Effect of microwave irradiation on reaction of arylaldehyde derivatives with some active methylene compounds in aqueous media

Article abstract of DOI:10.1081/SCC-200050942

The effect of microwave irradiation on the condensation reactions of arylaldehydes 1 and active methylene compounds 2 in aqueous media was studied and compared with "classical" conditions. The results show that the condensation was carried out only under microwave irradiation in the presence of ammonium chloride as a catalyst, followed by dehydration, to afford (E)-olefins 3. The protocol was used to synthesize coumarins by a condensation reaction of salicylaldehyde or its derivatives with various derivatives of ethylacetate 5 (e.g., R³CH₂CO₂Et; R³: CO ₂Et, CO₂Me, COMe, CN) in high yields. These investigations will contribute to the development of environmentally friendly and inexpensive processes in organic synthesis.

Full text of DOI:10.1081/SCC-200050942

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Effect of Microwave Irradiation on Reaction
of Arylaldehyde Derivatives with Some Active
Methylene Compounds in Aqueous Media
Hassan Valizadeh a , Manouchehr Mamaghani b & Abed Badrian b
a Department of Chemistry, Faculty of Science , Azarbaydjan University of
Tarbiat Moallem , Tabriz, Iran
b Department of Chemistry, Faculty of Science , Guilan University , Rasht,
Iran
Published online: 20 Aug 2006.
To cite this article: Hassan Valizadeh , Manouchehr Mamaghani & Abed Badrian (2005) Effect of Microwave
Irradiation on Reaction of Arylaldehyde Derivatives with Some Active Methylene Compounds in Aqueous
Media, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 35:6, 785-790, DOI: 10.1081/SCC-200050942
To link to this article: http://dx.doi.org/10.1081/SCC-200050942
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Synthetic Communicationsw, 35: 785–790, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200050942
Effect of Microwave Irradiation on Reaction
of Arylaldehyde Derivatives with Some
Active Methylene Compounds in
Aqueous Media
Hassan Valizadeh
Department of Chemistry, Faculty of Science, Azarbaydjan University of
Tarbiat Moallem, Tabriz, Iran
Manouchehr Mamaghani and Abed Badrian
Department of Chemistry, Faculty of Science, Guilan University,
Rasht, Iran
Abstract: The effect of microwave irradiation on the condensation reactions of
arylaldehydes 1 and active methylene compounds 2 in aqueous media was studied
and compared with “classical” conditions. The results show that the condensation
was carried out only under microwave irradiation in the presence of ammonium
chloride as a catalyst, followed by dehydration, to afford (E)-olefins 3. The protocol
was used to synthesize coumarins by a condensation reaction of salicylaldehyde or its
derivatives with various derivatives of ethylacetate 5 (e.g., R3CH2CO2Et; R3: CO2Et,
CO2Me, COMe, CN) in high yields. These investigations will contribute to the develop-
ment of environmentally friendly and inexpensive processes in organic synthesis.
Keywords: Aqueous media, coumarin, MW irradiation
Chemical processes employ large amounts of hazardous and toxic solvents.
The choice of pursuing a clean and inexpensive aqueous reaction medium,
Received in the U.K. August 19, 2004
Address correspondence to Hassan Valizadeh, Department of Chemistry, Faculty of
Science, Azarbaydjan University of Tarbiat Moallem, P. O. Box 53714-161, Tabriz,
Iran. Fax: 0098-412-4524991; E-mail: h-valizadeh@azaruniv.edu

