100+ NMR Questions & Answers
1. Basics of NMR (Q1–Q10)
Q1: What is NMR spectroscopy?
A: NMR spectroscopy is a technique that uses the magnetic properties of
atomic nuclei to determine molecular structure.
Q2: Why is NMR important in R&D?
A: It helps identify and confirm molecular structures, monitor
reactions, and analyze purity.
Q3: What is the basic principle of NMR?
A: It involves resonance absorption of radiofrequency radiation by
nuclei in a magnetic field.
Q4: Which nuclei are NMR-active?
A: Nuclei with non-zero spin, like ¹H, ¹³C, ¹⁹F, and ³¹P, are
NMR-active.
Q5: What does "chemical shift" mean?
A: Chemical shift is the position of a resonance relative to a standard,
measured in ppm.
Q6: Why do we measure NMR in ppm?
A: PPM normalizes the resonance frequency and makes data comparable
across instruments.
Q7: What is Larmor frequency?
A: It is the frequency at which a nucleus precesses in a magnetic field.
Q8: What is relaxation time (T1 and T2)?
A: T1 is spin-lattice relaxation, and T2 is spin-spin relaxation time,
affecting peak shape.
Q9: What is the role of superconducting magnets in
NMR?
A: They generate strong and stable magnetic fields for high-resolution
spectra.
Q10: Why is NMR non-destructive?
A: Samples remain unchanged because NMR uses non-ionizing radio waves.
2. ¹H
NMR Fundamentals (Q11–Q20)
Q11: What information does ¹H NMR provide?
A: It reveals the number and environment of hydrogen atoms in a
molecule.
Q12: Why are hydrogen signals split into multiplets?
A: Because of spin-spin coupling with neighboring protons.
Q13: What does integration in ¹H NMR indicate?
A: It shows the relative number of protons producing each signal.
Q14: Why do aliphatic protons appear upfield?
A: They are less deshielded compared to aromatic or electronegative
environments.
Q15: How do electronegative groups affect proton shifts?
A: They pull electron density, deshielding protons and shifting peaks
downfield.
Q16: What is the typical range for ¹H chemical
shifts?
A: Most ¹H signals appear between 0–12 ppm.
Q17: Why is deuterated solvent used in ¹H NMR?
A: It avoids overlapping proton signals and provides a lock signal.
Q18: What is a singlet in ¹H NMR?
A: A peak with no splitting, indicating no adjacent protons.
Q19: What is the 'n+1' rule?
A: A proton with 'n' neighbors splits into 'n+1' peaks.
Q20: How do you interpret a triplet vs quartet?
A: Triplet: 2 neighbors; Quartet: 3 neighbors, common in –CH2–CH3
patterns.
3. ¹³C NMR Basics (Q21–Q30)
Q21: What is ¹³C NMR?
A: It is NMR spectroscopy of carbon-13 nuclei to determine carbon
skeletons of molecules.
Q22: Why is ¹³C less sensitive than ¹H?
A: ¹³C has lower natural abundance (~1.1%) and a smaller magnetic
moment.
Q23: What is broadband decoupling?
A: A technique to remove splitting from attached protons, giving singlet
peaks for carbons.
Q24: Why do ¹³C spectra take longer to record?
A: Low sensitivity requires longer acquisition times and more scans.
Q25: What is the typical chemical shift range of ¹³C?
A: 0–220 ppm for most organic compounds.
Q26: Why is TMS also used for ¹³C reference?
A: It provides a 0 ppm reference, similar to ¹H NMR.
Q27: What are DEPT experiments?
A: They differentiate CH, CH2, and CH3 groups using polarization
transfer.
Q28: Why do quaternary carbons have weak signals?
A: They relax slower and do not benefit from NOE enhancements.
Q29: How does hybridization affect ¹³C shifts?
A: sp2 carbons appear downfield (~100–160 ppm), sp3 upfield (~0–50 ppm).
