Synthesis of thiazole MCQs With Answer

Synthesis of thiazole MCQs With Answer: This concise introduction helps B. Pharm students grasp thiazole synthesis fundamentals and exam-focused concepts. Thiazole is a five-membered aromatic heterocycle (S and N heteroatoms) present in drugs and vitamins like thiamine (B1). Key topics covered include Hantzsch thiazole synthesis, α-haloketones, thioamides, mechanism steps (nucleophilic attack, cyclization, elimination), reagents (NBS, Lawesson’s reagent), reaction conditions, regioselectivity, spectroscopic identification and green/microwave methods. The MCQs emphasize practical lab considerations, spectral clues and medicinal relevance to reinforce learning for pharmacy exams. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the structural description of a thiazole ring?

• A six-membered aromatic ring with sulfur and oxygen
• A five-membered heterocycle containing sulfur and nitrogen
• A five-membered carbocycle with two double bonds
• A six-membered heterocycle with nitrogen and sulfur

Correct Answer: A five-membered heterocycle containing sulfur and nitrogen

Q2. Which positions do sulfur and nitrogen occupy in the standard numbering of thiazole?

• S at position 1 and N at position 3
• N at position 1 and S at position 3
• S at position 2 and N at position 4
• N at position 2 and S at position 5

Correct Answer: S at position 1 and N at position 3

Q3. How many π electrons contribute to the aromaticity of thiazole?

• 4 π electrons
• 6 π electrons
• 8 π electrons
• 10 π electrons

Correct Answer: 6 π electrons

Q4. Which classical synthetic route is most commonly taught for laboratory preparation of substituted thiazoles?

• Hantzsch thiazole synthesis
• Paal–Knorr synthesis
• Buchwald–Hartwig amination
• Fischer indole synthesis

Correct Answer: Hantzsch thiazole synthesis

Q5. The Hantzsch thiazole synthesis typically combines which two types of starting materials?

• α-Haloketones and thioamides
• Alkenes and amines
• Carboxylic acids and alcohols
• Diazonium salts and phenols

Correct Answer: α-Haloketones and thioamides

Q6. What is the initial nucleophilic site on a thioamide in the Hantzsch mechanism?

• Nitrogen atom
• Sulfur atom
• Carbonyl carbon
• Alpha-carbon

Correct Answer: Sulfur atom

Q7. Which leaving group is commonly displaced in α-haloketones during thiazole formation?

• Hydroxide
• Bromide or chloride
• Sulfonate ester
• Azide

Correct Answer: Bromide or chloride

Q8. Which reagent is often used to introduce an α-bromo substituent onto a ketone as a precursor for thiazole synthesis?

• N-Bromosuccinimide (NBS)
• Sodium borohydride
• m-CPBA
• Potassium permanganate

Correct Answer: N-Bromosuccinimide (NBS)

Q9. Which reagent is commonly used to convert an amide into a thioamide for thiazole synthesis?

• Lawesson’s reagent
• Sodium borohydride
• Chromic acid
• Hydrogen peroxide

Correct Answer: Lawesson’s reagent

Q10. In the Hantzsch thiazole synthesis mechanism, what is the key cyclization step?

• Electrophilic aromatic substitution on an aromatic ring
• Nucleophilic attack of sulfur followed by ring closure and elimination
• Radical addition to an alkene
• Pericyclic [4+2] cycloaddition

Correct Answer: Nucleophilic attack of sulfur followed by ring closure and elimination

Q11. Which common byproduct is formed during the cyclization of α-haloketones with thioamides?

• Water
• HX (e.g., HBr or HCl)
• Carbon dioxide
• Molecular hydrogen

Correct Answer: HX (e.g., HBr or HCl)

Q12. Which solvent type is frequently used to carry out Hantzsch thiazole reactions in the lab?

• Nonpolar solvent like hexane
• Polar protic solvent like ethanol
• Anhydrous ether only
• Liquid ammonia

Correct Answer: Polar protic solvent like ethanol

Q13. What is the typical laboratory workup to neutralize the acid formed during thiazole cyclization?

