Chapter 9 — Exercises
Forty-five problems on NMR spectroscopy: chemical shifts, integration, multiplicity, coupling, ¹³C, DEPT, 2D, and combined IR/MS/NMR. ∗ = full solution in Appendix Answers to Selected Exercises.
Section A — Counting environments
9.1∗ (routine) For each compound, predict the number of distinct $^1H$ NMR environments: (a) methane (b) ethanol (c) 2-butanol (d) benzene (e) toluene (f) p-xylene (1,4-dimethylbenzene)
9.2 (routine) For each compound, predict the number of distinct $^{13}C$ NMR environments: (a) ethanol (b) methyl benzoate (c) cyclohexane (d) cyclohexanone (e) p-xylene
9.3 (moderate) Distinguish chemical equivalence from magnetic equivalence. Give an example of chemically equivalent but magnetically nonequivalent protons.
Section B — Splitting patterns
9.4∗ (routine) For each compound, predict the splitting pattern for each proton: (a) $CH_3CH_2Cl$ (b) $(CH_3)_2CHCl$ (c) $CH_3CH_2CH_3$ (d) $CH_3CHO$ (e) $ClCH_2CH_2Cl$ (f) $CH_3CH_2OCH_3$ (methyl ethyl ether)
9.5 (routine) Apply the n+1 rule to predict multiplicity: (a) -CH₃ next to -CH₂- = triplet (b) -CH₂- between two -CH₃ groups (each CH₃ split independently) = ? (c) -CH (with 6 equivalent neighbors) = ?
9.6 (moderate) A compound has 1H heptet (septet) at δ 4.0. What does this tell you about the carbon's neighbors?
Section C — Chemical shifts
9.7∗ (routine) Predict approximate chemical shifts for: (a) -CH₃ of toluene (b) aldehyde H in acetaldehyde (c) aromatic H of benzene (d) -OH of ethanol (e) vinyl H of propene (f) α-H to carbonyl in 2-butanone
9.8 (moderate) Why does the α-H of acetone (δ 2.15) appear at higher chemical shift than a typical alkane CH₃ (δ 0.9)?
9.9 (moderate) Why does the aromatic H of benzene (δ 7.26) appear at much higher chemical shift than a typical sp³ CH (δ 1-2)? (Hint: ring current.)
9.10 (challenge) Predict and explain the chemical shift of the central -CH₂- in: (a) HOCH₂CH₂OH (b) ClCH₂CH₂Cl (c) CH₃OCH₂OCH₃
Section D — Coupling constants
9.11 (routine) Two adjacent peaks in a multiplet are 7 Hz apart. What is the coupling constant?
9.12 (routine) A vinyl proton appears as a doublet with $J = 17$ Hz. cis or trans alkene? Why?
9.13 (moderate) A vinyl proton appears as a doublet with $J = 8$ Hz. cis or trans alkene? Why?
9.14 (moderate) Apply the Karplus equation. Predict $^3J$ for two vicinal protons with dihedral angle: (a) 0° (eclipsed) (b) 60° (gauche) (c) 90° (d) 180° (anti)
9.15 (challenge) Use the Karplus relationship to predict whether a sugar's α- and β-anomers can be distinguished by ¹H NMR coupling constants.
Section E — Solving simple unknowns
9.16∗ (moderate) A compound $C_3H_6O$: - 1H singlet at 9.8 ppm - 2H doublet at 2.4 ppm - 1H multiplet at 9.8 ppm... wait, let me restate. - 1H singlet (or doublet of doublet) at 9.8 ppm - 2H multiplet at ~2.4 ppm - 3H triplet at 1.0 ppm
IR: 1725 cm⁻¹.
Identify the compound.
9.17 (moderate) A compound $C_4H_{10}O$: - 1H broad singlet at 2.5 ppm (variable) - 1H multiplet at 4.0 ppm (no, that's wrong; let me restate) - 6H doublet at 1.16 ppm - 1H multiplet (septet) at 4.0 ppm - 1H broad at 2.5 ppm
IR: 3350 cm⁻¹ broad.
Identify.
9.18 (moderate) A compound $C_4H_{10}O$: - 3H triplet at 0.92 ppm - 2H sextet at 1.55 ppm - 2H quintet at 1.40 ppm... no, this needs cleanup. Let me re-do: - 3H triplet at 0.93 ppm - 2H multiplet at 1.4 ppm - 2H multiplet at 1.6 ppm - 2H triplet at 3.6 ppm - 1H broad at 2.5 ppm
IR: 3350 cm⁻¹ broad. MW = 74.
Identify.
9.19 (moderate) A compound $C_8H_{10}$: - 5H multiplet at 7.2 ppm - 2H quartet at 2.6 ppm - 3H triplet at 1.2 ppm
IR: aromatic C=C signals (1500, 1600).
Identify.
