3.1-3.11
3.1
The chemistry of cycloalkanes is similar to that of open-chain alkanes: both are nonpolar and fairly inert.
Important differences exist between cycloalkanes and open-chain alkanes.
Cycloalkanes are less flexible than open-chain alkanes.
In open-chain alkanes, there is relatively free rotation around single bonds.
In cycloalkanes, there is much less freedom of rotation.
Cyclopropane must be a rigid, planar molecule due to the three carbon atoms defining a plane.
No bond rotation can occur around a cyclopropane carbon–carbon bond without breaking the ring.
3.2
In ethane, rotation occurs around carbon-carbon bonds.
In cyclopropane, no rotation is possible around carbon-carbon bonds without breaking the ring.
Larger cycloalkanes have increasing rotational freedom.
Very large rings (C25 and up) are nearly indistinguishable from open-chain alkanes.
Common ring sizes (C3–C7) have restricted molecular motions.
Cycloalkanes have two faces (top and bottom) when viewed edge-on.
Isomerism occurs in substituted cycloalkanes.
Example: 1,2-dimethylcyclopropane has two isomers:
Cis: methyl groups on the same face of the ring.
Trans: methyl groups on opposite faces of the ring.
The two isomers are stable and cannot convert without breaking bonds.
1,2-dimethylcyclopropanes differ in spatial orientation though they have the same connections.
These compounds are called stereochemical isomers (or stereoisomers).
Stereochemistry refers to the three-dimensional aspects of structure and reactivity.
1,2-Dimethylcyclopropanes are stereoisomers classified as cis–trans isomers, distinguished by the prefixes cis- (same side) and trans- (across). This type of isomerism is common in substituted cycloalkanes and various cyclic biological molecules.
3.3
To measure strain in a compound:
Measure total energy of compound.
Subtract energy of strain-free reference compound.
Difference shows extra energy due to strain.
Simplest method for cycloalkanes:
Measure heat of combustion (energy released when burned with oxygen).
More strain = more heat released.
Reaction: (CH2)n + 3n/2 O2 → n CO2 + n H2O + Heat
Heat of combustion depends on size:
Examine heats of combustion per CH2 unit.
Calculate strain energy:
Subtract reference value from strain-free alkane.
Multiply by number of CH2 units in the ring.
Cycloalkane strain energies involve:
Calculating the difference in heat of combustion per CH2 between cycloalkanes and acyclic alkanes.
Multiplying by the number of CH2 units in the ring.
Small and medium rings are strained.
Cyclohexane and large rings (C14 and above) are strain-free.
Baeyer’s theory:
Correct for cyclopropane and cyclobutane being strained.
Incorrect about cyclopentane being more strained than expected and cyclohexane being strain-free.
Baeyer assumed all cycloalkanes are flat, which is wrong.
Most cycloalkanes are puckered, with bond angles close to tetrahedral.
Types of strain in cycloalkanes:
Angle strain: Due to bond angle changes.
Torsional strain: Due to eclipsing bonds between neighboring atoms.
Steric strain: Due to repulsion from closely approaching atoms.
3.4
Cyclopropane has the highest strain among rings due to:
60° C−C−C bond angles (angle strain)
Eclipsed C−H bonds create torsional strain
Bonds in cyclopropane are bent, leading to:
Distorted bond angles from 109° (typical) to 60° (cyclopropane)
Weaker and more reactive bonds
Bond strength comparison:
Cyclopropane: 255 kJ/mol (61 kcal/mol)
Open-chain propane: 370 kJ/mol (88 kcal/mol)
Cyclobutane
Less angle strain than cyclopropane
More torsional strain due to more ring hydrogens
Total strain:
Cyclobutane: 110 kJ/mol (26.4 kcal/mol)
Cyclopropane: 115 kJ/mol (27.5 kcal/mol)
Slightly bent structure (one carbon ~25° above plane of others)
Slight bend increases angle strain but decreases torsional strain
Cyclopentane
Predicted to be nearly strain-free by Baeyer
Total strain energy: 26 kJ/mol (6.2 kcal/mol)
Practically no angle strain in planar form
Large torsional strain causes it to twist into a puckered, nonplanar shape
Four carbon atoms in roughly the same plane, fifth bent out of plane
Most hydrogens staggered relative to neighbors.
3.5
Substituted cyclohexanes are common in nature.
They are found in various compounds, including steroids and pharmaceuticals.
Example: menthol has three substituents on a six-membered ring.
Cyclohexane has a chair conformation, resembling a lounge chair.
The chair conformation is strain-free, with no angle or torsional strain.
C−C−C bond angles are close to 109° (tetrahedral structure).
Neighboring C−H bonds are staggered, minimizing strain.
3.6
Chair conformation of cyclohexane influences chemical behavior, especially in substituted cyclohexanes.
Simple carbohydrates like glucose adopt chair conformation, affecting their chemistry.
Two types of substituent positions on cyclohexane: axial (parallel to ring axis) and equatorial (in the plane of the ring).
Each carbon in chair cyclohexane has one axial hydrogen and one equatorial hydrogen.
Each side of the ring has 3 axial and 3 equatorial hydrogens arranged alternately.
