Continuous Flow Synthesis of a-terpineol – Different strategies

a-Terpineol is a monoterpene naturally present in essential oils, of high value on the market as it is a compound widely used as a flavoring, aromatic substance in the cosmetics and food industry. Likewise it is also used as an antifungal agent on the pharmaceutical industry, and as a disinfectant and odorant substance in the cleaning product industry among other numerous applications.1 Therefore, several approaches to obtaining α-terpineol are known, such as the extraction from pine or turpentine oil, however, due to the market demand growth most of its production is synthetic. Different groups such as Prakoso et. al.,2 Román-Aguirre et. al.1 and Baptistella et. al.,3 for example, proposed distinct synthetic routes. This study aims to produce α-terpineol by two different synthetic strategies using both batch and continuous flow systems, focusing on the optimization of the process, improving the reaction conversion and selectivity.
The first strategy accomplished was a two-step cascade reaction with limonene as starting material (Scheme bellow), where the first step is a chemo specific double bond addition using trifluoroacetic acid, and the second step is the ester hydrolysis promoted by a solution of sodium hydroxide (2,25M) in methanol(1:1). This reaction was adapted to a continuous flow condition, where all steps happen in a residence time of 40 minutes, at 25ºC, with no quenching between steps required, giving a conversion of 97% and selectivity of 81%. This result showed the reduction of reaction time from 2,5 hours to 38 minutes, and an improvement of 43% in conversion, with the same value of selectivity (81%) when compared with previous literature works.3,4 The second strategy is a one-stage hydration reaction of α-pinene by an aqueous solution of cloroacetic acid in continuous flow conditions. This reaction is still to be performed as described in the scheme presented, and is expected to reduce the total reaction time for the α-terpineol synthesis, and to improve its selectivity and conversion when compared with other works.1,2