Reaction Progress Kinetic Analysis and route optimization MCQs With Answer

Reaction Progress Kinetic Analysis (RPKA) and route optimization are essential tools for M.Pharm students involved in process chemistry and drug development. This blog provides a focused set of MCQs that bridge kinetic analysis methods with practical route selection considerations. You will review how RPKA experiments reveal catalytic behavior, orders, inhibition, and deactivation from full concentration–time profiles, and how these insights guide optimization of steps, solvents, and safety for scalable synthesis. Questions emphasize mechanistic interpretation, VTNA, competitive and same/different-excess experiments, plus green metrics and strategic choices that improve yield, cost, and robustness of pharmaceutical routes.

Q1. Which primary advantage distinguishes Reaction Progress Kinetic Analysis (RPKA) from traditional initial-rate methods?

• RPKA requires measurement only at very low concentrations
• RPKA focuses on full concentration–time profiles from a single run to identify changes in rate behavior
• RPKA eliminates the need for temperature control during experiments
• RPKA only measures product formation at reaction completion

Correct Answer: RPKA focuses on full concentration–time profiles from a single run to identify changes in rate behavior

Q2. In RPKA, a “same-excess” experiment is primarily used to detect:

• Initial rate constant at infinite dilution
• Changes due to catalyst activation, deactivation, or induction periods
• The thermodynamic equilibrium constant
• Solvent polarity effects on rate

Correct Answer: Changes due to catalyst activation, deactivation, or induction periods

Q3. Variable Time Normalization Analysis (VTNA) is employed in RPKA to:

• Determine absolute rate constants without concentration data
• Collapse concentration–time data from different initial concentrations onto a single master curve to deduce reaction orders
• Normalize temperature fluctuations across experiments
• Measure activation energy directly from one experiment

Correct Answer: Collapse concentration–time data from different initial concentrations onto a single master curve to deduce reaction orders

Q4. Which observation in a concentration–time plot suggests product inhibition of a catalyst?

• Rate increases steadily as product accumulates
• Rate decreases as product concentration increases, disproportionate to substrate depletion
• Rate is unaffected by product concentration
• Reaction shows an initial induction period followed by constant rate

Correct Answer: Rate decreases as product concentration increases, disproportionate to substrate depletion

Q5. In “different-excess” RPKA experiments, varying the initial concentration of one reactant while keeping others constant primarily helps to determine:

• Temperature dependence of the reaction
• Selective formation of side-products
• The order of reaction with respect to the varied reactant
• The identity of the solvent required

Correct Answer: The order of reaction with respect to the varied reactant

Q6. When RPKA shows that reaction rate is independent of substrate concentration but proportional to catalyst concentration, the likely kinetic model is:

• Zero-order in catalyst, first-order in substrate
• First-order in catalyst, zero-order in substrate (catalyst-limited regime)
• Second-order in both catalyst and substrate
• Autocatalytic with substrate inhibition

Correct Answer: First-order in catalyst, zero-order in substrate (catalyst-limited regime)

Q7. Which of the following mechanistic inferences can RPKA most reliably provide?

• Exact transition-state structure
• Presence and kinetic significance of off-cycle catalyst species such as deactivated complexes or product-bound catalyst
• Absolute entropy of activation without temperature variation
• Thermodynamic stability of intermediates at equilibrium

Correct Answer: Presence and kinetic significance of off-cycle catalyst species such as deactivated complexes or product-bound catalyst

Q8. For route optimization, “step economy” primarily aims to:

• Maximize the number of purification steps to ensure purity
• Minimize the total number of synthetic steps to reduce yield losses and resources
• Increase the stoichiometric excess of reagents
• Favor the longest feasible reaction sequences for better control

Correct Answer: Minimize the total number of synthetic steps to reduce yield losses and resources

Q9. Which metric best evaluates the mass efficiency of a synthetic route from an environmental standpoint?

• Retention time in chromatography
• E-factor (mass of waste per mass of product)
• Melting point of the final API
• Boiling point of the solvent

Correct Answer: E-factor (mass of waste per mass of product)

Q10. During route selection, why might a chemist prefer telescoping multiple steps without isolation?

