Entropies of cyclization

These authors conclude that the problem of internal solvation is still an experimental and theoretical challenge GB measurements for this type of molecules of low volatility are not always in good agreement194. Molecular orbital calculations may help to solve the difficult experimental problems, but they have to take into account conformational isomerisms and the prototropic tautomerisms of the amidine and guanidine moieties. In light of the above discussion, the proton affinities deduced from the experimental GB values should be based on accurate estimations of the entropy of cyclization 86. 

The course of intramolecular enone alkene photocycloaddition is dependent on the number of atoms between the two reactive C=C bonds. For example, E- and Z-isomers of 1-acylhepta-1,6-diene (147) form a 1 1 mixture of stereoisomeric cycloadducts 148 and 149 upon irradiation, while no E Z isomerization occurs (Scheme 6.67a).764 The initial bonding takes place between the C2 (Cp) and C6 atoms, in agreement with the empirical rule of five,165 the regioselective, kinetically preferred formation of five-membered ring biradical intermediates over larger rings due to the entropies of cyclization. As a result, the biradical 150 is not observed. For comparison, the acylhexadiene 151 photolysis also proceeds via a 1,4-biradical (152) formed by an initial 1,5-cyclization (Scheme 6.67b).766... 

Standard entropy of cyclization caldeg mo Polymeric selenium to cyclooctaselenium -5.5 (4)... 

Standard entropy of cyclization cal deg mol Polymeric sulphur to cyclooctasuUur -4.63 (12)... 

While five-membered ring formation occurs smoothly with a large array of substrates, six-membered ring formation appears less general, presumably because the higher entropy of cyclization to the six-membered ring allowed competing noncyclization reactions to predominate. Functionalization of cyclic intermediates and cyclization via Pd-catalyzed allylation will be presented as in the previous sections. 

The equilibrium for cyclic hemiacetal formation is favorable, in contrast to its intermolecular variant. What tips the balance is the relatively more favorable (or, better, less unfavorable) entropy of cyclization (Section 17-7). 

It is interesting to note that although the first examples of template effects were observed in nitrogen macrocycles (see chapter 2) no template effect appears to operate in the synthesis of 72. Richman and Atkins note this in their original report . The authors replaced the sodium cation with tetramethylammonium cations and still obtained greater than 50% yield of tetra-N-tosyl-72. Shaw considered this problem and suggested that because of the bulky N-tosyl groups, .. . the loss of internal entropy on cyclization is small He offered this as an explanation for the apparent lack of a template effect in the cyclization. 

These groups will reduce the number of conformational degrees of freedom (such as bond rotation) in the reactants and/or intermediates. It is this reduction which is thought to facilitate cyclization relative to polymerization for these systems in essence, the enhancement of cyclization can be considered to be largely a consequence of favourable entropy effects. 

A scheme depicting general base catalysis is shown in Fig. 7.2,b. Because the HO anion is more nucleophilic than any base-activated H20 molecule, intermolecular general base catalysis (Fig. 7.2,bl) is all but impossible in water, except for highly reactive esters (see below). In contrast, entropy may greatly facilitate intramolecular general base catalysis (Fig. 7.2,b2) under conditions of very low HO anion concentrations. Alkaline ester hydrolysis is a particular case of intermolecular nucleophilic attack (Fig. 7.2,cl). Intramolecular nucleophilic attacks (Fig. 7.2,c2) are reactions of cyclization-elimination to be discussed in Chapt. 8. 

Formation of 2//-azirines by thermal decomposition of vinyl azides has been shown to exhibit small entropy of activation and insensitivity to solvent polarity acyclic vinyl azides decompose more readily than analogous cyclic ones and it is advantageous to have a hydrogen atom cis to the azido group ( -are more reactive than Z-isomers). These results and the linear correlation found for ring-substiment effects on decomposition of a-styryl azides are consistent with a nonconcerted mechanism in which elimination of nitrogen and cyclization into a three-membered ring proceeds synchronously. 

The formation of the transition state AB leads to the loss of translational and rotational entropy as described above, although there are some compensating gains in internal rotation and vibration. The intramolecular cyclization in equation 2.23 involves the loss of only some entropy of internal rotation. 

As part of a biomimetic study for the enzyme class II aldolase" the equilibrium was reported for the cyclen complex, hydroxo-Zn(II)-l-(4-bromophenacyl)-l,4,7,10-tetraaza-cyclododecane and the intramolecular enolate 20, formed from Zn(II) and the enolate of l-(4-bromophenacyl)cyclen. This cyclization reaction was shown to be endothermic by 8.7 kJmol. However, with an entropy of 19 JmoU K it proceeds readily enough to show facile H/D exchange from the CH2 group of the exocyclic ligand. We wonder about the enthalpy and entropy changes associated with a different choice of other polyamines and/or central metals. 

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