Chair conformation equilibrium

The various conformations of cyclohexane are m rapid equilibrium with one another but at any moment almost all of the molecules exist m the chair conformation Not more than one or two molecules per thousand are present m the skew boat confer matron Thus the discussion of cyclohexane conformational analysis that follows focuses exclusively on the chair conformation... 

Substitution on a cyclohexane ring does not greatly affect the rate of conformational inversion but does change the equilibrium distribution between alternative chair forms. All substituents that are axial in one chair conformation become equatorial on ring inversion, and vice versa. For methylcyclohexane, AG for the equilibrium... 

No annular tautomeric equilibrium transformations in compounds of the diox-ane series have been reported yet recently (97JCC1392), however, the optimized geometries and total energies of unsubstituted isomeric 3,4-dihydro-1,2-dioxin 22 and 3,6-dihydro-1,2-dioxin 23 were calculated using ab initio 3-21G, 6-31G, and MP2/6-31G //6-31G methods. All the methods applied revealed that the total energies for half-chair conformations of 22 and 23 are approximately the same. 

Steric hindrance also seems to provide information as to whether yn-aldolates or cmb-adducts predominate in the equilibrium. Considering the chair conformations of the syn- and owz -aldolates, the latter seems to be thermodynamically more stable since it avoids the axial position of the substituent Y which it occupies in the s> -isomer. Indeed, the azzb-diastereomcr is favored in most reversible aldol additions ... 

Optimization of the valence and dihedral angles yields planar cyclic structures for the 3- to 5-ring intermediates in contrast to a chair conformation for that of the 6-ring. In the cases of n = 4, 5, 6 the oxygen atom is placed almost in the plane of the three C-atoms directly bonded to it. Therefore, an intramolecular solvation of the cationic chain end by methoxy groups which are bonded to the polymer backbone is preferred in the gas phase. The calculations show that for a non-polar solvent such as CH2C12 a decrease in stability of the cyclic intermediates exists. But this decrease does not result in a total break of the intramolecular solvation (Table 13). An equilibrium between open chain and cyclic intermediates must only be taken into account in more polar solvents, due to the competition of intra- and intermolecular solvation. 

In six-membered rings containing heteroatoms, the basic principles are the same that is, there are chair, twist, and boat forms, axial and equatorial groups, and so on. The conformational equilibrium for tetrahydropyridines, for example has been studied. In certain compounds, a number of new factors enter the picture. We deal with only two of these. ... 

The pyranoid monosaccharides provide a wide range of asymmetric molecules for study by the c.d. spectroscopist. However, these compounds are not without their difficulties. In aqueous solution, these compounds exist in a complex equilibrium involving the two possible chair conformers of the pyranoses, the furanoses, a and p anomers, and the acyclic form, as well as septanoses for aldohexoses and higher sugars. 

The two chair conformations of tertiary methylcyclohexyl cation 43 and 44 are in rapid equilibrium. 

Catalytic reduction of bridgehead enol lactone over Pd/C indicates that, indeed, the syn addition from the exo face of the bridgehead double bound establishes the relative configuration of all substituents [264], Equilibration studies performed in EtONa/EtOH also established that the ratio of the epimers corresponds to an equilibrium mixture. Under mild basic conditions (NajCOj/ EtOH), the product isomerization occurs to a very small extent. The product distribution is best understood by rapid conformational relaxation to one of the two low-eneigy half-chair conformations. The stereochemistry is established at the subsequent protonation step. This takes place with a strong preference for axial protonation from the /I face at carbon 2 to produce the most stable chair conformation (Scheme 14.12). 

The chair conformation is the preferred conformer for the oxane ring and substituted derivatives. In the case of poly-substitution (e.g., 1,3-diaxial groups), twist conformers can also participate in the equilibrium. Substituents can adopt the axial and equatorial positions ring interconversion between the chair conformers is fast on the NMR timescale at ambient temperature but becomes slow at low temperature (AG = 10.3 kcal mol- ) (73JA4634). 

The C chemical shifts of 29 alkyl (Me,Et) substituted oxanes (830MR94) were used to train a neural network to simulate the C NMR spectra. The neural network, thus trained, was employed to simulate the C NMR spectra of 2-Et, franj-3,5-di-Me-, and 2,2,6-tri-Me-oxanes, respectively, compounds that exist >95% in one preferred chair conformation. In one case, the deviation for one methyl substituent proved to be considerable and was related to other conformers participating in the conformational equilibrium (94ACA221). 

