Facile condensation of aromatic aldehydes with chroman-4-ones and 1-thiochroman-4-ones catalysed by amberlyst-15 under microwave irradiation condition

Article abstract of DOI:10.1155/2011/426560

Different aromatic aldehydes and cinnamaldehyde undergo crossaldol condensation with chroman-4-ones and 1-thiochroman-4-ones in the presence of amberlyst-15 under microwave irradiation in solvent free condition to afford rapidly the corresponding E-3-arylidene and E-3-cinnamylidene derivatives, respectively, in high yield. This process is simple, efficient and environmentally benign.

Full text of DOI:10.1155/2011/426560

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(2), 863-869
http://www.e-journals.net
Facile Condensation of Aromatic Aldehydes with
Chroman-4-ones and 1-Thiochroman-4-ones
Catalysed by Amberlyst-15 under
Microwave Irradiation Condition
TAPAS K. MANDAL, RAMMOHAN PAL,
RINA MONDAL and ASOK K. MALLIK*
Department of Chemistry
Jadavpur University, Kolkata-700032, India
mallikak52@yahoo.co.in
Received 17 August 2010; Accepted 8 November 2010
Abstract: Different aromatic aldehydes and cinnamaldehyde undergo cross-
aldol condensation with chroman-4-ones and 1-thiochroman-4-ones in the
presence of amberlyst-15 under microwave irradiation in solvent free condition
to afford rapidly the corresponding E-3-arylidene and E-3-cinnamylidene
derivatives, respectively, in high yield. This process is simple, efficient and
environmentally benign.
Keywords: Amberlyst-15, Microwave irradiation, E-3-Arylidenechroman-4-ones, E-3-Cinnamylidene
chroman-4-ones, E-3-Arylidenethiochroman-4-ones, E-3-Cinnamylidenethiochroman-4-ones.
Introduction
Both natural and synthetic chromone derivatives are known to show important biological
activities1,2. Thiochromones are mostly synthetic compounds and some of their derivatives
are reported to show medicinal properties3,4. Current literature shows that there has been a
growing trend towards synthesis of heterocycles containing these two ring systems5. The
corresponding reduced systems, chroman-4-ones and 1-thiochroman-4-ones possess a
ketomethylene moiety. Condensation of aldehydes at this moiety appears to be an entry
point for synthesis of complex molecules containing chromone and thiochromone units. In
this connection special mention may be made for the synthesis of natural homoiso
flavonoids, some of which are known to act as anti-inflammatory and cytotoxic agents6. The
said condensation has been reported to be performed in a number of ways. The initial
methods were base-catalysed processes7 and subsequently, acid-catalysed methods have also
been developed8. Modifications like condensation using acetic anhydride9 or piperidine10

