Alicyclic Chemistry Notes

Alicyclic Chemistry

• Alicyclic chemistry is the chemistry of ring-shaped compounds.

Cycloalkanes

• Cycloalkanes, also called alicyclic compounds, are cyclic alkanes with carbon atoms arranged in a ring.
• The ring structure causes cycloalkanes to have fewer hydrogen atoms than acyclic compounds.
• General formula of cycloalkanes: $C<em>nH</em>{2n}$
• To name simple cycloalkanes, add the prefix cyclo to the alkane name.
• Structure is shown as a regular polygon with the number of vertices equal to the number of carbons.

Nomenclature of Cycloalkanes

• Rules for naming cycloalkanes are similar to alkanes with two additional rules:
  • Rule 1: Decide whether the cyclic or acyclic portion contains more carbons to determine the base name.
    • Alkyl-substituted cycloalkane or cycloalkane-substituted alkane
    • If the number of carbon atoms in the ring is equal to or greater than the number in the substituent, the compound is named as an alkyl-substituted cycloalkane.
  • Rule 2: Carbons are numbered to give the lowest numbers for substituted carbons.
• Numbering starts at the most substituted carbon and goes around to give the lowest numbers.

Physical Properties

• Boiling and melting points increase with increasing molecular mass and are higher than comparable alkanes.
• The rigid structure of cycloalkanes permits greater attractive interactions.
• Higher density is due to rigid structure allowing molecules to pack more effectively, increasing mass per unit volume.

Geometric Isomerism in Cycloalkanes

• Open-chain alkanes have free rotation about their $C-C$ bonds.
• Alkenes, with double bonds, cannot undergo free rotation.
• Cycloalkanes, with their ring structure, also cannot undergo free rotation about their $C-C$ bonds.
• Substituents are fixed on one side of the ring; substituted cycloalkanes can give rise to geometric isomers (cis and trans isomers).
• If two non-hydrogen substituents are on the same side of the ring, it is the cis isomer; if they are on opposite sides, it is the trans isomer.

Ring Strain in Cycloalkanes - Stability of Cycloalkanes

• Baeyer (1885) postulated a theory of angle strain for cycloalkanes. The difference between a tetrahedral angle (109.5^") and the internal angle of a polygon is used as a measure of stability.
• When carbon is bonded to four other atoms, the angle between any pair of bonds is the tetrahedral angle 109.5^".
• If a cycloalkane requires bond angles different from 109.5^",$the$sp^3 orbitals cannot overlap as efficiently as possible. This gives rise to angle strain (Baeyer strain).
• Deviations from this angle in cyclic compounds such as cyclopropane cause molecules to be strained and therefore relatively unstable.
• The greater the deviation from this angle, the more unstable a molecule is and thus the more prone it is to ring-opening reactions.
• Parts of Baeyer’s theory have been discarded. The theory does not apply to rings with more than four carbon atoms.
• Rings of all sizes (3C to 30C) can now be easily prepared.

Limitations of Baeyer's Theory

• The angles used for each ring are based on the assumption that the rings of all cycloalkanes are planar (flat).
• Cycloalkanes, in reality, adopt puckered three-dimensional conformations that allow all the bond angles to be nearly tetrahedral.
• Cyclopentane should be more stable than cyclohexane, according to the theory. However, experiments reveal it is in fact the reverse.
• Larger ring systems are not possible as they have negative strain, according to the theory, but they do exist and are stable.

Types of Strain

• Angle strain: Expansion or compression of bond angles away from the most stable angle.
• Torsional/bond strain: Due to the eclipsing of bonds on neighboring atoms.
• Steric strain: Repulsive interactions between non-bonded atoms in close proximity.

Ring Strain Calculation

• Ring strain is calculated with heats of combustion.
• The energy released is the heat of combustion. This value can be converted into useful information.
• Cyclopropane and cyclobutane are highly strained.
• Cyclopentane and cycloheptane have low ring strain.
• Cyclohexane has no ring strain.

Cyclopropane

• Cyclopropane is the most strained cycloalkane due to angle strain and torsional strain.
• Bonding overlap is reduced because the enforced 60^",$bond angle leads to poor overlap of the$sp^3 orbitals (bonds are bent and therefore weakened).
• The three-membered ring has to be planar, and all the C-H bonds are eclipsed.
• The angle strain is larger than the torsional effects for cyclopropane.

Cyclobutane

• Cyclobutane is neither planar nor a perfect square, so it does not have 90^".
• A planar geometry would force all the C-H bonds into eclipsing positions.
• Cyclobutane adopts a slightly puckered conformation (one carbon atom is about 25^",$above) with bond angles of$88^".
  • This increases angle strain but reduces torsional strain.
• It has less angle strain than cyclopropane but more torsional strain because of its larger number of ring hydrogens.

Cyclopentane

• Planar cyclopentane would have very little angle strain but a large amount of torsional strain.
• Cyclopentane is not planar either, since this would also require all C-H’s to be eclipsing.
• The molecule adopts a puckered ‘envelope’ conformation, which reduces the torsional strain.
  • Carbons 1-4 are in the same plane, while carbon 5 is twisted out of plane (above or below).

