N-substituted Sulfonamides Research Articles

ChemInform Abstract: Nucleophilic Substitution Reactions of Polyfluoroalkylsulfonamides.

Abstract The sulfonamides CF 3 SO 2 N(CH 3 )Na and CF 3 SO 2 N(H)Na have been reacted with polyfluoro cyclic, acyclic and inorganic chlorine and bromine-containing species. Nucleophilic displacement of chlorine or bromine in 1,2-dichloroperfluorocyclobutene, 1,2-dichloroperfluorocyclopentene, benzyl bromide, cyanuric chloride and oxalyl chloride has been found to occur under mild conditions to give good yields of N-substituted polyfluoroalkyl and polyfluoroaryl sulfonamides. The effects of solvent and substrate structure on the conditions necessary for reaction to occur, and the yields obtained of the desired products are discussed.

Spectroscopic, magnetic, and electrochemical studies of a dimeric N-substituted-sulfanilamide copper(II) complex. X-ray and molecular structure of the Cu 2( N-(pyridin-2-yl)biphenyl-4-sulfonamidate) 4 complex

A dinuclear copper(II) complex with a N-substituted sulfonamide as ligand has been investigated. The new N-(pyridin-2-yl)biphenyl-4-sulfonamide ligand has been prepared and structurally characterized. The copper(II) complex has been synthesized and its crystal structure, magnetic properties and EPR spectra were studied in detail. The metal centers are bridged by four nonlinear triatomic NCN groups. The coordination geometry of the copper(II) ions in the dinuclear entity is distorted square planar with two N-pyridyl and two N-sulfonamido atoms. Magnetic susceptibility data show a moderate antiferromagnetic coupling, with −2 J = 284 cm −1. The EPR spectrum of the polycrystalline sample of the title compound has been measured at the X-band frequency at different temperatures.

Structure and biological properties of first row d-transition metal complexes with N-substituted sulfonamides

Cobalt (II), copper (II), nickel (II) and zinc (II) complexes with 2-hydroxy-1-naphthaldehyde derived N-substituted sulfonamides have been synthesized and the nature of bonding and structure of compounds have been deduced from physical, analytical and spectral (IR, 1H NMR, 13C NMR, Mass and electronic) data. An octahedral geometry has been suggested for the complexes. Complexes along with the ligands were assessed for their antibacterial and antifungal activities on different species of pathogenic bacteria and fungi. The results revealed the ligands to possess moderate to significant antibacterial activity which was, in many cases, enhanced on chelation. Similar results were observed for antifungal activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.

Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

Orthogonally protected α,β-diaminopropionic acids have been synthesised in good yields by the reaction of N-trityl l-serine esters with N-substituted sulfonamides under Mitsunobu reaction conditions (DEAD, PPh 3, THF). The best isolated yields were obtained when N-Boc p-toluenesulfonamide was used as the nitrogen nucleophile precursor in the Mitsunobu reaction. Subsequently, the N-trityl group was efficiently replaced with the more stable allyloxycarbonyl (alloc) group.

Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin

A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethylsufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD50 = 2.9072 × 10− 4 and 3.2844 × 10− 4 M, respectively, displayed potent cytotoxic activity against Artemia salina

Functional superoxide dismutase mimics. Structural characterization and magnetic exchange interactions of copper(II)-N-substituted sulfonamide dimer complexes.

Dinuclear copper(II) complexes with N-substituted sulfonamide ligands as superoxide dismutase (SOD) mimics have been investigated. The new N-(thiazol-2-yl)toluenesulfonamide (Htz-tol) and N-(thiazol-2-yl)naphthalenesulfonamide (Htz-naf) ligands have been prepared and structurally characterized. The complexes derived from these ligands, [Cu(2)(tz-tol)(4)] (1) and [Cu(2)(tz-naf)(4)] (2), have been synthesized, and their crystal structure, magnetic properties, and EPR spectra were studied in detail. In both compounds the metal centers are bridged by four nonlinear triatomic NCN groups. The coordination geometry of the coppers in the dinuclear entity of 1 and 2 is distorted square planar with two N-thiazole and two N-sulfonamido atoms. Magnetic susceptibility data show a strong antiferromagnetic coupling, with -2J = 121.3 cm(-1) for compound 1 and -2J = 104.3 cm(-1) for compound 2. The EPR spectra of the polycrystalline samples of compounds 1 and 2 have been measured at the X- and Q-band frequencies at different temperatures. Above 20 K the spectra are characteristic of S = 1 species with zero-field splitting parameter D = 0.230 cm(-1) for compound 1 and 0.229 cm(-1) for compound 2. The EPR parameters are discussed in terms of the known binuclear structures. The complexes exhibit high SOD activity, as shown by the low IC(50) values obtained with the xanthine/xanthine oxidase/NBT assay: 0.13 microM for compound 1; 0.17 microM for compound 2.

