Solvent requirements in NMR MCQs With Answer

Introduction: Solvent requirements in NMR MCQs With Answer is a targeted study aid for M.Pharm students preparing for Advanced Instrumental Analysis. This blog focuses on the critical role of solvents in NMR spectroscopy — why deuteration is needed, how solvent polarity, viscosity, and hydrogen-bonding influence chemical shifts and relaxation times, and how solvent impurities and residual peaks affect spectral interpretation. It also covers practical choices for 1H, 13C and heteronuclear NMR, solvent suppression methods, referencing and locking strategies, and handling exchangeable protons. The MCQs are designed to test conceptual understanding and practical decision-making required for accurate NMR data acquisition and analysis in pharmaceutical research.

Q1. Why are deuterated solvents commonly used in proton (1H) NMR spectroscopy?

• They provide a source of protons to enhance signal strength
• They reduce proton background signals and enable spectrometer locking
• They chemically react with analytes to form stable complexes
• They increase sample viscosity to improve shimming

Correct Answer: They reduce proton background signals and enable spectrometer locking

Q2. Which property of a solvent most directly affects the chemical shift of solute protons through dielectric effects?

• Boiling point
• Dielectric constant (polarity)
• Viscosity
• Vapor pressure

Correct Answer: Dielectric constant (polarity)

Q3. What is the primary purpose of adding tetramethylsilane (TMS) to an NMR sample?

• To act as a relaxation agent and shorten T1 times
• To function as an internal chemical shift reference at 0 ppm
• To increase solubility of polar analytes in organic solvents
• To suppress solvent residual peaks during acquisition

Correct Answer: To function as an internal chemical shift reference at 0 ppm

Q4. Which deuterated solvent is most appropriate for dissolving highly polar, hydrogen-bonding pharmaceutical compounds for 1H NMR?

• CDCl3 (deuterated chloroform)
• DMSO-d6 (deuterated dimethyl sulfoxide)
• C6D6 (deuterated benzene)
• CD2Cl2 (deuterated dichloromethane)

Correct Answer: DMSO-d6 (deuterated dimethyl sulfoxide)

Q5. Residual solvent peaks are often observed in 1H NMR. Which strategy is best to identify them?

• Assume all small singlets are impurities and ignore them
• Compare observed peaks with a published table of residual solvent chemical shifts
• Only use TMS as an internal standard and do not consider residual peaks
• Always evaporate the solvent completely before running NMR

Correct Answer: Compare observed peaks with a published table of residual solvent chemical shifts

Q6. Which solvent property most strongly affects line broadening and longer T1 relaxation times in NMR spectra?

• High dielectric constant
• High viscosity
• Low vapor pressure
• Low refractive index

Correct Answer: High viscosity

Q7. For quantitative 1H NMR (qNMR) of a drug molecule, which solvent consideration is most important?

• Use any non-deuterated solvent to maximize signal
• Select a solvent with minimal overlapping residual peaks and stable baseline
• Choose the most viscous solvent available
• Always add paramagnetic impurities to shorten acquisition time

Correct Answer: Select a solvent with minimal overlapping residual peaks and stable baseline

Q8. Which deuterated solvent is commonly used for 13C NMR when minimizing 1H–13C coupling is desired?

• CDCl3 because it provides good signal and minimal proton coupling with 13C when proton-decoupled
• C6D6 because aromatic solvents fully eliminate 1H–13C coupling
• D2O because it contains no 13C and thus reduces coupling
• Py-d5 because nitrogen-containing solvents do not couple to 13C

Correct Answer: CDCl3 because it provides good signal and minimal proton coupling with 13C when proton-decoupled

Q9. Why is D2O frequently used for NMR studies of exchangeable protons (–OH, –NH)?

• D2O stabilizes exchangeable protons, making them sharper in the spectrum
• Exchange with deuterium removes the 1H signals of exchangeable protons, simplifying spectra
• D2O increases chemical shift dispersion for protons
• D2O has a lower boiling point that helps in evaporation post-acquisition

Correct Answer: Exchange with deuterium removes the 1H signals of exchangeable protons, simplifying spectra

Q10. Which practice reduces water signal interference when recording 1H NMR in aqueous or partially aqueous samples?

