Crystal Structure and Conformation of a Dipyrrylmethane. The gem-Dimethyl Effect

Abstract

A crystal structure determination of the new dipyrrylmethane diethyl-2, 3,5,5,7,8hexamethyl-5,10-dihydrodipyrrin-1,9-dicarboxylate (1) is only the third reported for a dipyrrylmethane and the ®rst with a gem-dimethyl group at the bridging carbon atom. Conformation determining torsion angles are compared to those from molecular mechanics calculations and to the corresponding data for an analogous dipyrrylmethane (2) with no gem-dimethyl moiety. The crystal structures of 1 and 2 differ signi®cantly: 1 adopts the ac,ac or Àac,Àac conformation, whereas 2 exists in the Àac,sc conformation in an intermolecularly hydrogen bonded dimer. There is no evidence for hydrogen bonding in crystals of 1, and its ac conformation is unlike that found about the central core of bilirubin (sc,sc). Taken collectively, the data indicate that the presence of a sterically demanding and potentially conformation distorting gem-dimethyl group located at the bridging carbon of a dipyrrylmethane (i) stabilizes a conformation that brings the pyrrole NH groups syn to the gem-dimethyls and (ii) would destabilize the ridge-title conformation of 10,10-dimethylbilirubin.

Anion binding properties of 5,5′-dicarboxamido-dipyrrolylmethanes

“…Whilst being more stable, Lightner and co-workers have predicted, using molecular mechanics calculations on dipyrrolylmethanes, that the gem-dimethyl effect present due to the substitution on the meso carbon may de-stabilise conformations favourable for the formation of a convergent binding site by the four hydrogen bond donors. 24 Hence whilst the new compounds may be more stable than 1 or 2, they may also have lower affinities for anions. The question remained whether this effect would preclude these receptors from functioning in partially aqueous DMSO solution.…”

“…Compounds 3 and 4 were synthesised by reaction of ethyl 5-(2-(5-(ethoxycarbonyl)-3,4-dimethyl-1H-pyrrol-2-yl)propan-2-yl)-3,4-dimethyl-1H-pyrrole-2-carboxylate (prepared according Lightner and co-workers' method 24 ) with aniline or n-butylamine in the presence of trimethylaluminium in dry dichloromethane at 35 °C. After quenching and purification by column chromatography, compounds 3 and 4 were isolated 32 and 11% respective yields.…”