Pyrrole, acylation

Pyrrole, l-(2-acylaminophenyl)-intramolecular aeylation, 4, 223 Pyrrole, 3-acyl-2-ehloromethyl-reactions, 4, 274 Pyrrole, 3-acyl-2-formyl-reactions... 

Pyridine, nucleophilic addition to 4-chloro-l,3-din1trobenzenc, 62, 134 Pyridinlum, 3-carbamoyl-l-6-D-r1bofuranosyl hydroxide, 5 5 - ester with adenosine 5 -(trihydrogen pyrophosphate). Inner salt, 63, 17 Pyr1do(2,l,6-de)qu1noll2lne, dodecahydro-, c1s,cis- (3ao,6ao,9aa) [57147-56-6] cis.trans- 3aa,6ac,9ae) [57194-67-9], 61, 108 Pyrrole, 3-acyl, 62, 115 Pyrrole, S-d-hydroxyalkyl), 62, 115... 

Pyrrole, 2-acetyl-1 -(2-hydroxyethyl)-5-nitro-cydization, 4, 74 ipso substitution, 4, 243 Pyrrole, 2-acetyl-1-methyl-dipole moment, 4, 194 photocydization reactions with 2,3-dimethylbut-2-ene, 4, 269 Pyrrole, 3-acetyl-4-methyl-Vilsmeier-Haack formylation, 4, 222 Pyrrole, 2-acetyl-3-nitro-reduction, 4, 297 Pyrrole, acyl-basicity, 4, 207 isomerization, 4, 208 oximes... 

To test the generality of this reaction, the indole systems 70a,b were prepared from hexahydro-8-oxopyrrolo[ 1,2-a]indole 67 and tetrahydro-4-oxindole 68 (Scheme 11). These compounds in turn were readily obtained from cyclohexane-1,3-one and the appropriate amino acid salt according to Franck s pyrrole acylation protocol.53 Attempts to directly oxidize 67 or 68 to the hydroxyindole oxidation state using DDQ met with failure despite numerous attempts involving variation in solvent and reaction temperature. To circumvent this limitation, it was reasoned that... 

Heterocycles such as furan and pyrrole can be efficiently acetylated with AAN in the presence of zeolite ZSM-5. The higher yields are % of 2-acetylfuran at 93% conversion of furan and 76% of 2-acetylp5u-role af 78% conversion of pyrrole over ZSM-5(30). On the contrary, the catalytic activity of Y is low due to its higher acidity compared to ZSM-5-type catalysts this confirms that the pyrrole acylation reaction prefers moderate acidic centers. 

For a complete description of the synthetic utility of the Houben-Hoesch reaction as it applies to other aromatic systems, as well as some mechanistic discussions, the reader is directed to two reviews on the subject. Due to the diminished electrophilic reactivity of nitriles compared to other carboxylic acid derivatives as well as the broad number of Friedel-Crafts substrates, most Houben-Hoesch pyrrole acylation reactions are conducted intramolecularly. However, an impressive intermolecular example was delineated by Chang and co-workers in efforts directed toward the synthesis of novel 2-[5-aroylpyrrolo]alkanoic acids, for evaluation of their potential analgesic and anti-inflammatory activities. Treatment of substituted pyrrole 4 and 3-cyanopyridine (5) with acid in dry chloroform resulted in the preparation of 6 in good yield. 

The synthesis will therefore normally produce a 2,4-substituted pyrrole, with in addition an ester group or an acyl group at the 3-position, if a keto ster or a diketone respectively has been employed, and an ester group or an alkyl (aryl) group at the 5-position, according to the nature of the amino-ketone. 

N-Acylation is readily carried out by reaction of the alkaU metal salts with the appropriate acid chloride. C-Acylation of pyrroles carrying negative substituents occurs in the presence of Friedel-Crafts catalysts. Pyrrole and alkylpyrroles can be acylated noncatalyticaHy with an acid chloride or an acid anhydride. The formation of trichloromethyl 2-pyrryl ketone [35302-72-8] (20, R = CCI3) is a particularly useful procedure because the ketonic product can be readily converted to the corresponding pyrrolecarboxyUc acid or ester by treatment with aqueous base or alcohoHc base, respectively (31). 

The most generally useful method for acylation or formyl a ti on of pyrroles is the Vil smeier-Ha ack reaction (32,33). The pyrrole is treated with the phosphoryl complex of A/ A -dialkjlamide and the intermediate imine salt is hydroly2ed. 

The a-hydioxypyiioles, which exist piimadly in the tautomeric pyiiolin-2-one form, can be synthesized either by oxidation of pyrroles that ate unsubstituted in the a-position or by ting synthesis. P-Hydtoxypyttoles also exist primarily in the keto form but do not display the ordinary reactions of ketones because of the contributions of the polar form (25). They can be teaddy O-alkylated and -acylated (41). 

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