Understanding Conditions for optical activity in biphenyl compounds MCQs With Answer is essential for B. Pharm students studying stereochemistry and chiral drug design. This concise, keyword-rich introduction covers how axial chirality arises in biphenyls: restricted rotation about the central C–C bond, significant ortho-substitution, steric and electronic effects, and configurational stability (atropisomerism). It connects theory to pharmaceutical relevance—chiral purity, enantiomerization barriers, measurement of optical rotation and CD, and factors affecting racemization. Clear, exam-focused explanations help you apply concepts to real biphenyl scaffolds and analytical challenges. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which primary structural condition leads to optical activity in substituted biphenyl compounds?
- Presence of a stereogenic carbon atom
- Restricted rotation about the central C–C bond due to ortho-substitution
- Conjugation with a carbonyl group
- Planar symmetry of the biphenyl system
Correct Answer: Restricted rotation about the central C–C bond due to ortho-substitution
Q2. What term describes the stable chiral conformers of hindered biphenyls?
- Stereocenters
- Atropisomers
- Meso forms
- Enols
Correct Answer: Atropisomers
Q3. Which substitution pattern on biphenyl most effectively produces axial chirality?
- Para-substitution on both rings
- Meta-substitution on one ring and para on the other
- Sterically bulky ortho-substituents on one or both rings
- No substitution (unsubstituted biphenyl)
Correct Answer: Sterically bulky ortho-substituents on one or both rings
Q4. Why does ortho-substitution restrict rotation in biphenyls?
- It increases conjugation across the bond
- It creates steric hindrance between ortho-groups that raises the rotational energy barrier
- It adds hydrogen-bonding that locks the molecule
- It introduces ionic interactions between rings
Correct Answer: It creates steric hindrance between ortho-groups that raises the rotational energy barrier
Q5. Which symmetry element absence is required for a molecule to be optically active?
- Absence of a center of inversion and mirror plane
- Absence of any rotational axis
- Presence of a horizontal mirror plane
- Presence of a center of inversion only
Correct Answer: Absence of a center of inversion and mirror plane
Q6. What experimental method is commonly used to detect optical activity in biphenyl atropisomers?
- NMR spectroscopy only
- Polarimetry to measure optical rotation
- Infrared spectroscopy only
- Mass spectrometry to measure mass differences
Correct Answer: Polarimetry to measure optical rotation
Q7. Which factor increases the configurational stability of a chiral biphenyl?
- Smaller ortho-substituents
- Higher temperature
- Stronger steric bulk at ortho positions
- Increased solvent polarity only
Correct Answer: Stronger steric bulk at ortho positions
Q8. Which of the following substituents is most likely to induce atropisomerism in biphenyl?
- Hydrogen
- Methyl
- Tert-butyl
- Fluorine
Correct Answer: Tert-butyl
Q9. How does temperature generally affect the observed optical activity of a biphenyl atropisomer?
- Increasing temperature always increases optical rotation magnitude
- Increasing temperature can lead to faster racemization and loss of optical activity
- Temperature has no effect on optical activity
- Lower temperatures promote racemization
Correct Answer: Increasing temperature can lead to faster racemization and loss of optical activity
Q10. What is enantiomerization in the context of biphenyl atropisomers?
- Formation of new covalent bonds between rings
- Interconversion between enantiomeric atropisomers by rotation about the central bond
- Conversion of an enantiomer to a diastereomer through substitution
- Polymerization of biphenyl units
Correct Answer: Interconversion between enantiomeric atropisomers by rotation about the central bond
Q11. Which measurement gives information about the energy barrier to racemization of a biphenyl?
- Optical rotation at a single temperature
- Kinetic studies of racemization rate as a function of temperature
- Melting point determination
- Thin-layer chromatography retention factor
Correct Answer: Kinetic studies of racemization rate as a function of temperature
Q12. In biphenyls, what is the role of electron-withdrawing or electron-donating ortho-substituents on optical activity?
- They have no effect on rotational barrier
- They only affect color, not chirality
- They can influence dihedral angle and conjugation, altering stability of chiral conformers
- They always decrease steric hindrance
Correct Answer: They can influence dihedral angle and conjugation, altering stability of chiral conformers
Q13. Which dihedral angle between the two aryl rings typically favors isolable atropisomers?
