CHAPTER 4 Cyclic Alkanes

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CHAPTER 4Cyclic Alkanes
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Names and Physical Properties of Cycloalkanes
4-1
The names of the cycloalkanes follow IUPAC
rules. The general formula of a cyclealkane is
CnH2n.
To name a cycloalkane, prefix the alkane name
with cyclo.
Numbering a cycloalkane ring is necessary only
when there is more than one substituent. In
nonsubstituted cycloalkanes, the attached carbon
is numbered number 1.
3

• Use the lowest possible numbering sequence for
  polysubstituted cycloalkanes. If two identical
  numbering sequences are possible, use
  alphabetical precedence.
• Substituted cycloalkanes are sometimes named as
  cycloalkyl derivatives. The smaller unit is
  generally treated as a substituent to the larger
  unit.
• Propylcyclopentane (not cyclopentylpropane)
• Cyclohexyloctane (not octylcyclohexane)

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Disubstituted cycloalkanes possess
stereoisomers. Disubstituted cycloalkanes having
substituents on different carbons possess cis
(same side) / trans (opposite side) isomers.
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Cis/trans isomers are examples of stereoisomers.
These are non-superimposable molecules having the
same molecular formula and connectivity.
Conformers are also stereoisomers but can be
interconverted by rotations about C-C bonds.
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• The properties of the cycloalkanes differ from
  those of their straight chain analogs.
• Cycloalkanes have higher boiling points, melting
  points, and densities than their straight-chain
  analogs.
• Increased London forces are due to more rigid and
  symmetric cyclic systems.
• The smaller cycloalkanes with an odd number of
  carbon atoms have lower melting points than
  expected compared to cycloalkanes with an even
  number of carbon atoms. This is attributed to
  crystal-packing forces between the two types of
  cycloalkanes.

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Ring Strain and the Structure of Cycloalkanes
4-2
The heats of combustion of the cycloalkanes
reveal the presence of ring strain. Cyclopropane
(60o) and cyclobutane (90o) possess C-C-C bond
angles significantly different from 109.5o and
are strained. This is termed ring
strain. Cyclohexane has essentially no ring
strain. The ring strain in cycloalkanes can be
estimated by comparing the theoretical heats of
combustion to the measured heats of combustion
Four groupings Small (3,4) Common (5,6,7) Medium
(8-12) Large (gt12)
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Strain affects the structures and conformational
function of the smaller cycloalkanes. Cyclopropane
All of the methylene hydrogens are eclipsed
(eclipsing strain) There is no available bond
rotation to achieve a staggered conformation. The
C-C-C bond angles are 60o, far from the
unstrained value of 109.5o. The C-C bond energy
is about 65 kcal mol-1 The ring of cyclopropane
is easily opened, for instance by hydrogenation
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Cyclobutane Cyclobutane is puckered with a
bending angle of about 26o.
The bent cyclobutane molecules flips rapidly from
one puckered conformation to another. The
puckered conformation partially relieves the
strain caused by the otherwise eight eclipsing
hydrogens. The C-C bond strength is about 63 kcal
mol-1. Cyclobutane also undergoes ring opening
but is less reactive than cyclopropane.
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Cyclopentane A regular pentagon has interior
angles of 108o (close to tetrahedral). However,
cyclopentane is puckered, not planar.
The puckering in cyclopentane relieves some of
the hydrogen eclipsing, however, it somewhat
increases the bond strain. The observed
structures balances these two opposing factors to
achieve a structure of lowest energy. There are
two puckered conformations, the envelope and the
half chair. There is little energy difference
between them and they rapidly interconvert.
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Cyclohexane A Strain-Free Cycloalkane
4-3
The chair conformation of cyclohexane is strain
free. Cyclohexane has several conformations, one
of which is called the chair conformation.
In the chair conformation, eclipsing of the
hydrogens is completely prevented, the C-C-C bond
angles are very nearly tetrahedral, and the
molecule is nearly strain free.
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Cyclohexane also has several less stable
conformations. A second, less stable conformation
of cyclohexane is the boat form, which is less
stable than the chair form by 6.9 kcal mol-1.
The higher energy is due to the eclipsing of the
8 hydrogens at the base of the boat, and the
transannular (steric crowding across a ring)
strain between the two hydrogens in the boat
framework.
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The boat form of cyclohexane is flexible and
actually represents a transition state between
two slightly more stable twist-boat (or
skew-boat) conformations. The stabilization of
the twist forms to the boat form is about 1.4
kcal mol-1, The activation energy for
interconversion of the chair form and boat forms
is 10.8 kcal mol-1. Normally cyclohexane exists
primarily as the chair confomer with very small
amounts of the twist boat form and no actual boat
form.
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• Cyclohexane has axial and equatorial hydrogen
  atoms.
• In the chair form, cyclohexane has two types of
  hydrogens
• Axial 6 H parallel to the principle
  molecular axis
• Equitorial 6 H perpendicular to the principle
  molecular axis