• Adding excess TMS to mask the water peak
• Using water suppression pulse sequences (e.g., presaturation, WATERGATE)
• Increasing acquisition temperature to evaporate water
• Switching to non-deuterated solvents to dilute water signal

Correct Answer: Using water suppression pulse sequences (e.g., presaturation, WATERGATE)

Q11. How can paramagnetic impurities in solvent affect NMR spectra?

• They sharpen peaks by reducing T2 relaxation times
• They broaden peaks and shift chemical shifts due to enhanced relaxation and paramagnetic shifts
• They only affect IR spectra, not NMR
• They increase solvent deuterium content by catalyzing exchange

Correct Answer: They broaden peaks and shift chemical shifts due to enhanced relaxation and paramagnetic shifts

Q12. Which solvent choice is least appropriate for studying a nonpolar aromatic drug molecule by 1H NMR?

• C6D6 (deuterated benzene)
• CDCl3 (deuterated chloroform)
• DMSO-d6 (deuterated dimethyl sulfoxide)
• CD3OD (deuterated methanol)

Correct Answer: CD3OD (deuterated methanol)

Q13. What is one major reason to degas NMR solvents before sample preparation?

• To remove dissolved oxygen that can cause paramagnetic broadening
• To increase solvent polarity for better solubility
• To add deuterium to non-deuterated solvents
• To sterilize the solvent for biological assays

Correct Answer: To remove dissolved oxygen that can cause paramagnetic broadening

Q14. When performing heteronuclear 15N NMR, which solvent feature is particularly important?

• Low refractive index
• Minimal 1H exchange with 15N and compatibility with heteronuclear decoupling
• High aromatic content to increase sensitivity
• High chlorine content to enhance 15N relaxation

Correct Answer: Minimal 1H exchange with 15N and compatibility with heteronuclear decoupling

Q15. How does solvent hydrogen bonding with a solute typically affect proton chemical shifts?

• Hydrogen bonding always causes upfield shifts
• Hydrogen bonding generally causes downfield shifts of the involved protons
• Hydrogen bonding eliminates the proton signals completely
• Hydrogen bonding has no measurable effect on chemical shift

Correct Answer: Hydrogen bonding generally causes downfield shifts of the involved protons

Q16. Which solvent is recommended when using cryoprobes for improved sensitivity but where low freezing point is necessary?

• C6D6 because it has the lowest freezing point of common solvents
• DMSO-d6 because it prevents freezing in cryoprobes
• CD3OD since methanol-d4 has relatively low freezing point and good polarity
• H2O because it provides best locking for cryoprobes

Correct Answer: CD3OD since methanol-d4 has relatively low freezing point and good polarity

Q17. In 2D NMR experiments (e.g., HSQC, HMBC), why is solvent choice critical?

• Because solvent determines the temperature the probe can withstand
• Because solvent residual signals and viscosity affect coherence transfer and sensitivity
• Because only aromatic solvents provide long-lived coherences
• Because solvents with halogens enhance heteronuclear coupling constants

Correct Answer: Because solvent residual signals and viscosity affect coherence transfer and sensitivity

Q18. Which statement about residual deuterium signals used for locking is correct?

• Protonated solvents provide the best lock signal
• Residual deuterium in deuterated solvents provides a lock frequency with minimal interference in 1H spectrum
• Locking is unnecessary if TMS is used as a reference
• Locking is only required for 13C NMR, not 1H

Correct Answer: Residual deuterium in deuterated solvents provides a lock frequency with minimal interference in 1H spectrum

Q19. Which practice helps minimize solvent-related peak overlap with analyte signals in routine 1H NMR?

• Use the most concentrated sample possible regardless of solubility
• Screen several deuterated solvents and choose one with non-overlapping residual peaks
• Always use C6D6 to push aromatic signals upfield
• Reduce acquisition time to avoid observing solvent peaks

Correct Answer: Screen several deuterated solvents and choose one with non-overlapping residual peaks

Q20. Which factor is least important when selecting a solvent for high-resolution NMR of a pharmaceutical compound?

• Solvent’s ability to dissolve the analyte at required concentration
• Compatibility with the NMR probe and absence of paramagnetic impurities
• Solvent’s color and odor for lab comfort
• Presence and position of residual solvent peaks relative to analyte signals

Correct Answer: Solvent’s color and odor for lab comfort

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