Sulfamoyl Chlorides Research Articles

Access to β‐Lactam Sulfonamides from Sulfamoyl Chlorides via Photoredox Catalyzed C−S Bond Formation

AbstractSulfonyl chlorides are a synthetically attractive source of sulfonyl radicals in photoredox catalysis and are useful precursors in the synthesis of sulfones. Sulfamoyl chlorides, on the other hand, remain poorly represented despite their similar potential. In this study, N‐chlorosulfonylated β‐lactams were prepared from readily available precursors and utilized in an atom transfer radical addition (ATRA) reaction with a variety of olefins, producing β‐lactam sulfonamides in 49–95% yields. β‐Lactams fused to a dihydro‐1,2‐thiazine ring which closely resemble carbacephems, a widely used class of antibiotics, were also synthesized by an intra‐molecular ATRA reaction. This methodology enables the preparation of β‐lactam sulfonamides, a class of compounds that are of great interest in pharmacology.

Photocatalyst-Free Activation of Sulfamoyl Chlorides for Regioselective Sulfamoyl-Oximation of Alkenes via Hydrogen Atom Transfer (HAT) and Halogen-Atom Transfer (XAT) Relay Strategy.

The use of readily available and diverse sulfamoyl chlorides for synthesizing sulfonamide compounds presents an intriguing, yet significantly underexplored strategy. Activating sulfamoyl chlorides via single-electron reduction poses challenges due to their high reduction potential. Alternatively, the SO2-Cl bond in sulfamoyl chlorides could be readily cleaved by XAT. However, the existing methodologies have been limited to either the use of photocatalyst or the monofunctionalization of activated alkenes. Here, we report a regioselective sulfamoyl-oximation of alkenes by involving the activation of sulfamoyl chlorides through a HAT and XAT relay strategy in a photocatalyst-free way. The key to this success lies in the dual roles of tert-butyl nitrite (TBN), which not only serves as the source of oximes but also acts as the HAT reagent to generate the crucial XAT reactive species. The exclusion of metal catalysts or photosensitizers for utilizing light energy renders this protocol versatile and universally applicable for synthesizing a broad range of structurally diverse oxime-containing alkyl sulfonamides.

Modular access to diarylmethyl sulfonamides via visible light-promoted cross-coupling reactions.

We report a novel and efficient method for the preparation of diarylmethyl sulfonamide derivatives through visible-light-induced sulfamoylation of para-quinone methides with sulfamoyl chlorides under mild, metal-free conditions. This protocol demonstrates excellent tolerance toward a wide range of functional groups, affording the corresponding products in moderate to high yields. Preliminary mechanism studies revealed that the excited photocatalyst rhodamine 6G* was mainly quenched by para-quinone methides and the generated diarylmethyl radical intermediates then underwent radical-radical cross-coupling with sulfamoyl radicals to yield the diarylmethyl sulfonamides.

Synergistic Photoredox and Iron Catalyzed 1,2-Thiosulfonylation of Alkenes with Thiophenols and Sulfonyl Chlorides.

Herein, a three-component 1,2-thiosulfonylation of alkenes with thiophenols and sulfonyl chlorides via synergistic photoredox and iron catalysis is described. Compared with previous studies, this protocol avoids tedious pre-synthesis of thiosulfonates and employs more readily accessible sulfonyl chlorides as a sulfonation reagent. Moreover, the reaction exhibits high compatibility with styrenes and unactivated alkenes as well as diverse sulfonyl chlorides, especially sulfamoyl chlorides. Preliminary mechanism investigations reveal that a radical pathway is involved in the catalytic cycle.

Photoinduced Vicinal 1,2-Difunctionalization of Olefins for the Synthesis of Alkyl Sulfonamides.

Alkyl sulfonamides are an important class of bioactive molecules. Historical syntheses have relied on multistep sequences incorporating harsh reaction conditions. Photochemical methods have been limited to hydrosulfamoylation, installing only one substituent across an olefin. Herein, radical/polar crossover (RPC) is used to establish the first multicomponent 1,2-difunctionalization reaction incorporating a sulfonamide moiety and a second reaction partner. This protocol, exemplified on a range of olefins, utilizes various commercial sulfamoyl chlorides and organotrifluoroborates as coupling partners.

Photocatalytic C(sp2)–H sulfamoylation of enamides: regio- and stereoselective construction of (E)-β-sulfamoyl enamides

A photocatalytic, regio- and stereoselective olefinic β-C–H sulfamoylation of enamides with commercially available sulfamoyl chlorides was developed.

