The document discusses atropisomerism in biphenyl compounds, emphasizing that biphenyl's chirality arises from ortho-position substitutions that restrict rotation around the bond connecting the two phenyl rings. It outlines various conditions necessary for biphenyls to be chiral and resolvable, including the need for bulky ortho substituents that create steric hindrance. Additionally, it examines the effects of substituent arrangement and size on the stability of atropisomers and racemization rates.

1. Atropisomerism in Biphenyl compounds
Stereochemistry

2. Biphenyl compounds
 Biphenyl is an aromatic hydrocarbon with a molecular formula
(C6H5)2. The biphenyl molecule consists of two connected
phenyl rings.
 Biphenyl’s ortho positions are substituted with two different
bulky groups makes it chiral (and resolvable) due restricted
rotation through pivotal bond.
 Unsubstituted biphenyls are opically inactive due to the
presence of plane of symmetry.
 The ortho-substituted (diff subs:groups) derivatives are
sterically hindered and for this reason, some substituted
biphenyls show atropisomerism.

3. Atropisomerism
 Atropisomers can be defined as isomers that can be
isolated due to prevention or restriction of rotation
about a given single bond, usually between two planar
moieties.
Atropisomerism is also called axial chirality.

4. Case of unsubstituted biphenyl:-
 The equilibrium torsional/dihedral angle is 44.4°.
 Then torsional barriers are quite small,
 6.0 kJ/mol at 0°
 6.5 kJ/mol at 90°.
 On adding ortho substituents greatly increases the
barrier:
 In the case of the 2, 2'-dimethyl derivative, the barrier is 17.4
kcal/mol (72.8 kJ/mol).

5. Case of substituted biphenyl:-
 Biphenyls substituted on ortho- position (which contains a
chiral axis along the biphenyl linkage) the biphenyl rings
need to be perpendicular to each other in order to
minimize steric clashes between the four ortho-
substituents.
 It means that rotation about the biphenyl bond through pivotal
bond is restricted.
 The interconversion between the two isomers (θ=0-90°) is
restricted (slow) therefore two isomers are separate entities,
and can resolved to its separate enantiomers.

6. Conditions for biphenyls to be
enantiomeric/resolvable:
1. The planes of two aryl groups must be non-planar.
 This can be done by introducing bulky groups in the ortho-
positions so that the planar conformations are destabilized due
to steric repulsion.

7. Conditions for biphenyls to be
enantiomeric/resolvable:
2. Ortho substituent increases the restriction of rotation
through pivotal bond (atropisomerism) in non-bridged biaryl
compounds by their steric repulsion.
 If the Van der Walls radiuses of the substituents are more than
hydrogen atom, rotation through pivotal bond will be more
restricted and molecule will show the atropisomerism.
 The Van der Walls radius I > Br > Cl > NO2 > COOH > OMe > F >
H.

8. Conditions for biphenyls to be
enantiomeric/resolvable:
3. Mono ortho substituted biaryl compounds do not form
stable atropisomer at room temperature.
 This type of compound show atropisomerism only if both
substituents are bulky.

9. Conditions for biphenyls to be
enantiomeric/resolvable:
4. In addition to the bulkiness of the ortho- substituents, the
nature and position of other substituents in the ring play
some role in configuration stability of the atropisomers.
 The bulky groups adjacent to the ortho- substituents exert a
buttressing effect (It is a of restriction in rotation of a ring due to
presence of a meta-substituted ring in biphenyls).
 The buttressing effect of the some of the groups are in the following
order: NO2>Br>Cl>Me.

10. Conditions for biphenyls to be
enantiomeric/resolvable:
 The rate of racemization (conversion to other enantiomer through
rotation) is much lower in compound (I) than the compound (II).
 In compound (I) the bulkier group (NO2) is adjacent to methoxy but
in case of compound (II) the bulkier group is adjacent to hydrogen.
 Compound (I) is having more buttressing effect and racemization is
slow compared to the compound (II)

11. Conditions for biphenyls to be
enantiomeric/resolvable:
5. If two substituents on ortho position are similar but on meta
position substituents are different then these type of
molecules are chiral and are less common.
R = D, NH2, Br, I

12. Conditions for biphenyls to be
enantiomeric/resolvable:
6. In a biaryl compound, where four ortho substituents are
equal and if these are connected pairwise through two
bridges as a diether, it also show the axial chirality.

13. Conditions for biphenyls to be
enantiomeric:
7. Heteroaromatic system provides chirality even though their
ortho substituents are same.
 In this molecule, both phenyl rings A and B are perpendicular to each
other.

14. NEXT SESSION
 Stereospecific & Stereoselective reactions.