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Two draw chair cyclohexanes, follow these steps
1.) Draw the carbon chair.
2.) Add the axial hydrogens.
3.) Draw the C1 and C4 equitorial hydrogens.
4.) Draw the remaining equatorial hydrogens.
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Conformational flipping interconverts axial and
equatorial hydrogens. Starting with a chair form
having C1 down and C4 up, the boat form can be
reached by flipping C1 up. If in returning to
the chair form, C4 is flipped down, rather than
C1, the effect is to interconvert the axial and
equitorial hydrogens on the cyclohexane molecule
The energy of activation for this conversion is
10.8 kcal mol-1 which is very low, and at room
temperature this interconversion occurs
approximately 100,000 times per second. When
substituents replace one or more hydrogens, one
confomer may be more stable than the other,
affecting both stereochemistry and reactivity.
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Substituted Cyclohexanes
4-4
Axial and equatorial methylcyclohexanes are not
equivalent in energy. In methylcyclohexane, the
confomer having the methyl group in an equatorial
position is more stable by about 1.7 kcal mol-1.
The 1,3-diaxial interaction is the same as the
result in the gauche conformation of butane.
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Newman projections more clearly show the
unfavorable 1,3- diaxial interactions
Energy differences for other monosubstituted
cyclohexanes
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Substituents compete for equatorial
positions. Consider the following disubstituted
cycloalkanes
Equal energies
Equal energies
Diequatorial more stable
Large group equitorial more stable.
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Larger Cycloalkanes
4-5

• Rings larger that cyclohexane have more strain.
• Bond angle distortion
• Partial eclipsing of hydrogens
• Transannular steric repulsions
• Medium sized rings adopt several conformations
  that are very close in energies, such as
  cyclodecane

Strain energy of 14 kcal mol-1.
Strain energy of 14 kcal mol-1.
Large-sized cycloalkanes such as cyclotetradecane
are able to adopt staggered and all-anti
conformations similar to straight chain alkanes
and are essentially strain free. Attachment of
substituents, however, usually introduces some
strain.
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Polycyclic Alkanes
4-5
Polycyclic alkanes may contain fused or bridged
rings. The fused system, decalin, can be compared
to the disubstituted molecule, 1,2-diethylcyclohex
ane.
Decalin is an example of a fused bicyclic ring
system. The shared carbon atoms are called
ring-fusion carbons. Groups attached to the
ring-fusion carbons are called ring-fusion
substituents.
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A second example of ring fusion, norborane, can
be compared to the compound, cis-1,3-dimethylcyclo
pentane
Norborane is an example of a bridged bicyclic
ring system. Two non-adjacent carbon atoms belong
to both rings and are called bridgehead carbon
atoms.
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Bicyclic ring systems can be either cis- or
trans-fused
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Do hydrocarbons have strain limits? Many
interesting molecules have been synthesized to
examine the limits of strain in hydrocarbon bonds
66.5 kcal mol-1
129 kcal mol-1
Unknown
166 kcal mol-1
61 kcal mol-1
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Carbocyclic Products in Nature
4-6

• Natural products are organic compounds produced
  by living organisms.
• Four classification schemes are used for natural
  products
• Chemical structure
• Physiological activity
• Organism or plant specificity (taxonomy)
• Biochemical origin
• Terpenes and steroids have received much
  attention from organic chemists.

