Aqueous-phase aerobic oxidation of alcohols by Ru/C in the presence of cyclodextrin: One-pot biomimetic approach to quinoxaline synthesis

Article abstract of DOI:10.1055/s-0030-1258775

The aerobic oxidation of alcohols and synthesis of quinoxalines was developed in a one-pot biomimetic approach using recyclable ruthenium on charcoal and randomly methylated β-cyclodextrin in water under neutral conditions overcoming many of the drawbacks in the earlier methodologies. The catalytic system can be recycled up to five cycles without loss of activity. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1258775

LETTER
2571
Aqueous-Phase Aerobic Oxidation of Alcohols by Ru/C in the Presence of
Cyclodextrin: One-Pot Biomimetic Approach to Quinoxaline Synthesis
O
V
ne-Pot Biomimet
i
ic
A
pp
j
roach t
a
o Quinoxali
y
ne Synthesis Kumar Akkilagunta, Vutukuri Prakash Reddy, Rama Rao Kakulapati*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500607, India
Fax +91(40)27160512; E-mail: kakulapatirama@gmail.com
Received 9 July 2010
In view of the above facts, we attempted the oxidation of
Abstract: The aerobic oxidation of alcohols and synthesis of qui-
noxalines was developed in a one-pot biomimetic approach using
recyclable ruthenium on charcoal and randomly methylated b-cy-
benzyl alcohol in the presence of Ru/C (10 mol%), b-CD,
and water under O atmosphere at 75 °C, and to our de-
2
clodextrin in water under neutral conditions overcoming many of light, we isolated 82% of benzaldehyde as the sole prod-
the drawbacks in the earlier methodologies. The catalytic system uct. Encouraged with this result we screened various other
can be recycled up to five cycles without loss of activity.
cyclodextrins, polysaccharides, surfactants (ionic/nonion-
Key words: alcohols, biomimetic synthesis, cyclodextrins, oxida- ic), quaternary bases, etc. for the benzyl alcohol oxidation
tion, Ru/C
and found randomly methylated b-cyclodextrins (Ra-Me-
b-CD) to be efficient in catalytic amount to convert benzyl
alcohol into benzaldehyde in 99% yield at 75 °C with 10
mol% Ru/C under oxygen atmosphere. It was found that
the presence of Ra-Me-b-CD was crucial for the aerobic
oxidation and no oxidation took place when only Ru/C
was employed. We have also optimized the amount of Ra-
Me-b-CD required to achieve an efficient conversion of
The advent of aerobic oxidation has revolutionized the al-
cohol oxidation and made the oxidation procedures more
efficient, economical, and sustainable. Various methods
and protocols using Cu, Co, V, Pd, Ru, Rh, Mo and with
additives for the aerobic oxidation of alcohols are all well
1
,3f
established. The metal-supported or immobilized cata- benzyl alcohol (1 mmol) into benzaldehyde (Figure 1).
lytic systems for the aerobic oxidations are more propense
due to the advantage of recoverability of catalyst, but at
present, their utility is restricted due to the use of organic
solvents, high pressures of oxygen or air, and high reac-
tion temperatures under strong basic conditions. This
makes them unfriendly both from environment as well as
economic points of view. Hence we are interested in de-
veloping a methodology for the aerobic oxidation of alco- Figure 1 Benzaldehyde conversion with variation of Ra-Me-b-CD
hols with Ru/C in aqueous phase devoid of organic
solvents at low temperatures under neutral conditions,
With the optimized conditions in hand, we tested various
since Ru/C is less expensive than Pd/C, Pt/C, Au/C. How-
alcohols for their conversions. The benzylic/heterocyclic
ever, recently Naota et al. reported that Ru/C was inactive
alcohols, benzoins, and cyclic aliphatic alcohols were ef-
ficiently converted into aldehydes/ketones in good to ex-
2
a
for the aerobic oxidation of alcohols in water.
In continuation of our efforts to develop sustainable cellent yields (Table 1) without any side-product
3
methods for organic transformations under benign condi- formation. The aliphatic alcohols were also converted but
tions using cyclodextrins as supramolecular catalysts we the oxidation was sluggish as the length of the chain in-
4
report herein a novel protocol using Ru/C and cyclodex- creased.
trins combination for the aerobic oxidation of alcohols at
From the above results it is clearly evident that CD has a
neutral pH employing water as the only solvent. Cyclo-
definite role to play in this reaction (Table 2). So, to in-
dextrins are widely used as mass transporters among inter-
voke the role of Ra-Me-b-CD in the aerobic oxidation, we
performed NOESY studies to prove the inclusion-com-
facial systems for carrying the substrates from one phase
to the other by inclusion complex formation with hydro-
plex formation between Ra-Me-b-CD and benzyl alcohol.
5
phobic substrates. However, it has been recently reported
The inclusion complex studies were done in D O by tak-
2
that methylated cyclodextrins can also increase the disper-
ing benzyl alcohol: Ra-Me-b-CD in 1:1 ratio at room tem-
perature. The NOESY spectrum (see Supporting
Information) illustrates the evidence for the complex for-
sion of supported metal in water and so increase the activ-
ity of the catalyst.6
mation. The cross-peaks contour appearance at the inter-
section of d = 3.4–3.7 ppm (H , H of Ra-Me-b-CD) and
3
5
d = 7.2 ppm (of benzyl alcohol) clearly proves the inclu-
sion-complex formation of CD alcohol during the reaction
course. The NOESY studies clearly support the role of
SYNLETT 2010, No. 17, pp 2571–2574
Advanced online publication: 30.09.2010
DOI: 10.1055/s-0030-1258775; Art ID: G22110ST
x
x
.x
x
.2
0
1
0
©
Georg Thieme Verlag Stuttgart · New York

