Remarkable synergism in methylimidazole-promoted decarboxylation of substituted cinnamic acid derivatives in basic water medium under microwave irradiation: a clean synthesis of hydroxylated (E)-stilbenes

Article abstract of DOI:10.1016/j.tet.2007.05.046

A metal-free protocol for decarboxylation of substituted α-phenylcinnamic acid derivatives in aqueous media is developed, wherein a remarkable synergism between methylimidazole and aq NaHCO₃ in polyethylene glycol under microwave furnished the corresponding para/ortho hydroxylated (E)-stilbenes in a mild and efficient manner. The critical role of water in facilitating the decarboxylation imparts an interesting facet to the synthetic utility of water mediated organic transformations. The developed protocol provides a clean alternative to the hitherto indispensable multistep approaches involving toxic quinoline and a copper salt combination as the common decarboxylating agent.

Full text of DOI:10.1016/j.tet.2007.05.046

Tetrahedron 63 (2007) 7640–7646
Remarkable synergism in methylimidazole-promoted
decarboxylation of substituted cinnamic acid derivatives in
basic water medium under microwave irradiation: a clean
synthesis of hydroxylated (E)-stilbenes*
*
Vinod Kumar, Abhishek Sharma, Anuj Sharma and Arun K. Sinha
Natural Plant Products Division, Institute of Himalayan Bioresource Technology, Post Box No. 6, Palampur 176061, HP, India
Received 11 December 2006; revised 28 April 2007; accepted 10 May 2007
Available online 17 May 2007
Abstract—A metal-free protocol for decarboxylation of substituted a-phenylcinnamic acid derivatives in aqueous media is developed,
wherein a remarkable synergism between methylimidazole and aq NaHCO3 in polyethylene glycol under microwave furnished the corre-
sponding para/ortho hydroxylated (E)-stilbenes in a mild and efficient manner. The critical role of water in facilitating the decarboxylation
imparts an interesting facet to the synthetic utility of water mediated organic transformations. The developed protocol provides a clean alter-
native to the hitherto indispensable multistep approaches involving toxic quinoline and a copper salt combination as the common decarb-
oxylating agent.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
a-phenylcinnamic acids obtained via the Perkin conden-
sation between benzaldehydes and phenylacetic acids
occupies a prominent position.9 Since the pioneering inves-
tigations of Shepard et al., the use of quinoline/copper salts10
with strong heating has been the method of choice for car-
rying out these decarboxylations11 with periodic improve-
ments in the form of alternative organic bases12 and
energy sources like microwave.13 However, in addition to
its toxicity, the quinoline/copper salt mediated decarboxyl-
ation protocol often provides poor yields of the product,14
thus rendering the above protocols to be undesirable in
view of concerns regarding overall synthetic efficiency and
environmental impact. In our pursuit of developing a mild
synthetic methodology for stilbenes, we were thus con-
fronted with the task of devising a benign and efficient decar-
boxylation protocol.
Hydroxylated (E)-stilbenes are natural polyphenols widely
present in fruits like grapes, raspberries, peanuts and several
medicinal plants. These compounds have been of consider-
able interest in recent times owing to their biological activi-
ties,1 putative potential as nutraceuticals,2 and their
application in molecular photonics and optoelectronics.3
For instance, resveratrol (3,40,5-trihydroxy-(E)-stilbene),
a major component of red wine, has been implicated as a po-
tent cardio protective agent thus lending credence to the con-
jecture that red wine consumption retards cardiovascular
mortality.4 In addition, several epidemiological and immu-
nological studies have identified resveratrol as a potent
therapeutical agent for Alzheimer’s disease.5 Similarly, ptero-
stilbene (3,5-dimethoxy-40-hydroxy-(E)-stilbene) has been
recognized to possess remarkable antitumour and antidia-
betic activities.6 Subsequent intensive pursuit of many other
stilbenes has also revealed their wide spectrum of applica-
tions.7
Water, besides being nature’s preferred solvent, is useful due
to its versatile solvent properties,15 safety and abundance. In
addition to its ecofriendly and economical nature, there has
also been a growing realization of the ability of water to fa-
cilitate organic transformations.16 Though there have been
some seminal attempts17 to undertake decarboxylation of
cinnamic acids with mineral acids or bases, but these in-
vestigations were mainly mechanistic in nature and the
corresponding method was found to be comparatively inef-
fective for decarboxylation of a-phenylcinnamic acids into
stilbenes. In view of this, we sought to ask the specific
question, can a suitable decarboxylation protocol for
Amongst the prevalent synthetic methodologies8 for these
bioactive stilbenes, decarboxylation of the corresponding
*
IHBT Communication No. 0644.
