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pubs.acs.org/OPRD

Continuous, Fast, and Safe Aerobic Oxidation of 2Ethylhexanal:

Pushing the Limits of the Simple Tube Reactor for a Gas/Liquid
Reaction
Laurent Vanoye, Jiadi Wang, Mertxe Pablos, Regis Philippe, Claude de Bellefon,
and Alain Favre-Reguillon*,,

Laboratoire de Genie des Procedes Catalytiques, UMR 5285, CPE Lyon, 43 bld du 11 nov. 1918, 69100 Villeurbanne, France
Conservatoire National des Arts et Metiers, CASER-SITI, 292 rue Saint Martin, 75003 Paris, France

S Supporting Information
*

demonstrated to be a valuable alternative for the safe and

ecient chemical processing2124 and among them aerobic
oxidation of aldehydes.25,26 While this reaction could be
performed without neither catalysts nor radical initiators, the
reaction rate was greatly increased using metal ions as catalysts,
such as Mn(II) and pure oxygen, inside segmented ow
reactors.27,28
Other advantages of continuous microreactors are the small
inventory of potentially hazardous chemicals and intermediate
species and their large surface to volume ratio which, besides its
interest for mass and heat transfers, could contribute to inhibit
gas-phase free-radical reactions by recombination on the reactor
walls.21
The selectivity of the oxidation process is known to be highly
dependent on the aldehyde structure.2732 While high
selectivity was observed with linear aliphatic aldehyde,26
selectivity below 80% toward the corresponding carboxylic
acid was obtained for the target reaction, i.e., the oxidation of 2ethylhexanal 3.12,25,27,30 The synergistic use of alkali metals salts
(i.e., sodium 2-ethylhexanoate) or organic carboxylate salt (i.e.,
ionic liquid) and Mn(II) as catalyst can improve the selectivity
up to 98% while maintaining good productivity of the
process.27,28 Under these conditions, total conversion of the
aldehyde 3 was achieved using ow chemistry, and the
selectivity was kept high.
Herein, a study about further intensication of the aldehyde
oxidation to the corresponding carboxylic acid using a simple
tube continuous-ow reactor that used cheap, disposable PFA
tubing and undergoing a G-L segmented ow (Taylor ow) is
reported. Also, we sought to use this reactor for the visual
monitoring of the ow. An increase of the internal diameter
(i.d.) of PFA tubing (from 1 mm to 1.65 mm) was the only
modication to our lab scale microreactor.25,27 For higher i.d.,
regular Taylor ow could not be easily obtained within the
range of the ow rates used. The productivity of this simple
experimental setup was pushed to its limits using tools such as
oxygen mass transfer, catalyst loading, and concentration in
order to maximize the acid yield under safe conditions with a
high purity of the product.

ABSTRACT: A continuous-ow microreactor is applied

for the selective aerobic neat oxidation of 2-ethylhexanal.
Under 7.5 bar of O2 and 10 ppm of Mn(II) as catalyst, a
production of up to 130 g/h of 2-ethylhexanoic acid can be
obtained with a PFA tubing of 7 m ( 1.65 mm, reactor
volume ca. 15 mL). The synergistic use of alkali metal salts
and Mn(II) as catalyst improve the selectivity up to 94%
under those conditions. We show that the productivity of
this simple tube microreactor is limited by the thermal
management.

INTRODUCTION
2-Ethylhexanoic acid 1 is an important chemical intermediate
used in the production of synthetic lubricants, lm plasticizers
for polyvinyl butyral, stabilizers for PVC as well as oil additives,
and functional uids like automotive coolants.1,2 Moreover,
metal salts of 2-ethylhexanoic acid are used in wood
preservatives, as catalyst for polyurethane synthesis, as metal
soaps in paint dryers, and in various other applications.3 This
product belongs to the C8 compounds family and is obtained
through the aldol condensation of butyraldehyde 2.4,5 An
overview of the industrial synthetic pathway to 1 is shown in
Scheme 1.
According to the patent literature, the oxidation of 2ethylhexanal 3 to 2-ethylhexanoic acid 1 is typically performed
in a gas sparged stirred tank or gas lift bubble column reactors
with air or enriched air as the gas phase using molecular oxygen
as the terminal oxidant and with the optional presence of a
catalyst.69 However, this oxidation is strongly exothermic
(rH = 287 kJ/mol, adiabatic temperature rise of 1065 K for
pure aldehyde) and proceeds via highly reactive free radical
species; thus an ecient temperature control is claimed to be
critical for the selectivity, the productivity, and the safety of the
process.69 This intrinsically fast reaction presents gasliquid
mass transfer limitation in most industrial reactors.611 As a
matter of fact, even at the lab scale, the productivities published
in recent articles on aerobic oxidation are aected by the gas to
liquid oxygen mass transfer rate.12,13 In order to reach the
chemical regime and improve the productivity, advanced
microreactors can be used. They are known to provide better
mass and heat transfers than classical vessels.1420 Thus,
continuous ow micro- and millimetric reactors were
2015 American Chemical Society

