Stereochemistry & Asymmetric Synthesis: CIP rules, resolution methods MCQs With Answer

Stereochemistry & Asymmetric Synthesis: CIP rules, resolution methods MCQs With Answer

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Stereochemistry & Asymmetric Synthesis: CIP rules, resolution methods MCQs With Answer

This quiz set is tailored for M.Pharm students preparing for MPC 202T Advanced Organic Chemistry II. It focuses on the Cahn-Ingold-Prelog (CIP) sequence rules for assigning stereochemical descriptors (R/S, E/Z, etc.), subtleties like pseudoasymmetric centers, handling isotopes and multiple bonds, and practical resolution strategies used in asymmetric synthesis and chiral separations. Expect questions that probe mechanistic reasoning, priority-determination in complex substrates, and comparisons of classical and modern resolution techniques (diastereomeric salt formation, enzymatic and kinetic resolutions, chiral chromatography). Each MCQ includes concise explanations through precise options and a correct answer to reinforce deeper conceptual understanding for application in pharmaceutical contexts.

Q1. In the CIP priority sequence, which factor is the first to be considered when two substituents are different?

  • The number of atoms in each substituent chain
  • The atomic numbers of the atoms directly attached to the stereocenter
  • The mass numbers of isotopes present
  • The total number of π-bonds in the substituents

Correct Answer: The atomic numbers of the atoms directly attached to the stereocenter

Q2. According to CIP rules, how is a double bond treated when comparing priorities?

  • As if the double-bonded atoms are connected to a single phantom atom of highest atomic number
  • As if each multiple bond is replaced by the atom duplicated or triplicated so each bond contributes a phantom atom
  • Double bonds are ignored in priority and only single-bonded atoms are counted
  • Count the number of π-electrons and use that number to rank priorities

Correct Answer: As if each multiple bond is replaced by the atom duplicated or triplicated so each bond contributes a phantom atom

Q3. When resolving a tie after comparing the first atoms attached to a stereocenter, CIP instructs you to:

  • Compare the atomic masses of the substituents as a whole
  • Compare the next set of atoms outward atom-by-atom until a point of difference is found
  • Prefer substituents containing the greater number of hydrogen atoms
  • Assign the higher priority to the substituent with more bonds

Correct Answer: Compare the next set of atoms outward atom-by-atom until a point of difference is found

Q4. How are isotopes handled under CIP priority rules?

  • All isotopes are considered identical and given equal priority
  • The isotope with the greater atomic mass (mass number) has higher priority
  • Priority is given by natural abundance of the isotope
  • Priority is assigned by considering the isotope as if it were replaced by hydrogen

Correct Answer: The isotope with the greater atomic mass (mass number) has higher priority

Q5. For a stereocenter bearing a lone pair (e.g., on nitrogen in an ammonium center), how are lone pairs treated in CIP ranking when required?

  • Lone pairs are always ignored in CIP comparisons
  • Lone pairs are treated as phantom atoms of atomic number zero and lowest priority
  • Lone pairs are treated as if they were atoms of atomic number 1
  • Lone pairs are replaced by ghost atoms corresponding to the central atom to reflect bonding

Correct Answer: Lone pairs are treated as phantom atoms of atomic number zero and lowest priority

Q6. Which statement correctly describes a pseudoasymmetric center?

  • A stereocenter where interchange of two identical substituents gives enantiomers
  • A stereocenter bearing four different substituents that are all stereochemically inert
  • A stereocenter at which the two substituents that differ are enantiomeric, so the center is labeled with lowercase r or s
  • A chiral center that produces a racemic mixture upon replacement of one substituent

Correct Answer: A stereocenter at which the two substituents that differ are enantiomeric, so the center is labeled with lowercase r or s

Q7. When assigning R/S configuration, if the lowest priority group is pointing toward the viewer (front), which procedure gives the correct designation?

  • Assign configuration directly from observed order of 1→2→3
  • Invert the configuration obtained from the 1→2→3 order because the lowest priority is in front
  • Ignore the lowest priority group and assign using remaining three groups only
  • Reverse the numbering of substituents to compensate and then assign

Correct Answer: Invert the configuration obtained from the 1→2→3 order because the lowest priority is in front

Q8. Which of the following best describes meso compounds?

  • Compounds that have no stereocenters but are optically active
  • Achiral compounds with stereocenters due to an internal plane of symmetry leading to optical inactivity
  • Compounds that are mixtures of enantiomers in equal amounts
  • Compounds where one stereocenter is R and the other is also R resulting in racemic behavior

Correct Answer: Achiral compounds with stereocenters due to an internal plane of symmetry leading to optical inactivity

Q9. What is the correct CIP-based approach to assign E/Z to an alkene?

  • Compare the atomic numbers of atoms directly bonded to each double-bond carbon; higher priorities on same side = Z
  • Assign E if the substituents of greater mass are on opposite sides regardless of atomic number
  • Use only configuration (R/S) of substituents to determine E/Z
  • E is always favored for trans-alkenes and Z for cis without priority rules

Correct Answer: Compare the atomic numbers of atoms directly bonded to each double-bond carbon; higher priorities on same side = Z

Q10. A racemic mixture has an enantiomeric excess (ee) of 0%. Which statement is true regarding its optical rotation and composition?

