AHA! Moments  
June 16,  2004
An unexpected dimerization uncovered some 35 years ago led to an Aha! moment


Some years ago when I was a bench scientist at Pfizer Central Research, I had occasion to study the reaction product of the Bischler-Napieralski cyclization of N-formyl-3-phenylpropylamine. The expected product, the seven-membered-ring imine (1), was found, surprisingly, to exist in equilibrium with the 14-membered-ring imine dimerization product (2). Both monomer and dimer were isolable and well characterized.


The pivotal moment in the study was the observation of a rapidly changing NMR spectrum of the crystalline reaction product in deuterochloroform solution, with diagnostic shifts of the aromatic and azomethine hydrogens. The Aha! moment was the subsequent mass spectral finding that the crystalline reaction product was the 14-membered-ring dimer of the target seven-membered-ring product, and that the original reaction product before crystallization was, in fact, the seven-membered-ring structure. The ready interconversion of monomer and dimer was found to be acid-catalyzed, with the monomer/dimer equilibrium constant in the range of 15.

This work was subsequently published as a Communication in the Journal of the American Chemical Society [91, 4941 (1969)]—my one and only. Science can be full of some wonderful—if not profound—surprises.

Irving M. Goldman, a member of ACS for more than 50 years, is the person who suggested the Aha! moment series to C&EN. He resides in Burlington, Vt., in retirement after a 36.5-year career at Pfizer. He notes that some Aha! moments are more momentous than others, but all are important in their own ways: “All are rewarding and motivational, and some few are harbingers of real progress in science.”