzoylsuccinimide was found to be the most reactive, with reduced reactivity observed for N-mesityl-, N-tosyl-, and N-Boc-substituted tertiary benzoyl amides. Cross-reactions between a diverse range of N-benzoylsuccinimides and arylsulfonyl hydrazides successfully produced the corresponding N-acyl-N′-sulfonyl hydrazides with yields ranging from 63% to 94%.

Iodophor-/H2O2-Mediated 2-Sulfonylation of Indoles and N-Methylpyrrole in Aqueous Phase.

A convenient and efficient strategy for the preparation of 2-sulfonylindoles has been achieved through iodophor-/H2O2-mediated 2-sulfonylation of indoles with readily available sulfonyl hydrazides in the aqueous phase. Iodophor is commercially available and serves as the green catalyst and aqueous phase. A series of 2-sulfonylated products from indoles and N-methylpyrrole were synthesized in moderate yields in only 10 min. Control experiments were also conducted to reveal the mechanism of action. This method is environment friendly, easy to operate and suitable for a wide range of substrates.

Molecular Hybrid Design, Synthesis, In Vitro Cytotoxicity, In Silico ADME and Molecular Docking Studies of New Benzoate Ester-Linked Arylsulfonyl Hydrazones.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

Electrochemical Sulfonylation/Cyclization of N-Alkenylacrylamides with Sodium Sulfinates or Sulfonyl Hydrazides.

Two general protocols for the regioselective electrochemically enabled sulfonylation cyclization of N-alkenylacrylamides with sodium sulfinates or sulfonyl hydrazides were described. These methods were carried out under mild, chemical oxidant-free, and transition-metal-free conditions with a broad substrate scope and good functional group tolerance to provide sulfonyl-containing 4-pyrrolin-2-ones, which is readily scalable to the gram scale.

Iodine promoted sulfenylation of pyrrolo[1,2-a]quinoxalines with sulfonyl hydrazides

A method for transition-metal-free sulfenylation of pyrrolo[1,2-a]quinoxalines was developed. Selective functionalization of C1H bonds was achieved via an electrophilic substitution with thiodiazonium adduct presumably derived from combination of sulfonyl hydrazides and molecular iodine. The conditions were well tolerated with a wide range of functionalities as well as heterocycles. Our method would offer a rare example for direct sulfenylation of C1H bonds in pyrrolo[1,2-a]quinoxalines in the absence of transition metals or strong oxidants.

Pushing Boundaries: What's Next in Metal-Free C-H Functionalization for Sulfenylation?

The synthesis of thioether derivatives has been explored widely due to the potential application of these derivatives in medicinal chemistry, pharmaceutical industry and material chemistry. Within this context, there has been an increasing demand for the environmentally benign construction of C-S bonds via C-H functionalization under metal-free conditions. In the present article, we highlight recent developments in metal-free sulfenylation that have occurred in the past three years. The synthesis of organosulfur compounds via a metal-free approach using a variety of sulfur sources, including thiophenols, disulfides, sulfonyl hydrazides, sulfonyl chlorides, elemental sulfur and sulfinates, is discussed. Non-conventional strategies, which refer to the development of thioether derivatives under visible light and electrochemically mediated conditions, are also discussed. The key advantages of the reviewed methodologies include broad substrate scope and high reaction yields under environmentally benign conditions. This comprehensive review will provide chemists with a synthetic tool that will facilitate further development in this field.

Iodosulfonylation of [1.1.1]Propellane

AbstractAn efficient disubstituted functionalization of [1.1.1]propellane has been developed. The protocol utilizes sulfonyl hydrazides and N-iodosuccinimide, enabling the introduction of iodine and sulfonyl groups into bicyclo[1.1.1]pentane (BCP) in moderate to excellent yields. It has the advantages of simple operation, mild conditions, and broad substrate scope.

Synthesis of Naphthalimide Azocarboxylates Showing Turn-On Fluorescence by Substitution Reaction with Sulfinates.

The synthesis and characterization of sulfinate addition-responsive fluorescent molecules are described. We found that addition reaction of sulfinates to naphthalimide-substituted azocarboxylates afforded the corresponding sulfonyl hydrazides with high fluorescence quantum yields (up to 0.91 in THF and 0.54 in methanol), which exhibited a large Stokes shift (105 nm) in protic methanol solvent, while the unsubstituted hydrazide and the sulfonyl-position isomer showed no fluorescence in polar solvents.

Electrochemical Synthesis of Selenosulfonates from Diselenides and Sulfonyl Hydrazides.