Keywords: a-Phenylcinnamic acids; (E)-Stilbenes; Decarboxylation; Meth-
ylimidazole; Water chemistry.
* Corresponding author. Tel.: +91 1894 230426; fax: +91 1894 230433;
e-mail: aksinha08@rediffmail.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.046

V. Kumar et al. / Tetrahedron 63 (2007) 7640–7646
7641
Table 1. Effect of different solvents and bases on the yield of 1b under
a-phenylcinnamic acids be developed in basic aqueous con-
ditions? Herein, we report the realization of this expectation
with a remarkable synergism in methylimidazole-promoted
decarboxylation of substituted cinnamic acids in basic aque-
ous medium under microwave irradiation.
microwave irradiationa
base/solvent
MW
COOH
H3COCO
HO
OMe
OMe
Yield (%)
2. Results and discussion
Sr. no.
Solvent
Aq base
1
2
3
4
5
6
7
8
9
—
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaOH
KOH
Na2CO3
K2CO3
18
24
22
34
39
36
35
38
38
As part of our ongoing interest in microwave induced syn-
thesis of important bioactive compounds18 including the
one pot two-step synthesis of hydroxystyrenes19 under mi-
crowave, we were interested in devising an environmentally
friendly and efficient synthetic methodology for bioactive
stilbenes. To this end, we employed the Perkin condensation
between vanillin (4-hydroxy-3-methoxybenzaldehyde) and
phenylacetic acid in the presence of triethylamine and acetic
anhydride to obtain the corresponding acetoxylated a-phe-
nylcinnamic acid.9 We thought to perform the subsequent
decarboxylation of acetoxylated a-phenylcinnamic acid un-
der basic aqueous conditions due to several inherent advan-
tages. Water is rapidly heated by microwave irradiation to
high reaction temperatures, which enables it to behave as
a pseudo-organic solvent.15 In addition, water has been
known to significantly enhance the equilibrium constant
for the formation of charged intermediates through intermo-
lecular charge-dipole as well as hydrogen bonding interac-
tions.20 In this light, we hypothesized that water might
also help stabilize the transition state/intermediate(s) in the
base induced decarboxylation of a-phenylcinnamic acids.
N,N-Dimethylformamide
Dimethyl sulfoxide
Ethylene glycol
Polyethylene glycol
Polyethylene glycol
Polyethylene glycol
Polyethylene glycol
Polyethylene glycol
a
CEM monomode microwave; for 1 (150 W, 110 ꢀC); for others (200 W,
180 ꢀC); conditions 1a (0.0037 mol), base (10% aq soln 6–7 mL), solvent
(10–12 mL) for 20 min.
(Table 2, entry 4), which delivered 1b in a highest 65% yield.
