Pyrrole-2,5-dione amine

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. 

A useful expansion of the pyrrole-ring annelation methodology was found when 3-alkynyl-6,8-dimethylpyrimido[4,5-< ]pyridazine-5,7(6//,8//)-dione reacts with an amine and silver permanganate pyridine complex. It was postulated that first amination at the C4-position takes place, followed by an intramolecular cyclization into the pyrrolopyridazinopyrimidine derivative (Scheme 35). A similar reaction was reported with 6-alkynyl-l,3-dimethylpyrimido[4,5-Z]pyrazinedione (03MI3). 

What we need is an amine— ammonia in this case—and a diketone. If the two carbonyl groups have a 1,4 relationship we will get a pyrrole out of this reaction. So hexane-2)5-dione reacts with ammonia to give a high yield of 2,5-dimethyl pyrrole. 

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>. 

The condensation of 2,5-disubstituted pyrroles or 1,2,5-trisubstituted pyrroles with 1,4-diones under acidic conditions generates the isoindole system. This is a convenient route (i.e., with 2,5-disubstituted pyrroles) to JV-unsubstituted (and therefore potentially tautomeric) compounds.5 76-78 Certain isoindoles can be obtained directly from the 1,4-dione and ammonia or primary amine under acidic conditions77 or by the self-condensation of 2,5-disubstituted pyrroles under acidic conditions78 (Scheme 8). The pyrrole self-condensation may be rationalized as shown in Eq. (13) the other reactions are mechanistically analogous. 

The Paal-Knorr synthesis, in which 1,4-dicarbonyl compounds are treated with NH3 or primary amines (or with ammonium or alkylammonium salts) in ethanol or acetic acid, leads to 2,5-disubstituted pyrroles, and is universally applicable. For instance, hexane-2,5-dione 8 reacts with NH3 to yield 2,5-dimethylpyrrole 9 ... 

An autorecyling process is suggested to account for the greater than 100% yields obtained for the oxidation of some amines by 6,9-disubstituted cyclohepta[Z)]pyrimido[5,4-d]pyrrole-8(6//),10(9i/)-dione derivatives such as... 

Pyrrole 38 was generated from nitrobenzene and a 1,4-diketone with indium metal in acetic acid. The reductive conditions convert nitrobenzene to aniline in situ cyclization then occurs with the dione in moderate to excellent yield (40-98%, 21 examples) (13T6698). A Pd(OCOCF3)2-catalyzed cascade furnished tetrasubstituted pyrrole 39 from 1,3-dicarbonyl compounds and primary amines in good yield (13CC4667). 

Method 1. Montmorillonite-KSF clay (1 g), amine (1 1.2 mmol), and hexane-2,5-dione (2 1 mmol) were mixed together thoroughly using dichloromethane (1 mL). The solvent was then evaporated out, and the mixture was kept at room temperature for specified period (10-25 h for varying entries). On completion of the reaction, the solid mixture was washed with dichloromethane and the washings were evaporated to obtain substituted pyrrole 3 followed by required purification (70-98% yield). 

Hydroxylamine hydrochloride and sodium carbonate in ethanol with pyrroles lead to dioximes of 1,4-dicarbonyl compounds [109], for example, 2,5-dimethyl-N-alkylpyrroles give the dioxime of hexane-2,5-dione (32) and primary amines R-NH2 ... 

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