Sulphonamide moiety

Interestingly, the sulphonamide moiety which essentially possesses a geometric structural entity thus allowing an equally perfect fit compatible into the cavity of the enzyme CA also get bound quite securedly and effectively, perhaps to the same four areas by H-bonds as depicted in Fig. 14.1(Z)). 

The palladium catalysed addition of N-H or O-H bonds onto allenes has successfully been exploited in the preparation of oxazepines, diazepines, oxazocines and diazocines. The nucleophilic attack of the pendant alcohol or sulphonamide function on the allene moiety was followed by the incorporation of the alcohol, used as solvent, to give the desired cyclic products in good yield (5.15. and 5.16.). The bromoallene in these processes is the synthetic equivalent of an allylic dication.15... 

Further evidence against the ECbECN carbocation mechanism is claimed by Sartori and co-workers [186] from their work on the fluorination of N,N-dime-thyltrifluoromethanesulphonamides at different temperatures (-15°C and + 5°C). According to the carbocation mechanism, it is stated, introduction of fluorine atoms into the sulphonamide should take place stepwise, first in one methyl group and then into the other however, detailed examination of the reaction mixture by 19F NMR spectroscopy showed no trace of compounds containing the moieties... 

In sulphonamides, the 33S chemical shift is sensitive to the electronic properties of both the a-group and of the substituent on the nitrogen atom.64 The replacement of both hydrogen atoms of the -NH2 moiety with methyl groups induces a downfield shift of 23 ppm, and the substitution of one hydrogen bond with another NH2 group causes a downfield shift of 18 ppm. 

Accordingly, the spectrum of applicability of these CSPs can be derived. It appears that cellulose- and amylose-carbamate CSPs are excellent for the enantioseparation of SAs with hydrogen donor and/or acceptor sites (amides, carbamates, sulphonamides, hydroxy groups) as well as aromatic moieties, advantageously in combination with bulky groups close to the interaction sites. Due to the broad range of applicability a more detailed list of resolvable SAs would extend this report. However, further information is available from the application guide [172], from review articles [47,99,1(X), and from recently published enantioseparations (Table 9.4). 

The sulfasalazine molecule comprises sulfa-piridine and 5-aminosalicylic acid linked by an azo-bond which is split by colonic bacteria, releasing the component parts. Sulfapiridine, as a sulphonamide, has an antifolate action which is believed to benefit rheumatoid arthritis, while it is the salicylate moiety that is thought to be effective in inflammatory bowel disease a fuller description appears on page 64. Sulfasalazine is used as a DMARD for rheumatoid arthritis, spondyloarthropathy with peripheral joint involvement, and psoriatic arthritis. 

In the previous sections we have discussed reactions in which the carbon-azide bond is formed by substitution on carbon of a preformed azide moiety or by its addition to various multiple bonds. Processes in which the azide nitrogen atoms are introduced in a stepwise manner are now considered. These syntheses include the reactions of diazo-nium salts with nucleophiles such as ammonia, chloramine, hydroxyl-amine, hydrazine, sulphonamides and azide ion. Recent work on... 

Binary encoding technology [71-73] has been used to identify selective CAII inhibitors from two libraries (6,727 members and 1,143 members) [419, 420]. The first library was composed of acyclic and cyclic amino acids and the second library was composed of dihydrobenzopyrans. The arylsul-phonamide moiety, a known pharmacophore for CAII inhibition, was included in order to bias the library. The active compounds identified from the first library exhibited a preference for lipophilic groups at R2 (library 35 Kd 4 nM) [419]. Again active members from the 1143 dihydrobenzopy-ran compound library were 4-carboxybenzene sulphonamide derivatives (library 36 Kd 15 nM) [420],... 

Sulphonamides are stable to oxidation and any use of oxidation agents in analysis must be accompanied by a drastic reaction, e.g. oxidation with H202 gives sulphate, detected by Ba(II)177 or similar oxidation and then determination of the ammonia moiety of the ammonium sulphate formed402. Such methods must apply to many classes of sulphur-containing compounds. 

The latter reaction occurs with all types of substituents R1 and R2 (aliphatic or/and aromatic) since the presence of an aromatic moiety associated with the —S02— group renders the whole class of aromatic sulphonamides electroactive. On the other hand, anilides of aliphatic sulfonic acids are not reduced under similar experimental conditions (aqueous electrolyte) as given in Reference 2. Thus the presence of the arenesulphonyl group appears then to be a necessary condition to permit the preliminary electron transfer and therefore to allow the deprotection of amines. 

Chlorosulphonation of 4 -chloro-o-acetotoluidine yields the eorresponding sulphonyl chloride derivative whieh on amination forms the sulphonamide derivative. Oxidation of the methyl moiety gives the respeetive anthranilamide derivative whieh on hydrolysis eliminates the acetyl group to yield the substituted anthranilic acid. Fusion of this amino acid with propionamide first gives rise to an intermediate by the loss of a mole of water and ultimately helps in the closure of the ring to generate the quinazoline ring system. Catalytic reduction of this finally produces the official compound. 

Furthermore, it can be expatiated by considering the fact that because the proton-donating form of the functional moiety (i.e., sulphonamide) bears absolutely no charge, one may even characterize the same as an HA acid, just in the same vein as phenols, thiols and carboxyl groups. 

Toluene-p-sulphonyl chloride either on heating with ammonium carbonate or liquid ammonia replaces the chloro group with an amino moiety to result the formation of toluene-p-sulphonamide and a mole of HCl gets eliminated. 

Tiimethylsilyl)ethanesulphonyl chloride, Me3SiCH2CH2S02Cl, is useful for the protection of primary and secondary amines as sulphonamides, which are smoothly cleaved by fluoride ion. Use of the triazene moiety as a protecting group for aromatic amines is illustrated in eqnation 110. The protected compounds react with s-butyllithium, followed by an electrophile E (carbon dioxide, acetophenone or trimethylsilyl chloride), to give, respectively, the corresponding carboxyhc acid, alcohol or trimethylsilyl daivative, which are converted into the free amines by the action of nickel -aluminium alloy in aqueous-methanolic potassium hydroxide-... 

More recently, several polymer versions of the efficient Corey-Bakshi-Shibata (CBS) catalyst have been prepared [47], Different approaches have been used to bind the catalytic moieties to the polymer support the diphenyl prolinol reacted with beads bearing benzene sulfonyl chloride residues (catalytic moieties boimd to the nitrogen atom as part of a sulphonamide link), the diphenyl prolinol is boimd to a polymer support or the aminoalcohol... 

The R substiment represents the only possible moiety that can be altered in the generic sulphonamide stmcture without impairing antibacterial activity. 

---