Synthetic Reagents: Diazomethane and applications MCQs With Answer

This quiz set focuses on diazomethane — a versatile and widely used synthetic reagent in advanced organic chemistry. Designed for M.Pharm students, the questions probe preparation methods, reaction mechanisms, selectivity, safety considerations, and key applications such as methylation, cyclopropanation, and the Wolff rearrangement. Emphasis is placed on mechanistic understanding, practical laboratory handling, and distinguishing diazomethane reactivity from related reagents. Working through these MCQs will reinforce critical concepts needed in drug synthesis and functional group transformations, while highlighting the precautions required when using this hazardous but invaluable reagent in research and industrial settings.

Q1. Which of the following is the most common laboratory precursor used to generate diazomethane safely?

• N-methyl-N-nitroso-p-toluenesulfonamide (Diazald)
• Methyl iodide and sodium azide
• Nitrosomethylurea
• Trimethylsilyldiazomethane

Correct Answer: N-methyl-N-nitroso-p-toluenesulfonamide (Diazald)

Q2. Diazomethane reacts with carboxylic acids primarily to give which product?

• Diazoketones
• Methyl esters
• Acyl chlorides
• Alcohols

Correct Answer: Methyl esters

Q3. Which spectroscopic feature is most characteristic of diazomethane in the IR spectrum?

• A strong band around 1700 cm^-1 (C=O)
• A strong band near 2100 cm^-1 (diazo stretch)
• A broad O–H stretch around 3300 cm^-1
• A band at 1500 cm^-1 (aromatic C=C)

Correct Answer: A strong band near 2100 cm^-1 (diazo stretch)

Q4. The Wolff rearrangement of a diazoketone gives which intermediate that leads to homologation of carboxylic acids?

• Keteniminium ion
• Carbanion
• Ketene
• Acyl radical

Correct Answer: Ketene

Q5. Which of the following statements about diazomethane methylation is correct?

• Diazomethane selectively methylates amides faster than carboxylic acids.
• Diazomethane converts carboxylic acids to methyl esters without prior activation.
• Diazomethane requires strong Lewis acids to methylate phenols.
• Diazomethane cannot methylate enols or phenols.

Correct Answer: Diazomethane converts carboxylic acids to methyl esters without prior activation.

Q6. Which hazard is most associated with diazomethane and dictates special laboratory precautions?

• It is a strong oxidizer and causes spontaneous combustion.
• It is highly explosive and toxic, requiring dilute solutions and proper ventilation.
• It polymerizes rapidly on storage, producing heat.
• It forms peroxides on exposure to air.

Correct Answer: It is highly explosive and toxic, requiring dilute solutions and proper ventilation.

Q7. In the Arndt–Eistert homologation sequence, which reagent is treated with diazomethane to form a diazoketone?

• Alcohol
• Acid chloride
• Aldehyde
• Ketone

Correct Answer: Acid chloride

Q8. Which of the following best describes the role of diazomethane under photolysis or thermolysis conditions?

• It acts as a radical initiator to form alkyl radicals.
• It generates a methylene (:CH2) carbene that can insert or add to multiple bonds.
• It reduces carbonyl compounds to alcohols.
• It forms diazonium salts for Sandmeyer-type reactions.

Correct Answer: It generates a methylene (:CH2) carbene that can insert or add to multiple bonds.

Q9. Diazomethane effects cyclopropanation of alkenes. Which stereochemical outcome is generally observed in concerted cyclopropanation?

• Retention of relative stereochemistry of the alkene (cis → cis, trans → trans)
• Complete racemization at adjacent stereocenters
• Exclusive inversion of configuration (cis → trans)
• Formation of only the trans-cyclopropane regardless of alkene geometry

Correct Answer: Retention of relative stereochemistry of the alkene (cis → cis, trans → trans)

Q10. Which reagent is a safer alternative to diazomethane for methylation reactions in many cases?

• Dimethyl sulfate
• Methyl iodide
• Trimethylsilyldiazomethane
• Sodium methoxide

Correct Answer: Trimethylsilyldiazomethane

Q11. Which mechanistic step is key in converting a carboxylic acid to a methyl ester using diazomethane?

• Nucleophilic attack of diazomethane on a protonated carbonyl
• Deprotonation of the acid and nucleophilic methyl transfer to the carboxylate
• Formation of an acyl radical followed by recombination with CH3•
• Oxidative addition of the acid to diazomethane

Correct Answer: Deprotonation of the acid and nucleophilic methyl transfer to the carboxylate

Q12. Which functional group is least likely to be methylated by diazomethane under typical conditions?

• Carboxylic acids
• Phenols
• Primary alcohols
• Enols

Correct Answer: Primary alcohols

Q13. During preparation, diazomethane solutions are usually generated and stored in which solvent for safety and stability?

• Water
• Diethyl ether
• Acetonitrile
• Dimethyl sulfoxide (DMSO)

Correct Answer: Diethyl ether

Q14. Which by-product is released during the methylation of carboxylic acids by diazomethane?

• Carbon monoxide (CO)
• Nitrogen gas (N2)
• Methane (CH4)
• Nitrous oxide (N2O)

Correct Answer: Nitrogen gas (N2)

Q15. In mass spectrometry, the molecular ion peak for diazomethane (CH2N2) should correspond to which m/z value?

• 30
• 42
• 58
• 72

Correct Answer: 42

Q16. Which transformation commonly uses diazomethane as an intermediate step followed by Wolff rearrangement to increase carbon chain length by one carbon?

• Baeyer–Villiger oxidation
• Arndt–Eistert homologation
• Buchwald–Hartwig amination
• Fischer esterification

Correct Answer: Arndt–Eistert homologation

Q17. Which reagent is typically used to quench excess diazomethane safely at the end of a reaction?

• Sodium borohydride
• Acetic acid (glacial acetic acid)
• Sodium hydroxide
• Hydrazine hydrate

Correct Answer: Acetic acid (glacial acetic acid)

Q18. Which statement best contrasts diazomethane and trimethylsilyldiazomethane (TMS-diazomethane) for methylation?

• TMS-diazomethane is more explosive and less selective than diazomethane.
• TMS-diazomethane is a safer, bench-stable alternative and often used to methylate acids without explosive hazards.
• Diazomethane cannot methylate phenols, whereas TMS-diazomethane can.
• Both reagents are equally toxic and interchangeable in all conditions.

Correct Answer: TMS-diazomethane is a safer, bench-stable alternative and often used to methylate acids without explosive hazards.

Q19. Diazomethane reacts with aldehydes and ketones under certain conditions to give which primary type of product when a Wolff rearrangement occurs from a diazoketone?

• Alcohols by direct reduction
• Homologated acids or esters via ketene intermediate
• Allylic halides
• α,β-Unsaturated carbonyl compounds via elimination

Correct Answer: Homologated acids or esters via ketene intermediate

Q20. Which mechanistic pathway explains cyclopropanation of alkenes by diazomethane-derived methylene?

• Stepwise radical addition followed by radical coupling
• Concerted [2+1] cycloaddition via singlet carbene leading to stereospecific products
• Nucleophilic substitution at the alkene carbon
• Electrophilic aromatic substitution-like mechanism

Correct Answer: Concerted [2+1] cycloaddition via singlet carbene leading to stereospecific products

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