Conformational isomers

B. Pharm. Stereichemistry presentation. for pharmacy students

1. CONFORMATIONAL
ISOMERS

a x IR. G
waa Eo
CHR I a 2
IS Ho “x = ad ÉS,

OCOCH;

Synclinal

Antiperiplanar Amit Chaudhari

2. CONFORMATION

CONFORMATIONAL ISOMERS

{19> Conformations are different spatial arrangements of a molecule
that are generated by rotation about single bonds.

[sun14, sum12, sum 10] [win14]
- Different conformations of the same molecule are sometimes called
conformers or rotamers or conformational isomers.

Newman projectians,
Hu

Ethane yr Hoy fs — Bo

Wedge-and-dash Sawhorse Newman
projection
jarmacestical Chemistry. Organic Chesräsiry—|_AZC_2016_Stesenchernisiry 2D 2

representations
of conformation

3. CONFORMATION

TORSION ANGLE OR DIHEDRALANGLE

- angle between the H-C-C plane and the C-C-H plane. The torsion
angle is easily seen in a Newman projection of ethane

0°

HH H H
>

Torsion angle = 0° Torsion angle = 60° Torsion angle = 180°
Eclipsed Gauche Anti

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4. CONFORMATIO

CONFORMATIONS OF ETHANE

-Ethane has two conformations called the staggered and eclipsed
conformations.

eclipsed conformers
HH HH HH HH
H H H H
E H H i H Hi H
A H
8
5
5 2.9 kcal/mol
3 or 12 kJ/mol
El |
2 H H H
H H H H H H
H H H H H H
H H H
staggered conformers
1 1 1 1 1 L 1
0° 60° 120° 180° 240° 300° 360°
Degrees of rotation 4

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5. CONFORMATION

CONFORMATIONS OF ETHANE

why is the eclipsed conformation higher in energy than the

staggered conformation?
[sun15] [wint3, win11]

- there is some steric repulsion between the hydrogen atoms in the
eclipsed conformation that is reduced in the staggered conformation.

- in eclipsed conformation the electron cloud of C-H bonds are most
nearer and thus their repulsion increases.

- These repulsive forces creates torsional strain in molecule
- the more strain, the more will be internal energy of conformer

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6. CONFORMATION

CONFORMATIONAL ANALYSIS OF n-BUTANE
[sum14, sum 10] [win14]

Bee E
| 1 |
aa a0 me
H HHH He |. H
u ee
n-Butane H
mi
Isobutane

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7. relative energy /kJ mol?

CONFORMATION

CONFORMATIONALANALY SIS OF n-BUTANE

- Various conformational isomers with their internal energy are shown

as bellow
symperiplanar

syn-periplanar
Me Me je
anticlinal anticlinal le Me
hi iH Me H

Me
“3 A A
45Keal\ smcinaor = HS A or
gauche gauche .

a antiperiplanar

10 —

5 —|

o —

0

60 120 180 240 300 0]
Pirrrnacestical Chesnisiry—Yl_Organic Chesnisiry—11_AZC_2016_Stereochesnistry 2D
Gihedral angle 4 in degrees

8. CONFORMATION

CONFORMATIONAL ANALYSIS OF n-BUTANE
Eclipsed conformation
- syn-periplanar conformer - dihedral angle is 0° and 360°
- max. energy
- Anticlinal conformer - dihedral angle is 120° and 240°
- energy is lower but not least

Staggered conformation
- synclinal (gauche) conformer - dihedral angle is 60° and 300°
- Energy is 0.9 Kcal
-anti- periplanar conformer - dihedral angle is 180°
- have least internal energy than others

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9. CONFORMATION

CONFORMATIONAL ANALYSIS OF n-BUTANE

Energy difference (stability and potential energy changes Jin
conformers is due to,

- Steric repulsion observed in diff. conformers

E.g.

