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MODULE

1. Atropisomerism in Biphenyl compounds Stereochemistry

2. Biphenyl compounds Biphenyl is an aromatic hydrocarbon with a molecular formula (C 6 H 5 ) 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. T he 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. C ase of un substituted biphenyl:- T he 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: I n the case of the 2, 2'-dimethyl derivative, the barrier is 17.4 kcal/ mol (72.8 kJ/ mol ).

5. C ase 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: 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 : 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 : 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 : 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 : 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, NH 2 , Br, I

12. Conditions for biphenyls to be enantiomeric /resolvable : 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 : 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 S ESSION Stereospecific & Stereoselective reactions.