Michael T. Huggins

Synthesis and molecular recognition studies of pyrrole sulfonamides

We report the synthesis and characterization of the pyrrole sulfonamide as a new class of potential molecular receptors, including conformational analysis and molecular recognition studies for four pyrrole sulfonamide derivatives.

Short, Efficient Syntheses of Pyrrole α-Amides

Abstract We report an inexpensive method for producing a diverse array of pyrrole amides on a large scale and in good yield. The synthetic sequence allows for the preparation of a number of pyrrole amide derivatives in excellent to moderate yields from commercially available compounds. The diketene adduct, in the presence of an amine nucleophile, provides an excellent method for acetoacetylation. For diversity and versatility, a second method utilizing Meldrums acid was successfully employed for the preparation of additional acetoacetamide derivatives. Using the Knorr pyrrole synthesis, pyrrole amides were readily prepared from the oxime of the acetoacetamides.

Amide to carboxylic acid hydrogen bonding. The dipyrrinone receptor

Hydrogen bonding between carboxylic acid and amide groups was demonstrated for a series of amides called [n]-semirubins consisting of a dipyrrinone attached to the end of an n-carbon alkanoic acid. Such hydrogen bonding is more effective than the alternative amide to amide or acid to acid types for all of the semirubins studied: n = 1, 3–7, 10 and 20. As determined by 1H NMR and vapour pressure osmometry, [n]-semirubins, where n = 5–20, are intramolecularly hydrogen bonded in CHCl3 or CDCl3; [4]-semirubin is intermolecularly hydrogen bonded as a dimer; [3]-semirubin is a tetramer; and [1]-semirubin is a dimer – all with carboxylic acid to amide hydrogen bonding. The dipyrrinone amide and adjacent pyrrole constitute an efficacious receptor for the carboxylic acid group.

Dipyrrinone imines: controlling self-association

We report the synthesis of three new dipyrrinone imine analogues and the characterisation of their self-association properties. Based on vapour pressure osmometry and nuclear magnetic resonance studies, placing the imine functional group at C(9) of the dipyrrinone disrupts the native self-association of the dipyrrinone core in a manner that correlates with the conformational A-value of the imine N-substituent.