Chemistry 125: Lecture 59 March 22, 2010 NMR Spectroscopy Chemical Shift and Spin-Spin Coupling This For copyright notice see final page of this file

NMR: locating protons within molecules using uniform field ?

HO-CH 2 -CH 3 Oscilliscope Trace (1951) The “Chemical” Shift 2.48 ppm Fractional difference in applied field ! Requires very high uniformity of field to avoid “MRI” H Listen at fixed frequency. Tune H to “hear” precession.

Dr. Lauterbur became interested in possible biological applications of nuclear magnetic resonance after reading a paper in 1971 by Raymond V. Damadian, who described how some cancerous tissues responded differently to the magnetic fields than normal tissue. Until then, most scientists placed the samples in a uniform magnetic field, and the radio signals emanated from the entire sample. Dr. Lauterbur realized that if a non-uniform magnetic field were used, then the radio signals would come from just one slice of the sample, allowing a two-dimensional image to be created. The nuclear magnetic resonance machine at SUNY was shared among the chemistry professors, and the other professors needed to perform their measurements in a uniform magnetic field. Dr. Lauterbur had to conduct his work at night, returning the machine to its original settings each morning. i.e. one particular frequency

Some of the Magnetic Resonance Spectrometers in Yale's Chemistry Department have put classical structure proof by chemical transformation (and even IR!) out of business. One Yale “natural products” organic professor, whose research used chemical transformations to determine molecular structures, abandoned organic chemistry to take up fundamental research on quantum theory (and later became a professional studio photographer).

500 MHz

600 MHz

800 MHz ~8 3 = 512 times as sensitive as 100 MHz (not to mention the chemical shift advantage discussed below) * 1) Boltzmann factor 2) Energy quantum 3) Electronics sensitivity *

EPR (Electron Paramagnetic Resonance) (for Free Radicals with SOMOs) e magnet is 660x H + !

EPR (Electron Paramagnetic Resonance) 9 GHz ~3000 Gauss (0.3 Tesla)

NHFML - Florida State University Varian Associates New 900 MHz (21 Tesla) NMR spectrometers NHFML now has a pulsed field NMR at 45 Tesla (there is no charge for use, but you have to have a great experiment

HO-CH 2 -CH 3 Oscilliscope Trace (1951) Area (integral) Which peak is which set of protons?  number of protons, because they are so similar (not like IR)

Advertisement 1) O 3 2) H 2 O 2 C-OH HO-C OO cis-caronic acid 1:11:1 Structural proof by chemical degradation (venerable) 3:13:1 ? ? O O O O O O O O H C C H

Advantage of “similarity” of protons (unlike IR where various modes have very different changes in dipole moment, and thus very different signal strengths) Higher Resolution Shows Splitting 1959

Ethyl Acetate averages field inhomogeneities 1959

A 90° pulse makes spinning nuclei ( 1 H, 13 C) “broadcast” a frequency that tells their LOCAL magnetic field.

Components of Effective Magnetic Field. Inhomogeneous ~ 30,000 G for MRI CAT scan. (4 G/cm for humans, 50 G/cm for small animals) Applied Field: Homogeneous for Chemical NMR Spectroscopy (spin sample) Molecular Field: Net electron orbiting - “Chemical Shift” (Range ~12 ppm for 1 H, ~ 200 ppm for 13 C) Nearby magnetic nuclei - “Spin-Spin Splitting” (In solution J HH 0-30 Hz ; J CH Hz) B effective B molecular (diamagnetic) B applied

Chemical Shift and Shielding high electron density shielded upfield high e - density low chemical shift low frequency deshielded downfield low e - density high chemical shift high frequency CH 3 C C-H ? ! ??? TMS B effective B molecular (diamagnetic) B applied Note: Electron orbiting to give B is driven by B; so B  B. Cf. Table 15.4 p. 720

ZERO! Suppose molecule undergoes rotational averaging. average over sphere average around circle  1/r 3 Electrons Orbiting Other Nuclei Diamagnetism from Orbiting Electrons B applied PPM Ignore them!

ZERO! average over sphere Electrons Orbiting Other Nuclei Unless orbiting depends on molecular orientation B applied Diamagnetic “Anisotropy” (depends on direction) NOT

Diamagnetic Anisotropy Benzene “Ring Current” B 0 can only drive circulation about a path to which it is perpendicular. If the ring rotates so that it is no longer perpendicular to B 0, the ring current stops

Aromaticity: PMR Chemical Shift Criterion HCCl 3 TMS   electrons (4  3 + 2) DIAMAGNETIC ANISOTROPY! ? DIAMAGNETIC ANISOTROPY 8 H2 H TMS 10  electrons (distorted)

Diamagnetic Anisotropy Acetylene “Ring Current” Warning! This handy picture of diamagnetic anisotropy due to ring current may well be nonsense! (Prof. Wiberg showed it to be nonsense for 13 C.) The H nuclei of benzene lie outside the orbital path when there is ring current. (B 0 augmented; signal shifts downfield). The H nuclei of acetylene lie on the orbital axis when there is ring current. (B 0 diminshed; signal shifts upfield)

Spin-Spin Splitting

15.36.jpg Three peaks from four different sets of molecules in the sample. ~1:2:1 Triplet

15.37.jpg ~1:3:3:1 Quartet

Isotropic J H-H is mediated by bonding electrons (through-space part is anisotropic, averaged to zero by tumbling)

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