Klein 15.3-15.7

15.1–15.13 NMR Spectroscopy: Comprehensive Study Notes

• Overview

  • Nuclear magnetic resonance (NMR) spectroscopy is a powerful, broadly applicable technique for structure determination in organic chemistry. Often used in combination with IR spectroscopy and mass spectrometry for comprehensive structure elucidation.
  • NMR probes the interaction of electromagnetic radiation with atomic nuclei. nuclei that can be studied include $^{1}\mathrm{H},$ $^{13}\mathrm{C},$ $^{15}\mathrm{N},$ $^{19}\mathrm{F},$ and $^{31}\mathrm{P}.$ In practice, $^{1}\mathrm{H}$ and $^{13}\mathrm{C}$ are used most often because H and C are the main constituents of organic compounds.
  • A nucleus with an odd number of protons and/or neutrons has a quantum mechanical property called nuclear spin. A proton (the nucleus of $^{1}\mathrm{H}$) has spin, not because of actual rotation but as a quantum property. A spinning proton can be modeled as a rotating sphere of charge that generates a magnetic moment, akin to a bar magnet.
  • Not all nuclei have spin. For example, $^{12}\mathrm{C}$ has an even number of protons and neutrons and does not possess this spin, whereas $^{13}\mathrm{C}$ does (odd number of neutrons).
  • When subjected to an external magnetic field, the interaction between the magnetic moment and the field is quantized, giving α (alpha) and β (beta) spin states: α aligned with the field, β aligned against it. The energy gap between these states is denoted $\Delta E$ (energy gap).
  • Resonance occurs when a nucleus in the α state absorbs a photon with energy equal to $\Delta E$, flipping to the β state. In strong magnetic fields, the required radiation is in the radio frequency (rf) region.
  • Important conceptual caveat: “resonance” in NMR is not the same as resonance structures in organic chemistry.

• Diamagnetism and shielding (conceptual opener)

  • In a strong magnetic field, electrons circulate and create a local induced magnetic field that opposes the external field. This diamagnetic effect shields protons; they experience a net field slightly weaker than the external field.
  • Protons in different electronic environments experience different degrees of shielding, leading to different resonance frequencies. More electron density (shielding) → smaller ΔE effectively, lower observed frequency; less electron density (deshielding) → higher observed frequency.
  • Diamagnetism is universal (all materials have some diamagnetic response), and it is essential for the informative power of NMR: protons in different environments give signals at different chemical shifts.

• 15.2 Acquiring a 1H NMR Spectrum

  • A strong external magnetic field creates the energy gap that enables rf absorption by nuclei. The gap grows with magnetic field strength, so higher field → wider range of resonant frequencies but easier resolution.
  • Example field strengths and operating frequencies: a field of $1.41\ \mathrm{T}$ yields resonances near $60\ \mathrm{MHz}$; a field of $7.04\ \mathrm{T}$ yields resonances near $300\ \mathrm{MHz}.$ Operating frequency corresponds to the spectrometer’s field.
  • Field strengths are often reported in gauss: $1\ \mathrm{T} = 10^4\ \mathrm{G}$.
  • Instrumentation:
  • Continuous-wave (CW) spectroscopy (older): sweep rf frequency or field to detect resonance.
  • Fourier-transform NMR (FT-NMR) (modern): hold the field constant and apply a short rf pulse that excites a broad range of frequencies; the resulting free induction decay (FID) is Fourier transformed to yield the spectrum. Multiple FIDs can be averaged to improve signal-to-noise, enabling practical 13C spectroscopy as well.
  • Sample preparation:
  • Compounds are typically dissolved in a deuterated solvent and placed in a narrow NMR tube.
  • Deuterated solvents are used to minimize solvent signals in the proton spectrum; deuterium has a different resonance range and is effectively invisible in the proton spectrum for the usual 1H NMR window.
  • Common practice is to use solvents like CCl4-d, CDCl3-d, etc., which lack protons in the observed region but can dissolve many samples.

• 15.3 Characteristics of a 1H NMR Spectrum (three key features per signal)

  • Each signal has three main characteristics:
    1) Chemical shift (location) — indicates electronic environment of the protons producing the signal.
    2) Integration (area under the signal) — proportional to the number of protons giving rise to that signal.
    3) Multiplicity (shape) — indicates the number of neighboring protons and thus provides information about the proton’s environment.
  • These are interpreted in Sections 15.4–15.7 and are used to deduce structure.

