(225d) Aerobic Oxidations in Flow: The Functionalization of Olefins

Introduction
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.^[1] 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.^[2]
So a tunable dosage of oxygen is desirable. Conceptually, microreactors are a
promising approach to tackle all these issues.

Presentation Outline

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.^[3] 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.^[6]

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,^[7] as well as product selectivity.^[8]
 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.

References

[1]   G.
Franz, R.A. Sheldon, "Oxidation" in Ullmann's Encycl. of Industrial Chemistry, Wiley-VCH, Weinheim
2000.

[2]   U.
Neuenschwander, F. Guignard, I. Hermans, ChemSusChem
2010, 3, 75.

[3]   U.
Neuenschwander, K.F. Jensen, in
preparation.

[4]   U.
Neuenschwander, E. Meier, I. Hermans, ChemSusChem
2011, 4, 1613.

[5]   U.
Neuenschwander, I. Hermans, PCCP 2010, 12, 10542.

[6]   J.
Achkar, T. Sonke, patent WO2011074954, 2011.

[7]   U.
Neuenschwander, I. Hermans, J. Catal. 2012, 287, 1.

[8]   U.
Neuenschwander, E. Meier, I. Hermans, Chem.
Eur. J. 2012, in press.