## 3 Results and Discussion  
The chemical upgrading of biomass-sourced phenolics is a promising approach to obtaining industrially relevant building blocks with enhanced properties. To minimize exposure to harmful chemicals during the chloromethylation process, paraformaldehyde (PF) was selected as the alkylating agent instead of 37% aqueous formaldehyde. This substitution also reduced the amount of water in the reaction medium, resulting in a faster reaction. Vanillin (**1a**) was chosen as the initial starting material, as it is one of the main phenolic monomers obtainable through the oxidation of lignin [41]. Initial experiments were conducted at 25 \({}^{\circ}\)C using one molar equivalent of PF, along with a small amount of DCM to improve the uniformity of the reaction medium. A five- to eight-fold molar excess of hydrochloric acid relative to PF was found to be necessary to obtain a chloromethylated product free of alcohol byproducts. Initially, substrate conversion was limited, reaching only 51%, with the selective formation of the monoalkylated product **2a** (Table 1, entry 1) [35]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Entry** & **Temp (\({}^{\circ}\)C)** & **Time (h)** & **97\% H\({}_{2}\)SO\({}_{4}\) (mmol)** & **Yield of 2a (\%)** \\ \hline
1 \({}^{\mathrm{a}}\) & 25 & 24 & - & 51 \\
2 \({}^{\mathrm{a}}\) & 25 & 16 & 3 & 70 \\
3 \({}^{\mathrm{a}}\) & 25 & 24 & 3 & 89 \\
4 \({}^{\mathrm{a}}\) & 40 & 16 & 3 & 90 \\
5 & 40 & 6 & 2 & 75 \\
6 & 40 & 6 & 3 & 95 \\
7 & 40 & 6 & 4 & 84 \\ \hline \hline \end{tabular} \({}^{\mathrm{a}}\) Reaction conditions. **1a** (1.5 mmol); PF (1.5 mmol); HCl (37%, 1.0 mL). (*) DCM (0.5 mL).  
\end{table} 
Table 1: Chloromethylation of vanillin *. Many established Blanc-Quelet procedures employ a metal salt catalyst, in addition to 37% aqueous HCl, to promote the reaction. A typical example is ZnCl\({}_{2}\), which is particularly effective for deactivated substrates [42]. However, in light of sustainability considerations, we opted for a metal-free approach. Concentrated H\({}_{2}\)SO\({}_{4}\), a cost-effective and efficient alternative, was introduced from entry 2 onward. Its addition significantly enhanced the formation of **2a**, with further improvements observed by extending the reaction time (entry 3) or increasing the temperature (entry 4). Subsequent investigations (entries 5-7) revealed that two molar equivalents of H\({}_{2}\)SO\({}_{4}\) yielded the best results. Notably, omitting DCM (entries 5-7) led to a faster reaction and slightly improved yields in a shorter time frame. Under vigorous stirring, the chloromethylation of vanillin can be efficiently performed in water at 60 \({}^{\circ}\)C, achieving completion in just 6 h. No dichloromethanelylated products were detected in any of the experiments, even when increased amounts of PF were used, suggesting a specific deactivation of the positions _ortho_ to the aldehyde group. The amidation of **2a** was subsequently investigated through the _N_-alkylation of formamide. When carried out in a small amount of THF under reflux conditions and using an excess of formamide, a clean and complete conversion to compound **3a** was achieved (Figure 2). Continuing the investigation with salicaldehyde (**1b**), which was selected as the second bio-based phenolic substrate, the application of the developed chloromethylation protocol resulted in incomplete conversions at 40 \({}^{\circ}\)C. This is likely due to the lower activation of the aromatic ring, attributed to the absence of the methoxy group present in vanillin. However, unlike the previous case, a mixture of mono- and dichloromethanelylated derivatives was obtained. Increasing the reaction temperature to 70 \({}^{\circ}\)C proved effective in achieving complete conversion and enhanced selectivity toward the dialkylated product **2b**, a trend consistent with previous reports [36]. Some attempts to attain the selective preparation of a monoalkylated product by limiting the amount of PF were unsuccessful.