*2.1. Catalyst Screening*

Catalysts with 5 wt.% M/Al2O3 (M = Ru, Ag, Fe, Mn, Cu) were initially tested for the aerobic oxidation of GGGE into guaiacol, vanillin and vanillic acid in acetonitrile at 160 ◦C with 5 bar 20% oxygen in argon for 20 h. The results are presented in Table 1.

**Table 1.** Catalytic oxidation of guaiacyl glycerol-β-guaiacyl ether (GGGE) over different metal/alumina catalysts a.


a Reaction conditions: 10 mL 0.017 M GGGE in acetonitrile, 40 mg catalyst, 160 ◦C, 5 bar (20% oxygen in argon), 20 h. b Catalyst prepared using ruthenium(III) chloride. c 100 mg vanillin used as a substrate in 10 mL acetonitrile. d Catalyst prepared using ruthenium(III) acetylacetonate. e Catalyst prepared using ruthenium(IV) oxide.

In blank experiments with alumina support alone or without the catalyst about 70% of GGGE was converted, however, as expected only low yields of the desired product guaiacol (<15%) and traces of vanillin and vanillic acid (<1%) were obtained, suggesting that GGGE was possibly transformed into (unidentified) byproducts, e.g., polymers (Table 1, entries 1 and 2). In contrast, when employing the Ru/Al2O3 and Ag/Al2O3 catalysts the yield of guaiacol improved to 28 and 27%, respectively, with the former catalyst performing the best and providing the highest yields of both vanillin (11%) and vanillic acid (11%) (Table 1, entries 6 and 7). When applying the other 5 wt.% metal/alumina catalysts the GGGE conversion remained also close to quantitative, but lower yields of the targeted products were obtained (Table 1, entries 3–5). Notably, in the case of 5 wt.% Cu/Al2O3 the transformation of GGGE to (unidentified) byproducts was even promoted compared to the blank experiments. With the 5 wt.% Ru/Al2O3 (1) catalyst, an additional experiment was performed using vanillin as the starting substrate instead of GGGE (under similar reaction conditions) to examine whether guaiacol was partly formed from vanillin by consecutive decarbonylation of vanillin (Table 1, entry 8). The obtained results showed a poor yield of guaiacol (3%) and vanillic acid (6%) along with a moderate conversion of vanillin (58%), inferring that guaiacol predominantly formed from the cleaving of the β-O-4 linkage in GGGE and vanillic acid predominantly formed from oxidation of vanillin.

### *2.2. E*ff*ect of Ru Precursor, Ru Loading and Catalyst Support*

For metal/metal oxide catalysts it is typically found that the metal loading, metal precursor and support material influence the catalytic performance through changes in the physical- and structural properties [35–39]. Accordingly, Ru/Al2O3 catalysts were prepared with different metal loadings and supports using ruthenium(III) chloride precursor and the resultant catalysts were tested for the GGGE oxidation. Similarly, catalysts with 5 wt.% Ru were prepared with the three different precursors ruthenium(III) chloride, ruthenium(III) acetylacetonate and ruthenium(IV) oxide (Ru/Al2O3 (1),Ru/Al2O3(2)andRu/Al2O3(3),respectively)andtheresultantcatalystsweretested(Tables 1 and 2).

For the catalysts with 1 and 3 wt.% Ru loading, the yields of guaiacol (18–20%) as well as vanillin (8%) and vanillic acid (6%) were lower than for 5 wt.% Ru/Al2O3 (1), confirming that the catalytic activity was dependent on the amount of the metal inventory (Table 1, entries 9 and 10). TEM images of the catalysts further showed that the former catalysts possessed relatively large Ru-particles of sizes 80–100 nm, while the 5 wt.% catalyst had particles with sizes of 40–60 nm, implying that smaller particles improved the catalytic conversion of GGGE to guaiacol, vanillin and vanillic acid (Figure S1). With the preferred 5 wt.% Ru metal loading, the yields of guaiacol, vanillin and vanillic acid were lower when ruthenium(III) acetylacetonate (i.e. Ru/Al2O3 (2)) was used as the precursor instead of ruthenium(III) chloride (Table 1, entry 11). In contrast, a slightly improved catalytic activity in terms of vanillin (34%) and guaiacol yields (13%) was observed when employing ruthenium(IV) oxide precursor (i.e. Ru/Al2O3 (3)) compared to Ru/Al2O3 (1) (Table 1, entry 12), whereas the yield of vanillic acid remained unchanged (11%). TEM images revealed that the Ru-particle sizes of the catalysts decreased in the order Ru/Al2O3 (2) (100–200 nm) > Ru/Al2O3 (1) (40–60 nm) > Ru/Al2O3 (3) (10–40 nm) (Figure 2). This size order followed the order of catalytic performance toward formation of guaiacol, vanillin and vanillic acid, corroborating that the metal precursor influenced particle formation, and the corresponding catalytic performance, as also observed previously when catalysts were prepared with different metal precursors [38].

The BET surface areas of the Ru catalysts as well as the other metal-based catalysts (148–166 m<sup>2</sup>/g) were significantly lower than the alumina support alone (204 m<sup>2</sup>/g), indicating some pore blocking in the catalysts by metal oxide particles and therefore likely also some change in pore size distributions for the different catalysts. For the 5 wt.% Ru/Al2O3 (1) catalyst with the lowest surface area, the increased acidity of the ruthenium(III) chloride precursor solution may have also possibly contributed in part to lowering the surface area by alteration of the Al2O3 support surface. Notably, for analogous Ru/Al2O3 catalysts prepared by similar methods a comparable relative decrease (20–30%) in surface area has also been found [37].

