Synthesis near thermodynamic equilibrium

A small group of researchers preferred synthesis near thermodynamic equilibrium. Jacobson et al. (1989) applied very early the equilibration of mixtures of 123-06 and I23-O7 in a closed system. A similar method was used by Radaelli et al. (1992). Conder et al. (1994a,b), Kruger et al. (1994, 1997), Kaldis (1997) and Kaldis et al. (1997b) used equilibration via the vapor phase of locally separated 123-0 and Y metal for their nearequilibrium samples (table 2). 

Barron defined true and false chirality in systems and pointed out that only true chirality in a system allows absolute asymmetric synthesis when the system is near thermodynamic equilibrium, but that false chirality may also be effective... 

Unsymmetrical ketones can yield two different enolates, and in some cases the one that is the less stable thermodynamically is formed faster.148 Scheme 24 illustrates the example of 2-methylcyclopentanone. When this ketone is added slowly to excess f-butyllithium, the proton is removed preferentially from the less substituted carbon. If excess ketone is added, it can serve as a proton donor to allow equilibrium to be established, and nearly all the enolate is then the more highly substituted one.149 It may be possible in some cases to take advantage of such a selective formation of one of two possible enolates in synthesis. A more general procedure is to use a compound in which the desired position is activated... 

Methanol synthesis from waste C02 streams has the potential to contribute to the limitation of worldwide C02 emissions and to serve as an alternative carbon source to fossil fuels if a renewable source of hydrogen is available (see Section 5.3.1). The main obstacle to methanol synthesis from C02-rich streams is thermodynamics. The equilibrium yield of methanol from 25% C0/C02 75% H2 mixtures of varying C0/C02 ratio is shown in Figure 5.3.5. For pure CO, a one-pass methanol yield of nearly 55% can be obtained at 525 K, while pure C02 would only yield 18%. Besides the addition of CO, this equilibrium limitation can be overcome by operating at lower temperatures (an option that requires more active catalysts), implementing higher recycle ratios, or product extraction (an option that requires higher capital investment) [8]. 

In addition to its acceptance of unnatural substrates, several other characteristics make NeuAc aldolase a useful synthesis catalyst. The cloning of the enzyme has reduced its cost and offers the potential to produce large quantities of new proteins with improved stability or with altered stereoselectivity. This approach could be used to extend the chain of a variety of aldoses by two carbon units. Although the optimal pH for activity of NeuAc aldolase is near pH 7.5 at 37 °C, the enzyme is active at pH 7-9.82.83 TTie protein is stable in the presence of oxygen and does not require added cofactors. - One drawback is that an excess of pyruvate (the less expensive reagent) must be used in synthetic reactions to shift the equilibrium towards the formation of product approximately 7 equiv. of pyruvate are needed to attain 90% conversion of ManNAc to NeuAc at equilibrium. It may be possible to avoid the need for an excess of pyruvate by coupling the synthesis of NeuAc to a more thermodynamically favored process. 

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