Microwave-assisted Claisen rearrangement on a silica gel support

Article abstract of DOI:10.1016/j.tetlet.2004.11.012

A fast, efficient and environmentally benign solvent-free procedure has been developed for microwave-assisted Claisen rearrangement on a silica gel support. A fast, efficient and environmentally benign solvent-free procedure has been developed for microwave-assisted Claisen rearrangement on a silica gel support. Various bis-allyl ketones were prepared using this protocol.

Full text of DOI:10.1016/j.tetlet.2004.11.012

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9603–9605
Microwave-assisted Claisen rearrangement on a silica gel support
*
Sambasivarao Kotha, Kalyaneswar Mandal, Ashoke Chandra Deb and Shaibal Banerjee
Department of Chemistry, Indian Institute of Technology, Bombay, Powai, Mumbai 400 076, India
Received 30 August 2004; revised 27 October 2004; accepted 2 November 2004
This paper is dedicated to Professor Srinivasan Chandrasekaran on the occasion of his 60th birthday
Abstract—A fast, efficient and environmentally benign solvent-free procedure has been developed for microwave-assisted Claisen
rearrangement on a silica gel support. Various bis-allyl ketones were prepared using this protocol.
Ó 2004 Published by Elsevier Ltd.
In recent years, solvent-free reactions using either
organic or inorganic solid supports have received in-
creasing attention. There are several advantages to per-
forming synthesis in dry media: (i) short reaction times,
In connection with a project related to ring-closing
metathesis, we observed that a tetra substituted 1,4-
bis-hydroxybenzene derivative was partially trans-
formed to the corresponding quinone derivative during
1
5
(
ii) increased safety, (iii) economic advantages due to
purification on a silica gel column (Scheme 2). This crit-
the absence of solvent. Silica gel is effective because
the end products can easily be separated. Moreover,
silica gel can function as a convenient medium and also
ical observation led to the development of a one-pot
conversion of 1,4-bis-allyloxybenzene derivatives to
2,3-bis-allyl-1,4-quinone derivatives by taking advan-
tage of the cumulative effect of the silica gel support
and MWI under solvent-free conditions.
2
act as a mild acidic catalyst.
Microwave irradiation (MWI) has become an estab-
lished tool in organic synthesis, because of the rate
enhancements, higher yields and often, improved selec-
tivity, with respect to the conventional reaction condi-
tions. In addition, solvent-free MWI processes are
also clean and efficient.
Among various solid supports, including silica gel, alu-
mina and the highly acidic montmorillonite clay, silica
gel was found to be the most efficient medium for this
transformation. Here, the role of silica gel may be two-
fold: (i) Physisorption of reactants on the silica surface
leading to an increase in local concentration, which in
turn enhances the rate of reaction. (ii) The acidic
nature of the silica surface promotes the oxidation of
phenol to quinone. Some other oxidation processes
induced by acidic silica gel have been reported in the
3
Herein, we report a rapid procedure for the synthesis of
bis-allyl ketones by microwave-assisted Claisen rear-
4
rangement on a silica gel support (Scheme 1) under
solvent-free conditions.
6
literature.
The required O-allylated starting materials were pre-
pared by standard procedures as shown in Scheme 3.
These O-allylated compounds were then heated in an
unmodified domestic MW oven with a maximum power
O
O
O
O
MWI (800 W)
silica gel support
OH
O
Scheme 1.
silica gel column
chromatography
Keywords: Claisen rearrangement; Microwave irradiation; Silica gel
support; Solvent-free synthesis.
OH
O
*
Corresponding author. Tel.: +9122 2576 7160; fax: +91 22 2572
480; e-mail: srk@chem.iitb.ac.in
3
Scheme 2.
0
040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.11.012

