Oxidation of primary aromatic amines under irradiation with ultrasound and/or microwaves

Article abstract of DOI:10.1080/00397910802219387

The oxidation of primary aromatic amines, p-methylaniline, p-ethylaniline and p-chloroaniline to the corresponding azo- and azoxy-compounds has been observed in ultrasound and/or microwaves systems. The individual irradiation of microwaves and its simultaneous irradiation with ultrasound obviously elevate the conversion of amines, as compared with the individual irradiation of ultrasound and the heating in a plain water bath. However, the formation of formamidine resulted in poor selectivity toward azo and azoxy products in the presence of dimethylformamide (DMF). Copyright Taylor & Francis Group, LLC.

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Oxidation of Primary Aromatic
Amines under Irradiation with
Ultrasound and/or Microwaves
Zhilin Wu a , Bernd Ondruschka a , Giancarlo
Cravotto b , Davide Garella b & Jila Asgari a c
a Institute of Technical Chemistry and Environmental
Chemistry, Friedrich–Schiller University, Jena,
Germany
b Department of Science and Technology of
Pharmacy, University of Turin, Italy
c Department of Chemistry, Science Faculty, Gorgan
University of Agricultural Science and Natural
Resources, Gorgan, Iran
Published online: 09 Sep 2008.
To cite this article: Zhilin Wu , Bernd Ondruschka , Giancarlo Cravotto , Davide
Garella & Jila Asgari (2008): Oxidation of Primary Aromatic Amines under Irradiation
with Ultrasound and/or Microwaves, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 38:15, 2619-2624
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Synthetic Communications1, 38: 2619–2624, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802219387
Oxidation of Primary Aromatic Amines under
Irradiation with Ultrasound and/or Microwaves
Zhilin Wu,1 Bernd Ondruschka,1 Giancarlo Cravotto,2
Davide Garella,2 and Jila Asgari1,3
1Institute of Technical Chemistry and Environmental Chemistry,
Friedrich–Schiller University, Jena, Germany
2Department of Science and Technology of Pharmacy, University of Turin, Italy
3Department of Chemistry, Science Faculty, Gorgan University of Agricultural
Science and Natural Resources, Gorgan, Iran
Abstract: The oxidation of primary aromatic amines, p-methylaniline, p-ethyla-
niline and p-chloroaniline to the corresponding azo- and azoxy-compounds has
been observed in ultrasound and=or microwaves systems. The individual
irradiation of microwaves and its simultaneous irradiation with ultrasound obvi-
ously elevate the conversion of amines, as compared with the individual
irradiation of ultrasound and the heating in a plain water bath. However, the for-
mation of formamidine resulted in poor selectivity toward azo and azoxy pro-
ducts in the presence of dimethylformamide (DMF).
Aromatic azo and azoxy compounds are important dyes and are widely
used in biological and chemical research as analytical reagents, reducing
agents, stabilizers, and polymerization inhibitors. Aromatic azo com-
pounds are traditionally synthesized by coupling diazo compounds with
amines or phenols, oxidation of hydrazine and hydrazo compounds, the
reduction of nitro compounds in alkaline solution, or molecular
rearrangement of diazoamines. Azo compounds are converted into azoxy
compounds by oxidizing agents.
The formation of azobenzene by oxidation of aniline in basic solution
has also been long known, and its mechanism was clarified in the 1960s.[1,2]
Received in the U.K. October 26, 2007
Address correspondence to Bernd Ondruschka, Institute of Technical Chemis-
try and Environmental Chemistry, Friedrich–Schiller University, Jena. E-mail:
bernd.ondruschka@uni-jena.de
2619

2620
Z. Wu et al.
The catalytic oxidation of primary aromatic amines to azo derivatives with
H2O2 in the presence of titanium silicate molecular sieves, sodium per-
iodate in the presence of manganese(III) tetraphenylporphyrin, or titania
pillared montmorillonite clays was recently reported.[3–7] Primary aromatic
amines can also be oxidized to azo compounds by permanganate under sol-
vent-free conditions, a green method.[8]
The reaction mechanism in which azobenzene is formed by oxidation
of aniline in aqueous solution under irradiation with 21-kHz ultrasound
(US) was explained.[9] Sonically generated Hꢀ and OHꢀ radicals convert
aniline to PhNHꢀ and PhNꢀ radicals that can combine to yield
=
PhNHNHPh and PhN NPh. Microwave (MW) irradiation has afforded
another new procedure for the selective oxidation of aromatic amines.
Using alumina as a solid support, azobenzene was prepared in 75% yield
in 5 h at room temperature.[8] The oxidation of aniline with MnO2=SiO2
under MW irradiation (420 W) for just 4 min gave azobenzene in 84%
yield.[10] Although the existing catalytic methods can achieve comparable
yields of azo and azoxy compounds, the use of MW–US has the advan-
tage of reducing catalyst load or dispensing with it altogether, besides
facilitating the separation of products and significantly shortening
production times.
The chemoselective reduction of nitroarenes to azo and azoxy com-
pounds under US=MW irradiation has also been reported.[11] Either
energy source, as well as their combination, promoted the reactions
and increased their yields. The simultaneous use of US and MW rep-
resent an emerging technological innovation that deserves wider attention
in fine chemical and pharmaceutical research. Although cavitation and
MW effects are not fully understood, there is no doubt that processes
requiring enhanced heat transfer and mass transport can greatly benefit
from the use of this technique.[12]
The present communication deals with the use (so far unreported) of
the simultaneous irradiation of microwaves and ultrasound for the selec-
tive oxidation of primary aromatic amines to azo and azoxy compounds
(Scheme 1).
Reactions were carried out in batches in a 100-ml specially designed
glass vessel placed in the center of a professional multimode MW oven
Scheme 1. Oxidation of primary aromatic amines under irradiation with ultra-
sound and=or microwaves.

