Two-dimensional NMR spectroscopy on a desktop NMR system
Bertram Manza, Juan Perlob, Andrew Coya, and Federico Casanovaba) Magritek Ltd, Salamanca Road, Wellington, New Zealandb) Magritek GmbH, Pauwelsstr. 19, D-52074, Aachen, Germany

Correlation spectroscopy

Desktop NMR system
Two-dimensional (2D) NMR spectroscopy is a general concept that enables chemical
information to be encoded into a second dimension making use of spin-spin interactions likethe J-coupling. It is particularly useful to simplify 1D spectra with overlapping signals and toidentify coupled chemical groups. While 2D techniques are routinely used at high field they
are not exploited on desktop spectrometers. One of the main reasons for this is the highstability required to sample the data along the indirect dimension. To keep the frequency
stable with the accuracy required by these methods, conventional spectrometers are equippedwith a lock system that eliminates any drift or fluctuation of the magnetic field. Furthermore,
the acquisition of meaningful 2D spectra is only possible if the spectrometer provides
enough resolution and high signal-to-noise, otherwise the acquisition time for a 2D spectrum
can become excessively long.
In this work we demonstrate the performance of 2D NMR on a 1 Tesla permanent
magnet. The magnetic field homogeneity of the magnet can be finely shimmed to achieve
sub Hertz resolution by means of shim coils up to order three (see Fig. 1), and high fieldstability is achieved by means of an external lock system. The results presented here
demonstrate that 2D NMR is of great assistance at low field where the spectrum of small
molecules may appear crowded due to the strong coupling limit.

a)b)

One of the most common 2D experiment used by organic chemists is the homonuclear
correlation spectroscopy (COSY) experiment. A COSY spectrum identifies the proton signals
from magnetically coupled chemical groups, which in many cases can be directly related tocarbon skeleton connectivity in molecules. In this work we implemented a phase sensitive
COSY (a) and a phase sensitive double quantum filtered (DQF) COSY sequence (b).

b)a)

High Spectral Resolution
Height[%]Line width[Hz]Line width[ppm]

500.6

0.015

1050.11 .

0.55

280.65 .

Figure 1: a) Desktop High-resolution NMR system. b) Spectrum of chloroform illustrating the highresolution and sensitivity of the NMR spectrometer.

Methods and sample
The basic scheme of 2D NMR consists of four intervals (Figure 2a). The spin system isprepared to a non-equilibrium state during the preparation period. During the evolution
period, the spin system evolves under the influence of certain couplings. In order to obtain a
two-dimensional spectrum, a series of spectra is obtained where the duration t1 of theevolution delay is incremented. The mixing process selects the type of spin coherence to beobserved during the detection period. Usually, the duration of the mixing period is fixed in a2D experiment. During the detection period, the transverse magnetization is measured as afunction of t2 in the same way as it is measured in 1D spectroscopy. Since the signal isdetected directly along the t2 dimension, this dimension is usually referred to as the direct
dimension, whilst the t1 dimension is called the indirect dimension. From the large variety ofavailable 2D pulse sequences we tested the performance of J-resolved spectroscopy,
correlation spectroscopy (COSY), and double quantum filtered COSY.

Preparation	  Evolution	  t1	  Mixing	  a)b)
Strong	  coupling	  satellite	  Doublet	  Doublet	  Doublet	  Figure 2. a) General 2D NMR scheme. B) 1D spectrum of 200 mM Ibuprofen in CDCl3. The
spectrum was acquired with a single 10 second scan

J-resolved 2D spectroscopy
The homonuclear J-resolved 2D experiment is used to resolve proton mutiplets in instanceswhere resonance overlap in a 1D spectrum makes the assignment difficult. A schematic of thepulse sequence consists of a spin-echo sequence, where the echo time is stepped as evolution
delay t1 (Figure 4a). The chemical shift and multiplet splitting of each group are displayed in
the direct f2 domain, while the indirect f1 domain only contains proton-proton coupling
information (in Hz). Following a simple shear operation, the J-multiplets appear in theindirect dimension and the homonuclear decoupled 1H spectrum in the direct dimension.

Quartet	  The example molecule used ina) this work is Ibuprofen (Fig. 2b).
Detection	  This fairly small molecule (M =time	   206 g mol-1) exhibits a 1D proton
t2	  spectrum which has someoverlapping multiplets,b) particularly in the region
between 0.50 and 3.00 ppm. To
the untrained eye, it may not beclear whether the multiplicitiesof these peaks are multiplet
splittings belonging to the samefunctional group, or result fromthe chemical shifts of different
functional groups.

Figure 3. COSY (a) and DQF-COSY (b) of Ibuprofen. The 2D experiments were measured
with 256 steps along the indirect dimension with a dwell time of 2 ms. Along the direct
dimension 2 sec were acquired using a dwell time of 1 ms. Four and eight scans were used
respectively with the phases required to apply the States method to produce pure absorptive
2D spectra. While the COSY spectrum has dispersive diagonal peaks, the DQF version
produce pure absorptive cross and diagonal peaks. This is particularly advantageous at low
field where J couplings are comparable to chemical shifts.	

Figure 4: J-resolved 2D spectra can bemeasured with a comparatively smallnumber of scans in the indirect dimension
and tremendously simplify the analysis of
low-field spectra in precisely determining Jcoupling constants and identifying chemical
shifts. This is shown using the example of
200 mM Ibuprofen in CDCl 3 . For
comparison, the 1D spectrum with peakassignments is shown as the blue curve. The
projection along f1, corresponding to the“decoupled” 1D spectrum is displayed
above the 2D spectrum. All multipletscollapse into a single peak at the centre
frequency, resulting in a single peak perfunctional group. The vertical spectrum is avertical slice along the dotted line throughthe 2D spectrum at the position of the mostupfield peak (1.0 ppm). It clearly shows adoublet with a splitting of 6.4 Hz.

1. J. Perlo, F. Casanova, and B. Blümich, Science, 315, 1110-1112 (2007).
2. E. Danieli, J.Perlo, B. Blümich, and F. Casanova, Angew. Chem. Int. Ed., 49, 4133-4135L-Ala(2010). stretched (Ξ = 1)
3. K. Kobzar, H. Kessler, and B. Luy, Angew. Chem. Int. Ed., 44, 3145 –3147 (2005).