Nuclear Magnetic Resonance Spectroscopy (NMR)

Introduction NMR spectroscopy dates from the 1950 - 1960’s and in the space of some 40 years has revolutionized organic chemistry as tool for structural elucidation, kinetic studies, and quality control. If you have attended an Edmonton Eskimo game or read reports on injured Oilers, you will have heard of magnetic-resonance imaging, a technique which monitors the 1H magnetic resonance signals from water in the body. This application of NMR science enables physicians to image body organs without recourse to X-rays.

Introduction We have seen that IR spectroscopy is a vital tool for the identification of the functional groups present in organic molecules. NMR provides an image of the molecule’s hydrocarbon skeleton. NMR spectra result from the absorption of radio frequency radiation when certain atomic nuclei are placed in magnetic fields. Why?

Nuclear magnetic resonance The nuclei of the elements fall into two categories: those which have a spin and those which do not. The 1H, 13C, 19F nuclei and many others posses a spin. As they are positively charged, the spinning nucleus generates a tiny magnetic moment - it behaves like a small bar magnet.

The effect of the magnetic field In the absence of an applied magnetic field, these “little magnets” are randomly oriented. When placed between the poles of a strong magnet, they are either aligned with (parallel) or against (antiparallel) the field. The parallel spin state is slightly more stable than the antiparallel state. For every 1,000,000 protons, some 500,005 - 500,010 have the parallel state! Not a large difference but it is the basis of NMR!

The effect of the magnetic field When a molecule is placed in a magnetic field and is subjected to electromagnetic radiation (radio frequency), the nuclear spin can flip from the parallel to the antiparallel state - the nuclei are said to be in resonance. h spin aligned with the applied field antiparallel spin magnetic field

The effect of the magnetic field The difference in energy, DE, between the two spin states depends on the strength of the applied field, H0. The stronger the field, the larger the value of DE:

Schematic representation of the NMR spectrometer sample N S radio frequency detector radio wave generator

1H NMR spectrometers The sample is placed in a glass tube which is then placed between the two poles of a very strong magnet. It is then irradiated using radiation of a constant low frequency. The magnetic field is varied. When it reaches the correct strength, the nuclei absorb energy and resonance occurs. The absorption causes a tiny electrical current to flow in a receiver coil surrounding the sample which is displayed as a peak.

Fourier Transform NMR Spectrometers The instrument irradiates the sample with a short pulse of RF radiation for about 10-5 s. This pulse excites all the nuclei at once. A computer performs a mathematical calculation known as a Fourier transform and a spectrum is produced.

CH3CH2OH

Homotopic hydrogen atoms Such atoms can be identified by replacing each in turn with some other atom such as a bromine. If one gets the same compound, the atoms being replaced are chemically equivalent or homotopic. These protons are not homotopic!

Homotopic hydrogen atoms Such atoms can be identified by replacing each in turn with some other atom such as a bromine. If one gets the same compound, the atoms being replaced are chemically equivalent or homotopic. These protons are homotopic!

Identify the number of groups of peaks in the 1H NMR spectra of the following:

Shielding effects The position of an NMR peak is controlled by the shielding or deshielding of the nucleus (by electrons). The free proton is a nucleus free of any influence by exterior, electronic factors. However organic molecules contain covalently bonded nuclei, not free protons......

Shielding effects Protons in organic molecules are surrounded by electrons. The electron density about the protons varies according to several factors: bond polarity the hybridization state of the atom to which a given hydrogen is bonded the presence of electron attracting or donating groups

Shielding effects When a nucleus is placed in a magnetic field, the electrons surrounding it are in motion about the nucleus and create a small, localized magnetic field which opposes the applied field. Thus the electrons generate a small magnetic field that shields the proton from the external field.

Shielding effects The result is that one observes a decrease in the intensity of the total field near to the nucleus. The nucleus is said to be shielded. Thus the position of an NMR absorption depends on the electron density about the hydrogen.

Chemical shifts The position of an NMR absorption is called the chemical shift. An internal standard is added and the positions of the peaks are measured relative to that of the internal standard, tetramethylsilane:

Tetramethylsilane The protons in TMS are shielded and resonate at a position far removed from the spectral zone in which one usually finds proton absorption. The chemical shifts are measured (in Hz) relative to this reference.

