Conformational Effects on Reactivity

Because its hydroxyl group occupies an equatorial position, the trans isomer 2 is more stable than the cis isomer 1 by an amount equal to -AG° for the hydroxyl 

A similar analysis of the hydrolysis of the esters 3 and 4 is possible. From Table 3.5 (p. 118), we see that the conformational free energy of the carbethoxy substituent is 1.2 kcal/mol. The cis isomer should be placed above 4, then, by about 

2 kcal/mol. The saponification transition states resemble intermediates M and N. The substituent group increases in size as the transition state is reached, and, as a result, the difference in energy between M and N is greater than 1.2 kcal/mol. As a 

These examples serve to illustrate some of the ways in which conformation can affect reactivity. In later chapters and in Part B, other examples will be given as specific reactions are discussed. One other important point relating conformation to reactivity will be raised in Chapter 4. This is the Curtin-Hammett principle, which states an important limitation on the validity of arguments that attribute reactivity differences to conformational effects. 

The diaxial interactions that are responsible for a large portion of the conformational free energy of the hydroxyl group are relieved in the transition state as the reaction proceeds toward sp hybridization at the carbon atom undergoing oxidation. Because the substituent is effectively becoming smaller as reaction proceeds, the energy difference between the diastereomeric transition states is less than that 

Isomers with equatorial 2-alkoxy groups are more reactive than those with axial 2-alkoxy groups/ The greater reactivity of the equatorial isomers is the result of the alignment of the lone pairs on both the endocyclic and the exocyclic oxygen to assist in abstraction of the hydrogen. 

Other reagents which oxidize acetals such as ozone and JV-bromosuccinimide show similar reactivity trends.  

Another example is the lack of oxygen exchange with solvent in the hydrolysis of gluconolactone. Simple acyclic esters usually undergo oxygen exchange at a rate that is competitive with hydrolysis. This occurs through the intermediacy of the addition intermediate. 

Even though proton exchange can occur in the tetrahedral intermediate, the anomeric effect leads to preferential loss of the axial oxygen. 

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Conformational effects, on reactivity of cycloamyloses, 23 242, 245-249 Constant Ci, values for, 33 273, 274 Contact catalysis, mechanism of, 2 251 Contact catalysts, surface area measurements for studying, 1 65... 

Counterion effects similar to those in ionic chain copolymerizations of alkenes (Secs. 6-4a-2, 6-4b-2) are present. Thus, copolymerizations of cyclopentene and norbomene with rhenium- and ruthenium-based initiators yield copolymers very rich in norbomene, while a more reactive (less discriminating) tungsten-based initiator yields a copolymer with comparable amounts of the two comonomers [Ivin, 1987]. Monomer reactivity ratios are also sensitive to solvent and temperature. Polymer conformational effects on reactivity have been observed in NCA copolymerizations where the particular polymer chain conformation, which is usually solvent-dependent, results in different interactions with each monomer [Imanishi, 1984]. 

Conformational effects on reactivity can be considered under the heading of steric effects,11 though in these cases we are considering not the effect of a group X and that of another group X upon reactivity at a site Y but the effect of the conformation of the molecule. Many reactions fail entirely unless the molecules are able to assume the proper conformation. An example is the rearrangement of N-benzoylnorephedrine. The two dia-... 

If two different three-dimensional arrangements of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are conformations otherwise, they are configurations. Configurations represent isomers that can be separated however, conformers cannot be separated. Conformational effects on reactivity may be considered under the steric effects. 

Many of the conformational effects on reactivity can be described and analyzed in terms of the difference between van der Waals interactions in the ground state and the transition state. Some cyclic molecules contain another type of strain, known as angle strain, resulting from distortion of bond angles from optimal values. We would now like to consider how such distortions might effect reactivity. 

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