Sulfamides amines

For the addition of an organometailic compound to an imine to give a primary amine, R in RCH=NR would have to be H, and such compounds are seldom stable. However, the conversion has been done, for R = aryl, by the use of the masked reagents (ArCH=N)2S02 [prepared from an aldehyde RCHO and sulfamide (NH2)2S02]. Addition of R"MgX or R"Li to these compounds gives ArCHR"NH2 after hydrolysis. ... 

Scheme 17.23 Sulfamide substrates for rhodium-catalyzed C-H amination...

This brief discussion on the synthetic utihty of oxathiazinanes is only intended to highhght the versatihty of these reagents. Readers who seek a more detailed review on the chemistry of sulfamidites and sulfamidates are referred to a recent, comprehensive account by LubeU [121]. Apphcations for these unusual heterocychc building blocks should see continued growth with the oxidative amination technologies now available for their preparation. 

When the 1,2,5-thiadiazole-1,1-dioxide is fused to an aromatic ring, the nucleophilic addition occurs at sulfur not carbon. In these cases, the reduced thiadiazole behaves as a classic sulfamide, readily undergoing amine exchange (Scheme 8) <82JCR(S)84>. 

Sulfonamides, like carboxamides, react at the amine side to form sulfonyliminosulfur difluorides. Thus, sulfamide reacts with sulfur tetrafluoride at ambient temperature in the presence of sodium fluoride as a hydrogen fluoride scavenger to give Af,AT-sulfonylbis(iminosulfur difluoride) (2)207 but at elevated temperatures (fluorosulfonyl)iminosulfur difluoride (3) is the main product.173 The latter is also formed from sulfamic acid173 and fluorosulfonamide.208... 

The traditional synthesis of cyclic sulfimidates from /3-aminoalcohols and SOCl2 in the presence of amine as a base has been developed further to the preparation of the enantiopure monocyclic as well fused sulfimidates (Schemes 26 and 27). 1,2,3-Oxathiazolidine mono-.Y-oxides are readily oxidized to corresponding sulfamidates by RuCR and NalCb, and the synthesis of sulfamidates can be performed in a one-pot procedure from -aminoalcohols without isolation of intermediate sulfimidates (Equation 37). The reaction of sulfamate esters 145 with PhI(OAc)2 and various catalysts proved to be a reliable method for the enantioselective preparation of cyclic sulfamidates 146 (Equation 35). 

Single crystals of difluoromethane bis(sulfinic acid) anhydride 17 were isolated, after the cesium salt 119 was stored in the presence of traces of water vapor for several weeks <1998JFC(89)55>. Treatment of difluoromethane-l,l-bis(sulfonyl fluoride) 120 with liquid ammonia led to the formation of the cyclic ammonium imide 121 <1997ZNB359, 1997WO9731909>, while reaction of sulfamide 122 with trifluoroacetaldehyde O-ethyl hemiacetal afforded the cyclic aminal 60 (Scheme 41) < 1999S1731 >. 

Alkyl and aryl A -substituted 1,2,5-thiadiazolidine-1,1-dioxides 316 are synthesized in good yield from the reaction of sulfuryl chloride with 2-chloroethylamine. 2-Chloroethylamine hydrochloride is heated at 80°C with sulfuryl chloride in acetonitrile, and corresponding mono(chloroalkyl)sulfamyl chloride 314 is then extracted with diethyl ether to separate from unreacted amine hydrochloride. This ether solution is added to a solution of primary amine, and the resultant A -aryl (chloroalkyl)sulfamide 315 is treated with potassium carbonate in DMSO to afford A -substituted 1,2,5-thiadiazolidine-l,1-dioxides 316 <03TL5483>. 

Scheme 22 Allylic amination via [2,3]-sigmatropic rearrangement of 2-alkenyl sulfamid-ines...

