Methyl 5-formylpyrrole-2-carboxylate

Aminomethyl)pyrrole-2-carboxylic acid (85) was prepared from methyl 5-formylpyrrole-2-carboxylate by conversion to the oxime and subsequent reduction, Boc protection, and saponificationJ74 ... 

The Vilsmeier-H2iack reagent, a chloroiminium salt, is a weak electrophile. Therefore, the Vilsmeier-Haack reaction works better with electron-rich carbocycles and heterocycles. Since pyrrole is very electron-rich, the Vilsmeier-Haack reaction readily takes place. Formylation of methyl pyrrole-2-carboxylate was achieved using the Vilsmeier-Haack reaction. The mechanism is shown below. The resulting methyl 5-formylpyrrole-2-carboxylate, in turn, was converted into nonpeptidic analogues of neurotesin(8-13), which are potential treatment for neuropsychiatric diseases such as schizophrenia and Parkinson s disease. 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyi-l-methylpyrrole and with 3-formylindole produces (443 Hetero= l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

Examples of selective side-chain oxidation were reported for two reagents Ceric ammonium nitrate was found to convert 5-methylpyrrole-2-carboxylates to 5-formylpyrrole-2-carboxylates. <95TL4345> Several examples of oxidation of C2 and C3 methyl groups to formyl in 1-(phenylsulfonyl)indoles with Mn02 were reported. <95SC2407>... 

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