A number of cis/trans 4,6-dialkyl-2,2-dimethyl-l,3-dioxanes were studied by C NMR spectroscopy (93JOC5251). The C NMR shifts of C -Me groups (Scheme 8) were found to be very sensitive to the 1,3-dioxane conformation [chair form Me(ax) ca. 19 ppm and Me(eq) ca. 30 ppm— pure 30.89 ppm in the twist-boat form both methyl carbons resonate at ca. 25 ppm (pure 24.70 ppm)]. With these values, AG° of the chair to twist-boat equilibrium was calculated (Table IV). For 13a (nitrile), 13b (alkyne), and 13e (methyl ester) (Scheme 8) in CH2CI2, the temperature dependence of the AG° values was determined. Depending on the substituent, small negative or positive entropy terms were found generally the enthalpy term dominates the -AG° value. In the tram isomers 13, the cyano and alkyne substituents favor the chair conformation, but CHO, ester, alkene, and alkyl substituents, respectively, clearly favor the twist-boat conforma-... 

The conformational equilibrium of 1,3-dithiane 1-oxide (the sulfoxide) was studied by low-temperature H and NMR spectroscopy <1999RJC5> at —80 to —90°C the two chair conformers could be detected (the one with the equatorial S —> O bond preferred by ca. 90%). Besides discussing the influence of the sulfoxide conformation on both NMR spectra, the enthalpy and entropy differences AH° = 0.55 0.1 kcal mol AS° = 1.88 e.u.) between the two conformers were detected in CDCl3 CS2= 1 2. 

Both theoretical and experimental studies have been reported for as- and /ra r-l,3,5,7-tetraazadecalin systems 66 and 67 <1996AJC285, 1998JOC8850>. The former is reportedly more stable as the iV-inside form 66a (calc. AH( 29.6 kj mol ) than as the A -outside form 66b (calc. AH( 56.3 kj mol ), although the two forms exist in equilibrium. The more crystalline trans-form 67 again exists in two all-chair conformations, 67a and 67b, of which the former (calc. AH I 37.8 vs. 46.1 kJ mol for R = H) is more stable <1996AJC285>. The conformational effect of changing the 2- and 6-substituents is reportedly small. 

A number of studies have now been made, notably by Buchanan and coworkers, with the object of determining the position of the equilibrium between the various pairs of interconvertible epoxides the findings are summarized in Chart I. For the dianhydro compounds, the epoxides that contain the free hydroxyl group quasi-axial, and that also have the possibility of a polar interaction between the epoxide ring and the 1,6-anhydro bridge, are clearly less stable than those in which it is quasi-equatorial, although the relative importance of these two factors is uncertain. The situation is less clear for the monocyclic epoxides. The half-chair conformations indicated are considered to be favored on the basis that the alkyl... 

Several cyclodipeptides have been subjected to base-catalyzed epimerization (EtOH/NaOEt at 30-75°C) and the ratio of cis-to-trans isomers at equilibrium has been determined (74JA3985). The results have been correlated with the conformation of the molecules. Thus, cyclo(Pro-Pro) NMR studies (73JA6142) have indicated a boat form in the cis and a planar form in the trans diastereomer. In the latter, the pyrrolidine rings take up a half-chair conformation, which is greatly strained as long as the amide bonds are planar. This renders the trans less stable than the cis diastereomer. Consequently, at equilibrium, only cis diastereomer is found the trans isomer occurs to the extent of less than 0.5%. 

Dynamic NMR shows the presence of two conformations in 1,3,5,7-tetroxocane a crown and a boat-chair. The equilibrium constant is strongly solvent and temperature dependent, with the highly symmetrical crown, which has a high dipole moment, having a lower entropy than the boat chair by about 6 J K-1 mol-1 (72JA1390,1389). Hie interconversion barrier is 50 kJ mol-1, and no ring inversion nor pseudorotation process has been detected in the boat-chair. 

LH-and 13C-NMR spectra are consistent with the twin-chair conformation 169 for trans-decahydroisoquinoline, and 13C-NMR spectroscopy gives AG° 5go of 0.37 kcal mol -1 (70% N-inside conformation 170) for the cis-decahydroisoquinoline equilibrium 170 171,82 reflecting the difference between a gauche-butane and a gauche-propylamine interaction. The 3-methyl-cis-decahydroisoquinolines prefer the equatorial methyl conformations 172 and 173.82... 

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