256969 Aerobic Oxidations in Flow: The Functionalization of Olefins
Aerobic oxidations (i.e. the direct use of triplet dioxygen as terminal oxidant) are widespread in bulk chemical processes. The oxidation of cyclohexane and xylene to K/A-oil and terephthalic acid, respectively, are the most promient ones, having a combined scale of about 8×1010 kg/a. Due to the optimal atom economy, it is desirable to extend the scope of aerobic oxidations to the synthesis of fine chemicals. However, there are challenges associated with these reactions, since they are most often radical-chain propagated. For instance, a significant part of the primary product distribution consists of hazardous peroxides. In combination with the high exothermicities, this requires a precise control over the reaction parameters. Moreover, the product selectivity is often highly dependent on the precise conversion. So a tunable dosage of oxygen is desirable. Conceptually, microreactors are a promising approach to tackle all these issues.
In this contribution, we will present our efforts for performing aerobic oxidations of olefins in pressurized microreactors at elevated temperatures under Taylor-flow conditions (Fig. 1). Chemically inert channel walls ensure innocent behavior of the reactor, even for the high surface-to-volume area that is inherent to the system. By working under solvent-free conditions, partial (sacrificial) oxidation of the solvent is effectively avoided.
Fig. 1 Direct allylic oxidation of olefins, carried out in a spiral microreactor.
By taking benefit of the improved mass transfer conditions, a significant process intensification can be achieved. Moreover, direct control over the desired end-conversion – and therefore a constant product selectivity – is possible by choosing an appropriate dose of the oxidant. This is an effective way for getting enhanced control over the reaction. The obtained results will be quantitatively benchmarked to the two most established reactor concepts: ambient-pressure bubble column and high-pressure autoclave reactors (Fig. 2).[4,5] One key advantage of the microreactor is that the amount of peroxide in the heated zone of the reactor is minimized to only 20 μmol (~0.1 M in 200 μL), as compared to 2 mmol (~0.2 M in 10 mL) in the classical batch reactors. This greatly reduces the hazardous potential of these reactions and lowers the cost for safety installations, e.g. associated with conventional high-pressure reactors.
Fig. 2 Comparison of oxidation kinetics in microreactor (blue dots) with bubble column (red crosses). The hashed lines indicate the two mass-transfer limits for the two reactor systems.
It is noteworthy that the developed system's scope of application encompasses the use of valuable raw materials, e.g. natural oil extracts. Therefore it is of particular interest to flavor and fragrance chemistry. Some according case studies will be illustrated, including the pinene-derived sandalwood fragrances and the valencene-derived citrus flavor nootkatone. The direct aerobic oxidation of the latter aubstrate is promising in terms of space-time-yield, when compared to the currently used biotechnological approach.
Moreover, the effects of transition metal catalysts (based on cobalt and molybdenum) on the presented oxidation system will be addressed. They provide an extra degree of freedom for increasing the rate of oxidation, as well as product selectivity. Rigorous kinetic evaluation of the data allows to get rate constants for these catalyzed reactions. Mechanistic propositions are made therefrom, further supported by ab initio calculations.
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