Aniline Oxidation in a Ball Mill
FULL PAPER
nese dioxide resulting from the reduction of KMnO4 tends
to form a muddy mass that can be rather difficult to work
up. In contrast, the ball milling procedure results in a
powder that is easily extractable with an organic solvent
prior to analysis or isolation. The solvent-free, conventional-
ly heated or microwave-assisted performance of the reaction
was also assessed. However, the corresponding yields were
not reliable with regard to statistical spread of the results.
Clearly, improper mixing of the solid reactants was responsi-
ble for this artifact. Another advantage of the use of ball
mills is the intense mixing, which enables the apparatus to
be used for both reaction and mixing in one device.
In addition to the comparison of chemical performance,
the reaction of p-toluidine in different reaction environ-
ments was assessed with respect to energy conversion.
Energy consumption of 0.035, 0.02, 0.38, 0.20, 0.29, and
0.015 kWh were measured for the reaction conditions listed
in Table 6, respectively. Considering that both of the ball
mills were operated with two equally filled milling beakers
and that, in the case of sonication, a reduced batch size was
used, the molar energy conversion could be calculated
(Figure 4).[17] The data indicate that the solvent-free proce-
Conclusion
A fast and solvent-free method for the oxidation of primary
aromatic amines to azo and azoxy compounds in a planetary
ball mill is described. It was shown that conversion and se-
lectivities can be controlled by the choice of oxidant and
grinding auxiliary. Furthermore, the experiments showed
good reproducibility. Reaction screening of various anilines
showed substituent effects for the oxidation with KMnO4
furnishing the azo compounds with high selectivities. Em-
ploying Oxone instead of KMnO4 afforded the correspond-
ing azoxy compounds with similar selectivities. Again, con-
version is related to the substitution of the starting materi-
als. Compared to methods in solution (microwave, conven-
tional heating, ultrasound), the solvent-free procedure in the
ball mill is more efficient in terms of both chemical yield
and energy consumption. The avoidance of organic solvents
and the easy, fast, and energy-saving aspects of the reaction
make this ball-milling method a real alternative to conven-
tional reaction protocols.
Experimental Section
General: Chemicals are commercially available from Sigma–Aldrich or
Alfa Aesar and were used as received. Reactions were performed in a
Fritsch “Pulverisette 7 classic line” planetary ball mill using 45 mL grind-
ing beakers (agate or ZrO2) and milling balls (6ꢁ15 mm; agate or ZrO2).
All reaction vessels were cleaned with ethanolic HCl (1m) prior to use to
avoid any contamination or memory effects.
GC–FID and GC–MSD measurements were performed with a 6890-GC
or a 6890N-GC-MS instrument, respectively, both from Agilent Technol-
ogies. Conditions for GC–FID: HP 5, 30 mꢁ0.32 mmꢁ0.25 mm, H2-
10 psi, program: 708C (hold for 3 min), 15 KminÀ1 up to 2808C (hold for
10 min), injector temperature: 2808C, detector temperature: 3008C. Con-
ditions for GC–MSD: HP 5, 30 mꢁ0.32 mmꢁ0.25 mm, He-10 psi, pro-
gram: 708C (hold for 3 min), 15 KminÀ1 up to 2808C (hold for 7 min), in-
jector temperature: 2808C, detector: EI (70 eV). NMR spectra were re-
corded with a Bruker Avance 200 MHz system at RT in CDCl3 as solvent
using tetramethylsilane as internal standard.
Figure 4. Energy consumption for the oxidation of p-toluidine (2 mmol)
with KMnO4 using the reaction conditions listed in Table 6 (calculated
according to Schneider et al.[17]).
Data reported herein (conversion, selectivity) were calculated from the
GC data and are comparable with those for the isolated products. The re-
ported yields were adjusted by correcting for the different FID sensitivity
for substrate and product. Isolated yields for the target products in
Tables 3 and 4 are provided within the Supporting Information and are
given in relation to the employed amine. Isolation was performed for
those reactions in Tables 3 and 4 that were performed with ZrO2 as the
grinding material.
dure is superior to solvent-based methods. Only the reaction
performed in an ultrasound reactor had comparable energy
efficiency, and only if the energy for cooling was neglected.
Generally, the reactions in solution needed 0.01 kWh minÀ1
to operate the cryostat (the same cryostat was used for all
processes; cryostat temperature=108C). Including this fact,
the efficiency of the ball milling procedure is highlighted
even more. The lower energy efficiency of the planetary ball
mill compared to the vibration ball mill was due to technical
differences.[18] Because the moving masses are significantly
higher for the former, a higher moment of inertia has to be
overcome to provide proper movement of the milling balls.
However, reaction scale-up is only possible with the planeta-
ry ball mill.
General reaction procedure for the oxidation of anilines: Grinding beak-
ers (45 mL; agate or ZrO2) were equipped with six milling balls of the
same material (d=15 mm), and the milling auxiliary (4 g), the amine
(2 mmol), and the oxidant (4 mmol) were added in the given order. Mill-
ing was performed at 800 rpm for 10 min. After cooling of the grinding
beakers to RT, the crude products were washed through a thin silica
layer using methyl tert-butyl ether (MTBE; 3ꢁ10 mL). The solvent was
evaporated in vacuum and the crude products were dried, redissolved in
MTBE (1.5 mL) and analyzed by GC–FID and GC–MS. Analytical sam-
ples for NMR spectroscopic investigations were isolated by column chro-
matography using a n-hexane/toluene mixture as eluent. Products were
identified by comparison with literature data. For analytical details of the
isolated products, see the Supporting Information.
Chem. Eur. J. 2010, 16, 13236 – 13242
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
13241