Chemical shifts The absorptions are measured in relation to their distance from the TMS peak. These distances vary according to the strength of the applied magnetic field. Peaks separated by 54Hz at 60MHz are separated by 72Hz at 80MHz, 270Hz at 300MHz and by 540Hz at 600MHz.

Chemical shifts This complication is eliminated by dividing the distance between the peak and that of TMS (in Hz) by the radio frequency of the spectrometer (in MHz): distance between peak and that of (CH3)4Si in Hz  = ppm frequency of the spectrometer in MHz

Typical chemical shifts Type of hydrogen Chemical shift,  (ppm) primary alkyl RCH3 0.8 - 1.0 secondary alkyl RCH2R’ 1.2 - 1.4 tertiary alkyl R3CH 1.4 - 1.7 allylic C=C-CH3 1.6 - 1.9 benzylic ArCH2R 2.2 - 2.5

Typical chemical shifts Type of hydrogen Chemical shift,  (ppm) chloroalkane RCH2Cl 3.6 - 3.8 bromoalkane RCH2Br 3.4 - 3.6 iodoalkane RCH2I 3.1 - 3.3 ether RCH2OR’ 3.3 - 3.9 alcohol RCH2OH 3.3 - 4.0 ketone CH3-C=O 2.1 - 2.6

Typical chemical shifts Type of hydrogen Chemical shift,  (ppm) aldehyde H-C=O 9.5 - 9.6 terminal alkene R2C=CH2 4.6 - 5.0 alkene C=CH 5.2 - 5.7 aromatic ArH 6.0 - 9.5 alkyne RCCH 1.7 - 3.1 alcoholic OH ROH 0.5 - 5.0 (variable) amine RNH2 0.5 - 5.0 (variable) carboxylic RCO2H 10.5 - 12

Peak areas The area under an NMR peak is directly proportional to the number of protons giving rise to the peak.

A problem – C11H16

Spin - spin coupling – CH3CH2I There are two principal absorptions. These are divided into three and four component peaks which are equally spaced.

Spin - spin coupling Let’s examine a simple molecule: Consider the absorption by the CH2Br protons in the absence of the other proton of the -CBr2H : a single peak

The CH2Br protons The magnetic field experienced by these protons at any given moment is either slightly increased or reduced due to the spin of the CHBr2 proton.

The CH2Br protons The magnetic field is increased if this proton is aligned with the applied field. Therefore a lower external field is necessary to maintain resonance and the peak is situated at lower applied field:

The CH2Br protons The magnetic field is reduced if this proton is aligned against this applied field. The exterior field must be increased to maintain resonance and so we observe a peak at higher field:

Spin - spin coupling The signal due to the CH2Br protons is divided into two peaks:- A doublet of peaks of equal size.

Spin - spin coupling Now let’s look at the absorption due to the -CHBr2 group. It is affected by the spin of the neighboring protons. There are 4 possible spin combinations which are equally possible: 1 : 2 : 1 a triplet

Spin-spin coupling constants J J

CH3CH2CH3 Predict its 1H NMR spectrum..... TMS

Spin - spin coupling n equivalent neighbouring protons divide an NMR signal into n + 1 peaks.

Pascal’s triangle The relative peak areas are given by Pascal’s triangle: 1 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

Coupling constants J = 2-6 Hz J = 0-7 Hz J = 2-13 Hz J = 5-14 Hz cis - J = 2-15 Hz trans - J = 10-21 Hz

Proton exchange Protons bonded to electronegative atoms undergo rapid exchange and do not show spin - spin coupling with neighboring protons. A time-averaged spectrum is observed, a singlet. If such a proton is suspected, add a few drops of D2O. The rapid exchange of H - D causes the OH peak to disappear.

C8H9Br

Degree of unsaturation Degree of unsaturation = (2NC - NX + NN – NH + 2)/2 NC = number of carbons NX = number of halogens NN = number of nitrogens NH = number of hydrogens

C6H14O SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/ 24/7/02

C6H14O

C8H8O2 SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/ 25/7/02

C8H8O2

C9H12O SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/ 25/7/02

C9H12O

C8H11NO SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/ 25/7/02

C8H11NO

Problems Try problems 9.29 - 9.34 on pages 441 - 443 of Solomons and Fryhle 8th Edition or 9.28 – 9.33 on pages 421 – 423 of the 9th Edition.

Sketch a spectrum