Thermodynamics thermodynamically controlled process

It was clearly shown by NMR spectroscopy that the addition of ammonia or primary or secondary alkylamines at position 5 of the 1,2,4-triazine 4-oxides to give the adducts 89 is a kinetically controlled process, while addition at position 3 to form the ring-opening products 85 is a thermodynamically controlled process. 

Self-assembly is a thermodynamically controlled process. The formation of the capsules and the exchange of guest molecules proceed within seconds to hours, sometimes days, but finally, an equilibrium is reached which is governed by a finely balanced interplay of enthalpy and entropy. A... 

In the Michael addition reaction depicted in eq. [146] the diastereomeric sulfoxides 312 are formed under kinetic control conditions, therefore, the addition of sodium diethyl malonate is an irreversible process. On the contrary, addition of sodium methoxide to the sulfoxide 311 is a thermodynamically controlled process and leads to a mixture of diastereomeric ]3-methoxysulfoxides 313 in a 31 69 ratio (320). 

The above observations are consistent with a thermodynamically controlled process shown in Figure 9.17. Thus, when two strands, A and B, with complementary H bonding sequences and termini that can be reversible cross-linked, are present in the same solution under redox conditions, products A-A (or self-cyclized A ), B-B (or self-cyclized B ), and A-B, may be generated. Among these products, A-B gains the most stabilization from the newly generated, complementary intramolecular H bonds because of the formation of the two disulfide bonds. Thus,... 

In Figure 10.1 the time course of thermodynamically and kinetically controlled processes catalysed by biocatalysts are compared. The product yield at the maximum or end point is influenced by pH, temperature, ionic strength, and the solubility of the product. In the kinetically controlled process (but not in the thermodynamically controlled process) the maximum yield also depends on the properties of the enzyme (see next sections). In both processes the enzyme properties determine the time required to reach the desired end point. The conditions under which maximum product yields are obtained do not generally coincide with the conditions where the enzyme has its optimal kinetic properties or stability. The primary objective is to obtain maximum yields. For this aim it is not sufficient to know the kinetic properties of the enzyme as functions of various parameters. It is also necessary to know how the thermodynamically or the kinetically controlled maximum is influenced by pH, temperature and ionic strength, and how this may be influenced by the immobilization of the biocatalysts on different supports. 

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 ... 

The optimum yield of a condensation product is obtained at the pH where Ka has a maximum. For peptide synthesis with serine proteases this coincides with the pH where the enzyme kinetic properties have their maxima. For the synthesis of penicillins with penicillin amidase, or esters with serine proteases or esterases, the pH of maximum product yield is much lower than the pH optimum of the enzymes. For penicillin amidase the pH stability is also markedly reduced at pH 4-5. Thus, in these cases, thermodynamically controlled processes for the synthesis of the condensation products are not favorable. When these enzymes are used as catalysts in thermodynamically controlled hydrolysis reactions an increase in pH increases the product yield. Penicilhn hydrolysis is generally carried out at pH about 8.0, where the enzyme has its optimum. At this pH the equiUbrium yield of hydrolysis product is about 97%. It could be further increased by increasing the pH. Due to the limited stability of the enzyme and the product 6-aminopenicillanic acid at pH>8, a higher pH is not used in the biotechnological process. 

The temperature dependence of the equilibrium concentration of a product in a thermodynamically controlled process is determined by the heat (enthalpy change) of the catalyzed reaction. For an exothermic process an increase in temperature... 

In the subsequent, thermodynamically controlled process the more stable adduct At becomes predominant through a reequilibration via the starting substrate. The observed pseudo first-order rate constant is given by Eq. (10).46... 

Unfortunately, equilibrium and rate data in this area are practically nonexistent. However, sometimes it has been possible to obtain evidence for kinetically and thermodynamically controlled processes. 

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. 

