Synthetic Reagents: Osmium tetroxide, TiCl4, DEAZO reagents MCQs With Answer

This quiz set focuses on three important classes of synthetic reagents — osmium tetroxide (OsO4), titanium tetrachloride (TiCl4), and deazotization (deazo) reagents — frequently encountered in advanced organic synthesis and medicinal chemistry. The questions are designed for M.Pharm students preparing for MPC 102T Advanced Organic Chemistry I, emphasizing mechanistic understanding, practical applications, stereochemical outcomes, and laboratory safety. Expect items on catalytic cycles, stereospecificity, Lewis-acid activation, common transformations (dihydroxylation, McMurry coupling, Sandmeyer/deazotization), and appropriate choice of reagents and conditions. Use these MCQs to test and reinforce deep conceptual knowledge relevant to synthetic strategy and reaction planning.

Q1. What is the stereochemical outcome when an alkene undergoes osmium tetroxide-catalyzed dihydroxylation?

• Anti addition producing trans-diols
• Syn addition producing cis-diols
• Radical addition producing racemic mixture
• Concerted elimination producing epoxides

Correct Answer: Syn addition producing cis-diols

Q2. Which statement best describes the role of N-methylmorpholine N-oxide (NMO) in OsO4-mediated dihydroxylation?

• NMO acts as a co-oxidant to regenerate Os(VIII) from reduced osmium species
• NMO is the source of hydroxyl groups added across the double bond
• NMO acts as a ligand that makes OsO4 more electrophilic for cycloaddition
• NMO acts as a solvent to dissolve OsO4 and alkene

Correct Answer: NMO acts as a co-oxidant to regenerate Os(VIII) from reduced osmium species

Q3. Which mechanistic intermediate is typically invoked in the OsO4 dihydroxylation of alkenes?

• Carbocation intermediate stabilized by osmium
• Osmate(VI) cyclic ester (osmate ester)
• Free radical intermediate followed by oxygen rebound
• Epoxide intermediate formed by oxygen transfer

Correct Answer: Osmate(VI) cyclic ester (osmate ester)

Q4. Which safety or practical consideration is most important when handling OsO4 in the lab?

• OsO4 is non-toxic but highly flammable; store away from heat
• OsO4 is volatile and highly toxic; handle in a fume hood with appropriate PPE
• OsO4 is corrosive to glass and must be stored in plastic only
• OsO4 is a strong base and reacts violently with acids

Correct Answer: OsO4 is volatile and highly toxic; handle in a fume hood with appropriate PPE

Q5. In asymmetric dihydroxylation developed by Sharpless, what additional component is essential to induce enantioselectivity?

• Chiral ligand (e.g., cinchona alkaloid derived ligand) in AD-mix
• High-pressure oxygen atmosphere
• Strong acid catalyst to protonate the alkene
• Stoichiometric OsO4 without any ligand

Correct Answer: Chiral ligand (e.g., cinchona alkaloid derived ligand) in AD-mix

Q6. Which transformation is titanium tetrachloride (TiCl4) most commonly used to promote?

• Radical halogenation of alkanes
• Lewis-acid-promoted activation of carbonyls for nucleophilic addition
• Oxidative cleavage of vicinal diols to carbonyls
• Photochemical [2+2] cycloaddition under visible light

Correct Answer: Lewis-acid-promoted activation of carbonyls for nucleophilic addition

Q7. Which of the following reactions commonly uses TiCl4 to form a titanium enolate for subsequent C–C bond formation?

• Aldol condensation (TiCl4-mediated aldol)
• Nitration of aromatic rings
• Hydroboration–oxidation of alkenes
• Wittig olefination

Correct Answer: Aldol condensation (TiCl4-mediated aldol)

Q8. Which factor contributes to the high Lewis acidity of TiCl4?

• Presence of a filled d10 electron shell
• Ti4+ has an empty d-orbital and strong electron-withdrawing chlorides
• Large ionic radius that prevents coordination
• Ability to donate electrons to substrates

Correct Answer: Ti4+ has an empty d-orbital and strong electron-withdrawing chlorides

Q9. Which practical precaution is required when using TiCl4 in reactions?

• TiCl4 is stable to water and requires no special drying
• TiCl4 reacts violently with water releasing HCl; use inert, anhydrous conditions
• TiCl4 is a weak oxidant and must be handled under oxygen to activate it
• TiCl4 is a mild base that deprotonates acidic solvents

Correct Answer: TiCl4 reacts violently with water releasing HCl; use inert, anhydrous conditions

Q10. In McMurry coupling, TiCl4 is used with a reducing metal (e.g., Zn or LiAlH4). What is the net transformation achieved?

• Reductive dimerization of two carbonyl compounds to form an alkene
• Oxidation of alcohols to carboxylic acids
• Hydrolysis of esters to alcohols and acids
• Conversion of carbonyls to epoxides via oxygen insertion

Correct Answer: Reductive dimerization of two carbonyl compounds to form an alkene

Q11. Which description fits a common deazotization (deazo) reagent used to replace an aromatic diazonium group with hydrogen?