Chair cyclohexane has axial and equatorial positions.
Each carbon has one axial and one equatorial position.
Positions alternate around the ring:
Axial: points up or down.
Equatorial: points outward.
Two hydrogens on the same side of the ring = cis.
Two hydrogens on opposite sides = trans.
Expected two isomeric forms for monosubstituted cyclohexanes, but:
Only one form exists for each substituent (e.g., methylcyclohexane, bromocyclohexane, cyclohexanol).
Cyclohexane rings can change shape easily at room temperature.
Different chair conformations of cyclohexane can swap axial and equatorial positions through a process called ring-flip.
In a ring-flip:
Axial positions become equatorial.
Equatorial positions become axial.
To perform a ring-flip, the middle four carbon atoms stay in place while the end carbons fold.
Example: Axial bromocyclohexane becomes equatorial bromocyclohexane after the flip.
The energy barrier for flipping between chair forms is about 45 kJ/mol (10.8 kcal/mol), so this flip happens quickly at room temperature.
3.7
Cyclohexane conformational changes are influenced by equilibrium factors.
The equilibrium constant (Keq) reflects the ratio of product to reactant concentrations:Keq = [C]ᶜ[D]ᵈ / [A]ᵃ[B]ᵇ.
A Keq much larger than 1 suggests products are favored, near 1 indicates both reactants and products are present, and less than 1 suggests the reaction favors reactants.
Keq informs about equilibrium position but not reaction rate.
Cyclohexane ring flips happen quickly; the equatorial form of methylcyclohexane is more stable by 7.6 kJ/mol than the axial form.
The percentage of isomers at equilibrium can be calculated using ΔG = -RT ln K.
Energy differences due to steric strain from 1,3-diaxial interactions impact stability between axial and equatorial positions.
The strain increases with substituent size (e.g., CH3 < CH2CH3 < (CH3)3C).
The degree of 1,3-diaxial strain can be quantified and varies based on substituent nature.
3.8
Monosubstituted cyclohexanes are more stable with substituent in equatorial position.
Disubstituted cyclohexanes are complex due to steric effects of both substituents.
Analyze all steric interactions in chair conformations before determining favored conformation.
Example: 1,2-dimethylcyclohexane
Two isomers: cis and trans.
In cis, both methyl groups on the same face; exists in two equivalent chair conformations.
Each conformation has one axial and one equatorial methyl group.
Energy and strain calculations yield the same energy for both cis conformations.
In trans, methyl groups on opposite sides; conformation comparisons differ.
Top trans conformation has both groups equatorial (favored).
Flipped conformation has both groups axial, causing more steric strain.
Trans-1,2-dimethylcyclohexane favors diequatorial conformation (more stable).
Stability varies with substituent size and arrangement.
Example comparison: glucose (equatorial substituents) vs mannose (one axial substituent, more strained).
3.9
Polycyclic Molecules: Formed by fusing two or more cycloalkane rings along a common bond.
Decalin: Consists of two cyclohexane rings sharing two carbon atoms (C1 and C6).
Can exist as cis or trans isomers.
Cis-decalin: Hydrogen atoms at bridgehead carbons are on the same side.
Trans-decalin: Hydrogen atoms are on opposite sides.
Isomers are non-interconvertible; they are cis-trans stereoisomers.
Common in Nature: Polycyclic compounds include steroids (e.g., testosterone) with fused rings.
Norbornane: A bicycloalkane structure (bicyclo[2.2.1]heptane) with 7 carbons and three bridges.
Has a locked boat conformation with carbons 1 and 4 connected by an additional CH2 group.
A molecular model can help visualize the structure.
Substituted Norbornanes: Found in nature, including important compounds like camphor.
3.10
Carbon–carbon double bond can be described via two methods: valence bond theory and molecular orbital theory.
In valence bond theory:
Carbons are sp2-hybridized with three hybrid orbitals at 120° angles in a plane.
σ bond forms from head-on overlap of sp2 orbitals.
π bond forms from sideways overlap of unhybridized p orbitals.
In molecular orbital theory:
P orbital interactions create one bonding (π) and one antibonding (π*) molecular orbital.
π bonding MO has no node and is formed from similar p orbital lobes; π antibonding MO has a node and is formed from different lobes.
Single bonds allow free rotation, but double bonds do not due to the need to break the π bond to rotate.
Estimated energy barrier for double bond rotation: 350 kJ/mol (84 kcal/mol).
Example: 2-butene can exist as cis (substituents on the same side) and trans (substituents on opposite sides) isomers, similar to substituted cycloalkanes.
cis-trans isomerism occurs when both double-bond carbons are bonded to different groups; identical groups prevent this.
3.11
Cis-trans naming works for disubstituted alkenes (two non-hydrogen substituents on the double bond).
More complex alkenes (trisubstituted and tetrasubstituted) need a general method for double-bond geometry.
Trisubstituted = three non-hydrogen substituents; Tetrasubstituted = four non-hydrogen substituents.
The E,Z system is used to describe alkene stereochemistry for more complex structures.
E,Z system follows Cahn–Ingold–Prelog sequence rules.
Detailed explanation of these rules will be provided in Section 4.4.