Strong protective action of Copper(II) N-substituted sulfonamide complexes against reactive oxygen species

Copper(II) complexes of N-benzothiazolsulfonamides, [Cu( N-2-(5,6-dimethylbenzothiazole)toluenesulfonamidate) 2(dmso) 2] ( 1), [Cu( N-2-(6-chlorobenzothiazole)benzenesulfonamidate) 2(dmso) 2] ( 2) and [Cu( N-2-(6-chlorobenzothiazole)toluenesulfonamidate) 2(dmso) 2] ( 3) with interesting protective properties against superoxide radicals have been prepared. The compounds have been characterized by X-ray diffraction and their chemical properties have been studied by spectroscopic methods. The crystal structure of 1 shows that the copper(II) is surrounded by two benzothiazole N atoms from the sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a square planar arrangement. The coordination polyhedron around copper(II) in 2 and 3 is distorted square pyramidal being the metal ion linked to benzothiazole N and sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The three complexes have a strong protective action over Δ sod1 mutant of Saccharomyces cerevisiae against reactive oxygen radicals derived from respiration and against those generated by hydrogen peroxide and menadione.

Structural and functional models for the dinuclear copper active site in catechol oxidases: Synthesis, X-ray crystal structures, magnetic and spectroscopic properties of μ-methoxo-bridged dinuclear copper(II) complexes with N-substituted sulfonamide ligands

Two new μ-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(μ-OMe)(L)(NH 3)] 2 ( 1) and [Cu(μ-OMe)(L)(DMSO)] 2 ( 2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C 2/ c with a=22.0678(18), b=7.9134(7), c=21.1186(18)Å, β=113.788(4)° and Z=8. Compound 2 crystallizes in the monoclinic space group C 2/ c with a=18.0900(10), b=9.5720(10), c=24.2620(10) Å, β=98.7120(10)° and Z=8. In both complexes the copper atoms have square–planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2 J<−1000 cm −1). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di- tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.

Amidation of unfunctionalized hydrocarbons catalyzed by ruthenium cyclic amine or bipyridine complexes

Selective amidation of simple hydrocarbons with pre-isolated and in-situ formed iminoiodanes catalyzed by ruthenium complexes [Ru(III)(Me(3)tacn)(CF(3)CO(2))(3).H(2)O] (2b, Me(3)tacn = N,N', N"-trimethyl-1,4,7-triazacyclononane) and cis-[Ru(II)(6, 6'-Cl(2)bpy)(2)Cl(2)] (3, 6,6'-Cl(2)bpy = 6,6'-dichloro-2, 2'-bipyridine) was investigated. With PhI=NTs as nitrogen source, both catalysts efficiently promote the amidation of adamantane, cyclohexene, ethylbenzene, cumene, indan, tetralin, and diphenylmethane to afford N-substituted sulfonamides in 80-93% yields with high selectivity. Competitive amidations of para-substituted ethylbenzenes and kinetic isotope effect for the amidation of cyclohexene/cyclohexene-d(10) suggest that the amidation processes probably proceed via the hydrogen abstraction by a reactive Ru=NTs species to form a carboradical intermediate. The amidation with PhI(OAc)(2)/TsNH(2) gave results comparable to those obtained with PhI=NTs. Extension of the "PhI(OAc)(2)/TsNH(2) + catalyst 2b or 3" protocol to MeSO(2)NH(2) and PhCONH(2) with ethylbenzene as substrate produced the corresponding N-substituted amides in up to 89% yield.

A New Routine for the Synthesis of N-substituted-N-(sulfonyl) bromoacetamides with ZnCl2 as a Catalyst

A series of N-acylated N-substituted sulfonamides was prepared for the first time in good yields and with excellent conversion by the reaction of N-substituted-N-(p-toluene) sulfonamides (1) with acetyl chloride and bromoacetyl bromide (2), respectively, in the presence of a catalytic amount of anhydrous ZnCl2.

Mitsunobu-type alkylation of p-toluenesulfonamide. A convenient new route to primary and secondary amines

p-Toluenesulfonamide, which is known to form phosphine imides under Mitsunobu conditions, was shown to be alkylated in the presence of cyanomethylenetributylphsphorane to give N-substituted sulfonamides in excellent yields. The reaction can be applied to the synthesis of symmetrical and unsymmetrical N, N-disubstituted amides. When coupled with the desulfurization reactions, the reaction provides a new versatile synthetic route to primary and secondary amines from ammonia.

ChemInform Abstract: N‐Substituted Sulfonamide Carbonic Anhydrase Inhibitors with Topical Effects on Intraocular Pressure.

