Question

Treatment of methyl \(\beta\) - D-glucopyramoside with benzaldehyde forms a six- membered cyclic acetal. Draw the most stable conformation of this acetal. Identify each new chiral center in the acetal.

Short answer

Answer: The most stable conformation of the six-membered cyclic acetal is the chair conformation, with the benzene ring in the axial position to minimize steric hindrance. The new chiral center is on the former carbonyl carbon of the benzaldehyde molecule.

Step-by-step solution

Understand the structure of the starting materials

Methyl β-D-glucopyranoside is a type of carbohydrate with 6-membered ring including an oxygen atom (hence, it is a pyranose). The methyl group is attached to the anomeric carbon (C1) in the ring. This is β-D-glucopyranoside, meaning that the oxygen atom forming the acetal linkage is on the opposite side of the ring as the carbon 6 (C6) substituent. Benzaldehyde has a structure of C6H5-CHO, where CHO is the aldehyde group.

Formation of the acetal

Methyl β-D-glucopyranoside reacts with benzaldehyde to form a six-membered cyclic acetal. This happens when the hemiacetal hydroxyl group in the glucopyranoside (present on the anomeric carbon C1) reacts with the aldehyde group of benzaldehyde. The formation of the acetal is an equilibrium reaction, so it occurs under mildly acidic or basic conditions.

Drawing the most stable conformation

The most stable conformation is called the chair conformation. In this conformation, every atom is staggered and has a maximum 60 degree dihedral angle. To draw the chair conformation, start by drawing a standard chair conformation of methyl β-D-glucopyranoside. Add the benzaldehyde molecule to the C1 anomeric position, with the benzene ring in the axial position to minimize steric hindrance.

Identify the new chiral centers

Once the acetal is formed, there will be one new chiral center created during the formation, which lies on the former carbonyl carbon of the benzaldehyde molecule. Its configuration could be R or S. You can use Cahn-Ingold-Prelog rules to assign its configuration with the priorities determined by atomic number.

Key concepts

Methyl β-D-glucopyranoside

This compound is a derivative of glucose, specifically a pyranose sugar, which means it features a six-membered ring containing an oxygen atom. The "D" designation indicates the orientation of the hydroxyl group at the fifth carbon in the molecule matches that of D-glyceraldehyde, an important reference sugar. The "β" label refers to the anomeric carbon (C1), where the methoxy group is attached. In β-D-glucopyranoside, the methoxy group lies on the opposite side of the ring compared to the hydroxyl group at C6. This orientation is crucial in determining how other molecules, like benzaldehyde, interact during chemical reactions.

Benzaldehyde Reaction

Benzaldehyde, a simple aromatic aldehyde, is the key reactant in forming cyclic acetals through a reaction with methyl β-D-glucopyranoside. It consists of a benzene ring and a formyl group (CHO). The aldehyde group is highly reactive, making it an ideal candidate for acetal formation. During the reaction, the hemiacetal hydroxyl group at C1 of the glucopyranoside attacks the carbonyl carbon of benzaldehyde. This reaction forms a new oxygen-carbon bond, culminating in a six-membered cyclic acetal structure. The reaction typically requires either acidic or basic conditions to proceed efficiently.

New Chiral Centers

When an acetal forms between methyl β-D-glucopyranoside and benzaldehyde, a new chiral center emerges on what was the carbonyl carbon of benzaldehyde. A chiral center is a carbon atom attached to four different substituents, allowing for distinct spatial arrangements. The formation of the acetal introduces asymmetry, providing two possible configurations, labeled as R or S, based on the Cahn-Ingold-Prelog priority rules. These rules consider the atomic number of atoms directly attached to a chiral center, helping assign configuration and thus affect the stereochemical outcome of the reaction.

Chair Conformation

The chair conformation is a three-dimensional representation critical for understanding the stability and reactivity of cyclic compounds. For compounds like methyl β-D-glucopyranoside, adopting a chair conformation allows for minimization of steric hindrance and torsional strain.
This conformation ensures that bulky groups, such as the benzene ring from benzaldehyde, are positioned in less hindered spaces. To draw such a structure, recognize the C1 carbon, where the acetal linkage occurs, and place the benzene substituent in an axial or equatorial position based on its size and to reduce potential clashes with neighboring groups.

Hemiacetal Reaction

Hemiacetal formation is a key step in acetal synthesis, bridging simple sugars and aldehydes like benzaldehyde. In this reaction, a nucleophilic hydroxyl group from the hemiacetal at C1 of glucopyranoside attacks the electrophilic carbonyl carbon of benzaldehyde. This initiates the process of forming an acetal linkage, a reversible reaction pivotal in organic synthesis.
The reaction is equilibrium-based, with equilibrium conditions influencing whether the reaction favors hemiacetal or acetal formation. Understanding this balance can be crucial in synthetic approaches involving similar sugar modifications and transformations.