Sulfamate ester

R—O—S03H R—NH--SO3H sulfate ester sulfamate heparin... 

Synonyms 5-Butyl-2-ethylamino-6-methylpyrimidin-4-yl dimethylsulfamate Dimethylsulfamic acid 5-butyl-2-(ethylamino)-6-methyl-4-pyrimidinyl ester Sulfamic acid, dimethyl-, 5-butyl-2-(ethylamino)-6-methyl-4-pyrimidinyl ester Empirical C13H24N4O3S Properties Lt. tan waxy solid sol. in most org. soivs. very si. sol. in water m.w. 316.47 m.p. 50-... 

Cellulose sulfated usiag sulfamic acid degrades less than if sulfated usiag sulfuric acid (23). Cellulose esters of sulfamic acids are formed by the reaction of sulfamyl haHdes ia the presence of tertiary organic bases (see Cellulose esters). 

In sulfamation, also termed A/-sulfonation, compounds of the general stmcture R2NSO2H are formed as well as their corresponding salts, acid hahdes, and esters. The reagents are sulfamic acid (amido—sulfuric acid), SO —pyridine complex, SO —tertiary amine complexes, ahphatic amine—SO. adducts, and chlorine isocyanate—SO complexes (3). 

With the iron complex [Fe(Cl3terpy)2]( 104)2 (Clsterpy = 4,4, 4"-trichloro-2,2 6, 2"-terpyridine) as catalyst, sulfamate esters react with Phl(OAc)2 to generate iminoiodanes in situ which subsequently undergo intramolecular nitrenoid C-H insertion to give amidation products in good yields (Scheme 30) [48]. 

When sulfamate esters 114 are used as substrates, six-membered-ring formation is favored, and results in the selective formation of 1,2,3-oxathiazinane-2,2-dioxide heterocycles 115.251 Nevertheless, five-membered cyclic sulfamidates could be obtained when no alternative cyclization was possible. 1,3-Amino alcohols and related /2-amino acids are thus readily accessible from the same simple alcohols 113 by converting them into sulfamates 114 (Equation (90)). Furthermore, in comparison to the carbamate reaction (Scheme 9), the sulfamate substrates have... 

The sulfamate ester variant of this chemistry has already been shown to be a very powerful protocol for the syntheses of 1,3-amino alcohols and related /3-amino acids (Equation (90)), as well as iminium ion equivalents (Equation (91)). The further showcases of this chemistry are the total syntheses of the bromopyrrole alkaloids, manzacidins A and C (Scheme 13).234 The cyclic sulfamidate 129 was obtained diastereospecifically from sulfamate 128 using intramolecular rhodium-catalyzed G-H insertion. It was then found to react with sodium azide in NfN-dimethylformamide at room temperature after introduction of the Boc-activating group to afford the 1,3-diamino precursor 130 in 78% yield over 3 steps. Four subsequent manipulations afford the target structure 131. 

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

Non-linear kinetics have been reported for aminolysis of sulfamate esters RNHSO2ONP (Np=/7-N02C6H4) in chloroform. The first-order rate constants obs for reaction with imidazoles (primarily) under pseudo-first-order conditions display saturation curvature with increasing amine concentration, according to the expression... 

A report of a more extensive Hammett smdy has included estimates of values of Pacyi for aminolysis of members of the sulfamate ester series (XC6H4NHSO2ONP) in chloroform and acetonitrile using piperidine and a set of five pyridines variation of the pyridines allowed the determination of Ppyr values for several esters. The Pacyi values become less negative with decrease in amine basicity, apparently as a consequence of diminished H cleavage and a progression from a partial carbanion-like transition state to a more central E2 type mechanism (10). 

Scheme 17.15 Sulfamate esters as substrates for oxidative cyclization ...

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

The advent of sulfamate ester oxidative cyclization makes available a myriad of oxathia-zinane derivatives from simple alcohol precursors. These unusual heterocycles have enjoyed only sparing use despite their potential as electrophiHc azetidine equivalents. By contrast, five-membered ring sutfamidates and cycHc sulfates are broadly recog-... 

Scheme 17.41 Nickel-catalyzed cross-coupling of phenol-derived sulfamate esters.

Scheme 17.43 Bromopyrrole alkaloid assembly, highlighting sulfamate ester oxidation.

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