Synthon Approach & Retrosynthesis: Principles and terminology MCQs With Answer

Introduction

This quiz collection on Synthon Approach & Retrosynthesis: Principles and Terminology is designed for M.Pharm students preparing for MPC 102T Advanced Organic Chemistry I. It focuses on core retrosynthetic concepts — synthons, synthetic equivalents, disconnection strategies, retrons, and polarity (umpolung) — and develops the ability to plan syntheses backwards from complex targets. Questions emphasize practical reasoning: choosing strategic bonds for disconnection, recognizing functional group interconversions, and selecting appropriate synthetic equivalents and protecting-group strategies. The set includes conceptual and application-based MCQs to strengthen problem-solving skills required for designing efficient, chemoselective and convergent syntheses in pharmaceutical contexts.

Q1. Which statement best defines a “synthon” in retrosynthetic analysis?

• An actual reagent used in a laboratory synthesis
• A hypothetical ideal fragment generated by disconnection that indicates types of reagents needed
• A protecting group applied to a functional group
• A by-product formed during a reaction

Correct Answer: A hypothetical ideal fragment generated by disconnection that indicates types of reagents needed

Q2. What is a “synthetic equivalent” (or synthone equivalent)?

• A synonym for retrosynthetic disconnection
• A real reagent or reagent combination that implements a synthon in forward synthesis
• A theoretical bond not present in the target molecule
• An enzyme used in biocatalysis

Correct Answer: A real reagent or reagent combination that implements a synthon in forward synthesis

Q3. In retrosynthesis, what is a “retrons”?

• A fragment that remains unchanged during the synthesis
• A structural feature in the target molecule that suggests a possible disconnection or synthetic route
• A reagent that must be avoided due to hazard
• A protecting group strategy for multifunctional molecules

Correct Answer: A structural feature in the target molecule that suggests a possible disconnection or synthetic route

Q4. Which of the following is an example of an acyl anion synthetic equivalent used to perform umpolung of carbonyl compounds?

• DIBAL-H
• 1,3-dithiane (after lithiation) as in the Corey-Seebach reaction
• Sodium borohydride (NaBH4)
• PCC (pyridinium chlorochromate)

Correct Answer: 1,3-dithiane (after lithiation) as in the Corey-Seebach reaction

Q5. Which disconnection is described as “heteroatom-initiated” or “polar disconnection”?

• Breaking a C–C bond to reveal two radical synthons
• Breaking a bond adjacent to a heteroatom to give nucleophilic and electrophilic synthons
• Breaking only aromatic C–H bonds
• Disconnection of a bond without considering polarity

Correct Answer: Breaking a bond adjacent to a heteroatom to give nucleophilic and electrophilic synthons

Q6. Which of these best illustrates umpolung (polarity inversion) in organic synthesis?

• Converting an alcohol to an ester by acid catalysis
• Using cyanide to convert an aldehyde into a nucleophilic carbon center (as in benzoin-like chemistry)
• Oxidizing a primary alcohol to a carboxylic acid
• Hydrogenation of an alkene to an alkane

Correct Answer: Using cyanide to convert an aldehyde into a nucleophilic carbon center (as in benzoin-like chemistry)

Q7. Which of the following correctly classifies synthons?

• Synthons are classified only as electrophilic or nucleophilic, never as radical
• Synthons are classified as nucleophilic, electrophilic, or radical
• Synthons refer only to protecting groups in retrosynthesis
• Synthons are classified by color codes in retrosynthetic schemes

Correct Answer: Synthons are classified as nucleophilic, electrophilic, or radical

Q8. In retrosynthesis of a secondary alcohol from an alkene, which strategic disconnection is most common?

• Disconnection at an aromatic C–H bond
• Retrosynthetic cleavage to an alkene and a hydride source
• Disconnection to reveal a carbonyl plus a nucleophilic carbon (e.g., reduction of ketone)
• Disconnection into two radicals only

Correct Answer: Disconnection to reveal a carbonyl plus a nucleophilic carbon (e.g., reduction of ketone)

Q9. What is meant by a “strategic bond” in retrosynthetic analysis?

• A bond whose disconnection leads to simple, readily available synthons and simplifies synthesis design
• A bond that must never be broken during synthesis
• A bond formed only via photochemical reactions
• A bond that connects two protecting groups

Correct Answer: A bond whose disconnection leads to simple, readily available synthons and simplifies synthesis design

Q10. Which forward reagent is a common synthetic equivalent for a nucleophilic carbon synthon (C:-)?

