Conformational barriers

Annelation can introduce large conformational barriers, to the extent of making possible the resolution into enantiomers of a tribenzoxepine (71CB2923). Chapters 5.16, 5.17, 5.18 and 5.19 contain much more information on inversion barriers, bond lengths and bond angles. 

Molecules that are chiral as a result of barriers to conformational interconversion can be racemized if the enantiomeric conformers are interconverted. The rate of racemization will depend upon the conformational barrier. For example, -cyclooctene is chiral. E-Cycloalkenes can be racemized by a conformational process involving reorienting of the... 

Malloy, T. B., Jr., Conformational Barriers and Interconversion Pathways in some Small-Ring Molecules, 11, 97. 

Conformational Barriers and Interconveision Pathways in Some Small Ring Molecules (Malloy, Bauman and Carreira) 11 97... 

EPR spectroscopy is the most important method for determining the structures of transient radicals. Information obtained from the EPR spectra of organic radicals in solution are (i) the centre position of the spectra associated with g factors, (ii) the number and spacing of the spectral lines related to hyperfine splitting (hfs) constants, (iii) the total absorption intensity which corresponds to the radical concentration, and (iv) the line widths which can offer kinetic information such as rotational or conformational barriers. The basic principles as well as extensive treatments of EPR spectroscopy have been described in a number of books and reviews and the reader is referred to this literature for a general discussion [28 30]. 

While it is difficult to verify experimentally the calculated heights of conformational barriers, it seems that flexible-residue methods can give better results. Energies based on rigid residues increase to artificially high values at large distances from the starting < ), conformation (22). ... 

Conformational Barriers and Interconversion Pathways in Some Small... 

The conformational barriers in acyclic radicals are smaller than those in closed-shell acycles, with the barrier to rotation in the ethyl radical on the order of tenths of a kilocalorie per mole. The barriers increase for heteroatom-substituted radicals, such as the hydroxymethyl radical, which has a rotational barrier of 5 kcal/mol. Radicals that are conjugated with a n system, such as allyl, benzyl, and radicals adjacent to a carbonyl group, have barriers to rotation on the order of 10 kcal/mol. Such barriers can lead to rotational rate constants that are smaller than the rate constants of competing radical reactions, as was demonstrated with a-amide radicals, and this type of effect permits acyclic stereocontrol in some cases. "... 

The main interest in (212) and related dibenzo and dinaphtho compounds is in the conformational barrier to racemization of optically active derivatives, which requires deformation of the tub to the planar form. The compounds have proven to be optically stable at very high temperatures (64JCS2326). A minimum AH value of 71 kJ mol-1 has been calculated for racemization of the resolved 3,10-dicarboxylic esters of (212). Thermal decomposition sets in at 240 °C and leads to the phenanthridine (214) and benzonitrile, presumably via a diradical (213) (63JOC3007). 

In solution the barriers to conformational change are often small, even when the molecule has a built-in restriction on motion. Conformational barriers calculated for isolated molecules in the gas phase that reveal the nature of some of these barriers are likely to be good reflections of the real barriers in solvents such as chloroform. There usually are many conformations present at any time in such solutions and they are in equilibrium. The equilibria are likely to be much more restricted in polar media. It is very important for us to discover the extent of the equilibrium, that is, the number of conformations involved, the relative proportion of each, and the rate of transformation between them. Such a task is virtually impossible from theoretical considerations, and two major approaches using physical techniques, mainly nmr, are possible. These have been discussed in some detail for small molecules and can be summarized as follows. 

The predominant conformation of the 3,4-dimethyl compound (39) has the 3-methyl axial and the 4-methyl equatorial <76JCS(P2)l86l). The diequatorial conformation is thought (77JCS(P2)1816> to make no appreciable contribution and the measured conformational barrier (AH = 55 kJ mol-1) is probably due to slowing of a nitrogen inversion process. The related bicyclic system (40) has also been studied (80MI22802). 

As we have seen, the anomeric effect confers a double-bond character to each C—0 bond of conformer D the energy barrier for a C —0 bond rotation in acetals must therefore be higher than that observed in simple alkanes. Borgen and Dale (41) may have provided the first evidence for this point by observing that 1,3,7,9-tetraoxacyclododecane (37) has a much higher conformational barrier (11 kcal/mol) than comparable 12-membered rings such as cyclododecane (7.3 kcal/mol (42) or 1,4,7,10-tetraoxacyclododecane (5.5 and 6.8 kcal/mol (43)). It was also shown that the two 1,3-dioxa groupings in 37 exist in a conformation identical to that of dimethoxymethane, i.e. the conformation D. 

In 1978, Haenel19) reported the synthesis of pyridinophanes 23 (65%) and 24 (44%). According to variable temperature HNMR studies, the conformational barrier in 23 in 12.3 kcal/mole, a slightly higher value than that observed for 2. The H NMR spectrum of 24 remains unchanged to —90 °C this is consistent with... 

Durig and Little (1981) determined the conformational barriers to internal rotation of methyl vinyl ketone by IR and Raman spectroscopy. They recorded IR spectra of the gaseous and the solid states and the Raman spectrum of the liquid state. They also determined the potential function for internal rotation of the asymmetric top and obtained the following potential constants VI = 180 9, V2 = 827 107, V 3 = 113 8, and V4 = 150 34 cm. According to these data, the s-trans conformer is the predominant form at ambient temperature, and the enthalpy difference between the s-trans and the s-cis conformer in the gas phase is 280 cm. The relative intensities of the Raman bands as a function of the temperature afford an enthalpy difference of 172 cm for the liquid. 

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