Sulphamidates cyclic

Both compounds are soluble in water and are readily hydrolysed to sulphamic acid, HjN S03" andammonia the hydrogen atoms are in each case replaceable by metals to form salts. Many derivatives of sulphamide and cyclic derivatives of sulphimide are known. 

When cyclic sulphamides (18 and 19) were studied148, it was found that the six-membered rings are more acidic than their acyclic analogues by ca 2.5 pKa units and that the five-membered cyclic sulphamides are ca 4 pK units more acidic than the model open-chain counterparts. 

Many other non-peptide inhibitors of HIV protease (dihydropyrone, cyclic urea and sulphamide series of compounds) were obtained by modifications of random screening leads. Examples of these include a cyclic sulph-one derivative 147 and 148 (PNU-140690) that showed activity against a variety of HIV t)rpe 1... 

Cyclic sulphamides provide enantiomerically pure products in good yields by nucleophilic substitution at oxygen66,67. The title product 45 has been synthesized68 in 4 steps... 

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 transamination of l,3-dihyro-2,l,3-benzothiadiazole-2,2-dioxides (cyclic sulphamides) (346) has successfully led to the formation of sulphamides353. Thus when cyclohexylamine, benzylamine and n-butylamine are used in a 1 1 ratio with 346, the fully exchanged iV,iV -dialkylsulphamides were obtained in 60 to 80% yield (equation 107). 

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... 

Glycosidation reactions were also carried out on the unsubstituted cyclic sulphamides to yield nucleosides of 1,2,6-thiadiazine-1,1-dioxides (391)373. The thiadiazines were reacted with suitable sugar halides using mercuric cyanide and nitromethane. The site... 

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. 

Sulphamides containing boron have been prepared by Einholz382. Reaction (equation 135) of the silylated sulphamide 409 with 2-chloro-1,3-dimethyl-1,3,2-diazaborolidine (410) gives the diborylated sulphamide N,N -bis( 1,3-dimethyl-1,3,2-diazaborolidine-2-yl)-iV,iV -dimethylsulphamide (411). Reaction of the sulphamide 409 with ((CH3)2N)2BC1 yields the cyclic disulphamide, l,l,5,5-tetroxo-2,4,6,8-tetramethyl-3,7,-bis(dimethylamino)-U6,526,2,4,6,8,3,7-dithiatetrazadiboracin (412) (equation 136). The reaction of the sodium... 

Sulphamide reacts with bis (diphenylphosphino) methane (459) in the presence of diethylazodicarboxylate to give 69% yield of [(sulphamidodiphenylphospha-25-azeno)methyl] diphenylphosphine oxide (460)412 and 6% of the cyclic compound 3,3,5,5-tetraphenyl-4//-l,2,6,3,A5,525-thiadiazadiphosphorin-l,l-dioxide (461). 

The chemistry of the S -oxides of all four isomeric thiadiazoles has been reviewed in detail. The properties of these compounds are best accounted for by regarding their structures as cyclic sulphonylhydrazines (1), a- and /3-aniinosulphonamides (2), sulphamides (3), and hydrazinosulphones (4). 

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