**Figure 2.** High-resolution TEM images of 5 wt.% Ru/Al2O3 (1) (**a**), 5 wt.% Ru/Al2O3 (2) (**b**) and 5 wt.% Ru/Al2O3 (3) (**c**) catalysts.

The influence of the catalyst support was examined for catalysts containing 5 wt.% Ru prepared using ruthenium(III) chloride precursor and conventional supports such as SiO2, MgAl2O4 (spinel), HY (Si/Al ~ 6) and ZrO2 (Table 2). All the catalysts based on the alternative supports gave full GGGC conversion with product yields of guaiacol (15–22%), vanillin (7–12%) and vanillic acid (8–10%) (Table 2, entries 1–4), which were comparable to the analogous 5 wt.% Ru/Al2O3 (1) (Table 1, entry 7). This finding suggested that the characteristics of the support materials was of minor importance for the catalytic performance under the applied conditions.


**Table 2.** Catalytic oxidation of GGGE with alternative Ru/suppor<sup>t</sup> catalysts a.

a Reaction conditions: 10 ml 0.017 M GGGE in acetonitrile, 40 mg catalyst (prepared using ruthenium (III) chloride), 160 ◦C, 5 bar (20% oxygen in argon), 20 h. b BET surface areas of support materials. c The number in parenthesis corresponds to the Si/Al ratio.

### *2.3. E*ff*ect of Reaction Time, Reaction Temperature and Oxygen Pressure*

In order to optimize the reaction towards formation of guaiacol/vanillin/vanillic acid, the influence of reaction temperature and reaction time were examined using the 5 wt.% Ru/Al2O3 (3) catalyst and the results are illustrated in Figures 3 and 4, respectively. When the aerobic oxidation of GGGE was performed for 20 h at a relatively low temperature (120 ◦C), a low yield of guaiacol (8%) was obtained along with 8% vanillin and <2% vanillic acid with 52% conversion (Figure 3). At 140 ◦C, GGGE conversion (85%) product yields improved slightly, while full substrate conversion (>99%) and maximum product yields were found at 160 ◦C (see also Table 1, entry 12). With reaction times of less than 20 h at 160 ◦C, the GGGE conversion as well as the product formation was significantly lower and vanillic acid formed only after 3 h of reaction (Figure 4). Similarly, at a prolonged reaction time of 30 h the product yields decreased noticeably (21% guaiacol, 11% vanillin and 7% vanillic acid), indicating the formation of byproducts both by side reactions as well as product degradation. At even higher reaction temperatures (180 and 200 ◦C) the quantitative conversion was maintained but the yield of the products decreased significantly. This was likely due to deactivation of the Ru/Al2O3 (3) catalyst by Ru particle aggregation and formation of byproducts (unidentified) by consecutive reactions of the products, thus confirming 160 ◦C and 20 h to be the optimal conditions for obtaining the highest product yields.

**Figure 3.** Temperature study for the GGGE oxidation with 5 wt.% Ru/Al2O3 (3) catalyst. Reaction conditions: 10 mL 0.017 M GGGE in acetonitrile, 40 mg catalyst, 20 h, 5 bar (20% oxygen in argon).

**Figure 4.** Time-course study for the GGGE oxidation with 5 wt.% Ru/Al2O3 (3) catalyst. Reaction conditions: 10 mL 0.017 M GGGE in acetonitrile, 40 mg catalyst, 160 ◦C, 5 bar (20% oxygen in argon). All data were obtained from individual experiments.

The importance of oxygen being present for the product formation was further evaluated by performing a catalytic reaction under optimized conditions (160 ◦C, 20 h) with pure argon atmosphere (20 bar). The GGGE was quantitatively converted (>99%) as was found previously using 5 bar of 20% oxygen in argon (see Table 1, entry 12). However, only a moderate yield of guaiacol (24%) and very poor yields of vanillin (3%) and vanillic acid (<1%) were formed under argon atmosphere, thus confirming that oxygen promoted guaiacol formation and was a prerequisite for the production of vanillin and vanillic acid, as was also expected. Notably, full GGGE conversion and very similar product yields (32% guaiacol, 11% vanillin, 11% vanillic acid) were obtained using 5 bar of air instead of 5 bar of 20% oxygen in argon as also anticipated since both had similar oxygen content (i.e., PO2 ≈ 1 bar). In contrast, <1% yield of the desired oxidation products were obtained using water as the solvent under similar reaction conditions (results not shown), possibly due to low oxygen solubility at the reaction conditions.

High-resolution NMR analysis of the post-reaction mixture obtained at the optimal reaction conditions (160 ◦C and 20 h) was performed in order to validate the reaction products, and to obtain insight into byproduct formation with the aim of understanding the loss of carbon from the overall carbon balance of the process. Guaiacol, vanillin and vanillic acid were confirmed to be the predominant reaction products, while a variety of minor aromatic byproducts was formed (Figure 5). These byproducts included 2-methoxy-1,4-benzoquinone as the main aromatic byproduct (2.5% yield) and benzoic acid alongside its derivatives (2% yield), as well as a plethora of additional, unidentified aromatic byproducts contributing to the loss of carbon. The 2-methoxy-1,4-benzoquinone was identified using in situ spectroscopy on crude post-reaction material (Figure S2), and has previously been described as a degradation product in the manganese peroxidase-catalyzed oxidation of guaiacol [40]. Hence, its presence indicated that overoxidation of the main reaction products occured at reaction conditions that were more severe than the optimum conditions, thus rationalizing the decline especially in guaiacol and vanillin yields at longer times or higher temperatures (Figures 3 and 4).

**Figure 5.** 1H-13C HSQC spectrum of post-reaction mixture displayed showing the main products guaiacol (G), vanillin (VL) and vanillinc acid (VA) alongside a variety of minor byproducts, including benzoic acid and 2-methoxy-1,4-benzoquinone.