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides.

There have been several studies on the solvolysis mechanisms for alkanesulfonyl chlorides (RSO2Cl) and arenesulfonyl chlorides (ArSO2Cl). The earlier of these studies were reviewed a little over thirty years ago by Gordon, Maskill and Ruasse (Chem. Soc. Rev. 1989, 18, 123–151) in a contribution entitled “Sulfonyl Transfer Reactions”. The present review will emphasize more recent contributions and, in particular, the application of the extended Grunwald–Winstein equation and kinetic solvent isotope effects to the solvolysis reactions. There is also an appreciable number of reports concerning the corresponding anhydrides with the chloride leaving group replaced by the appropriate sulfonate leaving group, concerning sulfamoyl chlorides (ZZ'NSO2Cl) with Z and Z' being alkyl or aryl and concerning the solvolysis of chlorosulfate esters (alkoxy- or aryloxysulfonyl chlorides), with the structures ROSO2Cl or ArOSO2Cl. The solvolyses of these additional types of sulfur(VI) substrates will be the topics of a future review.

The photoredox-catalyzed hydrosulfamoylation of styrenes and its application in the novel synthesis of naratriptan.

The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.

Easy Access to Aliphatic Sulfonamides using Sulfamoyl Chlorides Under Visible Light Activation.

Sulfonamides are prevalent motifs in marketed drugs and natural products. Their synthesis represents a great interest to the pharmaceutical industry, due to their unique biological properties. Recently, several methods for the synthesis of aryl sulfonamides have been developed, but little effort has focused on developing one-step methodologies to access sulfonamides flanked by two alkyl groups. This protocol describes a practical and facile method for the net hydrosulfamoylation of electron-deficient alkenes using sulfamoyl chlorides as radical precursors under blue-light activation. This practical and cost-effective methodology is performed in the presence of the metal-free photocatalyst Eosin Y and uses light as a clean and traceless energy source. The procedure is scalable, displays a broad functional group tolerance, and can be applied for late-stage functionalization. All reagents used in this protocol are commercially available. Simple reaction set-up, the absence of work-up and easy purification, demonstrate the convenience of this protocol. The reaction is best applied to electron-deficient alkenes.

Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes.

Single electron reduction is more challenging for sulfamoyl chlorides than sulfonyl chlorides. However, sulfamoyl and sulfonyl chlorides can be easily activated by Cl-atom abstraction by a silyl radical with similar rates. This latter mode of activation was therefore selected to access aliphatic sulfonamides, applying a single-step hydrosulfamoylation using inexpensive olefins, tris(trimethylsilyl)silane, and photocatalyst Eosin Y. This late-stage functionalization protocol generates molecules as complex as sulfonamide-containing cyclobutyl-spirooxindoles for direct use in medicinal chemistry.

Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions

Isoquinolines activated with sulfamoyl chlorides were reacted with indoles in a 3-component reaction to generate a library of dihydroisoquinoline derivatives. Using a differential protecting group strategy, products could be further derivatised. Synthesis of isoquinoline starting materials using several different methods is also described.

Flash vacuum pyrolysis of sulfamoyl azides and chlorides: Facile gas-phase generation of transient N-sulfonylamines

Two sulfamoyl azides, H2NS(O)2N3 and MeN(H)S(O)2N3, have been isolated as neat substances and characterized. The solid-state structure of the parent molecule H2NS(O)2N3 has been established with X-ray crystallography. The thermal decomposition of both azides has been studied by combining flash vacuum pyrolysis (FVP, 400 °C) and matrix-isolation IR spectroscopy. In addition to the complete dissociation fragments for H2NS(O)2N3 (SO2, N2, and H2) and MeN(H)S(O)2N3 (SO2, N2, and CH2NH), the retro-ene decomposition products HN3 and N-sulfonylamines HNSO2 and MeNSO2 form, respectively. Alternatively, quantitative yield of both N-sulfonylamines in the gas phase occurs when sulfamoyl chlorides H2NS(O)2Cl and MeN(H)S(O)2Cl are used as the FVP precursors (400 °C). Consistent with these experimental observations, computational studies on the potential energy profiles for the decomposition of the two azides at the CCSD(T)/aug-cc-pVTZ//B3LYP/6-311++G(3df,3pd) level conclusively suggest that the N2-elimination is energetically more favorable than the HN3-elimination through either retro-ene reaction or 1,2-elimination. In contrast, the facile HCl-elimination from sulfamoyl chlorides provides a general method for the gas-phase generation of N-sulfonylamines, which were known as transient reactive intermediates in synthetic chemistry.

