Synthesis of aryl sulfonamides
The reaction of aminobenzaldehyde and dicholorotosyl chloride in presence of chloroform at ambient temperature to form impure sulfonamide compounds. Impure compounds washed with acetone and finally, crude compounds were recrystallized in acetonitrile with the good yield to form the pure product of arylaldehyde aryl sulfonamide(1).68N-arylacid aryl sulfonamide(2) was prepared by the reaction of amino benzoic acid and p-toluenesulfonyl chloride in water medium without organic solvent. The pH of the reaction was maintained due to the addition of Na2CO3 and concentrated HCl.69.Ates et al. (2012)70reported the preparation of pyrrole-p-toluene sulfonamide (3) by the reaction of heterocyclic pyrrole and p-toluenesulfonyl chloride in presence of tetra hydro furan and n-butyl lithium at temperature −78 °C under mild condition. A direct procedure for the synthesis of aryl sulfonamide derivatives(4) was reported by Kamal et al. (2008).71 The process involves the reaction of substituted arylamine and p-toluene sulphonyl chloride in presence of green solvent water at ambient temperature. The crude product of sulfonamide derivatives was purified by column chromatography on silica gel. An efficient method was developed for the synthesis of sulfonamide derivatives (5) involves two-component reaction of substituted acyl benzyl amine and tosyl-chloride using triethylamine (TEA) as catalyst and dichloromethane (DCM) as solvent at 0oC.72N-substituted -3H-benzo[d]imidazol-5-yl) benzenesulfonamide(6)compounds have been synthesized by the reaction of substituted benzo[d]imidazol-5-amine and benzene sulphonyl chloride in pyridine and acetone at room temperature.73Zarchi and Aslani,(2012)74investigated a new catalytic process for the synthesis of aryl-p-toluene sulfonamide(7). In this reaction, acetonitrile reacts with methoxyaniline in presence of catalyst poly (4-vinyl pyridine) [P4-VP] at ambient temperature. The reaction of ethyl 5-amino-3-methylbenzofuran-2-carboxylate and fluoro tosyl-chloride in dichloromethane (DCM) in presence of pyridine as a basic catalyst at ambient temperature afforded ethyl 5-(4-fluorophenylsulfonamido)-3-methylbenzofuran-2-carboxylate (8) in good yield.75
Synthesis of N, N-substituted benzenesulfonohydrazide (09) was carried out by the reaction of aryl triazenes, hydrazine and sulfur dioxide in presence of catalyst BF3.OEt2 and methylcynide at 60oC under mild conditions.76Wang et al. (2017)77developed method for the preparation of alkyl aryl sulfonamide derivatives(10). Aryl hydrazine, hydrazines and potassium metabisulfite (K2S2O5) react together in methylcynide under an air atmosphere at 40oC. In this process, aryl hydrazine was oxidized by air into aryl radicals and potassium metabisulfite was used to generate sulfur dioxide to the formation of sulfonamide derivatives.
