1H NMR Spectroscopy

Types of Spectroscopy

• Spectroscopy is a technique for analyzing molecular structures based on differences in the absorption of electromagnetic radiation.

• Common spectroscopic techniques in organic chemistry:- Nuclear Magnetic Resonance (NMR) spectroscopy

  • Infra-Red (IR) spectroscopy

  • Ultraviolet (UV) spectroscopy

  • Fluorescence spectroscopy

NMR Spectroscopy

• NMR spectroscopy probes the vicinity of individual nuclei in molecules, especially hydrogen (H1) and carbon (C13) atoms.

• It provides information regarding the atomic connectivity of a molecule.

• Molecules with symmetry (rotational symmetry, mirror plane) have simpler spectra because chemically equivalent protons have the same chemical shift.

NMR Spin States

• Random Orientation Without Magnetic Field: In the absence of an external magnetic field, nuclear spins are randomly oriented.

• Alignment in an External Magnetic Field: When placed in a magnetic field, nuclei align either parallel (low energy) or antiparallel (high energy) to the field.

• Spin-Flip and Resonance: When exposed to electromagnetic (EM) radiation of the correct frequency, lower-energy nuclei absorb energy and "spin-flip" to the higher-energy state, entering resonance.

• Magnetic Field Strength and Resonance Frequency: The energy required for resonance depends on both the magnetic field strength and the type of nucleus being studied. Stronger magnetic fields cause greater energy differences, requiring higher-frequency radiation for spin-flip.

• \gamma = magnetogyric ratio

• B_0 = magnetic field strength

• Applying a short radio frequency pulse (RF pulse) at right angles to B_0, the nuclei will flip down the ‘xy’ plan together and continue to precess.

• Excitation of Spin Nuclei: When a nuclei with a spin = ½ is exposed to an external applied field, there are two possible energy levels.

• By irradiating with a small amount energy (radiofrequency radiation), a nuclei can be promoted from one level to another. This transition is what is detected in NMR spectroscopy ∆E.

• FID = Free Induced Decay

• Signal generated by non-equilibrium nuclear spin magnetization precessing about the magnetic field (conventionally along z)

• Precessing magnetization will induce an alternating current in a coil (the same one used to generate the rf pulse) wound round the sample.

• The FID contains all of the information in the NMR spectrum, but it is difficult for us to discern the information in this format. Fourier transformation of the FID, a time domain signal, produces the frequency domain NMR spectrum. The resonance frequencies of the signals in the transformed spectrum correspond to the frequency of oscillations in the FID.

• Nuclear Spin Numbers All magnetic nuclei have a charge. In some nuclei the charge “spins” on an axis, which generates a magnetic dipole along the axis.

• The angular momentum of the spinning charge is described by a quantum spin number in increments of ½.

• Nuclei with a spin number of ½ can be easily analysed by NMR spectroscopy.

Nuclear Spin and Magnetic Moments

• The spin quantum number (I) determines whether a nucleus can interact with a magnetic field.

• The magnetic moment (μ) of the nucleus arises from nuclear spin and is responsible for NMR signals.

• Only nuclei with I ≠ 0 can interact with an external magnetic field, leading to energy level splitting (Zeeman effect) and producing an NMR signal.

Spin Quantum Number Rules

• The nuclear spin (I) depends on the sum of protons (Z) and neutrons (N):

  • Even Z and Even N → I = 0 (NMR inactive)- Example: 12C, 16O (No magnetic moment, no NMR signal)

  • Odd Z or Odd N → I = 1/2, 1, 3/2, etc. (NMR active)- Example: 1H (proton), 13C, 15N, 19F (All NMR active)

  • Odd Z and Odd N → I = Integer (NMR active but complex spectra)- Example: 2H (I = 1), 14N(I=1), 10B(I=3)

• Thus, nuclei with an odd number of protons or neutrons generally have a half-integer spin (e.g., I=1/2,3/2), making them suitable for NMR.

Why Are Even-Even Nuclei NMR Inactive?

• When both proton and neutron numbers are even, their nuclear spins pair up and cancel out.

• This results in I = 0, meaning the nucleus has no net magnetic moment and does not interact with a magnetic field.

• Example: 12C, 16O, and 32S are not NMR active.