Received: November 2, 2015

Published: December 22, 2015
90

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Communication

Scheme 1. Overview of the Industrial Synthetic Routes to 2-Ethylhexanoic Acid 1a

Reaction type: (a) hydroformylation; (b) aldol condensation; (c) hydrogenation; (d) oxidation.

EXPERIMENTAL EQUIPMENT
Analytical grade heptane and tetradecane (Aldrich) was used. 2Ethylhexanal 3 (96%) (Aldrich or Acros) was used as obtained
from the supplier and stored at 4 C under N2 with protection
from light. Mn(II) 2-ethylhexanoate (40% in mineral spirits)
was provided by STREM and used as obtained. Pressurized
oxygen (99.995%) was provided by Messer.
Figure 1 shows the experimental setup. A PFA tubing
(Upchurch Scientic) (internal diameter of 1.65 mm with

Figure 2. Initial rate as the function of catalyst loading. Reaction

conditions: 2-ethylhexanal 3 0.8 M in heptane, O2 5 bar, O2/aldehyde
molar ratio 5, PFA tubing 1 m, i.d. 1.65 mm, 25 C, catalyst Mn(II)
2-ethyl hexanoate, sodium 2-ethylhexanoate 2 wt %, and tetradecane 1
wt % as internal standard. The tendency curve is only displayed to help
reading. See also Figure S3 in the Supporting Information.
Figure 1. Experimental setup for the neat aldehyde aerobic oxidation
(O2 excess <10%, 6.7 m PFA tubing).

Metal catalysts in the ppm range strongly enhanced the rate of

oxidation of 2-ethylhexanal 3, and 50% of conversion could be
obtained in less than 60s with 10 ppm of Mn(II). Quantitative
conversion was obtained in the same time with 100 ppm of
Mn(II) (Figure S3 in the in the Supporting Information), and
thanks to the use of 2 wt % of sodium 2-ethylhexanoate, the
purity of the carboxylic acid was higher than 98%.27,28 Above
100 ppm, no noticeable improvement in the conversion could
be seen (Figure 2). This phenomenon could be explained by
the appearance of an oxygen mass transfer limitation. The
overall transformation rate is controlled by this physical step,
showing the limit of the Taylor ow regime to ensure a high
enough mass transfer rate under the chosen experimental
conditions (concentration, temperature, channel diameter, and
ow velocity).
However, this reaction was performed in a small reactor (1 m
long PFA tubing 2 mL), with aldehyde diluted in heptane
(0.8 M) and with a large excess of oxygen. These factors
strongly limit the productivity of the G/L microreactor.
Therefore, the experimental conditions and setup were
modied: (i) the length of the PFA tubing was increasing to
7 m (i.e., 15 mL). Note that, for higher tube length, regular
Taylor ow with neat 2-ethylhexanal 3 is not easy to manage
using our experimental setup; (ii) the concentration of
aldehyde was increased from 0.8 to 6.2 M (i.e., neat aldehyde).
2 wt % of sodium 2-ethylhexanoate was added to maintain the
selectivity of the process; (iii) the excess oxygen was decreased
from 400% to 510%, thus resulting in a larger holdup of liquid
in the reactor hence to a higher liquid residence time.
Compared to previous conditions (Figure 2), the initial total
ow velocity is several times higher but will decrease along the
reactor due to oxygen bubble shrinking. Under these

variable length (1.0 and 6.7 m) was used as reactor. The

organic phase (Harvard pumps PHD 4400) and the oxygen
(Analyt-MTC massow controller) were fed via two separate
lines and brought together using a T-mixer (Interchim). A back
pressure was applied using a homemade back pressure regulator
controlled with nitrogen ow (Analyt-MTC massow controller) and micrometering valve.
The GC analysis was performed on a Agilent 6890 GC
equipped with FID detector, an automated liquid sampler, and
Red dot FFAP column (5 m x 0.05 mm x 0.05 m). Conversion
and selectivity toward the carboxylic acid were determined on
the basis of the normalized peak areas for aldehyde, carboxylic
acid, and tetradecane (internal standard).