Some sulfonamide moieties containing compounds are available for commercial importance and widely used in the clinic. Sulfonamides antibiotics are clinically approved drugs were used to prevent many infectious diseases including pathogenic bacteria known as sulfa drugs Antibacterial drugsulfisoxazole (1) were reported in the modified form such as synthesized metal (II)-sulfonamide are [Ni (sulfisoxazole)2(H2O)4].2H2O and [Cu (sulfisoxazole)2(H2O)4].2H2O were reported as efficient antibacterial agents.78-79 Some new derivatives of sulfisoxazole containing 4-thiazolidinone and 2,3-dihydrothiazoles were evaluated against micro-organisms. Synthesized derivatives of sulfisoxazole possessed promising antimicrobial activity against various bacteria and fungus.80 Sulfamethoxazole (2) is clinical used well known antibacterial drug. Synthesized complexes of lanthanide metal (La, Pr, Nd, Sm, Gd, Tb, Dy and Y) with sulfamethoxazole shows antibacterial activity.81 The potential in-vitro release sulfamethoxazole drug is due to the water-soluble nature and shows an effective antibacterial property.82Majewsky et al.,(2014)83reported the synthesizedderivatives of sulfamethoxazole and substituted sulfamethoxazole are potent antimicrobial agents. Silver complex with sulfamethoxazole84and Pt(II) and Pd(II) sulfamethoxazole complex85 were synthesized and evaluated against bacterial strains. The antibacterial drug sulfathiazole (3) and modified form reported in the literature with antibacterial activity such as Ni (II) complex with cephalosporin and sulfathiazole86, silver complex with sulfathiazole84, Cu (II) complex with nimesulide and sulfathiazole as ligand87,sulfathiazole-amantadine is a promising antibacterial agent.88 Sulfamethizole (4) drug used for the treatment of various diseases but it’s also used as an antibacterial agent. The combination of sulfamethizole with amdinocilin was reported by efficient inhibition of Escherichia coli strain of infected mouse.89 Antibiotic sulfadiazine (5) were reported in modified form such as silver sulfadiazine as an antibacterial agent90, Synthesized antibacterial metal ligand [ML(H2O)3] complex, these transition metal are [M(II)=Co, Mn, Zn and Ni] with cephalothin and sulfadiazine as ligands.91Sulfamethazine (6) used as antibacterial drug and some modified and combined structure enhanced antibacterial activities such as p-aminobenzoic acid and sulfamethazine.92 Sulfamehazineand tiamulin mixture possessed synergistic antibacterial properties against pathogenic bacteria were isolated from pigs.93The chlorothiazide and hydro chlorothiazide are the class of sulphones series were evaluated as antibacterial and antifungal.94
Sulfonamide core moiety scaffolds have been found to exhibit diverse significant biological properties also found in some natural compounds. Generally, sulfonamide moiety compounds were isolated from marine actinomycetes. Cytotoxic monoterpene-alkaloid (-)-altemicidin were isolated from active fractions of Streptomyces sioyaensis.95(-)-Altemicidin showed inhibitory activity against bacterial strains (Muralidharan andDeecaraman, 2017)96were reported mild growth inhibition against Xanthomonas species. The bromotyrosine-cysteine derivatives, psammaplin A and C were extracted from the sponge Psammaplysilla purpurea are efficient antibacterial agents.97 Nucleocidin are fluorinated sugar structure used as an antibiotic and it were obtained from soil microbe Streptomyces calvus98andStreptomyces alboflavus.99In addition, potent antibacterial activity against both Gram (positive and negative) pathogenic bacteria strains.
1.2 Thiophene moiety containing sulfonamide derivatives
For the preparation of thiophene moiety containing sulfonamide derivatives via Suzuki cross-coupling reaction, a convenient approach was published in the literature.100Thiophene moiety containing compounds are excellent bioactive agents. They have been found to exhibit various biological activities such as antimicrobial101-102, anti-HIV103, anti-inflammatory104, anticancer.105Cytochrome inhibition has been observed in some thiophene derivatives.106
Thiophene-2-sulfonamides derivatives are also regarded as inhibitors of carbonic anhydrase, and the literature indicates that diuretic activity is also seen in many of its simple derivatives.107
