Amides – structure and properties MCQs With Answer

Amides – structure and properties MCQs With Answer: For B.Pharm students, understanding amide structure, resonance stabilization, and physicochemical properties is essential in pharmaceutical chemistry. This concise guide covers amide bonding, planarity, N‑substitution (primary, secondary, tertiary amides), hydrogen bonding, polarity, hydrolysis mechanisms (acidic and basic), synthesis from carboxylic acids and acyl chlorides, and analytical identification by IR and NMR. Emphasizing reactivity differences between amides, esters, and anilides helps in drug design and metabolism studies. Practice with targeted MCQs will reinforce concepts like rotational barriers, basicity, solubility, and spectroscopic signatures relevant to formulation and medicinal chemistry. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which resonance form contributes most to the stabilization of the amide bond?

• Neutral form with a C=O double bond and an N lone pair delocalized
• Iminium-like form with a C–N double bond and positive charge on nitrogen
• Carbanion form with negative carbonyl carbon
• Ether-like form with C–O–N connectivity

Correct Answer: Iminium-like form with a C–N double bond and positive charge on nitrogen

Q2. Which statement best explains why amides are less reactive toward nucleophilic acyl substitution than esters?

• Amides lack a carbonyl group
• Resonance donation from nitrogen decreases carbonyl electrophilicity
• Amides cannot form tetrahedral intermediates
• Amides have stronger leaving groups than esters

Correct Answer: Resonance donation from nitrogen decreases carbonyl electrophilicity

Q3. Which feature of an amide leads to partial double-bond character in the C–N bond?

• Hyperconjugation from alkyl groups
• n→π* resonance from nitrogen lone pair into the carbonyl
• Strong inductive electron withdrawal by nitrogen
• Hydrogen bonding to solvent

Correct Answer: n→π* resonance from nitrogen lone pair into the carbonyl

Q4. What is the typical IR carbonyl stretching frequency range for simple amides?

• 2100–2200 cm⁻¹
• 3200–3400 cm⁻¹
• 1640–1690 cm⁻¹
• 1750–1850 cm⁻¹

Correct Answer: 1640–1690 cm⁻¹

Q5. Which reagent is commonly used to reduce an amide to an amine?

• LiAlH4 (lithium aluminium hydride)
• PCC (pyridinium chlorochromate)
• KMnO4 (potassium permanganate)
• m-CPBA (meta-chloroperbenzoic acid)

Correct Answer: LiAlH4 (lithium aluminium hydride)

Q6. Which method is commonly used to synthesize amides from carboxylic acids in peptide chemistry?

• Friedel–Crafts acylation
• DCC (dicyclohexylcarbodiimide) coupling with amine
• Bromination followed by elimination
• Oxidative cleavage

Correct Answer: DCC (dicyclohexylcarbodiimide) coupling with amine

Q7. Which property of amides contributes to higher boiling points compared to corresponding hydrocarbons?

• Low molecular weight
• Strong hydrogen bonding and polarity
• Lack of dipole moment
• Weak London dispersion forces

Correct Answer: Strong hydrogen bonding and polarity

Q8. In Hofmann rearrangement, a primary amide is converted into which product?

• Secondary amide
• Primary amine with one fewer carbon atom
• Carboxylic acid with one extra carbon
• Nitrile

Correct Answer: Primary amine with one fewer carbon atom

Q9. Which statement about amide basicity is correct?

• Amides are stronger bases than aliphatic amines
• Amides are significantly less basic than amines due to delocalization
• Amide nitrogen is always protonated at physiological pH
• Tertiary amides are more basic than primary amides

Correct Answer: Amides are significantly less basic than amines due to delocalization

Q10. Which spectroscopic technique is most useful for identifying the amide N–H proton in small molecules?

• Mass spectrometry
• Infrared spectroscopy only
• 1H NMR spectroscopy
• UV–Vis spectroscopy

Correct Answer: 1H NMR spectroscopy

Q11. Which amide type cannot form N–H hydrogen bonds?

• Primary amide
• Secondary amide
• Tertiary amide
• Imide

Correct Answer: Tertiary amide

Q12. What structural feature gives peptides their planar amide bond geometry?

• Free rotation around the C–N bond
• Partial double-bond character of C–N due to resonance
• Steric hindrance from side chains only
• Hydrogen bonding with solvents exclusively

Correct Answer: Partial double-bond character of C–N due to resonance

Q13. Which reagent converts an amide into a nitrile under dehydrating conditions?