Q30: Why is ¹³C NMR crucial for structure
elucidation?
A: It reveals unique carbon environments not visible in ¹H NMR.
4. Chemical Shifts & Factors (Q31–Q40)
Q31: What causes chemical shift differences?
A: Electron density, hybridization, electronegativity, and aromatic ring
currents.
Q32: Why do aromatic protons appear around 7 ppm?
A: Due to deshielding from aromatic ring current effects.
Q33: Why do aldehyde protons appear near 9-10 ppm?
A: The deshielding effect of the carbonyl group pushes peaks downfield.
Q34: Why are vinyl protons (alkenes) around 5-6 ppm?
A: They are deshielded due to sp2 hybridization.
Q35: How does hydrogen bonding affect shifts?
A: Hydrogen bonding causes downfield shifts for –OH and –NH protons.
Q36: What is shielding in NMR?
A: Shielding means electrons protect the nucleus, shifting signals
upfield.
Q37: What is deshielding?
A: When electron density is pulled away, making nuclei absorb at lower
fields (downfield).
Q38: Why do alkyl protons appear upfield (0.5-2 ppm)?
A: They are highly shielded compared to functional groups.
Q39: How does solvent affect chemical shifts?
A: Polar solvents can cause small downfield shifts by interacting with
molecules.
Q40: What is anisotropy effect?
A: Magnetic fields generated by π electrons cause directional shielding
or deshielding.
5. Spin-Spin Coupling (Q41–Q50)
Q41: What is spin-spin coupling?
A: It is the splitting of NMR signals due to interactions between
neighboring spins.
Q42: What is a coupling constant?
A: The distance between split peaks, measured in Hz.
Q43: Why do CH2 groups show triplets?
A: The 2 protons couple with adjacent protons following the n+1 rule.
Q44: What are geminal couplings?
A: Coupling between two protons on the same carbon.
Q45: What are vicinal couplings?
A: Coupling between protons three bonds apart.
Q46: What is typical J value for vicinal protons?
A: Usually 6-8 Hz for alkyl groups.
Q47: Why do aromatic protons have smaller J values?
A: They are farther apart and have weaker coupling (~7-9 Hz ortho).
Q48: What is long-range coupling?
A: Coupling through more than three bonds, visible in conjugated
systems.
Q49: How does dihedral angle affect J?
A: Karplus relationship: coupling depends on angle between protons.
Q50: Why is fluorine coupling noticeable?
A: ¹⁹F has a strong magnetic moment, giving large J values
6. 2D NMR (COSY, HSQC, HMBC, NOESY) (Q51–Q60)
Q51: What is COSY?
A: Correlation Spectroscopy shows which protons are coupled to each
other.
Q52: What is HSQC?
A: Heteronuclear Single Quantum Coherence links ¹H with directly bonded
¹³C.
Q53: What is HMBC?
A: Heteronuclear Multiple Bond Correlation shows long-range ¹H-¹³C
couplings.
Q54: What is NOESY?
A: Nuclear Overhauser Effect Spectroscopy shows spatial proximity of
protons.
Q55: Why use 2D NMR?
A: To resolve overlapping peaks and determine connectivity of atoms.
Q56: What is TOCSY?
A: Total Correlation Spectroscopy highlights spin networks.
Q57: What is the difference between HSQC and HMQC?
A: HSQC is more sensitive and uses polarization transfer.
Q58: What is ROESY?
A: Rotating frame NOE spectroscopy, useful when NOESY fails.
Q59: Why is 2D NMR time-consuming?
A: It requires multiple scans and complex pulse sequences.
Q60: Where is 2D NMR crucial in R&D?
A: In drug structure confirmation and complex natural product analysis.
7. Solvent & Sample Preparation Tips (Q61–Q70)
Q61: Why use deuterated solvents?
A: They minimize background ¹H signals and allow spectrometer locking.
