NMR Spectroscopy

Nuclear Magnetic Resonance Spectroscopy Electron has a spin and that spinning creates and associated magnetic field. Electron can behave like a tiny bar magnet. Atomic nucleus can spin and behave as a tiny bar magnet. These spinning nuclei generate tiny magnetic fields Any nucleus will spin (odd mass or odd atomic number) Will not spin (if even mass or even atomic number) Tiny magnets interact with an external magnetic field, denoted B0 Proton (1H) and carbon (13C) are the most important nuclear spins to organic chemists

Recall Mass number (atomic mass) is number of protons plus neutrons and can vary from isotopes of the same element Atomic number (number of protons or electrons) is the same for all isotopes of that element

the nuclei of some atoms spin: 1H, 13C, 19F, … Nuclear Magnetic Resonance (NMR) the nuclei of some atoms spin: 1H, 13C, 19F, … Any nucleus will spin (odd mass or odd atomic number) the nuclei of many atoms do not spin: 2H, 12C, 16O, … Will not spin (if even mass or even atomic number) moving charged particles generate a magnetic field () when placed between the poles of a powerful magnet, spinning nuclei will align with or against the applied magnetic field creating an energy difference. Mass of the element

the nuclei of some atoms spin: 1H, 13C, 19F, … Nuclear Magnetic Resonance (NMR) the nuclei of some atoms spin: 1H, 13C, 19F, … Any nucleus will spin (odd mass or odd atomic number) the nuclei of many atoms do not spin: 2H, 12C, 16O, … Will not spin (if even mass or even atomic number) moving charged particles generate a magnetic field () when placed between the poles of a powerful magnet, spinning nuclei will align with or against the applied magnetic field creating an energy difference. Using a fixed radio frequency, the magnetic field is changed until the ΔE = EEM. When the energies match, the nuclei can change spin states (resonate) and give off a magnetic signal. ΔE Mass of the element

Nuclear Magnetic Resonance Spectroscopy Nuclear spins are oriented randomly in the absence (a) of an external magnetic field but have a specific orientation in the presence (b) of an external field, B0 Some nuclear spins are aligned parallel to the external field Lower energy orientation More likely Some nuclear spins are aligned antiparallel to the external field Higher energy orientation Less likely

Nuclear Magnetic Resonance Spectroscopy When nuclei that are aligned parallel with an external magnetic field are irradiated with the proper frequency of electromagnetic radiation the energy is absorbed and the nuclei “spin-flips” to the higher-energy antiparallel alignment Nuclei that undergo “spin-flips” in response to applied radiation are said to be in resonance with the applied radiation - nuclear magnetic resonance Frequency necessary for resonance depends on strength of external field and the identity of the nuclei

Nuclear Magnetic Resonance Spectroscopy The energy difference DE between nuclear spin states depends on the strength of the applied magnetic field Absorption of energy with frequency n converts a nucleus from a lower to a higher spin state DE = 8.0 x 10-5 kJ/mol for magnetic field strength of 4.7 T a For field strength of 4.7 T a radiofrequency (rf) of n = 200 MHz is required to bring 1H nuclei into resonance For a field strength of 4.7 T a radiofrequency (rf) of n = 50 MHz is required to bring 13C nuclei into resonance

Nuclear Magnetic Resonance Spectroscopy Many nuclei exhibit NMR phenomenon All nuclei with odd number of protons of neutrons Nuclei with even numbers of both protons and neutrons do not exhibit NMR phenomenon

The Nature of NMR Absorptions The absorption frequency is not the same for all 1H and 13C nuclei Nuclei in molecules are surrounded by electrons Electrons set up tiny local magnetic fields that act in opposition to the applied field, shielding the nucleus from the full effect of the external magnetic field The effective field actually felt by the nucleus is the applied field reduced by the local shielding effects Beffective = Bapplied – Blocal

The Nature of NMR Absorptions The absorption frequency is not the same for all 1H and 13C nuclei Each chemically distinct nucleus in a molecule has a slightly different electronic environment and consequently a different effective field Each chemically distinct 13C or 1H nucleus in a molecule experiences a different effective field and will exhibit a distinct 13C or 1H NMR signal Hydrogens in most organic molecules are surrounded by electrons and by other atoms.

