A facile solvent free synthesis of 3-arylidenechroman-4-ones using grinding technique

Article abstract of DOI:10.1155/2012/324907

An efficient method for the synthesis of 3-arylidenechroman-4-ones has been developed under solvent free conditions using grinding technique. Grinding of variously substituted chroman-4-ones with aromatic aldehydes in presence of anhydrous barium hydroxide at room temperature give 3-arylidenechroman-4-ones in high yield (75-92%). Products are obtained by just acidification of the reaction mixture in ice cold water. Reaction in solid state, with enhanced rate, high selectivity and manipulative simplicity are the attractive features of this environmentally benign protocol. The chroman-4-one derivatives required for the reaction have been obtained by polyphosphoric acid (PPA) catalysed cyclisation of phenoxypropanoic acids under microwave irradiations.

Full text of DOI:10.1155/2012/324907

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(3), 1251-1256
A Facile Solvent Free Synthesis of
3-arylidenechroman-4-ones Using Grinding
Technique
SURESH KUMAR* and JAGDISH K. MAKRANDI1
* Department of Chemistry, Kurukshetra University Kurukshetra (India)-136119
1Department of Chemistry, M.D. University Rohtak (India)-124001
duaskchem@gmail.com
Received 09 July 2011; Accepted 05 September 2011
Abstract: An efficient method for the synthesis of 3-arylidenechroman-4-ones
has been developed under solvent free conditions using grinding technique.
Grinding of variously substituted chroman-4-ones with aromatic aldehydes in
presence of anhydrous barium hydroxide at room temperature give 3-
arylidenechroman-4-ones in high yield (75-92%). Products are obtained by
just acidification of the reaction mixture in ice cold water. Reaction in solid
state, with enhanced rate, high selectivity and manipulative simplicity are the
attractive features of this environmentally benign protocol. The chroman-4-
one derivatives required for the reaction have been obtained by
polyphosphoric acid (PPA) catalysed cyclisation of phenoxypropanoic acids
under microwave irradiations.
Keywords: 3-Arylidenechroman-4-ones, chroman-4-ones, phenoxypropanoic acids, anhydrous
barium hydroxide, aromatic aldehydes, grinding.
Introduction
3-Arylidenechroman-4-ones belong to homoisoflavanoids, a class of naturally occurring
oxygen heterocyclic compounds, with C-16 skelton1. Chroman-4-one derivatives are known
to exhibit a broad range of pharmacological activities1,2 including anti-human-immune
deficiency virus (HIV-I) properties2 that causes acquired immune deficiency syndrome
(AIDS). 3-Benzylidenechroman-4-ones have been reported to inhibit the growth of the
sporogenesis and the enzymes involved in the infection mechanism of phytophtora
parasitica3 and also show antifungal activity4. These have also been found to display anti-
inflammatory, analgesic, platelet anti aggregating5, hypocholesterolemic6 and antioxidant
activities7. These are also used for the synthesis of some selective ligands required for

