And thermodynamically controlled reaction

A. Neuforth, P. G. Seybold, L. B. Kier, and C.- K. Cheng, Cellular automata models of kinet-ically and thermodynamically controlled reactions. Int. J. Chem. Kinet. 2000, 32, 529-534. 

Cellular Automata Models of Kinetically and Thermodynamically Controlled Reactions. 

Basic to protease catalyzed oligopeptide synthesis is equilibrium- or thermodynamic control to direct reversal of proteolysis . Difficulties encountered include low reaction rates, high stoichiometric amounts of enzyme, and the need to apply direct approaches to shift the reactions towards formation of desired products. Reaction conditions that lead to product precipitation or extraction increase efficiency of the reverse reaction. Kinetically controlled syntheses has proved useful for serine and cysteine proteases that form activated acyl enzyme intermediates during catalysis. This approach generally involves use of activated acyl moieties, such as esters, as donor components which significantly accelerate the reaction rate. This study makes use of principles from both kinetic and thermodynamically controlled reactions in that, reactants are activated by formation of esters and products precipitate fi om reactions. 

The variation in kinetically and thermodynamically controlled reactions is seen as an advantage in the formulation of further carbosilane systems of two general types ... 

In both cases, the phosphorus ylide (B), ( = Si)2C=PMe2X, where X=C1, Br, is the kinetically and thermodynamically controlled reaction product. The formation of the phosphino-substituted ylide C and the phosphane D was not observed. 

Unsaturated sugars are useful synthetic intermediates (11). The most commonly used are the so-called glycals (1,5- or 1,4-anhydroalditol-l-enes). In the presence of a Lewis-acid catalyst, 3,4,6-tri-0-acetyl-l,5-anhydro-2-deoxy-D-arabinohex-l-enitol [2873-29-2] commonly called D-glucal triacetate, adds nucleophiles in both kineticaHy controlled and thermodynamically controlled (soft bases predominately at C-3 and hard bases primarily at C-1) reactions (11,13). 

Variations in the proportions of the different components of product mixtures are observed in reactions that involve anhydrous HF31-80-82-84-85 and in pyridinium poly(hydrogen fluoride).86 These variations can also be explained in terms of kinetic and thermodynamic control. Thus, less stable, but more rapidly formed, dianhydrides isomerize under thermodynamic conditions to give more-stable products. It has also been noted that the starting isomeric forms of the ketose influence the kinetic outcome of the reaction.119... 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

This preferential formation of 1 1 adduct to form 1,4-hexadiene in a mixture of ethylene and butadiene was further studied by Cramer (4). He concluded that the results appeared to be the consequence of thermodynamic control reactions through a relatively stable 7r-crotyl Rh complex. 

A theoretical study at a HF/3-21G level of stationary structures in view of modeling the kinetic and thermodynamic controls by solvent effects was carried out by Andres and coworkers [294], The reaction mechanism for the addition of azide anion to methyl 2,3-dideaoxy-2,3-epimino-oeL-eiythrofuranoside, methyl 2,3-anhydro-a-L-ciythrofuranoside and methyl 2,3-anhydro-P-L-eiythrofuranoside were investigated. The reaction mechanism presents alternative pathways (with two saddle points of index 1) which act in a kinetically competitive way. The results indicate that the inclusion of solvent effects changes the order of stability of products and saddle points. From the structural point of view, the solvent affects the energy of the saddles but not their geometric parameters. Other stationary points geometries are also stable. 

Intramolecular nitroaldol reactions are a useful choice for the conversion of sugars into polyhydroxylated nitro cyclopentanes, nitro cyclohexanes and their derivatives.46 Baer et al. in the course of their studies on the cyclization of 6-deoxy-6-nitrohexoses under kinetic and thermodynamic control,47 established the reaction pathway involved in the formation of nitroinositols mediated by intramolecular Henry reactions. Firstly, a nitronate is formed and then, under thermodynamic control conditions, an epimerization occurs before cyclization. But, under kinetic controlled conditions, the cyclization occurs first.48... 