864
ASOK K. MALLIK et al.
have also been reported. The acid-catalysed processes are sometimes two-step processes, the
first step giving an aldol which is required to be dehydrated subsequently11. Moreover,
isomerisation12 and LAH reduction11,13 of these E-3-arylidene derivatives have been studied
with much interest. Amberlyst-15 is a sulphonated polystyrene resin14 that has been used for
a large number of transformations promoted by strong acids. Microwave irradiation is an
efficient and environmentally benign method to activate various organic transformations to
afford products in higher yields in shorter reaction periods. Among the MW-assisted
reactions, solvent free processes are of particular interest and importance in view of their
simplicity, tunability and ease of work-up15 . Herein we report a new method for synthesis of
E-3-arylidenechroman-4-ones and E-3-arylidene-1-thiochroman-4-ones with different
aromatic aldehydes and cinnamaldehyde done by use of amberlyst-15 as catalyst under
microwave irradiation in solvent free condition (Schemes 1 & 2).
X
X
Amberlyst-15
ArCHO
+
Ar
MW, 3.5-5 min.
R
R
O
O
Scheme 1
2
X = O, S
X
1
X
Amberlyst-15
CHO
+
Ph
Ph
MW, 5 min.
R
R
O
3
O
Scheme 2
1
X = O, S
Experimental
All melting points were recorded on a Köfler block and are uncorrected. IR spectra were
recorded on Perkin-Elmer FT-IR spectrophotometer (Spectrum RX 1) in KBr pellets. 1H and
13C NMR spectra were recorded in CDCl3 on a Bruker AV-300 (300 MHz) spectrometer
using TMS as internal standard. Analytical samples were routinely dried in vacuo at room
temperature. Column chromatography was performed with silica gel (100-200 mesh) and
o
TLC with silica gel G made of SRL Pvt. Ltd. Petroleum ether had the boiling range 60-80 C.
Amberlyst-15 used was made of fluka chemika. An unmodified domestic household
microwave oven (LG, DMO, Model No.-556P, 900 watt) equipped with inverter technology,
which provides a realistic control of the microwave power to the desired level (20% - 100%)
was used for microwave heating. The MW oven was operated at reduced MW-power level
of 60% (540 watt) and total power level 100% (900 watt).
General procedure for condensation reactions
In a typical procedure, a mixture of chroman-4-one / 1-thiochroman-4-one (2 mmol), aromatic
aldehyde / cinnamaldehyde (2 mmol), neutral alumina (5 g) and Amberlyst-15 (100 mg) were
thoroughly mixed and the whole mixture was taken in a Pyrex beaker (20 mL). The mixture was
then irradiated in the microwave oven for appropriate time. After irradiation the mixture was
cooled, shaken with chloroform (10 mL) and filtered. The filtrate was concentrated and subjected
to rapid column chromatography over silica gel using petroleum ether-ethyl acetate (9:1) as
eluent to obtain the crystalline pure product. Majority of the products were known compounds
and some of them were not known previously. The products were characterized from their
1
literature melting points, physical, analytical and spectral (IR and H and 13C NMR) data. The
spectral data of some of the compounds are given below:

