Dimethoxymethane anomeric effect

Even molecules as simple as dimethoxymethane give evidence of anomeric effects. The preferred conformation of dimethoxymethane aligns each C—O bond with a lone-pair orbital of the adjacent oxygen. ... 

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. 

Anet and collaborators (46) as well as Dale and co-workers (47) have also shown the 8-membered ring, 1,3-dioxacyclooctane and some derivatives, to exist only in the boat conformation 47. Conformer 47 has two anomeric effects and is virtually the same as that found in 40 or in dimethoxymethane. 

We will first examine what miqht occur when stereoelectronic effects are taken into account. An analysis of the conformations D, A, and (Fig. 17) of dimethoxymethane which have two, one, and zero anomeric effects respec-... 

Jeffrey et al. have calculated the energy of several conformations of dimethoxymethan as these are representative examples for the glycosidic bonds in a- or P-anomers (cf. Fig. 3) [59]-The calculations were carried out on the RHF/4-31G level. The obtained potential energies for the conformations of 0°, 90°, 180°, and 270° dihedral angles respectively revealed the presence of a strong exo anomeric effect in acetal... 

Fig. 4. Modelling of the torsion potential of the exo anomeric effect using the results of the ab initio calculation of dimethoxymethane. The difference between the non bonded terms and the ab initio calculation is fitted with the general function of torsion potentials to yield the equations for the oc-and the P-anomers discussed in Sect. 2.5.3 for the HSEA method...

In symmetrical systems, anomeric effects are acting in both directions, but it is clear that bond-shortening from the anomeric effect in the one direction is stronger than the bond-lengthening in the other, in line with the overall stabilisation provided by the anomeric effect. Thus, with dimethoxymethane 2.86,127 the central pair of C—O bonds are equal in length and both are shorter than normal because of the anomeric effects, while the other pair of C—O bonds, the O—Me groups, have normal C—O bond lengths. 

Praly and Lemieux (66) have estimated the exo anomeric effect to be 1.66 times as strong for j3-anomers ap, sc here competition between anomeric effects cannot operate) as for a ones (sc, sc). In order to evaluate the corresponding relation between anomeric effects in an acyclic system, let us return to dimethoxymethane (11, Scheme 9). The anomeric effect A for the ap, sc conformer of 11, calculated to be 21.1kJ/mol (cf. Scheme 6),... 

Let us focus on molecules I4a and 14b (Scheme 8) in which an anomeric effect (in AG° or AH° terms) is possible in the vapor phase. Usually, the dipole moment of 14a is less than that of 14b (125-128). Since the more polar form is stabilized in solution (114, 128) [as a rule, with several exceptions (29, 129) vide infra] it may happen that the anomeric effect (i.e., increased preference for 14a) disappears in solution or may even change its sense (from AG g > 0 to AG g < 0). Such a possibility has been supported by quantum chemical calculations for dimethoxymethane (128). It was shown that, while in CCI4 solution dimethoxymethane (11) exists almost exclusively as the most stable sc, sc conformer, in aqueous solution almost exclusive occurrence of the ap, ap conformation may be expected. Hence, all considerations regarding the presence, magnitude, or origin of the anomeric effect must take... 

The anomeric effect is readily rationalized in PMO terms, using the hybrid model for the lone pairs (see p. 27 and Deslongchamps, 1983). In the g g form of dimethoxymethane [21], one lone pair on each oxygen atom is anti-periplanar to the cr c o orbital involving the other oxygen atom. Thus two favourable n-o interactions exist in this conformation. The generalized anomeric effect was rationalized in similar terms by David et al. (1973) who used the canonical model for the lone pairs. Calculations for the CHCl—O—C system predicted stabilization of conformer [23a] due to the n-cf c-ci interaction by 3.3kcalmol with respect to conformer [23b], a... 

The anomeric effect is well reproduced at the 4-3IG level by ab initio calculations on methoxymethanol (Jeffrey et al., 1974). The most stable form, g g, is calculated to be B.Okcalmol" below the second, the ag form. In the former, two anomeric interactions are possible, and in the second only one. Similar results were obtained for dimethoxymethane with a 6-3IG basis set (Jeffrey et al., 1978). In this study, shortening of the central O—C—O bonds and lengthening of the terminal C—O bonds were observed, in agreement with experiment. These effects reflect the different degrees of double-bond character due to different degrees of back-donation of the lone pairs into the G c-o orbitals. 

To reproduce an exo-anomeric effect, separate energy functions, Eqs. [3] and [4], were incorporated for a- and p-anomers. The parameters for these equations were derived by fitting to the rotational energy curves for dimethox-ymethane computed with nonoptimized geometries at the HF/4-31G ab initio level.Dimethoxymethane is the simplest chemical model system for a gly-cosidic linkage. 

Also in 1990, Homans added a torsional term for the exo-anomeric effect to Brady s CHARAlm-type parameters and incorporated them into AMBER. As with more recent versions of HSEA, Homans exo-anomeric parameters were chosen to reproduce ab initio rotational energies computed at the HF/6-31G level for dimethoxymethane (Eqs. [12] and [13]). ... 

Figure 6.62 (a) Stereoelectronic basis for the anomeric effect illustrated In dimethoxymethane. (b) Contrasting shapes of pentane and dimethoxymethane ("2,3-dioxapentane"). Both p/sp and sp /sp representations of oxygen lone pairs are shown (in the panels a and b, respectively). NBO analysis finds that the p/sp model for the oxygen lone pairs is preferred. 

To see the relationship between the Bohlmann effect and the anomeric effect we can look at the valence bond stractures for methylamine and dimethoxymethane. Structure 4 ... 

The most simple compound that shows the classical anomeric effect is dihydroxymeth-ane. This compound exerts hydrogen bonding characteristics that may complicate the situation, so we will here examine the corresponding ether, dimethoxymethane, as our parent model compound. We will take up the energetic effects first, as historically these were the first indication of the anomeric effect. 

Discussion in the literature regarding the exo-anomeric effect has to do with the anomeric effect when it occurs with a pyranose ring, where one oxygen is in the ring and the other one is external (exo) to the ring. It was thought earlier that this particular arrangement led to unusual characteristics for the anomeric effect that seemed somewhat different from the ordinary anomeric effect found with simple molecules such as dimethoxymethane. Earlier, we showed that the so-called exo-anomeric effect is really just an ordinary anomeric effect, but it may occur in more complicated mole-... 

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