Entropy-controlled reaction

Two extreme situations should be noted. If p =0, then 8AG = — 78A5, and the reaction series is entirely entropy controlled it is said to be isoenthalpic. If I/p = 0, then 8AG = 8A//, and the series is enthalpy controlled, or isoentropic. All of these relationships apply also to equilibria, but we will be concerned with kinetic quantities. 

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... 

The activation parameters for the (bimolecular) addition and the (unim-olecular) heterolysis steps have been determined [28] for the case of Ri, R2, R3 = H or CH3 and the results are shown in Fig. 1. It is obvious that the heterolysis reaction is entropy controlled which is the consequence of the highly ionic transition state which leads to freezing of water molecules with the concomitant loss of entropy. 

K. N. Houk, N. G. Rondan, and J. Mareda, Theoretical Studies of Halocarbene Cycloaddition Selectivities. A New Interpretation of Negative Activation Energies and Entropy Control of Selectivities, Tetrahedron 1985, 41, 1555. Calculations on carbene addition reactions led to a general explanation of why it is possible for very exothermic, bimolecular reactions to have negative activation enthalpies. 

These are easily the largest values ever observed for bimolecular, chemically controlled reactions and imply an enormously loose transition state complex. Since collision frequencies are of the order of 1011 3 liter/mole-sec. we see that we need to account for a positive entropy of activation of the order of 4 Gibbs/mole. 

Negative activation energies for cycloaddition reactions of some carbenes are reported60 and they confirm the presence of a pre-association equilibrium on the reaction pathway. In addition, the entropy control of the cycloaddition of halocarbenes to the C=C double bond was extensively reported61 and explained by the presence of a weakly bound intermediate complex (25), which is reversibly formed and is probably a CT complex62. Its presence is also supported by direct kinetic data59,63. 

When you meet the new reactions awaiting you in the rest of the book you should reflect that each is controlled by an energy difference. If it is an equilibrium, A G° must be favourable, if a kinetically controlled reaction, AG must be favourable, and either of these could be dominated by enthalpy or entropy and could be modified by temperature control or by choice of solvent. 

In a very different area of organic chemistry Ken produced a series of landmark theoretical papers on carbene reactions. He developed a general theory, showing how orbital interactions influence reactivity and selectivity in carbene additions to alkenes. Ken also showed how entropy control of reactivity and negative activation barriers in carbene addition reactions could both be explained by a new, unified model. 

The potential stereoselectivity of this photocyclization process has recently been investigated for the two rigid 2-allylanilines 70 and 71169. Irradiation of compound 70 at room temperature gives a mixture of diastereomers trans-12 and cis-12 with a little stereoselectivity (equation 23). While a poor stereoselectivity is also observed for 71, the photocyclization is regioselective, where the products trans-12 and cis-12 are minor (equation 24). However, the diastereoselectivity of trans-12 vs cis-12 is increased in the case of 71 when the temperature is changed, indicating that the reaction is significantly entropy-controlled. In addition, the observation of fluorescent exciplex formation for 70 and 71 supports the electron-transfer mechanism for the photocyclization of 2-allylanilines. 

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