Chemical Shifts The NMR Chart The downfield, deshielded side is on the left, and requires a lower field strength for resonance The upfield, shielded side is on the right, and requires a higher field strength for resonance The tetramethylsilane (TMS) absorption is used as a reference point

Shielding and Deshielded Shielded (by the local environment) Greater electron density around each hydrogen Due to poor electron withdrawing group Due to poor inductive effect Deshielded (by the local environment) Less electron density around each hydrogen Due to high electronegative element Due to larger inductive effect

1H NMR Spectroscopy and Proton Equivalence 1H NMR spectroscopy determines how many kinds of electronically nonequivalent hydrogens are present in a molecule Equivalence or nonequivalence of two protons determined by replacing each H by an X (halogen group) Equivalent H give the same H-NMR signal Non equivalent H give different H-NMR signal Symmetrical compounds tend to contain a higher amount of equivalent hydrogens and thus fewer resonance signals in their NMRspectra

Protons are chemically identical and thus electronically equivalent Four possibilities: Protons are chemically unrelated and thus nonequivalent Protons are chemically identical and thus electronically equivalent Protons are electronically equivalent but not identical Replacement of a hydrogen gives a unique diastereomer (not mirror images of each other) with a second chirality center

1H NMR Spectroscopy and Proton Equivalence 1H NMR spectroscopy determines how many kinds of electronically nonequivalent hydrogens are present in a molecule Four possibilities: Protons that are unrelated and thus nonequivalent

1H NMR Spectroscopy and Proton Equivalence Protons are chemically identical and thus electronically equivalent Chemically identical protons are said to be homotopic

1H NMR Spectroscopy and Proton Equivalence Protons are electronically equivalent but not identical The two –CH2 – hydrogens on C2 of butane (as well as the two C3 hydrogens) are not identical because replacing one or the other would lead to a new chirality center Different enantiomers would result if pro-R or pro-S hydrogen were replaced Prochiral hydrogens are electronically equivalent and thus have the same NMR absorption

1H NMR Spectroscopy and Proton Equivalence Protons are electronically equivalent but not identical The two –CH2 – hydrogens on C2 of butane (as well as the two C3 hydrogens) are not identical because replacing one or the other would lead to a new chirality center Non-identical but electronically equivalent protons are said to be enantiotopic Different enantiomers would result if pro-R or pro-S hydrogen were replaced Prochiral hydrogens are electronically equivalent and thus have the same NMR absorption

1H NMR Spectroscopy and Proton Equivalence Replacement of a hydrogen gives a unique diastereomer (not mirror images of each other) with a second chirality center These hydrogens are neither electronically or chemically equivalent and will most likely show different 1H NMR absorptions

1H NMR Spectroscopy and Proton Equivalence Replacement of a hydrogen gives a unique diastereomer (not mirror images of each other) with a second chirality center Such hydrogens are diastereotopic Diastereotopic hydrogens are neither electronically or chemically equivalent and will most likely show different 1H NMR absorptions

Information from 1H-nmr spectra: Number of signals: How many different types of hydrogens in the molecule. Position of signals (chemical shift): What types of hydrogens. Relative areas under signals (integration): How many hydrogens of each type. Splitting pattern: How many neighboring hydrogens.

Number of signals: How many different types of hydrogens in the molecule

Practice, how many signals

Position of signals (chemical shift): what types of hydrogens. primary 0.9 ppm secondary 1.3 tertiary 1.5 aromatic 6-8.5 allyl 1.7 benzyl 2.2-3 chlorides 3-4 H-C-Cl bromides 2.5-4 H-C-Br iodides 2-4 H-C-I alcohols 3.4-4 H-C-O alcohols 1-5.5 H-O- (variable) Note: combinations may greatly influence chemical shifts. For example, the benzyl hydrogens in benzyl chloride are shifted to lower field by the chlorine and resonate at 4.5 ppm.

reference compound = tetramethylsilane (CH3)4Si @ 0.0 ppm remember: magnetic field   chemical shift convention: let most upfield signal = a, next most upfield = b, etc. … c b a tms

reference compound = tetramethylsilane (CH3)4Si @ 0.0 ppm remember: magnetic field   chemical shift convention: let most upfield signal = a, next most upfield = b, etc. … c b a tms

toluene b a

chemical shifts

Integration (relative areas under each signal): how many hydrogens of each type. a b c CH3CH2CH2Br a 3H a : b : c = 3 : 2 : 2 b 2H c 2H a b a CH3CHCH3 a 6H a : b = 6 : 1 Cl b 1H

integration

Integration of 1H NMR Absorptions: Proton Counting The area under each 1H NMR peak is proportional to the number of protons causing that peak Integrating (electronically measuring) the area under each peak makes it possible to determine the relative number of each kind of proton in a molecule Integrating the peaks of 2,2-dimethylpropanoate in a “stair-step” manner shows that they have 1:3 ratio, corresponding to the ratio of the numbers of protons (3:9)

