Benzothiazole-2-sulfonamide

Although the shrewd deductions of Schwartz from the accumulated observations were correct, and sulfanilamide proved to be a diuretic, the dose required was large and there were marked side effects. From this beginning, many laboratories set out to find other orally effective sulfonamides with greater potency and fewer unwanted actions. In 1950, Roblin and coworkers (43, 48) of the American Cyanamid Laboratories reported that heterocyclic sulfonamides show a high order of in vitro carbonic anhydrase inhibitory activity. Among the most active compounds was benzothiazole-2-sulfonamide, which had a potency several hundredfold (730 to 2500) that of sulfanilamide. 

The reaction of benzothiazole-2-sulfonamides with hydroxylamines yields the corresponding 2-hydroxybenzothiazoles. Here there is evidence that hydroxylamine, unusually, is acting as an oxygen nucleophile and attacks the benzothiazole to form... 

Other compounds under consideration include ammoniacal copper-fatty acids, isothiazolinones, benzothiazoles, sulfonamides, tetrachloroisophthalonitrile, salicylanilide derivatives, and 3-iodo-2-propynyl butylcarbamate (8-J3). 

Kao KD, Lu DW, Chiang CH, Huang HS. Corneal and scleral penetration studies of 6-hydroxyethoxy-2-benzothiazole sulfonamide a topical carbonic anhydrase inhibitor. J Ocul Pharmacol 1990 6 313 320. 

Delac . [Uniroyal] Benzothiazole sulfonamides delayed-action accelerator for natural and synthetic rubbers used in tire treads, carcass, mechanicals, and wire jackets. 

See N-Cyclohexyl-2-benzothiazolesulfenamide 2-Benzothiazolesulffenamide, N,N-diisopropyl-. See Diisopropyl benzothiazole sulfonamide... 

Santicizer 278. See Benzyl phthalate Santochlor 20] Santochlor Flakes] Santochlor Molten. See p-Dichlorobenzene Santocur CBS. See N-Cyclohexyl-2-benzothiazolesulfenamide Santocure DCBS. See Dicyclohexyl benzothiazyl-2-sulfenamide Santocure IPS. See Diisopropyl benzothiazole sulfonamide... 

Santocure MBS] Santocure MOR. See N-Oxydiethylene benzothiazole-2-sulfenamide Santocur NS] Santocure TBBS] Santocure TBSI. See Butyl 2-benzothiazole sulfonamide Santoflex 6PPD] Santoflex 13. See N-(1,3-Dimethylbutyl)-N -phenyl-p-phenylenediamine... 

These contain additives and their breakdown products such as benzothiazole, 2-mercaptobenzothiazole, N-cyclo-2-benzothiazole sulfonamide and 2-mercapto-benzothiazyl disulfide. 

Similarly, the N-cumyl benzene sulfonamide 7 (Scheme 5) undergoes metalation-diverse electrophile quench reactions its quenching with DMF leads to 8, which, after OTMS protection, may be further metalated and quenched with iodine to give 10 the latter is transformed under mild conditions into new benzothiazole derivatives 11 and 12 [12]. 

The radical anions of five isomers of nitrobenzothiazole (4-N02-, 5-N02-, 6-N02-, 7-N02- and 2-N02-) have been obtained by electrochemical reduction in DMSO and easily characterized by ESR spectroscopy [889], To the contrary, the chemical reduction in alkaline solution (t-BuOK in DMSO or glucose and MeOK in MeOH) presented some problems with 6-N02- and 4-N02-benzothiazoles, and 2-N02-benzothiazole did not provide any detectable paramagnetic species [889], Copper(II) complexes of 6-nitrobenzothiazole-A-sulfonamides as protective agents against superoxide anion have been investigated by ESR spectroscopy [890], The ESR spectrum of 5-nitro-2,l,3-benzothiadiazole RA obtained by electrochemical generation in DMF was reported [886], Unfortunately, the HFS constants of this radical anion are absent and we estimated the HFS constants from simulated spectrum (Table 3.40). 

