Synthesis of acridine MCQs With Answer is a concise, student-focused introduction to preparing acridine, a tricyclic heterocycle important in pharmaceuticals and dyes. This guide highlights key methods such as the Bernthsen synthesis, formation of the acridone intermediate, common catalysts (ZnCl2, polyphosphoric acid), mechanistic steps like Friedel–Crafts type cyclization and aromatization, and practical tips on reagents and conditions. Designed for B. Pharm students, it emphasizes reaction pathways, intermediates, spectral and biological properties, and safety considerations. Clear, exam-oriented questions reinforce understanding of both theory and lab-relevant synthesis strategies. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the characteristic intermediate in the Bernthsen synthesis of acridine?
- Acridone
- Anthracene
- Diphenylamine
- Acridine N-oxide
Correct Answer: Acridone
Q2. Which reagent is classically used as Lewis acid catalyst in the Bernthsen acridine synthesis?
- ZnCl2
- NaBH4
- H2O2
- LiAlH4
Correct Answer: ZnCl2
Q3. The Bernthsen method typically condenses diphenylamine with which type of compound to form acridine?
- Carboxylic acid
- Alcohol
- Alkene
- Nitrile
Correct Answer: Carboxylic acid
Q4. The ring-closure step in many acridine syntheses proceeds by which general mechanism?
- Friedel–Crafts type electrophilic acylation and cyclization
- Free-radical polymerization
- Nucleophilic aliphatic substitution (SN2)
- Pericyclic [4+2] cycloaddition
Correct Answer: Friedel–Crafts type electrophilic acylation and cyclization
Q5. Acridine is best described as which of the following?
- Tricyclic heteroaromatic compound
- Saturated aliphatic amine
- Polymeric dye resin
- Simple monocyclic aromatic
Correct Answer: Tricyclic heteroaromatic compound
Q6. The nitrogen atom in acridine is typically considered to be:
- sp2 hybridized and part of the aromatic system
- sp3 hybridized and non-aromatic
- sp hybridized with a triple bond
- protonated under all conditions
Correct Answer: sp2 hybridized and part of the aromatic system
Q7. How would you classify the basicity of acridine (parent compound)?
- Weakly basic due to delocalization of the lone pair
- Strong base like aliphatic amines
- Strong acid
- Non-basic and inert to protonation
Correct Answer: Weakly basic due to delocalization of the lone pair
Q8. Acridine and many of its derivatives are known for which photophysical property?
- Fluorescence under UV illumination
- Strong phosphorescence at room temperature
- No electronic absorption in UV–Vis
- Exclusive infrared emission
Correct Answer: Fluorescence under UV illumination
Q9. Which acid medium is commonly used as an alternative to ZnCl2 for cyclodehydration in acridine synthesis?
- Polyphosphoric acid (PPA)
- Sodium hydroxide solution
- Ammonia gas
- Dimethylformamide
Correct Answer: Polyphosphoric acid (PPA)
Q10. Acridine orange is best known as:
- A fluorescent nucleic acid dye used in microscopy
- An aliphatic surfactant
- A reducing agent in organic synthesis
- A polymerization inhibitor
Correct Answer: A fluorescent nucleic acid dye used in microscopy
Q11. Quinacrine is an acridine derivative historically used as an:
- Antimalarial and antiprotozoal drug
- Anticoagulant agent
- Beta blocker for cardiac disease
- Topical anesthetic
Correct Answer: Antimalarial and antiprotozoal drug
Q12. A major biological concern with many acridine derivatives is their ability to:
- Intercalate DNA and act as mutagens
- Act as strong systemic antioxidants
- Increase membrane rigidity without genetic effect
- Serve as essential nutrients
Correct Answer: Intercalate DNA and act as mutagens
Q13. What reagent class is commonly used to convert acridine to its N-oxide derivative?
- Peracids (e.g., m-CPBA)
- Hydride donors (e.g., NaBH4)
- Strong bases (e.g., NaOH)
- Metal catalysts (e.g., Pd/C) without oxidant
Correct Answer: Peracids (e.g., m-CPBA)
Q14. The final aromatization or dehydrogenation step in some acridine syntheses can be achieved using which oxidant?
- DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)
- Sodium cyanoborohydride
- Tetramethylsilane
- Triethylamine
Correct Answer: DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)
Q15. In the Bernthsen method, the initial acylation step typically forms which intermediate prior to ring closure?