- Exactly 0° (fully coplanar)
- Very small angle (<5°)
- A significant twist that prevents coplanarity, often >45° depending on substituents
- Exactly 180° only
Correct Answer: A significant twist that prevents coplanarity, often >45° depending on substituents
Q14. Which statement about meso forms in substituted biphenyl systems is correct?
- Meso forms are always optically active
- Meso forms are achiral despite having stereogenic elements due to an internal mirror plane
- Meso forms only occur in alkaloids
- Meso forms are racemic mixtures of enantiomers
Correct Answer: Meso forms are achiral despite having stereogenic elements due to an internal mirror plane
Q15. What analytical technique provides chiroptical information beyond simple optical rotation in biphenyls?
- Infrared spectroscopy (IR)
- Circular dichroism (CD) spectroscopy
- Mass spectrometry (MS)
- X-ray fluorescence
Correct Answer: Circular dichroism (CD) spectroscopy
Q16. Which stereochemical descriptor is used for axial chirality in biphenyls when conventional R/S is not applicable?
- cis/trans
- Meso/Enantiomer
- Ra and Sa (or (R)a and (S)a) for axial chirality
- ortho/meta
Correct Answer: Ra and Sa (or (R)a and (S)a) for axial chirality
Q17. Which factor can lower the rotational energy barrier and accelerate racemization?
- Larger ortho-substituents
- Solvent that stabilizes the transition state and high temperature
- Formation of hydrogen bonds that lock conformation
- Introduction of rigid bridging between rings
Correct Answer: Solvent that stabilizes the transition state and high temperature
Q18. How can chemists achieve enantiomeric separation of biphenyl atropisomers?
- By simple distillation
- By chiral chromatography or diastereomeric salt formation
- By heating to racemize
- By adding strong acids to break the rings
Correct Answer: By chiral chromatography or diastereomeric salt formation
Q19. Which of the following increases the likelihood of observing optical activity in a biphenyl?
- Symmetric substitution that creates an internal mirror plane
- Unsymmetrical bulky ortho-substituents that remove symmetry
- Planarization by strong conjugation
- Identical para substituents on both rings
Correct Answer: Unsymmetrical bulky ortho-substituents that remove symmetry
Q20. What is a common synthetic approach to prepare chiral biphenyls with restricted rotation?
- Direct hydrogenation of biphenyl
- Introduction of bulky ortho-substituents via Friedel–Crafts or cross-coupling followed by selective functionalization
- Reduction to form single-ring compounds
- Ozonolysis of biphenyl rings
Correct Answer: Introduction of bulky ortho-substituents via Friedel–Crafts or cross-coupling followed by selective functionalization
Q21. In a substituted biphenyl, what does a high optical rotation value indicate?
- High molecular weight only
- Significant enantiomeric excess and intrinsic chiroptical response
- Presence of only achiral impurities
- Complete racemization
Correct Answer: Significant enantiomeric excess and intrinsic chiroptical response
Q22. Which substituent arrangement can result in a racemic mixture even with bulky ortho groups?
- Unsymmetrical ortho-substitution removing all symmetry
- Symmetrical substitution leading to an internal mirror plane
- Different substituents at para positions only
- Bridged biphenyl locking chirality
Correct Answer: Symmetrical substitution leading to an internal mirror plane
Q23. Which kinetic parameter is used to quantify the racemization rate of atropisomers?
- Optical rotation at equilibrium only
- Rate constant (k) for enantiomerization
- Melting point depression
- Retention time in TLC
Correct Answer: Rate constant (k) for enantiomerization
Q24. What is the effect of intramolecular hydrogen bonding in ortho-substituted biphenyls on axial chirality?
- Always destroys chirality
- Can stabilize a specific twisted conformation and increase configurational stability
- Has no stereochemical consequence
- Converts axial chirality into central chirality
Correct Answer: Can stabilize a specific twisted conformation and increase configurational stability
Q25. For drug molecules containing biphenyl axial chirality, why is configurational stability important?
- Because chirality has no impact on pharmacology
- Because interconversion can change pharmacological profile and safety by producing different enantiomers
- Only to affect physical color of the drug
- Because it increases solubility only
Correct Answer: Because interconversion can change pharmacological profile and safety by producing different enantiomers
Q26. Which computational descriptor helps predict axial chirality in biphenyls?