Practical Implications in NMR

• 1H and 13C are widely used in organic spectroscopy because they have I = 1/2, leading to simple spectra

• Nuclei with I > 1/2 (e.g. 14N, 2H exhibit quadrupolar interactions, causing broader or more complex signals

• Understanding nuclear spin properties helps in choosing suitable nuclei for molecular characterization in NMR experiments

Information from a 1H NMR Spectrum

Four types of information can be obtained from a 1H NMR spectrum:

1. Chemical Shift (the location)

2. Integration (area under the peak)

3. Splitting Pattern (how many similar neighbouring atoms)

4. Coupling Constant (spatial orientation of atoms)

1H NMR Scale

• The most common scale is in units of parts per million (ppm).

• Spectra are typically examined between 0 and 10 ppm.

• The exact value is known as the chemical shift (σ).

• Sometimes the chemical shift is also reported in units of Hertz between values of 0 and 6000 Hz.

Chemical Shift

• The ideal solvent should contain no protons and be inert, low boiling, and inexpensive.

• Deuterated solvents are necessary for modern instruments because they depend on a deuterium signal to lock or stabilize the B_o field of the magnet.

• Instruments have a deuterium "channel" that constantly monitors and adjusts (locks) the B_o field to the frequency of the deuterated solvent.

• Typically, 1H NMR signals are in the order of 0.1 to several Hz wide out of 300,000,000 Hz (for a 300 MHz system), so the B_o field needs to be very stable and homogeneous

• The deuterium signal is also used to "shim" the Bo field. Instruments use small electromagnets (called shims) to bend the main magnetic field (Bo) so that the homogeneity of the field is precise at the center of the sample. Most modern instruments have approximately 20-30 electromagnetic shims; they are computer controlled, and can be adjusted in an automated manner.

• Deuterated chloroform (CDCl3) is used whenever circumstances permit-in fact most of the time. The small sharp proton peak at δ 7.26 from the CHCl3 impurity present rarely interferes seriously. For very dilute samples, CDCl_3 can be obtained in "100% isotope purity."

• Traces of ferromagnetic impurities cause severe broadening of absorption peaks because of reduction of T_1 relaxation times. Common sources are rust particles from tapwater, steel wool, Raney nickel, and particles from metal spatulas or fittings.

• Only a single proton peak should be expected from the interaction of rf energy and a strong magnetic field on all of the protons in accordance with the basic NMR equation (Section 3.2.2): v = (\gamma/2\pi)B_0 - where v is the applied frequency, B_0 is the flux density of the stationary magnetic field, and (\gamma/2\pi) is a constant.

• The basic NMR equation for all protons is now modified for an assemblage of equivalent protons in the molecule: veff = (\gamma/2\pi)B0(1-\sigma) - The symbol σ is the "shielding constant" whose value is proportional to the degree of shielding by its electron cloud. At a given value of B_0, the effective frequency at resonance is less than the applied frequency v. Electrons under the influence of a magnetic field circulate and, in circulating, generate their own magnetic field opposing the applied field; hence, the "shielding" effect.

• The difference in the absorption position of a particular proton from the absorption position of a reference proton is called the chemical shift of the particular proton.

• The most generally useful reference compound is tetramethylsilane (TMS). CH3-Si-CH3 | CH_3 - This material has several advantages: it is chemically inert, symmetrical, volatile (bp 27°C), and soluble in most organic solvents; it gives a single, intense, sharp, absorption peak, and its protons are more "shielded" than almost all organic protons.

  • When water or deuterium oxide is the solvent, TMS can be used as an "external reference" in a concentric capillary or the methyl protons of the water-soluble sodium 2, 2-dimethyl-2-silapentane-5-sulfonate (DSS), (CH3)3SiCH2CH2CH2SO3Na, are used as an internal reference (0.015 ppm).

• Historically and now by convention, the TMS reference peak is placed at the right-hand edge of the spectrum and designated zero on the either Hz or δ scale (defined below). Positive Hz or δ numbers increase to the left of TMS, negative numbers increase to the right. The term "shielded" means toward the right: "deshielded" means toward the left. It follows that the strongly deshielded protons of dimethyl ether, for example, are more exposed than those of TMS to the applied field; hence, resonance occurs at higher frequency-i.e.. to the left-relative to the TMS proton peak. Thus, both the Hz and the δ scales reflect the increase in applied frequency, at constant field, toward the left of the TMS resonance frequency. and the decrease in applied frequency toward the right.

• The concept of electronegativity of substituents near the proton in question is a dependable guide, up to a point, to chemical shifts

Chemical Shifts Trends Guided by Electronegativity

• The molecule is linear, and the triple bond is symmetrical about the axis. If this axis is aligned with the applied magnetic field, the electrons of the bond can circulate at right angles to the applied field, thus inducing their own magnetic field opposing the applied field. Since the protons lie along the magnetic axis, the magnetic lines of force induced by the circulating electrons act to shield the protons.