• 15.4 Number of Signals: chemical equivalence and symmetry

  • The number of signals equals the number of chemically distinct proton environments.
  • Protons that share an identical electronic environment are chemically equivalent and give a single signal.
  • Key definitions:
  • Homotopic protons: protons that can be interchanged by rotational symmetry; they are chemically equivalent.
  • Enantiotopic protons: protons that can be interchanged by reflectional symmetry; in an achiral solvent, they are chemically equivalent; in chiral solvents, they may become non-equivalent.
  • Diastereotopic protons: protons that are not interchangeable by symmetry (neither rotation nor reflection). They are not chemically equivalent and typically give separate signals.
  • Replacement test (practical method): replace one of two protons with deuterium in two drawings; if the two drawings are identical, protons are homotopic; if different by rotation but identical by reflection, protons are enantiotopic; if neither, they are diastereotopic.
  • Examples (from the text):
  • Propane middle carbons: the two protons on the middle carbon are homotopic (rotational symmetry).
  • Alpha-hydrogen of ethanol: protons are not homotopic (rotation doesn’t interchange them), but they are enantiotopic (reflection can interchange them).
  • Protons in (R)-2-butanol: diastereotopic (neither rotational nor reflective symmetry interchanges them).
  • Practical rules to estimate the number of signals (without exhaustive symmetry analysis):
  • CH3 groups: three protons are always equivalent → count as one signal.
  • CH2 groups: usually equivalent if no chiral centers; otherwise, CH2 protons can be non-equivalent in the presence of a chiral center.
  • Symmetry can make two CH2 groups equivalent, reducing the total number of signals.

• 15.5 Chemical Shift (δ) and references

  • Chemical shift δ is defined relative to the reference compound tetramethylsilane (TMS). In practice, TMS is present in deuterated solvents at trace amounts and defines the 0 ppm reference.
  • The frequency difference is given by
    ${\delta} = \dfrac{\nu<em>{signal} - \nu</em>{\mathrm{TMS}}}{\nu<em>{operating}}$ where $\nu</em>{signal}$ is the resonance frequency of the observed proton, $\nu<em>{\mathrm{TMS}}$ is the resonance frequency of TMS, and $\nu</em>{operating}$ is the spectrometer’s operating frequency.
  • The chemical shift is dimensionless (Hz/Hz) and typically reported in parts per million (ppm). For many organic compounds, signals fall in the 0–12 ppm range; some rare signals can be < 0 ppm.
  • Left side of the spectrum is downfield; right side is upfield. Historically, downfield corresponds to higher magnetic field strength due to deshielding; upfield corresponds to lower field, more shielding.
  • Benchmark chemical shifts (typical protons without strong neighboring electronegative effects):
  • Methyl (R–CH3): ≈ 0.9 ppm
  • Methylene (R–CH2–): ≈ 1.2 ppm
  • Methine (R–CH–): ≈ 1.7 ppm
  • Inductive effects from electronegative substituents deshield nearby protons, pushing signals downfield. Stronger electronegative atoms (F > Cl > Br) have larger deshielding effects; distance matters (alpha protons are most affected; beta somewhat less; gamma largely unaffected).
  • Functional-group effects on alpha protons (Table 15.1, summarized):
  • Oxygen of an alcohol or ether: +2.5 ppm
  • Oxygen of an ester: +3 ppm
  • Carbonyl group (C=O) in all carbonyl groups (ketones, aldehydes, esters, etc.): +1.0 ppm
  • Diamagnetic (anisotropic) effects from π systems: aromatic rings produce characteristic deshielding/anisotropy patterns.
  • Aromatic protons typically appear near ~7 ppm, often as a complex multiplet due to three different proton environments.
  • Protons directly attached to a benzenoid system can experience large deshielding near 7 ppm; substituent effects can shift nearby methylene/methyl protons (e.g., ethylbenzene shows a benzylic CH2 around 2.6 ppm instead of the 1.2 ppm benchmark).
  • Aromatic ring anisotropy can even create very upfield signals for protons located inside the ring, and downfield signals for protons outside the ring.
  • Common aromatic/aldehyde/acid regions: aldehyde protons ≈ 10 ppm; carboxylic acid protons ≈ 12 ppm.
  • Table 15.2 (chemical shifts by environment):
  • Methyl (R–CH3): ~0.9
  • Methylene (R–CH2–): ~1.2
  • Methine (R–CH–): ~1.7
  • Allylic: ~2
  • Alkynyl: ~2.5
  • Aromatic methyl: ~2.5
  • Alkyl halide: 2–4
  • Alcohol: 2–5
  • Vinylic: 4.5–6.5
  • Aryl: 6.5–8
  • Aldehyde: ~10
  • Carboxylic acid: ~12

