Kenneth Charles Westaway

The use of microwave ovens for rapid organic synthesis

Abstract Four different types of organic reactions have been studied and seven different organic compounds have been prepared, under pressure in a microwave oven. Considerable rate increases have been observed.

Using kinetic isotope effects to determine the structure of the transition states of SN2 reactions

Publisher Summary This chapter focuses on the use of kinetic isotope effects (KIEs) as a method of determining the mechanism and transition state structures of S N 2 reactions. A primary KIE is found when the bond to the isotopically labeled atom is breaking or forming in the transition state of the slow step of the reaction. Three basic relationships indicate how the magnitude of a primary KIE varies with transition state structure in S N 2 reactions. Because the smallest α-carbon KIE reported for an S N 2 reaction is 80% of the largest-observed KIE, the qualitative conclusion would be that all these S N 2 reactions have symmetric or almost symmetric transition states. A secondary KIE is observed when the bond to the isotopically substituted atom is not being broken or formed in the transition state of the rate-determining step of the reaction. KIEs still remain one of the most convincing probes of transition state structure and reaction mechanism, especially when applied at several positions in a reaction.

Secondary deuterium kinetic isotope effects and transition state structure

Publisher Summary This chapter is concerned with secondary deuterium kinetic isotope effects. The chapter illustrates some of the important recent advances in the interpretation and uses of these kinetic isotope effects to elucidate reaction mechanisms. Other excellent reviews of secondary deuterium kinetic isotope effects (KIEs) have also been discussed in the chapter. The chapter demonstrates the ways in which secondary deuterium and tritium KIEs can be used to elucidate the mechanisms of reactions and determine the structure of their transition states. Secondary a-deuterium KIEs have been widely used to determine the mechanism of S N reactions and to elucidate the structure of their transition states. Some of the significant studies illustrating these principles are presented in this chapter. In particular, the advantages of using both theoretical calculations and experimental data to solve these problems have been emphasized in the chapter.

Determining the Transition-State Structure for Different SN2 Reactions Using Experimental Nucleophile Carbon and Secondary α-Deuterium Kinetic Isotope Effects and Theory

Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/ k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S N2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller nucleophile KIE indicates the Nu-C alpha transition state bond is shorter and a smaller ( k H/ k D) alpha is found when the Nu-LG distance in the transition state is shorter) suggests that the transition state is tighter with a slightly shorter NC-C alpha bond and a much shorter C alpha-LG bond when the substrate has a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion. The results show that the experimental nucleophile (11)C/ (14)C KIEs can be used to determine transition-state structure in different reactions and that the usual method of interpreting these KIEs is correct. The magnitude of the experimental secondary alpha-deuterium KIE is related to the nucleophile-leaving group distance in the S N2 transition state ( R TS) for reactions with a halogen leaving group. Unfortunately, the calculated and experimental ( k H/ k D) alphas change oppositely with leaving group ability. However, the calculated ( k H/ k D) alphas duplicate both the trend in the KIE with leaving group ability and the magnitude of the ( k H/ k D) alphas for the ethyl halide reactions when different scale factors are used for the high and the low energy vibrations. This suggests it is critical that different scaling factors for the low and high energy vibrations be used if one wishes to duplicate experimental ( k H/ k D) alphas. Finally, neither the experimental nor the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction fit the trend found for the reactions with a halogen leaving group. This presumably is found because of the bulky (sterically hindered) leaving group in the tosylate reaction. From every prospective, the tosylate reaction is too different from the halogen reactions to be compared.

Large concentration effects on the magnitude of secondary alpha-deuterium kinetic isotope effects

Because the secondary alpha-deuterium kinetic isotope effects in some SN2 and E2 reactions are strongly concentration dependent, isotope effects measured at a single concentration could lead to erroneous conclusions about the mechanisms and transition state structures.

The effect of conjugation on the magnitude of secondary alpha deuterium kinetic isotope effects

Abstract The unexpectedly small secondary alpha deuterium KIE in the 4-methoxybenzyl chloride-thiophenoxide ion reaction is attributed to the increased conjugation between the aryl group and the alpha carbon in the S N 2 transition state.