Sulfonamides substituents

Incorporation of less than a stoichiometric amount of alkyl sulfonamides of copper phthalocyanines into copper phthalocyanine improves the pigment s properties in rotogravure inks (67). Monomeric and polymeric phthalocyanine derivatives with basic substituents adsorb strongly to the pigment surface and promote the adsorption of binder molecules (68—72). 

Developing agents must also be soluble in the aqueous alkaline processing solutions. Typically such solutions are maintained at about pH 10 by the presence of a carbonate buffer. Other buffers used include borate and, less frequendy, phosphate. Developer solubiUty can be enhanced by the presence of hydroxyl or sulfonamide groups, usually in the A/-alkyl substituent. The solubilization also serves to reduce developer allergenicity by reducing partitioning into the lipophilic phase of the skin (46). 

The selective reaction of anionic 3,6-dichloro-4-sulfanilamidopy-ridazine with excess methanolic methoxide at the 3-position is another indication of the absence of major steric effects in most nucleophilic substitutions, as a result of the direction of nucleophilic attack (cf. Section II, A, 1). The selectivity at the 3-position is an example of the interaction of substituent effects. The sulfonamide anion deactivates both the 3-chloro (ortho direct deactivation) and... 

Systematic modification of the sulfanilamide molecule in order to maximize the hypoglycemic activity led to the observation that the sulfonamide is best replaced by a sulfonylurea function. Modification on both the aromatic ring and the substituent on the terminal nitrogen modulates the activity of the products. ... 

It has been documented in an earlier volume that appropriately substituted molecules with two strongly electron withdrawing substituents meta to one another in a benzene ring often possess diuretic properties and, even though the prototypes usually have two substituted sulfonamide moieties so disposed, other groups can replace at least one of them. An example of this is piretanide (24), where one such group is a carboxyl... 

The substrate scope is limited, as electron-withdrawing groups (X = p-N02 or p-CF3) on the aromatic substituent are not tolerated. However, this route does provide valuable intermediates to unnatural a-amino phosphonic acid analogues and the sulfimine can readily be oxidized to the corresponding sulfonamide, thereby providing an activated aziridine for further manipulation, or it can easily be removed by treatment with a Grignard reagent. 

It was found, furthermore, that the substituent on the sulfonamide group of the chiral hgand strongly influenced the enantiofacial selectivity. Hence, ligand 81 bearing a tosyl substituent delivered the endo-(2il)-cycloadduct, whereas a trifluoromethanesulfonamide group afforded its enantiomer. The authors proposed that the latter substituent should increase the Lewis acid-... 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

Results obtained in the acylation of aromatic sulfonamides with acetic acid, in the presence of SnOTf based catalysts are presented in Table 48.4. The rate of the sulfonamide acylation follows the seqnence benzenesnlfonamide > p-nitrobenzenesulfonamide > />-methoxybenzenesnlfonamide, and is very sensitive towards the nature of the aromatic hydrogen substituent (the selectivity in acylated />-methoxybenzenesnlfonamide did not exceed 7% irrespective of the catalyst nature this corresponds to an approximate relative yield... 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

Amides and sulfonamides undergo intramolecular chemistry to form aryl amides and aryl sulfonamides (Equations (17)—(19)) in the presence of palladium catalysts ligated by arylphos-phines.35,89 Initially, complexes of P(furyl)3 and P(o-tol)3 were most effective catalysts, but complexes of Hayashi s MOP and van Leeuwen s DPEphos and xantphos have lately been shown to be more active.90 In the presence of catalysts containing one of these ligand systems, five-, six-, and seven-membered rings were formed from halogenated benzamides or from substrates containing an acetamide, an A-carbobenzyloxy, or a t-butylcarbamate substituent tethered to the aryl halide (Equations (18) and (19)) ... 

With sulfonamide-derived chloramine salts bearing smaller organic substituents on the sulfur, for example, methanesulfonamide-derived chloramine salt 111 (chloramine-M) as the oxidant, better results are obtained. This reagent can be prepared separately and added to the reaction mixture as the stable anhydrous... 

Numerous y-secretase inhibitors featuring sulfonamide- and sulfone-based scaffolds have been disclosed. Bicyclononane thiophene sulfonamide 40 reduced brain Ap in transgenic mice by 50% after a dose of 100 mg/kg [100]. High potency (A p IC50 = 0.5 nM) and improved oral activity (ID50 = 17 mg/kg) was found in a series of related sulfamides represented by 41 [101]. Tetrahydroquinoline (42) and piperidine (43-44) sulfonamides have been developed [102-104]. Elaboration of the piperidine series with the cyclopropyl substituent present in 44 improved in vitro potency (Aft IC50 = 2.1 nM in membrane assay) and in vivo activity in transgenic mice (plasma Ap = 2% of control after oral dose of 30 mg/kg). Reductions of A p in the cortex were reported to be comparable to those observed in plasma. 

A Jain, S. G. Huang, G. M. Whitesides, Lack of Effed of the Length of Oligoglydne- and 01igo(ethylene glycol)-Derived para-Substituents on the Affinity of Benzene-sulfonamides for Carbonic Anhydrase II in Solution ,/ Am. Chem. Soc. 1994,116,5057-5062. 

These data, e.g. predominant thiolytic cleavage of the semimercaptal at physiological GSH concentrations, is in line with the expected behavior in considering the positive Hammett constant of the sulfonamide substituent (op = +0.5855). It is to be expected that cells with lowered GSH content or impaired enzymic capacity to reduce GSSG will be... 

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