Thermodynamically controlled reactions

Tetrose (Section 25 3) A carbohydrate with four carbon atoms Thermochemistry (Section 2 18) The study of heat changes that accompany chemical processes Thermodynamically controlled reaction (Section 10 10) Re action in which the reaction conditions permit two or more products to equilibrate giving a predominance of the most stable product... 

Thermodynamically controlled reaction (Section 10.10) Reaction in which the reaction conditions permit two or more products to equilibrate, giving a predominance of the most stable product. 

Thermodynamically-Controlled Reaction. A reaction the product ratio for which is determined solely by the relative thermochemical stabilities of the different products (product formation must be reversible, or separate low-energy pathways interconnecting the products must exist). 

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. 

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. 

The distribution of products is dependant on the concentrations demonstrating that this is a truly thermodynamically controlled reaction. 

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. 

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. 

Boltzmann Equation. The equation governing the distribution of products in Thermodynamically-Controlled Reaction. 

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 ... 

Olefin metathesis is a thermodynamically controlled reaction that has become a highly versatile synthetic method for alkene preparation. Although originally discovered in the it was not until the mid-1980s that well-... 

A rate-controlled reaction is one whose major product is formed through the transition state with the lowest Aff. A thermodynamic-controlled reaction is one whose major product has the lower (more negative) Af/ of reaction. Reactions may shift from rate to thermodynamic control with increasing temperature, especially when the formation of the rate-controlled product is reversible. 

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. 

In general, reactions that aren t easily reversible are kinetically controlled because equilibrium is rarely established. In kinetically controlled reactions, the product with the lowest-energy transition state predominates. Reactions that are easily reversible are thermody namically controlled, unless something occurs that prevents equilibrium. In thermodynamically controlled reactions, the lowest-energy product predominates. 

The thermodynamically controlled reactions between ClCH2GeMe2Cl and O- or N-TMS derivatives of 5-ethyl-3-morpholinone493 and 2,5-piperazinedione489 yield the monochelate 147 and bis-chelate 148a, respectively. 

Selectivity Selectivity means that one of several reaction products is formed preferentially or exclusively. In the simplest case, for example, reaction product 1 is formed at the expense of reaction product 2. Selectivities of this type are usually the result of a kinetically controlled reaction process, or kinetic control. This means that they are usually not the consequence of an equilibrium being established under the reaction conditions between the alternative reaction products 1 and 2. In this latter case one would have a thermodynamically controlled reaction process, or thermodynamic control. ... 

Cellular Automata Models of Kinetically and Thermodynamically Controlled Reactions. 

The first formed product now cyclizes to form the second six-membered ring. This recreates a carbocation at the tertiary centre like the one that set off the fragmentation as the more nucleophilic end of the isolated alkene attacks the end of the conjugate electrophile. This is a thermodynamically controlled reaction with the new stereogenic centre choosing an equatorial substituent. 

By moving from kinetically controlled to thermodynamically controlled reactions (Fig. 27), MIMs can now be synthesized in near-quantitative yields, primarily... 

Fig. 27 Examples of thermodynamically controlled reactions employed in the near-quantitative synthesis of MIMs. (a) Disulfide-exchange reaction permits equilibration between a bis(ammo-nium) disulfide dumbbell and a crown ether macrocycle to yield a mixture of [2]- and [3]rotaxanes quantitatively [194], (b) Olefin metathesis at high concentration on a benzylic amide macrocycle greatly favors the catenated species [196]. (c) Self-correcting imine bonds allow for nearly quantitative selection of a [2]rotaxane from an appropriate dynamic combinatorial library [76], (d) A weak nucleophile (E) equilibrates the components of a donor-acceptor [2]catenane in a dynamic Sn2 reaction [205]...

In the early 1960s, seminal work by Jencks and coworkers demonstrated that formation and hydrolysis of C=N bonds were proceeding via a carbinolamine intermediate, thus leading to a more general mechanism of addition reactions on carbonyl groups [17-19]. The dynamic nature of the reaction of imine formation can be exploited to drive the equilibrium either forward or backwards. Since the reaction involves the loss of a molecule of water, adding or removing water from the reaction mixture proved an efficient way to shift the equilibrium in either direction. The responsive behavior of imines to external stimuli makes the reversible reaction of imine formation perfectly suited for DCC experiments [20], Thermodynamically controlled reactions based on imine chemistry include (1) imine condensation/hydrolysis, (2) transiminations, and (3) imine-metathesis reactions... 

Reaction of tetrahydro-4/7-thiopyranone 795 with meso-794 gave the bridged oxathiocins 775 in 68% yield and 92% ee, respectively. Oxazocine 775 existed exclusively in the hemiacetal form, suggesting that the stereocenter originating from C-6 in 794 could be set under thermodynamic control. Reaction of 795 with the readly available 3.5 1 mixture of ( )-794 and meso-794, respectively, produced 775 in the same yield and ee. 

The excellent yields of the cyclic tetramer over potentially accessible larger structures have been demonstrated to result from thermodynamic product control under equilibrating conditions <2006OL2755, 2006TL4041>. The facile and selective formation of a specific molecule in a thermodynamically controlled reaction, where the covalent bond has the ability to be formed and reversibly broken, is the subject matter of dynamic covalent chemistry <2002AGE898>. 

---