Hydrochloric Acid → Dipyrromethane

Participants

Reaction Steps

The earliest one-flask synthesis entailed reaction of 4-pyridine carboxaldehyde with 2.1 molar equiv of pyrrole in methanol acidified with gaseous HCl, whereupon the corresponding 5-(4-pyridyl)dipyrromethane precipitated as the hydrochloride salt.2 In most applications such precipitation is not possible, in which case all excess of pyrrole is employed to suppress the continued reaction leading to linear and cyclic oligomers. A number of reports in the early-mid 1990s described methods where the aldehyde (0.04–0.5 M) was treated with excess pyrrole (2.1–40 molar equiv) in an acidified organic solvent: BF3-etherate/CH2Cl2,3 acetic acid/DMF4 or THF,5 SnCl4/CH2Cl2,6 p-toluenesulfonic acid/MeOH7,8 or toluene,9 or aq. HCl/THF.10 Workup typically entailed several steps including column chromatography, though Hammel et al. employed flash chromatography followed by Kugelrohr distillation.3 In 1994, we reported a method that employed the reaction of the aldehyde (0.34 M) dissolved in neat pyrrole (˜14 M) with no other solvent, relying on column chromatography for purification (“1994 procedure”).11 Catalysis was achieved at room temperature with TFA or BF3.O(Et)2, or in some cases12 upon heating without added acid. The reaction proceeded in a few minutes at room temperature and afforded the dipyrromethane in yields of ˜40–60%, but the use of chromatography for purification limited the scale.

Provenance & Evidence