1- Alkyl-2-phenylpyrroles

A comparison of the relative basicities of pyrrole, furan and thiophene may be made by comparing the pK values of their 2,5-di-t-butyl derivatives, which were found to be -1.01, —10.01 and —10.16, respectively. In each case protonation was shown by NMR to occur at position 2. The base-strengthening effect of alkyl substitution is clearly apparent by comparison of pyrrole and its alkyl derivatives, e.g. A-methylpyrrole has a pKa. for a-protonation of -2.9 and 2,3,4,5-tetramethylpyrrole has a pK of 4-3.7. In general, protonation of a-alkylpyrroles occurs at the a -position whereas /3-alkylpyrroles are protonated at the adjacent a-position. As expected, electron-withdrawing groups are base-weakening thus A-phenylpyrrole is reported to have a p/sTa of -5.8. The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

Oximes of alkyl phenyl ketones were successfully involved in the reaction with acetylene (Scheme 5). In this way, previously unavailable 3-alkyl(phenyl)-2-phenylpyrroles (5) and previously unknown 3-alkyl-(phenyl)-2-phenyl-l-vinylpyrroles (6) (Table XIII) were prepared (78ZOR-2182). 

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%. 

Alkyl-2-phenylpyrrole are readily formed, according to Scheme 5, under atmospheric pressure as well (50-70°C, 5-10 hr, equimolar amount or slight excess of KOH relative to oxime, excess of DMSO). Table XV illustrates the effects of the reaction temperature and time as well as of the structure of ketoximes on the composition and the yield of end products. 

Effect of Alkyl Structure on the Conversion of Alkyl Phenyl Ketoxime" and the Yield of 3-Alkyl-2-phenylpyrroles (5,6) ... 

The reaction of the ketene-A S-acetals 15 with ethyl bromoacetate in the presence of base gave the 1-phenylpyrroles 16. Precursors 15, easily obtained from 1,3-dicarbonyl compounds and isothiocyanetes followed by S-alkylation, may also serve as starting materials for the synthesis of 2-aminothiophenes by reaction with ethyl thioglycolate <03T1557>. 

Lithium diisopropylamide itself has the potential to open the ring in trimethylsiloxy-substituted cydopropanes by desilylation. The ring-opened intermediate can be trapped by alkylation with various alkyl halides. When this reaction was performed in the presence of phenyl isocyanate and iodomethane, highly substituted A -phenylpyrrole derivatives were obtained after treatment with trifluoroacetic acid. ... 

The total synthesis (Scheme 25) of ( )-rhazinilam was achieved by viewing the alkaloid as a derivative of a 3-phenylpyrrole. Thus 2-methoxycarbonyl-4-(2-nitrophenyl)pyrrole was first synthesized and then the aliphatic portion of the molecule introduced by alkylation at the pyrrole nitrogen [ —>(111)] and the carbon skeleton completed by intramolecular Friedel-Crafts alkylation [— (112)] at the only available pyrrole a-position. 

Kaeriyama and Masuda [121,122] prepared homopolymers of pyrrole, 3-methylpyrrole, 3-octylpyrrole, 3-propanoylpyrrole and 3-phenylpyrrole at — 20°C using perchlorate as the supporting electrolyte in PC and found conductivity values of 160, 20, 2.0 and 0.8 S cm , respectively. This decrease in electrical conductivity with increasing alkyl chain length is more significant here than for the polythiophenes. There are other differences. 

Kim SK, Jun C, Kwak K, Park K, Chai K (2007) Synthesis of N-alkylated 4-fluoro-5-phenylpyrrole-2-carboxylate via isolable pyrroUne ionic intermediates. Bull Korean Chem Soc 28 2324-2328... 

Kagabu S, Tsuji H, Kawai I, Ozeki H (1995) Thermal rearrangement of N-alkyl-, and N-aryl-(2,2-dihalo-l-phenylcyclopropyl)methyleneamines to 1-alkyl-, and l-aryl-2 (or 3)-halo-4-phenylpyrroles. Bull Chem Soc Jap 68 341-349... 

Alkyl- and -aryl-2,5-diphenylpyrroles have been nitrated with acetic acid-nitric acid 73, 276 Nitration of 1-phenylpyrrole in acetic anhydride gives 2- and 3-nitro-1-phenylpyrrole. However, in sulphuric acid, presumably because of protonation of the pyrrole ring, l-/ -nitrophenylpyrrole is... 

A number of alkyl phenyl ketoximes is successfully involved in the reaction with acetylene. Thus, a series of hardly available 3-alkyl(phenyl)-2-phenylpyrroles [163-165,219] and hitherto unknown 3-alkyl(phenyl)-2-phenyl-N-vinylpyrroles have been synthesized (Scheme 1.45) [163,165,220]. 

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. 

The hydrogenation of 2-phenyl- and 3-alkyl-2-phenylpyrroles and their N-vinyl derivatives under the aforementioned conditions gives a complex mixture of products [433]. 

Trofimov, B.A., M.V. Markova, I.V. Tatarinova et al. 2010. Ij-Doped and pyrrole ring-iodinated semi-conducting oligomers of N-vinyl-3-alkyl-2-phenylpyrroles. Synthetic Met 160 2573-2580. 

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