Oxidative Coupling of Aldehydes with Alcohol for the Synthesis of Esters Promoted by Polystyrene-Supported N-Heterocyclic Carbene: Unraveling the Solvent Effect on the Catalyst Behavior Using NMR Relaxation

Heterogeneous organocatalysts hold great potential as they offer practical advantages in terms of purification and reusability compared with the homogeneous counterpart. A puzzling aspect is the solvent effect on their catalytic performance. Here we propose a new approach whereby T1/T2 NMR relaxation measurements are used to evaluate the strength of solvent–surface interactions in the polystyrene-supported N-heterocyclic carbene-promoted oxidation of aldehydes. The results reveal that solvents with high surface affinity lead to a decrease in catalyst activity.


Materials and methods
Homogeneous and heterogeneous oxidations of 2-chlorobenzaldehyde were performed under an argon atmosphere using oven-dried glassware. All solvents (THF : tetrahydrofuran; DCM : dichloromethane; DMF : dimethylformamide; toluene; cyclohexane) were dried using standard drying agent and freshly distilled prior to use.
Reactions performed at Temperature higher than the room temperature were carried out using an oil bath. Reactions were monitored by NMR using diphenyl ether as internal standard. Flash column chromatography was performed on silica gel 60 (200-400 mesh). 1 H NMR spectra were recorded in CDCl 3 at room temperature employing a Gemini Varian spectrometer. The chemical shifts in 1 H spectra were referenced to trimethylsilane (TMS). Elemental analyses were performed using a FLASH 2000 Series CHNS/O analyzer (ThermoFisher Scientific). Kharasch oxidant, DBU (1,5diazabiciclo(5.4.0)undec-7-ene), 2-chlorobenzaldehyde, 1-Methyl-1H-1,2,4-triazole and 1,4-dimethyl-4H-1,2,4-triazol-1-ium iodide were purchased from Sigma-Aldrich and used as received. Merriefield polymer chloride (Cl 3.5 mmol/gr) 2% DVB was purchased by Fluka and used as received. The estimated pore size is approximately 5.4 nm as reported in literature for this crosslinking percentage. 1 Particles size has been measured using a Mastersizer 3000 (Malvern Panalytical) employing water as dispersant. T 1 , T 2 and diffusion measurements have been performed using a Magritek Benchtop 43 MHz spinsolve.
After cooling to room temperature, the mixture was filtered and the solid was washed with CH 3 CN (2 × 10 mL) and Et 2 O (2 × 10 mL

Activation of pre-Cat for NMR measurements and test of the activated one to check the stability
To a suspension of NaH 60 % w/w mineral oil (0.71 mmol, 28 mg, previously washed with 5 mL of pentane to remove the paraffin wax) in anhydrous THF (20 mL), precatalyst PS1 (1 gr, 0.59 mmol) was added under an argon atmosphere keeping the suspension at 0 °C using an ice bath. The suspension was stirred for 16 hours a room temperature. Then the solid was filtered, washed several times with anhydrous DMF

Preparation of the samples for NMR measurements and T1 and T2 plots
Samples were prepared by soaking the activated catalyst in the liquid. After 24 hours the powder was dried on a pre-soaked filter paper, in order to remove any excess liquid on the external surface, and transferred into 5 mm diameter NMR tubes, which were then sealed.
A standard inversion recovery sequence was used to measure T 1 (see Figure SI1).

S8
The resulting FIDs were integrated and the values of the normalized signal intensity vs time were plotted to obtain the relaxation time constants using the two equations shown below, (1) and (2) to estimate T 1 and T 2 , respectively.

Diffusion measurements and Weisz-Prater criterion
The Weisz-Prater criterion is an established method to evaluate the influence of pore diffusion on reaction rates in heterogeneous catalysis. If the equation below is satisfied it is possible to assume negligible any pore diffusion limitation. Concentration 125.000 mol m -3