• 15.6 Integration (signal area)

  • Integration indicates the number of protons responsible for a signal.
  • After spectrum acquisition, integrals are scaled by the smallest integral value and then divided to yield relative proton counts. E.g., a set of integrals 1.0, 1.5, 3.0 would be scaled by 1.0 to become 1, 1.5, 3.0; then multiply by 2 to obtain whole numbers (2 : 3 : 6) if needed, corresponding to 2, 3, and 6 protons in each environment.
  • Real-world example: tert-butyl methyl ether (MTBE) has two kinds of protons (methyl vs tert-butyl): the relative integrals might be 1 : 3, but the exact numbers are 3 protons for the methyl and 9 protons for the tert-butyl group, so the actual ratio is 1 : 3 after appropriate scaling to sum to the molecule’s total proton count.
  • Symmetry can affect integration: e.g., 3-pentanone has only two kinds of protons because methylene groups are equivalent and methyl groups are equivalent, leading to two signals.

• 15.7 Multiplicity (spin-spin splitting) and the n + 1 rule

  • The splitting of a signal is caused by neighboring protons (Hb) that are not chemically equivalent to the signal’s own protons (Ha).
  • If Hb protons are equivalent to each other, Ha demonstrates the classic n + 1 rule, where the number of peaks equals n + 1, with relative intensities given by the binomial pattern:
  • n neighboring protons → multiplicity = n + 1
  • 0 neighbors: Singlet
  • 1 neighbor: Doublet (1:1)
  • 2 neighbors: Triplet (1:2:1)
  • 3 neighbors: Quartet (1:3:3:1)
  • 4 neighbors: Quintet (1:4:6:4:1)
  • 5 neighbors: Sextet (1:5:10:10:5:1)
  • 6 neighbors: Septet (1:6:15:20:15:6:1)
  • Two major factors determining splitting:
    1) Equivalent protons do not split each other. If neighbors are chemically equivalent, they do not cause additional splitting.
    2) Splitting is most commonly observed for neighbors separated by 2–3 σ bonds (vicinal or geminal relationships). Long-range coupling (>3 σ bonds) is rare except in rigid or special systems like bicyclics or allylic conjugation.
  • Complex splitting (multiplets) occurs when Hb protons are not equivalent (two different kinds of neighboring protons) or when J-values are similar in magnitude (leading to a sextet-like appearance when Jab ≈ Jbc, etc.). A completely simple pattern (e.g., a clean quartet or a clean triplet) is less common in real-world crowded spectra.
  • Examples of pattern recognition:
  • Isolated ethyl group: triplet (3 H) from CH3, quartet (2 H) from CH2, with Jab ≈ Jbc ensuring similar coupling constants across the two signals.
  • Isopropyl group: a doublet (6 H) adjacent to a septet (1 H) for a typical isopropyl arrangement.
  • tert-Butyl group: a singlet (9 H) because the tert-butyl methyls have no neighboring protons (the central quaternary carbon has no hydrogens).
  • Patterns help quickly identify functional groups (ethyl, isopropyl, tert-butyl) in a spectrum and are reinforced by pattern recognition charts (Fig. 15.15–15.18 references in the text).

• 15.8 Drawing the Expected 1H NMR Spectrum of a Compound

  • (Note: The transcript references this section but detailed content is not included here. Use the three signal-characteristics (δ, integration, multiplicity) and symmetry/equivalence principles to predict a spectrum for a given structure in exam practice.)

• 15.9 Using 1H NMR Spectroscopy to Distinguish Between Compounds

  • The combination of chemical shifts, integrations, and multiplicities provides a powerful means to distinguish isomers and related compounds. By comparing the predicted and observed spectral features, one can discriminate between candidate structures.

• 15.10 Analyzing a 1H NMR Spectrum

  • Practical workflow for spectral analysis (as implied by the chapter):
  • Determine the number of signals (count chemically distinct proton environments).
  • Assign chemical shifts δ to each signal and relate them to functional groups and electronic environments (use Tables 15.1 and 15.2 as references).
  • Use integrations to determine the relative numbers of protons per signal; scale to the molecular formula to deduce absolute numbers.
  • Use multiplicities (n + 1 rule) to locate neighboring protons and piece together the connectivity.
  • Consider symmetry and possible equivalence across the molecule; apply replacement tests if needed.

