Cyclization reactions, entropy change

Page and Jencks (16) estimated that the entropy changes in solution may correspond to an effective concentration of about 6 x 10 M, and high EM values [10 -10 M] have been measured for simple cyclization reactions (17). However, with rare exceptions, the simple approximation of reactants with the help of synthetic supramolecular assemblies results in rate increases that are tiny by comparison with those achieved by enzymes, as evidenced by typical EM values of less than 10 M. 

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. 

Entropy Changes During Cyclization Reactions 71 A Consequence of High Bond Strength ... 

Bond formation a to the heteroatom is a common path to azetidines, oxetanes, thietanes and many oxo derivatives. Attack by the heteroatom on the 7-position is disfavored by the entropy factor the reaction rates for cyclization are about 100 times less than for attack on (3-positions. However, exounsaturation can change this relation drastically in dimethyl sulfoxide at 50°C, (3-bromopropionate ion cyclizes about 250 times more rapidly than bromoacetate. 

As any ring-opening polymerization, the polymerization of lactams is characterized by competition between the intermolecular reaction resulting in a linear polyamide and the intramolecular reaction of cyclization. Thus, if thermodynamically feasible, as indicated by a negative value of the free-energy change of polymerization AGp, the conversion of lactam to the linear polyamide can be realized if an appropriate reaction path exists for a reasonable rate in a polymer-monomer equilibrium characterized by a preponderance of linear macromolecules. The corresponding equilibrium monomer concentration [M]g is related to the standard enthalpy and entropy ASp of polymerization and to... 

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