Pyrroles from amines

From i-PrOH. h From cyclohexane. c From MeCN. d The product was accompanied by 2-benzoyl-5-(benzylamino)-4-(phenylaminothi-oxomethyl)pyrrol-3-amine (85% yield). 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Pyrrolo[l,2-(7][l,2,5]benzotriazepin-ll-one 329 is the product of a sequence starting from N-(2-nitrophenyl)-lH-pyrrol-l-amine 327. The pathway included alkylation, reduction of the nitro group, formation of the isocyanate from intermediate 328 and intramolecular thermal cyclization (Scheme 69 (2000JHCl539)). 

The aminoboranes do not form stable complexes with neutral Lewis bases (see Section 24.2.2), but the amidotrihydroborates, M[BH3NR2], are relatively stable. Monophosphidobor-ates are also known but, apparently, hydroborates with more NR2 or PR2 groups are not stable. However, di- and tri-amidoborates derived from amines containing spz N (i.e. pyrrole, pyrazole, indole, indazole) are well known. 

The l//-pyrrol-2-amine 1387 reacted in dry CH2CI2 with 0.5 equiv of l//-pyrrole-2,5-dicarbonyl dichloride 1388 in the presence of Et3N, to give compound 1389, a new heterocyclic anion receptor, which was isolated in 47% yield (Equation 294) <20060L1593>. The moderate yields for this reaction are ascribed to the inherent instability of compound 1388 and to the formation of the three-ring dimer species 1390. Structural proof for receptor 1389 came from a single-crystal X-ray diffraction analysis. 

In an application of the Paal-Knorr pyrrole synthesis, the synthetic equivalents 3 of 1,4-ketoaldehydes were prepared by the radical addition of ketones 4 to vinyl pivalate. Treatment of the intermediates 3 with amines gave pyrroles 5 <03SL75>. Other new extensions of this popular pyrrole synthesis include the preparation of a number of pyrroles from hexane-2,5-dione and amines under solvent-free conditions in the presence of layered zirconium phosphate or phosphonate catalysts <03TL3923>, and the development of a solid-phase variant of this reaction <03SL711>. Likewise, the preparation of iV-acylpyrroles from primary amides and 2,5-dimethoxytetrahydrofuran in the presence of one equivalent of thionyl chloride has also been reported <03S1959>. 

Acetyl chloride (l.Og, lOmmol) in anhydrous THF (25ml) is dropped with stirring into an ice-cooled solution of iV-(2-aminophenyl)-17/-pyrrol-l-amine (1.73g, lOmmol) and triethylamine (l.Og, lOmmol) in the same solvent (50 ml). The mixture is kept at room temperature (1 h), tlien filtered and rotary evaporated. The solid residue crystallizes from aqueous ethanol (1.8 g, 84%, m.p. 172-174°C rw, 3250, 3300 and 1650cm- ). 

Reductive amination. The low-valent titanium species derived from TiCl, Li, and MojSiCl absorbs atmospheric nitrogen at ambient temperature to form a complex which is capable of elaborating nitrogen azacycles such as pyrroles from 1,4-dicarbonyl compounds,... 

Preparation of N-substituted pyrroles from 2,5-dialkoxytetrahydrofurans and primary amines. 

An interesting variant is the multicomponent synthesis of pyrroles from carbonyl compounds, primary amines, and nitroalkanes first described by Ishii et al. 

Zirconocene intermediates permit an unusual addition process which generates pyrroles from primary amines and alkynes with carbon monoxide serving as the C5 precursor (Scheme 84)... 

Pyrrole ring from amines via elimination of diethyl malonate... 

The Hantzsch pyrrole synthesis remains useful for the preparation of A/-substituted pyrroles from primary amines for materials chemistry and medicine. However, for pyrroles where N is unsubstituted, the Hantzsch pyrrole synthesis has largely been replaced by the Knorr pyrrole synthesis because the latter generally leads to higher product yields. 

Z. Hossaini, F. Rostami-Charati, S. Z. Sayyed-Alangi, Chin. Chem. Lett. 2012, 23, 1119-1121. Synthesis of highly functionalized pyrroles from primary amines and activated acetylenes in water. 

For another approach where dialkyl acetylenedicarboxylates were used in the synthesis of polysubstituted pyrroles, see N. Bhunia, B. Das, Synthesis 2013,45,1045-1050. One-pot synthesis of pentasubstituted pyrroles from propargyUc alcohols, amines, and dialkyl acetylenedicarboxylates tandem amination, propargylation and cycloisomerization catalyzed by molecular iodine. 

Reactions of 3-deoxyhexos-2-uloses with ketosamines derived from ammonia yield polyhydroxyalkyl substituted pyrroles and reactions of ketosamines derived from amines produce N-substituted polyhydroxyalkyl pyrroles. When the aforementioned uloses react with ketosamines in the presence of ammonia,... 

Jacobson MA, Willard PG (2002) Synthesis of 2,3-disubstituted pyrroles from 3, N-thlithio-N-(tert-butyldimethylsilyl)-2-buten-l-amine. J Org Chem 67 32-37... 

The AgNOs-mediated debromination of benzylic dibromides in hot aqueous ethanol affords benzaldehydes in high yields. However, poor to moderate yields of ketones are obtained from the corresponding gem-dibromides.Silver nitrate is used as the HI scavenger in the synthesis of multisubstituted pyrroles from the condensation of a-iodoketones, primary amines, and -dicarbonyl compounds under high-speed vibration milling conditions. ... 

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