RESULTS AND DISCUSSION

The inuence of the rst two factors (oxygen mass transfer rate
and catalyst loading) were evaluated using 2-ethylhexanal 3
diluted in heptane (0.8 M) under 5 bar of oxygen at 25 C with
a simple PFA tubing (1 m length and 1.65 mm i.d.) and an
excess of oxygen (O2/RCHO molar ratio of 5). Due to a very
low pressure drop (below 2% of the outlet pressure), the
oxygen pressure was considered to be constant in the entire
reactor. Under these conditions, a constant bubble length and
ow velocity were also presumed. Liquid and gas initial ow
rates were adjusted to obtain dierent residence times for
various catalyst contents, and the results are reported in Figure
2 (see also Figure S3 in Supporting Information).
As expected from previous studies, oxidation of aliphatic
aldehydes can be performed without catalysts or initiators.25
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conditions, in the rst part of the tube, the initial transfer rate is
improved, and consequently so is the apparent reaction rate.
When high conversion is reached, the total ow rate decreases
(due to O2 volume decreasing), and this phenomenon possibly
aects the oxygen mass transfer coecient and thus the
apparent reaction rate. Thus, residence time could not be
precisely determined under these conditions, but it can be
visually estimated to be around 1 min. Nevertheless conversion,
selectivity, and volumetric reactor productivity could be
precisely determined. One important consequence of the new
conditions is a ca. 10-fold increase of the heat ux from the
reaction (vide supra). As a precaution and to enhance cooling
of the reaction mixture, the PFA tubing was immersed in a
water bath at 25 C, and the slower uncatalyzed neat oxidation
of 2-ethylhexanal 3 was attempted rst.
Under neat conditions, the uncatalyzed aerobic oxidation of
3 proceeds gently (Table 1, entry 1). A low conversion and a

of the liquid occurs 4 cm above this vaporization zone, and a

Taylor ow is generated again. However, the length of the
liquid and gas slugs beyond that point were larger and less
regular than the rst ones. Both conversion (69%) and
selectivity (below 60%) were strongly aected by this
phenomenon. It should be noticed that such steady state was
maintained all along the experiment (around 15 min). A
temperature higher than 200 C could be measured inside the
tube in the vaporization zone.29 The low conversion obtained
under those conditions could be explained by several factors.
The main driving factor was the uncontrolled decomposition of
the Criegge intermediate at high temperature that produce
several byproducts (Figure 4), and among them, alcohol and
formate which are strong inhibitors of the radical pathway12
and to lesser extent a decrease of the oxygen mass transfer due
to the modication of the Taylor ow properties after the
condensation zone. Lower amounts of catalyst (typically 100
ppm) will still lead to lower selectivity, probably due to the
relatively high temperature reached along the reactor.
Furthermore, the repeatability was lower under those
conditions. It should be noticed that the use of a cold water
bath (5 C) inhibits the oxidation (Table 1, entry 5) and could
not simply be considered for the control of the selectivity.
Thus, the catalyst content was then reduced back to 10 ppm,
but oxygen pressure was increased to 7.5 bar (Table 1, entry 5).
The increase of the O2 pressure yielded quantitative conversion
(>99.5%) while maintaining a high selectivity (94%) toward the
carboxylic acid. Under these conditions, a production of nearly
1 mol (0.93 M, i.e., 134 g) of 2-ethylhexanoic 3 acid per hour
was achieved with a simple tube reactor in PFA. The selectivity
could be increased by decreasing the amount of catalyst in
order to lower the heat ux from the reaction. But to maintain a
quantitative conversion, the inlet gas and liquid ow rates were
divided by 2 to rise the residence time. Under those conditions,
the productivity was divided by 2, but a selectivity higher than
97% was obtained (Table 1, entry 6).

Table 1. Aerobic Oxidation of Neat 2-Ethylhexanal 3 Using

Single Tube Microreactora

entry

catalyst (ppm)

O2 (bar)

conv. (%)b

select. (%)b

1
2c
3d
4
5e
6f

0
10
200
10
10
5

6
6
6
7.5
7.5
7.5

9
95
69
>99.5
52
>99.5

95
95
56
94
94
97

a
General conditions: Inlet O2 ow: 200 NCCM, inlet aldehyde ow:
2.5 mL/min., neat 2-ethylhexanal 3 containing sodium 2-ethylhexanoate (2 wt %), tetradecane as internal standard (1 wt %), tube
length: 6.7 m, id: 1.65 mm, water bath at 25 C. bMean value of at
least three samples spaced 2 min. cSee movie No. 1. dVaporization of
the liquid phase was observed in the rst 10 cm, see movie No. 2.
e
Water bath at 5 C. fG and L ow rate divided by 2.