9604
S. Kotha et al. / Tetrahedron Letters 45 (2004) 9603–9605
Table 1. Silica gel supported synthesis of bis-allyl ketones from the
corresponding allyloxy compounds under microwave irradiation
OH
OH
O
a
Entry
Reactant
time, min)
Product
Yield
b
(%)
a
(
8
2%
O
O
27
1
1
2 (7)
39
43
OH
O
a
7
O
1
2
2
9
0
0
O
9
2%
3
47
OH
O
O
2
4 (15)
O
O
b
4%
4
9
58
3
4
5 (5)
8 (7)
59
O
O
OH
OH
c
c
c
73(96)
a,c
O
R
R
79
R= H (82%)
6
9
1
R= H
9
2
1
1
0
R= Br
10 R= Br (88%)
13 R= OMe (84%)
1
1
2 R= OMe
5
6
11 (7)
O
75(95)
78(95)
a
O
Br
2
2
R
89
1
1
R= H (90%)
14 (7)
O
1 R= Br (93%)
4 R= OMe (96%)
MeO
2
3
O
d
O
O
d
7
8
16 (7)
75
O
X
O
X
O
O
1
1
5 X= O
7 X= S
O
S
1
2
16 X= O (55%)
1
2
4
1
2
8
X= S (60%)
Scheme 3. Reagents and conditions: (a) allyl bromide, K , ace-
tone, rt; (b) IBX, DMSO; (c) MWI/silica gel support; (d) allyl bromide,
2
CO
3
O
18 (7)
65
8
–12
2
TBAF, THF/H O.
2
5
of 800W on silica gel support to produce the corre-
sponding bis-allylated ketones in moderate to good
yields (Table 1).
a
Irradiation at 800W using a Ken Star (OM-992E) household
microwave oven.
b
c
Isolated yield.
Yields in the parentheses refer to the yield based on recovered starting
Compound 4 on MWI gave the aromatized quinone 20.
The reaction times were optimized by monitoring the
reaction mixture at different intervals by TLC. In some
cases (entries 1–3, 7 and 8, Table 1) it was observed that
prolonged irradiation gave an intractable polymeric
material, thereby reducing the yield of the required
product. Reducing the power level to avoid polymeriza-
tion necessitated increased exposure times. Incomplete
conversions of the starting materials were observed in
entries 4–6 (Table 1). After 7min (optimized time) expo-
material.
GC yield.
d
sure to MWI, the ratio of the starting material and the
product remained constant. Even after prolonged expo-
sure (>20min) the starting material to product ratio
remained the same (entries 4–6). Our earlier synthesis
of 19 starting from 2 under conventional conditions
7
gave a low yield (26%), even prolonged heating (12h)
or forcing reaction conditions did not improve the yield