• 15.11 Acquiring a 13C NMR Spectrum

  • 13C NMR is a companion technique to 1H NMR and often requires signal averaging for adequate signal-to-noise due to lower natural abundance of $^{13}\mathrm{C}$ (~1.1%).
  • The text notes signal averaging as the primary practical approach for good 13C spectra, which is achieved by acquiring many FIDs and averaging them.

• 15.12 Chemical Shifts in 13C NMR Spectroscopy

  • While not elaborated in detail in the transcript excerpt, 13C NMR provides distinct chemical shift information for carbon environments (quaternary vs CH, CH2, CH3) and complements 1H data.

• 15.13 DEPT 13C NMR Spectroscopy

  • DEPT (Distortionless Enhancement by Polarization Transfer) is a common technique in 13C NMR that differentiates carbons by the number of attached protons (CH, CH2, CH3, quaternary). Details are not provided in the transcript excerpt, but DEPT is a standard 13C NMR technique.

• Additional context: “DID YOU EVER WONDER…” and foundational references

  • Did You Ever Wonder?: Diamagnetism and levitation in strong magnetic fields. Even small objects can levitate in sufficiently strong fields due to diamagnetic repulsion; this is a conceptual setup used to motivate the role of diamagnetism in NMR.
  • 1997 experiments (Radboud University) demonstrated levitation of hazelnuts, strawberries, and even frogs at about 16 T. Humans cannot levitate with current magnets, but stronger magnets could, in theory, enable weightless experiences without space travel.
  • The chapter uses diamagnetism to motivate why NMR provides rich structural information beyond other spectroscopic methods.

• Do You Remember? Foundational topics for preparing chapter knowledge

  • Quantum Mechanics (Section 1.6)
  • Stereoisomeric relationships: Enantiomers and diastereomers (Section 5.5)
  • Symmetry and chirality (Section 5.6)
  • Introduction to Spectroscopy (Section 14.1)
  • Hydrogen Deficiency Index (Section 14.16)
  • A quiz on these topics (WileyPLUS) helps gauge readiness for the chapter material.

• Practical notes and cross-links

  • Chemical shift is a relative measure that is independent of the instrument’s magnetic field strength, provided δ is reported in ppm with respect to TMS.
  • Shielding/deshielding effects arise from electron density around nuclei and from anisotropic effects due to π-systems (aromatics, alkenes).
  • Inductive effects from electronegative substituents (halogens, oxygen, carbonyls) can markedly deshield nearby protons, especially at the α-position, and to a lesser extent at β- and γ-positions.
  • Ring flipping dynamics (cyclohexane) average axial and equatorial environments at room temperature, often yielding a single signal; lowering temperature can “freeze” conformations and reveal separate signals for axial and equatorial protons.
  • Integration and symmetry considerations are essential for correct interpretation: identical integrals do not always mean identical environments if symmetry exists; conversely, non-equivalent protons can give different signals even if the molecule is symmetrical overall.
  • Long-range coupling is possible in rigid systems but generally not observed in standard introductory NMR problems.

• Quick reference to useful values and rules (summary)

  • Chemical shift references: TMS at 0 ppm; δ defined as a ratio of frequencies, independent of spectrum operating frequency.
  • Typical 1H NMR environments:
  • Alkanes: 0–2 ppm (with specific blocks for aliphatic groups)
  • Allylic: around 2 ppm
  • Alkynyl: around 2.5 ppm
  • Aromatic protons: ~6.5–8 ppm
  • Aldehydes: ~10 ppm
  • Carboxylic acids: ~12 ppm
  • Diamagnetic anisotropy leads to deshielding for protons outside aromatic rings (e.g., ethylbenzene: benzylic CH2 ~2.6 ppm; aryl protons ~7–8 ppm) and shielding inside rings (some inside-ring protons can appear upfield, even near 0 to -1 ppm in extreme cases).
  • 1H NMR multiplicities follow the n + 1 rule when neighboring protons are equivalent; complex splitting arises when neighboring protons are non-equivalent or when several coupling pathways exist (J-values often around 0–20 Hz, and are instrument-independent).
  • Typical splitting patterns (pattern recognition): ethyl group (triplet/quartet), isopropyl group (doublet/septet), tert-butyl group (singlet, 9 H).
  • The coupling constant Jab remains constant across spectrometers with different field strengths, illustrating the instrument-invariant nature of J-values, even though spectral dispersion (ppm) changes with field.

• Summary: How these ideas connect to real-world structure elucidation

  • By integrating information on chemical shifts, signal counts, integrals, multiplicities, and coupling patterns, a chemist can deduce the carbon-hydrogen framework of a molecule.