3- Aminopyrrole, protonation

An interesting example of the nucleophilic displacement of an amino group from a pyrrole system has been reported for the acid-catalyzed conversion of 3-amino-2-(2-amino-phenyl)pyrrole (147) into the pyrrolo[3,2-6]indoIe (148) (81JCS(Pl)l). That the nucleophilic attack occurs on the protonated aminopyrrole has been proven by 15N labelling of the... 

With the exception of 2,5-diaminopyrrole, which exists predominantly in the 2,5-bisiminopyrrolidine form, the C-aminopyrroles possess the structure of normal aromatic amines and this is generally reflected in their chemical properties. The C-aminopyrroles are, however, less basic than one might expect for an aromatic amine and it is evident that 2-aminopyrroles do not form the pyrrolylammonium ions, but are protonated at the 5-position, giving rise to the resonance-stabilized cations, e.g. (475) (68TL4605, 76S51). 

Amino pyrroles, although unstable, form stable picrates.208-211 The structure of these adducts has not been determined and they could either be true salts, with protonation either on the pyrrole ring or the amino group, or, alternatively, charge-transfer it complexes. There is evidence that in trifluoroacetic acid a-aminopyrroles are protonated on the ring carbon atom and most probably in the opposition.212... 

Aminopyrroles in DMSO/TFA undergo protonation at the amino group <1996JHC161>, with a downfield shift of the NH2 proton signal of 4-6ppm. The H-3 and NH protons show downfield shifts of c. 0.6-0.8 and 0.1 ppm, respectively, while no effect is experienced by the H-5 proton upon protonation of the 2-amino group. 

Protonation of the amino group produces expected opposite shifts of carbon signals of 2-aminopyrroles in DMSO/ TEA <1996JHC161> C-2 resonances shift upfield by 3-5 ppm (7-11 ppm in the case of AT-substituted derivatives), whereas C-3 carbons become deshielded and undergo downfield shifts of 1.5-2.5 ppm (5-9 ppm in AT-substituted derivatives) (Table 12). The magnitudes of these effects are smaller than those observed with 3-aminopyrroles, but no explanation has been offered for this difference. Notably, 2- and 3-aminopyrroles in pure TEA are protonated at the 5- and/or 3-positions of the ring, confirming similar behavior. 

Latvian chemists calculated by the Slater-type orbitals, three Gaussian (STO-3G) basis set the proton affinities for 1-aminopyrrole and N-aminoazoles (89KGS1221). 

An elegant method for the utility of unstable 3-unsubsti-tuted 2-aminothiophene derivatives 385 in the Yonemitsu-type reaction has been elaborated by Krayushkin et al. (Scheme 13.81) [153]. Starting from stable 4,5-disubstituted ethyl 2-aminothiophene-3-carboxylates 383, the ester functionality is hydrolyzed to yield the corresponding alkali metal carboxylates 384. These are directly subjected to the three-component Yonemitsu-type reaction in acetic acid as the reaction medium. Protonation of the carboxylate followed by decarboxylation generates the 2-aminothiophene derivatives 385 that directly undergo Yonemitsu reaction without the need of isolation of those intermediates. This method has been applied to methyl 2,4-diaminothiazole-5-carboxylates 388 [154], ethyl 5-aminopyrazole -carboxylates 389 [155], dimethyl 3-aminopyrrol-2,4-dicarboxylates 390 [156], 4,5-disubstituted methyl 3-aminothiophene-2-carboxylates 391 [157], dimethyl 3-amino-4-phenylthiophene-2,5-dicarboxylate 392 [156], and ethyl 5-amin(Mmidazol-4-carboxylates 393 [158]. 

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