• Add strong acid
• Add base such as sodium bicarbonate
• Add oxidizing agent
• Evaporate without treatment

Correct Answer: Add base such as sodium bicarbonate

Q14. Which analytical technique gives the best definitive structural information for confirming thiazole formation and substitution pattern?

• Thin layer chromatography (TLC) alone
• Proton and carbon-13 NMR spectroscopy
• Simple melting point
• Paper chromatography

Correct Answer: Proton and carbon-13 NMR spectroscopy

Q15. In 1H NMR, aromatic protons of thiazole rings typically appear in which chemical shift range?

• 0–2 ppm
• 3–5 ppm
• 7–9 ppm
• 10–12 ppm

Correct Answer: 7–9 ppm

Q16. Which absorption band in IR spectroscopy is commonly associated with C=N or heteroaromatic stretches in thiazoles?

• Around 3400 cm⁻¹
• Around 1700 cm⁻¹
• Around 1600 cm⁻¹
• Around 2200 cm⁻¹

Correct Answer: Around 1600 cm⁻¹

Q17. Compared to pyridine, how basic is thiazole?

• Much more basic than pyridine
• About equally basic as pyridine
• Much less basic than pyridine
• Non-basic

Correct Answer: Much less basic than pyridine

Q18. Which position on the thiazole ring is most reactive toward electrophilic substitution?

• Position 2
• Position 3
• Position 4
• Position 5

Correct Answer: Position 5

Q19. Which functional group in thioamides directs nucleophilic attack during thiazole synthesis?

• Thione (C=S)
• Hydroxyl (OH)
• Ether (ROR)
• Nitro (NO2)

Correct Answer: Thione (C=S)

Q20. Which classical laboratory precaution is important when working with α-haloketones during thiazole synthesis?

• They are inert and need no special handling
• They can be volatile and lachrymatory; use fume hood and PPE
• They explode on contact with water
• They are strong oxidizers and require metal containers

Correct Answer: They can be volatile and lachrymatory; use fume hood and PPE

Q21. Which reagent is commonly used as a base to scavenge acid produced in Hantzsch reactions?

• Pyridinium chloride
• Sodium bicarbonate
• Hydrochloric acid
• Magnesium sulfate

Correct Answer: Sodium bicarbonate

Q22. Which of the following pharmaceuticals or biomolecules contains a thiazole moiety?

• Thiamine (Vitamin B1)
• Vitamin C (ascorbic acid)
• Acetylsalicylic acid
• Glucose

Correct Answer: Thiamine (Vitamin B1)

Q23. Which green chemistry technique can accelerate thiazole synthesis and improve yields in small-scale lab practice?

• Microwave-assisted synthesis
• Using excess heavy metal catalysts
• High-pressure hydrogenation
• Long room-temperature stirring only

Correct Answer: Microwave-assisted synthesis

Q24. In medicinal chemistry, why is the thiazole ring an important scaffold?

• It is highly unstable and rarely used
• It confers planarity, heteroatom interactions and metabolic stability
• It is only used as a solvent
• It prevents any biological activity

Correct Answer: It confers planarity, heteroatom interactions and metabolic stability

Q25. Which reagent would you choose to desulfurize a thioamide back to an amide (if needed during multistep synthesis)?

• P2S5
• Raney nickel (hydrogenolysis)
• Hydrochloric acid
• N-Bromosuccinimide

Correct Answer: Raney nickel (hydrogenolysis)

Q26. In designing a synthesis to a 2-amino-substituted thiazole, which nucleophile provides the amino functionality during ring formation?

• Thioamide with an amino substituent
• Alkyl halide
• Alcohol
• Carboxylic acid

Correct Answer: Thioamide with an amino substituent

Q27. Which reagent is most suitable to convert a carbonyl (C=O) to a thiocarbonyl (C=S) for preparing thioamide precursors?

