Chapter 13 Structure Determination: Nuclear Magnetic Resonance Spectroscopy

Learning Objectives (13.1) Nuclear magnetic resonance spectroscopy (13.2) The nature of NMR absorptions (13.3) The chemical shift (13.4) Chemical shifts in 1H NMR spectroscopy

Learning Objectives (13.5) Integration of 1H NMR absorptions: Proton counting (13.6) Spin–spin splitting in 1H NMR spectra (13.7) 1H NMR spectroscopy and proton equivalence (13.8) More complex spin–spin splitting patterns

Learning Objectives (13.9) Uses of 1H NMR spectroscopy (13.10) 13C NMR spectroscopy: Signal averaging and FT–NMR (13.11) Characteristics of 13C NMR spectroscopy (13.12) DEPT 13C NMR spectroscopy

Learning Objectives (13.13) Uses of 13C NMR spectroscopy

Nuclear Magnetic Resonance Spectroscopy Nuclei are positively charged and interact with an external magnetic field denoted by B0 Magnetic rotation of nuclei is random in the absence of a magnetic field In the presence of a strong magnet, nuclei adopt specific orientations Nuclear magnetic resonance spectroscopy

Nuclear Magnetic Resonance Spectroscopy When exposed to a certain frequency of electromagnetic radiation, oriented nuclei absorb energy and causes a spinflip from a state of lower energy to higher energy Nuclear magnetic resonance - Nuclei are in resonance with applied radiation Frequency that causes resonance depends on: Strength of external magnetic field Identity of the nucleus Electronic environment of the nucleus Nuclear magnetic resonance spectroscopy

Nuclear Magnetic Resonance Spectroscopy Larmor equation Relation between Resonance frequency of a nucleus Magnetic field and the magnetogyric ratio of the nucleus Nuclear magnetic resonance spectroscopy

Worked Example Calculate the amount of energy required to spin-flip a proton in a spectrometer operating at 300 MHz Analyze if the increase of spectrometer frequency from 200 MHz to 300 MHz increases or decreases the amount of energy necessary for resonance Nuclear magnetic resonance spectroscopy

Worked Example Solution: Increasing the spectrometer frequency from 200 MHz to 300 MHz increases the amount of energy needed for resonance Nuclear magnetic resonance spectroscopy

The Nature of NMR Absorptions Absorption frequencies differ across 1H and 13C molecules Shielding: Opposing magnetic field produced by electrons surrounding nuclei to counteract the effects of an external magnetic field Effect on the nucleus is lesser than the applied magnetic field Beffective = Bapplied – Blocal Individual variances in the electronic environment of nuclei leads to different shielding intensities The nature of NMR absorptions

Figure 13.3 - NMR Spectrum of 1H and 13C The nature of NMR absorptions

Working of an NMR Spectrometer Organic sample dissolved in a suitable solvent is placed in a thin glass tube between the poles of a magnet 1H and 13C nuclei respond to the magnetic field by aligning themselves to one of the two possible orientations followed by rf irradiation Constant and varied strength of the applied field causes each nucleus to resonate at a slightly varied field strength Absorption of rf energy is monitored by a sensitive detector that displays signals as a peak The nature of NMR absorptions

Figure 13.4 - Operation of a Basic NMR Spectrometer The nature of NMR absorptions

NMR Spectrometer Time taken by IR spectroscopy is about 10–13 s Time taken by NMR spectroscopy is about 10–3 s Provides a blurring effect that is used in the measurement of rates and activation energies of vary fast processes The nature of NMR absorptions

Worked Example Explain why 2-chloropropene shows signals for three kinds of protons in its 1H NMR spectrum Solution: 2-Chloropropene has three kinds of protons Protons b and c differ because one is cis to the chlorine and the other is trans The nature of NMR absorptions

The Chemical Shift The left segment of the chart is the downfield Nuclei absorbing on the downfield have less shielding as they require a lower field for resistance The right segment is the upfield Nuclei absorbing on the upfield have more shielding as they require a higher field strength for resistance The chemical shift

Figure 13.5 - The NMR Chart The chemical shift

The Chemical Shift Chemical shift is the position on the chart at which a nucleus absorbs The delta (δ) scale is used in calibration of the NMR chart 1 δ = 1 part-per-million of the spectrometer operating frequency The delta scale is used as the units of measurement can be used to compare values across other instruments The chemical shift

Worked Example The 1H NMR peak of CHCl3 was recorded on a spectrometer operating at 200 MHz providing the value of 1454 Hz Convert 1454 Hz into δ units Solution: The chemical shift