- Calculated dihedral angle and rotational energy barrier from DFT
- Boiling point estimation only
- Simple molecular weight calculation
- UV absorption maximum only
Correct Answer: Calculated dihedral angle and rotational energy barrier from DFT
Q27. What is the likely product when a biphenyl with small ortho substituents is cooled to low temperature?
- Permanent stable atropisomers due to freezing out of rotation
- Immediate formation of covalent bridge between rings
- No change; rotamers interconvert rapidly at all temperatures
- Lower temperature can slow rotation but may not give isolable atropisomers if barrier is low
Correct Answer: Lower temperature can slow rotation but may not give isolable atropisomers if barrier is low
Q28. Which condition alone is NOT sufficient to guarantee optical activity in biphenyls?
- Presence of bulky ortho groups
- Absence of symmetry elements (mirror plane, inversion center)
- Planar conformation with C2v symmetry
- Significant rotational barrier preventing interconversion
Correct Answer: Planar conformation with C2v symmetry
Q29. How does substitution at both ortho positions of one ring versus both rings affect chirality?
- Substitution on only one ring never leads to chirality
- Substitution on both rings is more likely to increase barrier and produce stable atropisomers
- Substitution pattern does not matter
- Substitution at para positions produces higher barriers than ortho
Correct Answer: Substitution on both rings is more likely to increase barrier and produce stable atropisomers
Q30. Which statement best describes atropisomerism in biphenyls?
- It is a type of conformational isomerism with rapidly interconverting rotamers
- It is dynamic stereochemistry where rotation is slow enough to isolate enantiomers
- It requires a chiral carbon center
- It is only observed in saturated hydrocarbons
Correct Answer: It is dynamic stereochemistry where rotation is slow enough to isolate enantiomers
Q31. Which experimental change would you use to determine activation energy for racemization?
- Measure optical rotation at one temperature
- Measure rate constants at several temperatures and apply the Arrhenius equation
- Measure color change over time
- Record IR spectra before and after racemization
Correct Answer: Measure rate constants at several temperatures and apply the Arrhenius equation
Q32. In biphenyls, what role can bulky ortho substituents with heteroatoms play besides steric hindrance?
- They can form intramolecular interactions (H-bonds, coordination) that further stabilize a conformation
- They always decrease rotational barriers
- They eliminate any conjugation effects
- They make the molecule achiral
Correct Answer: They can form intramolecular interactions (H-bonds, coordination) that further stabilize a conformation
Q33. Which biphenyl is most likely to be optically inactive?
- Unsubstituted biphenyl at room temperature (rapid rotation)
- 2,2′-di-tert-butylbiphenyl with high barrier
- Unsymmetrical 2,2′,6,6′-tetra-substituted biphenyl with no mirror plane
- 1,1′-binaphthyl with rigid axial chirality
Correct Answer: Unsubstituted biphenyl at room temperature (rapid rotation)
Q34. Which of the following observations indicates a racemization process is occurring in solution?
- Optical rotation gradually decreases to zero over time
- UV absorption wavelength shifts slightly
- Mass spectrum shows fragmentation
- Melting point increases
Correct Answer: Optical rotation gradually decreases to zero over time
Q35. Why might a biphenyl display temperature-dependent optical rotation sign or magnitude?
- Because of solvent evaporation only
- Because different conformers with different chiroptical properties populate at different temperatures
- Because the instrument is unstable
- Because biphenyl decomposes at all temperatures
Correct Answer: Because different conformers with different chiroptical properties populate at different temperatures
Q36. Which of the following is a structural strategy to lock in axial chirality permanently?
- Remove all ortho substituents
- Introduce a covalent bridge between the two rings to prevent rotation
- Use small substituents at para positions
- Increase solvent polarity
Correct Answer: Introduce a covalent bridge between the two rings to prevent rotation
Q37. In the CIP (Cahn–Ingold–Prelog) approach to assign axial chirality, what is compared?
- Relative priorities of substituents on the two proximate atoms across the axis
- Boiling points of the substituents
- UV absorbance intensities
- Number of hydrogen atoms only
Correct Answer: Relative priorities of substituents on the two proximate atoms across the axis
Q38. How can circular dichroism (CD) complement polarimetry for biphenyl chirality studies?
- CD provides no additional information compared to polarimetry
- CD gives wavelength-dependent chiroptical signatures, aiding absolute configuration assignment
- CD measures molecular weight directly
- CD only detects achiral impurities
Correct Answer: CD gives wavelength-dependent chiroptical signatures, aiding absolute configuration assignment
Q39. For a biphenyl drug candidate, why is it critical to report enantiomeric purity and racemization stability?
