Unravelling transition metal-catalyzed terpenic alcohol esterification: a straightforward process for the synthesis of fragrances

Abstract

Iron nitrate is a simple and commercially available Lewis acid and is demonstrated to be able to catalyze β-citronellol esterification with acetic acid, achieving high conversion and ester selectivity (ca. 80 and 70%, respectively), within shorter reaction times than those reported in the literature. To the best of our knowledge, this is the first report of a terpenic alcohol esterification reaction catalyzed by Fe(NO₃)₃. This process is an attractive alternative to the slow and expensive enzymatic processes commonly used in terpenic alcohol esterification. Moreover, it avoids the undesirable steps of neutralizing the products, which are always required in mineral acid-catalyzed reactions. We have performed a study of the activity of different metal Lewis acid catalysts, and found that their efficiency is directly linked to the ability of the metal cation to generate H⁺ ions from acetic acid ionization. The measurement of pH as well as the conversions achieved in the reactions allowed us to obtain the following trend: Fe(NO₃)₃ > Al(NO₃)₃ > Cu(NO₃)₂ > Ni(NO₃)₂ > Zn(NO₃)₂ > Mn(NO₃)₂ > Co(NO₃)₂ > LiNO₃. The first three are recognized as stronger Lewis acids and they generate more acidic solutions. When we carried out reactions with different iron salts, it was possible to conclude that the type of anion affects the solubility of the catalyst, as well as the conversion and selectivity of the process. Fe₂(SO₄)₃ and FeSO₄ were insoluble and less active. Conversely, though they were equally soluble, Fe(NO₃)₃ was more selective for the formation of β-citronellyl acetate than FeCl₃. We assessed the effects of the main reaction variables such as reactant stoichiometry, temperature, and catalyst concentration. In addition to citronellol, we investigated the efficiency of the iron(III) catalyst in the solvent free esterification of several terpenic alcohols (geraniol, nerol, linalool, α-terpineol) as well as other carboxylic acids.