In our desire to further augment the yield of 1b, we explored
the dependence of yield on structural changes in the imid-
azole moiety. Interestingly, while methylimidazole (Table
2, entry 5) provided 1b in an enhanced yield of 87%, histi-
dine (Table 2, entry 6) and 1-butyl-3-methylimidazolium
chloride (Table 2, entry 7) gave 1b in only 38% and 42%
yield, respectively. To reinforce our premise of synergistic
action, cinnamic acid 1a was treated with aq methylimid-
azole in PEG, i.e., without NaHCO3, but the stilbene could
be obtained in only 28% yield even after prolonged reaction
times of 60 min. It may be mentioned that the above reaction
was also conducted by treating 1a and aq methylimidazole in
PEG by replacing NaHCO3 with an ionic salt like NaCl,
however, the reaction provided 1b in only 32% yield. The
foregoing observation ruled out the role of NaHCO3 as a sim-
ple ionic conduit and thus indicated a synergistic interaction
between methylimidazole and aq NaHCO3.
In order to test this hypothesis, a mixture of a-phenyl-4-
acetoxy-3-methoxycinnamic acid (1a) and 10% aq NaHCO3
solution was irradiated under microwave (150 W, 110 ꢀC)
for 20 min. It was indeed a delight to observe the corre-
sponding (E)-stilbene 1b albeit in 18% yield along with
the deacetylated a-phenyl-4-hydroxy-3-methoxycinnamic
acid. This partial success inspired us to further refine our
protocol. We realized that the low yield of stilbene might
in part be attributed to the inability of low boiling aqueous
solution to attain temperatures appropriate for decarboxyl-
ation. Thereafter, a number of high boiling solvents (DMF,
DMSO, EG, PEG) were screened for the above reaction
under microwave (200 W, 180 ꢀC; Table 1) and 10% aq
NaHCO3 in PEG was found to augment the yield of 1b by
up to 39%. Our attempts to further optimize the reaction con-
ditions proved futile in improving the performance of the
reaction. For instance, the replacement of NaHCO3 with
NaOH17 or KOH did provide 1b in comparative yield but
it led to the formation of some side products due to the en-
hanced basicity.21 In view of the ineptness of a single base
to bring about the desired transformation, we subsequently
focused our attention towards the synergistic application of
two bases. A number of literature precedents have reported
the efficacy of such a combination.22 Consequently, various
base combinations were explored towards the decarboxyl-
ation of cinnamic acid into stilbenes. To our fascination,
an increased yield of 1b was obtained in almost all instances
(Table 2). For instance, the combination of NaHCO3 with
catalytic amount of organic bases such as triethylamine, pyr-
idine or piperidine had almost a similar effect as the yield of
1b was increased by up to 45–52% in these cases. Nonethe-
less, it was the aq NaHCO3-imidazole (cat.) combination
The observed synergism might result from the tendency of
methylimidazole (pKa¼7) to participate in proton exchange
with water, which effectively reduces the number of neutral
methylimidazole molecules capable of acting as a base23
(Fig. 1). The presence of NaHCO3 in the reaction mixture
might then lead to a suppression of this proton exchange, thus
increasing the effective molarity of free methylimidazole
Table 2. Effect of different organic bases with aq NaHCO3 in PEG on the
yield of 1b under microwave irradiationa
Sr. no.
Base
Yield (%)
1
2
3
4
5
6
7
8
Triethylamine
Pyridine
Piperidine
Imidazole
Methylimidazole
Histidine
45
48
52
65
87
38
42
54
1-Butyl-3-methylimidazolium chloride
Quinoline
a
CEM monomode microwave (200 W, 180 ꢀC); conditions 1a
(0.0037 mol), NaHCO3 (10% aq soln 6–7 mL), organic base
(0.0018 mol), solvent (10–12 mL) for 20 min.

