To flame-seal or not to the NMR tubes: The role of liquid-vapor equilibria on the accuracy of variable temperature experiments.

In NMR experiments, it is crucial to control the temperature of the sample, especially when measuring kinetic parameters. Usually, it takes two to five minutes for the temperature of the sample inside the NMR probe to stabilize at a fixed value set for the experiment. However, in some cases, the NMR sample tubes are flame-sealed, such as when working with volatile solvents, atmosphere-sensitive samples, or calibration samples for long-term use. When these samples are placed inside the NMR probe, the spectrometer controls the lower portion (liquid phase) of the NMR sample tube with a gas flow at a fixed temperature, while the upper portion (vapor) is at ambient temperature. This probe design creates a unique temperature gradient across the sample, leading to vapor pressure build-up, particularly inside a sealed NMR tube. By analyzing the temperature-dependent line shape changes of a chemical exchange process, we report that under standard experimental conditions, the sample temperature can take up to two to three hours (instead of minutes) to stabilize. The time scale of the liquid-vapor equilibrium process is much slower, with a half-life exceeding 35 minutes, in contrast to the two-minute duration required to obtain each spectrum. As a result, each spectrum represents the time-averaged status of the double bond rotation observable from the liquid phase of the sample. This phenomenon is exclusively due to the liquid-vapor equilibrium process of the flame-sealed NMR tube and is not observable otherwise.