Splitting pattern: how many neighboring hydrogens. In general, n-equivalent neighboring hydrogens will split a 1H signal into an ( n + 1 ) Pascal pattern. “neighboring” – no more than three bonds away n n + 1 Pascal pattern: 0 1 1 singlet 1 2 1 1 doublet 2 3 1 2 1 triplet 3 4 1 3 3 1 quartet 4 5 1 4 6 4 1 quintet

Spin-Spin Splitting in 1H NMR Spectra Multiple absorptions, called spin-spin splitting, are caused by the interaction (coupling) of the spins of nearby nuclei Tiny magnetic fields produced by one nucleus affects the magnetic field felt by neighboring nuclei If protons align with the applied field the effective field felt by neighboring protons is slightly larger If protons align against the applied field the effective field felt by neighboring protons is slightly smaller

note: the alcohol hydrogen –OH usually does not split neighboring hydrogen signals nor is it split. Normally a singlet of integration 1 between 1 – 5.5 ppm (variable).

splitting pattern?

Spin-Spin Splitting in 1H NMR Spectra The absorption of a proton can split into multiple peaks called a multiplet Remember ( n + 1 ) for splitting signals 1H NMR spectrum of bromoethane shows four peaks (a quartet) at 3.42 d for –CH2Br protons and three peaks (a triplet) at 1.68 d for –CH3 protons

Spin-Spin Splitting in 1H NMR Spectra Each –CH2Br proton of CH3CH2Br has its own nuclear spin which can align either with or against the applied field, producing a small change in the effective field experienced by the –CH3 protons Three possible spin states (combinations) Both protons spin in alignment with applied field Effective field felt by neighboring –CH3 protons is larger Applied field necessary to cause resonance is reduced One proton spin is aligned with and one proton spin is aligned against the applied field (two possible combinations) No effect on neighboring protons Both proton spins align against applied field Effective field felt by neighboring –CH3 is smaller Applied field necessary to cause resonance is increased

Spin-Spin Splitting in 1H NMR Spectra The origin of spin-spin splitting in bromoethane. The nuclear spins of – CH2Br protons, indicated by horizontal arrows, align either with or against the applied field, causing the splitting of –CH3 absorptions into a triplet

Spin-Spin Splitting in 1H NMR Spectra n + 1 rule Protons that have n equivalent neighboring protons show n + 1 peaks in their 1H NMR spectrum The septet is caused by splitting of the –CHBr- proton signal at 4.28 d by six equivalent neighboring protons on the two methyl groups (n = 6 leads to 6+1 = 7 peaks) The doublet at 1.71 d is due to signal splitting of the six equivalent methyl protons by the single –CHBr- proton (n = 1 leads to 2 peaks)

cyclohexane a singlet 12H

isopropyl chloride a b a CH3CHCH3 Cl a doublet 6H b septet 1H

The Isopropyl Group: Equivalent Neighbors

Peak Intensity Variation

alcohols

C13 NMR: Differences from 1H NMR Signal for a carbon atom is 10-4 times weaker than hydrogen Carbon signals are spread over a much wider range All signals appear as singlets. Signal intensity varies and can not be used to determine how many carbon atoms are responsible for each signal

13C – nmr 13C ~ 1.1% of carbons number of signals: how many different types of carbons splitting: number of hydrogens on the carbon chemical shift: hybridization of carbon sp, sp2, sp3 chemical shift: evironment

Characteristics of 13C NMR Spectroscopy Factors that affect chemical shifts: Chemical shift affected by nearby electronegative atoms Carbons bonded to electronegative atoms absorb downfield from typical alkane carbons Hybridization of carbon atoms sp3-hybridized carbons generally absorb from 0 to 90 d sp2-hybridized carbons generally absorb from 110 to 220 d C=O carbons absorb from 160 to 220 d

13C-nmr 2-bromobutane a c d b CH3CH2CHCH3 Br

Characteristics of 13C NMR Spectroscopy 13C spectrum for butan-2-one Butan-2-one contains 4 chemically nonequivalent carbon atoms Carbonyl carbons (C=O) are always found at the low-field end of the spectrum from 160 to 220 d

Practice Predicting Chemical Shifts in 13C NMR Spectra At what approximate positions would you expect ethyl acrylate, H2C=CHCO2CH2CH3, to show 13C NMR absorptions?

Solution Predicting Chemical Shifts in 13C NMR Spectra Ethyl acrylate has five distinct carbons: two different C=C, one C=O, one C(O)-C, and one alkyl C. From Figure 11.7, the likely absorptions are The actual absorptions are at 14.1, 60.5, 128.5, 130.3, and 166.0 d