CONCLUSION
These experiments demonstrate the capability of simple tube
microreactor (total volume of 15 mL, overall footprint of half
the size of standard laboratory fume hood) to perform
continuous reactions under explosive conditions. A daily
production of 3.22 kg of 2-ethylhexanoic acid with a purity of
94% could be reached without further purication nor solvent
separation with simple, cheap, and readily available materials
and equipment. Such productivity could not be considered
using a classical 10 L lab-scale batch reactor for safety reasons
due to the explosive gas mixture,33,34 the adiabatic temperature
rise of 1065 K and the required heat removal capability of about
700 W. The use of PFA tubing allows the visual control of the
ow associate to a low permeability to liquids, gases, organic
vapors, and wide operating temperature range (240 C to
+260 C). However, the relatively low heat transfer coecient
of PFA (0.195 W/mK) does not allow ecient management of
the reaction heat ux. Thus, the catalyst amount had to be
decreased to maintain the high conversion and selectivity of the
process. Higher oxygen pressure and total ow velocity
associated with a better heat management integration would
help to improve the productivity by reaching a more favorable
process window.

high selectivity toward the acid were observed. Then, 10 ppm

of Mn(II) was used as catalyst. Under these conditions, a
regular and stable Taylor ow was seen in the rst few
centimeters of the PFA tubing (Figure 3 upper picture and
movie No. 1 in the Supporting Information). Bubble shrinking
was also noticed along the PFA tubing due to O2 consumption.
This implies a decrease of the linear velocity of the liquid ow
that could impact oxygen mass transfer rate. Inlet O2 and
aldehyde ows were thus optimized to obtain a conversion up
to 95%. Under these conditions, a selectivity of 95% toward
carboxylic acid could be obtained (Table 1, entry 2 and Figure
4, upper chromatogram). The temperature rise inside the PFA
tubing induced by the oxidation was below 20 C (controlled
with a thermocouple in a dedicated experiment) and has almost
no inuence on the selectivity of the process.29
The rst attempt to increase the productivity was an increase
in the catalytic amount of Mn(II), while the inlet gas and liquid
ow rates were kept constant. However, using 200 ppm of
Mn(II), a completely dierent ow pattern was noticed (Figure
3, bottom picture and movie No. 2 in the Supporting
Information) as well as signicantly lower conversion and
selectivity (Table 1, entry 3). Within the rst 6 cm, a regular
and stable Taylor ow was observed followed by a rapid
disappearance of the liquid slug in less than 1 cm. Reappearance
92

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Figure 3. Top view of the PFA tubing layout and visualization of the segmented G/L ow during the aerobic oxidation of 2-ethylhexanal 3. Reaction
conditions: neat 2-ethylhexanal 3 + 2 wt % of sodium 2-ethylhexanoate, 6 bar of O2, PFA tube length: 6.7 m, i.d.: 1.65 mm, water bath at 25 C, 10
or 200 ppm, respectively, of Mn(II) for the upper and for the lower picture (images taken from the movies, see the Supporting Information).

liquid ow rate), and calculations of heat transfer

resistance distribution at the reactor wall (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: afr@lgpc.cpe.fr.
Notes

The authors declare no competing nancial interest.

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Figure 4. Comparison of GC chromatogram obtained during the neat

oxidation of 2-ethylhexanal 3 with 10 ppm of Mn(II) (top) and with
200 ppm of Mn(II) (down). Experimental conditions: see Table 1.

REFERENCES

ASSOCIATED CONTENT

S Supporting Information
*

The Supporting Information is available free of charge on the

ACS Publications website at DOI: 10.1021/acs.oprd.5b00359.
Movie No. 1 showing the top view of the PFA tubing
during the oxidation of 2-ethylhexanal 3 with 10 ppm of
Mn(II) (AVI)
Movie No. 2 showing the top view of the PFA tubing
during the oxidation of 2-ethylhexanal 3 with 200 ppm of
Mn(II) (AVI)
Experimental setup for diluted aldehyde oxidation and
neat aldehyde oxidation (Figure S1 and S2). Data used
for Figure 1 (gas ow rate, liquid ow rate and calculated
residence time), conversion as the function of residence
time and catalytic amount of Mn(II) (Figure S3), data
used for Table 1 (O2 pressure, inlet gas ow rate, and
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