Of the various possible types of -substituted sulfamoyl (sulfamyl) chlorides, the dialkyl compounds are of particular interest because they serve as intermediates in the syntheses of substituted sulfamides (synthesis 28) and of certain of their derivatives (synthesis 29). The dialkyIsul-famoyl chlorides have been prepared by the reaction of sulfuryl chloride with an appropriate amine or its hydrochloride, " by the treatment of secondary 7V-chloroamines with liquid sulfur dioxide, and by the reaction of dialkyl-aminosulfinic acids with chlorine in carbon tetrachloride. Although either of the first two procedures can be recommended in terms of convenience and yield, the availability of starting materials normally dictates that the first be used. It is of interest that treatment of sulfuryl chloride with either ammonia or ammonium chloride in terms of this procedure does not give the parent sulfamoyl chloride, H2NSO2CI. This compound is obtained in an altogether different way. ... 

The method of synthesis described herein is the best procedure for preparing unsymmetrically substituted sulfamides, but it can be applied also to the symmetrically substituted ones. However, it may be a longer procedure for the latter, although the yields obtained will be consistently higher than those obtained by either direct aminolysis of sulfinyl chloride or deamination of sulfamide. The direct aminolysis of sulfuryl chloride does not work well with aromatic amines, for which ring chlorination is a complication. 

Bis(trichlorophosphoranylidene)sulfamide is extremely reactive. Vigorous reaction occurs with water. Complete replacement of the chlorine atoms is effected by treating with alcohols, phenols, amines, and organometallic compounds. 

Aryl chlorosulfonates (115) react with amines to give the sulfamoyl chlorides (104), formed by the amine attacking the electrophilic sulfur atom with subsequent loss of the phenol via sulfur-oxygen bond cleavage. The sulfamoyl chloride (104) then reacts with a second mole of the amine to yield the sulfamide (116) (Scheme 48). 

Sulfamide (136) can be prepared by reaction of sulfuryl chloride (128) with excess ammonia in dichloromethane at -50°C, followed by extraction of the product with acetonitrile (Scheme 55). By using primary amines in the condensation, the method can be extended to obtain N,N -disubstituted sulfamides (137) (Scheme 55). A valuable route to di- and trisubstituted sulfamides involves the reaction of catechol sulfate (138) with aniline. Aniline reacts slowly with (138) to give the sulfamoyl ester (139). The unreacted aniline then promotes base-catalysed elimination of catechol to form the transient, highly reactive N-phenylsulfonylimine (140) which is trapped by aniline to yield N,N -diphenylsulfamide (141). By reaction of the ester (139) with an alkylamine, the procedure can be used to obtain trisubstituted sulfamides (142) (Scheme 56). In general, the amination of the 2-hydroxyphenyl sulfamate esters using alkylamines is an efficient route for the synthesis of trialkylsulfamides (143) (Scheme 57). 

CSI (57) (see p. 157) is a useful reagent for the synthesis of sulfamides. CSI (57) by sequential treatment with 2-chloroethanol and a primary or secondary amine affords the corresponding chloroethoxycarbonylsulfamide (144). In the reaction with the amine, the sulfonyl chloride is more reactive than the alkyl chloride and is therefore selectively substituted to yield (144) (Scheme 58). 

CSI (57) can also be used to obtain N,N-disubstituted sulfamides (145) by treatment with pentachlorophenol. This reaction gives the vsulfamide (146) via the unstable carbamic acid intermediate (147). On heating with a secondary amine, (146) affords a good yield of the corresponding N,N-dialkylsulfamide (145). The final step involves elimination of the pentachlorophenoxy anion, which is an excellent leaving group (Scheme 59). 

Thiadiazoline and thiadiazolidine dioxide rings are easily opened by reaction with nucleophiles. Thus, taking advantage of the known aminoexchange reactions of sulfamides first reported by Paquin (48AG316), compound 101a could be opened by treatment with amines yielding the... 

On the other hand, imidothiocarbonates 178 react with sulfamoyl chloride to give the sulfamide 179. Reaction with one equivalent of primary amine provides the isourea 180, which can be readily cyclized by refluxing with trimethyl orthoacetate or trimethyl orthoformate to give 177 (R = Me or H, respectively) (Scheme 65). 

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