• PCl5 (phosphorus pentachloride)
• SOCl2 (thionyl chloride) or P2O5 with heating
• NaBH4 (sodium borohydride)
• H2, Pt catalyst

Correct Answer: SOCl2 (thionyl chloride) or P2O5 with heating

Q14. Which hydrolysis condition will most effectively cleave an amide to a carboxylic acid and amine?

• Neutral aqueous conditions at room temperature
• Strong acid or strong base with heating
• Dry ether at low temperature
• Photolysis at ambient temperature

Correct Answer: Strong acid or strong base with heating

Q15. In 13C NMR, where does the amide carbonyl carbon typically resonate relative to esters?

• At much higher field (lower ppm) than esters
• At similar but slightly lower frequency than esters due to resonance
• Outside the observable 13C range
• At identical chemical shifts for all carbonyls

Correct Answer: At similar but slightly lower frequency than esters due to resonance

Q16. Which of the following best describes the influence of N-substitution on amide resonance?

• N-alkylation always increases resonance and planarity
• Bulky N-substituents can reduce resonance by steric twisting
• N-substitution converts amides into esters
• Only aromatic N-substitution affects resonance

Correct Answer: Bulky N-substituents can reduce resonance by steric twisting

Q17. Which named reaction transforms an acyl chloride and an amine directly into an amide?

• Fischer esterification
• Schotten–Baumann reaction (acylation under basic aqueous conditions)
• Wittig reaction
• Diels–Alder reaction

Correct Answer: Schotten–Baumann reaction (acylation under basic aqueous conditions)

Q18. Which of the following increases amide hydrolysis rate significantly?

• Electron-donating substituents on the carbonyl carbon
• Strong electron-withdrawing groups on the carbonyl or adjacent positions
• Increased resonance stabilization
• Steric protection around the carbonyl

Correct Answer: Strong electron-withdrawing groups on the carbonyl or adjacent positions

Q19. What is the product of aminolysis of an ester by an amine under appropriate conditions?

• Alcohol and amide
• Ketone and ammonia
• Carboxylic acid and ether
• Nitrile and water

Correct Answer: Alcohol and amide

Q20. Which factor most strongly lowers the basicity of an amide nitrogen?

• Solvent polarity only
• Delocalization of the lone pair into the carbonyl group
• Steric hindrance around nitrogen only
• Presence of an adjacent aromatic ring exclusively

Correct Answer: Delocalization of the lone pair into the carbonyl group

Q21. Which amide derivative is commonly used as a protecting group for carboxylic acids during peptide synthesis?

• Tert-butyloxycarbonyl (Boc) on the amine
• Alcohol ester
• Thioester
• Acyl chloride

Correct Answer: Tert-butyloxycarbonyl (Boc) on the amine

Q22. Which observation indicates intramolecular hydrogen bonding in a primary amide by IR?

• Absence of N–H stretch bands
• Shift of N–H stretch to lower frequency and broadening
• Appearance of a strong peak at 2200 cm⁻¹
• No change in IR spectrum compared to free N–H

Correct Answer: Shift of N–H stretch to lower frequency and broadening

Q23. Which reagent is used in the Curtius rearrangement precursor step to convert acyl chloride to an acyl azide?

• Sodium azide (NaN3)
• Lithium aluminium hydride
• PCC
• Grignard reagent

Correct Answer: Sodium azide (NaN3)

Q24. Which of the following correctly ranks reactivity toward nucleophilic acyl substitution (most to least)?

• Amide > Ester > Acid chloride
• Acid chloride > Anhydride > Ester > Amide
• Ester > Acid chloride > Amide
• Amide > Anhydride > Acid chloride

Correct Answer: Acid chloride > Anhydride > Ester > Amide

Q25. Which structural feature differentiates an anilide from an aliphatic amide?

• Anilide nitrogen is bonded to an aromatic ring
• Anilides lack carbonyl groups
• Anilides are tertiary amides only
• Anilides have sulfonyl groups instead of carbonyl

Correct Answer: Anilide nitrogen is bonded to an aromatic ring

Q26. During peptide bond formation, which atom acts as the nucleophile to attack the activated carboxyl carbon?

