Efficient one-pot, two-step synthesis of (E)-cinnmaldehydes by dehydrogenation-oxidation of arylpropanes using DDQ under ultrasonic irradiation

Article abstract of DOI:10.1016/j.tet.2005.12.028

A general, efficient and new approach to the synthesis of cinnamaldehydes with trans-selectivity has been accomplished starting from arylpropanes. One-pot, two-step dehydrogenation and oxidation of arylpropanes with excess DDQ in dioxane containing a few drops of acetic acid gave (E)-cinnmaldehydes under ultrasound irradiation.

Full text of DOI:10.1016/j.tet.2005.12.028

Tetrahedron 62 (2006) 2590–2593
Efficient one-pot, two-step synthesis of (E)-cinnmaldehydes by
dehydrogenation–oxidation of arylpropanes using DDQ under
ultrasonic irradiation*
*
Bhupendra P. Joshi, Anuj Sharma and Arun K. Sinha
Natural Plant Products Division, Institute of Himalayan Bioresource Technology, Palampur, HP 176061, India
Received 17 October 2005; revised 23 November 2005; accepted 15 December 2005
Available online 18 January 2006
Abstract—A general, efficient and new approach to the synthesis of cinnamaldehydes with trans-selectivity has been accomplished starting
from arylpropanes. One-pot, two-step dehydrogenation and oxidation of arylpropanes with excess DDQ in dioxane containing a few drops of
acetic acid gave (E)-cinnmaldehydes under ultrasound irradiation.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
problems such as side product formation, low yields and
polymerization of acrolein incited chemists to look for
alternatives. Direct oxidative18 coupling of aromatic
compounds with a,b-unsaturated aldehydes by palladium
acetate/molybdovanadophosphoric acid/oxygen19 system is
a meticulous entry, however, expensive reagents and side
product formation limit adoption of the protocol.
Cinnamaldehyde derivatives are common in nature1 and
they possess remarkable biological properties2 such as
antibacterial, antifungal, antitermitic, antioxidant and anti-
cancer activities. Moreover, cinnamaldehydes are used to
prevent darkening of skin3 caused by UV rays of sun and
also prevent hair-loss and promote hair growth.4 Cinnamal-
dehydes are often used as starting materials for the synthesis
of many bioactive compounds5 including cytostatic6 and
anti-viral7 drugs.
All these synthetic methods have also been exploited for
introduction of a,b-unsaturated aldehyde moiety in the
aromatic ring during the synthesis of various bioactive
compounds20 and natural products.21 However, limitations
such as harsh reaction conditions, heavy burden of
protection–deprotection steps and lengthy protocols warrant
alternative efficient and environmentally friendly pro-
cedures for the synthesis of (E)-cinnamaldehydes. The
application of ultrasound irradiation22 has emerged as a
useful synthetic tool. In this paper, we report the DDQ-
assisted one-pot, two-step dehydrogenation–oxidation of
arylpropanes in dioxane, containing a few drops of acetic
acid, into cinnamaldehydes with 100% (E)-selectivity under
ultrasonic irradiation (Scheme 1).
A number of reagents and processes are available for the
preparation8 of cinnmaldehydes including Wittig olefina-
tion reaction,9 oxidation of arylpropene,10 palladium
cluster11 or potassium dichromate12 catalysed oxidation of
allylic alcohols and most importantly, chain lengthening13
of arylaldehydes (C6–C1 unit) by a C2-unit. However, most
of these methods mainly suffer from poor yield, harsh
reaction conditions and contamination with small amounts
of the undesirable Z-isomer.14 Recently, some straight-
forward strategies have also been reported for the synthesis
of cinnamaldehydes with trans-selectivity15 and the most
common approach is the Heck16 reaction. Since the
inception of the Heck reaction, a number of modifications17
in the original protocols have been reported, however,
2. Results and discussion
The methods for formation of cinnamaldehyde basically fall
into three categories8–19 (a) combination of a C6 unit with a
C3 unit, (b) combination of a C6–C1 unit with a C2 unit, and
(c) modification of an already existing C6–C3 unit. Among
these three, use of a C6–C3 unit would ensure waste
minimization through atom economy23 as C6–C3 system in
* IHBT communication no. 0432.
Keywords: Arylalkane; Cinnamaldehyde; DDQ; trans-Selectivity;
Dehydrogenation–oxidation.
*
Corresponding author. Tel.: C91 1894 230426; fax: C91 1894 230433;
e-mail: aksinha08@rediffmail.com
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.028