2621

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Z. Wu et al.
where a Pyrex1 horn was directly inserted in the vessel.[11] In a typical
run, 4 mmol of KMnO4 were dispersed in a solution of 2 mmol of amine
in 30 ml of DMF–water (25:5). After the reaction was completed (20 min)
and the mixture had cooled down to room temperature, MnO2 was fil-
tered off, and the reaction mixture was extracted with ethyl acetate
(3 ꢂ 20 ml). The organic layer was dried over anhydrous MgSO4, then
the solvent was removed in a rotavapor and 10 ml of ethyl acetate were
added to redissolve the residue for GC analysis. The solution was
analyzed in a gas chromatograph (HP-5890) fitted with a HP-5 capillary
column (30 m ꢂ 0.32 mm ꢂ 0.25 mm) using H2 as carrier gas. The tempera-
ture was held at 70 ꢁC for 3 min, then raised to 250 ꢁC at the rate of
10 ꢁC=min, and finally kept at 250 ꢁC for 4 min. The identity of the
products was established by GC-MS (Agilent Technologies mass spec-
trometer, GC 6890N with MS detector 5973), fitted with a HP-5MS
capillary column (30 m ꢂ 0.25 mm ꢂ 0.25 mm) using He as carrier gas.
Results of the oxidation of amines under individual and simul-
taneous irradiations of MW and US are summarized in Table 1. More
than 70% conversions of p-methylaniline and p-ethylaniline were
obtained in 20 min by irradiating with MW or simultaneously with
MW and US, whereas 57 and 54% conversions of p-ethylaniline were
respectively observed with US irradiation as well as plain heating in a
water bath. As expected, the simultaneous irradiation with MW and
US significantly enhanced the conversion of p-chloroaniline as well.
The extent of conversion for p-methylaniline and p-ethylaniline
under different irradiation was found to vary in the order
MW > MW–US > US > heating in a plain water bath. Yields of azo
products did not vary significantly except in the case of p-chloroaniline.
The extent of conversion for p-chloroaniline under different irradiation
varied in the order MW–US > MW > US; however, yields of 4,40-
dichlorazobenzene followed the order US > MW–US > MW.
Because DMF is a good polar, aprotic solvent with a high boiling
point, its use is common in MW irradiation chemistry. However, in its
presence formation of formamidine and other by-products resulted in poor
selectivity toward azo and azoxy products (Scheme 2). No by-product was
formed when the amount of water in the medium was increased from 15 to
35 ml. However, the yields of azo and azoxy compounds also decreased.
Scheme 2. Formation of formamidine in the presence of DMF.

Oxidation of Amines under Irradiation
2623
Figure 1. Product distribution in the oxidation of p-ethylaniline under simul-
taneous irradiation with MW–US, as a function of temperature; 1 mmol of
p-ethylaniline, 4 mmol of KMnO4, 25 ml of DMF, 5 ml of H2O. MW: MLS-Ethos
MW system: 1 min at 1000 W to heat the mixture to 95ꢁC and further irradiated
for 19 min at 70 W to maintain this temperature. US: 20 kHz with a Pyrex horn1
(U 15 mm), nominal power 50 W.
Figure 1 shows how product distribution varied as a function of tem-
perature for the oxidation of p-ethylaniline under simultaneous MW–US
irradiation. As temperature increased from 75 to 95 ꢁC, the conversion
increased from 74 to 94% while product distribution for azo and azoxy
products increased slightly. As shown in Fig. 1, less formanidine and
other products were formed at 85 ꢁC than at 95 ꢁC.
To improve the conversion rate under simultaneous MW–US
irradiation, 2, 4, and 6 mmol of CuSO4ꢀ5H2O were added as catalyst to
30 ml of DMF–water (25:5) mixtures containing 1 mmol of p-ethylaniline.
As expected, the conversion at 85 ꢁC increased from 70 to 81%. The pro-
duct distribution to azo compound increased from 27 to 36%, and the
product distribution to azoxy compound increased from 22 to 35% while
formation of formamidine decreased from 39 to 1%.
In conclusion, a high conversion rate for amines can be achieved
under MW or simultaneous MW–US irradiation. An efficient MW–US
procedure for the preparation of azo and=or azoxy compounds from pri-
mary aromatic amines has been presented. In the future, the effect of
other solvents such as dimethyl sulfoxide (DMSO), acetonitrile, and etha-
nol will be investigated, with the aim to avoid the formation of formami-
dine and other by-products.

2624
Z. Wu et al.
ACKNOWLEDGMENT
The authors acknowledge support from Cesare Buffa for the building of
ultrasound device and from Markus Hoffman for embellishment of the
text.
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