S. Kotha et al. / Tetrahedron Letters 45 (2004) 9603–9605
9605
of product. However, a significant rate enhancement
and improved yield of the rearranged product was
observed under MWI conditions on a silica gel support
Acknowledgements
We thank the DST for financial support and the RSIC,
Mumbai for providing spectral data. K.M. and S.B.
thank the CSIR and UGC New Delhi respectively for
the award of Research Fellowships.
(
entry 1, Table 1).
In summary, we have developed a safe, economical and
green process for the synthesis of bis-allyl ketones via
microwave-assisted Claisen rearrangement on a silica
support under solvent-free conditions. A few notable
advantages of this procedure are: (i) reasonably good
yields (39–78%) of the rearranged products; (ii) fast
reaction times (5–7min); (iii) mild reaction conditions
and (iv) avoidance of toxic solvents.
References and notes
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2
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beaker was added pre-activated (pre-activation of the
silica gel was achieved by MWI [Ken Star, OM-992E]
for 5min) silica gel (100–200 mesh, 5–10 times the
weight of the starting substrate) and then the solvent
was evaporated. The resulting homogeneous mixture
of the substrate and silica gel was then irradiated in a
microwave oven, for the time given in Table 1. The reac-
tion mixture was purified by flash chromatography. Elu-
tion of the column with a mixture of ethyl acetate and
petroleum ether gave the required product.
3
1
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. For recent reviews on the Claisen rearrangements see: (a)
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mann, M.; Abraham, L. Eur. J. Org. Chem. 2002, 1461–
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Selected spectral data: 20: yellow liquid; H NMR
1
471; (d) Chai, Y.; Hong, S.; Lindsay, H. A.; McFarland,
(
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1
2
1
.6Hz), 5.02–5.09 (m, 4H), 5.82–5.92 (m, 2H), 7.82 (s,
1
3
H); C NMR (75.4MHz, CDCl ): d 20.3, 30.9, 116.9,
3
27.5, 130.2, 134.2, 143.4, 144.9, 185.0; HRMS (QTOF):
m/z calcd for C H O (M+H): 267.1385. Found:
1
2
CDCl ): d 2.54 (dd, 2H, J = 13.6, 7.2Hz), 2.89 (dd, 2H,
J = 13.6, 7.2Hz), 4.79–4.86 (m, 4H), 5.2–5.3 (m, 2H),
6.19 (d, 1H, J = 10.4Hz), 7.30 (s, 1H), 7.32 (d, 1H,
J = 2.4Hz), 7.45 (d, 1H, J = 2Hz), 7.55 (dd, 1H,
J = 8Hz, 2.2Hz); C NMR (75.4MHz, CDCl ): d
4
8
19
2
1
67.1382. 22: colourless liquid; H NMR (400MHz,
3
650; (h) Nguyen Van, T.; Debenedetti, S.; De Kimpe, N.
3
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6.1, 55.8, 118.5, 120.5, 127.2, 128.7, 131.9, 132.1,
32.5, 132.8, 142.5, 143.6, 202.4; HRMS (QTOF): m/z
1
calcd for C H OBr (M+H): 303.0385. Found:
3
1
6
16
1
03.0400. 23: colourless liquid; H NMR (400MHz,
5. Kotha, S.; Mandal, K., unpublished results.
6
. (a) Fields, J. D.; Kropp, P. J. J. Org. Chem. 2000, 65,
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Tung, J. C.; Loomis, B. R. J. Am. Chem. Soc. 2000, 122,
280–4285.
CDCl ): d 2.55 (dd, 2H, J = 13.4, 7.0Hz), 2.87 (dd, 2H,
3
5
J = 13.4, 7.4Hz), 3.85 (s, 3H), 4.77–4.87 (m, 4H), 5.22–
5.32 (m, 2H), 6.16 (d, 1H, J = 9.6Hz), 6.82 (d, 1H,
J = 2.8Hz), 7.0 (dd, 1H, J = 2.8, 8Hz), 7.34 (d, 1H,
J = 9.2Hz), 7.35 (s, 1H); C NMR (75.4MHz, CDCl3):
d 46.3, 55.29, 55.33, 113.8, 115.9, 118.0, 126.5, 128.1,
4
7
. Kotha, S.; Mandal, K. Tetrahedron Lett. 2004, 45, 2585–
2588.
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1
3
131.8, 132.7, 135.5, 145.1, 158.0, 203.4; HRMS (QTOF):
m/z calcd for C H O (M+H): 255.1385. Found:
1
7
19
2
1
55.1381. 24: colourless liquid; H NMR (400MHz,
1
802.
2
1
0. Matsunaga, N.; Kaku, T.; Ojida, A.; Tanaka, T.; Hara, T.;
Yamaoka, M.; Kusaka, M.; Tasaka, A. Bioorg. Med.
Chem. 2004, 12, 4313–4336.
1. Jaechon, J.; Heean, K.; Hyunsuk, L.; Jaeyoung, C.;
Kazumi, M.; Yoshitake, K.; Masahiro, N.; Myunghwa,
K.; Yoshikazu, N. WO 2001042186, 2001; Chem. Abstr.
CDCl ): d 2.51 (d, 4H, J = 6.4Hz), 4.41 (s, 2H), 5.14–
5
CDCl ): d 39.1, 54.1, 121.2, 130.2, 203.8, 209.8; Mass:
3
1
.19 (m, 4H), 5.59–5.69 (m, 2H); C NMR (75.4MHz,
3
3
1
+
1
(
(
EI) m/z 180 (M ). 25: colourless liquid; H NMR
400MHz, CDCl ): d 2.41–2.53 (m, 4H), 3.79 (s, 2H),
3
1
.09–5.13 (m, 4H), 5.57–5.67 (m, 2H); C NMR
3
5
2
001, 135, 19815.
(
2
75.4MHz, CDCl ): d 40.9, 41.2, 60.6, 120.7, 130.5,
12. Unpublished results: Deb, A. C. Ph.D. Dissertation,
Indian Institute of Technology, Bombay, 2004.
3
+
03.5, 207.7; Mass: (EI) m/z 196 (M ).