B. P. Joshi et al. / Tetrahedron 62 (2006) 2590–2593
2591
O
H
DDQ (3.1 equiv) / dry dioxane
ultrasound
R
R
R
Where
R= OMe, OEt, –OCH O–, OH etc.
2
Scheme 1.
the substrate is retained in the product. Recently, we have
reported24 that arylpropane25 effectively undergoes oxi-
dation with DDQ26 in wet dioxane leading to the formation
of propiophenone while dehydrogenation of arylpropane
with DDQ in anhydrous dioxane to form (E)-arylpropene24
along with traces of (E)-cinnamaldehyde.27 Hence, we
decided to pursue both dehydrogenation and oxidation in
one-pot for the formation of cinnamaldehydes. This would
be achieved through the DDQ-assisted conversion of
arylpropane directly into cinnamaldehyde via formation of
intermediate (E)-arylpropene under ultrasound irradiation.
3. Conclusion
In conclusion, we have realised a convenient synthetic
approach towards the preparation of a number of
(E)-cinnmaldehydes (2a–2i) via dehydrogenation–oxidation
Table 2. DDQ assisted dehydrogenation–oxidation of arylpropanes (1) into
cinnamaldehydes (2)
S. no.
Substrate (1)
Product (2)
Yield
(%)
OMe
OMe
Thus, treatment of 3-(2,4,5-trimethoxyphenyl)propane24 1a
with 2 equiv of DDQ in dioxane for 6 h under ultrasonica-
tion provided (E)-2,4,5-trimethoxycinnamaldehyde15c 2a in
48% yield along with some amount of starting 1a.
Subsequently, it was found that 3.1 equiv of DDQ was
optimum for providing 73% yield of the product 2a in 3.5 h
under ultrasonication. Finally, conditions were optimized
and we observed that addition of a catalytic amount of acetic
acid (2–3 drops) increased the yield of 2a up to 82% in 2 h.
Acetic acid was found best among other homogeneous and
heterogeneous acid catalysts (Table 1). After success of the
above reactions for conversion of 1a into 2a, the same
methodology was employed towards dehydrogenation–
oxidation of other arylpropanes (1b–1i), which successfully
provided the corresponding cinnmaldehydes (2b–2i) in
moderate to good yield (Table 2). It is obvious from Table 2
that higher yields are obtained with the more electron rich
aromatics and no cinnamaldehyde was formed in the case of
unsubstituted phenylpropane 1j. To make a comparative
analysis, dehydrogenation and oxidation of 1a with DDQ
(3.1 equiv) in dioxane containing a few drops of acetic acid
at room temperature (20 h) or reflux temperature (8 h)
provided 2a in 76% yield under conventional method. The
results clearly showed that ultrasound activation afforded a
better yield in a shorter reaction time compared to the
classical method. We also found that small alterations in the
reaction conditions such as changing the amount of DDQ
and using hydrated or anhydrous conditions24 provide a
range of products as shown in Scheme 2.
CHO
CHO
CHO
a
82
MeO
MeO
OMe
OMe
OMe
OMe
MeO
MeO
MeO
MeO
b
c
d
e
79
78
76
72
OMe
OMe
MeO
MeO
CHO
O
O
O
O
OMe
OMe
CHO
OMe
OMe
CHO
f
32
72
72
HO
HO
OMe
OMe
CHO
CHO
g
h
MeO
EtO
MeO
EtO
OMe
Br
OMe
Br
Table 1. Effect of catalyst on the yield of cinnamaldehyde (1b) under
ultrasonic irradiation
CHO
i
j
74
0
Support
Reaction time
(in hours)
Product yield (%)
MeO
MeO
OMe
OMe
Acetic acid
Silica gel
Alumina (acidic)
Hydrochloric acid
2
2
2
2
82
78
76
42
CHO