Facile Condensation of Aromatic Aldehydes with Chroman-4-ones
865
1
Compound 2f : Yellow crystals; IR (KBr) cm-1: 1666 (C=O), H NMR (300 MHz,
CDCl3): δ 5.34 (2H, s, H2-2), 6.02 (OCH2O), 6.78 (1H, br. s, H-2′), 6.82 (1H, d, J = 8.2 Hz,
H-5′), 6.88 (1H, d, J = 8 Hz, H-6′), 6.95 (1H, d, J = 8.3 Hz, H-8),7.06 (1H, br. t, J = 7.5 Hz,
H-6), 7.47 (1H, br. t, J =7.7 Hz, H-7), 7.77 (1H, br. s, H-β) and 8.00 (1H, d, J = 7.8 Hz,
H-5). 13C NMR (75 MHz, CDCl3) δ 67.7, 101.6, 108.6, 109.8, 117.8, 121.8, 122.1, 125.4,
127.9, 128.5, 129.4, 135.7, 137.3, 148.1, 148.9, 160.9 and 182.0 (C=O). Anal. (%) Calcd.
for C17H12O4 (280.27): C, 72.85: H, 4.32. Found C, 72.56: H, 4.44.
1
Compound 2l : Yellow crystals; IR (KBr) cm-1 : 1660 (C=O), H NMR (300 MHz,
CDCl3): δ 2.33 (3H, s, CH3), 3.05 (6H, s, NMe2), 5.39 (2H, s, H2-2), 6.55 (1H, br. s, H-3′),
6.72 (2H, d, J = 8.7Hz, H-3′ & H-5′), 6.85 (1H, d, J =8.3Hz, H-7), 7.25-7.27(3H, H-8, H-2′
& H-6′), 7.81(1H, s, H-β ), 7.82(1H, s, H-5) Anal.(%) Calcd. for C19H19O2N (293.36): C,
77.79: H, 6.53, N, 4.77. Found C, 77.60: H, 6.45: N, 4.68.
1
Compound 2m : Yellow crystals; IR (KBr) cm-1 : 1670 (C=O), H NMR (300 MHz,
CDCl3): δ 2.31 (3H, s, CH3), 5.31 (2H, s, H2-2), 6.03 (OCH2O), 6.79-7.30 (Ar-H), 7.77 (1H,
br. s, H-β) and 7.79 (1H, s, H-5). Anal. (%) Calcd. for C18H14O4 (294.30): C, 73.46: H, 4.79.
Found C, 73.36: H, 4.86.
1
Compound 2n : Yellow needles; IR (KBr) cm-1 1667 (C=O), H NMR (300 MHz,
CDCl3): δ 2.33 (3H, s, CH3), 5.67 (2H, s, H2-2), 6.55 (1H, br. s, H-4′ ), 6.74 (1H, d, J = 3.1
Hz, H-3′ ), 6.89 (1H, d, J = 8.4 Hz, H-8 ), 7.28 (1H, br. d, J = 8.4 Hz, H-7 ), 7.51, 7.61 and
7.79 (each 1H, br. s, H-5, H- β and H-5′). Anal. (%) Calcd. for C15H12O3 (240.25): C, 74.99:
H, 5.03. Found C, 74.76: H, 4.92.
1
Compound 3c : Yellow crystals; IR (KBr) cm-1 : 1664 (C=O), H NMR (300 MHz,
CDCl3): δ 2.33 (3H, s, CH3), 5.23 (2H, s, H2-2), 6.86-7.10 (3H, m, H-8, H-γ & H-δ), 7.27-
7.40 (4H, m, Ar-H), 7.47-7.56 (3H, m, H-β & Ar-H), 7.80 (1H, br. s, H-5). Anal.(%) Calcd.
for C19H16O2 (276.33): C, 82.58: H, 5.84. Found C, 82.45: H, 5.98.
Results and Discussion
A number of aromatic aldehydes as well as cinnamaldehyde underwent rapid cross-aldol
condensation with 4-chromanones and 1-thio-4-chromanone when subjected to microwave
irradiation in the presence of amberlyst-15 on neutral alumina. The products were E-3-arylidene
and E-3-cinnamylidene derivatives of chroman-4-ones and 1-thiochroman-4-ones and their
yields were very good to excellent (Tables 1 & 2). The reactions were performed in solvent free
condition. They were very fast (complete within 3.5-5 minutes), clean and environmentally
benign. Conversions were partial when these reactions were carried out under thermal condition
for 4 h. This clearly indicated the role of microwave in enhancing the reaction rates as well as
the yields. Thus, microwave irradiation, which has become a powerful synthetic tool for the
preparation of various biologically active molecules under solvent-free conditions, can also be
used for the preparation of many classical organic reactions. Among various materials providing
solid surface, neutral alumina is attractive because of its low cost and nontoxic nature.
Moreover, it is very simple to apply during reactions and can be reused.
In a previous method for synthesis of compounds 2, their isomerisation to corresponding
endocyclic compounds [i.e., to 3-(arylmethyl)chromones or 3-(arylmethyl)thiochromones]
were reported18. In the present method no trace of such isomerisation was observed
(3-(arylmethyl)chromones and 3-(arylmethyl)thiochromones are known to give a two-proton
singlet around δ 3.85 and 4.00, respectively, for their methylene protons18. However, any
product giving such spectral features could not be isolated by us).

