Solvent-free basic or KF/alumina-assisted dehydrogenation of hydrazo compounds

Article abstract of DOI:10.1055/s-2007-984878

A reduction of organic solvents in the organic chemical industry is of serious importance for sustainable chemistry. With this viewpoint, we successfully established the useful dehydrogenation of hydrazo compounds using basic alumina or KF/alumina under s

Full text of DOI:10.1055/s-2007-984878

2
124
LETTER
Solvent-Free Basic or KF/Alumina-Assisted Dehydrogenation of Hydrazo
Compounds
D
M
ehydrogenation of
H
a
ydrazo
C
om
s
pounds atoshi Mihara,* Takeo Nakai, Toshiyuki Iwai, Takatoshi Ito, Takumi Mizuno
Osaka Municipal Technical Research Institute, Morinomiya 1-6-50, Joto-ku, Osaka 536-8553, Japan
Fax +81(6)69638049; E-mail: mihara@omtri.city.osaka.jp
Received 7 May 2007
15
dioxide were employed to accomplish this transforma-
tion. In addition, heterogeneous dehydrogenation was
Abstract: A reduction of organic solvents in the organic chemical
industry is of serious importance for sustainable chemistry. With
this viewpoint, we successfully established the useful dehydrogena-
16
recently achieved using manganese dioxide, sodium ni-
17
tion of hydrazo compounds using basic alumina or KF/alumina trite–sodium hydrogen sulfate–silica gel, and polymer-
1
8
under solvent-free conditions to afford azo compounds in good to supported periodate resin. The described methods, how-
excellent yields.
ever, require the use of organic solvents. Furthermore,
Key words: solvent-free, alumina, dehydrogenation, hydrazo com- they suffer from drawbacks such as the need for an exces-
pounds, azo compounds
sive amount of dehydrogenation agents, a cumbersome
procedure, and tedious pretreatment. Therefore, there is a
continuing search for a new method of dehydrogenation
that may circumvent these problems. Herein, we wish to
report on solvent-free dehydrogenation of hydrazo com-
pounds using readily available alumina, which makes the
process more efficient and simpler.
Much effort has been directed toward the development of
the methodology for a reduction of organic solvents used
in organic synthesis from the standpoint of sustainable
1
2
chemistry. Supercritical carbon dioxide, ionic liquids,
etc. are already well known as alternative solvents which
escape both toxicity and the environmental damage of
organic solvents. However, since they present problems
with regard to the requirement of high-pressure conditions
The dehydrogenation of hydrazobenzene (1a) on inorgan-
ic porous solids was examined under solvent-free condi-
tions and the results are summarized in Table 1.
19
19
Commercially available basic alumina or KF/alumina
3
and expensive reagents, the best solvent is no solvent. In
strongly accelerated the dehydrogenation of 1a under air
to give the corresponding azobenzene (2a) in excellent
yields, in contrast with no formation of 2a in the absence
of an inorganic solid (entries 1–4). The best yield of 2a
was obtained when 1a (1 mmol) was treated with KF/alu-
recent years, the use of inorganic porous solids in organic
synthesis has received considerable attention because of
their environmental compatibility as well as high reactiv-
4
ity, selectivity, and simple operations. In particular, it is
interesting that the synthetic method can offer a solvent-
free approach with less environmental impact, which
Table 1 Dehydrogenation of 1a to 2a under Solvent-Free
avoids the need for the disposal of solvents and trouble- Conditions
some recycling. For example, the surface of alumina can
work as a support, a promoter, and a reagent in the
H
base, air
N
Ph
N
Ph
Ph
N
Ph
N
H
absence of solvent, thereby permitting several trans-
5
6
7
formations such as oxidation, coupling, substitution,
1a
2a
8
9
elimination, and addition under mild conditions. These
findings prompted us to apply alumina to a further sol-
vent-free reaction.
Entry Base (g)a
Temp Time Yield
Recovery
b
b
(
°C) (min) of 2a (%) of 1a (%)
1
2
3
4
5
6
7
8
–
80
80
80
80
80
80
50
20
20
1
95
2
A variety of azo compounds have long played a signi-
1
0
11
ficant role in dyes and analytical reagents, and are
widely used at present. Thus, the development of their
synthetic methods is of much current importance. Among
these methods, dehydrogenation of hydrazo compounds is
one of the useful approaches for producing azo com-
pounds, and various methods have been reported. Thus
far, numerous reagents, such as sodium hydroxide,12 tri-
Al O (basic, 2)
77
2
3
Al O (basic, 1)
30
87 (73)c
2
2
3
92 (85)c
KF/Al O (0.5)
30
1
2
3
MgO (2)
20
75
12
70
66
5
NaOH (2)
20
78
12
21
1
3
aryl phenol–potassium ferricyanide–sodium hydroxide,
iron chloride,
1
4
Al O (basic, 2)
180
30
and polyethylene glycol–nitrogen
2
3
Al O (basic, 0.5) 80
2
3
a
b
c
Weight per 1 mmol of 1a.
NMR yields.
Isolated yields.
SYNLETT 2007, No. 13, pp 2124–2126
Advanced online publication: 12.07.2007
DOI: 10.1055/s-2007-984878; Art ID: U04507ST
1
3
.0
8
.2
0
0
7
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Dehydrogenation of Hydrazo Compounds
2125
mina (0.5 g) at 80 °C for 30 minutes under blowing air (1
H
H
Al2O3
N
Ph
O2
