CHAPTER 4

Cyclic Alkanes

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.

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)

Disubstituted cycloalkanes possess stereoisomers. Disubstituted cycloalkanes having substituents on different carbons possess cis (same side) / trans (opposite side) isomers.

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.

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.

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 (>12)

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:

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.

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.

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.

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.

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.

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

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.

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 conformer may be more stable than the other, affecting both stereochemistry and reactivity.

Substituted Cyclohexanes 4-4

Axial and equatorial methylcyclohexanes are not equivalent in energy.

In methylcyclohexane, the conformer 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.

Newman projections more clearly show the unfavorable 1,3- diaxial interactions:

Energy differences for other monosubstituted cyclohexanes:

Substituents compete for equatorial positions. Consider the following disubstituted cycloalkanes:

Equal energies Equal energies

Diequatorial more stable Large group equitorial more stable.

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.

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.

Strain energy of 14 kcal mol-1.

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-diethylcyclohexane.

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.

A second example of ring fusion, norborane, can be compared to the compound, cis-1,3-dimethylcyclopentane:

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.

Bicyclic ring systems can be either cis- or trans-fused:

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

61 kcal mol-1

166 kcal mol-1

Unknown

129 kcal mol-1

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.

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).

Examples of terpenes include:

•  Chrysanthemic acid

Natural insecticide

•  Grandisol

Boll weevil sex attractant

•  Menthol

Peppermint oil

•  Camphor

Camphor Tree

•  β-Cadinene

Juniper and ceder trees

•  Taxol

Pacific yew tree,

Anti-tumor drug

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.

Groups attached above the plane of the steroid ring structure are termed β while those below are termed α.

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.

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 participates in regulation of menstrual cycle.

• Progesterone:

Responsible for preparing the uterus for the implantation of an egg.

Important Concepts 4

1.  Cycloalkane Nomenclature: Derived from that of the straight chain alkanes.

2.  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.

3.  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.

Important Concepts 4

4.  Bond angle strain in small molecules: Formation of bent bonds.

5.  Strain in cycloalkanes other than cyclopropane: Deviations from planarity.

6.  Ring Strain in Small Cycloalkanes: Reactions result in ring opening.

7.  Deviations from Planarity: Lead to conformationally mobile structures. For cyclohexane, chair, boat, and twist-boat conformations lead to an almost strain-free structure.

8.  Chair Cyclohexane: Axial and equatorial hydrogens are rapidly interconverted at room temperature by chair-chair interconversion (activation energy: 10.8 kcal/mol)

Important Concepts 4

9.  Monosubstituted Cyclohexanes: Chair-chair interconversion ΔGo is substituent dependent. Axial substituents exhibit 1,3-diaxial interactions.

10. More Highly Substituted Cyclohexanes: Substitutent effects are often additive. Bulkiest substituents most likely to be equatorial.\

11.  Completely Strain Free Cycloalkanes: Adopt an all-anti conformation and lack transannular interactions.

12. Bicyclic Ring Systems: May be fused or bridged. Fusion may be cis or trans.

13. Natural Products: Classified by structure, physiological activity, taxonomy, and biochemical origin.

Important Concepts 4

14.  Terpenes: Made of of 5 carbon isoprene units. 15. 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.

16. Sex Hormones: Steroids controlling physiological functions, including fertility.