Palladium–copper-catalyzed desulfitative amination of benzo[d]oxazole C–H bond

An efficient palladium–copper-catalyzed direct C–H amination of substituted benzoxazoles with various sulfamoyl chlorides as nitrogen group sources has been developed. The system does not need a strong base and tolerates a series of functional groups, such as chloro, methyl, and nitro groups, providing the amination products in moderate to excellent yields.

Ionic liquid enabled sulfamoylation of arenes: an ambient, expeditious and regioselective protocol for aryl sulfonamides

The ionic liquid, 1-butyl-3-methylimidazolium chloroaluminate, [bmim]Cl·AlCl 3, N=0.67 mediated syntheses of aromatic sulfonamides via electrophilic substitution of arenes is reported. The protocol serves as a distinctly expeditious and ambient route towards the syntheses of these pharmaceutically useful compounds, yielding quantitative conversions at room temperature within 5–30 min in most of the cases. The Lewis acidity and molar stoichiometry of the ionic liquid influences the extent of conversion. The method has been used for the syntheses of a diverse range of sulfonamides by variation of arenes and sulfamoyl chlorides. With monosubstituted benzenes, the protocol offers an added advantage of exclusive selectivity towards the formation of para substituted sulfonamides over the ortho products.

Catalytic Arylation of Sulfamoyl Chlorides: A Practical Synthesis of Sulfonamides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic Arylation of Sulfamoyl Chlorides: A Practical Synthesis of Sulfonamides

Commercially available indium(III) triflate is shown to be an efficient catalyst for the sulfamoylation of aromatics.

Elimination mechanisms in the anilinolysis of sulfamoyl chlorides in chloroform and acetonitrile

The kinetics of the reaction of various sulfamoyl chlorides, R1R2NSO2Cl (R1 = Ph, Me, c-C6H11, But, R2 = H and R1 = R2 = Me and R1 = R2 = PhCH2) with anilines in chloroform and acetonitrile have been studied. Reaction is first order in both chloride and aniline and pseudo first order and second order rate constants have been determined for various chlorides and para- and meta-substituted anilines. Hammett ρ values vary from –4.76 to –2.63 for varying XC6H4NH2 depending on the halide, X. Substituents in XC6H4NHSO2Cl have only small effects on the rates. There is a ca. 106-fold rate difference between PhNHSO2Cl and (PhCH2)2NSO2Cl reacting with p-anisidine in chloroform at 25 °C. This finding, coupled with the observation of hydrogen/deuterium isotope effects, supports the operation of an elimination mechanism involving an N-sulfonylamine, [PhNSO2], as a transient species. In chloroform an E2-type mechanism is suggested, while in acetonitrile the activation parameters (ΔH, ΔS) may indicate a more E1cB-like E2 mechanism.

ChemInform Abstract: Reaction of N‐Sulfonylimines with Methylenediamines.

AbstractThe N‐alkylsulfonylimines (II), generated in situ from the sulfamoyl chlorides (I), react with the diaminomethanes (III) to give the asymmetric sulfamides (IV) and/or (V) depending on the substituents.

ChemInform Abstract: Synthesis of 1,2,5‐Thiadiazolidin‐3‐one 1,1‐Dioxides: X‐Ray Structure Determination of 4,4‐Diphenyl‐1,2,5‐thiadiazolidin‐3‐one 1,1‐Dioxide.

AbstractChlorosulfonyl isocyanate (I) is converted into the sulfamoyl chlorides (III) which are coupled with diphenylglycine methyl ester (IV), yielding the diphenylmethoxycarbonylmethylsulfamides (V).

SULFAMOYLATION OF ESTER ENOLATE ANIONS

Abstract Stabilized carbanions such as the α-carbanions of carboxylic acid esters react with sulfamoyl chlorides by nucleophilic displacement at chlorine which results in chlorination of the carbanion. Thus direct sulfamoylation of these carbanions with sulfamoyl chlorides fails. Conversion of sulfamoyl chlorides to N-sulfonylamines followed by addition of carbanions at -78°C results in sulfamoylation of the carbanion. The method has not been successful with carbanions from diethyl acetamidomalonate and ethyl diphenylacetate.