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Terpenes are constructed in plants from isoprene
units. Terpenes are volatile compounds usually
containing 10 (monoterpenes), 15 (sesquiterpenes)
, or 20 (ditepenes) carbon atoms. Terpenes are
synthesized in plants by linking two or more 5
carbon fragments called isoprene
(2-methyl-1,3-butadiene).
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• Examples of terpenes include
• Chrysanthemic acid
• Natural insecticide
• Grandisol
• Boll weevil sex attractant
• Menthol
• Peppermint oil
• Camphor
• Camphor Tree
• ?-Cadinene
• Juniper and ceder trees
• Taxol
• Pacific yew tree,
• Anti-tumor drug

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Steroids are tetracyclic natural products with
powerful physiological activities. Steroids
frequently function as hormones, or regulators of
biological activities. Synthetic steroids are
used in the treatment of cancer, arthritis,
allergies, and in birth control. Steroids consist
of 3 fused cyclohexane rings fused to a
cyclopentane ring. The ring junctions are usually
trans.
The rings are labeled A,B,C,D. Methyl groups at
C10 and C13 and oxygen at C3 and C17 are
common. Due to the trans ring fusion, an all
chair conformation is assumed with the ring
junction hydrogens and methyl groups in axial
positions.
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Groups attached above the plane of the steroid
ring structure are termed ? while those below are
termed ?. Axial methyl groups are referred to as
angular methyls because they sharply protrude
from the framework. Three common steroids are
Cholesterol is present in almost all human and
animal tissue. It can precipitate in the
arteries, causing arteriosclerosis and heart
disease. It is a precursor for bile acids and
steroid hormones. Cholic acid is a bile acid
involved in emulsification, digestion and
absorption of fats. Cortisone is involved in
regulating electrolyte and water balance in the
body, as well as carbohydrate and protein
metabolism.
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Sex hormones are divided into three types Male
sex hormones (androgens), female sex hormones
(estrogens), and pregnancy hormones
(progestins). Examples of each are

• Testosterone
• Produced by testes. Responsible for masculine
  characteristics.
• Estradiol
• Responsible for secondary female characteristics
  and participitates in regulation of menstrual
  cycle.
• Progesterone
• Responsible for preparing the uterus for the
  implantation of an egg.

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Important Concepts
4

• Cycloalkane Nomenclature Derived from that of
  the straight chain alkanes.
• Cycloalkanes exist as two isomers unless they are
  1,1-disubstituted. Cis both substituents on the
  same face of the molecule Trans substituents on
  opposite faces. These are examples of
  stereoisomers.
• Cycloalkanes may be strained.
• Bond angle strain Distortion about tetrahedral
  carbon.
• Torsional strain Inability to adopt staggered
  conformations.
• Transannular strain Steric repulsion between
  atoms across a ring.

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Important Concepts
4

• Bond angle strain in small molecules Formation
  of bent bonds.
• Strain in cycloalkanes other than cyclopropane
  Deviations from planarity.
• Ring Strain in Small Cycloalkanes Reactions
  result in ring opening.
• Deviations from Planarity Lead to
  conformationally mobile structures. For
  cyclohexane, chair, boat, and twist-boat
  conformations lead to an almost strain-free
  structure.
• Chair Cyclohexane Axial and equitorial hydrogens
  are rapidly interconverted at room temperature by
  chair-chair interconversion (activation energy
  10.8 kcal/mol)

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Important Concepts
4

• Monosubstituted Cyclohexanes Chair-chair
  interconversion ?Go is substituent dependent.
  Axial substituents exhibit 1,3-diaxial
  interactions.
• More Highly Substituted Cyclohexanes
  Substitutent effects are often additive.
  Bulkiest substituents most likely to be
  equitorial.\
• Completely Strain Free Cycloalkanes Adopt an
  all-anti conformation and lack transannular
  interactions.
• Bicyclic Ring Systems May be fused or bridged.
  Fusion may be cis or trans.
• Natural Products Classified by structure,
  physiological activity, taxonomy, and biochemical
  origin.

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Important Concepts
4

• Terpenes Made of of 5 carbon isoprene units.
• Steroids Three angularly fused cyclohexanes
  (A,B,C rings) attached to a cyclopentane D ring.
• Beta substituents above the molecular plane.
• Alpha substituents below the molecular plane.
• Sex Hormones Steroids controlling physiological
  functions, including fertility.