Relative thermodynamic stability

The composition of the products from the isomerization of an unsaturated compound under the influence of a catalytic amount of a base is governed by the relative thermodynamic stabilities of the starting compound and the product. Of particular synthetic interest are isomerizations in which there is an accumulation of an isomer in the isomerization sequence. Isolation of the desired intermediate in a reasonable state of purity is often a matter of careful selection of the base and the solvent. The following reactions are representative examples ... 

By protodetritiation of the thiazolium salt (152) and of 2 tritiothiamine (153) Kemp and O Brien (432) measured a kinetic isotope effect, of 2.7 for (152). They evaluated the rate of protonation of the corresponding yiides and found that the enzyme-mediated reaction of thiamine with pyruvate is at least 10 times faster than the maximum rate possible with 152. The scale of this rate ratio establishes the presence within the enzyme of a higher concentration of thiamine ylide than can be realized in water. Thus a major role of the enzyme might be to change the relative thermodynamic stabilities of thiamine and its ylide (432). 

The relative stability of the intermediates determines the position of substitution under kinetically controlled conditions. For naphthalene, the preferred site for electrophilic attack is the 1-position. Two factors can result in substitution at the 2-position. If the electrophile is very bulky, the hydrogen on the adjacent ring may cause a steric preference for attack at C-2. Under conditions of reversible substitution, where relative thermodynamic stability is the controlling factor, 2-substitution is frequently preferred. An example of this behavior is in sulfonation, where low-temperature reaction gives the 1-isomer but at elevated temperatures the 2-isomer is formed. ... 

The higher strain energy in thiirene dioxides (19) compared to thiirane dioxides (17) is obvious. Yet, the elimination of sulfur dioxide from the latter is significantly faster than one would expect for a thermally allowed concerted process. Consequently, either aromatic-type conjugative stabilization effects are operative in thiirene dioxides2,12 or the relative ease of S02 elimination reflects the relative thermodynamic stability of the (diradical )99 intermediates involved in the nonconcerted stepwise elimination process. 

Another elegant example of the thermal generation and subsequent intramolecular cycloaddition of an o-QM can be found in Snider s biomimetic synthesis of the tetracyclic core of bisabosquals.2 Treatment of the starting material with acid causes the MOM ethers to cleave from the phenol core (Fig. 4.3). Under thermal conditions, a proton transfer ensues from one of the phenols to its neighboring benzylic alcohol residue. Upon expulsion of water, an o-QM forms. The E or Z geometry of the o-QM intermediate and its propensity toward interception by formaldehyde, water, or itself, again prove inconsequential as the outcome is decided by the relative thermodynamic stabilities among accessible products. 

A review11 with 123 references is given on amino acid bonding preferences in complexes of platinum and palladium. The preferences for a particular donor atom for Pd11 depends primarily on relative thermodynamic stabilities of the complexes formed. Sizes of potential chelate rings often play a crucial role in determining donor atom preferences. 

However, examination of the spectral properties of the starting ketones and isolated photoproducts indicated that the product distribution was determined by the photochemical properties of the molecules rather than their relative thermodynamic stabilities. These workers proposed that these... 

This is a situation that must rise where the alternative products are mutually interconvertible under the conditions of the reaction, either by direct isomerisation or by reversal of the reaction to form the starting material which then undergoes new attack to yield a more thermodynamically stable isomer. It is important to emphasise that the relative proportions of alternative products formed will be defined by their relative thermodynamic stabilities under the conditions of the reaction, which may possibly differ from those of the isolated molecules. Thus if m-dimethylbenzene is heated at 82° with HF and a catalytic amount of BF3 the proportions of the three isomeric dimethylbenzenes in the product resemble very closely those calculated thermodynamically ... 

Support for the actual elimination step, in each case, being E2 is provided by the fact that changing the alkyl substituents on C and Cfi results in reaction rates that, in general, increase with the relative thermodynamic stability of the product alkene. 

In the above examples the composition of the equilibrium mixture is, of course, governed by the relative thermodynamic stability of the... 

Fig. 3. Most favorable isomer for each of the several species 2a-7a of the generic [Nin(octadienediyl)PH3] complex, together with the relative thermodynamic stabilities (AG in...

Numerous disperse dyes are marketed in a metastable crystalline form that gives significantly higher uptake than the corresponding more stable modification. The molar free enthalpy difference can be used as a criterion of the relative thermodynamic stabilities of two different modifications [53]. Certain dyes can be isolated in several different morphological forms. For example, an azopyrazole yellow disperse dye (3.52) was prepared in five different crystal forms and applied to cellulose acetate fibres. Each form exhibited a different saturation limit, the less stable modifications giving the higher values [54]. 

