John E. McMurry
http://www.cengage.com/chemistry/mcmurry
Chapter 4
Organic Compounds:
Cycloalkanes and Their
Stereochemistry
Javier E. Horta, M.D., Ph.D. • University of Massachusetts Lowell
Cyclics
Most organic compounds contain rings of carbon atoms
Chrysanthemic acid
• Occurs naturally as esters
• Active insecticidal
constituents of chrysanthemum
flowers
Prostaglandins
• Potent hormones
• Control physiological functions
in humans
Steroids
Contain four joined rings
Naturally occurring hormones
in plants and animals
•
•
4.1 Naming Cycloalkanes
Cycloalkanes or Alicyclic Compounds (aliphatic cyclic)
• Saturated cyclic hydrocarbons containing rings of carbon
atoms
• (CH2)n or CnH2n
Naming Cycloalkanes
Rule 1 – Find the parent by counting carbon atoms
Named as alkyl-substituted cycloalkane
• The number of carbon atoms in the ring is equal to or
greater than the number in the substituent
Named as cycloalkyl-substituted alkane
• The number of carbon atoms in the largest substituent is
greater than the number in the ring
Naming Cycloalkanes
Rule 2 – Number the substituents, and write the name
•
Choose attachment point as carbon 1 and number carbon
atoms on the ring so that second substitutent has lowest
number possible.
Naming Cycloalkanes
•
If ambiguity exists, number
carbon atoms so that third or
fourth substituent has lowest
number possible.
Naming Cycloalkanes
• When two or more substituents could potentially receive the
same numbers, number by alphabetical priority:
Naming Cycloalkanes
• If halogens are present, treat them just like alkyl groups:
• Additional examples:
4.2 Cis-Trans Isomerism in Cycloalkanes
Cycloalkanes vs. Open-chain Alkanes
• Similarities – nonpolar; fairly inert
• Differences – cycloalkanes are less flexible than open-
chain alkanes
•
•
Rotation occurs around the carbon-carbon bond in ethane
No rotation is possible around the carbon-carbon bonds in
cyclopropane without breaking open the ring
Cis-Trans Isomerism in Cycloalkanes
• Cycloalkanes: Two faces (as viewed edge on)
Top face
Bottom face
• Isomerism possible in substituted cycloalkanes
Cis-Trans Isomerism in Cycloalkanes
Constitutional Isomers
• Isomers that have their
atoms connected in a
different order
Stereoisomers
• Isomers that have their
atoms connected in the
same order but differ in
three-dimensional geometry
cis isomer
trans isomer
Cis-Trans Isomerism in Cycloalkanes
cis-trans isomers
• Stereoisomers that differ in their stereochemistry
about a double bond or ring
• cis- (Latin, “on the same side”)
• trans- (Latin, “across”)
Worked Example 4.1
Naming Cycloalkanes
Name the following substances, including cis- or transprefix
Worked Example 4.1
Naming Cycloalkanes
Solution
(a) trans-1,3-Dimethylcyclopentane
(b) cis-1,2-Dichlorocyclohexane
4.3 Stability of Cycloalkanes: Ring Strain
Angle strain
•
The strain induced in a molecule when bond angles are forced to
deviate from the ideal 109º tetrahedral value (Adolf von Baeyer – 1885)
Stability of Cycloalkanes: Ring Strain
Angle strain
• Experimental data show that Baeyer’s theory is only partially
correct
•
•
Baeyer assumed all cycloalkanes to be flat
Angle strain occurs only in small rings that have little flexibility
Stability of Cycloalkanes: Ring Strain
The three kinds of strain that contribute to the overall
energy of a cycloalkane:
Angle strain – the strain due to expansion or
compression of bond angles
2. Torsional strain – the strain due to eclipsing of bonds on
neighboring atoms
3. Steric strain – the strain due to repulsive interactions
when atoms approach each other too closely
1.
4.4 Conformations of Cycloalkanes
Cyclopropane
•
•
•
Most strained of all the rings
Angle strain – caused by 60º C-C-C bond angles
Torsional strain – caused by the eclipsed C-H bonds on neighboring
carbon atoms
a) Structure of cyclopropane showing the eclipsing of neighboring CH bonds giving rise to torsional strain
b) Newman projection along a C-C bond of cyclopropane
Conformations of Cycloalkanes
•
Bent C-C bonds
• Orbitals can’t point directly toward each other
• Orbitals overlap at a slight angle (i.e., “banana bonds”)
• Bonds are weaker and more reactive than typical alkane bonds
•
C-C bond:
255 kJ/mol (61 kcal/mol) for cyclopropane
355 kJ/mol (85 kcal/mol) for open-chain propane
Conformations of Cycloalkanes
Cyclobutane
• Total strain is nearly same as cyclopropane
• Angle strain – less than cyclopropane
Torsional strain – more than cyclopropane because of larger
number of ring hydrogens
• Not planar (not flat)
• One carbon atom lies 25º above the plane of the other three
• Newman projection along C1-C2 bond shows that neighboring C-H
bonds are not quite eclipsed
•
Conformations of Cycloalkanes
Cyclopentane
• Less strain than cyclopropane or cyclobutane
• Planar cyclopentane exhibits:
• Angle strain – very minimal
• Torsional strain – large amount
• Cyclopentane twists to a nonplanar (puckered) conformation
• C1, C2, C3 and C4 are nearly planar but C5 is out of the plane
• Balance between increased angle strain and a decreased torsional strain
4.5 Conformations of Cyclohexane
Substituted cyclohexanes
• Most common cycloalkanes
• Occur widely in nature
• Steroids
• Pharmaceutical agents
Conformations of Cyclohexane
Cyclohexane
• Adopts chair conformation
• No angle strain
• All C-C-C bonds are 111.5º, close to the ideal 109º
• No torsional strain
• Neighboring C-H bonds are staggered
Conformations of Cyclohexane
Drawing chair conformation of
cyclohexane
• Step 1 – draw parallel lines, slanted downward
and slightly offset from each other
• Step 2 – place topmost carbon atom above
and to the right of the plane of the other four,
and connect the bonds
• Step 3 – place bottommost carbon atom below
and to the left of the plane of the middle four,
and connect the bonds
Note: Bonds to the bottommost carbon atom are parallel to
the bonds to the topmost carbon.
