The Logic behind a Physical–Organic Chemist’s Research Topics

Abstract

Abstract. Although my research has no common theme or defining area, a coherence connects the diverse topics, insofar as one project leads logically to another. Thus studies on mechanisms of hydrogen exchange in amides and amidines led to the influence of hydrogenbonding and to NMR methods for chemical kinetics, including 2D-EXSY spectroscopy.Another connection was the OH --catalyzed NH exchange in amines that had supported the hypothesis of stereoelectronic control. We therefore analyzed that hypothesis critically, tested it, found counterexamples, and proposed an alternative hypothesis. We next addressed one-bond NMR coupling constants in ethers and the reverse anomeric effect. The latter studies required a highly accurate NMR titration method that we developed to measure the additional steric bulk resulting from protonation of a substituent. This method is also applicable to measuring secondary isotope effects on acidity, and we could demonstrate that they arise from n-* delocalization, not from an inductive effect. Other studies included kinetic isotope effects for both dissociation and H exchange of aqueous NH 4 + , for C-N rotation in amides, and for a hydride transfer. The role of hydrogen-bonding led us to the rotation of NH 4 + within its solvent cage and then to the symmetry of hydrogen bonds. This review article is based on an address presented at the 249th National Meeting of the American Chemical Society in Denver CO, on the occasion of the James Flack Norris Award in Physical-Organic Chemistry. 1 It demonstrates the ways whereby one physicalorganic chemist, and physical-organic chemists in general, have investigated how molecular structure affects chemical reactivity. It also seeks to confirm my claim that "In my opinion, 2 physical organic chemistry represents the intellectual basis of organic chemistry. It asks (and answers!) fundamental questions about how chemical substances behave, and it rationalizes that behavior." 2 The reason that I won the James Flack Norris Award was for my "insight, rigorous analysis, and understanding of mechanisms and reactive intermediates", rather than any distinctive area of research with which I am associated. Instead of choosing one area to review here, I have tried to describe the path of my research for the past 40 years, as an expansion of an earlier article on this topic. 3 Each area seems to have engendered additional questions, leading to additional areas. Often those questions are marked by an intense skepticism, and the answers to those questions are supported by a logical analysis that I am proud of. I hope that this article will be as interesting, informative, and enjoyable to the reader as the research described here has been for me. A Beginner's ResearchMy Ph.D. thesis research was on mercuration of benzene, an electrophilic aromatic substitution that is accelerated by strong acid, and where we measured the H/D kinetic isotope effect. 4 To understand the origin of the acceleration it was necessary to consider acidity functions, including a new one, H...

Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD+ Analogues in Their Hydride Tunneling Reactions in Solution

“…The inverse 2°N-CH 3 /CD 3 EIEs (0.91−0.81) for the conversion from MAH/DMAH/DMPBIH to MA + / DMA + /DMPBI + are consistent with the "negative hyperconjugative effect" explanation, which uses the concept that the CD 3 -N base is stronger than the CH 3 -N base (Table 1). 35,36 The 10-N-CH 3 /CD 3 EIE on the conversion from MAH to MA + (0.883) is more inverse than that from DMAH to DMA + (0.905) (Table 1). This can be interpreted in terms of more electron density localized on N in MAH available for the negative hyperconjugative effect (due to less planar sp 2.31 hybridization) than in DMAH (more planar with sp 2.07 hybridization) (Table 3).…”

“…It was found that the CD 3 base is stronger than the CH 3 base, leading to EIE < 1. The current explanation uses the concept of negative hyperconjugative effect between the lone pair electrons in sp 3 -hybridized N and the empty σ* orbital of the β-C–L bond. , This effect weakens the C–L bond (via an S N 2-like mechanism, Scheme ). When CL 3 –NR 2 is protonated, forming CL 3 –N + HR 2 , this effect disappears, strengthening the C–L bond and thus resulting in an inverse EIE.…”

Bloch equations for proton exchange reactions in an aqueous solution

“…These rather complicated behaviors of amides suggest the existence of multiple proton exchange mechanisms due to the delocalization of the lone electron pair of its nitrogen. [45][46][47][48] Therefore, more reactions should be considered in the extension of the Bloch equations.…”

Chitosan as a Coupling Agent for Phosphate Glass Fibre/Polycaprolactone Composites

“…The phosphate glass immersed in aqueous solution will generate O − groups at the glass surface due to the rapid release of sodium ions, whilst the CS in low-pH aqueous solution could have generated NH 3 + groups (see Figure 9) [46]. Strong hydrogen bonds of 20-40 kcal/mol could be formed between the charged donor and acceptor groups that are nearly as strong as covalent bonds [48]. Kohl et al [49] reported that glass fibres with native surface hydroxyl groups could have strong hydrogen-bonding interactions (high surface energy) with polar functional groups of the polymers in glass fibre-reinforced composites.…”