Monitoring by GC provided evidence [25] for several intermediates in the isomerisation of tetrahydrodicyclopentadiene (39) to adamantane (40), Scheme 2.15, a thermodynamically controlled process (discovered serendipitously) [26]. Molecular mechanics calculations indicated that the slow step of the rearrangement could occur prior to formation of exo-41, which rearranges in a few minutes to 40 on treatment with AlBr3 in CS2 at 25°C. When the reaction of exo-41 was conducted at — 10°C and monitored by GC over a period of 100 minutes, the presence of two additional intermediates (42 and 43) was revealed [25]. 

As a brief aside, we note that many chemical reactions are similarly kinetically rather than thermodynamically controlled [72-77], in like manner as Eq. (8). While only chemical reactions are discussed in Refs. [72-77], the same principle likewise applies with respect to all kinetically rather than thermodynamically controlled processes, for example kinetically rather than thermodynamically controlled physical and nuclear reactions. As we discussed in Sect. 4 if nuclear reactions were thermodynamically rather than kinetically controlled then there would be nothing but (iron + equilibrium blackbody radiation) — an iron-dead Universe. 

There has been no systematic study of the Reformatsky reaction of conjugated enones under conditions where both 1,2- and 1,4-products could be determined. In general, only 1,2-addition products are obtained with a-bromoacetates. However, in one favorable case, exclusive 1,4-addition was observed (equation 23). Reactions with a-bromoisobutyrates commonly give 1,4-addition products. It is not known whether these are the result of a kinetically or thermodynamically controlled process. Low temperature reactions of conjugated enones with preformed Reformatsky reagents of a-bromoisobutyrates, conditions most favorable for a kinetically controlled process, have apparently never been reported. 

Patents are still appearing on further substitution reactions of naphthalene disulphonic acids by both kinetically and thermodynamically controlled processes, which have been of great commercial importance for many years. Isomer distributions for the sulphonation of other arenesulphonic acids and some alkyl derivatives have been compiled142. 

Metal/halogen exchange with 2,5-dibromopyridine leads exclusively and efficiently to 2-bromo-5-lithiopyridine in a thermodynamically controlled process it has been suggested that the 2-pyridyl anion is destabilised by electrostatic repulsion between nitrogen lone pair and the adjacent anion " this same factor is probably important in the greater difficulty found in generating 2,3-pyridyne (see section 5.3.2). The example below illustrates the use of the Weinreb amide of formic acid as a formyl-transfer reagent. ... 

Metallatiou of cumene. Cumene (I) is metallated by n-pentylsodium in the presence of TMEDA in octane on the ring and is then isomerized to a-cumyl-sodium (2) in a thermodynamically controlled process. 

Intramolecular reactions are often more favored than analogous intermole-cular reactions. This advantage is known either as the proximity effect or as the chelate effect. To set it on a quantitative scale, the effective molarity (EM) parameter has been devised [54-56]. For thermodynamically controlled processes, the EM is defined by Eq. 11, where iCintra and iCinter are the equilibrium constants for the intramolecular process leading to a cyclic species and the corresponding intermolecular process leading to a linear adduct (Fig. 9). 

Two Co(ll) coordination polymers with formulas [Co(oda)(H20)2 H20]n and [Co(oda)(H20)-H20]n (H2oda=oxydiacetic acid) were characterized by single crystal XRD and TG. [Co(oda)(H20)2 H20]n has a covalently linked 1-D chain structure, while [Co(oda)(H20) H20]ii has a covalently linked 3-D chiral network with channels. The structures showed an unusual example of topological isomerism, and the structural interconversion between [Co(oda)(H20)2 H20]n and [Co(oda)(H20)-H20]n revealed that self-assembly in the synthesis and interconversion of crystalline solids is a thermodynamically controlled process [135]. 

A particularly interesting example of a chiral scaffold was given by Komarov, Borner and co-workers. They reported the intramolecular resolution of a P-stereogenic centre by a thermodynamically controlled process (Scheme 2.61). 

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