Kinetic product distribution rationalizing

Priebe and coworkers [107,178] have attempted to rationalize the product distribution in terms of Pearson s theory of hard and soft acids and bases (HSAB) [179], concluding as a broad generalization that soft bases (S-, N- and C-nucleophiles) form bonds at the softer C-3 electrophilic center, whereas hard bases (O-based nucleophiles) react preferentially at the harder C-l center to give glycosides. They acknowledge that other factors may overrule this interpretation, such as when C-nucleophiles give kinetic C-l-alkylated products whose formation is not reversible. 

It has therefore been established170 from the product distributions that, while the oxymercuration is reversible, unless a base (e.g. sodium acetate) is added to the reaction medium, and gives almost exclusively the more stable compound 199, the aminomercu-ration takes place to give the kinetically controlled adduct 200, or under thermodynamic control the aminomercurial 201. Reactions are kinetically controlled when the mercurating species is a mercury(II) salt deriving from a weak acid such as mercury(II) acetate. Conversely, they are thermodynamically controlled with the covalent mercury(II) chloride. In the latter case, the presence of a strong acid in the medium allows the thermodynamically controlled product to be obtained. 

This chapter provides examples showing how molecular modeling can be used not only to rationalize observed product distributions in kinetically-controlled reactions, but also to anticipate and ultimately control the distribution of products. 

The rational design of a reaction system to produce a desired polymer is more feasible today by virtue of mathematical tools which permit one to predict product distribution as affected by reactor type and conditions. New analytical tools such as gel permeation chromatography are beginning to be used to check technical predictions and to aid in defining molecular parameters as they affect product properties. The vast majority of work concerns bulk or solution polymerization in isothermal batch or continuous stirred tank reactors. There is a clear need to develop techniques to permit fuller application of reaction engineering to realistic nonisothermal systems, emulsion systems, and systems at high conversion found industrially. A mathematical framework is also needed which will start with carefully planned experimental data and efficiently indicate a polymerization mechanism and statistical estimates of kinetic constants rather than vice-versa. 

These results can be rationalized by the reaction coordinate diagram shown in Figure 6.27. Because AG for conversion of 72 to 73 is smaller than the value of AG for conversion of 72 to 74, formation of 73 is faster. Therefore, more of 73 is formed during the early stages of the reaction, so the distribution of products is said to reflect kinetic control. As the reaction proceeds, the much slower processes that convert 73 first to 72 and then to 74 become more significant. Eventually, equilibrium is established between 73 and 74, and the product distribution at the end of the reaction is said to reflect thermodynamic control. 

A kinetic study with analysis of the exchange network has shownthat two deuterium atoms from the prochiral a-carbon atoms of [2, 5,5- Hjcyclopentanone are removed as much as 70 times faster than the other two by the catalyst (1/ S,-3/J,41 )-3-dimethylaminomethyl-l,7,7-trimethyl-2-norbomanamine. The reactions of cyclopentadiene with BrCl and amine-BrG complexes have been examined in an attempt to distinguish different modes of reaction. The product distributions using the two reagents differ considerably BrQ gives more ds 1,4-addition whereas all the complexes give more trans 1,2-addition. The results have been rationalized on the basis of the expected ion-pair intermediate occurring before and after the transition state for the complexes and BrCl, respectively. 

Liquid-liquid-solid reactors are commonly used for biphasic reactions catalyzed by immobilized phase-transfer catalysts (which form the third, solid phase). Certain basic aspects of such reactors were considered in Chapter 19. Three-phase reactions of this type are also encountered in biological reactions, for example, the enzymatic synthesis of amino acid esters in polyphasic media (Vidaluc et al., 1983), and the production of L-phenylalanine utilizing enzymatic resolution in the presence of an organic solvent (Dahod and Empie, 1986). Predictably, the performance of these reactors is influenced by the usual kinetic and mass transfer aspects of heterogeneous systems (see Lilly, 1982 Chen et al., 1982 Woodley et al., 1991a,b). Additionally, performance is also influenced by the complex hydrodynamics associated with the flow of two liquids past a bed of solids (Mitarai and Kawakami, 1994 Huneke and Flaschel, 1998). It is noteworthy, for instance, that phase distribution within the reactor is different from that in the feed and is also a function of position within the reactor and within the voids of each pellet in the bed. More intensive research is needed before these reactors can be rationally designed. 

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