Activation entropy structural effects

One should expect the activation entropy (AS ) to C=C rotation in Case 1 push-pull ethylenes to be negative, since the increase in polarity in the transition state should increase the order in the solvated structure. The effect should increase with increasing difference in polarity between ground and transition states, and also with increasing solvent polarity. These expectations have been completely borne out by experiments (78,140,143), as Table 22 shows. Contrary to what is generally found for conformational processes (144), AS values -20 e.u. are frequently found for C=C rotation in push-pull systems. 

The 5,6-dihydropyrimidine-6-yl radicals discussed above behave, in their reactions with nitrobenzenes, like the simpler radicals CH2OH and CH(al-kyl)Oalkyl do, i.e. they react exclusively by addition to give nitroxyl radicals and uncatalyzed heterolysis is not observed (khs < 10 s ). If, however, a methyl group is introduced at C(6) (= CJ of the pyrimidine-6-yl radical, the corresponding nitroxyl radicals heterolyze with rate constants at 20 °C of 10 to 5 X 10 s depending on the structure of the pyrimidine and of the nitrobenzene (Eq. 16). This SnI type reaction is characterized by activation enthalpies of 30-40 kJ mol and activation entropies of — 89 to — 7 Jmol K (entropy control) [27]. The rate-enhancing effect of the methyl group is, of course, due to... 

Quantum chemical calculations need not be limited to the description of the structures and properties of stable molecules, that is, molecules which can actually be observed and characterized experimentally. They may as easily be applied to molecules which are highly reactive ( reactive intermediates ) and, even more interesting, to molecules which are not minima on the overall potential energy surface, but rather correspond to species which connect energy minima ( transition states or transition structures ). In the latter case, there are (and there can be) no experimental structure data. Transition states do not exist in the sense that they can be observed let alone characterized. However, the energies of transition states, relative to energies of reactants, may be inferred from experimental reaction rates, and qualitative information about transition-state geometries may be inferred from such quantities as activation entropies and activation volumes as well as kinetic isotope effects. 

Experiments cannot tell us what transition states look like. The fact is that transition states cannot even be detected experimentally let alone characterized, at least not directly. While measured activation energies relate to the energies of transition states above reactants, and while activation entropies and activation volumes, as well as kinetic isotope effects, may be invoked to imply some aspects of transition-state structure, no experiment can actually provide direct information about the detailed geometries and/or other physical properties of transition states. Quite simply, transition states do not exist in terms of a stable population of molecules on which experimental measurements may be made. Experimental activation parameters provide some guide, but tell us little detail about what actually transpires in going from reactants to products. 

IV. Entropy of Activation and Structure From the inception of transition state theory, entropies of activation have been discussed from the twin aspects of molecular structure and reaction mechanism. Even though there is considerable overlap between these two aspects we shall utilize a formal separation, reserving much of the discussion of mechanism for the next section. In this section our primary concern shall be the effect that structural change in a non-reacting part of a molecule has upon the entropy and enthalpy of activation for that molecule. The nature of interactions (polar, steric, and resonance) between the substituent group and the reaction center clearly relates to the problem of reaction mechanism, the solution of which involves, in the final analysis, a detailed description of the disposition of the atoms in the transition state and the interactions among them. 

For reactions between ions of like sign, solvation effects give a decrease in entropy on activation. Consideration of the internal structure leads again to a decrease in entropy on activation. The two effects reinforce each other, and also are in the same direction as predicted by the electrostatic treatment as given in Section 7.4.5. This would indicate p factors of less than unity. 

In the ionization mechanism exemplified by benzhydryl thiocyanate, the reaction is strictly first order over a wide concentration range. The rate of isomerization increases with increasing solvent polarity Tracer and stereochemical evidence indicates that this involves an internal ion-pair mechanism. Isomerization is faster than isotopic exchange and so it was concluded that the former process occurs via an intimate ion pair which was shown to collapse to thiocyanate and isothiocyanate in the ratio of 5 1. In the case of optically active 4-chlorobenzhydryl thiocyanate in acetonitrile, racemization occurs at a rate comparable with isomerization. With a given solvent the structural effect acts essentially on the energy term and for a given substrate, the solvent effect acts essentially on the entropy term. 

We have recently reported a detailed discussion on solvation effects in this particular reaction [17]. Briefly, the experimental activation energy value at 298 K in the gas phase has been reported to be 19.7 kcal/mol [70]. In toluene, the experimental activation enthalpy was reported at 15.8 1.4 kcal/mol, with an activation entropy of —38 4 cal/mol K [71]. Four possible reaction pathways are possible for the acrolein and s-cis butadiene reaction. Consistent with previous conventions [17,72,73], the transition structures are denoted as NC (endo, s-cis acrolein), XC (exo, s-cis acrolein), NT (endo, s-trans acrolein), and XT (exo, s-trans acrolein), as illustrated for the parent reaction in vacuum in Fig. 5. 

Table 8.5 lists data for acetolysis of 2-substituted cyclohexyl brosylates having the general structure 25. The data confirm that a trans acetate reacts faster than does a cis acetate. The activation entropy data suggest a more ordered transition structure for the acetolysis of the trans isomer, consistent with the model of anchimeric assistance. A trans bromine is nearly as effective as a trans acetoxy, but a trans chloro group is far less effective—apparently due to the low stability of a chloronium ion in comparison with a bromonium ion. 

We examined more closely the thermodynamics of the reaction between the diene 2p and but-2-enone by measuring the activation parameters of the reactions conducted in water and in a water-methanol mixture (50 50, v/v, the rate of the reaction in pure methanol is too small to be recorded with reliability). To check if there is a special effect due to the presence of the sugar moiety linked to die buta-1,3-diene unit, we studied the cycloaddition between methoxybutadiene and but-2-enone under the same conditions. TTie results are summarized in Table IV. As anticipated, the second-order rate constant increases in pure water and the rate enhancement comes only from an increase of the activation entropy (+32.3 J.mole . T" from water-methanol to pure water). It must also be noted that the increase of the activation entropy is even more important in the case of the diene 2P than for methoxybutadiene. This could be related with the interaction of the glucose moiety with the water structure and could have some importance in connection with biological problems. In fact, it seems that glucose acts as a structure-making compound and enhances the hydrophobic effect. We have thus demonstrated, as previously postulated, that the rate enhancements in aqueous cycloadditions have an entropic origin. 

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