  • It shows no net optical rotation and contains equal amounts of both enantiomers
  • It shows maximum optical rotation but still contains equal enantiomers
  • It contains only one enantiomer but has no optical rotation due to impurity
  • It may have optical rotation depending on solvent despite equal enantiomeric composition

Correct Answer: It shows no net optical rotation and contains equal amounts of both enantiomers

Q11. In classical resolution by diastereomeric salt formation, what property enables separation of enantiomers?

  • The enantiomers form salts with identical solubility and cannot be separated
  • Diastereomeric salts have different physical properties (e.g., solubility, melting points) allowing separation
  • Enantiomers react to form identical diastereomeric salts which are separated by chiral chromatography only
  • Only one enantiomer forms a salt while the other remains free and can be decanted

Correct Answer: Diastereomeric salts have different physical properties (e.g., solubility, melting points) allowing separation

Q12. Which method describes kinetic resolution?

  • Separating enantiomers by forming diastereomeric salts with a chiral reagent
  • Using a chiral catalyst or enzyme that reacts faster with one enantiomer than the other, leading to selective conversion
  • Resolving a racemate by repeated recrystallization until one enantiomer crystallizes selectively
  • Converting both enantiomers into identical achiral products to remove chirality

Correct Answer: Using a chiral catalyst or enzyme that reacts faster with one enantiomer than the other, leading to selective conversion

Q13. Dynamic kinetic resolution (DKR) differs from simple kinetic resolution by:

  • Using only stoichiometric chiral resolving agents and no catalysts
  • Simultaneously racemizing the slower-reacting enantiomer so it can be converted and theoretical yield of one enantiomer exceeds 50%
  • Separating enantiomers physically without chemical transformation
  • Applying high-pressure chromatography to force resolution

Correct Answer: Simultaneously racemizing the slower-reacting enantiomer so it can be converted and theoretical yield of one enantiomer exceeds 50%

Q14. Which resolution technique is most suitable for large-scale industrial production of an enantiomerically enriched drug when a stable diastereomeric salt can be formed?

  • Chiral HPLC for preparative multigram production
  • Classical resolution by formation and recrystallization of diastereomeric salts
  • Small-scale enzymatic resolution only
  • Direct separation by achiral distillation

Correct Answer: Classical resolution by formation and recrystallization of diastereomeric salts

Q15. Which of the following best characterizes a successful asymmetric synthesis?

  • Formation of both enantiomers in equal amounts
  • Formation of predominantly one enantiomer with high enantiomeric excess (ee) using chiral reagents, catalysts, or auxiliaries
  • Only racemic products that are later separated physically
  • Generating achiral products from chiral starting materials

Correct Answer: Formation of predominantly one enantiomer with high enantiomeric excess (ee) using chiral reagents, catalysts, or auxiliaries

Q16. How is enantiomeric excess (ee) defined mathematically?

  • (% major enantiomer – % minor enantiomer) / 100
  • (% major enantiomer – % minor enantiomer)
  • (% major enantiomer + % minor enantiomer) / 2
  • % major enantiomer only

Correct Answer: (% major enantiomer – % minor enantiomer)

Q17. Which statement about chiral chromatography (e.g., chiral HPLC) is correct?

  • It converts racemates into diastereomers prior to separation
  • It separates enantiomers directly based on differential interactions with a chiral stationary phase
  • It relies exclusively on mass differences between enantiomers
  • It only works for gaseous compounds

Correct Answer: It separates enantiomers directly based on differential interactions with a chiral stationary phase

Q18. In an SN2 reaction at a stereocenter, what stereochemical outcome is typically observed?

  • Retention of configuration at the stereocenter
  • Inversion of configuration (Walden inversion)
  • Formation of a racemic mixture due to planar intermediate
  • No change because SN2 cannot occur at stereocenters

Correct Answer: Inversion of configuration (Walden inversion)

Q19. When assigning priorities for an allene (cumulene) with two different substituents on each terminal carbon, the substituents are ranked by:

  • Comparing the two substituents on one end only and ignoring the other end
  • Applying CIP rules considering the sequence outward from each terminal carbon and treating orthogonal planes accordingly
  • Assigning higher priority to the substituent with greater mass regardless of identity
  • Using E/Z rules instead of CIP because allenes cannot be assigned R/S

Correct Answer: Applying CIP rules considering the sequence outward from each terminal carbon and treating orthogonal planes accordingly

Q20. Which of the following is NOT an advantage of enzymatic resolution in pharmaceutical synthesis?

  • High enantioselectivity under mild conditions
  • Usually environmentally benign and highly specific
  • Often high reaction rates and simple operational conditions
  • Always provides >99% yield of one enantiomer without need for further steps

Correct Answer: Always provides >99% yield of one enantiomer without need for further steps

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