• Lawesson’s reagent
• Sodium hydroxide
• Hydrogen peroxide
• Acetic anhydride

Correct Answer: Lawesson’s reagent

Q28. Which of the following is a common synthetic alternative to form substituted thiazoles via cyclodehydration?

• Condensation of α-halocarbonyl compounds with thioamides
• Radical chlorination of alkanes
• Direct oxidation of alkenes to epoxides
• Grignard addition to esters only

Correct Answer: Condensation of α-halocarbonyl compounds with thioamides

Q29. Which step in the Hantzsch thiazole synthesis increases conjugation and leads to aromatic stabilization?

• Initial protonation of solvent
• Elimination to form the C=C and C=N conjugated system
• Formation of a saturated cyclic ether
• Reduction to form an alkane

Correct Answer: Elimination to form the C=C and C=N conjugated system

Q30. In a substitution pattern analysis, which analytical method helps assign positions on the thiazole ring by observing coupling constants and chemical shifts?

• UV-Visible spectroscopy
• 1H and 13C NMR spectroscopy with 2D techniques
• Simple refractive index
• pH titration

Correct Answer: 1H and 13C NMR spectroscopy with 2D techniques

Q31. Which reagent is commonly used to prepare α-haloketones from ketones as precursors for thiazole synthesis?

• Phosphorus pentachloride (PCl5)
• Bromine in acetic acid or NBS
• Sodium cyanoborohydride
• Tert-butylhydroperoxide

Correct Answer: Bromine in acetic acid or NBS

Q32. Which of these is an expected mass spectral feature for simple substituted thiazoles?

• Strong M+ at extremely high m/z >1000 only
• Characteristic molecular ion and fragments corresponding to cleavage at ring substituents
• No molecular ion at all
• Only loss of nitrogen as N2

Correct Answer: Characteristic molecular ion and fragments corresponding to cleavage at ring substituents

Q33. Which protecting group is commonly used to protect amines during multistep thiazole synthesis?

• Tert-butyloxycarbonyl (Boc)
• Methyl group (no cleavage possible)
• Trifluoromethyl
• Nitro group

Correct Answer: Tert-butyloxycarbonyl (Boc)

Q34. During scale-up, which factor most commonly affects yield in thiazole syntheses?

• Color of the glassware only
• Stoichiometry, mixing, and heat transfer control
• Brand of magnetic stir bar
• Ambient music in the lab

Correct Answer: Stoichiometry, mixing, and heat transfer control

Q35. Which heteroatom contribution helps maintain aromaticity of thiazole?

• Both S and N contribute lone pairs equally to the π system
• N contributes a lone pair to the π system while S contributes one of its lone pairs
• Only carbon atoms contribute to aromaticity
• S and N do not contribute any electrons to the π system

Correct Answer: N contributes a lone pair to the π system while S contributes one of its lone pairs

Q36. In biosynthesis of the thiazole ring of thiamine, which amino acid is a key precursor?

• Lysine
• Cysteine
• Phenylalanine
• Glycine

Correct Answer: Cysteine

Q37. For introducing an electron-withdrawing substituent to the thiazole ring, which strategy is commonly used?

• Electrophilic nitration at an unactivated position
• Install substituent on precursor α-haloketone prior to cyclization
• Random oxidations after ring formation only
• Expose ring to UV light without reagents

Correct Answer: Install substituent on precursor α-haloketone prior to cyclization

Q38. Which catalyst class is frequently used for C–H activation and functionalization of thiazole rings in modern synthetic methods?

• Organocatalysts only
• Palladium or copper transition-metal catalysts
• Only radical photoinitiators
• Saccharide catalysts

Correct Answer: Palladium or copper transition-metal catalysts

Q39. When working with thioamides and α-haloketones, which side reaction can lower yield if not controlled?

• Polymerization of the solvent
• Hydrolysis of reactive intermediates to give diketones or amides
• Complete conversion to noble metals
• Spontaneous combustion

Correct Answer: Hydrolysis of reactive intermediates to give diketones or amides

Q40. Which substituent on the α-haloketone most directly influences regioselectivity of thiazole substitution?