Q62: What are common deuterated solvents?
A: CDCl₃, DMSO-d6, CD₃OD, acetone-d6, benzene-d6.
Q63: Why is TMS added to NMR samples?
A: As an internal reference at 0 ppm.
Q64: How much sample is needed for NMR?
A: Typically 5-20 mg in 0.6 mL solvent.
Q65: Why avoid water contamination?
A: Water peaks interfere with spectral interpretation.
Q66: What is shimming?
A: Adjusting the magnetic field for better resolution.
Q67: What is spinning in NMR tubes?
A: It averages out field inhomogeneities.
Q68: Why use thin-walled NMR tubes?
A: To reduce background and improve sensitivity.
Q69: What are residual solvent peaks?
A: Remaining non-deuterated solvent signals (e.g., CHCl₃ at 7.26 ppm).
Q70: Why filter samples?
A: To avoid line broadening from particulates.
8. Troubleshooting & Common Errors (Q71–Q80)
Q71: Why are peaks broad?
A: Due to poor shimming, impurities, or paramagnetic species.
Q72: What causes baseline distortions?
A: Improper phasing or solvent suppression issues.
Q73: Why is there no signal?
A: Low sample concentration, wrong frequency, or instrument error.
Q74: Why do signals overlap?
A: Complex mixtures or insufficient resolution.
Q75: What causes spinning sidebands?
A: Artifacts from sample spinning.
Q76: How to fix phase errors?
A: Adjust zero and first-order phase correction.
Q77: Why is lock signal important?
A: It stabilizes magnetic field during acquisition.
Q78: What causes noisy spectra?
A: Low concentration or insufficient scans (NS).
Q79: Why use multiple scans?
A: To improve signal-to-noise ratio (SNR).
Q80: What is solvent suppression?
A: A technique to remove strong solvent peaks.
9. Advanced NMR Techniques (Q81–Q90)
Q81: What is qNMR?
A: Quantitative NMR for determining purity or concentration.
Q82: What is DEPT-90?
A: It shows only CH groups.
Q83: What is DEPT-135?
A: CH and CH3 appear positive, CH2 negative.
Q84: What is INEPT?
A: Insensitive nuclei enhanced by polarization transfer.
Q85: What is APT?
A: Attached Proton Test, shows CH/CH3 vs CH2 carbons.
Q86: What is solid-state NMR?
A: NMR of solid samples using MAS (magic angle spinning).
Q87: What is MAS?
A: Magic Angle Spinning averages out anisotropic interactions.
Q88: What is CP-MAS?
A: Cross polarization combined with MAS for ¹³C in solids.
Q89: What is dynamic nuclear polarization?
A: Enhancing NMR signals via electron polarization transfer.
Q90: Where is qNMR used in pharma?
A: For assay of API purity and standardization.
10. Applications & Recommendations (Q91–Q100)
Q91: How is NMR used for API structure confirmation?
A: By comparing chemical shifts and coupling patterns with reference
data.
Q92: How does NMR help in impurity profiling?
A: It detects unknown impurities by 1D and 2D spectra.
Q93: How is qNMR used in R&D?
A: To quantify active ingredients and impurities.
Q94: What role does NMR play in reaction monitoring?
A: It tracks reaction intermediates in real-time.
Q95: Why use NMR over IR?
A: NMR provides detailed structural information, not just functional
groups.
Q96: What is in vivo NMR?
A: NMR used for studying metabolic changes in living systems.
Q97: Why is NMR critical for polymorphism studies?
A: Solid-state NMR identifies different crystalline forms.
Q98: How does NMR complement mass spectrometry?
A: MS gives molecular weight, NMR gives structure.
Q99: What is metabolite identification?
A: NMR characterizes drug metabolites in biological fluids.
Q100: What are future trends in NMR?
A: Benchtop NMR, AI-driven analysis, and ultra-fast 2D techniques.
