Pharmaceutical organic chemistry

1. PHYSICAL &
CHEMICAL
PROPERTIES

2. Physical Properties
1. The first two members cyclopropane and cyclobutane
are gases, the next three members are liquids and higher
members are solid.
2. These are nonpolar and hence are soluble in alcohol or
acetone but insoluble in water.
3. As we move down the series, both density and molecular
weight increase. Because density of cyclohexane is lower
than that of water, cyclohexane foats over it.
4. The boiling point is higher than their corresponding
alkenes and alkanes. The boiling points increase with
increase in molecular weight.

3. Chemical Properties
Cycloalkanes are very akin (same) to the alkanes in
relation to reactivity, excluding for the very small
ones—in particular cyclopropane. Cyclopropane is
very reactive than expected because of the ring
strain. In general, carbon compounds are
tetrahedral and the bond angles are of 109.5°. But in
case of cyclopropane, they are 60°. As the electron
pairs are very close, the repulsion between the
bonding pairs, which keep the carbon atoms
together, makes the bond easier to break.

4. Therefore because of the angle strain,cyclobutane
are comparatively less stable and more reactive
(following Baeyer’s strain theory). The cycloalkanes
then form cyclopentane and after that show notable
similarity with alkanes because of their stability.
Higher alkanes are less reactive due to less strain in
the ring and the bond angle is very close to 109.5°.
Hence higher cycloalkanes do not easily react with
acids, alkalies, etc.

5. 1. Free radical substitution:
Cycloalkanes are halogenated in presence of sunlight or UV light like alkane.

6. 2. Addition reactions:

7. a. Due to the strained ring, cyclopropane (bond angle 60°) is very
reactive and undergoes addition reactions like alkenes. b.
Cyclobutane (bond angle 90°) is relatively less reactive because of less
ring strain and therefore does not undergo addition reactions under
normal conditions.
3. Oxidation: Dicarboxylic acids are formed when
cycloalkanes are oxidized by alkaline potassium
permanganate.

8. Relative Stability of Cycloalkanes (Baeyer’s Strain
Theory)
In 1885, Adolf von Baeyer proposed a theory to enlighten the
relative stability of the cycloalkanes. The postulates of the
theory are as follows:
1. The carbon atoms constituting the ring lie in the same
plane and thusall the cycloalkanes are planar.
2. A strain in the ring is caused by the deviation of bond angle
angle from the normal tetrahedral angle (109°28′) and this is
called angle strain .
3. Greater the angle strain, greater is the instability of the
ring.

9. The angle strain in various cycloalkanes is calculated by
Baeyer. In cyclopropane, the three carbon atoms occupy the
corners of an equilateral triangle and hence C—C—C bond
angle is 60°. The normal tetrahedral angle is 109°28′.
During the formation of cyclopropane, the normal angle of
109°28′ has been reduced to 60°. Hence, the angle strain in
cyclopropane is calculated as ½ (l09°28′ – 60°) = 24°64′

11. Advantages of Baeyer’s Strain Theory
1. Lower cycloalkanes such as cyclopropane,
cyclobutane have higher angle strain and are
more reactive.
2. Cyclopentane is most stable because the angle
strain is minimum.
3. The relative stabilities of cycloalkanes up to
cyclopentane can be explained satisfactorily.

12. Limitations of Baeyer’s Strain Theory
1. The theory gives planar model of
cycloalkanes.
2. According to this theory, cyclohexane is less
stable than cyclopentane. However,
cyclohexane and other higher cycloalkanes
are found to be more stable than
cyclopentane.
3. Carbon–carbon double bond is easily
formed. But according to Baeyer’s strain

13. Heat of Combustion and Stability of Cycloalkanes
Every cycloalkane does not have a similar degree of stability. It is
determined based on their enthalpies of combustion values given in
Table 7.2 . Higher the enthalpy per CH 2 group, lower is its stability.

14. An additional sign, which explains the relative
stability, is the ease with which the cycloalkane ring
opens up. Lesser the stability of the ring, more easily it
opens up. The following are the conditions for
hydrogenation of cycloalkanes.

15. Sachse-Mohr Theory of Strainless Rings
Sachse and Mohr proposed a theory of stainless rings to give
give explanation for the stability of higher cycloalkanes. This
This theory says that the ring with six or more carbon atoms
atoms becomes free from stain as all the ring carbon atoms
are not forced into one plane. Hence the higher the
cycloalkanes, the carbon atoms occupy different planes so
that the normal tetahedral angle is retained. The rings
formed are called strainless rings.

16. For example, cyclohexane exists in two puckered
conformations. They are (1) chair form and (2) boat form .
Both these forms are without any angle strain. Hence, they
are strainless rings.
Chair form of cyclohexane is more stable than the boat
form due to the subsequent reasons.
1. In the chair conformation, the adjacent C—H bonds on
all the neighbouring carbon atoms are staggered. In the
boat form, the adjacent C—H bonds on C 2 —C 3 and C 5
— C 6 are eclipsed. Hence energy of boat form becomes
more than the chair form.

17. 2. Out of the twelve hydrogens, six of them point up or down
perpendicular to the plane of the molecule. These are called axial
hydrogens. The other six hydrogens are found either above or below the
plane of the molecule. They are equatorial hydrogens. In the boat form,
the two axial hydrogens on C 2 and C 4 are closer than in the chair
form. Hence the energy of boat form is more than the chair form.

18. Effects of Cyclohexane on Human Beings and
Environment
The effects of cyclohexane on human health and the
environment depend on the extent cyclohexane is present and
the length and frequency of exposure. Such effects also depend
on the health of a person or the condition of the environment
when exposure occurs.
Human health effects associated with breathing or taking in
smaller amounts of cyclohexane over long periods of time are
not known. But cyclohexane adversely affects the human
nervous system if a person breathes large amounts of it for
short periods of time. Its effects range from headaches to

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