Alkyl-2-arylpyrroles

It was intended (85KGS1501) to find milder synthetic conditions for further simplifying the purification of 3-alkyl-2-phenylpyrroles (5,6) (Scheme 5). It was necessary to increase the DMSO content of the reaction mixture. So, when the synthesis was carried out under pressure in a 10-fold excess (of the total mass of reagents) of DMSO with an equimolar (with respect to ketoxime) amount of KOH, it was possible to decrease considerably the reaction temperature (to 50-60°) and prepare 3-alkyl-2-arylpyrroles (5) and their 1-vinyl derivatives (6) (which more readily undergo purification) in total yield up to 90%. 

Representatives of Arylpyrroles Prepared from Alkyl Aryl Ketoximes... 

The pyrrolization of various alkyl aryl ketoximes (Scheme 6) was also studied [78KGS489 84ZOR1960 90ZOR(ip)], and it was confirmed that the corresponding 2-arylpyrroles (7) could also be obtained successfully in this way (see Table XIII). 

Arylpyrroles, substituted or unsubstituted at the nitrogen, undergo a much more drastic oxidation than alkyl derivatives by the action of hydrogen peroxide. In most cases opening of the heterocyclic ring occurs, both at the bond between the heteroatom and the a-carbon and between the a- and )8-carbon atoms. From 2,5-diphenylpyrrole in acetic medium benzoic acid and acetophenone are formed.51 From 2,3,5-triphenyl-pyrrole (58, R = H) the product is 59,61 while from 58 (R = benzyl) the compounds 60 (R = benzyl) and 61 are produced.62 Other pyrroles that were found to behave similarly are listed below. 

A review of synthetic methods for arylpyrroles focuses particularly on the Trofimov reaction of oximes of alkyl aryl ketones with acetylene (192 references). ... 

This new synthesis of 3-alkyl(phenyl)-2-phenylpyrroles has been extended over alkyl aryl ketoximes (Scheme 1.46) [163,221], As a consequence, earlier unknown or difficult to produce 2-arylpyrroles can be synthesized using this methodology. 

Gupton and coworkers developed a six-step stereoselective synthesis of N-substituted 5-benzyhdene-4-arylpyrrol-2-ones (2010T9113). Within this sequence, Gupton treated a variety of (Z)-5-benzyUdene-4-arylfuran-2-ones with alkyl- and arylamines in methylene chloride at room temperature to afford corresponding 5-benzyl-5-hydroxy-4-arylpytrol-2-ones. 

A -Alkyl- and A-arylpyrroles are readily a-lithiated. For example, /Y-methylpyrrole is deprotonated v/iihEthyllithiumITMEDA and the lithiated product has been treated with Carbon Dioxide to give the corresponding carboxylic acid in 70% yield (eq 3). ... 

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