• The so-called "ring-current effect" is another example of diamagnetic anisotropy and accounts for the large deshielding of benzene ring protons.

Chemical Shifts

• To reiterate the position of an NMR absorption is called the chemical shift.

• The chemical shift depends on the electron density around an atom, which is influenced by the structural environment about the nucleus- The chemical shift range for 1H NMR typically ranges between 0 and 10 ppm but may go up to 15 ppm.

• Unlike infrared and UV-visible spectroscopy, where absorption peaks are uniquely located by a frequency or wavelength, the location of different NMR resonance signals is dependent on both the external magnetic field strength and the rf frequency.

The Position of an NMR Signal

• The position of an NMR signal depends on the electronic environment of the nucleus

• Bound hydrogens are surrounded by orbitals whose electron density varies depending on the polarity of the bond, the hybridization of the attached atom, and the presence of electron-donating or withdrawing groups. When a nucleus surrounded by electrons is exposed to a magnetic field of strength Ho, these electrons move in such a way as to generate a small local magnetic field, hlocal opposing Ho. As a consequence, the total field strength near the hydrogen nucleus is reduced, and the nucleus is thus said to be shielded from Ho by its electron cloud.

• The chemical shift describes the position of an NMR peak

  δ = \frac{\text{distance of peak from }(CH3)4Si \text{ in hertz}}{\text{spectrometer frequency in megahertz}} \text{ppm}

  Functional groups cause characteristic chemical shifts

Typical Hydrogen Chemical Shifts in Organic Molecules

Effect of Diamagnetic Anisotropy

• However, there are apparent anomalies that can be explained by ring currents. For example, the terminal protons of alkynes have a σ 1.80 ppm while the proton of an aldehyde has a σ 9.97 ppm.

• Acetylene is a linear molecule. When aligned with the magnetic field, the ‘π’ electrons of the bond circulate at right angle to the field. Aldehyde is a flat molecule. When aligned against the magnetic field, the proton is at the edge of the ring current.

• Diamagnetic Anisotropy: the shielding or deshielding of proton “through space” an applied external magnetic field.

• Benzene experiences a “ring-current effect”. The aryl protons are at the edge of the induced magnetic field. However, a proton that could be held directly above or below the ring would be highly shielded.

• Chemical Shifts σ The most common reference compound is tetramethylsilane (TMS). It is assigned a value of 0.00 ppm. Because of the symmetry of the molecule it give a single sharp peak. It has several advantages:1. Chemically inert

  2. Symmetrical molecule (single peak)

  3. Soluble in most organic solvents

  4. Appears to the right of almost all other organic protons. It is said to be more “shielded” and is assigned a σ of 0.00 ppm

Spectacular Examples of Diamagnetic Anisotropy

• provides an example of a molecule that has protons that are both shielded and deshielded. At -60 ℃ the protons on the outside are strongly deshielded (σ 9.3 ppm) and those inside are strongly shielded (σ -3.0 ppm) i.e. more deshielded than TMS

• summary - chemical shift is influenced by inductive effects and field effects

  Four types of information can be obtained from a 1H NMR Spectrum:

• Chemical shift (the location)

• Integration (area under the peak)

• Splitting pattern (how many similar neighbouring atoms)

• Coupling constant (spatial orientation of atoms)

Solvent Effects

• Chloroform-d (CDCl_3) is the most common solvent for NMR measurements, thanks to its good solubilizing character and relative unreactive nature ( except for 1º and 2º-amines).

• Other deuterium labelled compounds, such as deuterium oxide (D2O), benzene-d6 (C6D6), acetone-d6 (CD3COCD3) and DMSO-d6 (CD3SOCD_3) are also available for use as NMR solvents.

• Because some of these solvents have -electron functions and/or may serve as hydrogen bonding partners, the chemical shifts of different groups of protons may change depending on the solvent being used.

Chemical Shift Variation

1. Solvents can cause small shifts in NMR signals due to hydrogen bonding, polarity, or electronic effects.- Example: Protic solvents (e.g., D_2O, MeOD) can broaden and shift peaks due to exchange with labile protons (e.g., -OH, -NH).

   • Solvent Residual Peaks

2. Deuterated solvents contain residual non-deuterated (protonated) impurities that appear as small peaks.- Example: CDCl3 has a residual CHCl3 peak at ~7.26 ppm in 1H NMR.

   • Solvent Polarity Effects

3. Polar solvents influence electron density around nuclei, shifting signals.- Example: Acetone-d₆ vs. CDCl_3 may show slight shifts for polar functional groups due to different solvation environments.

