Kcal/mol 5.7 X X X X X EIMSNMR

To here! Nuclear Magnetic Resonance (NMR) Spectroscopy From here…

The Nobel Prize in Physics 1952 " for their development of new methods for nuclear magnetic precision measurements and discoveries in connection therewith " Felix BlochEdward Mills Purcell

Magnetic nuclei are in resonance with external magnetic field if they absorb energy and “spin-flip” from low energy state (parallel orientation) to high energy state (antiparallel orientation).

5 atomic nuclei in absence of magnetic field atomic nuclei in presence of external magnetic field atomic nuclei can either align parallel (lower E) or antiparallel (higher E)

Magnetic nuclei are in resonance with external magnetic field if they absorb energy and “spin-flip” from low energy state (parallel orientation) to high energy state (antiparallel orientation).

Dependence of the difference in energy between lower and higher nuclear spin levels of the hydrogen atom

Nuclei in different environments (i.e. with different amounts of electron density around them) will require different amounts of energy to “flip” to higher energy different spin state

9 Magnetic: o All nuclei with odd number of protons o All nuclei with odd number of neutrons Nonmagnetic: o Nuclei with even number of both protons and neutrons

Fig. 13-4, p. 444

11

Really Old School: Continuous wave (CW) 40 MHz NMR spectrometer 1960

A little less old school: Continuous wave (CW) 60 MHz NMR spectrum 1964

Not quite so old school: 1980’s 60 MHz

The Nobel Prize in Chemistry 1991 "for his contributions to the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy" Richard R. Ernst

900 MHz NMR spectrometer Center for Biomolecular NMR, Heinrich-Heine-Universität Düsseldorf State-of-the-art

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel 17

Free-induction decay data and proton-decoupled 13C nuclear magnetic resonance spectra

Fig. 13-6, p C NMR spectrum 1-pentanol : 1 scan

Fig. 13-6, p C NMR spectrum 1-pentanol : 1 scan 13 C NMR spectrum 1-pentanol : 200 scans

The Nature of NMR Absorptions 1 H NMR spectrum 13 C NMR spectrum

The Nobel Prize in Chemistry 2002 "for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution" Kurt Wüthrich

The Nobel Prize in Medicine 2003 " for their discoveries concerning magnetic resonance imaging " Paul C. Lauterbur Sir Peter Mansfield

More energy to flip nucleus Less energy to flip nucleus , ppm chemical shift

25 Magnetically distinct 13 C NMR of methyl acetate Chemically equivalent nuclei always show the same absorption

26 Magnetically distinct hydrogens and carbons!

Fig. 13-7, p ppm CDCl 3

Fig. 13-7, p ppm CDCl 3 sp3

29

31 For each molecule below: Determine the number of distinct carbon peaks Assign chemical shifts for each distinct carbon

Fig a, p. 451

Information in a 1 H NMR spectrum 13 C NMR spectrum 1 H NMR spectrum

Table 13-2, p. 457

Table 13-3, p. 458

6.5 – 8.0

37 1 H NMR Integration Area under each peak is proportional to number of protons causing that peak. Gives ratio, not always exact number!

spin-spin splitting

Fig , p. 424 Spin – Spin Splitting Absorption of a proton can split into multiple peaks (multiplet) Tiny magnetic field produced by one nucleus affects magnetic field felt by neighboring nuclei

Fig , p. 460

 3.42 Chemical shift – middle of multiplet

Common NMR splitting patterns

Fig , p. 425 C 3 H 7 Br

Fig , p. 425 C 3 H 7 Br 12 2

Fig , p C 10 H 12 O 2

C 10 H 12 O

Fig , p. 466

p. 409