866
ASOK K. MALLIK et al.
Table 1. Microwave assisted synthesis of E-3-arylidenechroman-4-ones and E-3-arylidene-
1-thiochroman-4-ones
Ketone
(1)
Time
min.
Product
(2)
Yield,
%
M.P, oC
Obs. (Lit.)
Entry†
Aldehyde
O
CHO
111
(110)16
Chr.
Chr.
4.0
3.5
89
91
a
O
O
Cl
CHO
170
(168)16
b
Cl
O
O
OMe
Br
CHO
131
(132)16
Chr.
Chr.
Chr.
5.0
4.0
5.0
85
88
85
c
d
e
MeO
O
O
CHO
175
(174)16
Br
Me
O
O
O
Me
CHO
CHO
116
(118)16
O
O
O
O
115
*
Chr.
Chr.
Chr.
4.5
5.0
3.5
84
81
92
f
O
O
O
O
105
*
g
O
CHO
CHO
O
O
NO2
223
(223)16
h
O2N
O
O
O
CHO
CHO
6-Me-
Chr.
133
*
5.0
3.5
88
91
i
Me
Me
O
Cl
Me
6-Me-
Chr.
144
*
j
Cl
O
O
CHO
CHO
6-Me-
Chr
120
*
4.5
5.0
86
90
k
l
Me
Me
Me
O
O
NMe2
6-Me-
Chr.
140
*
Me2N
O
O
CHO
O
O
6-Me-
Chr.
135
m
4.5
82
O
Me
*
O
O
O
6-Me-
Chr.
101
5.0
4.0
78
87
n
o
O
Me
CHO
CHO
O
*
O
O
6-Cl-
Chr.
134
Cl
*
O
Contd…

Facile Condensation of Aromatic Aldehydes with Chroman-4-ones
867
O
Cl
CHO
CHO
CHO
6-Cl-
Chr.
195
*
3.5
4.0
89
82
p
q
Cl
Cl
Cl
O
O
Me
6-Cl-
Chr.
131
*
Me
O
O
O
O
6-Cl-
Chr.
170
*
4.0
85
r
O
Cl
O
O
O
O
6-Cl-
Chr.
132
*
4.0
5.0
5.0
5.0
84
82
83
79
s
t
O
CHO
Cl
O
S
104
(105)16
CHO
Th-chr.
Th-chr.
Th-chr.
O
S
Cl
CHO
132
(135)16
u
v
Cl
O
S
CHO
OMe
112
(113)16
MeO
O
S
Br
CHO
CHO
150
(149)16
Th-chr.
Th-chr.
5.0
5.0
82
80
w
x
Br
O
S
Me
105
(107)16
Me
O
†Chr. = Chroman-4-one, 6-Me-Chr.= 6-Methylchroman-4-one, 6-Cl-Chr. = 6- Chlorochroman-4-one,
Th-chr. = 1-Thiochroman-4-one * Showed the following characteristic 1H NMR signals: 2H, s, around
δ5.35 (H2-2); 1H, s, around δ7.80 (H-β)
Table 2. Microwave assisted synthesis of E-3-cinnamylidenechroman-4-ones and E-3-
cinnamylidene-1-thiochroman-4-ones
Ketone
(1)
Time,
min.
Product
(3)
Yield
%
M.P, oC
Obs. (Lit.)
Entry†
Aldehyde
O
Cinnamal-
dehyde
135
(136)17
Ph
Chr.
5.0
5.0
87
88
a
O
O
6-Cl-
Chr
Cinnamal-
dehyde
151, Shows chara-
cteristic IR & 1H
NMR spectral data
148, Characterised
by spectral data
given in
Ph
b
Cl
O
O
6-Me-
Chr.
Cinnamal-
dehyde
Ph
5.0
5.0
85
78
c
Me
O
S
Experimental
Cinnamal-
dehyde
144
(145)17
Ph
Th-Chr.
d
O
†Chr. = Chroman-4-one, 6-Me-Chr.= 6-Methylchroman-4-one, 6-Cl-Chr. = 6- Chlorochroman-4-one,
Th-chr. = 1-Thiochroman-4-one

868
ASOK K. MALLIK et al.
Conclusion
A new methodology for the synthesis of E-3-arylidene and E-3-cinnamylidene derivatives of
chroman-4-ones and 1-thiochroman-4-ones has been developed. The method is very
efficient, simple and environmentally benign.
Acknowledgment
Financial assistance from the CAS programme, Department of Chemistry is gratefully
acknowledged. The authors also acknowledge the DST-FIST programme to the Department
of Chemistry, Jadavpur University for providing the NMR spectral data.
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