Pyrrole-2-sulfonic acid

FIGURE 18 / 0 0 A heterocycle-release strategy was [433] applied to solid-supported a-tosyloxy ketones in the synthesis of a pentasubsti-tuted pyrrole. Sulfonic acid resin, prepared from commercially available sulfo-nyl chloride resin or polystyrene, was employed. 

Indole is sulfonated under similar conditions to pyrrole though in this case the 3-sulfonic acid is formed. Benzo[Z>]thiophene is also sulfonated in the 3-position (71AHC(13)235). 

The major development in the Knorr pyrrole synthesis has been access to the amine component. For example, use of preformed diethyl aminomalonate with 1,3-diketones affords much higher yields of pyrroles 14. Reaction of 6-dicarbonyl compounds with hydroxylamine 0-sulfonic acid gives pyrroles 15 in one step. Weinreb a-aminoamides have found use in the Knorr pyrrole synthesis of a wide variety of pyrroles 16. °... 

In the tris-pentafluorophenyl analog (TFPC), in contrast to other Co corroles, aromatic amines can substitute PPh3 to form six-coordinate trivalent bis(amine) complexes.788 Bis-chlorosulfon-ation of TFPC occurs regioselectively to give the 2,17-(pyrrole)-bis-chlorosulfonated derivative fully characterized as its triphenylphosphinecobalt(III) complex.789 The amphiphilic bis-sulfonic acid was also obtained. 

The most widely applicable method for synthesis of unsymmetrically substituted dipyrrylmethanes (129) requires the condensation of a 2-unsubstituted pyrrole (124) with a 2-acetoxymethylpyrrole (128). This reaction was originally carried out with sodium acetate in hot acetic acid (60JA4389), but subsequent developments have shown that the conditions can be much milder if a catalytic quantity of toluene-p-sulfonic acid (in warm methanol or acetic acid) is employed (73JCS(Pl)247l). 

The text states that electrophilic aromatic substitution in furan, thiophene, and pyrrole occurs at C-2. The sulfonation of thiophene gives thiophene-2-sulfonic acid. 

Both pyrrole and furan can be sulfonated with the pyridinesulfur trioxide complex. The pyrrole product is now known to be the 3-sulfonic acid (Scheme 25) <2000TL6605>. The reaction of l-methyl-2-tri- -butylstannylpyrrole with trimethylsilyl chlorosulfonate, followed by quenching with aqueous NaHC03 generates sodium l-methylpyrrole-3-sulfonate. Furan-2-sulfonic acid can be further sulfonated with pyridineS03 to give the 2,5-disulfonate. 

Tamura, Y., Kato, S., Ikeda, M. One-Step Knorr pyrrole synthesis with hydroxylamine 0-sulfonic acid. Chem. Ind. 1971,767. 

Sulfur trioxide is the active sulfonating agent in sulfuric acid and it has been used in the form of complexes, e.g. sulfur trioxide-pyridine, for the sulfonation of molecules that decompose in strongly acidic media.5 The complex thus can be applied to obtain the sulfonic acids (27) and (28) from the parent furan and pyrrole heterocycles (29) and (30) (Scheme 24). 

The pyridine-sulfur trioxide adduct is a valuable reagent for the sulfonation of acid sensitive substrates like the heterocycles furan and pyrrole, which are polymerised by strong acids like sulfuric acid. Pyridine-sulfur trioxide thus converts furan (40) and pyrrole (41) into the corresponding 2-sulfonic acids (Scheme 21). 

Beller and coworkers recently reported a new strategy for the synthesis of poly-substituted anilines based on a three-component-coupling reaction and a domino deprotec-tion/aromatization reaction (equation l)44. A mixture of O-benzyl carbamate, p-toluene-sulfonic acid, aldehyde, AC2O and dienophile in /V-rnclhy I pyrrol idone was allowed to react for 24 h at 120 °C, followed by Pd/C catalyzed dehydrogenation in triglyme at 140 °C. A variety of tri-, tetra- and penta-substituted anilines were efficiently created by this domino process. 

The action of methanolic sodium methoxide on hydroxylamine 0-sulfonic acid generates nitrene NH, which adds to butadiene in situ to give a low yield of I //-pyrrol inc 295 (equation 154) " . 

The electrophilic amination of the sodium salts of a-unsubstituted 3-dicarbonyl compounds is one of the few examples of an amination where hydroxylamine O-sulfonic acid gives useful yields (Eq. 161) 472 with two equivalents of the substrate, pyrroles are formed.472,473 Chloramine,62 64 O-arylhydroxylamines,93,124,474 O-sulfonylhydroxylamines,134 and 0-(diarylphos-phinoyl)hydroxylamines106,139,475 have also been employed, although a low yield and formation of the hydroxylation product as a side product have been reported in one instance with (4-Me0C6H4)2P(0)0NH2.145 Some of these animations use chiral auxiliaries in the substrates with modest diastereoselectivities,124,475,476 but these have been superseded by the catalytic methods discussed below. 

For sulfonation, a mild reagent of low acidity must be used the pyridine-sulfur trioxide compound smoothly converts pyrrole into a sulfonate initially believed to be the 2-isomer, but subsequently shown to be pyrrole-3-sulfonic acid. It seems likely that this isomer results from reversibility of the sulfonation, and the eventual formation of the more stable acid. Chlorosulfonation of 1-phenylsulfonylpyrrole is clean... 

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