1252 Suresh Kumar
antiestrogen-binding sites8 and as precursors for the synthesis of various other
homoisoflavanoids9.
The general synthesis of 3-arylidenechroman-4-ones involves the condensation of
chroman-4-ones with aromatic aldehydes in the presence of acidic or basic reagents10. But
the use of acidic reagents for the condensation is usually preferred11,12 as the chroman-4-one
ring is more stable to acidic reagents13. Use of bases such as alcoholic KOH, NaOH,
NaOCH3, piperidine and acetic anhydride10,14 have also been reported for the synthesis of
these compounds. In a recent approach Amberlyst-15 under MW irradiations have been
reported for this reaction15. Ring closure of an acrylic acid derivative with trifuoroacetic
anhydride in dichloromethane medium is also a route for the synthesis of 3-
arylidenechroman-4-ones, but is not of much interest16.
Degradation of ecosystem due to toxic nature of chemicals used, poor yields,
formation of isomeric products, complexity of the procedure and high temperature required
for the reaction, are the major limitations with which the reported methods suffer. In these
days, much emphasis is being laid by the chemists to develop synthetic procedures which
could avoid the use of toxic and hazardous chemicals including solvents17. Grinding
technique, due to its operational simplicity, now has got the attention of the chemists as an
important tool for green synthesis18. In continuation of our work to develop eco-friendly
organic transformations19, here in we are reporting, a facile solvent free green synthesis of 3-
arylidenechroman-4-ones using grinding technique. (Scheme 1).
R1 R2
R2
OCH2CH2COOH
O R1
O
R3
O
O
OHC
R3
PPA, M.W.
6 X 5 sec.
anhyd. Ba(OH)2,
grinding
R
R
R
1
3 (a-k)
x + y min.
2 (a-c)
Scheme 1. Synthesis of 3-arylidenechroman-4-ones.
Experimental
Grinding in all the reaction was carried out in porcelain mortar with pestle. Melting points
were determined in open capillary tubes and are uncorrected. The compounds were
1
characterized from their spectral data (IR & H-NMR) and by comparison with authentic
1
sample. The H NMR spectra were recorded on Bruker Avance II 400 spectrometer at 400
MHz in CDCl3 using TMS as internal standard. Chemical shifts (δ) are reported in ppm and
coupling constant in Hz. The IR spectra were recorded using Perkin Elmer spectrometer
(KBr plates). Reaction involving the use of microwaves were carried out in a domestic
microwave oven (Samsung output energy 900W, frequency 2450MHz, with temperature
control arrangement No. CE 118KF) using 40% power for all the experiments.

A Facile Solvent Free Synthesis of 3-arylidenechroman-4-ones 1253
General procedure
Synthesis of chroman-4-ones (2 a-c)
Phenoxypropanoic acid (15 g) was added to freshly prepared polyphosphoric acid (10 ml) in
a round bottom flask fitted with guard tube and was thoroughly mixed by glass rod. The
resulting mixture was then irradiated with microwaves for 30 seconds (6 x 5 sec.) using 40
% power of the oven, with shaking after each interval of 5 seconds. Pasty residue so
obtained was decomposed with crushed ice (50 g). Cold suspension was then extracted with
diethyl ether, washed with 10 % aq. sodium bicarbonate (2 x 25 ml) followed by water and
dried over magnesium sulphate. The solvent was removed by distillation and residue thus
obtained was recrystallised from petroleum ether-diethyl ether mixture to give product i.e.
chroman-4-one derivatives (2 a-c).
Synthesis of 3-arylidenechroman-4-ones (3 a-k)
A mixture of chroman-4-one (4 mmol), aromatic aldehyde (4.1 mmol) and
anhydrous barium hydroxide (2.5 g) was taken in a mortar and ground well with pestle for 5
minutes. Progress of the reaction was checked on TLC. For completion of the reaction,
reaction mixture was left at room temperature for 5 minutes. It was then worked up by
acidifying the reaction mixture in ice cold conditions, when solid residue was separated out
which was suction filtered, washed with water and recrystallised from petroleum ether-
diethyl ether mixture to give 3-arylidenechroman-4-one (3 a-k). Spectral data of the
compounds synthesized are given below.
6-methyl-3-(4-methylbenzylidene)chroman-4-one (3e):
IR (KBr): 1667 cm-1(C=O).
1H-NMR (CDCl3):  3.04 & 3.30 (each s, 6H, 2  CH3), 5.33 (d, 2H,-OCH2-, J = 1.84 Hz),
6.86 (d, J = 8.4 Hz, 1H, H-8), 7.20-7.31 (m, 5H, H-7, H-2, H-3, H-5, H-6), 7.81 (d, J =
1.80 Hz, 1H, H-5), 7.55 (s, 1H, = CH - Ph).
6-methyl-3-(4-methoxybenzylidene)chroman-4-one (3f):
IR (KBr): 1667 cm-1(C=O).
-
1H-NMR (CDCl3):  2.34 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 5.35 (d, J = 1.8 Hz, 2H, -O-CH2
), 6.87 (d, J = 8.4 Hz, 1H, H-8), 6.8 – 7.59 (m, 5H, H-7, H-2, H-3, H-5,H-6), 7.74 (d, 1H,
H-5, J = 1.8 Hz), 7.85 (s, 1H = CH-).
6-bromo-3-benzylidenechroman-4-one (3g):
IR (KBr): 1670 cm-1(C=O).
1H-NMR (CDCl3):  5.35 (d, J = 1.84 Hz, 2H, -OCH2-), 6.88 (d, J = 8.8 Hz, 1H, H-8), 7.26-
7.32 (m, 3H, H-3, H-4, H-5), 7.44-7.46 (m, 2H, H-2, H-6), 7.55-7.58 (dd, J = 2.52 Hz, &
8.76 Hz, 1H, H-7), 7.89 (s, 1H, = CH-), 8.13 (s, 1H, H-5).
6-bromo-3-(4-methoxybenzylidene)chroman-4-one (3h):
IR (KBr): 1670 cm-1(C=O).
1H-NMR (CDCl3):  3.86 (s, 3H, OCH3), 5.37 (d, J = 1.8 Hz, 2H, -OCH2-), 6.87 (d, J = 8.8
Hz, 1H, H-8), 6.96-6.98 (m, 2H, H-3, H-5), 7.26-7.29 (m, 2H, H-2, H-6), 7.53 (dd, J =
2.56 & 8.8 Hz, 1H, H-7), 7.84 (s, 1H, = CH-), 8.11 (d, J = 2.52 Hz, 1H, H-5).