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V. Kumar et al. / Tetrahedron 63 (2007) 7640–7646
MImH+ +OH -
(Alkaline bicarbonate soln.
helps shift the equilibrium
towards Methylimidazole (MIm))
H2O
MIm
COOH
CO2
+
HO
HO
catalytic cycle
-
COO MImH+
-
C
O
MIm+HO
O
HO
H+
MIm
C O-
MIm
H-O
O
Figure 1.
molecules, which subsequently get implicated in the decarb-
oxylative pathway.
obtained in low yield due to formation of polymeric side
products. Following the success with cinnamic acid deriva-
tives, the above method was explored towards decarboxyl-
ation of aromatic acids. However, aromatic acids such as
4-hydroxy substituted phenylpropanoic acid (entry 20), phe-
nylacetic acid (entry 21) and benzoic acid (entry 22) did not
undergo the above reaction, thus indicating a probable selec-
tivity towards cinnamic acid derivatives as compared to
aromatic acids. It is worth mentioning that the prevalent de-
carboxylation protocol involving quinoline/copper salt does
not allow the selective decarboxylation of cinnamic acid
moiety9–11 in comparison to aromatic acids.13b In this
context, the pronounced selectivity observed with MIm/
NaHCO3 (Scheme 1) can be a useful synthetic tool for
chemoselective decarboxylation in total synthesis of com-
plex organic compounds including natural products.
In order to discern the significance of aqueous medium in
bringing about the transformation of 1a to 1b, the above re-
action was conducted with NaHCO3 and methylimidazole in
PEG under anhydrous conditions. Interestingly, the product
1b was obtained in only 64% yield, thus unequivocally dem-
onstrating the critical role of water in bringing about the
decarboxylation of 1a.
The substrate scope of the developed method (Scheme 1)
was gauged by extending the reaction to other optionally
substituted a-phenylcinnamic acids (Table 3). It is apparent
from Table 3 that 2- or 4-hydroxy substitution at the aryl ring
of cinnamic acid moiety is necessary for the decarboxylation
of a-phenylcinnamic acids under the given conditions. Pre-
sumably, the acetoxylated a-phenylcinnamic acids under-
went deacetylation before being incorporated in the
decarboxylation pathway. Surprisingly, a very rapid trans-
formation was observed with the substrate possessing 4-
acetoxy substitution at both aromatic rings (Table 3, entry
9), however, the stilbene was formed in only 56% yield along
with several side products. It is also evident from Table 3 that
the methoxylated substrate gave the expected product only
in traces (Table 3, entry 14). Further, the reaction with a-
phenyl-20-acetoxy-30-methoxycinnamic acid (Table 3, entry
10) provided the corresponding stilbene in 64% yield along
with the formation of some side products including couma-
rin.24 Interestingly, a simultaneous hydrolysis–decarboxyl-
ation was observed in case of a-phenylcinnamic ester
(Table 3, entry 16) and the product was obtained in 78%
yield. Surprisingly, the decarboxylation product was ob-
tained in traces when the hydroxy substituent was present
at para position of a-phenyl ring (Table 3, entry 13) instead
of the aromatic ring of cinnamic acid moiety. Later on, the
method was also extended towards the decarboxylation of
hydroxylated cinnamic acid (Table 3, entries 18 and 19)
into the corresponding styrenes, but the product could be
aq. NaHCO3/ cat. MIm
COOR'
RO
PEG, MW
HO
OMe
OMe
R = H, CH3CO etc
R' = H, CH3 etc
Scheme 1.
Thus, the developed protocol allowed us to synthesize the
immensely important (E)-stilbenes in a mild and stereo-
selective manner. It is pertinent to mention that a secondary
nonetheless useful advantage of the method lies in the one
pot deacetylation–decarboxylation or debenzoylation–
decarboxylation of acetoxylated/benzoylated a-phenylcin-
namic acids, which could considerably simplify the
synthetic strategy and subsequent workup procedures for
the synthesis of stilbenes.25
In order to ascertain the efficacy of microwaves, 1a was
refluxed with aq NaHCO3/methylimidazole (cat.) in PEG

V. Kumar et al. / Tetrahedron 63 (2007) 7640–7646
7643
Table 3. Decarboxylation of cinnamic acid derivatives (1a–19a) under microwave irradiationa
aq. NaHCO3/ cat. methylimidazole
PEG, MW
COOR'
RO
HO
R= H,CH3CO, C6H5CO etc.