1.2.1 Method of preparation
Synthesis of thiophene moiety containing sulfonamide derivatives
An efficient process was developed for the synthesis of thiophene sulfonamide derivatives (1). It was two-component reactions of thiophene sulfonylcholoride and aminoacid in presence of triethylamine (Et3N) as a catalyst in solvent water and dioxane.108 These compounds were used as metalloproteinase inhibitors.The reaction of bromothiophene-2-sulfonylchloride and tert-butyl 2-aminoethylcarbamate in DCM gives tert-butyl 2-(3-bromothiophene-2-sulfonamide)ethylcarbamate which on reaction with 2-substituted oxyphenylboronic acid catalyzed by Pd(OAc)2 gives N-(2-aminoethyl)-3-(2-methoxyphenyl)thiophene-2-sulfonamides (2).109(R)-N-(2-(4-(4-(5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2oxoethyl)thiophene-2-sulfonamide (3) synthesized by the reaction of (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4-(2-aminoacetyl)piperazin-1-yl)-3-fluorophenyl)oxazolidin-2-one with 2-thiophenesulfonyl chloride in triethanolamine (TEA) and CH3CN exhibits significant antibacterial activity.110
The reaction of benzenesulfonamide and (benzothiophen-3-yl)-3-chloropropan-1-one using THF as solvent and K2CO3 as catalyst affords substituted benzothiophene (N-aryl) sulfonamide (4) in good yield.111The synthesized thiophene aryl sulfonamide (5) was evaluated in-vitro antibacterial activity against pathogenic bacteria such as B.subtilis, E.coli, B. megaterium and P.flourescens.112Thiophene moiety containing N-substituted aryl sulfonamides (6) have been synthesized from the reaction of 3-(thiophene-2-ylmethylamino)propanenitrile with p-toluenesulfonyl chloride using Et3N as catalyst and DCM as a solvent.113(E)-3-(dimethylamino)-1-(thiophene-2yl) prop-2-en-1-one reacts with 4-amino-N-substituted benzenesulfonamide in absolute ethanol and glacial acetic acid to afford (E)-4-(3-oxo-3-(thiophene-2-yl)prop-1-enylamino)benzenesulfonamide (7).114Nasr et al. (2014)115reported the synthesis of N-substituted thiophene aryl sulfonamide (8) by the condensation reaction of N-substituted isoxazole aryl sulfonamide and pyrazol-3-oxo-propanenitile in dioxane to form intermediate product under reflux condition then further reaction with isothiocyanatomethane and chloropropan-2-one in presence of NaOEt gives isoxazole-thiophene aryl sulfonamide. The compound has been found to exhibit inhibitory activity against microbes.
Some compounds of thiophene containing aryl sulfonamide possessed co-ordinate bond with various metal and act as a multi-dentate ligand. The (E)-N-(4-methoxy-1,2,5-thiadiazole-3-yl)-4-(thiophene-2-ylmethyleneamino)benzene sulfonamide(9) were used as ligand to formed metal complexes with a transition metal such metals are Fe(II), Fe(III), Co(II), Cu(II), Cd(II), NI(II) and Zn(II) were assayed antibacterial activities.116Zemede et al. (2015)117 reported the synthesis of metal complex (10), thiophene aryl sulfonamide used as ligand and attached with the transition metal. Co-ordination complex of the metal with ligands having two moles of thiophene aryl sulfonamide occurs. Such ligand and metal complexes possessed efficient antibacterial properties.
Some compounds widely used as antibacterial agents such as (oxalylamino-methylene)-thiophene sulfonamide (OMTS)(1) compound was evaluated for the selective inhibition of bacterial protein. The pathogenic bacteria, Mycobacterium tuberculosis inhibited by OMTS were reported by Grundner et al. (2007).118Naidu et al. (2015)119reported for the evaluation of 6-(4-(5-bromothiophen-2-ylsulfonyl)piperazin-1-yl)phenanthridine(2) antibacterial activity against pathogenic Mycobacterium tuberculosis bacteria.Substituted benzyl thiophene sulfonamide(3) compounds showed potent antimicrobial activity against pathogenic bacteria Campylobacter jejuni and Campylobacter coli in humans and chickens.120 The synthesized hydroxyl-thiophene containing sulfonamides(4) compound used for dyeing polyester fabrics and fabrics possessed antibacterial properties against most of the bacterial strain positive as well as negative.121
Thiophene-sulfonamide compound does not exist in a natural source. Thiophene exists in natural sources with promising biological applications but the compounds of thiophene moiety sulfonamide scaffold only available in synthesized form.