   • Exchangeable Protons

• Labile protons (e.g., -OH, -NH) can exchange with solvent, affecting peak visibility. In D_2O, exchangeable protons disappear in 1H NMR due to H/D exchange.- Spin-Spin Coupling Changes

• Solvent effects may alter J-coupling constants due to changes in molecular conformation and interactions.- Paramagnetic or Impure Solvents

• Traces of paramagnetic impurities (e.g., O_2, metal ions) in solvents can cause peak broadening and signal loss.

Integration

• The integration indicates the relative number of hydrogen atoms for an NMR peak.

• The more hydrogen atoms of one kind, the more intense the NMR absorption peak relative to other signals. Usually, the area under the peak is measured (“integrating area”) by a software program.

• However, a ruler can also be used to measure the distance between the horizontal plateaus to get a relative height.

• Integration of Benzyl Acetate Peaks The measured relative height of integrals with a ruler can be used to determine the relative number of hydrogen atoms from.

• Influence of the Applied Field Strength on Resolution

Pascal’s Triangle

• The splitting pattern is given by the N+1 rule based on the number of neighbouring atoms.

• When there are no neighbouring non-equivalent protons, the observed peak is a singlet.

Spin-Spin Splitting

• Neighboring hydrogen nuclei can complicate the spectrum as the result of a phenomenon called spin-spin splitting or spin-spin coupling.

• In conjunction with chemical shifts and integration, spin-spin splitting frequently helps us arrive at a complete structure for an unknown compound. How can we interpret this information?

  • One neighbor splits the signal of a resonating nucleus into a doublet

• The single absorption expected for a neighbor-free Ha is said to be split by Hb into a doublet. Integration of each peak of this doublet shows a 50% contribution of each hydrogen. The chemical shift of H_a is reported as the center of the doublet.

• The signal for Hb is subject to similar considerations. This hydrogen also has two types of hydrogens as neighbors-Ha(\alpha) and Ha(\beta). Consequently its absorption lines appear in the form of a doublet. So, in NMR jargon, Hb is split by H_a. The amount of this mutual splitting is equal; that is, the distance (in hertz) between the individual peaks making up each doublet is identical. This distance is termed the coupling constant, J.

• Spin-spin splitting is generally observed only between hydrogens that are immediate neighbors, bound either to the same carbon atom [geminal coupling (geminus, Latin, twin)] or to two adjacent carbons [vicinal coupling (vicinus, Latin, neighboring)]. Hydrogen nuclei separated by more than two carbon atoms are usually too far apart to exhibit appreciable coupling. Moreover, equivalent nuclei do not exhibit mutual spin-spin splitting. Splitting is observed only between nuclei with different chemical shifts.

Local-field contributions from more than one hydrogen are additive

• This nucleus is exposed to four different types of Hd proton combinations as neighbors: one in which all protons are aligned with the field (H{d(aaa)}); three equivalent arrangements in which one Hd is opposed to the external field and the other two are aligned with it (H{(\beta aa)},H{(\alpha\beta a)},H{(\alpha\alpha\beta)}); another set of three equivalent arrangements in which only one proton remains aligned with the field (H{(\beta\beta a)},H{(\beta\alpha\beta)},H{(\alpha\beta\beta)}); and a final possibility in which all Hd oppose the external magnetic field (H{(\beta\beta\beta)}). The resulting spectrum is predicted-and observed to consist of a 1:3:3:1 quartet (integrated intensity 4). The coupling constant Jed is identical with that measured in the triplet for He (8 Hz).

• Note: The splitting pattern of a hydrogen NMR signal gives you the number of neighboring hydrogens. It provides no information about the absorbing hydrogen itself.

  In many cases, spin-spin splitting is given by the N + 1 rule

Pascal's Triangle and NMR Splitting Patterns

General Trends for Spin-Spin Splitting of Common Alkyl Groups

Pascal's Triangle and NMR Multiplicity

• Pascal’s Triangle is a mathematical arrangement of numbers in a triangular pattern, where each number is the sum of the two numbers directly above it. It is used in NMR spectroscopy to predict peak intensities in spin-spin coupling (multiplicity patterns).

• Each neighbouring proton can either align (↑) or oppose (↓) the external magnetic field.

• The shape of the multiplet arises from the probability of different spin states of neighbouring protons.

• Up-Up (↑↑) → Lowest energy peak

• Up-Down or Down-Up (↑↓, ↓↑) → Middle energy peaks (twice as likely, so stronger intensity)

• Down-Down (↓↓) → Highest energy peak

Multiplicity

• Multiplicity helps determine molecular structure by showing how many hydrogen neighbours are present.

