Microwave‐accelerated synthesis of benzyl 3,5‐dimethyl‐pyrrole‐2‐carboxylate

Abstract

m ic ro wa ve en er gyEt hylen e g lyco l, p -TS A m ic ro wa ve en er gyBenzyl 3,5-dimethyl-pyrrole-2-carboxylate, a very useful pyrrole in porphyrin and dipyrromethene synthesis, can be synthesized via the Knorr-type reaction, but in low yield. Alternative routes to benzyl 3,5-dimethyl-pyrrole-2-carboxylate have been developed involving the trans-esterification of ethyl 3,5-dimethyl-pyrrole-2-carboxylate and the de-acetylation of benzyl 4-acetyl-3,5-dimethyl-2-carboxylate, both precursors being easily obtained using the Knorr reaction. These traditional methods involve treatment of the known products with a strong basic solution or heating for extended periods which often lead to decomposition. The use of microwave energy to promote these two reactions proves to be an extremely efficient way to obtain benzyl 3,5-dimethyl-pyrrole-2-carboxylate quickly, in high yield, and in excellent purity with no need for recrystallization. Of particular note is the use of catalytic sodium methoxide in benzyl alcohol, rather than stoichiometric amounts of sodium benzoxide, to effect benzylation.

Synthesis and Anti-Cancer Activity of C-Ring-Functionalized Prodigiosin Analogues

“…Diesters 21 − 23 were mono-saponified, and the resultant mono-acids were chlorinated to give the chlorocarbonyl esters 27 − 29 . Subsequent Friedel−Crafts acylation of benzyl 3,5-dimethyl-pyrrole-2-carboxylate gave the pyrroles 30 − 32 , which were hydrogenolyzed, and the resultant carboxylic acids ( 33 − 35 ) were decarboxylated by treatment with TFA . Finally, in-situ Vilsmeier−Haack formylation 40 gave the formyl pyrroles 36 − 38 .…”

Synthesis of dipyrrins bearing chirality adjacent to the conjugated skeleton — Electron-poor pyrroles exhibit dramatically reduced nucleophilicity

“…Synthesis of the first dipyrrin bearing a 4-(2,2,2-trifluoro-1-hydroxyethyl)-substitutent was achieved according to Scheme 1. Benzyl 3,5-dimethyl-pyrrole-2-carboxylate (1) 22 was converted to the corresponding trifluoroacetoxy-substituted pyrrole 2 using TFAA under acidic conditions. 23 Reduction of 2 with borane gave racemic alcohol 3 and the use of the CBS protocol gave S-3 with 99:1 enantiomeric ratio (er), akin to that reported by Kumadaki and co-workers.…”

Synthesis and reactivity of 2-thionoester pyrroles: a route to 2-formyl pyrroles

“…The title compound was synthesised following a modied literature procedure. 43 Ethylene glycol (1.5 mL), para-toluene sulfonic acid (16 mg, 0.08 mmol) and 1e (174 mg, 0.77 mmol) were added to a 2 mL microwave vial equipped with a stir bar. The vial was sealed and the mixture was pre-stirred for 1 minute then heated for 2 minutes at 100 C in a laboratory microwave.…”