Cycloheptane pseudorotation

Die Pseudorotation des Cycloheptans erfordert nach Hendrickson 25> nur eine Aktivierungsenergie von etwa 2 kcal/Mol. 

Wahrend beim Cycloheptan das Umklappen des Siebenringes aus-schlieBlich durch Pseudorotation erfolgen sollte 25>, sind fiir substituierte und heterocyclische Derivate oft beide Moglichkeiten zu beriicksichtigen, da dort einzelne Pseudorotationsschritte stark erschwert sein konnen. 

Beim N-Methyl-homopiperidin (N-Methyl-hexahydro-azepin) 86 ist zu erwarten, daB die Pseudorotation und damit die Ringinversion ebenso wie beim Cycloheptan eine sehr kleine Aktivierungsenergie besitzt. 

The term pseudorotation was first appUed to cyclopentane like inversion, it has an atomic analogue in 5-coordinate compounds (e.g. PF5). ) The name means false rotation , and it is therefore appropriate for any conformational process which results in a conformation superposable on the original, and which differs from the original in being apparenUy rotated about one or more axes. Pseudorotation, in analogy with real molecular and internal rotations, can be free, as in cyclopentane, or more or less hindered, eis in cycloheptane and higher cycloalkanes. In moderately to severely hindered pseudorotation, it is appropriate to consider distinct stable conformations which are pseudorotation partners, and these cases are often amenable to study by dynamic nmr methods. When the barrier to pseudorotation is very low, or in the limit when pseudorotation is free, it is not really justified to talk about separate stable conformations (e.g. the C2 and Cg forms of cyclopentane), because strictly there is only one conformation, and the pseudorotation is simply a molecular vibration. 

Benzene annelation significantly increases the barrier to ring inversion processes. Saturated seven-membered rings can invert by pseudorotation (pseudorotation barrier is 2 kcal/mole) which has not been measured by NMR techniques. The AG for the ring inversion process for the benzene-annellated derivatives of cycloheptane (which probably exists in a chair form) was determined to be 10.9 kcal/mole at Tj, = — 57°C (186, 298, 322). Equilibria in tricyclic organic derivatives have been studied more extensively. Several different inversion processes have been reported and depend on structural type. The following are examples of ring inversion processes. 

As ring size increases, there are progressively more conformations that have to be considered. For cycloheptane, four conformations have been calculated to be particularly stable. NMR investigations indicate that the twist-chair is the most stable. Various derivatives adopt mainly twist-chair conformations. The individual twist-chair conformations interconvert rapidly by pseudorotation. The most recent MM4 and CCSD/6-311+ + G computations (see Section 2.3) indicate the following relative energies. Figure 2.17 shows the conformations. 

Cycloheptane and cyclooctane data on the thermal properties are also given in Table 3.1 They show little change from the cyclopentane and cyclohexane properties. Again, there is no indication of increasing amounts of conformational entropy in the transition entropies. For cyclooctane in solution H and NMR could prove ring-inversions and pseudorotation among the boat-chair conformations through the twist-boat-chair intermediate to very low temperatures (100 K). Only about 6% of the cydooctane could be found at about 300 K in the other three crown-family... 

By this analysis, planar cyclopentane should be most stable, then cyclohexane, cyclobutane (which is about the same as cycloheptane), and finally cyclopropane. However, this is not the correct order for the inherent stability of cyclic alkanes. The energy inherent to each ring is shown in Table 8.1. The data in this table clearly show that cyclopropane is the highest in energy, but they also show that cyclohexane is lower in energy than cyclopentane. Indeed, cyclopentane and cyclohexane are the more stable (lowest energy) cyclic alkanes in the series 45-49 because cUc alkanes are not planar. The pseudorotation mentioned before leads to conformations that are lower in energy than... 

This flattening is due to the presence of an odd niimber of carbons in the ring and it means that there will be some torsion strain due to eclipsing bonds and atoms in this form of cycloheptane. Some twisting of the ring can occur to relieve this strain, but such pseudorotation may increase strain elsewhere in the molecule. This increase in strain makes conformations 49A and 49B for cycloheptane higher in energy than the chair conformations of cyclohexane. 

In contrast to the six-membered rings, the seven-membered cychc systems are much more flexible. The cycloheptane rings occur in complex pseudoro-tational equihbria that has numerous conformations of similar energy with the absence of significant pseudorotational barriers. Owing to these reasons the study of such compounds is difficult using experimental techniques and therefore condensation with a benzene ring or the introduction of a double bond freezes the pseudorotational equflibrium at a low temperature [107]. 

Semi-quantitative potential-energy curves for pseudorotation within chair and boat forms of 1,1-dimethyl- and 1,1,2,2-, 1,1,3,3-, and 1,1,4,4-tetramethyl-cycloheptanes have been constructed interconversion of the preferred twist-chair forms of the latter is calculated to proceed via the twist-boat form rather than by pseudorotation within the chair family. 

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