NMR Spectroscopy
NMR Phenomenon Nuclear Magnetic Resonance µ A spinning charged particle generates a magnetic field. A nucleus with a spin angular momentum will generate a magnetic moment (μ). If these tiny magnets are placed in an applied magnetic field (Bo), they will adopt two different states - one aligned with the field and one aligned against the field. The energy difference between these two states is what we are observing with NMR. B 0 2
Nuclear Spin States aligned against B 0 E Energy difference between the states at a particular magnet strength. In the R f range of the EM Spectrum. aligned with B 0 B 0 When EM waves at this energy are directed at the nuclei - it will absorb. Spins will flip from lower energy to higher energy. At that energy, nuclei are In Resonance. 3
NMR Active Nuclei Many nuclei are NMR Active Spin Quantum Number I 0 1 H -- I = ½; 13 -- I = ½ 12, 16 -- I = 0 -- an t be observed ther nuclei that are NMR active 2 H (D), 14 N, 19 F, 31 P 4
NMR Instrumentation 5
Magnetic Resonance Imaging NMR is the basis for MRI 6
To summarize µ A spinning charged particle generates a magnetic field. A nucleus with a spin angular momentum will generate a magnetic moment (m). When placed in a magnetic field (Bo), they will adopt two different states - one aligned with the field and one aligned against the field. B 0 aligned against B 0 E Energy difference between the states at a particular magnet strength. In the R f range of the EM Spectrum. aligned with B 0 B 0 7
Methyl Acetate - Proton NMR H 3 H 3 8
Methyl Acetate - arbon NMR H 3 H 3 solvent 9
Electronic Shielding - Local Environments B local µ B effective = B 0 - B local Actual magnetic field felt by the nucleus B 0 B effective 10
Methyl Acetate - Proton NMR H 3 H 3 11
Methyl Acetate - arbon NMR H 3 H 3 solvent 12
hemical Shift The difference in resonance frequency of a nuclei relative to a standard Most Shielded Relatively Inert Volatile H 3 H 3 Si H 3 Resonance of standard is set to 0 H 3 TMS TetraMethylSilane 13
NMR Scale X-Axis - frequency axis NMR Spectrum Low Field Little electron shielding (more electron withdrawing groups) High Field More electron shielding (less electron withdrawing groups) peaks measured as a shift (in Hz) away from TMS Reference TMS 10 Hz 0 14
Different Spectrometer Frequencies Each specific instrument has it s own magnetic field strength - resonace occurs at different frequencies. aligned against B 0 100 MHz NMR 300 MHz NMR E B 0 Energy difference between the states at a particular magnet strength. In the R f range of the EM Spectrum. aligned with B 0 Reference TMS 300 Hz 100 Hz 0 15
Standard Scale δ = ppm = hemical Shift from TMS (Hz) Spectrometer Frequency (MHz) 100 MHz NMR 300 MHz NMR 100 Hz 100 MHz 300 Hz 300 MHz = 1.0 ppm = 1.0 ppm Reference TMS 1.0 ppm 0 16
NMR Scale 17
13 NMR Difficult - arbon 13 only 1.1% of all carbon. Number of different carbons Functional Group Regions 13 NMR R R R R R NR 2 N X δ 200 150 100 50 0 ppm 18
13 NMR H 19
Symmetry Symmetry in molecules can make carbons hemically Equivalent l H 3 H 3 same electronic environment Br 20
Symmetry Some molecules have more than one mirror plane H 3 H 3 H 3 H 3 21
Symmetry H 3 H 3 H 3 H 3 22
Symmetry H 3 H 3 H 3 H 3 23
Substitution of arbon The intensity of the peaks roughly correlates with the number of hydrogens on the carbon. 24
13 NMR Regions 13 NMR R R R R R NR 2 N X δ 200 150 100 50 0 p 25
Bromooctanol H Br 26
Bromooctanal H Br 27
Alanine Me-Ester Hl H 3 H 3 NH 3 l 28
Alaninol H H 3 NH 2 29
Alaninol - phthalimide H H 3 N 30
DEPT-13 H A - normal 13 B - H carbons only - dd # up (H3 and H) Even # down (H2) 31
Example from 13.7 l KH ethanol or 32
A Real Example NH NH R NH N N N H 2, Pd/ H 2, Pd/ NH NH R NH N N In the alkane region there would only be 4 peaks due to symmetry N In the alkane region there would be 6 different peaks 33
The Answer Is... NH N NH N 34
