Curious Cases of Strong Coupling

Frequently, second-order effects are observed in NMR spectra which could obscure the analysis or the verification of the product of a reaction. Some examples are included below, which required additional numerical analysis using spectral simulations and lineshape fittings.

1) Due to fast exchange in the NMR time scale, protons denoted as H₁ below become equivalent:

Signals of cyclic protons H₁ and H₂ show signs of second-order effects in CD₃OD (400 MHz, 298 K) and for accurate determination of values of J couplings, full lineshape analysis was carried out using gNMR. In the screenshot shown below the experimental spectrum is shown in red and the fitted spectrum is shown in black:

While proton H₂ appears as a doublet of doublets with splittings of 10.8 and 13.6 Hz at 3.90 ppm, the analysis shows that none of these is the true value of the ³J(H₁,H₂) coupling. The value of this coupling determined from the full lineshape analysis is 12.40 Hz.

2) Both ¹H and ¹⁵N NMR spectra of urea with two ¹⁵N labelled nitrogens (urea-¹⁵N₂) in DMSO-d₆ show unusual lineshapes, which attracted the attention of many in the mailing list of NMR spectroscopists, AMMRL. While experimental spectra can be fitted using lineshape simulations, the agreement for outer components of the "triplet" observed in the ¹⁵N spectrum was relatively poor. In the gNMR screenshot below the experimental ¹⁵N spectrum is shown in blue, the experimental ¹H spectrum is shown in red and iteratively fitted lineshapes are shown in black:

After much search for the reason of such disagreement, the solution was found by your humble servant. It turned out that the NH₂ protons of urea are exchanging slowly with protons of water present in DMSO-d₆. On inclusion the intermolecular exchange into lineshape fittings, the agreement between the calculated and experimental spectra improved considerably (click here for high-resolution image):

Note that the rotation around the N-C bond of urea in DMSO solution is very fast in the NMR time scale at room temperature, thus equalising "equatorial" and "axial" urea protons defined relative to the direction of the carbonyl bond.

3) In certain cases, the only way to extract chemical shifts and J couplings is through full line shape analysis. The 600 MHz ¹H NMR spectrum of the ~1:1 mixture of two diastereomers of the shown below cyclobutane derivative was analysed in this manner in order to determine NMR parameters.