R'= H, CH3 etc.
OMe
OMe
Substrate (a)
Sr. no.
1
Reaction time
in min
Product (b)
Yield (%)
87
References
28b,f
H3CO
COOH
H3CO
HO
C6H5
C6H5
C6H5
C6H5
20
20
20
20
20
20
20
C6H5
H3COCO
H3CO
HO
COOH
H3CO
HO
2
3
4
5
6
7
91
83
86
81b
84
84
28b,f
28b,f
28b,f
—
C6H5
COOH
C6H5
H3COCO
HO
HO
COOH
C6H5
HO
H3CO
COOH
H3CO
HO
C6H4(4-OCH3)
C6H3(3,5-OH)
C6H4(4-OCH3)
H3COCO
COOH
28e
6
C6H3(3,5-OCOCH3)
H3COCO
HO
COOH
C6H3(3,5-OCH3)
C6H3(3,5-OCH3)
H3COCO
HO
H3COCO
H3COCO
COOH
HO
HO
C6H4(3-OCH3)
C6H4(4-OH)
8
9
20
8
82
56
28d
28i
C6H4(3-OCH3)
H3CO
COOH
H3CO
HO
C6H4(4-OCOCH3)
H3COCO
OCOCH3
OH
H3CO
COOH
H3CO
C6H5
10
11
12
25
20
20
64
28c
—
C6H5
H3CO
HO
H3CO
HO
C6H4(4-Cl)
COOH
78b
C6H4(4-Cl)
COOH
C6H5
NDc
1c
C6H5
OH
OH
H3CO
H3CO
COOH
H3CO
H3CO
C6H4(4-OH)
13
40
Traces
28i
C6H4(4-OH)
(continued)

7644
V. Kumar et al. / Tetrahedron 63 (2007) 7640–7646
Table 3. (continued)
Sr. no.
Substrate (a)
Reaction time
in min
Product (b)
Yield (%)
NDc
References
28h
H3CO
COOH
C6H5
H3CO
H3CO
C6H5
C6H5
C6H5
C6H5
14
15
16
17
18
19
20
21
40
40
20
20
20
20
40
H3CO
COOH
C6H5
NDc
28a
O2N
O2N
H3CO
COOCH3
C6H5
H3CO
HO
78
28b,f
H3COCO
H3CO
COOH
C6H5
H3CO
HO
76
28b,f
C6H5COO
H3CO
HO
COOH
COOH
COOH
H3CO
HO
38
18d,19,28g
18,19,28g
34
HO
HO
HO
NDc
HO
COOH
COOH
40
40
NDc
NDc
HO
HO
HO
22
HO
a
CEM monomode microwave, (200 W, 180 ꢀC).
Spectral data of the new compounds is given in Section 4.
Not detected, general conditions: substrate 1a–22a (0.0037 mol), NaHCO3 (10% aq soln 6–7 mL), methylimidazole (0.0018 mol) and PEG (10–12 mL).
b
c
under conventional method for 16 h or heated in a sealed
tube for 5 h, but the expected stilbene could be obtained in
only 62% and 64% yield, respectively. The foregoing evi-
dently emphasizes the significance of microwave in effec-
tively bringing about the transformation of 1a to 1b.
3. Conclusion
In conclusion, we disclose a methylimidazole-promoted,
metal-free decarboxylation protocol for substituted
cinnamic acids in basic water medium under microwave
irradiation. The striking synergism between catalytic meth-
ylimidazole and aq NaHCO3 gives a facile access to bio-
logically important stilbenes. The critical role of water in
facilitating the reaction imparts an interesting facet to the
synthetic utility of water mediated organic transformations.