The electrochemical oxidative radical-radical cross-coupling of sulfonyl hydrazides with diselenides for the synthesis of selenosulfonates was successfully accomplished. The method is applicable to a wide range of aromatic/aliphatic sulfonyl hydrazides and diselenides, providing products in good to excellent yields. Notably, this protocol stands out for its green and sustainable nature, as it does not rely on transition metals and oxidizing agents, and the starting materials are cost-effective and readily available.

Hypervalent Iodine Mediated Synthesis of Thiosulfonates from Sulfonyl Hydrazides and Their Transformation into Symmetrical Disulfides

AbstractA transition-metal-free synthesis of thiosulfonates has been accomplished by the disproportionate coupling of readily available and inexpensive sulfonyl hydrazides embracing hypervalent iodine(III) [phenyliodine(III) diacetate (PIDA)] as an oxidant. This synthesis involves cleavage of the S–N bond and is endowed with creation of a new S–S bond. The thiosulfonates were further reduced with CS2/KOH to obtain symmetrical disulfides. This protocol features mild reaction conditions in open air, an inexpensive oxidant, and high functional group tolerance with good to excellent product yields.

Electrochemical Radical Retro-Allylation of Homoallylic Alcohols with Sulfonyl Hydrazides.

We report herein the first examples of electrochemical radical retro-allylation of homoallylic alcohols via the cleavage of the C(sp3)-C(sp3) bond. In this reaction, a variety of sulfonyl hydrazides were employed as the environmentally friendly radical sources via an electrochemical dehydrazination with the release of N2 and H2 as the byproducts, leading to sulfonyl allylic compounds in moderate to good yields. The reaction features metal- and base-free reaction conditions, broad functional group tolerance, and a broad substrate scope.

Electrochemical synthesis of sulfinic and sulfonic esters from sulfonyl hydrazides.

An electrochemical synthetic method for the synthesis of sulfinic esters and sulfonic esters from sulfonyl hydrazides was developed. Alkyl sulfinic esters were synthesized by treating sulfonyl hydrazides with trialkyl orthoformate in a DMF solvent at a constant current of 5 mA and then optimizing the reaction conditions. Conversely, alkyl sulfonic esters were exclusively obtained when the reaction was conducted in alkyl alcohol solvents at a constant current of 15 mA. The various substituted arylsulfonyl hydrazides afforded moderate to good yields of the desired sulfinic esters and sulfonic esters. Mechanistic investigations revealed that sulfonyl radicals were formed through electrochemical oxidation and that they react with alkyl radicals or alkoxy radicals to generate the respective ester products.

Catalyst-free regioselective sulfonylation of phenoxazine with sulfonyl hydrazides in H2O/HFIP.

A facile catalyst-free sulfonylation of phenoxazine with sulfonyl hydrazides was efficiently developed in H2O/HFIP without any catalyst. This metal- and catalyst-free protocol is suitable for aromatic and aliphatic reagents to afford the corresponding sulfones in moderate to high yields. A gram-scale experiment was performed to assess the practicability of the method.

Catalytic oxidative cyclization of α-carbonyl-γ-alkynyl sulfoxonium ylides for stereospecific synthesis of (1Z,3Z)-1,3-bismethyleneisobenzofurans

A new copper(ii)-catalyzed reaction of α-carbonyl-γ-alkynyl sulfoxonium ylides with sulfonyl hydrazides in the presence of tert-butyl hydroperoxide (TBHP) is reported, regio- and stereoselectively accessing (1Z,3Z)-1,3-bismethyleneisobenzofurans.

Iodophor-catalyzed sulfenylation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles

An iodophor-catalyzed 3-sulfenylation of indoles using sulfonyl hydrazides as sulfur source in aqueous phase has been achieved. Iodophor as catalyst and solvent is inexpensive, commercially available and no innocuous to the environment.

N-Sulfonylation of azoles with sulfonyl hydrazides enabled by electrocatalysis

We report an electrochemical strategy for N-sulfonylation of azoles with sulfonyl hydrazides via radical–radical cross-coupling.

Neutral nickel-catalyzed dehydrosulfonylation of unactivated allylic alcohols under mild conditions.

Allyl sulfones are important sulfur-containing compounds that have widespread applications in organic synthesis, medicinal chemistry and materials science. Herein, nickel-catalysed dehydrosulfonylation of unactivated allyl alcohols with aryl sulfonyl hydrazides without additional active agents under mild conditions was developed. A variety of functional allyl sulfones could be efficiently synthesized in the presence of air-stable Ni(acac)2 as the catalyst and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) as the ligand.