2592
B. P. Joshi et al. / Tetrahedron 62 (2006) 2590–2593
O
DDQ(2.2 equiv)/wet dioxane
DDQ (1.25 equiv)/dry dioxane
R
R
R
Scheme 2.
of available arylpropanes (1a–1i) with DDQ utilizing
ultrasound irradiation. The merits of the protocol lie in
one-pot, two-steps methodology, economical substrate,
atom economy and consequent waste minimization,
ultrasound irradiation and 100% (E)-selectivity. The
method may be useful in natural product synthesis due to
mild nature of the protocol.
4.2.3. (E)-3,4-Dimethoxycinnamaldehyde2b,8e (2c).
Yellow solid; 2.54 g (78% yield); mp 81–82 8C (lit.8e mp
83–84 8C).
4.2.4. (E)-3,4-Methylenedioxycinnamaldehyde9,31 (2d).
Yellow solid; 2.27 g (76% yield); mp 78 8C (lit.9 mp 77–
79 8C, lit.31 mp 83–84 8C).
4.2.5. (E)-2,6-Dimethoxycinnamaldehyde1b (2e). Yellow
solid; 2.35 g (72% yield); mp 78 8C (lit.1b mp 77–78 8C).
4. Experimental
4.2.6. (E)-4-Hydroxy-3-methoxycinnamaldehyde1d,31
(2f). Yellow solid; 0.97 g (32% yield); mp 83–84 8C (lit.31
mp 84 8C).
4.1. General methods
All melting points were determined with a Metler FP80
micromelting point apparatus. IR spectra were recorded on a
Perkin-Elmer spectrophotometer. H (300 MHz) and 13C
1
4.2.7. (E)-4-Methoxycinnamaldehyde15b,19,31 (2g). Light
yellow solid; 1.98 g (72% yield); mp 58 8C (lit.15b,31 mp
58–59 8C).
(75.4 MHz) NMR spectra were taken on a Bruker AM-300
spectrometer, using TMS as internal reference standard in
CDCl3. HRMS spectra were determined using a Micromass
Q-TOF Ultima spectrometer. Sonication (20 kHz, 400 W;
pulse length:10 s; 75% duty) was used for all the given
reactions. Commercial reagents and solvents were of
analytical grade and were purified by standard procedures
prior to use. Column chromatographic separations have
been carried out on neutral alumina (Qualigens India).
4.2.8. (E)-4-Ethoxy-3-methoxycinnamaldehyde (2h).
Yellow solid; 2.52 g (72% yield); mp 78–80 8C; IR (KBr)
1670 cmK1 (conjugated carbonyl); 1H NMR (CDCl3): d
9.59 (1H, d, JZ7.8 Hz, H-30), 7.36 (1H, d, JZ15.8 Hz,
H-10), 7.07 (1H, d, JZ8.1 Hz, H-6), 7.00 (1H, s, H-2), 6.83
(1H, d, JZ8.1 Hz, H-5), 6.56 (1H, dd, JZ15.8, 7.8 Hz, H-
20), 4.11 (2H, q, JZ6.9 Hz, 4-OCH2), 3.83 (3H, s, 3-OCH3),
1.44 (3H, t, JZ6.9 Hz, 4-CH3); 130 C NMR (75.4 MHz,
CDCl3): d 193.6 (C-30), 152.9 (C-1 ), 151.4 (C-4), 149.5
(C-3), 126.8 (C-20), 126.6 (C-1), 123.4 (C-6), 112.1 (C-5),
110.2 (C-2), 64.4 (4-OCH2), 56.0 (3-OCH3), 14.6 (4-CH3);
HRMS (MCNa) m/z: 229.2335 (Calcd for C12H14O3Na:
229.2321).
4.2. General procedure for ultrasound-assisted dehy-
drogenation–oxidation of arylpropanes (1a–1i) into
cinnamaldehydes (2a–2i)
To a solution of 1a–1i (0.017 mol) in dry dioxane (100 mL),
a catalytic amount of acetic acid (2–4 drops) and DDQ
(0.053 mol) was added. The reaction mixture was sonicated
for 2 h or till disappearance of starting material on TLC
plate. After completion of the reaction, the precipitated solid
DDQH2 was removed by filtration and the filtrate was
evaporated. The residue was taken in ethyl acetate (70 mL)
and was washed with water (2!10 mL), 2% sodium
bicarbonate (2!5 mL), brine (2!10 mL), dried over
Na2SO4 and filtered. The filtrate was evaporated to afford
a crude yellow liquid, which was chromatographed on
neutral alumina using hexane–ethyl acetate mixture with
increasing proportion of ethyl acetate up to 40% to provide
2a–2i whose spectral data agreed well with the reported
values.1a–d,2b,8e,15b–c,19,24
4.2.9. (E)-2-Bromo-4,5-dimethoxycinnamaldehyde (2i).
Yellow solid; 3.41 g (74% yield); mp 136–138 8C; IR (KBr)
1671 cmK1 (conjugated carbonyl); 1H NMR (CDCl3): d
9.66 (1H, d, JZ7.8 Hz, H-30), 7.75 (1H, d, JZ15.8 Hz,
H-10), 7.19 (1H, s, H-3), 7.02 (1H, s, H-6), 6.53 (1H, dd, JZ
15.8, 7.8 Hz, H-20), 3.84 (3H, s, 4-OCH3), 3.82 (3H, s,
13
5-OCH3); C NMR (75.4 MHz, CDCl3): d 193.4 (C-30),
152.1 (C-10), 150.5 (C-5), 148.8 (C-4), 128.6 (C-1),
125.8 (C-20), 118.0 (C-3), 115.7 (C-6), 109.3 (C-2), 56.3
(4-OCH3), 56.1 (5-OCH3); HRMS (MCNa) m/z: 294.1006
(Calcd for C11H11O3BrNa: 294.1012).
4.2.1. (E)-2,4,5-Trimethoxycinnamaldehyde1c,15c,31 (2a).
Yellow solid; 3.09 g (82% yield); mp 139–140 8C (lit.15c,31
140–141 8C).
Acknowledgements
Two of us (B.P.J. and A.S.) are indebted to CSIR, Delhi for
the award of SRF. The authors gratefully acknowledge the
Director of IHBT, Palampur for his kind cooperation and
encouragement.
4.2.2. (E)-3,4,5-Trimethoxycinnamaldehyde1a,31 (2b).
Yellow solid; 2.98 g (79% yield); mp 110 8C (lit.31
109–111 8C).

B. P. Joshi et al. / Tetrahedron 62 (2006) 2590–2593
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