1,3-Dioxane, axial protonation

The rates of removal of axial and equatorial protons from 4-t-butylcyclohexane in NaOD/dioxan have been measured by an NMR technique. The rate of removal of an axial proton is 5.5 times faster than for an equatorial proton. What explanation can you offer for this difference ... 

Chemical shift trends for the remaining protons in the 1,3-series and related compounds can be deduced from the representative data given in Table 6. The rules outlined above also satisfactorily accommodate the data for methylene groups adjacent to just one heteroatom in the 1,3-dithiane the opposing effects of the j3 C—C and C—S bonds cancel whereas in the 1,3-dioxane the effect of the C—C and C—O bonds reinforce. At the C-5 methylene group, the axial proton is to lower field of the equatorial proton in the 1,3-dioxane and 1,3-oxathiane but to higher field in the 1,3-dithiane. +... 

When, however, methyl 4,6-0-benzylidene-2,3-di-0-methyl-a-D-gluco- and -galacto-pyranoside were prepared (for the first time) under kinetic control, they found, for each, two benzyl signals,49,50 indicating the presence of both diastereoisomers. The chemical shifts for the diastereoisomers were as shown. The smaller values in each pair are similar to those for axial protons in that chair form of 2-phenyl-l,3-dioxanes having axial protons on the same side of the ring. These isomers are the thermodynamically favored ones. 

Reverse Perlin effect In contrast to cyclohexane, axial protons at the p-carbons of heterosubstituted cyclohexanes may have coupling constants larger than those of the equatorial protons (i.e. the reverse Perlin effect). In 1,3-dioxanes and 1,3-dithianes, equatorial C-H bonds at the five-position have been shown to display this behavior (Figure 12.42). 

Ganguly and Fuchs studied negatively and positively (protonated) charged 1,3-dioxanes at the MP2/6-31+G level of theory (97JOC8901) and proved that the preferred site of protonation of 1,3-dioxane is axial because the equatorial lone pair was hyperconjugatively stabilized. 

In undeuterated dioxane, Hgq and coincidentally have the same chemical shift (at the field studied), so they cannot be differentiated at low temperatures. (See Sections 1-8 and 5-2.) In l,4-dioxane- 7 (an impurity in commercial l,4-dioxane- 5 g), both and Hgq exhibit isotope shifts to a lower frequency, but H x is shifted somewhat farther. As a result, the axial and equatorial protons give separate resonances at low temperatures, in contrast to the undeuterated material. Because of a chlorine isotope effect, chloroform is a poor substance for an internal lock or a resolution standard at fields above about 9.4 T. At high resolution, the chloroform proton resonance shows up as several closely spaced peaks, due to CH( 5c1)( C1)2, CH( C1)2( C1), CH( C1)3, and CH( C1)3. 

The analysis of H and C data, particularly H chemical shifts and C-H coupling constants, is indeed often used to determine C-H bond orientation. In cyclohexane, / C-H coupling constants of equatorial C-H bonds ( /c-Heq) greater than those of axial bonds ( /c-Hax) (the Perlin effect). This effect also operates in 1,3-dioxanes for the C-2 position protons <73ACS2676>. In contrast, the C-5 position protons display a reverse Perlin effect when the conformation is locked by a 2-t-butyl substituent <94JCS(P2)ii5i>. Such a reverse Perlin effect has been observed for all ring protons in... 

The presence of a reverse anomeric effect was suggested (29) for chlo-romethyl, CICH2—, and bromomethyl, BrCHj—, groups located at the anomeric carbon atom of a 1,3-dioxane ring. This claim was based on the observed reversed dependence of axial preference on solvent polarity, that is, more polar solvents increased the population of axial conformers. This observation is in line with the fact that a-glucopyranosylimidazoles in water (very polar solvent) do not change conformation on protonation (162). 

An oxonium ion is formed (5 -> 6) in the rate-determining step after a reversible (9-protonation and O/C-2 fission. Its formation is also responsible for the epimerization of 5-substituted 1,3-dioxanes, and is brought about by the action of nonaqueous protic or Lewis acids. It is important for the conformational analysis of these systems (by equilibration of the conformers 7 and 8 which occupy an equatorial and axial position, respectively). 

The reductive lithiation has been extended to 4-cyano-l,3-dioxanes such as 60 [Eq. (21)] [45]. Obviously, protonation of the axial Hthium intermediate 63 is... 

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