Heterocyclic molecules, conformational analysis

Unusual Properties of Usual Molecules. Conformational Analysis of Cyclohexene, Its Derivatives and Heterocyclic Analogues... 

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... 

Empirical force field calculations (MM2(8S)) using atomic point charges calculated by AMI calculations (MM2 // AMI) correctly reproduce the AMI surface for heterocyclic betaines 55, 126, and 127 (93JST105). The methodology allows extensive conformational analysis of medium to large-size molecules by semiempirical calculations (AMI). The interaction energies for the dimerization of these betaines have also been well reproduced. 

An analysis of conformational flexibility of pyrimidine ring in related molecules (purine, aminopyrimidine, and unsubstituted pyrimidine (Scheme 21.4)) indicates that the flat character of the potential energy surface around minimum is a general property of pyrimidine ring. A presence of amino group and fused imidazole ring only promotes increase of conformational flexibility of heterocycle. 

The most complete picture of conformational flexibility of pyrimidine rings in nucleic acid bases has been provided by molecular dynamics study of isolated molecules using ab initio Carr-Parinello method [45]. According to these studies, the population of planar conformation of heterocycle does not exceed 20% for thymine, cytosine, and guanine and amounts to about 30% for adenine (Table 21.4). These values are considerably smaller as compared to estimations based on vibrational frequencies mentioned above. Such difference is quite natural because in the case of vibrational analysis, only the lowest ring out-of-plane normal mode is considered. However, there are also smaller contributions of the other ring out-of-plane vibrations not included in this analysis. Therefore, such estimation should be considered as an upper limit for assessment of population of planar conformation of ring. 

We have covered a lot of ground in this chapter, and have used the huge topic of saturated heterocycles to explain a lot, not just about the reactivity and conformation of rings. Many of these explanations involved consideration of the alignment of orbitals— we called these stereoelectronic effects. The same analysis allowed us to make sense of the NMR spectra, and in particular the coupling constants, of cyclic molecules, both heterocycUc and carbocyclic. And by thinking about symmetry in these cyclic molecules we were also able to deduce the origins of symmetry-related features (such as diastereotopic protons) in the NMR spectra of acycUc compounds. 

In this chapter we would like to demonstrate that careful analysis of conformational properties of such simple molecules as cyclohexene, its derivatives and heterocyclic analogues provides new and unexpected information about general background of modern stereochemistry. Especially this concerns character of ring inversion process. 

As tlie configurational and conformational analyses for the unsatoated heterocyclic rings are not informative owing to the adoption of planar conformation, then it is essential to study intermolecular interactions. The detailed analysis was carried out for isoxazole, imidazole, and indole molecules. Since there wasn t any significant difference in the pattern of interaction for these aromatic rings, these results can be extrapolated to all other heteroaromatic... 

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