Organic Chemistry: Chair Conformations and Carbonyl Reactions

Learning Outcomes

• Understand chair conformations and flipped structures
• Analyze which chair conformation is most stable
• Predict products from reactions with carbonyls
• Draw plausible mechanisms for carbonyl reactions

Conformations of Rings

• Cyclopropane:
  • Only one conformation due to rigidity; planar with angle strain due to deviation from tetrahedral angle (109.5°).
• Larger Rings:
  • Non-planar; puckered shape to minimize angle strain.
• Cyclohexane:
  • A planar conformation would face torsional and angle strain so it exists in chair form.
  • Hydrogen Types:
  • Axial Hydrogens: Perpendicular to the plane of the ring.
  • Equatorial Hydrogens: Parallel to the plane of the ring.

Drawing Cyclohexanes

1. Draw 3 parallel lines for ring structure.
2. Place 1st axial hydrogen pointing up on top C.
3. Alternate axial hydrogen directions on other C’s.
4. Position equatorial Hs parallel to first set of C-C bonds.
5. Label all hydrogens as axial/equatorial.

Flipped Cyclohexanes

• Ring Flip Mechanics:
  • Partial rotation of C-C bonds allows for "ring flip" where axial becomes equatorial and vice versa.
  • Visualize by drawing flipped structures and observing carbon shifts clockwise.

Drawing Monosubstituted Cyclohexanes

1. Start with a chair conformation.
2. Place substituent at either axial or equatorial position.
3. Draw the ring flip.
4. Identify axial and equatorial on flipped structure.

1,3-Diaxial Interactions in Cyclohexanes

• A substituent in the equatorial position is more stable due to fewer 1,3-diaxial interactions.
• 1,3-Diaxial Interaction: Steric interactions between two axial substituents (e.g., CH₃ and H).
• General rule: Larger substituents prefer equatorial conformation (e.g., tert-butyl groups).

Isomer Stability: Cis vs. Trans-Dimethylcyclohexane

• Cis-Dimethylcyclohexane:
  • Evaluate 1,3-diaxial (2) and gauche (1) interactions.
• Trans-Dimethylcyclohexane:
  • More diaxial interactions (4) and one gauche interaction.
• Conclusion: Equatorial groups = more stable conformations.

Energy Values for 1,3-Diaxial Interactions

• Table of common substituents and their energy costs in kJ/mol:
  • Cl: 2.0 (70:30)
  • OH: 4.2 (83:17)
  • CH₃: 7.6 (95:5)
  • CH₂CH₃: 8.0 (96:4)
  • C(CH₃)₃: 22.8 (9999:1)

Conversion of Alcohols to Carbonyls

• 1° alcohols to aldehydes/carboxylic acids: Use Na₂Cr₂O₇ or CrO₃, DMP, etc.
• 2° alcohols to ketones: Oxidation possible; 3° alcohols are not oxidizable.

Nucleophilic Addition Mechanism

1. Nucleophile (Nu) adds to electrophile (M⁺).
2. Water (H₂O) is introduced for protonation:
   HO-Nu (resulting in bonds setup).

Formation of Cyanohydrins

• Use HCN or KCN:
  • Significantly increases carbon count in molecule.

Hemiacetals and Acetals Formation

• Hemiacetal:
  • Formed from reactions of carbonyls with alcohols (R + R'OH in presence of acid).
• Acetal: More stable; reverse process leads to hydrolysis of acetals back to carbonyls.

Thioacetals and Hydrolysis

• Thioacetals: Formed from thioalcohols and similar mechanisms.

Amine Nomenclature and Characteristics

• Primary Amine (1°): 1 group on nitrogen.
• Secondary Amine (2°): 2 groups on nitrogen.
• Tertiary Amine (3°): 3 groups on nitrogen.

Primary Nitrogen Nucleophiles: Imines

• Formation: Via reaction of amines with carbonyls, produces imines (Schiff bases) utilizing hydronium.

Reduction with Hydride Reagents

• NaBH₄: Reduces aldehydes/ketones; forms alcohols through nucleophilic attack.
• LiAlH₄: Suitable for stronger reductions including carboxylic acids and esters.

Grignard Reactions: Aldehydes and Ketones

• Formation of Alcohols:
  1. Grignard reagent reacts with carbonyls: R-MgX + R'CHO
  2. Forms alkoxide anion, protonation leads to alcohol formation.

Summary of Mechanisms

• Mechanisms often involve sequential steps where nucleophiles add, water is incorporated or groups are reoriented between axial/equatorial configurations for stability.