- In syn-periplanar conformer on n-butane -- methyl groups are most
nearer to each other, cause steric repulsion and reach to most highest
energy state of 4.5 Kcal

- In anticlinal conformer — cause steric repulsion btwn methyl group
and H atom

- In anti- periplanar conformer all atoms are far apart especially
methyl groups, cause least steric repulsion and reach to most lowest
energy state i.c. most stable conformer of n-butane

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10. CONFORMATION

CONFORMATIONALANALY SIS OF n-BUTANE

GTU Q- What are the different possible conformations of 1,2-
dibromoethane? Which one is more stable? Why? [sum12]

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11. CONFORMATION

CONFORMATIONAL ANALYSIS OF n-BUTANE

GTU Q- What are the different possible conformations of 1,2-
dibromoethane? Which one is more stable? Why? [sum12]

"In n-butane conformers remove —CH3 and put -Br
"Forgot the exact value of energy

"The relative energy of conformers remains same

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12. CONFORMATION

CYCLOHEXANE

[sun!5, suni5, sun13]

- Draw a structure of cyclohexane .................

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13. CONFORMATION

CYCLOHEXANE

“planar”
bond

-All C are sp3 hybridized thus all bonds must creates 109° bond
angles.

-This leads 2 types of conformation in 3D — Boat shape and chair
shape

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14. CONFORMATION

CYCLOHEXANE

¢ Chair conformation

Axia]C—H bonds Equatorial C—H bonds Axial and equatorial
bonds together

Axial And Equatorial Bonds In Cyclohexane

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15. CONFORMATION

CONFORMATIONAL ANALYSIS OF CYCLOHEXANE

[sun!5, suni5, sun13]
- Relative stability of conformers is as shown in diagram
A

Half chair Half chair
ch) oes
E a
Pt
5
Twist boat Twist boat
O | AAA A AAA a onne
TEN ring inversion Ek
Chair A Chair

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16. CONFORMATION

CONFORMATION A TL AINA ILS RSIS €

Conformers and their internal energy

- Chair - nearly zero , most stable
- Boat - 25KJ/mol

- Half chair - 43 KJ/mol

- Twist boat - 21 KJ/nol

- Boat form can be obtained from chair conformer by bending the

bonds.

- During transformation two other forms arise i.e. half chair and twist

boat.

- Chair A to Chair B conversion is called as ring inversion or ring
ippin

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17. CONFORMATION

CONFORMATIONAIL AINAILY BIS OF EN

€

Chair form is most stable form
- Bc all bonds forms tetrahedron bond angle of 109°
- It adopts staggered arrangement

- All this makes chair conformation with least torsional strain than
other isomers

view along C-C

H H
H CH; H
IL Staggered arrangement of
CH; H

H bonds in chair conformer

H H

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18. CONFORMATION

CONFORMATIONAL ANALYSIS OF METHYL

CYCLOHEXANE
[Sum 11]

- Itis monosubstituted cyclohexane

- Cyclohexane has two equivalent chair conformers (Chair A and
Chair B)

- the two chair conformers of a monosubstituted cyclohexane such
as methylcyclohexane are not equivalent.

- The methyl substituent is in an equatorial position in one
conformer and in an axial position in the other.

the methyl group is in
an equatorial position

VA : 7 the methyl group is
ET ring flip era in an axial position

more stable | a CH,
chair conformer less stable

chair conformer
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19. CONFORMATIO

CONFORMATTIONAIL ANALES Our RADA A

The chair conformer with the methyl substituent in an equatorial
position is the more stable conformer

- because a substituent has more space (are less hindered) and,
therefore, fewer steric interactions when it is in an equatorial
position.

- In contrast, when the methyl group is in an axial position, there
are unfavorable steric interactions between the axial methyl group
and both the axial substituent on C-3 and the axial substituent on
C-5 (in this case, hydrogens).

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20. CONFORMATIO

mS Om MACRO SE NCA

E

1,3-diaxial interactions
- Because the interacting substituents are on 1,3-positions relative
to each other, these unfavorable steric interactions are called 1, 3-

diaxial interactions.

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21. Isomer
no
Constitutional Sterio
Tautomers a . a .
Conformatonal Configurational
f ]
Enantiomer Diasteriomer
Geometrical
Apimer

Anomer - o and f CH

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22. End of topic

Reterence:

Organic Ghemistry- Morrison & boyd
Organic Chemistry - PL Sony
Organic Chemistry - Bahl & Bahl
Urganic Chemistry - Clayden