- N-acyl diarylamine (which cyclizes to acridone)
- Alkyl halide
- Carbocation stabilized by oxygen
- Azide intermediate
Correct Answer: N-acyl diarylamine (which cyclizes to acridone)
Q16. Which condition is most important for successful cyclization to acridine in classical syntheses?
- High temperature to promote dehydration and ring closure
- Low temperature to avoid side reactions
- Strictly anhydrous and cold conditions below 0°C
- Light irradiation at visible wavelengths
Correct Answer: High temperature to promote dehydration and ring closure
Q17. Which statement about regioselectivity in acridine synthesis is true?
- Substituents on starting diarylamines direct electrophilic attack and influence the substitution pattern on the acridine core
- Regioselectivity is irrelevant; all positions are equivalent
- Only steric effects, never electronic effects, determine the position of substitution
- Substituents always migrate during the reaction to give a single product
Correct Answer: Substituents on starting diarylamines direct electrophilic attack and influence the substitution pattern on the acridine core
Q18. The name “acridine” is chemically equivalent to which systematic name?
- 9-azaanthracene
- Benzimidazole
- Indole
- Pyridine
Correct Answer: 9-azaanthracene
Q19. Which analytical technique is most useful to confirm acridine formation and conjugation?
- UV–Vis absorption and fluorescence spectroscopy
- Polarimetry only
- Gel permeation chromatography for small molecules
- Millimeter-wave rotational spectroscopy
Correct Answer: UV–Vis absorption and fluorescence spectroscopy
Q20. For laboratory-scale syntheses of acridine derivatives, which purification method is commonly applied?
- Column chromatography followed by recrystallization
- Distillation under ambient pressure only
- Lyophilization of the crude melt
- Direct sublimation from aqueous solution
Correct Answer: Column chromatography followed by recrystallization
Q21. Which safety concern is especially relevant when handling many acridine dyes or derivatives in the lab?
- Potential mutagenicity and skin absorption; use gloves and engineering controls
- Spontaneous ignition in air at room temperature
- Extreme volatility leading to explosive vapors
- Instant polymerization on contact with glass
Correct Answer: Potential mutagenicity and skin absorption; use gloves and engineering controls
Q22. An effective strategy to improve yields in acridine formation is to:
- Optimize the acid catalyst and reaction temperature to favor cyclization over side reactions
- Run the reaction at the lowest possible temperature for weeks
- Exclude catalysts entirely to prevent decomposition
- Always use stoichiometric oxidants from the start
Correct Answer: Optimize the acid catalyst and reaction temperature to favor cyclization over side reactions
Q23. Which of the following is a common synthetic route to substituted acridines (other than Bernthsen)?
- Friedel–Crafts acylation of anilines followed by intramolecular cyclization
- Diels–Alder between two aliphatic olefins
- Base-catalyzed epoxide ring opening to form acridine
- Direct nitration of benzene to acridine
Correct Answer: Friedel–Crafts acylation of anilines followed by intramolecular cyclization
Q24. Which functional group transformation commonly leads to the acridine core during synthesis?
- Intramolecular acylation (formation of a new C–C bond with concomitant ring closure)
- Simple ester hydrolysis without further reaction
- Direct alkene hydrogenation only
- Thiolation of an aliphatic chain
Correct Answer: Intramolecular acylation (formation of a new C–C bond with concomitant ring closure)
Q25. In synthetic planning, converting acridone to acridine requires removal of which atom from acridone?
- Oxygen (deoxygenation) to form the fully conjugated acridine
- Nitrogen to give a hydrocarbon product
- Sulfur to form thiaacridine
- Phosphorus insertion at C-9
Correct Answer: Oxygen (deoxygenation) to form the fully conjugated acridine
Q26. Which of the following describes a practical way to introduce substituents at the 9-position (central ring) of acridine?
- Using substituted carboxylic acids or acyl chloride partners during condensation
- Adding alkali metals to acridine in water
- Direct electrophilic nitration always gives 9-substitution exclusively
- Photochemical degradation of acridine
Correct Answer: Using substituted carboxylic acids or acyl chloride partners during condensation
Q27. The resistance of the acridine nitrogen lone pair to protonation is due to:
- Delocalization of the lone pair into the aromatic pi-system
- Steric hindrance blocking proton access only
- Complete localization on an sp3 nitrogen
- Its involvement in a metal coordination complex by default
Correct Answer: Delocalization of the lone pair into the aromatic pi-system
Q28. Which type of catalysis is most central to classical acridine ring formation reactions?