The developed method provides an efficient and eco-
friendly alternative to the prevalent multistep protocols
involving quinoline/metal salt, a toxic decarboxylating
agent for the synthesis of stilbenes. In addition, the one
pot deacetylation–decarboxylation of acetoxylated a-
phenylcinnamic acids could considerably help simplify
the associated workup procedures. Further investigations
to improve the scope of the developed method are currently
underway.
Mechanistically, the above reactions are believed to proceed
via the base catalyzed formation of a quinomethine interme-
diate, which subsequently gets decarboxylated.26 The same
process was presumably occurring in our case (Fig. 1). In
addition, methylimidazole might also help promote the
reaction due to the formation of polar methylimidazole
carboxylate salts, which can efficiently absorb microwave
energy.27 It is evident from Figure 1 that all the intermediates
in the proposed mechanistic pathway are more polar than the
substrate itself, hence the reaction proceeds smoothly under
the coupling of aqueous conditions with microwave irradia-
tion. Further studies regarding elucidation of the precise
mechanism are currently under progress.

V. Kumar et al. / Tetrahedron 63 (2007) 7640–7646
7645
4. Experimental section
4.1. General procedure
References and notes
1. (a) Borman, S. Chem. Eng. News 2005, 83, 36–37; (b) Jang, M.;
Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.; Beecher,
C. W. W.; Fong, H. H. S.; Farnsworth, N. R.; Kinghorn, A. D.;
Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. Science 1997, 275,
218–220; (c) Ohguchi, K.; Tanaka, T.; Kido, T.; Baba, K.;
Iinuma, M.; Matsumoto, K.; Akao, Y.; Nozawa, Y. Biochem.
Biophys. Res. Commun. 2003, 307, 861–863.
2. (a) Iriti, M.; Faoro, F. Med. Hypotheses 2006, 67, 833–838.
3. (a) Marder, S. R.; Kippelen, B.; Jen, A. K. Y.; Peyghambarian,
N. Nature 1997, 388, 845–851; (b) Grimsdale, A.; Holmes,
A. C. Angew. Chem., Int. Ed. 1998, 37, 402–428; (c) Meier,
H.; Lehmann, M. Angew. Chem., Int. Ed. 1998, 37, 643–645.
4. (a) Poussier, B.; Cordova, A. C.; Becquemin, J. P.; Sumpio,
B. E. J. Vasc. Surg. 2005, 42, 1190–1197; (b) Wang, Z.; Zou,
J.; Cao, K.; Hsieh, T. C.; Huang, Y.; Wu, J. M. Int. J. Mol.
Med. 2005, 16, 533–540.
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280, 37377–37382; (b) Anekonda, T. S. Brain Res. Rev.
2006, 52, 316–326.
6. (a) Manickam, M.; Ramanathan, M.; Jahromi, M. A. F.;
Chansouria, J. P. N.; Ray, A. B. J. Nat. Prod. 1997, 60, 609–
610; (b) Rimando, A. M.; Cuendet, M.; Desmarchelier, C.;
Mehta, R. G.; Pezzuto, J. M.; Duke, S. O. J. Agric. Food
Chem. 2002, 50, 3453–3457.
The cinnamic acid derivatives were obtained as a mixture
of cis and trans isomers through the Perkin reaction.9 1
H
(300 MHz) and 13C (75.4 MHz) NMR spectra were recorded
on a Bruker Avance-300 spectrometer. A CEM DiscoverÓ
focused microwave (2450 MHz, 300 W) was used wherever
mentioned. HREIMS spectra were determined using micro-
mass Q-TOF ultima spectrometer.
