Unravelling stereoisomerism in the acid catalysed lignin conversion: an integration of experimental trends and theoretical evaluations

For the effective valorization of lignin, which is a significant component in agricultural residues, its reactivity needs to be understood in detail. Selective acid-catalyzed depolymerisation of the lignin β-O-4 linking...


S1.0 Analytical procedures
High-performance liquid chromatography (HPLC) was performed on a Shimadzu prominence system equipped with a photodiode detector (Shimadzu SPD-M20A Prominence). The column is Agilent Eclipse XDB-C18 5 Column (5 μm 4.6 × 150 mm). Data analysis was processed with Shimadzu Lab Solutions Version 5.51 software. 1,2,4,5-tetramethylbenzene was used as an internal standard. All samples were run using MeCN (0.1% formic acid) (A)/H2O (0.1% formic acid) (B) gradient follow with a flow rate of 1.0 mL/min. The method started with 5% A/95% B for 10 min followed by a gradient to 95% A/5% B over 30 min followed by 10 min at 95% A/5% B followed by a gradient to 5% A/95% B over 5 min followed by 5 min at 5% A/95% B a flow rate of 1.0 mL/min. Preparative High-Performance Liquid Chromatography was performed on a Shimadzu prominence system equipped with a photodiode detector (Shimadzu SPD-M20A Prominence), and a FRC-10A fraction collector was used. The column is Xbridge BEH130 Prep C18 Column (10 μm, 10 × 150 mm). Data analysis was processed with Shimadzu Lab Solutions Version 5.51 software. Samples were run using MeCN (0.1% formic acid) (A)/H2O (0.1% formic acid) (B) in a ratio of 20% A/80% B for 30 min following by a flow rate of 1.0 mL/min. Ultra-high performance liquid chromatography-mass spectrometry (UPLCMS) was performed using a Waters Acquity Ultra Performance LC system equipped with a TQ detector and an Acquity UPLC HSS T3 Column (1.8 μm 2.1 × 150 mm). Analysis was performed using MassLynx V4.1 software.
Gas chromatography-mass spectrometry (GC-MS) was performed using an Agilent 6890 series GC system equipped with a HP973 mass detector with helium as carrier gas.
NMR: NMR spectra were recorded on a Varian Oxford Mercury AS 400, an Agilent Technologies 400/54 Premium shielded spectrometer or a Bruker Ascend 600 using CDCl3 or DMSO-d6 as solvent at room temperature. Chemical shift values are reported in part per million (ppm) with the solvent resonance as the internal standard. Data report followed the bellowing pattern: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br. = broad, m = multiplet), coupling constants (Hz), and integration.
Thin layer chromatography was performed on pre-coated aluminum plates (60/kieselguhr F254 Merk) and visualized under UV light (254 nm) or by staining with KMnO4. Spectral data were consistent with the values reported in literature. 2 Substrate A in erythro configuration (100 g, 0.2991 mmol) was dissolved in 1,4-dioxane (5 mL) and EG (5 mL). 3 eq. of HCl (from a 4N HCl in 1,4-dioxane solution) was added to the mixture and the reaction refluxed for 2 h, after which no more starting material was visible by TLC. The reaction was quench by addition of 10 mL sat. aqueous NaHCO3 and extracted into EtOAc. The organic layers were combined and washed with brine and dried over MgSO4 prior to being filtered and concentrated in vacuo. The crude product was purified via column chromatography (30-60% Acetone/PET Ether) to obtain the product as a clear semi-solid. The isomer mixture of B was further separated by preparative HPLC as fraction 1 (threo) and fraction 2 (erythro), which was confirmed by comparing the typical coupling constant between Hα and Hβ with literature. [3][4][5][6] Ethylene glycol adduct in threo configuration: and trimethylamine (0.1 mL, 2.1 eq.). The resulted mixture was stirred at 0 °C for 30 min and then allowed to warm up to room temperature. After stirring overnight, the reaction mixture was diluted with water (5 mL) and extracted with DCM. The organic phase was successively washed with 10 mL of a 1 M HCl solution, brine (15 mL), then dried over MgSO4. The solvent was removed under reduced pressure. The product was purified by column chromatography (pentane/acetone = 97/3) to obtain a cis/trans isomer mixture (cis/trans = 7.7/1). The ratio obtained by quantitative proton NMR was used for HPLC calibration of the separate isomers. Spectral data were consistent with the values reported in literature. 7

S 3.0 Typical procedure for the time course reaction
A typical procedure for the time course reaction was followed as used in our previous investigation. 8      Yields were obtained via HPLC analysis using 1,2,4,5-tetramethylbenzene as the internal standard.

S 4.0 Multi-scale modeling
The torsional angles of the main chain, connecting the two rings, and those of the side chains, were analyzed to classify the structures and displayed as energy contour plots or mere distributions in the case of the side moieties (see Fig. S1-S3).