- Lewis acid catalysis
- Enzymatic catalysis
- Phase-transfer catalysis exclusively
- Photoredox catalysis in water
Correct Answer: Lewis acid catalysis
Q29. Which chromatographic detector is particularly useful for acridine derivatives during purification monitoring?
- UV detector due to strong absorbance of acridine chromophore
- Evaporative light scattering detector only
- Flame ionization detector for non-volatile aromatics
- Refractive index detector with no UV capability
Correct Answer: UV detector due to strong absorbance of acridine chromophore
Q30. When designing safer lab work with acridine dyes, which precaution is most appropriate?
- Work in a fume hood with gloves and eye protection to limit exposure
- Avoid ventilation to keep fumes contained in the lab
- Store large open containers on the bench for convenience
- Use bare hands when handling powders to detect quantity by feel
Correct Answer: Work in a fume hood with gloves and eye protection to limit exposure
Q31. The formation of acridine from diarylamines generally involves which bond formation sequence?
- Formation of a new C–C bond followed by ring fusion to the nitrogen-containing ring
- Sequential formation of two C–O bonds only
- Direct N–N bond formation between anilines
- Formation of an aliphatic C–C chain then cyclization to a macrocycle
Correct Answer: Formation of a new C–C bond followed by ring fusion to the nitrogen-containing ring
Q32. Which property of acridine contributes to its use as a fluorescent probe for nucleic acids?
- Ability to intercalate into DNA and emit fluorescence upon binding
- Complete inertness to biological macromolecules
- Strong basicity that denatures proteins
- Exclusive reactivity with lipids only
Correct Answer: Ability to intercalate into DNA and emit fluorescence upon binding
Q33. In mechanism discussions, acridone formation is often described as which type of cyclization?
- Intramolecular electrophilic aromatic substitution leading to a lactam-like acridone
- Concerted sigmatropic rearrangement only
- Intermolecular nucleophilic attack from solvent
- Radical chain scission of an aliphatic precursor
Correct Answer: Intramolecular electrophilic aromatic substitution leading to a lactam-like acridone
Q34. Substituents that activate aromatic rings toward electrophilic attack (e.g., methoxy) will typically:
- Increase the rate of cyclization in acridine-forming reactions when appropriately positioned
- Always prevent cyclization by steric blockage
- Have no effect on reaction outcome
- Convert the substrate into an aliphatic hydrocarbon
Correct Answer: Increase the rate of cyclization in acridine-forming reactions when appropriately positioned
Q35. Which laboratory practice helps minimize oxidation of sensitive acridine intermediates?
- Conducting reactions under inert atmosphere (nitrogen or argon)
- Exposing reaction mixtures to direct sunlight
- Adding large excesses of strong oxidants early
- Storing everything at elevated temperatures
Correct Answer: Conducting reactions under inert atmosphere (nitrogen or argon)
Q36. Which of the following best describes a common route to prepare 9-substituted acridines?
- Use of substituted acylating agents during cyclization to place substituents at C-9
- Selective hydrogenation of acridine to install substituents at C-9
- Oxidative cleavage of acridine to open the central ring
- Radical halogenation of benzene prior to ring assembly
Correct Answer: Use of substituted acylating agents during cyclization to place substituents at C-9
Q37. Which spectroscopic change indicates conversion of acridone to acridine?
- Increase in conjugation seen by a bathochromic shift in UV–Vis absorbance and change in fluorescence
- Complete loss of all UV absorption bands
- Emergence of a strong IR O–H stretch only
- Appearance of an NMR signal at 0 ppm only
Correct Answer: Increase in conjugation seen by a bathochromic shift in UV–Vis absorbance and change in fluorescence
Q38. Which reagent class is commonly used to deoxygenate lactams and related carbonyls en route to heteroaromatics like acridine?
- Phosphorus-based reagents or reductive deoxygenation protocols
- Strong oxidants like permanganate
- Alkali metal hydroxides at room temperature only
- Inert gases without reagent addition
Correct Answer: Phosphorus-based reagents or reductive deoxygenation protocols
Q39. Which of the following is a direct application of acridine derivatives in pharmaceutical science?
