Perrin, Charles
Physical-organic chemistry: stereoelectronic effects; hydrogen bonding; isotope effects; ionic solvation; naked anions; malonic anhydrides

Contact Information
Distinguished Professor Emeritus of Chemistry and Biochemistry (Recalled)

Office: Pacific Hall 5223A
Phone: 858-534-2164
Group: View group members
1963 Ph.D., Harvard
1959 A.B.scl, Harvard
Awards and Academic Honors
Distinguished Professor in the Graduate Division
Distinguished Scientist Award of ACS San Diego Section
American Chemical Society James Flack Norris Award in Physical Organic Chemistry
Murray Goodman Endowed Chair
Andrew Streitwieser Lecturer, UCBerkeley
Wawzonek Memorial Lecturer, University of Iowa
Visiting Professor, Gothenburg Univrsity
Phi Beta Kappa lecturer, UCSD
UCSD Chancellor's Associates' Faculty Excellence Award for teaching
UCSD Academic Senate Distinguished Teaching Award
Danish Research Academy Visiting Professor
NATO Visiting Professor, University of Padua
Fellow, Amer. Assn. Adv. Science
NIH Special Research Fellow, Gothenburg University
Alfred P. Sloan Fellow
NSF Postdoctoral Fellow, University of California, Berkeley
Research Interests
Our research in physical-organic chemistry is concerned with molecular structure, mechanisms of organic reactions, and effects of structure on reactivity. Areas of current activity include NMR studies of hydrogen-bond symmetry, of isotope effects, of stereochemical effects on reactivity, of the anomeric effect, and of steric hindrance.

Is a hydrogen bond symmetric or asymmetric? The NMR method of isotopic perturbation can answer this for monoanions of 18O-labeled dicarboxylic acids and for various NHN species. The former had always been considered as having a symmetric intramolecular hydrogen bond. Nevertheless, the observed 13C spectra show that all of these exist as a pair of tautomers in solution.

Cationic groups were thought to prefer the equatorial position on a sugar molecule. We reinvestigated this so-called reverse anomeric effect by measuring axial/equatorial ratios of various glucosylamines and glycosylimidazoles. The conformational changes that occur upon N-protonation can be accounted for on the basis of steric effects and an enhancement of the normal anomeric effect. Substituted glucosylanilines fine-tune the localization of positive charge, which increases the steric hindrance to ionic solvation but enhances the anomeric effect to an even greater extent.

A highly accurate (±0.002 pH units!) NMR titration method, applicable to a mixture of closely related molecules, has been developed. We use this method to measure isotope effects on basicity and steric hindrance to ionic solvation. For amines we have demonstrated that the increased basicity on deuteration is of stereoelectronic origin. In contrast, computations and experimental evidence show that the well-known reduction of one-bond NMR coupling constants is not due to lone-pair delocalization, even though this had been the accepted interpretation for forty years.

We have discovered a remarkable new reaction, the addition of nucleophiles to a p-benzyne biradical. As evidence, we showed that the enediyne cyclodeca-1,5-diyn-3-ene, in the presence of lithium halide and a weak acid, can be converted to a good yield of 1-halotetrahydronaphthalene. The reaction is simply first-order in enediyne, and independent of the concentrations of acid and halide. These kinetics are consistent with rate-limiting cyclization to a p-benzyne biradical that rapidly adds halide, to form an aryl anion, which is then protonated. The reaction thus involves nucleophilic addition of halide, which is novel and quite different from the usual radical reactivity of a p-benzyne biradical.

The aldol condensation is a key reaction of organic chemistry, but its complete mechanism had never been elucidated. Now, through solvent kinetic isotope effects we have shown that Step 5, the final loss of hydroxide, is rate-limiting in the reactions between a benzaldehyde and an acetophenone.
Primary Research Area
Organic Chemistry
Interdisciplinary interests
Physical Organic
Physical Organic

Outreach Activities
Research in my lab has provided a small number of graduate students with an excellent opportunity to develop problem-solving skills while learning new relationships between molecular structure and reactivity.

In my lab, I have mentored numerous undergraduate, graduate, and postdoctoral scholars from diverse backgrounds. I have also taken advantage of our proximity to Mexico to present seminars at the Instituto Tecnológico de Tijuana and to participate in congresses of the Mexican Chemical Society.
Image Gallery

symmetric or asymmetric hydrogen bond?

transition state for decomposition of malonic anhydride to ketene + CO2

nucleophilic addition to para-benzyne diradical

Selected Publications   See