• Carbonyl oxygen of the acceptor
• Amino nitrogen of the incoming amino acid
• Alpha carbon of the donor amino acid
• Side-chain sulfur atom

Correct Answer: Amino nitrogen of the incoming amino acid

Q27. Which condition favors formation of the cis amide conformation in proline-containing peptides?

• Hydrogen bonding to water strongly favors trans only
• Steric similarity and ring constraints in proline increase cis population
• All amide bonds are exclusively trans
• High temperature exclusively favors cis

Correct Answer: Steric similarity and ring constraints in proline increase cis population

Q28. What is the expected effect of N-alkylation (to form tertiary amide) on amide IR N–H bands?

• N–H bands become more intense
• N–H bands disappear because tertiary amides lack N–H
• N–H band shifts to 3000 cm⁻¹ exactly
• N–H bands split into multiple peaks

Correct Answer: N–H bands disappear because tertiary amides lack N–H

Q29. Which reagent converts a primary amide to a primary amine while retaining carbon count (direct reduction)?

• LiAlH4 (lithium aluminium hydride)
• H2O2
• PCl3
• Br2 in alkaline solution

Correct Answer: LiAlH4 (lithium aluminium hydride)

Q30. What effect does conjugation of an amide with an aromatic ring (anilide) have on its resonance?

• No effect; resonance is identical to aliphatic amides
• Additional delocalization into the aromatic ring can reduce C=O electrophilicity
• Prevents formation of a carbonyl group
• Makes the amide more basic than aliphatic amides

Correct Answer: Additional delocalization into the aromatic ring can reduce C=O electrophilicity

Q31. Which functional group transformation directly converts an amide to an imine equivalent under dehydrating conditions?

• Beckmann rearrangement
• Dehydration to nitrile
• Loss of oxygen to form iminium species (e.g., via activation then elimination)
• Hydrolysis to carboxylic acid

Correct Answer: Loss of oxygen to form iminium species (e.g., via activation then elimination)

Q32. Why are amide bonds critical in drug metabolism studies?

• They are inert and never metabolized
• Their hydrolysis can change pharmacokinetics and generate active/inactive metabolites
• Amide bonds prevent all enzymatic interactions
• They always increase a drug’s half-life

Correct Answer: Their hydrolysis can change pharmacokinetics and generate active/inactive metabolites

Q33. Which analytical observation supports the presence of an amide rather than an ester?

• Strong C–O stretch at 1100 cm⁻¹ only
• N–H stretch(s) in IR and characteristic 1H NMR NH signals
• Mass spectrum showing M+ only
• Color change on addition of base

Correct Answer: N–H stretch(s) in IR and characteristic 1H NMR NH signals

Q34. Which of the following is a common activation strategy to form amides from carboxylic acids?

• Direct heating of acid and amine without catalysts
• Conversion to acid chloride or use of coupling reagents like EDC/HOBt
• Oxidation of the acid to an anhydride with KMnO4
• Photochemical activation only

Correct Answer: Conversion to acid chloride or use of coupling reagents like EDC/HOBt

Q35. Which structural change increases the rotational barrier around the C–N amide bond?

• Disruption of resonance with electron-withdrawing substituents
• Increased n→π* delocalization enhancing double-bond character
• Conversion to a tertiary amide always lowers barrier
• Solvation exclusively increases rotation freedom

Correct Answer: Increased n→π* delocalization enhancing double-bond character

Q36. Which reagent is used in the Beckmann rearrangement context (related to amide chemistry transformations)?

• Hydroxylamine to form oximes followed by acid promotes rearrangement to amides
• Lithium aluminium hydride for oxidation
• Sodium borohydride for nitrile formation
• Grignard reagent for hydrolysis

Correct Answer: Hydroxylamine to form oximes followed by acid promotes rearrangement to amides

Q37. How does replacing an amide oxygen with sulfur (thioamide) generally affect resonance and reactivity?

• Thioamides have identical properties to amides
• Thioamides show reduced resonance and different IR/NMR signatures; often more nucleophilic sulfur
• Thioamides are nonpolar gases at room temperature
• Thioamides cannot be hydrolyzed

Correct Answer: Thioamides show reduced resonance and different IR/NMR signatures; often more nucleophilic sulfur

Q38. Which of the following best describes the acidity of the N–H in a primary amide compared to an alcohol?

