Ester Formation in Alcohol Microdroplet Sprays: Enhanced Reactivity of C8 to C16 Carboxylic Acids with C1 to C3 Alcohols and the Effect of Water.

Esterification reactions are key reactions in organic synthesis with significant industrial and environmental implications. Esterification reactions typically require acids or solid catalysts and/or heat to overcome the activation energy barrier for this condensation reaction. Here, we demonstrate a new approach facilitated by organic acid-alcohol microdroplets formed from bulk solutions of carboxylic acids (C8, C9, C12, and C16) dissolved in an excess of methanol, ethanol, or isopropanol. Utilizing a Collison nebulizer, a spray of microdroplets is produced and then deposited onto a CaF2 substrate and analyzed with Optical-Photothermal Infrared (O-PTIR) spectroscopy. Following evaporation of the alcohol solvent and water byproduct, individual 1 to 15 μm-sized single particle residues were analyzed. Our analysis reveals ester formation in the microdroplet, as indicated by an intense band at 1745 cm-1 in the O-PTIR spectrum of individual particles. This band is due to the characteristic C═O stretching vibrational mode of the ester. Confirmation of the ester product is also seen with high-resolution mass spectrometry. Although no ester formation occurs in the bulk solution, the reactivity within the microdroplet spray suggests that the reaction occurs at the microdroplet-air interface. Furthermore, our results indicate that under ambient conditions, the shorter-chain acids (C8, C9) undergo complete esterification with near-quantitative yields. In contrast, longer-chain acids (C12, C16) undergo partial esterification with some remaining carboxylic acid present. The addition of water to the alcohol solution significantly suppresses ester formation in the microdroplet sprays due to the deprotonation of the organic acid and a decrease in organic acid solubility. Overall, this study highlights a potentially efficient method for ester synthesis for shorter-chain esters, eliminating the need for external catalysts or thermal activation. These findings open new possibilities for chemistry applications by leveraging enhanced reaction kinetics observed for reactions in microdroplet alcohol sprays.