Oxanes, conformation

Calculation of the effect of the solvent on the abundance of the 2- oxan-2-yloxy)oxane conformers revealed that the solution behavior of the a, a) form is markedly different from that of other saccharides where laige differences in the solvent effect of aqueous and nonaqueous solution on the equilibrium around the glycosidic linkage have been found. The calculated population of the most stable conformer is 96.5%, in both the isolated molecule and in solution. The equilibrium composition of con-formers in the other two forms, (a, e) and e, e), depends on the solvent, and the solvent-solute electrostatic interactions (Eq. 7) are mainly responsible for the shift of equilibrium in solution. ... 

This article deals with the conformational analysis of substituted oxanes (tetrahydropyranes) and derivatives in which ring methylenes are replaced by further oxygen atoms (di-, tri-, tetroxanes, pentoxanes, and O ) or by carbonyl group(s) (oxanones, Meidrum s acid derivatives) and, if conforma-tionally of interest, systems incorporating these rings in polycyclic structures... 

Frozen conformational equilibria. Although the rate of the interconversion of the various conformers (chair, boat, twisted) of the oxane derivatives at ambient temperature is fast on the NMR timescale, this ring-inversion process is sufficiently slow at low temperature (T < -60°C) to permit the observation of individual signals for each conformer. Direct integration delivers K and -AG°, respectively [see Eqs. (1) and (2)]. 

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 conformational energies of monosubstituted oxanes studied to date are collected in Table I. In position 2, polar substituents (except NR2) prefer the axial position other substituents prefer the equatorial orientation, which is generally the case for groups in positions 3 and 4. Destabilizing 1,3-diaxial interactions cause the equatorial geometry to be usually favored in the 2-position, the anomeric effect stabilizes the axial conformation. A large purine moiety in position 2 of oxane, for example, prefers the equatorial position because the 1,3-diaxial interactions overcome the anomeric effect (75TL1553). 

The conformational equilibria of the various substituted oxanes in Table I are strongly dependent on the solvent. The polarity of the solvent and the possibility to form inter- or intramolecular hydrogen bonds are of significant influence (69CJC4427 87CJC213). 

In following the temperature dependence of AG°, Booth et al. [85JC-S(CC)467 87T4699]also determined A/f° and AS° for the conformational equilibria of 2-C1-, 2-OMe-, 2-OH-, and 2-NHMe-oxanes (see Table II) and discussed the results in terms of exo- or endo-anomeric effects (Section III,C,8). Employing the NOE and a number of H,H- and C,H-coupling constants as a means of analysis, the preferred rotamers of axial/equatorial-2-OMe-oxane were found to be in the conformations az and 2, respectively, as given in Scheme 1 (90T1525). 

Conformational Energies (Free Energy Differences, AC7kcal moL ) of Substituted Oxanes... 

Eliel et al. (82JA3635) examined the conformational equilibria of a number of disubstituted oxanes (Table III) by low-temperature C NMR spectroscopy (830MR94) and estimated the AG° values of 3-Me and 2-C=CH substituents (see Table I). The concentration of the axial 2-Me and 4-Me conformers, however, was so small and difficult to detect by NMR spectroscopy that they were forced to employ the use of counterpoised di-2-C=CH and ds-2-CH = CH2 groups to generate equilibria that were sufficiently balanced to measure accurately (AG° values in Table I). Eliel et al. (82JA3635) also discussed the conformational energies in terms of 1,3-diaxial interactions and the anomeric effect. 

Alcudia et al. [88JCS(P2)1225], in the same way, studied the conformational equilibria of the cis/trans isomeric 2-OMe-5-SR-substituted oxanes... 

Barby et al. [82JCS(P2)249] investigated the conformational equilibria of 2-NR2-substituted oxanes. The cis/trans isomeric 2-NR2-4-Me-derivatives proved to adopt preferred conformations (cis isomers 2-eq-A-eq trans isomers 2-ax-A-eq, except for /ram-2-NHMe-4-Me-oxane preferring the 2-ax-A-eq conformer by only 0.4 kcal mol ) the 2-NR2 monosubstituted oxanes (see Table I) prefer the equatorial position and do not show notable anom-eric interaction with the ring oxygen atom [82JCS(P2)249]. The same is true for 2-NHCOMe-oxane, but not for N3 and NCO substituents, respectively, in the 2-position (70ZOR863) (see Table I). 