• Peak intensities follow Pascal’s Triangle, providing a predictable pattern for interpretation.

• More complex splitting (second-order effects) occurs in molecules with non- equivalent neighbours or strong coupling interactions.

Spin Coupling in Ethylbenzene

• The observed splitting pattern in ethylbenzene is due to vicinal coupling between hydrogen atoms on adjacent carbon atoms.

Coupling Constant JAB

• Spin-spin splitting is generally observed between non-equivalent hydrogen atoms that are on the same carbon atom (geminal) or on adjacent carbon atoms (vicinal).

• Geminal coupling can be larger than vicinal coupling.

• Hydrogen atoms separated by more than two atoms tend to have little or no coupling between them.

Geminal vs Vicinal Coupling in NMR

• Geminal coupling (²J): Coupling between two protons on the same carbon.

• Vicinal coupling (³J): Coupling between two protons on adjacent carbons.

Key Factors Influencing Geminal Coupling

• Hybridization of Carbon sp2 carbons (alkenes, aromatics) have larger geminal couplings than sp3 carbons (alkanes).

• Electronegative Substituents

• Electronegative atoms (O, N, halogens) reduce electron density around the carbon, increasing geminal coupling.

  Ring Strain and Stereoelectronic Effects In strained rings (e.g., cyclopropane, epoxides), geminal coupling can be larger than vicinal coupling due to restricted bond angles and orbital overlap.

First Order Coupling

• Coupling is ordinarily not observed beyond three bonds (geminal and vicinal coupling). These gives rise to what is known as first order spectra.

• Definition: A system follows first-order coupling if coupled nuclei have significantly different chemical shifts (Δν) compared to their coupling constant (J).

• Peaks form well-defined multiplets (doublets, triplets, quartets, etc.), and the intensities follow Pascal’s Triangle.

Characteristics of First-Order Coupling

• (n+1) Rule Applies– A proton with n equivalent neighbours splits into n+1peaks

• Pascal’s Triangle Intensity Pattern– Peak heights follow a predictable pattern

• Peak Splitting is Symmetric– The peaks are evenly spaced

  Spin Coupling

Second Order Coupling

• Coupling beyond three bonds may occur in the following circumstances:

  Ring strain in small rings or bridged systems

• Delocalization in alkenes

• Delocalization in aromatic rings

• “W” configuration in aromatic rings

• Definition: Second-order coupling occurs when the chemical shift difference (Δν) is comparable to the coupling constant (J), meaning Δν ≈ J.

Characteristics of Second-Order Coupling:

• (n+1) Rule Does Not Strictly Apply– Splitting may not match expectations

• Distorted Peak Intensities– Pascal’s Triangle does not hold.

- Peak Splitting May Be Uneven– The peaks may appear leaned, broadened, or merged.

Here are some important theoretical concepts from the notes you provided on NMR Spectroscopy:

1. NMR Spectroscopy: A technique for analyzing molecular structures based on the absorption of electromagnetic radiation.

2. Nuclear Spin and Magnetic Moments: Nuclei with a non-zero spin quantum number (I ≠ 0) interact with a magnetic field, leading to energy level splitting (Zeeman effect) and NMR signals.

3. Spin Quantum Number Rules: Defines which nuclei are NMR active based on their number of protons (Z) and neutrons (N).

4. Chemical Shift: The position of an NMR absorption, dependent on the electron density around an atom and its structural environment. Influenced by electronegativity, shielding, and deshielding effects.

5. Diamagnetic Anisotropy: The shielding or deshielding of protons through space due to the orientation of π electrons in a magnetic field (e.g., ring currents in benzene).

6. Integration: Indicates the relative number of hydrogen atoms for an NMR peak, reflecting the quantity of each type of hydrogen in the molecule.

7. Spin-Spin Splitting: The interaction between neighboring non-equivalent hydrogen nuclei, causing splitting patterns in NMR signals. Governed by the N+1 rule and Pascal's Triangle.

8. Coupling Constant (J): The distance (in Hertz) between the individual peaks making up a multiplet, indicating the strength of spin-spin coupling.

9. First Order Coupling: Occurs when coupled nuclei have significantly different chemical shifts compared to their coupling constant (Δν >> J). Characterized by well-defined multiplets and symmetric peak splitting.

10. Second Order Coupling: Occurs when the chemical shift difference is comparable to the coupling constant (Δν ≈ J), leading to distorted peak intensities and uneven splitting.