786
H. Valizadeh, M. Mamaghani, and A. Badrian
to minimize the economic cost and environmental impact of a chemical
process, is becoming ever more urgent for the future.
Organic reactions under solvent-free[1,2] and aqueous[3–5] conditions
have increasingly attracted chemists’ interests, particularly from the
viewpoint of green chemistry.[6] As an important carbon–carbon bond-
forming reaction, condensation reactions have been extensively studied.
Generally, this type of reaction is catalyzed by a base or Lewis acid in the
liquid-phase system. In recent years, chemists paid more and more attention
to the clean synthesis of alkenes by condensation reactions. Recently,
several methods based on a solid-phase synthesis utilizing Kneovenagel
condensation for preparation of coumarins have been reported.[7–9] These
methods have their own merits and disadvantages; therefore, the introduction
of efficient and new methods based on green methodology is still in demand.
Microwave irradiation has been utilized as one of the most convenient and
efficient ways to promote organic reactions.[10,11] Recently, we have reported
the MgO-catalyzed Knoevenagel condensation in solventless system.[12]
Armed with these experiments, we report herein the condensation reaction
of arylaldehydes 1 with active methylene compounds 2 in aqueous media
under microwave irradiation.
We utilized the microwave-irradiation technique to promote the solvent-
free synthesis of coumarins via piperidine-catalyzed Knoevenagel conden-
sation of salicylaldehydes with active methylene compounds in high
yields.[13] The aim of this work was to study the same condensation
reactions in the presence of aqueous-soluble basic catalysts such as KOH,
NaOH, and K2CO3 via “classical” heating and under microwave irradiation
in aqueous media.
We began our studies with conventional refluxing of arylaldehyde in
water with nitroacetonitrile and the adequate KOH. After several hours,
refluxing the reaction did not proceed at various temperatures after a long
reaction time (12–24 h). Thus to speed reaction times, we used microwave
heating of the reaction mixture. We used a domestic microwave oven, and
the reactions were carried in a beaker. The irradiation was paused every
minute for an interval of 20 sec so as to prohibit very high temperatures.
The monitoring of the reaction by Thin Layer Chromatography (TLC)
in the different solvent systems, visualizing spots with UV lamp or iodine
vapor, show that in no case the reaction did proceed. The addition of
catalytic amount of tetrabuthylammoniumbromide as a Phase Transfer
Catalyst (PTC) to the mixture had no effect on the progress of the reaction.
Ammonium chloride was added as a catalyst to the mixture of reactants in
aqueous media and the mixture was subjected to microwave irradiation. The
monitoring of the reaction by TLC show that the condensation reaction
proceeded in this condition (Scheme 1). Furthermore, the use of ammonium
chloride in water was sufficient to promote the reaction and no additives
such as KOH, NaOH, or K2CO3 were required for this reaction. The use of

Reactions of Arylaldehyde Derivatives
787
Scheme 1.
salicylaldehyde derivatives 4 in this reaction with ethylacetate derivatives 5
afforded to 3-substitutedcoumarins 6 in good yields (Scheme 2).
In summary, this method describes a noticeable improvement in
Knoevenagel condensations and synthesis of 3-substitutedcoumarins by the
Knoevenagel condensation and takes advantage of both aqueous media
reaction and microwave activation. As is shown in Tables 1 and 2, the
reaction time is reduced to only a few minutes by using microwave dielectric
heating. The reactions can be run safely in good yields.
EXPERIMENTAL
All of the melting points were determined on an Electrothermal 9100
apparatus and are uncorrected. IR spectra were recorded on a Perkin-Elmer
model 843. 1H-NMR (Proton nuclear magnetic resonance) spectra were
recorded on a Bruker Avance 500 MHz or JEOL FX90 MHz instruments.
Mass spectrum was obtained on a Shimadzu QP 1100EX instrument. Analyti-
cal calculation was obtained on a LECO CHNO-932 Analyzer instrument.
GENERAL PROCEDURE
Arylaldehyde (20 mmol), activated methylene compound (22 mmol), and
excess ammonium chloride were mixed in water thoroughly. The mixture
Scheme 2.

