## 3 Results and Discussion
The converging directing effects of the substrate's functional groups--_ortho/para_ for the hydroxyl and _meta_ for the aldehyde--facilitated electrophilic substitution at both positions with comparable speed (Figure 3). The amidation of **2b** cleanly afforded the diamide **3b** under conditions analogous to those previously established. Picool, or 4-hydroxyacetophenone (**1c**), a bio-based phenolic compound found in the needles and mycorrhizal roots of Norway spruc  
Figure 3: Chloromethylation of salicaldehyde towards dialkyl derivative **2b** and conversion of this to the di-formamide **3b**; (a) **1b** (1.0 eq), PF (2.5 eq), HCl (16.0 eq), H\({}_{2}\)SO\({}_{4}\) (0.9 eq), DCM, 70 \({}^{\circ}\)C, 16 h; (b) FA (4.0 eq), THF, reflux, 3 h.  
Figure 2: Amidation of the chloromethylated derivative (**2a**) of vanillin (**1a**). study. Its substitution pattern suggests a reactivity profile similar to that of **1b**, with a synergistic directing effect exerted by the carbonyl and hydroxyl functional groups. Indeed, its chloromethylation proceeded toward both mono- and dialkylation; however, unlike the previous case, both products could be obtained with excellent selectivity. This is likely due to the less deactivating nature of the ketone group in **1c**, compared to the aldehyde in **1b**, which allowed the formation of the monochloromethylated product **2c** (Figure 4) at temperatures as low as 40 \({}^{\circ}\)C. In contrast, higher amounts of PF and higher temperatures were necessary to obtain the doubly alkylated product **2c2**. Amidation of the monochloro-(**2c**) and dichloro-(**2c2**) compounds occurred with high selectivity, using a molar excess of formamide (2.0 and 4.0 eq., respectively) and operating in refluxing THF, in accordance with the previously established conditions. When considering bio-based phenolics, it is important to note that most of them lack electron-withdrawing groups, making them more prone to Ar-S\({}_{\text{E}}\) reactions. On the one hand, this favors chloromethylation, which could proceed even without sulphuric acid activation. On the other hand, it increases the likelihood of undesired coupling between two arene units and PF. For instance, eugenol (**1d**) is known to undergo condensation with formaldehyde and phosphoric acid, resulting in the formation of a bis-eugenol adduct [44]. As expected, applying the developed chloromethylation conditions to **1d** (6 h, 25 \({}^{\circ}\)C) led to a complex mixture of chloroalkylated products, alongside a minor amount of coupling products. Therefore, the removal of H\({}_{2}\)SO\({}_{4}\) was considered, resulting in improved selectivity towards chloromethylation products. However, the limited water solubility of eugenol led to the formation of a heterogeneous system, characterized by a sticky organic phase, complicating process understanding. This resulted in yields that were highly sensitive to minor experimental variations, along with the production of undesired by-products. This issue prompted the addition of a small amount of DCM, which significantly improved the repeatability of the experiments and allowed better control over the reaction outcome. Similar to the reaction on **1b**, selective monoalkylation of eugenol was not achieved, even with substoichiometric amounts of PF. Instead, selective dialkylation toward **2d** was observed when more than 2.5 equivalents of aldehyde were used (Figure 5). Amidation of **2d**, conducted under the same conditions as those for previous cases, proceeded without issues. Figure 4: Chloromethylation of piccol (**1c**) towards **2c** or **2c2**. Conversion of these benzyl chlorides to the corresponding formamides; (**a**) **1c**, PF (1.2 eq), 37% HCl (8.0 eq), H\({}_{2}\)SO\({}_{4}\) (0.5 eq) 40 \({}^{\circ}\)C, 6 h; (b) **2c**, FA (2.0 eq), THF, reflux, 3 h; (c) **1c**, PF (2.5 eq), 37% HCl (16.0 eq) H\({}_{2}\)SO\({}_{4}\) (0.9 eq), 100 \({}^{\circ}\)C, 6 h; (d) **2c2**, FA (4.0 eq), THF, reflux, 3 h.  
Guaiaocl is a major product of the hydrogenolysis of lignin [45] and wood pyrolysis [46].