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Stereo Isomerism in Biphenyl Compounds (Atropisomerism) and Conditions for Optical Activity

Atropisomerism is when isomers cannot be isolated under normal experimental conditions due to restricted rotation around a single bond.

Stereo Isomerism in Biphenyl Compounds

Atropisomerism

Atropisomerism is when isomers cannot be isolated under normal experimental conditions due to restricted rotation around a single bond.
Example -


Examples of atropisomerism without biphenyl system near sp2-sp2-sigma bonds include the following. The compounds are optically active and chiral. The restriction of rotation around C-C prevents them from quickly changing their conformations, resulting in two conformational isomers that can easily be separated from each other. That is, these compounds can be resolved.

The rotation about sp2-sp2 bonds is restricted in the following styrenes. Planar conformation results in distorted molecules due to the crowding of the groups.

Stereoisomers resulting from a rotational restriction around a single bond are called astropisomerisms.

Stereoisomers resulting from hindered rotation about single bonds are called tropoisomers (from Greek, a is not and tropos is turn). They exist when steric strain barriers to rotation are high enough to prevent conformational drift.

When bulky groups are arranged on ortho positions of biphenyls, or strained rings. Observing atropisomers is possible through the use of bulgy substituents or strained rings which enhance rotational barriers between different conformations.

Alternatively, tropisomerism is also known as axial chirality, and the chirality does not simply relate to a center or a plane, but rather to an axis.

It contains a chiral axis along the biphenyl linkage and is substituted in ortho position. The biphenyl rings are parallel to one another in order to avoid steric clashes between the three ortho substituents. This means rotation through pivotal bond is restricted around the biphenyl bond.


Conditions of Atropisomerism

Axial chirality is conditioned by two factors:
  • On both sides of the axis, there is a different substituent
  • A rotationally stable axis
Atropisomers can be distinguished physically as separate species when they have half-lives greater than 1000 seconds (16.7 minutes) [≥ 1000 seconds].

Here are the minimum free energy barriers that must be achieved at different temperatures. The ΔG200K value equals 61.6 kJmol-1 the ΔG300K value equals 93.5 kJmol-1 and ΔG350K value equals 109 kJmol-1.

Biaryl compounds with a chirality axis are known to have configurational stability mainly due to three factors:
  • A combination of steric demands of the substitutes on the axes in the vicinity.
  • Bridges exist, are long, and are rigid.
  • The mechanism of astropisomerisation is different from a purely physical rotation about an axis, such as a photochemical or chemical process.

Conditions for Optical Activity

Optic activity requires the following conditions:
  • Carbon atoms should be asymmetric in a compound
  • There should not be any symmetry in the molecules
  • Chiral axis should be present in the molecule.
  • A chiral plane should be present in the molecule.
Glyceraldehyde is an example of a material that is optically active.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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