Anderson and Sepp (68JOC3272) equilibrated some cis/trans isomeric 2-OR-4-Me-, 2-OR-6-Me-, and 2-OR-6-CH20H-oxanes and discussed their equilibria in terms of anomeric interactions. The corresponding conformational equilibria were assumed to be strongly one sided [e.g., the 2,4-isomers cis isomer 2-eq-4-axy, trans isomer 2-ax-A-eq)]. 

The H and NMR spectra of a number of 2,6-diphenyl-oxan-4-ones 7 and their oximes 8 (Scheme 4) were studied (80JOC4352 81SPL11). Whereas the oxan-4-ones were in the chair conformation 7a, the oximes... 

The conformations of spiro-compounds containing the oxane ring have been reported (Scheme 5) (81CJC1132). They exist only in conformation 9a at room temperature at lower temperature, no indication of a second conformer was found. The methyl-substituted derivatives 10a and similar tricyclic analogs occur in the same conformation 11a. 

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). 

Different reactivities of some substituted oxan-4-ols on oxidation by pyridinium chlorochromate (PCC) are rationalized on the basis of their conformational features, including twist conformations.2 A rate-determining carbon-carbon bond cleavage step in a glycol-PCC complex is proposed in the oxidation of butane-2,3-diol to acetaldehyde.3 Steroidal 6/i-hydroxy-4-en-3-onc was isolated as an intermediate in the oxidation of steroidal 5-en-3/i-ol with PCC.4... 

In 2-benzoyl-oxane (also in 2-benzoyl-thiane, -1,3-dithiane, 1,3-oxa-thiane) the benzoyl substituent adopts the equatorial conformation in the solid state (99IJC617). 

C3 synunetric confoimation Asyininetrij conformation 4nCH2a2,CHa3, oxane in H2O, MeOH, DMSO... 

As just mentioned, a more significant value for the anomeric effect of a polar substituent could be calculated if the A value at position 2 of oxane were known. But this can be measured only for weakly polar substituents such as methyl, hydroxymethyl, vinyl, and ethynyl, which are supposed to exhibit no anomeric effect. For such substituents, the A value at position 2 of oxane correlates fairly well with the conformational free energy in cyclohexane. 

In fact, the conformation of pyranoses is dominated by two effects, not present in the cyclohexane, which appear at positions 2 and 6 of the oxane. One of them is characteristic of hexopyranoses and I propose that we call this the coplanar effect in order not to imply a particularly restrictive structure by using the name of an effect already present in methoxyethane. The other effect, present in all pyranoses, is referred to as anomeric. This name, taken from the nomenclature of sugars because it was first recognized in this family, in fact disguises its general nature since it is also present in methyl chloromethyl ether. The consequences of these effects can be modulated by cyclohexane-type interactions, but not to the point where more than a qualitative discussion is necessary. 

For a monosubstituted oxane, the excess free enthalpy of the conformation with an axial substituent over the conformation with an equatorial substituent is, as we know by definition, the conformational free energy (CFE) of the substituent in oxane at this position. These values, possibly measured indirectly by utilizing intennediate compounds, are shown in Table 2.2. Equatorial conformations correspond to anti conformations in butane and methoxyethane, and the axial conformations (not represented) to gauche conformations. We can observe that the environment of derivative 2.20 is closest to that of the cyclohexane and that the CFE is of the same order. On the other hand, the presence of the cyclic oxygen lowers notably the CFE of derivative 2.19. The important point is the noteworthy increase in the CFE of compound 2.18, where the methyl group is close to the cyclic oxygen and possesses, on one side, an environment similar to that of methoxyethane. Let us look at the equilibrium (2.4) of the dimethylated derivative 2.21. 

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