Conformers

Stereochemistry: Conformers

Introduction

• This lecture focuses on conformers, particularly in the context of sugar chemistry.
• Previous lectures covered constitutional isomers (same formula, different connectivity) and stereoisomers (different spatial arrangement).
• Stereoisomers include diastereomers (EZ isomers, cycloalkanes with two or more chiral centers) and enantiomers (mirror images with chiral centers).

Conformers

• Conformers are different spatial arrangements of a molecule that can be interconverted by rotation around single bonds.
• Some conformers cannot be easily converted and are genuinely different molecules.
• Understanding how to draw molecules is crucial for understanding conformers.

Ethane Conformers

• Ethane ($CH<em>3CH</em>3$) serves as a basic example.
• Rotation around the C-C single bond creates different conformers of ethane.
• At room temperature, the rotation is very fast, so these conformers are essentially the same molecule.

Newman Projections

• Newman projections are used to visualize conformers by looking down the C-C bond.
• The front carbon is represented by a dot, and the back carbon by a circle.
• Substituents are drawn coming off the dot and the circle.

Stability of Ethane Conformers

• The most stable conformation of ethane is the staggered conformation, where hydrogens are as far apart as possible to minimize steric hindrance.
• The eclipsed conformation, where hydrogens line up, is less stable due to steric interactions.
• Ethane spends more time in the staggered conformation.

Butane Conformers and Steric Strain

• Butane ($CH<em>3CH</em>2CH<em>2CH</em>3$) exhibits stronger steric effects due to the bulkier methyl ($CH_3$) groups.
• The antiperiplanar conformation, where methyl groups are as far apart as possible, is the most stable.
• The syn-periplanar conformation, where methyl groups are eclipsed, is the least stable.
• Gauche conformations are intermediate in stability.
• The most stable conformers are those with bulky substituents as far apart as possible.

Cyclohexane Conformers

• Cyclohexane ($C<em>6H</em>{12}$) is not a flat molecule.
• Each carbon in cyclohexane is $sp^3$ hybridized with tetrahedral geometry.
• The bond angles are approximately 109 degrees, not 120 degrees, causing the ring to buckle.
• This leads to different conformers of cyclohexane.

Chair Conformation

• The chair conformation is the most stable conformation of cyclohexane.
• It features axial hydrogens (pointing straight up and down) and equatorial hydrogens (pointing out).

Boat Conformation

• The boat conformation is less stable due to steric hindrance between protons at the top of the boat.

Ring Flipping

• Cyclohexane can interconvert between chair conformations via the boat conformation.
• During ring flipping, axial and equatorial positions are interchanged.
• Large, bulky groups are more stable in equatorial positions due to reduced steric interactions.

Substituted Cyclohexanes

• In substituted cyclohexanes, the conformer with bulky groups in equatorial positions is preferred.
• If there are multiple substituents, the conformer with the most substituents in equatorial positions is the most stable.

Relevance to Sugar Chemistry: Glucose as an Example

• Glucose and other sugars are six-membered rings, similar to cyclohexane, with one substituent being oxygen.
• The conformation of the sugar ring is crucial for its properties.
• The different sugars are stereoisomers that vary based on the axial or equatorial positions of hydroxyl (OH) substituents.
• Glucose is usually drawn as a six membered ring with an oxygen in the ring and a $CH_2OH$ coming off the back.

Haworth Projections

• Sugars are often drawn using Haworth projections, which represent the three-dimensional structure of the ring.

D and L Notation for Sugars

• The D and L notation is used instead of R/S for sugars due to their multiple chiral centers.
• This notation is based on the Fischer projection, where the sugar is drawn in its open-chain form with the most oxidized carbon at the top.
• The chain is twisted so that the alcohol substituents are pointing out of the board.
• The D or L designation is determined by the position of the hydroxyl group on the penultimate carbon (the chiral center farthest from the aldehyde or ketone group).

Dextrorotatory (D) vs. Levorotatory (L)

• If the hydroxyl group is on the right, it is D (dextrorotatory), derived from dextrose (original name for glucose).
• If the hydroxyl group is on the left, it is L (levorotatory).
• The enantiomer of glucose is L-glucose.

Use in Amino Acids

• The D/L notation is also retained for amino acids.
• For example, the naturally occurring form of alanine is L-alanine, even though its R/S designation is S.
• The DL naming system is retained in biological chemistry due to sugars, which are too complicated to name any other way.

Trehalose and Tardigrades

• Trehalose, a disaccharide found in tardigrades (water bears), helps them survive extreme conditions like the vacuum of space.
• Trehalose encapsulates proteins, trapping water molecules and preventing dehydration.
• Trehalose is used to stabilize protein drugs, such as insulin, for shipping and storage.

Key Concepts Recap

• Be able to draw Newman projections by looking down a carbon-carbon bond.
• Understand that the most stable conformations are those with bulky substituents as far away from each other as possible.
• Understand the DL naming system and where it comes from. It is a different way of naming things which is also typical for amino acids.