• Amide N–H is much more acidic than alcohol O–H
• Amide N–H is less acidic than alcohol O–H
• Amide N–H and alcohol O–H have identical pKa values
• Amide N–H is not acidic at all

Correct Answer: Amide N–H is less acidic than alcohol O–H

Q39. What is the expected solubility trend of simple amides in water with increasing chain length?

• Solubility increases as chain length increases
• Solubility decreases as hydrophobic chain length increases
• Chain length does not affect solubility
• All amides are insoluble in water regardless of chain length

Correct Answer: Solubility decreases as hydrophobic chain length increases

Q40. Which enzymatic activity typically hydrolyzes peptide (amide) bonds in biological systems?

• Kinases
• Peptidases or proteases
• Polymerases
• Dehydrogenases

Correct Answer: Peptidases or proteases

Q41. Which structural isomerism is commonly restricted in amides due to partial double-bond character?

• Cis–trans isomerism about the C–N bond is restricted; trans usually favored
• Optical isomerism about the carbonyl carbon
• Free rotation about the C–C alpha bond is restricted
• Amides freely isomerize between many conformers

Correct Answer: Cis–trans isomerism about the C–N bond is restricted; trans usually favored

Q42. In medicinal chemistry, replacing an ester with an amide in a lead compound most often leads to what change?

• Increased metabolic lability and faster clearance
• Increased metabolic stability and often reduced hydrolysis
• Conversion to an inactive salt form
• Spontaneous polymerization in vivo

Correct Answer: Increased metabolic stability and often reduced hydrolysis

Q43. Which reagent sequence converts an amide to a carboxylic acid selectively (hydrolysis) under mild conditions in the lab?

• Acidic hydrolysis with HCl and heat
• Strong reducing agent like LiAlH4
• Dehydration with SOCl2
• Treatment with Grignard reagent

Correct Answer: Acidic hydrolysis with HCl and heat

Q44. Which of the following best describes the effect of electron-donating groups on the nitrogen of an amide?

• They always make the amide nonplanar and highly reactive
• They can increase electron density on nitrogen, slightly enhancing resonance donation into carbonyl
• They convert the amide into a carboxylic acid
• They eliminate hydrogen bonding capability entirely

Correct Answer: They can increase electron density on nitrogen, slightly enhancing resonance donation into carbonyl

Q45. Which analytical technique will differentiate an amide from a nitrile most directly?

• Thin-layer chromatography alone
• IR spectroscopy: nitriles show a sharp band near 2250 cm⁻¹ while amides show carbonyl and N–H bands
• Simple smell test
• Both have identical IR spectra so cannot be distinguished

Correct Answer: IR spectroscopy: nitriles show a sharp band near 2250 cm⁻¹ while amides show carbonyl and N–H bands

Q46. Which type of amide is formed when ammonia reacts with an acyl chloride?

• Primary amide
• Tertiary amide
• Imide
• Nitrile

Correct Answer: Primary amide

Q47. Which of the following is a common industrial application of amides?

• Plasticizers and solvents such as N,N‑dimethylformamide (DMF)
• Inert gases for packaging
• Primary explosives exclusively
• Metal catalysts in polymerization only

Correct Answer: Plasticizers and solvents such as N,N‑dimethylformamide (DMF)

Q48. In peptide chemistry, which bond is the amide bond linking amino acids and what character does it show?

• A C–C bond with no resonance
• A peptide (amide) bond with partial double-bond character and restricted rotation
• A pure ionic bond between residues
• A hydrogen bond linking backbone atoms

Correct Answer: A peptide (amide) bond with partial double-bond character and restricted rotation

Q49. Which transformation converts an amide to an isocyanate under unusual conditions (useful in some syntheses)?

• Hofmann rearrangement of primary amide
• Beckmann rearrangement of ketoxime
• Curtius rearrangement of acyl azide
• Pinner reaction on nitriles

Correct Answer: Curtius rearrangement of acyl azide

Q50. Which of the following best summarizes why amide bond geometry and properties are crucial for B.Pharm students?

• Amide bonds are irrelevant to pharmaceuticals
• Amide geometry affects drug conformation, stability, metabolism, and interactions with biological targets
• Amide bonds always make drugs inactive
• Only aliphatic chains matter in drug design

Correct Answer: Amide geometry affects drug conformation, stability, metabolism, and interactions with biological targets

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.

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