Sulphamides synthesis

Mitsunobu reaction has also found use for the synthesis of nucleoside analogues. The reactions of diphosphines with cyanamide or sulphamide in the presence of diethyl azodicarboxyl ate have given bis-azenes, e.g.,(76). In a similar manner tris-X -azenes have been obtained from triphosphines Bis(diphenyl-phosphino)methane reacts cleanly with trimethylsilylazide to give, initially, one isomeric form of the silylated monophosphazene (77)... 

Cyclocondensation and other reactions with S03 and adducts of S03 has led to the synthesis of a wide range of compounds including l,2,3-oxathiazin-4-one dioxides (142)189, cyclic sulphur trioxide adducts (143)190, piperidinone (144)191 and iV-isopropyl-iV -2-carbomethoxy sulphamide (145)192. 

The synthesis, physical and chemical properties of sulphamides have been the subject of various reviews down through the years333-338. Sowada339 has summarized the three main synthetic routes in the preparation of sulphamides as follows (a) reaction of primary amines (alkyl or aryl) with sulphuryl chloride (b) reaction of primary amines with chlorosulphonic acid (c) reaction of primary amines (alkyl, cycloalkyl and aryl) with sulphamide. 

Reaction of sulphamide 337 with a series of amines has led to the synthesis of 2-sulphamido-1.3,4.6.7,11b-2-hexahydro-2//-benzo[V]-quinolizines (349), R3 = NHS02NH2, and the anti-hypertensive activity of the compounds in rats has been reported355. 

Chlorosulphonyl isocyanate is a useful reagent for the synthesis of sulphamides. Reaction of chlorosulphonyl isocyanate with 2-haloethanols (X = Cl, Br) followed by reaction with primary and secondary amines (R = C6H5, 3-N02C6H4, 2-NCC6H4,... 

Hedayatullah and Hugueny358 developed a useful synthesis for the preparation of N,N -disubstituted sulphamides (354) using chlorosulphonylisocyanate. The reaction involves heating pentachlorophenol at 130 °C with chlorosulphonylisocyanate to yield the N-... 

The scope of the reaction was probed by extending the reaction to the synthesis of six-membered cyclic sulphamides. The reaction of 367 with acetamidine gave 1,2,4,6-thiatriazinone-1,1-dioxides 371 (equation 121) in yields of 20%. Fragmentation of the intermediates prior to cyclization is considered to account for the low yields. Modest yields of the pyridothiatriazinone 372 were obtained by condensation of aminopyridine with 367 (equation 122). Aminotriazoles when reacted with 367 yielded the triazolothiatriazinones 373 (equation 123). The reaction of 2-amino-3-ethoxycarbonyl 4,5,6,7-tetrahydro-l-benzothiophen (374) with isopropyl sulphamoyl chloride gives the iV-(isopropyl)-iV -(3-ethoxycarbonyl-4,5,6,7-tetrahydro-l-benzothiophene)sulphamide (375)369. Cyclization of 375 with 5% sodium hydroxide leads to the formation of the cyclic sulphamide 3-isopropyl-4-oxo-3,4,5,6,7,8-hexahydro-1H [ 1 ] -benzothieno [2,3-d] -2,1,3-thiadiazin-2,2-dioxide (376) in 42% yield. Decarboxylation of 375 also occurs in the reaction with the formation of iV-(isopropyl)-iV -(4,5,6,7-tetrahydro-l-benzothiophene)sulphamide 377... 

Two new nucleosides of cyclic sulphamides (392 and 393) have been reported by Vorbruggen and co workers374. The synthesis involves reaction (equation 128) of the 1,2,6-thiadiazine-1,1-dioxide (394) with l-0-acetyl-2,3,5-tri-0-benzoyl-/ -D-ribofuranose (395) the intermediate nucleoside (396) is debenzylated to give 3-amino-6-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-6//-1,2,6-thiadiazine-1,1 -dioxide (392). 3,6-Dihydro-3 -oxo-6-(/ -D-ribofuranosyl)-2//-1,2,6-thiadiazine-1,1 -dioxide (393) is prepared in a similar manner. 

Unterhalt and Hanemacker have recently reported the synthesis of sweet-tasting N-(phenyl)-iV -carboxymethyl sulphamides (401)377. The compounds were prepared by the reaction (equation 131) of amino carboxylic acids with sulphuryl chloride and subsequent condensation with 4-substituted anilines followed by hydrolysis in base. 

Unsubstituted sulphamide NH2S02NH2 has recently been reported to be useful in functional group synthesis. Reaction of sulphamide with acid chlorides leads to a one-pot synthesis of nitriles 402378 (equation 132). The reaction is successful for a large variety of aliphatic and aromatic acid chlorides with electron-withdrawing and electron-donating substituents. Sterically hindered as well as heterocyclic nitriles are also obtained in high yields. The reaction is considered to proceed via the iV-acylsulphamide, which is further enolized and cleaved to yield the nitrile 402 and sulphamic acid. 

Reports on the use of iV-sulphamoyl amidine derivatives as histamine H2 receptor antagonists has prompted interest in the synthesis of these compounds. Thus the Lewis acid catalysed reaction of propionitriles 419 (R = H, alkyl) with sulphamide gives the 3-(4-thiazolemethylthio)propionamidine 420 (equation 139)384. The compounds were found useful as gastric secretion inhibitors. 

The history of these drugs started with the serendipitous discovery of the hypoglycaemic effect of p-amino-benzene-sulphamide-isopropyl-thiodiazole, or IPTD, by Loubati res and his collaborators. Modification of this molecule led to the synthesis of more than 12,000 compounds, of which only a few have been approved for clinical use (Fig. 10). These compounds share the basic formula ... 

The condensation of sulphamide and diethyl oxalate produces 3,4-dihydroxy-1,2,5-thiadiazole 1,1-dioxide as the dipotassium salt in high yield. The free acid (177) is an excellent precursor for the preparation of other functional derivatives, and for building up fused ring systems incorporating the 1,2,5-thiadiazole 1,1-dioxide structure (see below). The two isomeric benzothiadiazole acetoximes (178) and (179) undergo the Beckmann reaction, resulting in the fission of their carbocyclic ring. This provides an effective synthesis of novel ajS-unsaturated 1,2,5-thiadiazoles (180 X = COaH, Y = CR=CHCN X =... 

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