• Substituent at the alpha-carbon adjacent to the carbonyl
• Substituent on solvent molecules
• Counterion of base only
• Color dye in reaction flask

Correct Answer: Substituent at the alpha-carbon adjacent to the carbonyl

Q41. Sulfathiazole is an example of a drug class in which the thiazole ring appears. Which class is it?

• Beta-lactam antibiotics
• Sulfonamide antibacterial agents
• Statins
• Antifungals only

Correct Answer: Sulfonamide antibacterial agents

Q42. Which step is crucial to purify crude thiazole product after reaction completion?

• Direct injection into biological assays
• Workup, extraction, drying and column chromatography or recrystallization
• Immediate freezing without purification
• Heating to 300 °C to sublime impurities

Correct Answer: Workup, extraction, drying and column chromatography or recrystallization

Q43. Which of the following statements about regiochemistry in thiazole synthesis is correct?

• Regiochemistry is random and cannot be influenced
• Regiochemistry can be directed by substituents on the α-haloketone and thioamide
• Only symmetrical products form regardless of precursors
• Thiazoles are always unsubstituted after synthesis

Correct Answer: Regiochemistry can be directed by substituents on the α-haloketone and thioamide

Q44. Which protective atmosphere is sometimes used when sensitive sulfur reagents are employed in thiazole synthesis?

• Oxygen-rich air
• Inert atmosphere such as nitrogen or argon
• Chlorine gas atmosphere
• Carbon monoxide atmosphere

Correct Answer: Inert atmosphere such as nitrogen or argon

Q45. If the reaction between an α-haloketone and a thioamide stalls, which practical troubleshooting step is reasonable?

• Add more solvent to dilute to 1 L regardless of scale
• Check stoichiometry, add mild base or raise temperature gradually
• Vigorously shake with bleach
• Discard reagents and start from scratch without analysis

Correct Answer: Check stoichiometry, add mild base or raise temperature gradually

Q46. During mechanism teaching, which intermediate is often shown immediately after nucleophilic attack of sulfur on the α-carbon?

• Carbanion stabilized by aromaticity
• Halide-stabilized carbocation
• Tetrahedral or salt-like intermediate bearing the nucleophile and leaving group
• Free radical centered on nitrogen

Correct Answer: Tetrahedral or salt-like intermediate bearing the nucleophile and leaving group

Q47. Which of the following is a green alternative reagent for halogenation that can be used in α-halogenation?

• Elemental chlorine bubbled in without control
• N-Bromosuccinimide (NBS) under controlled conditions
• Mercury(II) salts
• Lead tetraacetate

Correct Answer: N-Bromosuccinimide (NBS) under controlled conditions

Q48. For exam-level understanding, which description best summarizes the Hantzsch thiazole synthesis outcome?

• Formation of a saturated six-membered heterocycle
• Cyclization producing substituted aromatic thiazoles with loss of HX
• Conversion of thiazoles back to alkenes
• Oxidative cleavage of heterocycles

Correct Answer: Cyclization producing substituted aromatic thiazoles with loss of HX

Q49. Which laboratory hazard is particularly associated with many reagents used in thiazole synthesis (e.g., α-haloketones, brominating agents)?

• Radioactivity
• Lachrymation, corrosivity and toxicity requiring fume hood
• Spontaneous magnetization
• Instant sublimation to gases

Correct Answer: Lachrymation, corrosivity and toxicity requiring fume hood

Q50. For revision, which sequence correctly outlines a typical route to a substituted thiazole?

• Direct heating of aromatic ring with water
• Prepare α-haloketone → react with thioamide → cyclize → eliminate HX → purify
• Oxidize alkane to acid → esterify → distill
• Mix two amino acids and evaporate

Correct Answer: Prepare α-haloketone → react with thioamide → cyclize → eliminate HX → purify

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com