2
572
V. K. Akkilagunta et al.
LETTER
Table 1 Aerobic Oxidation of Alcohols Using Ru/C
Table 2 Aerobic Oxidation of Alcohols Using Ru/Ca
CHO
Ru/C
Ra-Me-β-CD
H2O (2 mL), O2
OH
Ru/C
OH
R2
O
H2O (2 mL), 75 °C, O2
R1
R1
R2
Entry
Additive
Time (h)
24
Yield (%)a
Entry Alcohol
Product
Time Yield
(h) (%)
b
1
2
3
4
5
6
7
8
9
Ra-Me-b-CD
b-CD
99
82
74
62
69
65
48
61
57
53
23
14
<5
24
CHO
CHO
OH
OH
1
24
24
99
86
2-HP-b-CDc
24
®
TWEEN 20
24
2
®
Triton X-100
24
N
N
®
CHO
Brij 30
24
OH
3
24
92
PEG-400
24
Cl
Cl
Bu NCl
24
CHO
4
OH
OH
OH
4
24
24
78
71
Bu NBr
24
4
OH
10
11
12
13
SDSd
24
CHO
5
S
k-carrageenan
alginic acid
none
24
S
OH
O
O
O
24
6
7
8
N
N
24
24
75
78
24
a
b
c
d
Isolated yield.
OH
OH
Randomly methylated b-CD.
Hydroxypropyl-b-CD.
Sodium dodecyl sulfate.
Ra-Me-b-CD which is forming an inclusion complex with
the alcohol and thereby allowing the aerobic oxidation to
happen, and the reaction does not proceed in the absence
of CD.
24
16
73
99
O
OH
Ph
O
O
To further extend the scope of this methodology, we at-
tempted the one-pot synthesis of quinoxalines directly
from benzoins and diamines. Initially, benzoin and o-phe-
nylenediamine (OPA) were added to check for the cy-
clization of OPA and the diketone formed by the
oxidation of benzoin. Surprisingly, quinoxaline was
formed at 75 °C in 96% yield. We checked various ben-
zoins and substituted diamines for their reactivity and
were able to synthesize a variety of quinoxalines in good
9
Ph
Ph
Ph
1
1
0
1
24 32
24 20
OH
CHO
CHO
OH
1
2
24 84
OH
O
a
Alcohol (1 mmol), Ru/C (10 mol%, 202 mg), H O (2 mL), Ra-Me-
2
to excellent yields. A slight decrease in yields was ob- b-CD (300 mg).
served when EWG on OPA and ERG on benzoin were
present on the substrates (Table 3).
After this we were interested in the recyclability of the
catalytic system. To check the recyclability and leaching
of ruthenium from the support we did a control experi-
ment by extracting the organic substrate from the reaction
mixture using ethyl acetate after the reaction. The recov-
ered catalytic system was used for the next oxidation cy-
cle. We were able to recycle the catalytic system up to five
cycles (Figure 2) with consistent conversion of benzyl al-
cohol into benzaldehyde.
Figure 2 Recyclability of catalytic system for oxidation of benzyl
alcohol
Synlett 2010, No. 17, 2571–2574 © Thieme Stuttgart · New York

LETTER
One-Pot Biomimetic Approach to Quinoxaline Synthesis
2573
Table 3 One-Pot Synthesis of Quinoxalines by Aerobic Oxidation
of Benzoins Using Ru/C
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Acknowledgment
We are grateful to UGC, New Delhi and CSIR, New Delhi for the
research fellowships to V.K.A. and V.P.R., respectively.
Synlett 2010, No. 17, 2571–2574 © Thieme Stuttgart · New York

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LETTER
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