ChemInformVolume 18, Issue 3 Natural Products ChemInform Abstract: N-Substituted Sulfonamide Carbonic Anhydrase Inhibitors with Topical Effects on Intraocular Pressure. M. W. DUFFEL, M. W. DUFFEL Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorI. S. ING, I. S. ING Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorT. M. SEGARRA, T. M. SEGARRA Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorJ. A. DIXSON, J. A. DIXSON Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorC. F. BARFKNECHT, C. F. BARFKNECHT Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorR. D. SCHOENWALD, R. D. SCHOENWALD Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this author M. W. DUFFEL, M. W. DUFFEL Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorI. S. ING, I. S. ING Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorT. M. SEGARRA, T. M. SEGARRA Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorJ. A. DIXSON, J. A. DIXSON Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorC. F. BARFKNECHT, C. F. BARFKNECHT Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this authorR. D. SCHOENWALD, R. D. SCHOENWALD Div. Med. Chem. Nat. Prod., Pharm., Coll. Pharm., Univ. Iowa, Iowa City, IA 52242, USASearch for more papers by this author First published: January 20, 1987 https://doi.org/10.1002/chin.198703343AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue3January 20, 1987 RelatedInformation

N-Substituted sulfonamide carbonic anhydrase inhibitors with topical effects on intraocular pressure.

N-Methylacetazolamide was shown to be active topically in reducing intraocular pressure (IOP) to a small but statistically significant level in the normotensive rabbit eye. In vivo experiments with N-methylacetazolamide suggest that ocular metabolism to acetazolamide was responsible for the observed topical activity. Examination of initial rate kinetics of carbonic anhydrase catalyzed p-nitrophenyl acetate hydrolysis showed that N-methylacetazolamide was a competitive inhibitor, in contrast to noncompetitive inhibition seen with acetazolamide and other primary sulfonamide inhibitors. N-Substituted and unsubstituted 4-chlorobenzene- and 4-nitrobenzenesulfonamides were also synthesized, and their biochemical characteristics and in vivo ability to lower IOP when applied topically were determined. The primary sulfonamides were reversible noncompetitive inhibitors of carbonic anhydrase, with no effect on IOP after topical administration. 4-Nitrobenzene- and 4-chlorobenzenesulfonamides containing both N-hydroxy and N-methyl substituents were model irreversible inhibitors of carbonic anhydrase and exhibited a trend toward topical activity in reducing IOP in normotensive rabbit eyes. Therefore, this paper describes the synthesis and characterization of two types of carbonic anhydrase inhibitors; the N-methyl-substituted sulfonamides are reversible competitive inhibitors of carbonic anhydrase, while the N-hydroxy-N-methyl-substituted sulfonamides are irreversible inhibitors.

Addition of Lithium Reagents of N-Substituted Sulfonamides to Schiff Bases

Abstract Lithium reagents of N-substituted sulfonamides react with aromatic Schiff bases to give N-substituted amides of β-arylaminoethanesulfonic acids.

Telomerization of alkane- and arenesulfonamides with butadiene catalyzed by palladium complexes

The catalyzed (by palladium complexes) telomerization of butadiene with butane- and p-toluenesulfonamides, which leads to difficult-to-obtain N-substituted unsaturated sulfonamides in high yields, was realized.

Inhibition of Human Erythrocyte Carbonic Anhydrase B by Chloroacetyl Sulfonamides with Labeling of the Active Site

Abstract In an attempt to characterize the active site of human erythrocyte carbonic anhydrase B, we have studied the inhibition of this enzyme by several specific sulfonamide inhibitors and their N-chloroacetyl derivatives. In addition, two of the modified inhibitors were found to react irreversibly with the enzyme, resulting in inactivation. Enzymatic activity was determined from its catalytic hydrolysis of p-nitrophenyl acetate. The CO2-hydrating activity was also determined in some experiments and paralleled the activity determined from the esterase assays. N-Chloroacetylation at an amino group on the inhibitor far from the sulfonamide group resulted in little change or a decrease in the Ki values of the two inhibitors tested. Modification at the sulfonamide group abolished the inhibitory ability of two inhibitors, but two others retained their ability to inhibit the enzyme although the Ki values were higher. These are the only amide N-substituted sulfonamides that have been clearly shown to inhibit carbonic anhydrase reversibly. These two inhibitors, chloroacetylchlorothiazide and chloroacetylcyclothiazide, also reacted slowly with 1 eq of histidine per molecule of enzyme and caused complete, irreversible inactivation. After removal of the zinc atom from the enzyme, chloroacetylchlorothiazide failed to undergo this specific irreversible reaction. It is thought that the reactive histidine must be at or near the active site.

The Preparation of Iminosulfonic Acid Derivatives by Means of Sulfinamides and N-Bromosuccinimide

Abstract It has been found that N-substituted benzenesulfinamides (I) react with thionyl chloride to give benzenesulfinyl chloride and the corresponding N-sulfinylamines, and that they are oxidized by treatment with bromine in an alkaline solution to give N-substituted sulfonamides. When these benzenesulfinamides are treated with bromine or N-bromosuccinimide (NBS) in the presence of various primary or secondary amines, the corresponding benzeneiminosulfonamides are obtained in high yields. Similarly, the reaction of I, NBS and sodium p-nitrophenolate or sodium benzoate yields p-nitrophenyl benzeneiminosulfonate or N-benzoylbenzensulfonamide. These reactions are considered to proceed through the benzeneiminosulfonyl bromides formed by the oxidation of sulfinamides with bromine or NBS.