Conformations of Cyclohexane
Chair conformation
• Angle strain – none
• Torsional strain – none
Twist-boat conformation
• About 23 kJ/mol (5.5 kcal/mol) higher in energy than chair
• Angle strain – minimal
• Torsional strain – large amount
• Steric strain – large amount
4.6 Axial and Equatorial Bonds in
Cyclohexane
Chair conformation of cyclohexane
• Chemical behavior of many substituted cyclohexanes is
influenced by conformation
• Simple carbohydrates (such as glucose) adopt a cyclohexane
chair conformation which directly affects their chemistry
Axial and Equatorial Bonds in Cyclohexane
Chair conformation of cyclohexane
• There are two kinds of positions for substituents on the
cyclohexane ring
• Axial positions – 6 axial positions perpendicular to ring
and parallel to ring axis.
• Equatorial positions – 6 equatorial positions are in rough
plane of the ring around the equator
axial positions
equatorial positions
Axial and Equatorial Bonds in Cyclohexane
Chair conformation of cyclohexane
• 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 pattern.
Axial and Equatorial Bonds in Cyclohexane
Chair conformation of cyclohexane
• Drawing axial and equatorial positions
Axial and Equatorial Bonds in Cyclohexane
Chair conformation of cyclohexane
• There is only one form of a monosubstituted cyclohexane.
• Cyclohexane rings are conformationally mobile.
• Different chair conformations readily interconvert exchanging
axial and equatorial positions - called a ring-flip.
Axial and Equatorial Bonds in Cyclohexane
Chair conformation of cyclohexane
• Ring-flip occurs by keeping the middle four carbon atoms in place
while folding the two end carbons in opposite directions
•
•
Axial substituent becomes an equatorial substituent after ring-flip
and vice versa
Energy barrier to ring-flip is about 45 kJ/mol (10.8 kcal/mol)
Worked Example 4.2
Drawing the Chair Conformation of a Substituted
Cyclohexane
Draw 1,1-dimethylcyclohexane in a chair
conformation, indicating which methyl group in
your drawing is axial and which is equatorial
Worked Example 4.2
Drawing the Chair Conformation of a Substituted
Cyclohexane
Solution
1,1-dimethylcyclohexane
4.7
Conformations of Monosubstituted
Cyclohexanes
The two conformers of a monosubstituted cyclohexane are not
equally stable
• Substituent is almost always more stable in equatorial
position
Conformations of Monosubstituted Cyclohexanes
Steric strain
• Origin of the steric strain between an axial methyl group and
an axial hydrogen atom in methylcyclohexane is identical to
the steric strain in gauche butane
•
Equatorial methylcyclohexane has no such interactions and is
more stable
4.8
Conformations of Disubstituted
Cyclohexanes
• Monosubstituted cyclohexanes
• Always have substituent in equatorial position
• Disubstituted cyclohexanes
• All steric interactions in both chain conformations must
be analyzed to determine most stable conformation
Conformations of Disubstituted Cyclohexanes
Disubstituted cyclohexane: 1,2-dimethylcyclohexane
• Cis- isomer
•
•
Both methyl groups are on same face of ring
Conformations are equal in energy because each has one axial
methyl group and one equatorial methyl group
Conformations of Disubstituted Cyclohexanes
Disubstituted cyclohexane: 1,2-dimethylcyclohexane
• Trans- isomer
•
•
Two methyl groups are on opposite faces of the ring
Exists almost exclusively in the diequatorial conformation
Conformations of Disubstituted Cyclohexanes
•
•
Conformational analysis can be done for any substituted cyclohexane
Glucose and manose (a carbohydrate found in seaweed)
• In glucose all substituents on the six-membered ring are equatorial
• In manose one of the –OH groups is axial, making manose more
strained
Worked Example 4.3
Drawing the Most Stable Conformation of a
Substituted Cyclohexane
Draw the most stable conformation of cis-1-tert
butyl-4-chlorocyclohexane.
Worked Example 4.3
Drawing the Most Stable Conformation of a
Substituted Cyclohexane
Solution
tert-butyl group is equatorial
chlorine is axial
tert-butyl group is axial
chlorine is equatorial
The conformation on the left is the lower energy conformation because the
more bulky tert-butyl group is not producing any 1,3-diaxial interactions
with ring hydrogens
4.9 Conformations of Polycyclic Molecules
Polycyclic Molecule
• Two or more cycloalkane rings that are fused together
• Decalin
•
Two fused cyclohexane rings
Conformations of Polycyclic Molecules
•
Decalin
• Can exist in two isomeric forms
• Cis-decalin
• Hydrogen atoms on same
face of ring
• Trans-decalin
• Hydrogen atoms on
opposite faces of the ring
• Cis- and trans-decalin are not
interconvertible by ring-flip or
other rotations
Conformations of Polycyclic Molecules
Polycyclic compounds
• Common in nature
Example: steroids
• The same principles apply as with those for the
conformation analysis of simple cyclohexane rings