Another method for evaluating carbocation stability involves the measurement of solvolysis rates (14,45). Typically, the transition state of the rate-determining step in SN1 reactions is assumed to closely resemble the intermediate ion pair, on the basis of the Hammond postulate (46). Thus, the free energy of activation for this reaction, AG, reflects the relative thermodynamic stabilities of the intermediate carbocations. 

Unsubstituted Copper Phthalocyanine Blue is polymorphous. X-ray diffraction diagrams point to five different crystal modifications (a, (3, y, 8, e) (Fig. 91). The relative thermodynamic stability of the individual cystal phases decreases in the following order (3>e>8>a = y [13-16],... 

The relative thermodynamic stability and therefore solubility of two polymorphs can take one of two forms, either monotropic or enantiotropic, depending on the relative values of AHm and Tm in Eq. 2 [7,8]. 

The isomers of the simplest allene, 1,2-propadiene 1, are propyne 2 and cydopro-pene 3 (Scheme 1.2). Their isomerization engergies have been measured and calculated [2-4]. Compound 2 is clearly the most stable isomer, 1 lies 2.1 kj higher and 3 about 22.3 kj. Hence in principle, if reversible, thermodynamics of an equilibrium should favor the alkyne. However, several factors can influence this in two ways, i.e. a change of the relative thermodynamic stability, for example by substituents, or a... 

In order to rationalize the factors determining the enantioselectivity of the hydrosilylation of the para-substituted styrenes, we have calculated the relative thermodynamic stabilities of all the intermediates of the catalytic cycle that are precursors of the two enantiomeric products as a function of the para-substituted substrates. Since, the 5 configuration product was formed in 64% ee from styrene, whereas 4-(dimethylamino)styrene afforded the R product with 64% ee [6], we have performed all calculations with these two different substrates. We shall demonstrate, in fact, that the relative thermodynamic stabilities of the fi3-allylic complexes are decisive for both the regio and the stereoselectivity. 

As mentioned above, the calculations performed for styrene as a substrate suggests that the enantioselectivity can be directly correlated with the relative thermodynamic stabilities of the r 3-allylic complexes. Indeed, the exo stereoisomer, precursor of the enantiomeric product found in excess experimentally, becomes favoured with respect to the endo one upon t 3-coordination, and remains thermodynamically more stable until product release. However, the observed energy differences in the relative stabilities of the different allylic forms (1-2 kcal/mol) are certainly at the limit of accuracy of density functional calculations. 

As an inversion of enantioselectivity was observed experimentally for 4-(dimethylamino)styrene, (64% R ee) as compared to styrene (64% S ee), we have recalculated the relative thermodynamic stabilities of endo and exo isomers for each step of the catalytic cycle using this second substrate. These calculations allow us to verify the quality of our findings by checking if an inversion in the relative stabilities of the endo and the exo-ri3-silyl-allyl intermediates (with the endo being more stable than the exo) is observed with 4-(dimethylamino)styrene. Using 4-(dimethylamino)styrene as the substrate, the calculated relative stabilities of the intermediates in the Chalk-Harrod mechanism are shown as parenthetic values in Figure 15. 

Considering this second substrate, the first part of the reaction pathway is very similar to the one computed for styrene. In fact, both the endo-K and alkyl complexes are thermodynamically more stable than the corresponding exo species by -0.8 and -0.7 kcal/mol, respectively. Interestingly, the relative thermodynamic stabilities still favour the endo isomers even upon formation of the t 3-silyl-allyl intermediates. This is opposite to that observed when unsubstituted styrene is the substrate where we have calculated an inversion in the relative stabilities ofthe exo and endo pathways at this point. 

A significant review of several aspects of the phase diagram computation (phase diagram calculations in teaching, research and industry) has been published by Chang (2006). The relationship between the characteristic features of a phase diagram and the relative thermodynamic stabilities of the phases involved has been there underlined and exemplified. Representative examples of binary, ternary and high-order alloy systems have been presented. Moreover a number of applications have... 

Such equilibria are governed by thermodynamics, and so the abundances of the different species in solution are dependent on their relative thermodynamic stabilities. If, however, such a mixture of species is applied in, for example, a conjugate addition reaction, the product formation will be controlled by kinetics, and it is most likely that Cu2Li2Mc4 would be kinetically the most active species present. 

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