2
0
N
Ph
N
Ph
atm, entry 4). Alumina, which possesses a basic nature,
was found to be a more favorable additive for this reaction
than other inorganic solids, such as neutral alumina, acidic
alumina, silica gel, and montmorillonite K10. Magnesium
Ph
δ
N
Ph
N
Ph
N
H
H
H
N
Ph
Ph
N
oxide showed a good result, next to basic alumina (entry Scheme 1
5
). It is noteworthy that the reaction in the presence of so-
dium hydroxide gave a low yield of 2a (entry 6), whereas
that in the presence of the solid base was smooth. In addi-
tion, the yield of 1a was influenced to a considerable ex-
tent by the temperature and the amount of the base used.
An increase in the reaction temperature from 50 °C to 80
tion than 1, was transformed to the dehydrogenated
products 4 in a yield of 51% by KF/alumina. Moreover,
the treatment of hydrazone 5 with KF/alumina provided a
4
4% yield of azine 6 (Scheme 2).
°
C led to an improved yield in a short reaction time (entry Table 3 Solvent-Free Dehydrogenation on Alumina
2
vs. 7). A decrease in the amount of basic alumina to 0.5
R
H
N
N
H
R
R
g reduced the efficiency of the reaction (entry 3 vs. 8).
base, air
N
N
The activity of recovered alumina was then examined
R
(
Table 2). Basic alumina was easily recovered from reac-
tion mixtures by filtration followed by washing with di-
ethyl ether. As shown in entries 1–3, the basic alumina
could be reused at least two times without any loss in ac-
tivity. On the other hand, KF/alumina was shown to pro-
vide a slight decrease in the yield in a second run if it was
reused without any pretreatment.
1
2
1
R
Basea
A
Temp (°C) Time (min) Yield of 2 (%)
1
1
1
1
1
a
H
80
80
30
30
30
30
40
40
73
85
71
95
74
84
a
b
b
c
H
B
Me
Me
Cl
Cl
A
110
110
110
110
Table 2 Solvent-Free Dehydrogenation of 1a to 2a on Recycled
Alumina
B
base, air
A
1a
2a
80 °C, 30 min
1
a
c
B
Entry
Base (g)a
Al O (basic, 1)
Yield of 2a (%)
A: Al O (basic), 1 g per 1 mmol of 1; B: KF/Al O , 0.5 g per
mmol of 1.
2
3
2
3
1
1
2
3
4
5
73
70
2
3
2nd use
O
O
H
N
a
3rd use
73
Ph
N
Ph
Ph
N
N
Ph
N
N
H
5
1%
92b
H
H
KF/Al O (0.5)
2
3
3
4
2nd use
78b
Ph
Ph
Ph
Ph
a
b
N
Ph
Ph
Weight per 1 mmol of 1a.
NMR yields.
N
b
N
NH2
44%
5
6
The detailed mechanism for this reaction has not yet been
clarified, but the acceleration in the dehydrogenation was
caused presumably by the basic sites on the surface of alu-
mina. Further, when the reaction of 1a on basic alumina
Scheme 2 Reagents and conditions: (a) KF/Al O (2 g per 1 mmol
2
3
of 3), air, 110 °C, 35 min; (b) KF/Al O (2 g per 1 mmol of 5; it was
2
3
heated at 110 °C for 10 min before use), air, 110 °C, 20 min.
(
Table 1, entry 3) was carried out in the presence of a
In conclusion, we established a new protocol for the dehy-
drogenation of hydrazo compounds using basic alumina
or KF/alumina as a base under air. The reactions proceed-
ed well in a short reaction time without any organic sol-
vent. In particular, basic alumina was readily recovered
and reused. Furthermore, the reaction on alumina could be
carried out with simple and nonaqueous workup. There-
fore, the reaction using alumina is characterized by the ab-
sence of solvents, ready recycling of the catalyst, good
yields of products, and simplicity of operations. Conse-
quently, the present method is environmentally benign,
efficient, and simple.
galvinoxyl free radical (0.1 equiv), it was observed that
the addition of the radical inhibitor brought about a 16%
decrease in the rate of conversion. Thus, the result may in-
dicate that the some part of this reaction proceeds through
radical species generated on the alumina (Scheme 1).
The dehydrogenation was successfully applied to 2,2¢-dis-
ubstituted hydrazobenzenes 1 to afford the corresponding
azobenzenes 2 in good to excellent yields (Table 3). The
higher temperature needed may be attributed to increased
steric hindrance in the conversion of 1b and 1c. In addi-
tion, semicarbazide 3, which is more resistant to air oxida-
Synlett 2007, No. 13, 2124–2126 © Thieme Stuttgart · New York

2
126
M. Mihara et al.
LETTER
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Acknowledgment
We would like to thank the Seika Corporation for the generous gift
of hydrazo compounds 1b and 1c.
(
(
(
(
(
12) Shine, H. J. J. Am. Chem. Soc. 1956, 78, 4807.
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6
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flask containing KF/alumina (0.5 g). The reaction mixture
was stirred at 80 °C for 30 min with blowing air under
(
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2
to the resulting mixture and filtered on a Büchner funnel to
remove the alumina. The alumina was washed with Et O and
2
the combined filtrate was concentrated in vacuo. After
purification by flash chromatography on silica gel eluting
with EtOAc–hexane, azobenzene (2a) was obtained in a
yield of 85%.
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alumina (5 g) following the same procedure except the
reaction time. After a heating time of 45 min, 2a was
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(
3
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