2.4.1. Synthesis Optimization

The synthesis of GAP was optimized to obtain sufficient amounts of this product in order to prepare marine coating formulations. A reproducible and feasible one-step synthesis of GAP was accomplished by sulfation of gallic acid with the triethylamine sulfur trioxide adduct (TEA·SO3) and triethylamine (TEA), in dimethylformamide (DMF), under MW heating (Scheme 1). Gallic acid is a commercially available and affordable raw material and it can be obtained from several sources, such as winery waste [25].

**Scheme 1.** Synthesis of gallic acid persulfate (GAP).

MW irradiation is a potent green chemistry tool and, in the last decade, also emerged as a new alternative approach to obtain sulfated derivatives [30–33]. The technique offers a simple, clean, fast, efficient, and economic strategy for the synthesis of a large number of organic molecules [34]. MW heating increased the efficiency of the synthetic method, demanding lower reaction times when compared to conventional heating, and significantly increased the yield of the reaction (Table 1).


**Table 1.** Comparative conditions for sulfation of gallic acid.

TEA·SO3: triethylamine-sulfur trioxide adduct; TEA: triethylamine; DMA: dimethylacetamide; DMF: dimethylformamide; h: hours; MW: microwave.

Additionally, the use of a free base in the reaction mixture allowed us to overcome the difficult persulfation of gallic acid, a tri-hydroxylated molecule. After the reaction, more triethylamine (33 eq/OH) was added to ensure the conversion of the sulfate groups into triethylamine salts, which were more easily separated in oil form in the crude product and led to an improved yield when compared to the previous purification process. The instability of the triethylamine salts was then overcome by quick conversion into sodium salts with sodium acetate. The grade of the newly synthesized GAP was similar to the grade of previous GAP (HPLC, Figure S1). The infrared and 1H nuclear magnetic resonance (NMR) spectra were in accordance with the literature [35].