4.2. Synthesis of stilbenes under focused microwave
irradiation
A
mixture of cinnamic acid derivatives (1a–19a)
(0.0037 mol), NaHCO3 (aq 10%, 6–7 mL), methylimidazole
(0.0018 mol) and PEG (10–12 mL) were mixed in a 100 mL
round bottom flask. The flask was shaken well and irradiated
under focused monomode microwave system fitted with
reflux condenser for 20–40 min (200 W, 180 ꢀC). After the
completion of reaction, the reaction mixture was cooled
and water (20 mL) was added to it, which resulted in the
precipitation of the product. The precipitated product was
filtered and recrystallized in most cases, to obtain pure
(E)-stilbene or purified further by Si-gel (60–120 mesh
size) column with a 1:5 mixture of ethylacetate and hexane.
Spectral data and melting point of obtained products agreed
well with the reported values.1c,6,18,19,28
7. (a) Pettit, G. R.; Grealish, M. P.; Jung, M. K.; Hamel, E.; Pettit,
R. K.; Chapuis, J. C.; Schmidt, J. M. J. Med. Chem. 2002, 45,
2534–2542; (b) Kim, S.; Ko, H.; Park, J. E.; Jung, S.; Lee, S. K.;
Chun, Y.-J. J. Med. Chem. 2002, 45, 160–164.
4.3. Spectral data of novel compounds
8. (a) Myers, A. G.; Tanaka, D.; Mannion, M. J. Am. Chem. Soc.
2002, 124, 11250–11251; (b) Wang, J.-X.; Fu, Y.; Hu, Y.
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Spatafora, C.; Tringali, C. Bioorg. Chem. 2005, 33, 22–33;
(e) Cross, G. G.; Eisnor, C. R.; Gossage, R. A.; Jenkins,
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4.3.1. Compound 5, Table 3: 40-hydroxy-3,40-dimethoxy-
stilbene. White crystalline solid (mp 163–166 ꢀC); 1H NMR
(CDCl3) d 7.36 (2H, d, J¼8.5 Hz), 6.94 (2H, m), 6.83 (5H,
m), 5.59 (1H, s), 3.86 (3H, s), 3.75 (3H, s); 13C NMR
(CDCl3) d 159.0, 146.7, 145.2, 130.3, 127.4, 126.6, 126.1,
120.1, 114.5, 114.1, 108.0, 55.9, and 55.3. HREIMS data:
m/z [M+H]+ for C16H17O3, calculated 257.3103; observed
257.3107.
9. (a) Gaukroger, K.; Hadfield, J. A.; Hepworth, L. A.; Lawrence,
N. J.; McGown, A. T. J. Org. Chem. 2001, 66, 8135–8138; (b)
ꢀ
Solladie, G.; Jacope, Y. P.; Maignan, J. Tetrahedron 2003, 59,
3315–3321; (c) Borrel, C.; Thoret, S.; Cachet, X.; Guenard,
D.; Tillequin, F.; Koch, M.; Michel, S. Bioorg. Med. Chem.
2005, 13, 3853–3864.
ꢀ
4.3.2. Compound 11, Table 3: 4-chloro-40-hydroxy-30-meth-
oxystilbene. White solid (mp 121–124 ꢀC); 1H NMR
(CDCl3) d 7.35 (2H, d, J¼8.5 Hz), 7.25 (2H, d, J¼8.1 Hz),
6.96 (3H, m), 6.87 (2H, d, J¼8.07 Hz), 5.72 (1H, s), 3.87
(3H, s); 13C NMR (CDCl3) d 146.8, 145.8, 136.1, 132.7,
129.6, 129.2, 128.8, 127.4, 125.1, 120.6, 114.6, 108.3 and
55.9. HREIMS data: m/z [M+H]+ for C15H14O2Cl, calcu-
lated 261.7229; observed 261.7228.
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Acknowledgements
Two of us (V.K. and Anuj Sharma) are indebted to UGC and
CSIR Delhi, respectively, for the award of SRF. The authors
gratefully acknowledge the Director of I.H.B.T., Palampur
for his kind cooperation and encouragement.
Supplementary data
Spectral data of synthesized products. Supplementary data
associated with this article can be found in the online
version, at doi:10.1016/j.tet.2007.05.046.

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