Chemical Shifts in 1H NMR Spectroscopy Chemical shifts are due to the varied electromagnetic fields produced by electrons surrounding nuclei Protons bonded to saturated, sp3-hybridized carbons absorb at higher fields Protons bonded to sp2-hybridized carbons absorb at lower fields Protons bonded to electronegative atoms absorb at lower fields Chemical shifts in 1H NMR spectroscopy

Table 13.2 - Regions of the 1H NMR Spectrum Chemical shifts in 1H NMR spectroscopy

Worked Example CH2Cl2 has a single 1H NMR peak Solution: Determine the location of absorption Solution: For CH2Cl2 , δ = 5.30 The location of absorption are the protons adjacent to the two halogens Chemical shifts in 1H NMR spectroscopy

Integration of 1H NMR Absorptions: Proton Counting In the figure, the peak caused by (CH3)3C–protons is larger than the peak caused by –OCH protons Integration of the area under the peak can be used to quantify the different kinds of protons in a molecule Integration of 1H NMR absorptions: Proton counting

Worked Example Mention the number of peaks in the 1H NMR spectrum of 1,4-dimethyl-benzene (para-xylene or p-xylene) Mention the ratio of peak areas possible on integration of the spectrum Integration of 1H NMR absorptions: Proton counting

Worked Example Solution: There are two absorptions in the 1H NMR spectrum of p-xylene The four ring protons absorb at 7.05 δ and the six methyl-groups absorb at 2.23 δ The peak ratio of methyl protons:ring protons is 3:2 Characteristics of 13C NMR spectroscopy

Worked Example Characteristics of 13C NMR spectroscopy

Spin-Spin Splitting in 1H NMR Spectra Multiplet: Absorption of a proton that splits into multiple peaks The phenomenon is called spin-spin splitting Caused by coupling of neighboring spins Spin-spin splitting in 1H NMR spectra

Spin-Spin Splitting in 1H NMR Spectra Alignment of –CH2Br proton spins with the applied field can result in: Slightly larger total effective field and slight reduction in the applied field to achieve resonance There is no effect if one of the –CH2Br proton spins aligns with the applied field and the other aligns against it Alignment of –CH2Br proton spins against the applied field results in: Smaller effective field and an increased applied field to achieve resonance Spin-spin splitting in 1H NMR spectra

Figure 13.8 - The Origin of Spin-Spin Splitting in Bromoethane Spin-spin splitting in 1H NMR spectra

Spin-Spin Splitting in 1H NMR Spectra n + 1 rule: Protons that exhibit n + 1 peaks in the NMR spectrum possess n = number of equivalent neighboring protons Coupling constant is the distance between peaks in a multiplet Spin-spin splitting in 1H NMR spectra

Spin-Spin Splitting in 1H NMR Spectra It is possible to identify multiplets in a complex NMR that are related Multiplets that have the same coupling constant can be related Multiplet-causing protons are situated adjacent to each other in the molecule Spin-spin splitting in 1H NMR spectra

Rules of Spin-Spin Splitting Chemically equivalent protons do not show spin-spin splitting The signal of a proton with n equivalent neighboring protons is split into a multiplet of n + 1 peaks with a coupling constant Two groups of photons coupled together have the same coupling constant, J Spin-spin splitting in 1H NMR spectra

Worked Example The integrated 1H NMR spectrum of a compound of formula C4H10O is shown below Propose a structure Spin-spin splitting in 1H NMR spectra

Worked Example Solution: The molecular formula (C4H10O) indicates that the compound has no multiple bonds or rings The 1H NMR spectrum shows two signals, corresponding to two types of hydrogens in the ratio 1.50:1.00, or 3:2 Since the unknown contains 10 hydrogens, four protons are of one type and six are of the other type The upfield signal at 1.22 δ is due to saturated primary protons Spin-spin splitting in 1H NMR spectra

Worked Example The downfield signal at 3.49 δ is due to protons on carbon adjacent to an electronegative atom - in this case, oxygen The signal at 1.23 δ is a triplet, indicating two neighboring protons The signal at 3.49 δ is a quartet, indicating three neighboring protons This splitting pattern is characteristic of an ethyl group The compound is diethyl ether, CH3CH2OCH2CH3 Spin-spin splitting in 1H NMR spectra

1H NMR Spectroscopy and Proton Equivalence Proton NMR is much more sensitive than 13C and the active nucleus (1H) is nearly 100 % of the natural abundance Shows how many kinds of nonequivalent hydrogens are in a compound Theoretical equivalence can be predicted by comparing structures formed by replacing each H with X gives the same or different outcome Equivalent H’s have the same signal while nonequivalent are different There are degrees of nonequivalence 1H NMR spectroscopy and proton equivalence

