Anomeric Effect

Objective

The objective of this exercise is to determine the origin of the anomeric effect.

Procedure

Substituents on a six-membered ring typically adopt the equatorial position to minimize steric interactions with the ring. In some instances, however, electronic effects result in a preference for the axial position, which is known as the anomeric effect. Polysaccharide provide common examples of anomeric linkages, in which axial oxygens frequently form the glycosidic bonds which join sugar rings.

In this exercise, you will search for an anomeric effect in 2-chlorotetrahydropyran.

A. Use the WebMO editor to build 2-chlorotetrahydropyran, with the chlorine atom in the axial position. Use PM3 to optimize the geometry of the resulting conformation, and measure its final energy. Using the optimized geometry, construct the equatorial conformation by simply changing two dihedral angles by 180°. Use PM3 to measure the final energy of the second conformation, and report the heats of formation of each conformation in the table below.

B. Repeat the calculations for chlorocyclohexane.

C. Calculate DfGeq-DfGax for each compound and compare your results in a table with the experimental results.

Compound DfGeq
(kJ/mol)		 DfGax
(kJ/mol)		 Calculated
DfGeq-DfGeq
(kJ/mol)		 Experimental
DfGeq-DfGeq
(kJ/mol)
2-chlorotetrahydropyran -259.9 -270.9 11.0 7.5
2-chlorotetrahydropyran -155.0 -153.5 -1.5 -2.1

For which compound does an anomeric effect exist? By comparing the structural differences between the two compounds, what factors likely cause the anomeric effect?

The anomeric effect exists for the pyran species, but not for the structurally similar cyclohexane species. Since the only difference between these species is the replacement of a carbon atom by an oxygen atom, we can deduce from this evidence that the anomeric effect must arise from an interaction between the oxygen atom and the axial chlorine atom. The most likely explanation is a bonding interaction between nonbonding oxygen electrons and an unoccupied atom orbital of chlorine (4p, 4d) or an unoccupied excited C-Cl molecular orbital, thus stabilizing the axial species, but not the equatorial one.

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