Lecture 2: conformation of a drug molecule

Question 1

What are conformational isomers?

Answer 1

Isomers that have different spatial arrangements due to bond rotation

Question 2

What are the three ways to represent conformation of a molecule?

Answer 2

1. Wedge and dash
2. Sawhorse
3. Newman projection
4. Fischer projection

Question 3

What is dihedral angle?

Answer 3

The angle between 2 bonds which are not directly linked to each other

Question 4

Why is the eclipsed conformer less stable than the staggered conformation?

Answer 4

1. There is electron repulsion in the eclipsed conformation because the C-H bonds are in close proximity.
2. In the staggered conformation, there is an interaction between the filled C-H molecular orbital and the empty C-H antibonding orbital, which stabilises the structure.

Question 5

What is torsional strain?

Answer 5

The difference in energy between the staggered and eclipsed conformations

Question 6

What is the torsional strain for a pair of eclipsing H atoms?

Answer 6

4kJ/mol

Question 7

What is the torsional strain of a H eclipsing a CH3 group?

Answer 7

6kJ/mol

Question 8

What is an anti conformer?

Answer 8

The conformer with a dihedral angle of 180deg.

Question 9

Why are anti conformers the most stable?

Answer 9

Because the groups are farthest apart from each other, so they experience the least amount of steric strain

Question 10

What is gauche interaction?

Answer 10

When the groups are close to each other, their electron clouds repel each other as they try to occupy the same amount of space.

Question 11

What is the amount of increase in energy due to gauche interaction?

Answer 11

3.8kJ/mol

Question 12

What is the torsional strain for a pair of eclipsing CH3 groups?

Answer 12

11kJ/mol

Question 13

What is the difference between torsional and steric strain?

Answer 13

1. Torsional strain is the repulsion due to electrostatic forces between electrons in adjacent orbitals
2. Steric strain is the repulsion when 2 bulky groups get too close and there is no space

Question 14

Why isn’t there any steric strain between a pair of eclipsing H atoms and a H atom and a CH3 group?

Answer 14

Because the H atoms are very small

(hence there is only torsional strain)

Question 15

Fill in the blank:
When the energy barrier to rotation is above _______kJ/mol, the rotation will be very slow, to the point that is is not observed/.

Answer 15

100

Question 16

What is angle strain?

Answer 16

Increase in energy associated with a bond angle that has deviated from the ideal sp3 angle of 109.5

Question 17

How do you calculate angle strain?

Answer 17

angle strain = 109.5 - internal angle (by geometry)

Question 18

What is the most stable cycloalkane?

Answer 18

Cyclohexane

Question 19

What is the most stable conformation of cyclohexane?

Answer 19

Chair conformation

Question 20

Why isn’t there any angle strain or torsional strain present in the chair conformation of cyclohexane?

Answer 20

1. No angle strain because the angles are 109.5
2. No torsional strain because all the adjacent C-H bonds are staggered

Question 21

What is the type of strain present in the chair conformation of cyclohexane?

Answer 21

Gauche interaction (between the middle 2 C atoms)

Question 22

What is the type of strain present in the boat conformation of cyclohexane?

Answer 22

1. Torsional strain due to the 4 pairs of eclipsing H atoms
2. Steric strain due to flagpole interactions
3. Gauche interaction (between the middle 2 C atoms)

Question 23

What are flagpole interactions?

Answer 23

It’s a type of steric strain, produced when the 2 substituents take up axial positions in the boat conformation of cyclohexane

Question 24

1,3-diaxial interactions are equivalent to ______ interactions

Answer 24

gauche