1H NMR Spectroscopy and Proton Equivalence One use of 1H NMR is to ascertain the number of electronically non-equivalent hydrogens present in a molecule In relatively small molecules, a brief look at the structure can help determine the kinds of protons present and the number of possible NMR absorptions Equivalence or nonequivalence of two protons can be determined by comparison of structures formed if each hydrogen were replaced by an X group 1H NMR spectroscopy and proton equivalence

1H NMR Spectroscopy and Proton Equivalence Possibilities If the protons are chemically unrelated and non-equivalent, the products formed by substitution would be different constitutional isomers 1H NMR spectroscopy and proton equivalence

1H NMR Spectroscopy and Proton Equivalence If the protons are chemically identical, the same product would be formed despite the substitution 1H NMR spectroscopy and proton equivalence

1H NMR Spectroscopy and Proton Equivalence If the hydrogens are homotopic but not identical, substitution will form a new chirality center Hydrogens that lead to formation of enantiomers upon substitution with X are called enantiotopic 1H NMR spectroscopy and proton equivalence

1H NMR Spectroscopy and Proton Equivalence If the hydrogens are neither homotopic nor enantiotopic, substitution of a hydrogen at C3 would form a second chirality center 1H NMR spectroscopy and proton equivalence

Worked Example How many absorptions will (S)-malate, an intermediate in carbohydrate metabolism have in its 1H NMR spectrum? Explain 1H NMR spectroscopy and proton equivalence

Worked Example Solution: Because (S)-malate already has a chirality center(starred), the two protons next to it are diastereotopic and absorb at different values The 1H NMR spectrum of (S)-malate has four absorptions 1H NMR spectroscopy and proton equivalence

More Complex Spin-Spin Splitting Patterns Some hydrogens in a molecule possess accidentally overlapping signals In the spectrum of toluene (methylbenzene), the five aromatic ring protons produce a complex, overlapping pattern though they are not equivalent More complex spin–spin splitting patterns

More Complex Spin-Spin Splitting Patterns Splitting of a signal by two or more nonequivalent kinds of protons causes a complication in 1H NMR spectroscopy More complex spin–spin splitting patterns

Figure 13.14 - Tree Diagram for the C2 proton of trans-cinnamaldehyde More complex spin–spin splitting patterns

Worked Example 3-Bromo-1-phenyl-1-propene shows a complex NMR spectrum in which the vinylic proton at C2 is couples with both the C1 vinylic proton (J = 16 Hz) and the C3 methylene protons (J = 8 Hz) Draw a tree diageam for the C2 proton signal and account for the fact that a live-line multiplet is observed More complex spin–spin splitting patterns

Worked Example Solution: C2 proton couples with vinylic proton (J = 16) Hz C2 proton’s signal is split into a doublet C2 proton also couples with the two C3 protons (J = 8 Hz) Each leg of the C2 proton doublet is split into a triplet to produce a total of six lines More complex spin–spin splitting patterns

Worked Example More complex spin–spin splitting patterns

Uses of 1H NMR Spectroscopy The technique is used to identify likely products in the laboratory quickly and easily NMR can help prove that hydroboration-oxidation of alkenes occurs with non-Markovnikov regiochemistry to yield the less highly substituted alcohol Uses of 1H NMR spectroscopy

Figure 13.15 - 1H NMR Spectra of Cyclohexylmethanol Uses of 1H NMR spectroscopy

Worked Example Mention how 1H NMR is used to determine the regiochemistry of electrophilic addition to alkenes Determine whether addition of HCl to 1-methylcyclohexene yields 1-chloro-1-nethylcyclohexane or 1-chloro-2-methylcyclohexane Uses of 1H NMR spectroscopy

Worked Example Solution: Referring to 1H NMR methyl group absorption The unslpit methyl group in the left appears as a doublet in the product on the right Bonding of a proton to a carbon that is also bonded to an electronegative atom causes a downfield absorption in the 2.5–4.0 region 1H NMR spectrum of the product would confirm the product to be 1-chloro-1-methylcyclohexane Uses of 1H NMR spectroscopy

13C NMR Spectroscopy: Signal Averaging and FT–NMR Carbon-13 is the only naturally occurring carbon isotope that possesses a nuclear spin, but its natural abundance is 1.1% Signal averaging and Fourier-transform NMR (FT–NMR) help in detecting carbon 13 Due to the excess random electronic background noise present in 13C NMR, an average is taken from hundreds or thousands of individual NMR spectra 13C NMR spectroscopy: Signal averaging and FT–NMR