Mononuclear and dinuclear Cu(II) complexes of TV-substituted nitrobenzothiazole-sulfonamides [214], alkylation products of 2-amino-6-nitro-benzothiazole [795] have been studied by UV visible spectroscopy. 

Since the discovery by Carpino et al.f l that A -Pbf-protected amino acids can be activated even as acid chlorides, such derivatives have been found to be well suited for the acylation of sterically demanding amino components (for details and experimental procedures, see Section 3.3.1). Oxazolone formation is prevented by this type of N -protection, racemization is not observed during activation and coupling.In line with these findings, further sulfonamide derivatives have been proposed such as l,3-benzothiazol-2-ylsulfonyl (Bts, 1Q4),[659,660] 5-methyl-l,3,4-thiadiazol-2-ylsulfonyl (105),f l 2-nitrophenylsulfonyl (oNbs, 4-nitrophenylsulfonyl (107),t l and 2,4-dinitrophenylsulfonyl group (108) (Scheme 49).f l... 

The A-sulfonyl protection in general,PI and more recently the 2-nitrophenylsulfonyl (oNps, 106), the l,3-benzothiazol-2-ylsulfonyl (Bts, 104), and the 5-methyl-l,3,4-thiadiazol-2-ylsulfonyl (105) groups have been used for terminal N-alkylation (Scheme 50), e.g. for the synthesis of polyamines.In fact, as the sulfonamide N—H bond is very acidic, deprotonation with 7-methyl-l,5,7-triazabicyclo[4.4.0]dec-5-ene and alkylation is possible... 

The sulfenamide S—N bond strength controls the scorch safety and cure rate. The more labile this bond, the more readily the active cure promoter mercapto-benzothiazole is released at the onset of the cross-linking process. A family of sulfonamides has been developed to span a range of cure rates. Common historical members of this class are shown in Table 3, arranged from fast curing to... 

Use as a Protecting Group for Nitrogen. Vedejs, who showed that benzothiazole-2-sulfonyl-aminoacids (Bts-aminoacids) could readily be converted to their acid chlorides without racemization, pioneered the use of the Bts group for the protection of amino acids. The acid chloride of Bts-protected amino acids were found to be effective for racemization free peptide couplings. The sulfonamide is readily prepared using... 

The sulfonamide 184 is an intermediate in the synthesis of herbicidal N-(pyrimidine aminocarbonyl) thiazolesulfonamides. In addition, several sulfonyl derivatives of isoxazole, pyrazole and thiazole have shown antifungal activity. Benzothiazole 185 is reported to react with chlorosulfonic acid to only give a salt later repetition" of the reaetion with chlorosulfonic acid at both RT and 100 °C confirmed this result. On the other hand, when benzothiazole 185 was heated with excess chlorosulfonic acid (six equivalents) at 150 °C (4i hours), followed by boiling with thionyl chloride (2 hours), the reaction gave the sulfonyl chloride as a gum. Subsequent treatment with amines afforded a mixture of the 4-and 7-sulfonamides 186 and 187 respectively (Equation 49)." ... 

The NMR spectra of the dimethylamide derivatives 186 R = Me and 187 R = Me, indicated that the product mixture contained 80% of the 4-sulfonamide and 20% of 7-isomer." The failure of the action of chlorosulfonic acid alone on benzothiazole to yield the sulfonyl chloride may be due to the 4-sulfonic acid existing as the stabilized hydrogen-bonded structure 188 which requires a more powerful chlorinating agent (thionyl chloride) to convert it into the sulfonyl chloride. This is analogous to the situation previously observed in the chlorosulfo-nation of diarylureas (see Chapter 4, p 112)... 

Styrylbenzothiazole 194, by treatment with excess chlorosulfonic acid (six equivalents) at RT (1 week), gave mainly the sulfonic acid, but when the product was reacted with thionyl chloride and subsequently with amines, the sulfonamides 195, 20-45%, were isolated. Under these conditions, sulfonation occurs exclusively on the styryl moiety and there is no attack on the benzothiazole ring, since this demands prolonged heating with excess chlorosulfonic acid. ... 

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