## 4 Conclusions  
In this paper, the chloromethylation of a series of bio-based phenolics was developed, demonstrating a practical and straightforward approach. Most chloromethylations on solid substrates can occur \"on water\", i.e., without the need for organic solvents. Moreover, as most chloromethylal products are solid, their isolation can often be achieved through a simple (solventless) filtration. In other cases, such as liquid or substrates with low water solubility (e.g., **1d**, **1e**, **1f**), the system benefits from the addition of small amount of DCM, resulting in satisfactory selectivity and repeatability. The success of the chloromethylation and its selectivity depend on the modulation of the chloromethylating reagent (PF:37% HCl \(\sim\) 1:6) in relation to the substitution pattern of the substrate, which governs its activation towards Ar-S\({}_{\text{E}}\) processes. Phenolics devoid of deactivating groups (**1d**, **1e**, **1f**) were promptly chloromethylated by the standard PF:37% HCl (\(\sim\)1:6) reagent at 25 \({}^{\circ}\)C, although highly activated substrates often attain limited selectivity (as observed for **2d** and **2e**). Instead, deactivated phenolics, such as those containing one aldehyde (**1a**, **1b**) or ketone (**1c**) function, require reagent activation, obtained through the addition of H\({}_{2}\)SO\({}_{4}\) (\(\sim\)0.9 eq with respect to PF) and, usually, a higher operating temperature. The number of chloromethylal groups incorporated into the product is primarily determined by the nature of the substrate. For instance, deactivated substrates such as **1a** and **1c** favor the formation of monoalkylated derivatives, whereas in other cases, such as **1b**, high selectivity for the dialkylated product is observed. Piccol (**1c**), characterized by a balanced activation for Ar-S\({}_{\text{E}}\), was the only case where a control of mono- vs. dialkylation was obtained by setting the process temperature. Most of the activated substrates investigated--such as **1d** and **1f**--exhibited a strong tendency toward dialkylation. However, substrates with excessive activation, such as guaiacol, led to complex mixtures  
Figure 7: Chloromethylation of \(p\)-cresol (**1f**) towards dialkyl derivative **2f** and conversion of this to the di-formamide **3f**; (a) **1f**, PF (2.2 eq), CH\({}_{2}\)Cl\({}_{2}\), 37% HCl (16 eq), 25 \({}^{\circ}\)C, 4 h; (b) **2f**, FA (4.0 eq), THF, reflux, 3 h.  
containing significant amounts of condensation byproducts. A controlled process for the formation of the trialkylated product **2e** was only achieved by reducing the reactivity of guaiacol through conversion into its \(O\)-acyl derivative (**1e**). The developed method, working with low solvent amounts, is suitable for upscaling. Considering the case of piceol, the production of **2c** was characterized by a volume-time output (VTO) of 83 L-h/kg, a PMI of around 8, and an E factor around 7. The obtained benzyl chlorides (**2a-f**), some of those previously not described, are characterized by a broad synthetic versatility and therefore represent valuable electrophilic building blocks for the chemical industry. Various applications in synthesis as well as in materials chemistry can be suggested based on the literature describing the reactivity of benzyl chlorides. As an application, their selective conversion to the corresponding \(N\)-formylamides (**3a-f**) was proven, through which the synthetic usefulness of the chloromethylated intermediates could be extended (see Figure 1 and the related description). Thanks to the high electrophilicity typical of these benzyl chlorides, the amidation process seamlessly proceeded to a clean and selective conversion.