TCMDC_ArylPyrrole

 

4-fluoroaniline (10.4 mL, 110 mmol, 1.1 equiv.) and 2,5-hexanedione (11.7 mL, 100 mmol, 1 equiv.) were heated to 110 °C (oil bath temp.). After 15 hours, reaction was cooled to room temperature. The mixture was dissolved in hot EtOH (15 mL) and a mixture of EtOH (30 mL) and aqueous solution of 10% citric acid (15 mL). The reaction was slowly cooled to approx. 10 °C with periodic shaking. The resulting crystals were filted and washed with water (approx. 200 mL) to obtain the product as a tan crystalline solid containing dark brown solid (16.7 g, 88 mmol) which was found to contain an impurity (NMR 1-1 A). A second pure fraction was obtained as a tan powder from the mother liquors (783 mg, 4.1 mmol, 4.1% yield) NMR 1-1 B. The first crop of crystals were redissolved in hot EtOH (15 mL) and a hot mixture of EtOH (30 mL) and aqueous solution of 10% citric acid (15 mL) was added. The reaction mixture was allowed to cool to room temperature whilst stirring and then gradually cooled to 10 ˚C with periodic swirling. The resulting crystals were filtered and washed with water to obtain the product as tan crystals (16.2 g, 86 mmol, 86% yield).

Total yield (16.9 g, 89 mmol, 89% yield)

Data
Data in agreement with Paul Ylioja's original synthesis, see below for link





References:

1. 
   
2. Manetti, F.; Magnani, M.; Castagnolo, D.; Passalacqua, L.; Botta, M.; Corelli, F.; Saddi, M.; Deidda, D; De Logu, A. ChemMedChem, 2006, 1, 973–989. doi: 10.1002/cmdc.200600026
   

Original Experiment:
Scale-up (100 mmol) of Paal-Knorr Synthesis of 1-aryl-2,5-dimethyl Pyrrole Core (PMY 1-6)

Structural Information
InChI=1S/C6H6FN/c7-5-1-3-6(8)4-2-5/h1-4H,8H2
and
InChI=1S/C6H10O2/c1-5(7)3-4-6(2)8/h3-4H2,1-2H3
gives: InChI=1S/C12H12FN/c1-9-3-4-10(2)14(9)12-7-5-11(13)6-8-12/h3-8H,1-2H3

Hazard and Risk Assessment: