4

Cycloalkanes
1. A Steroid is a type of organic compound that contains a characteristic arrangement of four
cycloalkane rings, three cyclohexane rings and one cyclopentane ring that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, the anti-inflammatory drug dexamethasone and Diosgenin which is obtained from root extract of Mexican yam and used as a starting material for synthesis of several commercial steroids.

Commonly, steroids have a methyl group at the carbons C-10 and C-13 and an alkyl side chain at carbon C-17. Further, they vary by three parameters 1. The configuration of the side chain 2. The number of additional methyl groups 3. The functional groups attached to the rings.

2. Cycloalkanes, Hydrocarbons containing single-bonded carbon atoms arranged in rings are

known as cyclic alkanes, carbocycles (in contrast to heterocycles), or cycloalkanes.

3. Construction of Cycloalkanes, removing a hydrogen atom from each terminal carbon of a

straight-chain alkane and allowing these carbons making the bond with each other.

4. The names of the cycloalkanes follow IUPAC rules

1. A substituted cyclic alkane requires numbering the individual ring carbons only if more than one substituent is attached to the ring. 2. For poly-substituted compounds, take care to provide the lowest possible numbering sequence.

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

3. When two such sequences are possible, the alphabetical order of the substituent names takes precedence. 4. The smaller unit is treated as a substituent to the larger one for example methylcyclopropane not cyclopropylmethane. 5. Prefix di in diethyl is not counted because it is merely multiplying the substituent whose name is ethyl. In contrast the di in dimethylcyclopropyl

5. Stereoisomers, compounds that have identical connectivity but differ in the arrangement of
their atoms in space. The two isomers (cis and trans) of disubstituted cycloalkane are stereoisomers. 1. cis, the two substituents are positioned on the same face, or same side, of the ring. 2. trans, the two substituents are positioned on the opposite face, or opposite side, of the ring.

6. cis and trans isomers can be interconverted only by breaking bonds, while conformers are
readily equilibrated by rotation about bonds.

7. Physical properties of Cycloalkanes:

1. Compared with the corresponding straight-chain alkanes, the cycloalkanes have higher boiling and melting points as well as higher densities because of increasing in London interaction (Cycloalkanes have more surface contact and symmetry so They have larger London interaction than acyclic alkanes) 2. In comparing the lower odd and even number of carbons cycloalkanes, we find a pronounced alternation in their melting points packing forces between the two series because of differences in crystal

8. Ring Strain, One notable feature of the first two members (Cyclopropane and Cyclobutane)
in the series of cycloalkanes is how difficult it is to close the ring but as the ring size increases, strain diminishes.

9. Heat Content, one measure of the stability of a molecule, which can be estimated for
alkanes by measuring of their heat of combustion.

10. How can we reach from comparing of heat content of alkanes with cycloalkanes to presence
of ring strain?

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

11. After averaging over a long number of alkane, for each additional
member of homologous series about 157.4 kcal/mol added to value of

in the successive ( ).

12. Cyclopropane,
1. All six methylene hydrogens are eclipsed. 2. Carbon skeleton in Cyclopropane is by necessity flat and quite rigid. 3. Cyclopropane has C C C bond angles of 60. 4. The discrepancy between the expected and observed values of heat of combustion is
27.6 kcal/mol. (9.2 kcal/mol for any of )

5. Reaction with hydrogen in the presence of a palladium catalyst opens the ring.

13. Cyclobutane,
1. It is not planar but puckered, with an approximate bending angle of 26. 2. It is not very rigid and can flips rapidly between its puckered conformations. 3. Non-Planarity relieves the strain introduced by the eight eclipsing hydrogens. 4. Bond-angle strain is considerably reduced relative to that in Cyclopropane. 5. Reaction with hydrogen in the presence of a palladium catalyst opens the ring.

14. Bond-angle strain, energy needed to distort the tetrahedral carbons enough to close the ring.

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

15. Eclipsing (torsional) strain, energy of the eclipsed form is higher than that of the more stable
staggered conformation.

16. Cyclobutane,
1. It might be expected to be planar because the angles in a regular pentagon are 108, close to tetrahedral. 2. It has ten H H eclipsing interactions. 3. Puckering (the envelope and the half chair conformations) relieves eclipsing. 4. Puckering also increases bond-angle strain. 5. Activation barriers for rapid inter-conversion are extremely low. 6. It has relatively little ring strain. 7. It dose not show the unusual reactivity of three or four-membered rings.

17. Cyclohexane, a hypothetical planar Cyclohexane would suffer from 12 H H eclipsing

interactions and six-fold bond-angle strain (regular bond angle in planar cyclohexane is 120). 1. Chair conformation, of cyclohexane, obtained by moving carbons 1 and 4 out of planarity in opposite directions. 2. Boat conformation, of cyclohexane, carbons 1 and 4 are out of the plane in the same direction. 3. Twist-boat (or Skew-boat) conformation, of cyclohexane, in boat conformation
one of the C C bonds is twisted relative to another.

Comparison of Conformations 1. Chair conformation, staggered arrangement of all substituent groups along the C C single bonds. 2. Chair conformation, nearly equal value of heat content of cyclohexane in both of experimentally and calculatedly procedures so is in fact strain free.

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

3. Chair conformation, because of its lack of strain, it is as inert as straight chain alkane 4. Boat conformation, eclipsing of eight hydrogen atoms at the base of the boat make it as an unstable but fairly flexible conformation.

18. Trans-Annular Strain, steric hindrance due to the close proximity of the two inside
hydrogens in boat conformation.

Twist-boat conformation, stabilized by partial removal of the transannular interaction relative

to the boat form. Two twist boat for are possible and interconvert rapidly

19. Axial and Equatorial methylcyclohexanes are not equivalent in energy. In the equatorial
conformer, the methyl group extends into space away from the remainder of the molecule. In contrast, in the axial conformer, the methyl substituent is close to the other two axial hydrogens (1, 3-diaxial interaction) on the same side of the molecule. 1. Axial positions, six carbon-hydrogen bonds are nearly parallel to the principle molecular axis. 2. Equatorial positions, six carbon-hydrogen bonds are nearly perpendicular to the axis and close to the equatorial plane.

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

20. Potential energy diagram for chair-chair inter-conversion of cyclohexane through the twistboat and boat form. 1. The boat cyclohexane is not a normally isolable species, the twist-boat form is present in very small amounts, and the chair form is the major conformer. 2. In a chair-chair inter-conversion (flipping) all axial hydrogens in one chair became equatorial in the other and vise versa. 3. Two chair forms inter-converted rapidly in room temperature (approx. 200,000 times per second) 4. The activation barrier separating the most stable chair form from the boat forms is 10.8 kcal/mol. 5. The activation barrier of methylcyclohexanes is similar to that in cyclohexane itself (about 11 kcal/mol)

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

21. The energy difference between the two forms increases with the size of the substituent, a
direct consequence of increasing unfavorable 1,3- diaxial interactions.

22. 1,1-dimethylcyclohexane, one methyl group is always equatorial and the other axial. The
two chair forms are identical and hence their energies are equal.

23.

-1,4-dimethylcyclohexane, both chairs have one axial and one equatorial substituent and are of equal energy.

24.

-1,4-dimethylcyclohexane, it can exist in two different chair conformations, one having two axial methyl groups and the other having two equatorial groups.

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th

25. In many substituted cyclohexane, we can apply additive behavior for calculation of free
energy of equilibriums, but sometimes the observed difference of free energy might be perturbed by additional 1,3-diaxial or 1,2-gauche interaction between substituents (just like as 1,4-dimethylcyclohexane or its isomer 1,3-dimethylcyclohexane) 1. -1,4-dimethylcyclohexane, the equatorial form is preferred over the diaxial form by 3.4 kcal/mol, exactly twice the free energy for mono substituted (axial) methylcyclohexane. 2. 3. -1-fluoro-4-methylcyclohexane, in one side of equilibrium both of the
substitutes are in axial positions so the corresponding free energy is -1.95 kcal/mol.

-1-fluoro-4-methylcyclohexane, two groups compete for equatorial positions

and the corresponding free energy is -1.45 kcal/mol

Chapter 4, Cycloalkanes | Vollhardt Organic Chemistry Structure Function 6th