Acid-base chemistry pyrrole

TPP is the simplest porphyrin to make. It is made by refluxing pyrrole with benzaldehyde in propionic acid for half an hour. The purple solid is filtered off after cooling. It is washed (to free the solid from black, soluble poly-pyrrolic impurities) and chromatographed on neutral alumina. This separates chlorin and other impurities. On recrystallisation, purple lustrous crystals are left on the filter. The yield is not large, about 20-25% (based on pyrrole), but the synthesis is simple and direct. Much porphyrin chemistry has been elucidated using this purple work-horse. 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

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