Question

Treatment of \(\beta\)-D-glucose with methanol in the presence of an acid catalyst converts it into a mixture of two compounds called methyl glucosides (Section 25.3A). In these representations, the six-membered rings are drawn as planar hexagons. (a) Propose a mechanism for this conversion, and account for the fact that only the - \(\mathrm{OH}\) on carbon 1 is transformed into an \(-\mathrm{OCH}_{3}\) group. (b) Draw the more stable chair conformation for each product. (c) Which of the two products has the chair conformation of greater stability? Explain.

Short answer

Question: Explain why only the OH group on carbon 1 is transformed in the reaction of β-D-glucose with methanol under acidic conditions and which chair conformation is more stable between α-methyl glucoside and β-methyl glucoside. Answer: In the reaction of β-D-glucose with methanol under acidic conditions, only the OH group on carbon 1 is transformed because the cyclization of glucose into an acetal or ketal will specifically affect the hemiacetal group at carbon 1, leaving other hydroxy groups unaffected. The chair conformation of β-methyl glucoside is more stable than α-methyl glucoside since all of its bulky substituents (OCH3 and OH groups) are in equatorial positions, reducing steric hindrance.

Step-by-step solution

(A) Reaction mechanism and reasoning for OH transformation at carbon 1

The reaction of β-D-glucose with methanol under acidic conditions involves the formation of an oxonium ion by protonation of the OH group at carbon 1. This ion is attacked by the methanol molecule, which results in the formation of a positively charged intermediate. Deprotonation of this intermediate will yield the methyl glucoside product. The cyclization of glucose into an acetal or ketal will only affect the hemiacetal group at carbon 1, leaving other hydroxy groups unaffected. This explains why the reaction is selective for the OH group on carbon 1.

(B) Chair conformation of the two methyl glucoside products

The reaction at carbon 1 can result in two different products, named α-methyl glucoside and β-methyl glucoside, depending on the stereochemistry of the newly formed OCH3 group at carbon 1. For each product, we must find its chair conformation. The more stable chair conformation has all bulky substituents in the equatorial positions to reduce steric hindrance. For α-methyl glucoside: 1. OCH3 group at carbon 1 is axial. 2. OH groups at carbons 2, 3, and 4 are equatorial. For β-methyl glucoside: 1. OCH3 group at carbon 1 is equatorial. 2. OH groups at carbons 2, 3, and 4 are also equatorial.

(C) Determining the more stable chair conformation and explaining the stability

Comparing the chair conformations of α- and β-methyl glucosides, we can see that in β-methyl glucoside, all the bulky substituents (OCH3 and OH groups) are in equatorial positions, while in α-methyl glucoside, the OCH3 group is axial. The steric hindrance around axial substituents is greater than around equatorial substituents, leading to higher energy in the chair conformation with axial substituents. Therefore, the chair conformation of β-methyl glucoside is more stable than the chair conformation of α-methyl glucoside.

Key concepts

Reaction Mechanism in Organic Chemistry

Understanding how reactants are converted into products is a staple in the study of organic chemistry, particularly when exploring reactions like the synthesis of methyl glucosides. The reaction mechanism involves a detailed sequence of steps that represent the journey from reactants to the final products. In the case of transforming β-D-glucose into methyl glucosides, we start by the protonation of the hydroxyl group on carbon 1. This protonation under acidic conditions increases the electrophilicity of the glucose molecule, prompting an attack from the nucleophilic methanol.

The result is the formation of an oxonium ion, which is a positively charged intermediate species. Now, methanol swoops in to donate a pair of electrons, connecting to the glucose molecule. Following this attack, the intermediate sheds a proton to stabilize itself, leading to the final methyl glucoside product. This mechanism highlights the selectivity towards the hydroxyl group on carbon 1 since it's this group that is involved in the formation of the new acetal or ketal bond, leaving the other alcohol groups unchanged.

Chair Conformation Stability

Chair conformations are like the yoga poses of molecules in the carbohydrate world - the stability of the pose, or conformation, is pivotal for understanding their reactivity and physical properties. The most stable chair conformation for a cyclohexane-like structure is when the bulky substituents adopt the equatorial position, minimizing steric clashes and reducing the molecule's energy.

In methyl glucosides, this principle is applied to evaluate which isomer - alpha or beta - is more stable.

Comparison between Alpha and Beta

The alpha-methyl glucoside features an OCH₃ group in a relatively crowded axial position, which increases the molecule's energy. On the flip side, beta-methyl glucoside luxuriously positions the same OCH₃ group equatorially, offering a comfortably low-energy state where it and the OH groups are not bumping into one another too aggressively. It's a more relaxing and therefore, a more favorable configuration from a molecular perspective.

Stereochemistry in Carbohydrates

Sugar molecules are not only sweet to the taste but also incredibly intricate in their three-dimensional structure. The stereochemistry of carbohydrates can be a complex affair, as the arrangement of atoms in space profoundly affects their behavior and reactivity. Stereochemistry concerns the orientation of substituent groups around the molecule's carbon framework.

With carbohydrates like glucose, subtle changes in stereochemistry, such as flipping the orientation of a hydroxyl (OH) group from one side of the molecule to the other, can lead to entirely different sugars. These variations, called anomers when they occur at the carbon atom of an acetal or hemiacetal group, are of immense biological significance.

Importance of Anomeric Carbon

The anomer is the carbon derived from the carbonyl group during ring formation, and its position as axial or equatorial in the chair conformation defines the alpha or beta anomer. As shown in the synthesis of methyl glucosides, the alpha anomer is less stable due to steric hindrance when the OCH₃ is axial, whereas the beta anomer enjoys greater stability thanks to its equatorial arrangement, underscoring the key role stereochemistry plays in the stability of carbohydrate molecules.