Sulphonamides cyclic

Saccharin (imide of o-sulphobenzoic acid). Upon oxidising o toluene-sulphonamide with potassium permanganate in alkaline solution, the sodium salt of o-sulphonamidobenzoic acid is formed, which upon acidifying with concentrated hydrochloric acid or warming passes spontaneously into the cyclic imide of o-sulphobenzoic acid or saccharin ... 

Aromatic substitution by sulphonyl azides has been applied to the synthesis of cyclic sulphonamides not as readily available by other methods 16h For example, thermolysis of biphenyl-2-sulphonyl azide (60) in w-dodecane or in cyclohexane 78> at 150 °C gives high yields (partic-... 

Table 5.25). Diazacycloalkanes are also obtained from the reaction of a,(o-dibromoalkanes with the bis(tosylamino)alkanes, whereas intermolecular reaction of l-bromo-10-tosylaminodecane yields both 1 1 and 2 2 cyclic products (55% and 8%) under the basic conditions (Scheme 5.13). The reaction of p-tolucncsulphonamide with H-bromododecane yields the di-A-alkylated sulphonamide (84%) [50],... 

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... 

Tolbutamide, N-[(butylamino)carbonyl]-4-methylbenzenesulphona-mide N-(butylamino) carbonyl-p-toluene sulphonamide is a sulphonlylurea that is orally active as a hypoglycemic agent. The drug stimulates the poncreatic islet beta cells to release extra insulin. It also inhibits phosphodiesterase, which preserves cyclic AMP and thus favor glycogenolysis in a number of tissues. 

Precursors of this class are compounds with an active methylene group and some sulphonamides in them two hydrogen atoms have been replaced by the phenyl-iodonio (Phl + ) group. The standard method for the preparation of yiides is the reaction of DIB with the appropriate precursor in aqueous or alcoholic alkali (preferably potassium hydroxide for non-cyclic precursors and sodium carbonate for cyclic ones). 

When j6-toluenesulphonyl azide was heated at 50-80° in isopropyl alcohol in the presence of diethyl peroxydicarbonate (20-3 azide 1 -4 peroxide), -toluenesulphonamide and acetone were obtained in 75 and 81% yields respectively " . It was thought that the 2-hydroxy-t-propyl radical (292) added to the azide to give 293 (equation 132) and that an intramolecular reduction and elimination of nitrogen occurred via a cyclic intermediate (294) to give the radical (295) and acetone. Hydrogen abstraction by (295) would then give the sulphonamide. 

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],... 

Finally, chlorosulphonyl isocyanate has been shown to react with some alkenes to produce a novel series of five-membered cyclic sulphonamides as shown in... 

Exchange of substituents in substituted sulphonamides may occur by transamination as shown in equation 114463. Helferich and Kleb464 and others465,466 have prepared sultams (cyclic sulphonamides) using a similar methodology, as shown in equation 115. 

The reaction of a sulphonyl chloride with amines to produce a sulphonamide also occurs in the presence of a base305,307,482,483. In this case, it is well established that the reaction proceeds via a sulphene intermediate, as shown in equation 117. Using this method for the preparation, some novel sulphonamides may be obtained. Thus, the reaction of sulphene with phthalimide give iV-methylsulphonylphthalimide484,485, as shown in equation 118. Reaction of sulphene with pyridine leads to a novel cyclic... 

The o-quinomethide 291 is formed on irradiation of the sultone 292 at room temperature261. S—O Bond fission is also the result of irradiation through quartz of the cyclic sulphonate 293. In this case the resultant biradical does not extrude S02 but ring closes to afford the sulphonamide 294262. 

Synthesis.—A new route to alkyl-substituted crown compounds involves" the reaction of polyethylene glycols with alkenes in the presence of a positive halogen source (Scheme 51), followed by base-catalysed cyclization of the halohydrins produced. One approach to aza-crown molecules relies on alkylation of toluene-p-sulphonamide anions, and a study of some methods for N-detosylation of the cyclic products has been published. 

Me5o-cyclic imide precursor of t/-biotin has successfully been reduced with BHs.SMe2 in the presence of polymer-supported sulphonamide catalyst 70 in THF imder reflux for 6 hours. (Scheme 33) [63]. The enantioselective hydroxylactam was obtained in 91% yield with an ee > 98.5%. The recycling of the chiral supported-sulfonamide in the reduction of the meso precursor of J-biotin could be involved at least 5 times with non change in activity and enantioselectivity. 

In OTJir invesrigarionB oi napntalene cro m-type compounds derivatives oi aromaric sulphonic acids we have obtained several cyclic sulphonamides /6,7/. 

Sulphonamides.— Oxidative amidation of sulphinic acids gives primary sulphon-amides, though the severe reaction conditions (18% oleum with NaNj) restrict the potential of this route. Selective amino sulphonation of anilines, using CISOjNCO and AlClj, depends on the formation of cyclic A-carbamoyl-sulphonamides. More conventional preparative methods are covered in the conversion of naphthalene-1-thiol into 4-(2-hydroxyethylsulphonyl)naphthalene-1-sulphonamide (an assessment of standard routes has been made), and in the preparation of alkanesulphonyl- and trifluoromethanesulphonyl-hydroxyl-amines from hydroxylamines and the sulphonyl chlorides. In the latter study,conditions favouring N- rather than 0-sulphonylation were established. 

Cyclization of aliphatic amino-olefins may be achieved by first converting the amine into the corresponding toluene-p-sulphonamide, followed by intramolecular Pd -catalysed cyclization. In this way good yields of cyclic tosylated enamines have been obtained, which in principle can be used further to introduce additional functionality. The same paper also describes the mild photolytic cleavage of the A -tosyl group. 

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