788
H. Valizadeh, M. Mamaghani, and A. Badrian
Table 1. Reaction of arylaldehydes 1 with active methylene compounds 2 in water to
give products 3
Time
(min)
Entry
R1
X
Y
M (8C)
Yield (%)
a
b
c
d
e
f
4-SMe
4-Me
4-OH
2-OMe
3-OMe
4-Cl
NO2
NO2
CN
CN
2.5
2
115–117
94–96
85
87
90
80
70
92
85
87
88
NO2
NO2
CN
CN
3
215–218
129–131
118–120
115–117
193–194
201–203
191–193
3
NO2
NO2
CN
CN
2
2.5
3
g
h
i
H
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
4-Me
2-Cl
2.5
3
was placed in a household microwave oven. The progress of reaction was
monitored by TLC. After the completion of the reaction, the reaction
mixture was then allowed to cool to room temperature and, after addition of
water, was extracted with ethylacetate and dried over anhydrous magnesium
sulfate. The solvent was removed by distillation under reduced pressure and
the resulting crude product was subjected to column chromatography using
hexane/AcOEt as solvent to obtain related products (Table 1 and Table 2).
SELECTED SPECTROSCOPIC DATA
1
3a: HNMR d (CDCl3): 2.55 (s, 3H, Me), 7.34 (br d,H, J 8.8 Hz, aromatic),
7.90 (br d, 2H, J 8.8 Hz, aromatic), 8.55(s, 1H, H-2). 13C NMR
(CD3COCD3): d 14.2, 112.4, 122.4, 124.3, 126.2, 133.2, 148.9, 151.4. MS:
m/z (%) 220 (98, Mþ), 174 (100), 173 (52), 159 (64), 127 (47). Anal. calc.
for C10H8N2O2S (220): C, 54.53; H, 3.66; N, 12.72. Found: C, 54.48; H,
3.67; N, 12.66%.
Table 2. Preparation of coumarins 6 via Knoevenagel reaction in water
Time
(min)
Entry
R2
X
M (8C)
Yield (%)
a
b
c
d
e
OH
OH
OH
H
CO2Et
CO2Me
CN
3
173–175
264–267
249–251
115–118
94–97
82
85
87
79
80
3
2.8
3
COMe
CO2Et
H
2.5

Reactions of Arylaldehyde Derivatives
789
1
3b: HNMR d (CDCl3): 2.51 (s, 3H, Me), 7.40 (br d, 2H, J 8.8 Hz,
aromatic), 7.92 (br d, 2H, J 8.8 Hz, aromatic), 8.63 (s, 1H, H-2). 13C NMR
(CD3COCD3) d 21.8, 112.1, 123.2, 125.9,131.0, 132.8, 147.8, 149.2. MS:
m/z (%) 188 (50, Mþ), 141 (45), 140 (61), 115 (100), 103 (53). Anal. calc.
for C10H8N2O2 (188): C, 63.82; H, 4.28; N, 14.89. Found: C, 63.90; H,
4.93; N, 14.87%.
1
3c: HNMR d (CD3COCD3): 7.11 (br d, 2H, J 8.8 Hz, aromatic), 8.12
(br d, 2H, J 8.8 Hz, aromatic), 8.78 (s, 1H, H-2), 9.97 (br s, 1H, OH-phenolic).
13C NMR (CD3COCD3) d 112.2, 117.3, 119.5, 120.1, 135.8, 148.7, 164.9.
MS: m/z (%) 190 (62, Mþ), 144 (54), 143 (100), 116 (47), 89 (100). Anal.
calc. for C9H6N2O3 (190): C, 56.85; H, 3.18; N, 14.73. Found: C, 56.78; H,
3.25; N, 14.66%.
3d: 1HNMR d (CDCl3): 4.01 (s, 3H, OMe), 6.97–8.31 (m, 4H, aromatic),
9.21 (s, 1H, H-2). 13C NMR (CD3COCD3) d 55.8, 111.4, 112.3, 116.5, 121.2,
123.2, 129.6, 137.6, 142.4, 160.6. MS: m/z (%) 204 (100, Mþ). 157 (65),
143(87), 115 (46), 103 (65). Anal. calc. for C10H8N2O3 (204): C, 58.82; H,
3.95; N, 13.72. Found: C, 58.92; H, 3.94; N,13.87%.
3e: 1HNMR d (CDCl3): 3.88 (s, 3H, OMe), 7.22–7.60 (m, 4H, aromatic),
8.62 (s, 1H, H-2). 13C NMR (CD3COCD3) d 55.7, 111.8, 116.6, 121.8, 124.1,
125.3, 129.6, 131.5, 149.2, 160.7. MS: m/z (%) 204 (100, Mþ). 143 (61),
115(65). Anal. Calc. for C10H8N2O3 (204): C, 58.82; H, 3.95; N,13.72.
Found: C, 58.88; H, 3.87; N, 13.64%.
3f: 1HNMR d (CDCl3): 7.54–8.11 (m, 4H, aromatic), 8.65 (s, 1H, H-2). 13
C
NMR (CD3COCD3) d 110.8, 123.6, 126.6, 129.7, 133.2, 140.6, 147.1. MS: m/z
(%) 208 (55, Mþ), 161 (85), 127 (100), 75 (61). Anal. calc. for C9H5ClN2O2
(208): C, 51.82; H, 2.42; N, 13.43. Found: C, 51.88; H, 2.33; N, 13.35%.
3g: 1HNMR d (CDCl3/DMSO d6): 7.35(3H, m), 7.6(1H, s, vinyl-H), 7.48
(2H, m). 13C NMR (CDCl3/DMSO-d6) d 169.12, 165, 140.2, 133.7, 130.9,
130, 129.5, 128.7. IR, n (KBr disc): 3300–2460, 1700, 1630, 1462 cm21
.
3h: 1HNMR d (CDCl3/DMSO d6): 2.34 (3H, s.Me), 7.03 (2H, d,
J ¼ 8.02 Hz), 7.37 (2H, d, J ¼ 8.07), 7.42 (1H, s, vinyl-H). 13C NMR
(CDCl3/DMSO-d6) d 169.04, 166.1, 141.2, 140, 130.9, 130.11, 128, 21.89.
IR, n (KBr disc): 3320–2465, 1701, 1610, 1450, 1298, 1245 cm21
.
3i: 1HNMR d (CDCl3/DMSO d6): 7.36–7.25(2H, m), 7.4 (1H, dd,
J ¼ 7.9 and 1.4 Hz), 7.5 (1H, dd, J ¼ 7.5 and 1.5 Hz), 7.7 (1H, s, vinyl-H).
13C NMR (CDCl3/DMSO-d6) d 168, 165, 136.1, 132.4, 131.7, 131.3,
129.7, 127.7. IR, n (KBr disc): 3400–3200, 3100–2910, 2210, 1670, 1600,
1590, 1240, 1110 cm21
.
6a: 1HNMR d (DMSO d6): 1.52 (t, 3H, Me), 4.55 (q, 2H, OCH2), 7–7.8
(m, 3H, aromatic protons), 8.68 (s, 1H, olefinic CH), OH is unobserved; IR, n
(KBr disc): 3300–3100, 1725, 1685 cm21
.
1
6b: HNMR d (DMSO d6): 3.8 (s, 3H, OMe), 6.9-7.7 (m, 3H, aromatic
protons), 6.69 (s, 1H, olefinic CH), OH is unobserved, IR, n (KBr disc):
3290–3090, 1715, 1680 cm21
.

