The aim of the grant proposal was to subject a number of S_N2 reactions to Non-Steady-State Kinetic (NSSK) studies for the purpose determining whether or not the data are compatible with the 1-step mechanism (eq. 1) and if not, to attempt to establish the generality of the 2-step mechanism (eq. 2) for these reactions.

The systems that the P.I.'s group, in collaboration with the Parker's group, has subjected to NSSK study during the first year of the project involve the S_N2 reactions of the nucleophile p-nitrophenoxide ion (PNPO) with various substrates including p-nitrobenzyl bromide (PNBB), methyl p-nitrobenzenesulfonate (MPNBS) and methyl p-toluenesulfonate (MPMBS). Results show that these S_N2 systems do not follow the one-step processes (1) and they most likely proceed by a 2-step mechanism accompanied with a kinetically significant intermediate prior to the traditionally-thought concerted S_N2 mechanistic step (2).

            The NSSK study of the systems was carried out by means of UV-Vis spectroscopy method together with the contemporary digital processing technology and the computational simulation approach. ^{1, 2} The kinetic method was initiated by Parker and co-workers. The kinetic data were collected by following the decay of the nucleophile over a wavelength range from 400nm-500nm. The extent of reaction vs. time profiles (E.R. - t) of the reactions deviate from those expected for the simple 1-step mechanism, indicating that the reactions do not follow the simple mechanism (1). In addition to the use of the E.R. – t profiles as mechanistic probes, time ratios (t_0.5/t_0.05) and rate constant ratios (k_init/k_s.s) were also determined and found to deviate from those of the simple mechanism. The fit of the experimental results to the 2-step mechanism suggest that these reactions follow the complex 2-step mechanism (2).

            The results were also subjected to the instantaneous rate constant (k_inst) analysis method developed very recently by Parker. ³ The k_inst was found to change with reaction time until when the reaction reaches steady-state. This analysis as well as the conventional pseudo first-order kinetic analysis over the systems studied clearly show the kinetic behavior expected for the 2-step S_N2 mechanism.

            While the research was expanded to the other systems proposed in the proposal, we have been striving to obtain the structural information of the intermediates suggested. Methods such as the UV-Vis and NMR spectroscopy have been applied. For example, the instantaneous rate constant analysis based on the absorbance data collected showed that the intermediate absorbs over the similar wavelength range as does the nucleophile, implicating that it would be a molecular complex between the two reactants. We propose that the intermediate would be an ion-dipole complex in which the nucleophilic oxygen of the phenoxide ion interacts with the electrophilic carbon center of the substrates. Further evidence is being gathered to provide insights into the detailed structure of the intermediates.

            Our work suggests that the NSSK method can be applied to provide mechanistic details for other S_N2 reactions. The results obtained in this research project will greatly enhance the depth of understanding of the relevant organic and biological reactions and eventually contribute to the pedagogy of the basic organic chemistry.

            Undergraduate and graduate students involved in this project have learned kinetic procedures, basic organic synthesis, mechanistic analysis techniques and the use of modern analytical instrumentation. Since this project involves computational simulation, students have been trained in using computer programs as well. We believe that the mastering of the knowledge and the techniques involved in this project will make students more competitive in their future careers.

1. Handoo, K. L.; Lu, Y.; Parker, V. D. J. Am. Chem. Soc.  2003, 125, 9381.
2. Lu, Y.; Handoo, K. L.; Parker, V. D. Org. Biomol. Chem.  2003, 1, 36.
3. Parker, V.D. J. Phys. Org. Chem. 2006, 19, 714.