9.20 (moderate) A compound $C_3H_6O_2$: - 1H broad at 11 ppm (very downfield) - 2H quartet at 2.4 ppm - 3H triplet at 1.1 ppm
IR: very broad O-H (2500-3300), strong C=O (1715).
Identify.
Section F — Distinguishing isomers
9.21∗ (moderate) Two isomers of $C_4H_8O_2$: ethyl acetate (CH₃COOCH₂CH₃) and methyl propanoate (CH₃CH₂COOCH₃). Predict their ¹H NMR. How would you distinguish them?
9.22 (moderate) Two isomers of $C_4H_8O$: 2-butanone (CH₃COCH₂CH₃) and 2-methylpropanal ((CH₃)₂CHCHO). Predict their ¹H NMR. How would you distinguish them?
9.23 (moderate) Two isomers of $C_3H_8O$: 1-propanol and 2-propanol. Predict their ¹H NMR. Distinguish.
9.24 (challenge) o-, m-, p-xylene: predict ¹H NMR aromatic patterns. Distinguish.
9.25 (challenge) (E)- and (Z)-2-butene: distinguish by ¹H NMR. (Hint: coupling constants.)
Section G — ¹³C NMR
9.26 (routine) How many distinct $^{13}C$ environments does each compound show? (a) benzene (b) toluene (c) ethyl acetate (d) (CH₃)₂CHOH (e) cyclohexanone
9.27 (moderate) A ¹³C NMR shows peaks at δ 14, 22, 35, 42, 207. Predict the structure (use chemical shift table). MW from MS = 86.
9.28 (challenge) A DEPT 135 of an unknown shows: 1 CH₃ up, 2 CH₂ down, 1 CH up, plus 2 quaternary C invisible (seen in regular ¹³C). Identify carbon types.
9.29 (challenge) A 4-carbon compound has 1 quaternary C at δ 173, 2 CH₂ at δ 28, 1 CH₃ at δ 12. Identify.
Section H — 2D NMR
9.30 (moderate) What information does a COSY spectrum provide that a 1D ¹H NMR alone does not?
9.31 (moderate) What information does an HSQC spectrum provide?
9.32 (challenge) Distinguish cis-1,2-dimethylcyclohexane from trans-1,2-dimethylcyclohexane by ¹H NOE measurement.
9.33 (challenge) A cyclic compound has two methyl groups; NOESY shows correlation between them. Are they cis or trans?
Section I — Combined IR/MS/NMR
9.34∗ (challenge) A compound has: - MW (from MS) = 102 - IR: strong C=O at 1735 cm⁻¹ - ¹H NMR: 6H singlet at 2.0; 4H multiplet at 4.1 - ¹³C NMR: 4 peaks; one at 170, one at 60, one at 20.
Identify.
9.35 (challenge) A compound has: - MW = 88 - IR: broad O-H 3300; C=O at 1740 (ester) - ¹H NMR: 3H singlet at 1.5; 6H doublet at 1.0... actually let me redo: - 3H singlet at 2.0; 1H singlet broad at 3.5; 6H singlet at 1.5
Identify a possible structure.
9.36 (challenge) A compound has: - MW = 134 - IR: 1735 (ester); aromatic C=C at 1500, 1600 - ¹H NMR: 5H multiplet at 7.3; 2H quartet at 4.1; 2H singlet at 3.5; 3H triplet at 1.2
Identify.
Section J — Stereochemistry by NMR
9.37 (moderate) A -CH₂- next to a chiral center shows two diastereotopic protons. They appear as separate doublets (AB pattern). Why?
9.38 (challenge) A -CH₂- in a meso compound shows two protons. Are they enantiotopic or diastereotopic? How will they appear in ¹H NMR?
9.39 (challenge) Use a chiral lanthanide shift reagent to measure ee of a chiral compound. Explain the strategy.
Section K — Practical NMR
9.40 (moderate) Why is CDCl₃ the most common NMR solvent? Why deuterated, not just CHCl₃?
9.41 (moderate) What's the difference between a 400 MHz and 600 MHz NMR? In what circumstances would you choose 600 MHz?
9.42 (challenge) Why does ¹³C NMR typically take much longer to acquire than ¹H NMR? Suggest two ways to improve ¹³C signal-to-noise.
Section L — Modern applications
9.43 (challenge) AlphaFold (Ch 33) predicts protein structure from sequence. Why might NMR still be needed even with AlphaFold?
9.44 (challenge) Solid-state NMR (instead of solution): what's different? When is it needed (e.g., insoluble polymers, membrane proteins).
9.45 (challenge) Reaction monitoring by NMR: a chemist follows a reaction in real-time using NMR. What information does this give that a TLC plate does not?
Notes for instructors: Common stumbling blocks for Chapter 9: (1) confusing chemical shift with coupling; (2) forgetting that exchangeable protons (OH, NH) often show as broad singlets and don't split adjacent CH; (3) miscounting equivalent protons; (4) overlooking diastereotopic protons; (5) confusing DEPT with regular ¹³C.