Analysis of Heterocyclic Molecules

Another important feature associated with heterocyclic rings is the reduced steric repulsions for axial substituents which results from replacement of a methylene group in cyclohexane by oxygen, nitrogen, or sulfur. This effect is readily apparent in d5-2-methyl-5-tert-butyl-l,3-dioxane, in which the preferred conformation has 

3- dithianes, along with their comparative -AG° values in cyclohexane. The general point to be recognized is that the conformational free energy is a function not only of the size of the group but also of the molecular environment which it encounters. 

The decreased preference for the equatorial orientation of a 5-alkyl group in 

3- dioxailes and 1,3-dithianes is evident from these data. It is also interesting that the increased preference for the equatorial orientation of a 2- or 4-methyl group in 

3- dioxane disappears in going to 1,3-dithiane. The conformational free energies of 2-alkyl substituents in 1,3-dithianes are very similar to those of cyclohexane (actually slightly smaller) because of the longer C-S bond length compared to C-O. 

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Photoelectron spectroscopy145 has been particularly useful in the conformational analysis of heterocyclic molecules possessing vicinal electron lone pairs, especially in the hexahydropyridazine system.12,145a In such a system the two lone-pair orbitals on nitrogen do not ionize at the same potential because of interactions with each other and with other orbitals. Lone-pair-lone-pair interactions are expected to dominate and are dependent upon the... 

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