Sulphamides reactions

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,... 

Another method of preparation for pure sulphamide is to dissolve the product of the reaction between sulphuryl chloride and liquid ammonia in a small quantity of water and acidify the solution in order to cause hydrolysis. After two or three days, when hydrolysis is complete, the mixture is evaporated to dryness in vacuo and the residue extracted with ethyl acetate. The sulphamide is dissolved out and on evaporating off the ethyl acetate, pure sulphamide is obtained.3... 

According to A. Loir and C. Drion, when liquid ammonia at —65° is poured on to cone, sulphuric acid, the liquids do not mix, and a reaction gradually sets in. According to V. A. Jaquelain anhydrous ammonia reacts with sulphuric acid, forming sulphamide, and, according to A. Woronin, ammonium amidosulphate. 

Sulphamide has been used to form polymers by means of a reaction... 

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)... 

The rearrangement of an Af-arylsulphonamide, or an JV-arylsulphamide, to the isomeric aminoaryl sulphonyl compound (equation 43) is now a well-known reaction. The reaction is the nitrogen analogue of the Fries rearrangement (Section III.A.). For sulphonamides, acid-catalysed, base-catalysed, thermally promoted and photochemically promoted rearrangements have been observed for sulphamides, only the thermal and base-catalysed processes have been reported. 

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. 

Sulphamoyl chloride when reacted with hydroperoxides in the presence of pyridine below — 30 °C leads to the formation of the novel alkyl sulphamoyl peroxides H2NS0200CH2R (R = CH2CH3, CH2CH2CH3) 303 (equation 98)305. Hydrolysis or ammonolysis of these compounds leads to formation of sulphamic acid or sulphamide respectively. 2-Nitrophenylsulphamoyl chloride (304), prepared from the corresponding sulphamic acid by reaction with PC15, has been used to prepare iV-(2-nitrophenyl)-iV -substituted sulphamides (305) and aryl esters (306) (equation 99)306. 

Copolymers have been prepared by reaction of sulphamides of type 336 with ClCH2CH2(OCH2CH2)2Cl332. 

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. 

Amination and amine exchange reactions of sulphamide and substituted sulphamides have been used to prepare a wide range of sulphamides347-352 (equation 106). 

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. 

C6H5C6H4, C6H5CH2, furyl, cyclohexyl, picolyl, adamantyl, pentyl, R1 = C6H5, CH3, C2H5 and H) in a two-step reaction leads to the formation of a new series of 2-chloroethoxycarbonyl sulphamides, 350 (equation 110)356,357. Intramolecular cyclocon-... 

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-... 

Diphenyl ether sulphamides of the type 356 were prepared by the reaction of the alcohols 357 (R = H, halogen, alkyl, N02, CF3 R1 = F, Cl) with chlorosulphonyl isocyanate359. The intermediate sulphamoyl halide 358 was then reacted with amines to... 

The reaction of either (R)- or (5)-a-methylbenzylamine (364) with sulphuryl chloride gives the (R,R) and (5,5) N,N bis(a-methylbenzyl) sulphamide 365. When 365 is added to LiAlH4 in the presence of A-benzylmethylamine in tetrahydrofuran, it leads to the asymmetric reduction of prochiral ketones 366 (equation 115)363. Optimization of the reaction was carried out with respect to enantioselectivity and reactivity of the reagents. The use of iV-benzylmethylamine as an additive was found to be superior to ethanol. Reaction at — 20 °C gave 87% selectivity with a one-hour reaction time. Both arylalkyl ketones and dialkyl ketones are asymmetrically reduced in the reaction. 

The reaction of sulphamoyl halides with amines is a useful synthetic route to the preparation of sulphamides. Unterhalt and Seebach364 have used this approach to prepare N,N,AT-trialkylsulphamides 345 (equation 116). The reaction was carried out at 50 °C in... 

Phase transfer reaction of the conjugate base of the JV,iV,iV -trialkylsulphamides (345) in the presence of benzyl triethylammonium chloride with chloromethyl ethyl ether or chloromethyl alkylthioethers yields the N,iV-dialkyl-iV -alkyl-iV -ether and thioether sulphamides (341)365 (equation 117). 

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... 

A similar reaction is observed for 4-ethoxycarbonyl-5-amino-l-phenylpyrazole (380) with isopropylsulphamoyl chloride and leads to the formation of N-(isopropyl)-jV -4-ethoxycarbonyl-l-phenylpyrazole sulphamide (381), which undergoes cyclization in base... 

Thiadiazine 1,1-dioxides (389) have been synthesized by Ochoa s group and a comparative study of their physiochemical properties with that of pyrazoles 390 has been made371,372. Rough parallels are observed in the tautomeric equilibria of (389) and (390) with 13C chemical shifts and the reactivity of the 4-position while differences in their aromaticity have been observed. The 1,2,6-thiadiazine-1,1-dioxides 389 are prepared either by reaction of sulphamide or substituted sulphamides with 1,3-dicarbonyl compounds or their acetal derivatives or by AT-alkylation of the unsubstituted derivatives. 

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 the element phosphorous have been reported by Arrington375, who prepared a series of triphenylphosphoranylidene sulphamides (398) by reaction of the novel compound (triphenylphosphoranylidene)sulphamoyl chloride (397) with amines (equation 129). 

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. 

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