Proton NMR Number of chemically different hydrogens Relative Ratios of protons (peak size) How many neighboring hydrogens hemical shifts and functional groups 35
Proton Equivalency Homotopic Diastereotopic H H H 3 H 3 replace H's - same Enantiotopic H H 3 H 3 H H l replace H's - diastereomers H H X H H X H X H 3 H 3 X H H 3 H 3 H 3 H2 H 3 H 3 H 3 H l H 3 H 3 H l replace H's - enantiomers X H H X H 3 H2 H 3 H 3 H2 H 3 36
Proton NMR Scale Range 0-10 ppm 1 H NMR H H H H H H H H H H H H H H H X δ 10 9 8 7 6 5 4 3 2 1 0 ppm 37
NMR orrelation hart Typical NMR hemical Shifts Functional Group Type 1 H hemical Shift (ppm) 13 hemical Shift (ppm) H Alkane 0.7-1.8 10-60 H Allylic or next to carbonyl 1.6-2.4 30-60 X H next to halogen or alcohol 2.5-4.0 20-85 H next to oxygen of an ester 4.0-5.0 50-85 H vinylic 4.5-6.5 110-150 H aromatic 6.5-8.0 110-140 H H X aldehyde 9.7-10.0 alcohol carbonyl of ester, amide, or carboxylic acid (X =, N) varies widely will exchange with D 2 N/A 190-220 N/A 165-185 carbonyl of ketone or aldehyde N/A 190-220 38
Methyl Acetate H 3 H 3 Area under peak corresponds to the number of H s for that resonance 39
Triphenyl Methanol H 40
Ethyl Acetate H 2 H 3 H 3 41
Spin Spin Splitting Protons on adjacent carbons also have an effect Resonances will split into n+1 number of peaks H a H b 1 H NMR (without coupling) H a H b H b 1 H NMR (with coupling) J J 42
Spin Spin Splitting Two hydrogens split neighbors into a triplet H a H b H b 1 H NMR (without coupling) H a H b H b 1 H NMR (with coupling) J J J 1 : 2 : 1 43
Spin Spin Splitting Every splitting can be broken down into a series of doublets H a H b H b 1 H NMR (without coupling) H a H b J 1 1 1 H NMR (with coupling) J J 1 : 2 : 1 44
Spin Spin Splitting Three neighbors - Quartet H a H b H b H b 1 H NMR (without coupling) H a H b H b 1 H NMR (with coupling) J J J J 1 1 : 3 : 3 : 1 1 45
Higher Spin Spin Splitting Pascal s Triangle H b H a H b H b H b H b H b H a will split into 7 peaks 64 different combinations of 6 spins singlet 1 doublet triplet quartet quintet sextet septet 1 1 1 2 1 1 3 3 1 1 4 6 4 1 1 5 10 10 5 1 1 6 15 20 15 6 1 46
Summary of Spin Spin Splitting Proton resonance split into n+1 number of peaks Relative ratio of peaks depends on number of spin states of the neighbors. Adjacent protons will couple with the same coupling constant. Protons farther away usually do not couple. hemically equivalent protons cannot couple (eg. lh 2 H 2 l). 47
Doublet Splitting H 3 Methyl sees 1 neighbor, Methine sees 3 H3 H NH 3 l 48
Ethanol Note that the H (and NH) usually don t couple. 49
1,1,2-Trichloroethane 50
2-Bromopropane 51
Butanone 52
para-methoxypropiophenone 53
Toluene Sometimes peaks overlap 54
innamaldehyde Multiple oupling 55
Spin Spin Splitting Every splitting can be broken down into a series of doublets H a H b H b 1 H NMR (without coupling) H a H b J 1 1 1 H NMR (with coupling) J J 1 : 2 : 1 56
oupling with the same J H a J a-b = 5 Hz J a-c = 5 Hz H b H a H c coupling with H b 5 coupling with H c 5 5 1 2 1 57
oupling with different J values H a J a-b = 5 Hz J a-c = 10 Hz coupling with H b 5 H b H a H c coupling with H c 1 1 1 1 10 10 H a coupling with H c 10 coupling with H b 5 5 1 1 1 1 58
innamaldehyde Multiple oupling J H1-H2 = 6 Hz, H2-H3 = 12 Hz 59
innemaldehyde 60
Multiple oupling - Identical J H a J a-b = 5 Hz J a-c = 5 Hz H b H a H c coupling with H b 5 H c coupling with H c 5 5 1 2 1 coupling with H c 1 3 3 1 5 5 5 61
Multiple oupling - Different J J a-b = 10 Hz J a-c = 5 Hz H a H b H a H c H c coupling with H c 5 coupling with H c 5 5 1 2 1 coupling with H b 1 2 2 2 1 10 10 10 62
Nitropropane 63
Strategies for Determining Unknows Given the Molecular Formula - calculate degrees of unsaturation. Identify functional groups Identify pieces of the structure Put the pieces together in a reasonable way Double check that your structure matches all the data given. 64