- Antiprotozoal agents and DNA-intercalating chemotherapeutics (research tools)
- Exclusive use as inhaled bronchodilators
- Primary function as dietary supplements
- Replacement for all antibiotics
Correct Answer: Antiprotozoal agents and DNA-intercalating chemotherapeutics (research tools)
Q40. Which factor is least likely to affect the outcome of an acridine synthesis?
- Choice of aromatic substituents and their electronic effects
- Reaction temperature and catalyst identity
- Solvent and concentration
- Color of the reaction vessel unrelated to light exposure
Correct Answer: Color of the reaction vessel unrelated to light exposure
Q41. N-alkylation of acridine nitrogen typically gives which class of compounds?
- Quaternary ammonium salts (if fully alkylated) or N-alkyl acridinium derivatives
- Carboxylic acids directly
- Simple alkanes by C–N bond cleavage
- Fully aromatized benzene derivatives only
Correct Answer: Quaternary ammonium salts (if fully alkylated) or N-alkyl acridinium derivatives
Q42. During mechanism study, which intermediate explains the planarity and conjugation of acridine after cyclization?
- The acridone intermediate that undergoes deoxygenation to produce a planar acridine system
- A twisted sp3 intermediate that remains non-conjugated
- A saturated bicyclic alkane intermediate
- A free radical that immediately fragments
Correct Answer: The acridone intermediate that undergoes deoxygenation to produce a planar acridine system
Q43. Which lab reagent would you choose to oxidize a dihydroacridine to acridine during work-up?
- DDQ or air in presence of Pd/C for dehydrogenation
- Sodium borohydride as a reducing agent
- Liquid ammonia to hydrogenate
- Tetramethylsilane as an inert solvent
Correct Answer: DDQ or air in presence of Pd/C for dehydrogenation
Q44. Why are acridine derivatives often brightly colored?
- Extended conjugation in the fused aromatic system leads to visible light absorption
- Presence of long aliphatic chains that reflect light
- They are colorless but appear colored due to impurities only
- Only because they form complexes with metals
Correct Answer: Extended conjugation in the fused aromatic system leads to visible light absorption
Q45. Which substitution pattern generally increases electron density on the acridine ring and enhances reactivity toward electrophiles?
- Electron-donating substituents (e.g., methoxy) on the peripheral rings
- Strong electron-withdrawing groups (e.g., nitro) only
- Bulky inert substituents with no electronic effect
- Halogens that always deactivate through resonance only
Correct Answer: Electron-donating substituents (e.g., methoxy) on the peripheral rings
Q46. A student isolates an acridine derivative as a yellow solid with strong UV absorption. The best next step to confirm structure is:
- Record 1H and 13C NMR and compare with literature data
- Only measure melting point and stop
- Assume identity based on color alone
- Dispose of the sample without analysis
Correct Answer: Record 1H and 13C NMR and compare with literature data
Q47. In medicinal chemistry, why might an acridine core be modified rather than used unchanged?
- To reduce toxicity, improve selectivity, and tune pharmacokinetic properties
- To make it more mutagenic for research purposes only
- Because acridine cannot be synthesized reliably
- To eliminate all aromaticity for better activity
Correct Answer: To reduce toxicity, improve selectivity, and tune pharmacokinetic properties
Q48. Which statement about scale-up of acridine synthesis is practical for B. Pharm students to consider?
- Heat management and safe handling of Lewis acids/oxidants are critical when moving from milligram to gram scale
- Scale-up never requires additional safety or engineering controls
- All reactions scale linearly without change in conditions
- Using larger glassware is sufficient without changing waste management
Correct Answer: Heat management and safe handling of Lewis acids/oxidants are critical when moving from milligram to gram scale
Q49. Which experimental observation would suggest formation of acridone rather than fully aromatized acridine?
- Presence of a carbonyl stretch in the IR spectrum
- Complete lack of any IR bands
- Strong NMR signals only at 0–1 ppm
- Immediate flame on contact with air
Correct Answer: Presence of a carbonyl stretch in the IR spectrum
Q50. For exam-style synthetic design, which combination of reagents is most appropriate to attempt a Bernthsen-type formation of acridine from diphenylamine and benzoic acid?
- ZnCl2 as Lewis acid, high temperature (heating), and dehydrating conditions
- Cold aqueous NaOH without catalyst
- Only catalytic hydrogenation with H2/Pd at 25°C
- Photochemical irradiation with no catalyst and water solvent
Correct Answer: ZnCl2 as Lewis acid, high temperature (heating), and dehydrating conditions
