Acetals conformational equilibria

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

As mentioned above, ring opening of conformationally unbiased epoxides is less regioselective and the two expected compounds can be obtained in a ratio depending on the conformational equilibrium between the C4 and chairs. Obviously the use of the 4,6-acetal ring allows opening... 

Lupanine is comparatively easily dehydrogenated with mercuric acetate 62, 69), a property not usual for cis-quinolizidine structures. The conformation, with ring C in boat form, appears to be the favored conformation equilibrium (5, 35, 70). 

In 1,5-anhydroxylitol (Figure 10), the conformational equilibrium is shifted to the equatorial form (right side). By accurate measurements, data could be obtained for determining the equilibrium, according to which the triaxial form amounts to about 13 for the acetate and to about 17 for the benzoate. 

In summary, these peracylated derivatives lead to conformational equilibria, except in the case where the issue is particularly obvious a-D-xylo, Ci -D-arabino, C4 configurations). The free pentoses in aqueous solution still remain to be seen. The diaxial interactions are stronger than with the acetates and the anomeric effect is weaker. Out of the eight D-pentose configurations, four of them (jS-D-arabinose, a-D-lyxose, a-D-ribose, and jS-D-ribose) lead to a conformational equilibrium. 

Polymer Structure. The structure of the acetal polymers has been determined by NMR spectroscopy. The conformational equilibrium for both els and trans Isomers of the dloxablcyclo(3.2.1)- and [2.2.2] octane polymers was calculated by the Interplay of two factors 1) the familiar preference of aUcyl substltutents to be In the equatorial position, and 2) the preference of the alkoiqr groups to be In the axial position, due to the anomerlc effect. 

The acetal RCH(OMe)2 can have a total of nine conformers, 30a-30i. We may ignore the broken red bonds, which are included to allow a quick conformational match with that of the cyclohexane chair and, thus, ascertain the geometrical relationships rather easily. The conformers 30a and 30e have two methyl groups within van der Waals distance and, hence, their contributions to the overall conformational equilibrium will be small, if not zero. We can therefore eliminate these conformers from further discussion. The conformers 30b and 30d, 30c and 30 g, and 30f and 30 h are mirror images and, thus, we need to consider only one conformer of each pair. Thus, we are left with four distinct conformers, namely 30b, 30c, 30f, and 30i, to consider for acid hydrolysis. The relative contributions of these conformers could be estimated from the understanding that they are laced with two, one, one and zero stereoelectronic effects, respectively. The conformers 30b and 30i are, respectively, the most contributing and the least contributing. The conformers 30c and 30f contribute at the medium level. 

Typically, in specific solvents, the process of monomer formation [9.57] is characterized by considerably lower dimerization constants, as compared with those in universal media. In fact, acetic acid dimerization constant in water-dioxane binary solvent, the components of which are solvation-active in respect to the acid, vary in the 0.05-1.2 range. Replacing the solvent is often the only method to vary the molecular association state of dissolved compound. To achieve dimer concentration in 0.1 M solution of phenol in n-hexane equal to dimer concentration in nitrobenzene solution (50% at 25 C), it would be necessary to heat the solution to 480 C, but it is impossible under ordinary experimental conditions. 9.4.3 MIXED SOLVENT INFLUENCE ON THE CONFORMER EQUILIBRIUM Equilibrium took place in solutions... 

Use of the combined QM/MM model for studying conformational equilibria has been described by Warshel, Jorgensen, 8o and by Field, Bash, and Karplus.35 The first computer simulation of the solvent effects on conformational equilibrium with a combined QM/MM approach, however, was carried out in 1992 in the investigation of the relative basicity of the syn and anti lone pairs of acetate ion in water. 81 In recognizing that the basicity difference... 

A prototype of such phenomena can be seen in even the simplest carboxylic acid, acetic acid (CH3CHOOH). Acidity is determined by the energy or free energy difference between the dissociated and nondissociated forms, whose energetics usually depend significantly on their conformation, e.g., the syn/anti conformational change of the carboxyl-ate group in the compound substantially affects the acid-base equilibrium. The coupled conformation and solvent effects on acidity is treated in Ref. 20. 

The difference in conformational energy between the two conformers of the trans-isomer is only 2.1 kJmol1, resulting in an equilibrium mixture of 30% of 29 and 70% of 30. Therefore, polymerization of 2 7 to a trans-1,4-tetrahydropyranoside polymer by direct displacement on the trialkyloxonium ion by monomer would be detected by -NMR as an axial acetal proton to equatorial acetal proton ratio (Hax)/(Heq) of 2.3. The most stereoregular polymer that obtained using 0.2 mol% of SiF4 at -78 °C possessed an (H /CHeq) ratio of 3.0. 

In an early work by Mertz and Pettitt, an open system was devised, in which an extended variable, representing the extent of protonation, was used to couple the system to a chemical potential reservoir [67], This method was demonstrated in the simulation of the acid-base reaction of acetic acid with water [67], Recently, PHMD methods based on continuous protonation states have been developed, in which a set of continuous titration coordinates, A, bound between 0 and 1, is propagated simultaneously with the conformational degrees of freedom in explicit or continuum solvent MD simulations. In the acidostat method developed by Borjesson and Hiinenberger for explicit solvent simulations [13], A. is relaxed towards the equilibrium value via a first-order coupling scheme in analogy to Berendsen s thermostat [10]. However, the theoretical basis for the equilibrium condition used in the derivation seems unclear [3], A test using the pKa calculation for several small amines did not yield HH titration behavior [13],... 

As the titration is continued by adding further increments of NaOH, the remaining nondissociated acetic acid is gradually converted into acetate. The end point of the titration occurs at about pH 7.0 all the acetic acid has lost its protons to OH-, to form H20 and acetate. Throughout the titration the two equilibria (Eqns 2-5, 2-6) coexist, each always conforming to its equilibrium constant. 

The first precise evaluation of the anomeric effect was realized by Descotes and co-workers in 1968 (22). These authors have studied the acid catalyzed isomerization of the cis and trans bicyclic acetals 6 and 6 and found that, at equilibrium, the mixture contains 57% ci s and 43% trans at 80°C. The cis isomer is therefore more stable than the trans by 0.17 kcal/mol. The cis isomer 5 has one (stabilizing) anomeric effect whereas the trans isomer 6 has none. Steric interactions in cis acetal 5 were estimated tobel.65 kcal/mol (one gauche form of ri-butane, 0.85 kcal/mol and an OR group axial to cyclohexane, 0.8 kcal/mol). By subtracting an entropy factor (0.42 kcal/ mol at 80°C) caused by the fact that the cis acetal S exists as a mixture of two conformations (cis decalin system), they arrived at a value of 1.4 kcal/mol for the anomeric effect. 

More recently, the equilibration of the conformationally rigid cis and trans tricyclic acetals 7 and 8 was carried out (23). The cis acetal 7 is less stable (45% at equilibrium) than the trans acetal 8 by 0.14 kcal/mol. Taking... 

D-(+)-galactose (15) is an example of the consecutive numbering of the carbon ring atoms in a monosaccharide (disaccharide see p. 253). Carbohydrates can exist in a cyclic and an acyclic structure. For this reason there is a special position in the structure of a monosaccharide, the carbon atom C-l and so called anomeric center. You can see that there is an equilibrium between er-anomer a-15 and / -anomer /3-15 of D-(+)-glucopyranose over the acyclic aldehyde structure 16. Both are cyclic hemi-acetals. The /Tanomer is the preferred conformation, but there are a few effects, like sterical or stereoelectronical effects (anomeric effect, inverse anomeric effect), which have influence on the a /i rate. 

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