- Because regulatory agencies require chiral characterization for safety and efficacy
- It is unnecessary for small molecules
- Only melting point matters for regulatory submission
- Because racemization always improves potency
Correct Answer: Because regulatory agencies require chiral characterization for safety and efficacy
Q40. Which observation would indicate that a biphenyl atropisomer has a very high racemization barrier?
- It racemizes within seconds at room temperature
- It remains optically pure after prolonged heating at elevated temperature
- Optical rotation fluctuates randomly
- It forms a meso compound immediately
Correct Answer: It remains optically pure after prolonged heating at elevated temperature
Q41. Which synthetic modification can lower the enantiomerization barrier intentionally?
- Replacing bulky ortho groups with hydrogens
- Adding larger tert-butyl groups
- Introducing covalent bridges
- Forming an intramolecular hydrogen bond that locks conformation
Correct Answer: Replacing bulky ortho groups with hydrogens
Q42. When designing biphenyl-based chiral ligands, why is axial chirality advantageous?
- It provides a rigid, well-defined chiral environment for asymmetric catalysis
- It always makes ligands water-soluble
- It eliminates the need for metal coordination
- It reduces melting point drastically
Correct Answer: It provides a rigid, well-defined chiral environment for asymmetric catalysis
Q43. Which of the following biphenyl derivatives is most likely to show atropisomerism at room temperature?
- 2,2′-dimethylbiphenyl
- 2,2′,6,6′-tetra-tert-butylbiphenyl
- Unsubstituted biphenyl
- 4,4′-dimethoxybiphenyl
Correct Answer: 2,2′,6,6′-tetra-tert-butylbiphenyl
Q44. How does conjugation between rings influence axial chirality in biphenyls?
- Increased conjugation always removes chirality by planarization
- Conjugation can favor coplanarity, reducing chirality unless steric factors force twist
- Conjugation has no effect on dihedral angle
- Conjugation makes racemization impossible
Correct Answer: Conjugation can favor coplanarity, reducing chirality unless steric factors force twist
Q45. Which property of atropisomeric biphenyls can be important for binding specificity in biological targets?
- Their color only
- Three-dimensional chiral shape and stereochemical orientation of substituents
- Only molecular weight matters for binding
- Ability to rapidly racemize in vivo
Correct Answer: Three-dimensional chiral shape and stereochemical orientation of substituents
Q46. What is a common sign that two enantiomers of a biphenyl are separable by chromatography?
- They have identical interactions with a chiral stationary phase
- They exhibit different retention times on a chiral column
- They are indistinguishable by any chromatographic method
- They co-elute with solvent front
Correct Answer: They exhibit different retention times on a chiral column
Q47. Which molecular design approach helps maintain axial chirality in a metabolically active environment?
- Using small flexible substituents prone to enzymatic cleavage
- Incorporating sterically hindered ortho groups resistant to metabolic transformation
- Making the molecule highly water-soluble to increase clearance
- Designing for rapid racemization to reduce activity
Correct Answer: Incorporating sterically hindered ortho groups resistant to metabolic transformation
Q48. Which descriptor best predicts whether a biphenyl will be configurationally stable at room temperature?
- Calculated rotational energy barrier relative to kT at 298 K
- Molecular weight alone
- Number of hydrogen atoms
- Presence of any substituent regardless of size
Correct Answer: Calculated rotational energy barrier relative to kT at 298 K
Q49. How can solvent choice influence the optical activity of biphenyl atropisomers during measurement?
- Solvent has no influence on optical activity
- Solvent can stabilize different conformers or transition states, altering observed rotation and racemization rate
- Only nonpolar solvents show optical activity
- Solvent only affects mass spectrometric signals
Correct Answer: Solvent can stabilize different conformers or transition states, altering observed rotation and racemization rate
Q50. Which experimental strategy helps determine absolute configuration of a chiral biphenyl?
- Compare melting point with literature values only
- Combine X-ray crystallography with anomalous dispersion or CD spectroscopy and computational correlation
- Mass spectrometry of the racemate only
- Measure pH of the solution
Correct Answer: Combine X-ray crystallography with anomalous dispersion or CD spectroscopy and computational correlation
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