Figure 13.16 - Carbon-13 NMR Spectra of 1-Pentanol 13C NMR spectroscopy: Signal averaging and FT–NMR

13C NMR Spectroscopy: Signal Averaging and FT–NMR Spin-spin splitting is observed only in 1H NMR The low natural abundance of 13C nucleus is the reason that coupling with adjacent carbons is highly unlikely Due to the broadband decoupling method used to record 13C spectra, hydrogen coupling is not seen 13C NMR spectroscopy: Signal averaging and FT–NMR

Characteristics of 13C NMR Spectroscopy 13C NMR provides a count of the different carbon atoms in a molecule 13C resonances are 0 to 220 ppm downfield from TMS Characteristics of 13C NMR spectroscopy

Characteristics of 13C NMR Spectroscopy General factors that determine chemical shifts The electronegativity of nearby atoms The diamagnetic anisotropy of pi systems The absorption of sp3-hybridized carbons and sp2 carbons Characteristics of 13C NMR spectroscopy

Figure 13.18 - Carbon-13 Spectra of 2-butanone and para-bromoacetophenone Characteristics of 13C NMR spectroscopy

Worked Example Classify the resonances in the 13C spectrum of methyl propanoate, CH3CH2CO2CH3 Characteristics of 13C NMR spectroscopy

Worked Example Solution: Methyl propanoate has four unique carbons that individually absorb in specific regions of the 13C spectrum Integration of 1H NMR absorptions: Proton counting

DEPT 13C NMR Spectroscopy DEPT-NMR (distortionless enhancement by polarization transfer) Stages of a DEPT experiment Run a broadband-decoupled spectrum Run a DEPT-90 Run a DEPT-135 The DEPT experiment manipulates the nuclear spins of carbon nuclei DEPT 13C NMR spectroscopy

Figure 13.20 – DEPT-NMR Spectra for 6-methyl-5-hepten-2-ol DEPT 13C NMR spectroscopy

Uses of 13C NMR Spectroscopy Helps in determining molecular structures Provides a count of non-equivalent carbons Provides information on the electronic environment of each carbon and the number of attached protons Provides answers on molecule structure that IR spectrometry or mass spectrometry cannot provide Uses of 13C NMR spectroscopy

Figure 13.21 - 13C NMR Spectrum of 1-methylcyclohexane Uses of 13C NMR spectroscopy

Worked Example Propose a structure for an aromatic hydrocarbon, C11H16, that has the following 13C NMR spectral data: Broadband decoupled: 29.5, 31.8, 50.2, 125.5, 127.5, 130.3, 139.8 δ DEPT-90: 125.5, 127.5, 130.3 δ DEPT-135: positive peaks at 29.5, 125.5, 127.5, 130.3 δ; negative peak at 50.2 δ Uses of 13C NMR spectroscopy

Worked Example Solution: Calculate the degree of unsaturation of the unknown compound C11H16 has 4 degrees of unsaturation Look for elements of symmetry 7 peaks appearing in the 13C NMR spectrum indicate a plane of symmetry According to the DEPT-90 spectrum, 3 of the kinds of carbons in the aromatic ring are CH carbons Spin–spin splitting in 1H NMR spectra

Worked Example The unknown structure is a monosubstituted benzene ring with a substituent containing CH2 and CH3 carbons Spin–spin splitting in 1H NMR spectra

Summary Nuclear magnetic resonance spectroscopy or NMR is the most important spectroscopic technique used in the determination of molecular structure Magnetic nuclei such as 1H and 13C spin-flip from a lower energy state to a higher energy state when they absorb radiofrequency waves Each 1H or 13C nucleus possesses a unique electromagnetic field that causes it to resonate at different values of the applied field causing peaks whose exact position is termed a chemical shift

Summary Delta (δ) is the unit of calibration in NMR charts Tetramethylsilane (TMS) is a reference point on the NMR chart TMS absorption that occurs at the right-hand (upfield) side of the chart is assigned a value of 0 δ Fourier-transform NMR (FT–NMR) spectrometers are used to obtain 13C spectra using broadband decoupling of proton spins

Summary Electronic integration of the area under each absorption peak in 1H NMR spectra is used to determine the number of hydrogens that cause each peak Neighboring nuclear spins can couple to cause the spin-spin splitting of NMR peaks into multiplets The NMR signal of a hydrogen neighbored by n equivalent adjacent hydrogens splits into n + 1 peaks (the n + 1 rule) with coupling constant J