1.3 Chromene moiety containing sulfonamide derivatives
The core entity of several biologically vigorous natural products, as well as synthetic therapeutic agents, consists of unsaturated 1-benzopyran derivatives, widely known as chromenes.122The chromene nucleus is, thus, widely known in medicinal chemistry as a privileged scaffold.1234H-chromene and 2H-chromene are an isomeric form of each other, which depending on their substitution pattern, can be differentiated by the site of unsaturation and show a range of pharmacological properties. Chromene moieties play a significant role with structural aryl sulfonamide scaffold which can be easily transformed into functionalized diverse biologically active molecules.124 Naturally occurring125 and synthetic chromene compounds possess antibacterial properties.126A number of pathways are available for their synthesis, but there is a significant need for approaches that include chromenes from precursors that are readily available.127
Some synthesized sulfonamide derived chromenes were investigated for antibacterial, antifungal and cytotoxic.128 Chromone is known as a single molecule that can be paired with various receptors groups.129 Due to its useful activities and low toxicity, chromone is regarded as a desirable source for the synthesis of new drugs.130
1.3.1 Method of preparation
Synthesis of chromene moiety containing sulfonamide derivatives
Ghorab et al., (2016)131developed method for the synthesis of sulfonamides containing chromene moiety. 3-(3-Dimethylamino)propnoyl)-2H-chromen-2-one reacts with 4-amino-N-substituted benzenesulfonamide in absolute ethanol and glacial acetic acid to form (E)-4-(3-oxo-3-(2-oxo-2H-chromen-3-yl)prop-1-enylamino) benzenesulfonamide (1). Significant in-vitro antibacterial activity against pathogenic bacterial strains were reported for 4-(((2,4-dioxo-2H-chrome-3(4H)-ylidene)methyl)amino)-N-substituted benzenesulfonamide (2) compounds synthesized by the reaction of 4-hydroxycoumarin, substituted sulfonamide and ethylorthoformate in 2-butanol.132Amin et al. (2018)133developed two-step synthesis for the preparation of furo[3,2-g] chromene aryl sulfonamide (3) by the reaction of furo[3,2-g] chromene and sulfurochloridic acid to form furo[3,2-g] chromene sulfonylcholride under ambient condition. While the next step of the reaction further proceeds by the addition of amine arylsulfonamide in presence of pyridine to form main product derivatives under reflux condition with high yields.Substituted 2-oxo-N-(4-(N-(pyrimidine-2-yl)sulfamoyl) phenyl)2H-chromene-3-carboxamide (4) were synthesized by the reaction of 2-cyano-N-(4-(pyrimidine-2-yl)sulfamoyl)phenyl)acetamide with substituted salicylaldehydes in presence of fused sodium acetate in acetic acid. The compounds exhibited excellent antibacterial activity.134
Reddy et al., (2005)135reported a process in which coumarin 3-(N-aryl) sulfonamides (5) were synthesized by the reaction of 3-anilino-3-oxopropionate with substituted salicylaldehydes using piperidine as catalyst and ethanol as solvent under reflux condition.A mild new method for the synthesis of benzochromene-p-toluene sulfonamide (6) was reported by Soussi et al. (2011)136using benzochromenone and aryl sulfonamide in presence of lead acetate, cesium carbonate and xantphos as catalyst and dioxane as solvent at 100oC.Okasha et al. (2019)137 reported the synthesis of substituted (Z)-4-((2-amino-3-cyano-4-phenyl-4H-chromen-6-yl) benzenesulfonamide (7) derivatives by the reaction of benzaldehyde, malanonitrile to form 2-benzylidenemalononitrile. 2-benzylidenemalononitrile further react with (E)-4-((2, 4-dihydroxyphenyl)diazenyl)benzenesulfonamide. Whole reaction completed at reflux temperature in the presence of piperidine as a catalyst in ethanol. Synthesized derivatives were evaluated against microbes (bacteria and fungi) and possessed effective antimicrobial properties. Sabt et al., (2018)138reported a process in which2H-chromen-2-one reacts with sulfurochloridic acid at 100oC to form 2-oxo-2H-chromene-6-sulfonyl chloride. Chromene sulfonyl chloride further reacts with 1-(4-aminophenyl)ethanone in pyridine to afford N-(4-acetylphenyl)-2-oxo-2H-chromene-6-sulfonamide (8).The reaction of cyanoacetamide aryl sulfonamide and salicylaldehyde in the presence of piperidine catalyst and dioxane solvent to afford 2-iminochromene aryl sulfonamide(9) was evaluated on microbes. 2-iminochromene aryl sulfonamide processed both antibacterial and antifungal activities.139
Chromene-sulfonamide compound does not exist in a natural source. Chromene and its derivatives exist in various natural sources with promising biological applications but the compounds of chromene moiety sulfonamide scaffold only available in synthesized form.