Efficient and Greener Process for the Production of p-Menthane-3,8-diols Using Biosourced Ammonium Salts as Catalysts

Abstract

p-Menthane-3,8-diol (PMD) is gradually dethroning the synthetic golden standard mosquito repellent, N,N-diethyl-m-toluamide (DEET), as PMD is natural and considered safer while displaying an excellent repellent activity. In this study, we revisited the synthetic route of PMD from citronellal in greener conditions, while maintaining the highest yield, and developed a sustainable post-reaction process. Biosourced ammonium salts were tested to catalyze the carbonyl-ene reaction-hydration transforming citronellal and essential oils rich in citronellal into PMD. Ammonium salts led to excellent conversions and selectivities toward PMD, better than previously reported, even at low catalytic loading and rapidly. Catalytic solution of ammonium salts could be directly reused, up to six times without any loss of activity. The sustainability of the methodology was evaluated using a holistic approach which gave excellent green metrics, such as the PMI (6), TON (708), TOF (17), and E-factor (0.68) in comparison to other processes. The repellent activities of PMD synthesized from citronellal and from essential oils were evaluated against Aedes albopictus, the most invasive mosquito in the world, and were as much or even more repellent than pure PMD.