Nuclear Magnetic Resonance NMR Phenomenon µ A spinning charged particle generates a magnetic field. A nucleus with a spin angular momentum will generate a magnetic moment (!). E Nuclear Spin States aligned against B 0 Energy difference between the states at a particular magnet strength. In the R f range of the EM Spectrum. 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 1 B 0 aligned with 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. 2 NMR Active Nuclei NMR Instrumentation Many nuclei are NMR Active Spin Quantum Number I! 0 1 -- I = "; 13 -- I = " 12, 16 -- I = 0 -- an t be observed ther nuclei that are NMR active 2 (D), 14 N, 19 F, 31 P 3 4
Magnetic Resonance Imaging To summarize NMR is the basis for MRI µ When placed in a magnetic field (Bo), they will adopt two different states - one aligned with the field and one aligned against the field. A spinning charged particle generates a magnetic field. A nucleus with a spin angular momentum will generate a magnetic moment (m). B0 aligned against B0 Energy difference between the states at a particular magnet strength. In the Rf range of the EM Spectrum. E aligned with B0 B0 5 6 Methyl Acetate - Proton NMR Methyl Acetate - arbon NMR 3 3 3 3 solvent 7 8
µ Electronic Shielding - Local Environments B local B effective = B 0 - B local 3 3 Methyl Acetate - Proton NMR Actual magnetic field felt by the nucleus B 0 B effective 9 10 3 3 Methyl Acetate - arbon NMR solvent hemical Shift The difference in resonance frequency of a nuclei relative to a standard Most Shielded Relatively Inert 3 Volatile 3 Si 3 Resonance of standard is set to 0 3 TMS TetraMethylSilane 11 12
NMR Scale Different Spectrometer Frequencies X-Axis - frequency axis NMR Spectrum Each specific instrument has it s own magnetic field strength - resonace occurs at different frequencies. aligned against B 0 Low Field Little electron shielding (more electron withdrawing groups) igh Field More electron shielding (less electron withdrawing groups) 100 Mz NMR 300 Mz 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 peaks measured as a shift (in z) away from TMS Reference TMS Reference TMS 10 z 0 300 z 100 z 0 13 14 Standard Scale NMR Scale! = ppm = hemical Shift from TMS (z) Spectrometer Frequency (Mz) 100 Mz NMR 300 Mz NMR 100 z 100 Mz 300 z 300 Mz = 1.0 ppm = 1.0 ppm Reference TMS 1.0 ppm 0 15 16
13 NMR 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! 200 150 100 50 0 ppm 17 18 Symmetry in molecules can make carbons hemically Equivalent Symmetry Symmetry Some molecules have more than one mirror plane l 3 3 3 3 3 same electronic environment Br 3 19 20
Symmetry Symmetry 3 3 3 3 3 3 3 3 21 22 Substitution of arbon 13 NMR Regions The intensity of the peaks roughly correlates with the number of hydrogens on the carbon. 13 NMR R R R R R NR 2 N X! 200 150 100 50 0 p 23 24
Bromooctanol Bromooctanal Br Br 25 26 Alanine Me-Ester l Alaninol 3 3 N 3 l 3 N 2 27 28
Alaninol - phthalimide DEPT-13 3 N A - normal 13 B - carbons only - dd # up (3 and ) Even # down (2) 29 30 Example from 13.7 A Real Example l K ethanol or N N N N R N N 2, Pd/ 2, Pd/ N N R N 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 31 32
The Answer Is... N Number of chemically different hydrogens Relative Ratios of protons (peak size) Proton NMR ow many neighboring hydrogens N hemical shifts and functional groups N N 33 34 Proton Equivalency Proton NMR Scale omotopic Diastereotopic Range 0-10 ppm 3 3 3 3 l X 3 3 replace 's - same X 3 3 Enantiotopic 3 2 3 replace 's - enantiomers X 3 3 l replace 's - diastereomers X 3 3 l 1 NMR X X X! 10 9 8 7 6 5 4 3 2 1 0 ppm 3 2 3 3 2 3 35 36
NMR orrelation hart Methyl Acetate Typical NMR hemical Shifts Functional Group X X 1 hemical Shift (ppm) 13 hemical Shift (ppm) Alkane 0.7-1.8 10-60 Allylic or next to carbonyl 1.6-2.4 30-60 next to halogen or alcohol 2.5-4.0 20-85 next to oxygen of an ester 4.0-5.0 50-85 vinylic 4.5-6.5 110-150 aromatic 6.5-8.0 110-140 aldehyde 9.7-10.0 190-220 alcohol varies widely will exchange with D2 N/A carbonyl of ester, amide, or carboxylic acid (X =, N) N/A 165-185 carbonyl of ketone or aldehyde N/A 190-220 3 3 Area under peak corresponds to the number of s for that resonance Type 37 38 Triphenyl Methanol Ethyl Acetate 3 39 2 3 40
Spin Spin Splitting Protons on adjacent carbons also have an effect Resonances will split into n+1 number of peaks Spin Spin Splitting Two hydrogens split neighbors into a triplet a b a b 1 NMR (without a b b 1 NMR (without a b b b 1 NMR (with 1 NMR (with 1 : 2 : 1 41 42 Spin Spin Splitting Spin Spin Splitting Every splitting can be broken down into a series of doublets a b b b 1 NMR (without a 1 1 Three neighbors - Quartet a b b b b 1 NMR (without a b 1 NMR (with 1 NMR (with 1 : 2 : 1 1 1 : 3 : 3 : 1 1 43 44
b b a b b b b a will split into 7 peaks 64 different combinations of 6 spins igher Spin Spin Splitting Pascal s Triangle singlet 1 doublet 1 1 triplet 1 2 1 quartet 1 3 3 1 quintet 1 4 6 4 1 sextet 1 5 10 10 5 1 septet 1 6 15 20 15 6 1 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. l 2 2 l). 45 46 Doublet Splitting Ethanol Note that the (and N) usually don t couple. 3 Methyl sees 1 neighbor, Methine sees 3 3 N 3 l 47 48
1,1,2-Trichloroethane 2-Bromopropane 49 50 Butanone para-methoxypropiophenone 51 52
Toluene innamaldehyde Sometimes peaks overlap Multiple oupling 53 54 Spin Spin Splitting oupling with the same Every splitting can be broken down into a series of doublets a b 1 NMR (without a a-b = 5 z a-c = 5 z a b b 1 1 b a c coupling with b 5 1 NMR (with coupling with c 5 5 1 2 1 1 : 2 : 1 55 56
oupling with different values innamaldehyde a Multiple oupling 1-2 = 6 z, 2-3 = 12 z a-b = 5 z a-c = 10 z coupling with b 5 b a c 10 coupling with 10 c 1 1 1 1 a coupling with c 10 coupling with b 5 5 1 1 1 1 57 58 innemaldehyde Multiple oupling - Identical a a-b = 5 z a-c = 5 z b a c coupling with b 5 c coupling with c 5 5 1 2 1 coupling with c 1 3 3 1 5 5 5 59 60
Multiple oupling - Different Nitropropane a-b = 10 z a-c = 5 z a b a c c coupling with c 5 coupling with c 5 5 1 2 1 coupling with b 1 2 2 2 1 10 10 10 61 62 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. 63