• It always improves stereoselectivity
• It reduces isolation/purification losses, solvent use and processing time, improving overall efficiency
• It ensures each intermediate is fully characterized
• It eliminates the need to control reaction temperature

Correct Answer: It reduces isolation/purification losses, solvent use and processing time, improving overall efficiency

Q11. In a catalytic reaction analyzed by RPKA, data show rate decreases over time despite constant substrate concentration; the most plausible cause is:

• Increasing product concentration always accelerates reaction
• Catalyst deactivation or loss of active catalyst concentration over time
• Constant temperature fluctuations cause the change
• Changing solvent polarity during reaction

Correct Answer: Catalyst deactivation or loss of active catalyst concentration over time

Q12. When optimizing a synthetic route for scale-up, which factor is least relevant?

• Reagent availability and cost
• Intrinsic reaction hazard and thermal runaway potential
• Ease of reaction monitoring on large scale
• Color of the laboratory walls

Correct Answer: Color of the laboratory walls

Q13. Which RPKA practice helps distinguish between true kinetic order and apparent order affected by competing equilibria?

• Using only initial-rate points at very short times
• Performing full reaction profiles at multiple initial concentrations and applying VTNA or integrated analyses
• Running reaction at only one concentration and extrapolating
• Ignoring product formation and measuring solvent consumption

Correct Answer: Performing full reaction profiles at multiple initial concentrations and applying VTNA or integrated analyses

Q14. For route optimization in pharma, which choice best balances green chemistry and regulatory acceptability?

• Use of highly toxic but cheap reagents because cost is primary
• Prefer noncritical, well-characterized solvents and fewer hazardous reagents, even if minor cost increase occurs
• Always choose the longest route with many protection–deprotection steps for better yields
• Maximize use of exotic catalysts regardless of downstream residuals

Correct Answer: Prefer noncritical, well-characterized solvents and fewer hazardous reagents, even if minor cost increase occurs

Q15. In RPKA, an observed kinetic isotope effect (KIE) supports which conclusion?

• Kinetic isotope effects are irrelevant to mechanism
• A bond to the isotopically labeled atom is likely involved in the rate-determining step if a significant KIE is observed
• The reaction is diffusion-limited only
• The labeled atom determines product distribution but not rate

Correct Answer: A bond to the isotopically labeled atom is likely involved in the rate-determining step if a significant KIE is observed

Q16. Which strategy is most appropriate when RPKA indicates competing parallel pathways that lower selectivity?

• Increase temperature indiscriminately to speed up both pathways
• Modify catalyst, solvent, or concentration to favor the desired pathway by changing relative rates
• Ignore the issue and purify the mixture later
• Replace all reagents with stronger oxidants

Correct Answer: Modify catalyst, solvent, or concentration to favor the desired pathway by changing relative rates

Q17. Productivity in continuous flow processing compared with batch is often improved because:

• Flow reactors always use more solvent
• Tighter control over heat and mass transfer enables safer scale-up, higher concentration, and improved selectivity
• Flow eliminates the need to consider kinetics
• Products formed in flow are always racemic

Correct Answer: Tighter control over heat and mass transfer enables safer scale-up, higher concentration, and improved selectivity

Q18. Which green-metric is defined as the total mass of raw materials used (including solvents) divided by mass of product?

• Atom economy
• Process Mass Intensity (PMI)
• Yield percentage
• Thermodynamic efficiency

Correct Answer: Process Mass Intensity (PMI)

Q19. In route optimization, protecting groups are used when necessary, but overuse is discouraged because:

• Protecting groups always increase overall yield
• They add steps, reagents, and waste, lowering step economy and green metrics
• They remove the need for purification
• They always improve atom economy

Correct Answer: They add steps, reagents, and waste, lowering step economy and green metrics

Q20. A kinetic profile from RPKA shows a second-order dependence on substrate A when plotted via VTNA. For route choice, this suggests:

• High sensitivity to A concentration; optimizing A stoichiometry and addition profile can strongly influence rate and selectivity
• A is irrelevant and can be omitted from the route
• The reaction will be independent of catalyst behavior
• Scale-up should always use a large excess of solvent to dilute A

Correct Answer: High sensitivity to A concentration; optimizing A stoichiometry and addition profile can strongly influence rate and selectivity

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