Equatorial preference

It is consistently found that 5-alkyl substituents in l,3-diqxane exhibit a smaller equatorial preference than they do in cyclohexane. This decreased preference is due to... 

The same equatorial preference is also manifested in the 3,3-disubstituted thietane oxides66,194. Thus, the NMR spectra of 5e,f contain two Me singlets at 1.23 and 1.30 ppm and two methylene multiplets at 3.03 and 3.53 ppm (in CDC13). The large difference in the chemical shifts of the axial and equatorial a-methylene hydrogens is characteristic of an axial nonbonded electron pair on sulfur (conformation 5e equation 73). This conformational preference is corroborated by the small differences in the chemical shifts of the two methyl groups, and fits the contention that 1,3-diaxial interactions are responsible for this ultimate result. Certainly, these interactions are greater in the conformer 5f. 

Other studies have also established the preference of the chair conformation with the oxygen in the axial position the rationale for this preference is different from the attractive interaction between the sulfoxide oxygen and the syn-axial hydrogens proposed previously . Rather, a repulsion effect is advocated the equatorial oxygen is squeezed between four vicinal hydrogens, while there are only two corresponding repulsions if it is in the axial position. The correlation between the predicted and observed conformational/orientational preferences in 3,3-dimethylthiane oxide (e.g., equatorial preference in the chair conformation) corroborates this interpretation. The axial preferences of the sulfur-oxygen bond in the thiane oxide is reversed in 3,3-dimethylthiane oxide because of the syn-axial interaction. 4,4-Dimethylthiane oxide, however, maintains a predominance of the axial isomers as deduced from the analysis of NMR data . ... 

In a previous section we have discussed the importance of n—a conjugative interactions in dictating the axial-equatorial preference of an electronegative substituent at C—1 of a pyranose ring, i. e. the anomeric effect . Here, we shall extend the discussion of n—a conjugative interactions to other saturated heterocyclic molecules. 

An axial or equatorial preference of the YH (Y=N, P) group can be dictated by a modification of the heterocyclic ring. This may be accomplished by substituting a more electronegative or electropositive atom for X=CH2 in the system shown below ... 

NMR has been used to show that the anomeric effect operates in 2-bromo- and 2-chloro-tetrahydropyrans, which exist predominantly with the halogen atom axial (66JOC544), whilst the equatorial preference of a 4-halogen atom is less pronounced than in cyclohexane and decreases with decreasing electronegativity (78SA(A)297). 

Little or no bias towards one particular conformer is shown by substituted 4-alkyl- or 4-aryl-5,6-dihydro-2//-pyrans except when the equatorial preference of a bulky substituent at C-6 dominates the situation (80CHE571). 

Calculations have also been performed for the monosulfoxides of 1,4-dithiane, 1,3-dithiane and 1,3,5-trithiane, the cis and trans disulfoxides of 1,4-dithiane and 1,3,5-trithiane and the cis and trans trisulfoxides of 1,3,5-trithiane (76T529). For all the compounds mentioned, a chair conformer is calculated to be most stable and the results are consistent with experimental findings which reveal that the S—O- bond exhibits an axial preference within 1,4-dithiane 1-oxide but an equatorial preference within 1,3-dithiane 1-oxide and 1,3,5-trithiane 1-oxide (Section 2.26.2.5). 

Based on the chemical shifts of H-4 in the low-temperature H NMR spectra of 4-benzyloxy and 4-silyloxy tetrahydrothiopyrans in CD2CI2, the equatorial preference appears to be related to the basicity of the oxygen atom of the substituent. In the case of both their as and trans sulfoxides, a preferential axial disposition of the substituent is noted and is almost exclusive for the latter 1-oxide and for the corresponding 1,1-dioxide <1995H(41)419>. MM3 calculations confirm this preference <1996JP0159>. 

The equilibrium constants derived from the 31P NMR spectra at temperatures below coalescence show that there is a considerable predominance of the axial conformer of 2-diphenylphosphinoyltetrahydrothiopyran (Table 26) which contrasts with the equatorial preference in the corresponding cyclohexane derivative. This result indicates a strong anomeric effect, estimated at 2.40 kcal mol-1. The corresponding data for the anancomeric cis and trans 4-/-butyl derivative at chemical equilibration are presented in Table 26. The large difference in AG° at 173 and 323 K is compatible with a significant entropy effect, calculated AS° = +4.8 0.7 cal K.mol-1, with... 

A similar effect had already been noted in a-O-glycosides, where it was dubbed the exo-anomeric effect 129 to distinguish it from the anomeric effect , which produces a preference for a- (axial) rather than / - (equatorial) glycosides27. Against all this is the evidence that when this chain of atoms is found in a ring system, then the anti form is preferred as seen in 13-16 (equatorial preferences shown in kcal mol-1 below each figure). These values suggest that the //-preference in C—C—C—O chains is 0.45 kcal mol-1, as compared to about 0.95 kcal mol-1 for C—C—C—C chains. 

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