• Diazomethane (CH2N2) for direct nucleophilic carbanion attacks in many contexts
• Water (H2O)
• Sodium chloride (NaCl)
• Molecular oxygen (O2)

Correct Answer: Diazomethane (CH2N2) for direct nucleophilic carbanion attacks in many contexts

Q11. Which retrosynthetic change is an example of functional group interconversion (FGI)?

• Disconnecting an ester into an alcohol and acyl synthon
• Changing an alcohol into an aldehyde in the retrosynthetic plan to allow a new disconnection
• Splitting a molecule into two radicals without changing functional groups
• Labeling a synthone as nucleophilic without any structural change

Correct Answer: Changing an alcohol into an aldehyde in the retrosynthetic plan to allow a new disconnection

Q12. Convergent synthesis in retrosynthetic planning is advantageous because:

• It builds the molecule in a strictly linear sequence of single-step operations
• Independent fragments are synthesized separately and coupled, often improving overall yield and speed
• It reduces the number of required reagents to one
• It always avoids the need for protecting groups

Correct Answer: Independent fragments are synthesized separately and coupled, often improving overall yield and speed

Q13. In retrosynthesis, what is the primary purpose of introducing a protecting group?

• To permanently change a functional group into another functional group
• To temporarily mask a reactive site so selective transformations can be performed elsewhere
• To increase the molecular weight of the target
• To oxidize a sensitive functional group

Correct Answer: To temporarily mask a reactive site so selective transformations can be performed elsewhere

Q14. Which disconnection would you choose to make a β-hydroxy ketone via an aldol reaction?

• Disconnection that reveals an alkyl radical and a halide
• Disconnection into an enolate (nucleophilic synthon) and an aldehyde or ketone (electrophilic synthon)
• Disconnection into two epoxides
• Disconnection to an acyl cation and an alkene

Correct Answer: Disconnection into an enolate (nucleophilic synthon) and an aldehyde or ketone (electrophilic synthon)

Q15. Which of the following is a correct example of a radical retrosynthetic disconnection?

• Cleaving an alkyl–alkyl bond to form two radical synthons that will be reformed by a radical coupling
• Disconnection of a carbonyl into hydride and oxygen synthons
• Converting an ester into an alcohol and acyl chloride
• Using a protecting group on an amine

Correct Answer: Cleaving an alkyl–alkyl bond to form two radical synthons that will be reformed by a radical coupling

Q16. Which of these best describes a “transform-based disconnection”?

• Disconnecting based purely on atom economy without regard to mechanism
• Choosing disconnections that correspond to known named reactions or reliable forward transforms
• Disconnecting only C–H bonds
• Using only enzymatic steps in the synthetic plan

Correct Answer: Choosing disconnections that correspond to known named reactions or reliable forward transforms

Q17. Which reagent pair is a classic example of implementing a nucleophilic acyl equivalent for an acylation reaction?

• Organolithium reagent reacting directly with carbon dioxide to give a carboxylic acid equivalent
• 1,3-dithiane (lithiated) followed by hydrolysis to reveal the carbonyl
• Pyridinium chlorochromate for oxidation of alcohols
• Sodium sulfate as a drying agent

Correct Answer: 1,3-dithiane (lithiated) followed by hydrolysis to reveal the carbonyl

Q18. When planning a retrosynthesis, why is consideration of chemoselectivity important?

• C​hemoselectivity determines the speed of a reaction but not product distribution
• It ensures that the chosen forward reactions will selectively transform the intended functional group without undesirable side reactions
• Chemoselectivity only matters for photochemical reactions
• It allows elimination of all protecting groups from the plan

Correct Answer: It ensures that the chosen forward reactions will selectively transform the intended functional group without undesirable side reactions

Q19. Which retrosynthetic idea is illustrated by planning a route that first disconnects the molecule into two equally complex fragments to be coupled?

• Linear synthesis strategy
• Convergent synthesis strategy
• Protecting-group-first strategy
• Random fragmentation

Correct Answer: Convergent synthesis strategy

Q20. In designing a retrosynthetic plan for a substituted benzaldehyde, which disconnection commonly reveals a simple synthetic equivalent?

• Breaking an aromatic C–C bond to give two aliphatic fragments
• Retrosynthetic transformation of benzaldehyde to benzyl alcohol (FGI), or use of a formyl synthon such as DMF-DMA in forward synthesis
• Disconnection into two radical fragments only
• Converting benzaldehyde to an epoxide directly in retrosynthesis

Correct Answer: Retrosynthetic transformation of benzaldehyde to benzyl alcohol (FGI), or use of a formyl synthon such as DMF-DMA in forward synthesis

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