Cyclohexane

• Cyclohexane is by far the most common cycloalkane in nature and also in organic chemistry.
• These conformations can occur with very little strain or zero strain.
• Zero ring strain implies the bond angles must be close to 109.5^",$(no angle strain) and also no eclipsing interactions between the$C-H bonds (no torsional strain).
• Cyclohexane has two conformations/configurations:
  • Chair
  • Boat

Cyclohexane - Chair Conformation

• Cyclohexane adopts a puckered structure. The most stable conformation for cyclohexane is called the chair conformation.
• In the chair conformation, all the bond angles are 109.5^",$and all the$C-H bonds are staggered (Zero ring strain)
  • This conformation has alternating atoms in a common plane and tetrahedral angles between all carbons

Cyclohexane - Boat Conformation

• Cyclohexane also exists in the boat conformation, which is just a chair with the footrest flipped up. This also has bond angles of 109.5^".
• It avoids any angle strain, but there is torsional strain. The two hydrogens at the ends of the boat are in close contact, causing torsional strain, and the flagpole hydrogens are eclipsed.

Cyclohexane - Conformations

• To avoid these unfavorable interactions, the boat conformation skews slightly, giving a twist-boat conformation.
• The chair is the lowest energy conformation, although since the energy barrier to ring flip is fairly small, there will always be some other conformations present.
• The half-chair is the point of highest energy and is not a stable conformation.

Axial and Equatorial Positions

• A snapshot of cyclohexane in a chair conformation has 2 types of C-H bonds:
  • Six of the C-H bonds point straight up and down (axial bonds).
  • Six of the C-H bonds point out from the ring (equatorial bonds).
• Notice the alternating pattern of the positions.
• Each carbon atom in cyclohexane has one axial and one equatorial hydrogen.
• Each face of the ring has three axial and three equatorial hydrogens in an alternating arrangement.

Conformational Mobility of Cyclohexane

• Chair conformations readily interconvert, resulting in the exchange of axial and equatorial positions by a ring-flip.

Conformations of Monosubstituted Cyclohexanes

• Cyclohexane ring rapidly flips between chair conformations at room temperature.
• A substituent on a cyclohexane ring can occupy either an axial or equatorial position. The substituent stability & reactivity depends on its position.
• Two conformations of monosubstituted cyclohexane aren’t equally stable.
• The chair conformation with the methyl in the axial position can interconvert into a chair conformation with the methyl in the equatorial position (ring flip).
• Interconversion changes axial to equatorial and equatorial to axial.
• Both chair conformations are lower in energy than the boat.
• In the Newman projection, when the methyl group is in the axial position, it is gauche to C3$and$C5.
• When the methyl is equatorial, it is anti to C3.
• Axial methylcyclohexane has 2 gauche interactions; each 0.9 kcal/3.8kJ added energy.
• Equatorial methylcyclohexane has no gauche interactions and higher energy (1.8kcal/7.6kJ).
• Gauche interaction is also known as a 1,3-diaxial interaction.
• The axial substituents on C1$and$C3 are close in space, and their electron clouds repel one another.
• Generally, a larger substituent gives rise to a larger difference in energy between the axial and equatorial conformations.
• Energy differences for various groups:
  • -F: 0.2 kcal/mol, 0.8 kJ/mol
  • -CN: 0.2 kcal/mol, 0.8 kJ/mol
  • -Cl: 0.5 kcal/mol, 2.1 kJ/mol
  • -Br: 0.6 kcal/mol, 2.5 kJ/mol
  • -OH: 1.0 kcal/mol, 4.1 kJ/mol
  • -COOH: 1.4 kcal/mol, 5.9 kJ/mol
  • -CH3: 1.7 kcal/mol, 7.6 kJ/mol
  • -CH2CH3: 1.8 kcal/mol, 7.9 kJ/mol
  • -CH(CH3)2: 2.1 kcal/mol, 8.8 kJ/mol
  • -C(CH3)3: 5.4 kcal/mol, 23 kJ/mol

Conformations of Disubstituted Cyclohexanes

• There is great steric interference when there are two large substituents in axial positions oriented on C1$and$C3$(or$C1$and$C5) (i.e., carbon atoms with 1,3-diaxial interactions).
  • Cis-1,3-dimethylcyclohexane
  • The less stable conformation has both methyl groups in axial positions (diaxial).
  • The more stable conformation has both methyl groups in equatorial positions (diequatorial).
• Trans-1,3-dimethylcyclohexane does not have a conformation with a 1,3-diaxial interaction between two methyl groups.
  • Both conformations of trans-1,3-dimethylcyclohexane are the same since they both contain a methyl group in an axial and equatorial position.

Geometric Isomerism in Disubstituted Cyclohexanes

• Like alkenes, they also exhibit geometric isomerism; the closed ring structure restricts rotation about the C-C$bond, so the 2 substituents on each ring$C may point up or down.
  • In order for cycloalkanes to show cis-trans isomerism, at least 2 ring C$$ atoms must have 2 different groups attached.
• When the two substituents are on the same face of the ring, it is the cis isomer; when on opposite faces of the ring, it is the trans isomer.

Substituents of Different Sizes

• Many substituted cyclohexanes have substituents of different sizes.
• The energy difference between axial and equatorial positions is generally higher for larger (bulkier) groups than for a smaller group.
• In determining the most stable conformations for substituents of different sizes, if both cannot be equatorial, the larger group goes equatorial, and the smaller goes axial.

Extremely Bulky Groups

• A group such as tert-butyl will always go to the equatorial position because it is so bulky.
• If two t-butyl groups are in the same cyclohexane, both will take equatorial positions.
• If they cannot, the molecules are forced into the twist-boat conformation, which will be less crowded and lower in energy.