• Hypophosphorous acid (H3PO2) acts as a reducing agent to give the hydrogen-substituted arene
• Potassium permanganate converts diazonium to nitro group
• Sodium azide converts diazonium to an alkyl group directly
• Hydrogen peroxide selectively replaces diazonium with chlorine

Correct Answer: Hypophosphorous acid (H3PO2) acts as a reducing agent to give the hydrogen-substituted arene

Q12. The Sandmeyer reaction (using CuCl or CuBr) converts an aryl diazonium into which functional group?

• Aryl chloride or bromide, depending on the copper halide used
• Aryl methyl via methylation
• Aryl hydroxide directly without further steps
• Aryl nitro group via oxidative substitution

Correct Answer: Aryl chloride or bromide, depending on the copper halide used

Q13. Which reagent pair is commonly used for the deazotization of an aryl diazonium salt to give an arene under mild conditions?

• Sodium borohydride in methanol
• Hypophosphorous acid (H3PO2) or ethanol as a hydrogen source
• Sodium cyanide and copper (I) chloride
• Chromic acid and acetic acid

Correct Answer: Hypophosphorous acid (H3PO2) or ethanol as a hydrogen source

Q14. Which mechanistic pathway is typically involved when a diazonium salt undergoes Sandmeyer halogenation?

• Electrophilic aromatic substitution via Wheland intermediate
• Single-electron transfer (SET) to generate an aryl radical that couples to halide
• Nucleophilic aromatic substitution at the diazonium nitrogen
• Concerted pericyclic substitution

Correct Answer: Single-electron transfer (SET) to generate an aryl radical that couples to halide

Q15. When planning a synthesis that requires converting an aniline to an aryl nitrile, which sequence using diazonium chemistry is most appropriate?

• Direct nitration of aniline under strong acidic conditions
• Form diazonium salt and then treat with CuCN (Sandmeyer) to introduce CN
• Oxidize aniline to nitro then reduce to nitrile
• Convert aniline to diazonium and hydrolyze to give nitrile directly

Correct Answer: Form diazonium salt and then treat with CuCN (Sandmeyer) to introduce CN

Q16. Which statement correctly contrasts OsO4 dihydroxylation and KMnO4 oxidation of alkenes?

• OsO4 typically gives syn-1,2-diols; cold, dilute KMnO4 can also give syn-diols but hot, concentrated KMnO4 cleaves to carbonyls/carboxylates
• OsO4 always cleaves alkenes into carbonyl fragments, while KMnO4 never cleaves
• KMnO4 is milder than OsO4 and gives better stereocontrol for asymmetric dihydroxylation
• Both reagents form epoxides as primary products under all conditions

Correct Answer: OsO4 typically gives syn-1,2-diols; cold, dilute KMnO4 can also give syn-diols but hot, concentrated KMnO4 cleaves to carbonyls/carboxylates

Q17. In a reaction where TiCl4 coordinates to an aldehyde oxygen, what is the primary electronic consequence that facilitates nucleophilic attack?

• Coordination raises the energy of the aldehyde HOMO making it less reactive
• Coordination increases the electrophilicity of the carbonyl carbon by lowering LUMO energy
• Coordination converts the carbonyl into a radical cation
• Coordination causes immediate cleavage of the C–O bond to form an acylium ion

Correct Answer: Coordination increases the electrophilicity of the carbonyl carbon by lowering LUMO energy

Q18. Which reagent is inappropriate for safely generating an aryl diazonium salt from an aniline?

• Sodium nitrite (NaNO2) with HCl at 0–5 °C
• Sodium nitrite (NaNO2) with H2SO4 and heat at 80 °C
• Isoamyl nitrite under controlled cold conditions
• tert-Butyl nitrite with appropriate acid at low temperature

Correct Answer: Sodium nitrite (NaNO2) with H2SO4 and heat at 80 °C

Q19. Which outcome is expected when an internal alkene bearing defined stereochemistry undergoes OsO4-mediated dihydroxylation?

• Loss of stereochemical information, giving a racemic mixture of diols
• Retention of relative stereochemistry leading to a single diastereomer via syn addition
• Formation of both cis- and trans-diols equally by stepwise radical mechanism
• Preferential formation of epoxide instead of diol under OsO4

Correct Answer: Retention of relative stereochemistry leading to a single diastereomer via syn addition

Q20. Which description best summarizes the strategic use of diazonium chemistry (including deazotization) in medicinal chemistry synthesis?

• Diazonium chemistry is of limited use because diazonium salts are inert and unreactive
• Diazonium salts permit versatile interconversions (halide, CN, H, OH, aryl–aryl couplings), enabling late-stage functionalization of aromatics
• Diazonium chemistry only allows conversion to azides and is not useful for creating diverse substituents
• Diazonium formation is always avoided in medicinal chemistry due to irreversible decomposition

Correct Answer: Diazonium salts permit versatile interconversions (halide, CN, H, OH, aryl–aryl couplings), enabling late-stage functionalization of aromatics

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