It was recognized in early examples of nucleophilic addition to acceptor-substituted allenes that formation of the non-conjugated product 158 is a kinetically controlled reaction. On the other hand, the conjugated product 159 is the result of a thermodynamically controlled reaction [205, 215]. Apparently, after the attack of the nucleophile on the central carbon atom of the allene 155, the intermediate 156 is formed first. This has to execute a torsion of 90° to merge into the allylic carbanion 157. Whereas 156 can only yield the product 158 by proton transfer, the protonation of 157 leads to both 158 and 159. 

In another article, however, [59] it was shown that in the most case this reaction gave mixtures of two heterocycles 53 and 54. To develop procedures allowing regioselective synthesis of both heterocyclic systems, the authors of [59] studied an influence of temperature regime and catalyst type on the direction of this MCR. With application of ultrasonication and microwave irradiation it was estabhshed that the reaction studied can pass under kinetic and thermodynamic control. 

While the Sn2 reaction represents an extreme case, it is clear that the solvent is capable of selectively stabilizing (or destabilizing) one product over another in a thermodynamically-controlled reaction, or one transition state over another in a kinetically-controlled reaction. Differentiation might be effected by steric and/or electronic considerations. 

Thermodynamically-Controlled Reaction. A chemical reaction which has gone all the way to completion, and the ratio of different possible products is related to their thermochemical stabilities according to the Boltzmann Equation. 

The product yield of a thermodynamically controlled reaction depends on pH when acids and bases participate in the reaction. This pH-dependence can be analyzed using known values of p AT -values of the acidic and basic groups of the reactants and the products. For thermodynamically controlled processes the apparent eqnilibrium constant for the product yield in condensation reactions, K, mnst be determined. This equilibrium constant is defined by the following equation ... 

There are two possible configurations, endo and exo, for bridged bicyclic compounds resulting from the reaction of a cyclic diene and cyclic dienophile. A substituent on a bridge is endo if it is closer to the longer of the two other bridges, and it is exo if it is closer to the shorter bridge. Most of these reactions result in an endo product. However, if this reaction is reversible, and thermodynamically controlled, the exo product is formed. 

A convenient preparation of 2-deoxy sugars [204] from glycosyl halides is based on the rapid and irreversible migration of an acyloxy group from C-2 to the anomeric center upon generation of the glycosyl radicals. This is a thermodynamically controlled reaction because it restores a d-a-d arrangement. 

The regioselective DoM effects can be rationalized in terms of kinetic and thermodynamic control of the reaction (83T2009). The relative thermodynamic acidity (NaNH2/NH3/-25°C) of pyridine hydrogens... 

The reactions of elemental fluorine with inorganic compounds are exothermic and often have little or no reaction associated activation energies. Most often the major synthetic problem is kinetic and thermodynamic control of these vigorous reactions. It is therefore a very unusual synthetic situation when reactions must be activated by methods such as high temperatures, plasmas, or photochemical means. Examples of such cases are the synthesis of NO+BF4 by the photochemically activated reaction of fluorine and oxygen with boronnitride (52) and the plasma-activated synthesis of (CF112)n from graphite (53). 

It is instructive, in this context, to compare the case of assembly of both nitrosylated iron sulfur tetranuclear clusters and the related clusters with pendant thiolate groups (13), with the laborious and stepwise initial synthesis (38) of cubane C8H8 this comparison is, of course, simply one between thermodynamically controlled processes, in the case of the iron sulfur systems, and kinetically controlled reactions for C8H8 synthesis. 

The scope and limitations of the metal anions of 2-halo-l,3-dithiane trans-1,3-dioxide as diastereoselective carbonyl anion equivalents has been explored with regard to reaction with aldehydes.79 Reactions of metallated trans-, 3-dithiolanc 1,3-dioxide (five-membered ring) with aldehydes under kinetic and thermodynamic control have also been studied and contrasted with those of the metallated monooxide, parent sulfide, and 1,3-dithiane 1,3-dioxide (six-membered ring).80... 

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