790
H. Valizadeh, M. Mamaghani, and A. Badrian
6c: 1HNMR d (DMSO d6): 6.9–7.9 (m, 3H, aromatic protons),
8.81(s, 1H, olefinic CH), OH is unobserved, IR, n (KBr disc): 3260–3080
2230, 1685 cm21
.
6d: HNMR d (CDCl3): 2.85 (s, 3H, Me), 7.3–7.85 (m, 4H, aromatic
1
protons), 8.62 (s, 1H, olefinic CH), IR, n (KBr disc): 1750, 1680 cm21
.
1
6e: HNMR d (CDCl3): 1.52(t, 3H, Me), 4.55 (q, 2H, OCH2), 7.4–7.9
(m, 4H, aromatic protons), 8.62 (s, 1H, olefinic CH); IR, n (KBr disc):
1790, 1650 cm21
.
ACKNOWLEDGMENT
The Office of Research, Vice Chancellor, Azarbaydan University of Tarbiat
Moallem has supported this work.
REFERENCES
1. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
2. Loupy, A. Top. Curr. Chem. 2000, 206, 153.
3. Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; John Wiley & Sons:
New York, 1997.
4. Grieco, P. A. Ed.; Organic Synthesis in Water; Blackie Academic and Pro-
fessional: London, 1998.
´
5. Lubineau, A.; Auge, J. Top. Curr. Chem. 1999, 206, 1.
6. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford Uni-
versity Press: Oxford, 1998.
7. Watson, B. T.; Christianson, G. E. Tetrahedron Lett. 1998, 39, 6087.
8. Kwon, P. S.; Kim, Y. M.; Joong, C.; Kwon, T. W. Synth. Commun. 1997, 27, 4091.
9. James, N. Y.; Aramini, M.; Germann, M. W.; Huang, Z. Tetrahedron Lett. 2000,
41, 6993.
10. Saddick, S. Tetrahedron 1995, 51, 10403.
11. Loupy, A.; Petti, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.; Mathe, D.
´
Synthesis 1998, 1213.
12. Shockravi, A.; Valizadeh, H.; Heravi, M. M.; Sharghi, H. Phosphorous, Sulfur
Silicon Relat. Elem. 2002, 177, 2555.