Solvent requirements in NMR MCQs With Answer

Solvent requirements in NMR MCQs With Answer

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Solvent requirements in NMR MCQs With Answer

NMR spectroscopy is indispensable in Modern Pharmaceutical Analytical Techniques, especially for structure elucidation, impurity profiling, and formulation studies. A critical but often underestimated element is solvent selection. The right solvent ensures adequate solubility, chemical inertness, sharp lines, stable lock, and minimal interference with analyte signals. Deuterated solvents, water suppression strategies, residual solvent referencing, and control over exchangeable protons are all central to high-quality spectra. This quiz focuses on practical solvent requirements in 1H, 13C, 19F, and 31P NMR relevant to M. Pharm learners—covering deuterated solvents, residual peaks, pD adjustment, solvent effects on chemical shifts, temperature and viscosity considerations, and common pitfalls like acidic impurities and labile proton exchange. Test and deepen your understanding below.

Q1. Why are deuterated solvents primarily used in 1H NMR for routine pharmaceutical analysis?

  • They improve mass sensitivity via spin polarization transfer
  • They provide a 2H lock signal and minimize intense solvent 1H background
  • They shorten relaxation times (T1) of all analyte protons
  • They eliminate all solvent signals completely

Correct Answer: They provide a 2H lock signal and minimize intense solvent 1H background

Q2. Which deuterated solvent shows a characteristic residual 1H signal at about 7.26 ppm?

  • DMSO-d6
  • CD3OD
  • CDCl3
  • D2O (HDO)

Correct Answer: CDCl3

Q3. In 13C NMR, the deuterated chloroform solvent signal appears near 77.16 ppm. What is its typical multiplicity and why?

  • Singlet; 13C is decoupled from 1H
  • Triplet; 13C couples to the deuterium (2H) nucleus
  • Quartet; long-range coupling to 35Cl
  • Doublet; geminal coupling to residual 1H

Correct Answer: Triplet; 13C couples to the deuterium (2H) nucleus

Q4. In aqueous 1H NMR, which internal reference is preferred over TMS?

  • Tetramethylsilane (TMS)
  • DSS (sodium 2,2-dimethyl-2-silapentane-5-sulfonate)
  • Nitromethane
  • Adamantane

Correct Answer: DSS (sodium 2,2-dimethyl-2-silapentane-5-sulfonate)

Q5. What happens to labile protons (e.g., OH, NH) when the sample is run in D2O?

  • They are strongly upfield shifted but remain sharp
  • They often exchange with deuterium and may disappear from the 1H spectrum
  • They become severely split by deuterium with large J values
  • They always appear as broad singlets near 0 ppm

Correct Answer: They often exchange with deuterium and may disappear from the 1H spectrum

Q6. When adjusting acidity in D2O-based samples, what approximate correction relates pD to the glass-electrode pH reading?

  • pD ≈ pH meter reading − 0.4
  • pD ≈ pH meter reading + 0.4
  • pD ≈ pH meter reading − 1.0
  • pD ≈ pH meter reading + 1.0

Correct Answer: pD ≈ pH meter reading + 0.4

Q7. For 19F NMR of a fluorine-containing drug, which solvent minimizes interference from solvent fluorine signals?

  • Trifluoroacetic acid-d (TFA-d)
  • Hexafluorobenzene
  • CDCl3
  • Perfluorohexane

Correct Answer: CDCl3

Q8. Which factor is most critical for maintaining a stable field–frequency lock during acquisition?

  • High analyte concentration
  • Presence of a deuterated solvent to supply a 2H lock signal
  • Using 1H decoupling during 1H acquisition
  • Low receiver gain

Correct Answer: Presence of a deuterated solvent to supply a 2H lock signal

Q9. For a water-soluble peptide where amide exchange is not a concern, which solvent is most appropriate?

  • CDCl3
  • D2O
  • Benzene-d6
  • Acetonitrile-d3

Correct Answer: D2O

Q10. Which statement about residual solvent signals is TRUE?

  • Residual solvent 1H signals must be fully suppressed and cannot be used for referencing
  • Residual solvent 1H signals can serve as internal chemical shift references when TMS/DSS is absent
  • Residual solvent peaks appear only in 13C NMR
  • Residual solvent peaks are identical in all solvents and temperatures

Correct Answer: Residual solvent 1H signals can serve as internal chemical shift references when TMS/DSS is absent

Q11. How do strong hydrogen-bond-accepting solvents like DMSO-d6 typically affect NH/OH resonances?

  • They move significantly upfield and broaden due to faster exchange
  • They often shift downfield and sharpen by reducing exchange with water
  • They become multiplets due to coupling with deuterium
  • They are completely suppressed by solvent presaturation

Correct Answer: They often shift downfield and sharpen by reducing exchange with water

Q12. Why is rigorous drying of deuterated solvents important for 1H NMR of APIs with labile protons?

  • Water lowers the magnetic field homogeneity
  • Water produces extra peaks and accelerates exchange, causing broadening or loss of OH/NH signals
  • Water destroys deuterium lock permanently
  • Water reduces digital resolution

Correct Answer: Water produces extra peaks and accelerates exchange, causing broadening or loss of OH/NH signals

Q13. What is the impact of using a highly viscous solvent (e.g., glycerol-d8) on 1H NMR spectra?

  • Narrower lines due to faster molecular tumbling
  • Increased line broadening due to slower molecular tumbling
  • Complete elimination of J-coupling
  • Improved deuterium lock sensitivity

Correct Answer: Increased line broadening due to slower molecular tumbling

Q14. Which deuterated solvent commonly contains trace acidic impurities (e.g., HCl) that can degrade base-sensitive compounds?

  • CDCl3
  • CD3OD
  • DMSO-d6
  • THF-d8

Correct Answer: CDCl3

Q15. Which technique is routinely used to reduce the intensity of the solvent peak in 1H NMR without affecting other resonances significantly?

  • Cross-polarization
  • Presaturation (or selective solvent suppression)
  • Magic-angle spinning
  • Quadrature detection

Correct Answer: Presaturation (or selective solvent suppression)

Q16. Why is TMS generally not used as an internal reference in D2O-based 1H NMR?

  • It reacts with water to form silanols
  • It is poorly soluble in D2O
  • It has overlapping peaks with HDO
  • It broadens all analyte signals

Correct Answer: It is poorly soluble in D2O

Q17. For high-temperature NMR studies of a thermally stable drug, which solvent is most suitable?

  • CDCl3 (bp ≈ 61 °C)
  • DMSO-d6 (bp ≈ 189 °C)
  • Acetone-d6 (bp ≈ 56 °C)
  • CD2Cl2 (bp ≈ 40 °C)

Correct Answer: DMSO-d6 (bp ≈ 189 °C)

Q18. Which deuterated solvent has a characteristic residual 1H signal near 2.05 ppm?

  • Acetone-d6
  • Acetonitrile-d3
  • DMSO-d6
  • Benzene-d6

Correct Answer: Acetone-d6

Q19. For an aqueous 1H NMR sample acquired in H2O, how much D2O is typically added to enable a stable lock?

  • 1% v/v
  • 5% v/v
  • About 10% v/v
  • 50% v/v

Correct Answer: About 10% v/v

Q20. Which solvent–residual peak pairing is correctly matched for 1H NMR at 25 °C?

  • DMSO-d6: 1.94 ppm
  • CD3OD: 3.31 ppm
  • Benzene-d6: 2.50 ppm
  • D2O (HDO): 7.16 ppm

Correct Answer: CD3OD: 3.31 ppm

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