1254 Suresh Kumar
6-bromo-3-(3-methoxybenzylidene)chroman-4-one (3i):
IR (KBr): 1669 cm-1(C=O).
1H-NMR (CDCl3):  3.84 (s, 3H, OCH3), 5.35 (d, J = 1.84 Hz, 2H, -OCH2-), 6.82-6.98 (m,
4H, H-8, H-2, H-4, H-5), 7.37 (t, 1H, H-6), 7.57 (dd, J = 2.52 & 8.76 Hz, 1H, H-7), 7.85
(s, 1H, = CH-), 8.13 (d, J = 2.51 Hz, 1H, H-5).
6-bromo-3-(4-methylbenzylidene)chroman-4-one (3j):
IR (KBr): 1670 cm-1(C=O).
1H-NMR (CDCl3):  2.41 (s, 3H, CH3), 5.36 (d, J = 1.88 Hz, 2H, -OCH2-), 6.87 (d, J = 8.76
Hz, 1H, H-8), 7.21 (d, J = 8.16 Hz, 2H, H-3, H-5), 7.25-7.27 (m, 2H, H-2, H-6), 7.55 (dd,
J = 2.52 & 8.8 Hz, 1H, H-7), 7.86 (s, 1H, = CH-), 8.12 (d, J =2.56 Hz, 1H, H-5).
6-bromo-(2,4-dimethoxy benzylidene)chroman-4-one (3k):
IR (KBr): 1668 cm-1(C=O).
1H-NMR (CDCl3):  3.85 (s, 6H, 2  OCH3), 5.25 (d, J = 1.72 Hz, 2H, -OCH2-), 6.49-6.54
(m, 2H, H-3, H-5), 6.85 (d, J = 8.8 Hz, 1H, H-8), 6.98 (d, J = 8.4 Hz, 1H, H-6), 7.53 (dd, J
= 2.56 & 8.76 Hz, 1H, H-7), 8.01 (s, 1H, = CH-), 8.12 (d, J = 2.52 Hz, 1H, H-5).
Results and Discussions
In an attempt to develop solvent free, green synthesis of 3-arylidenechroman-4-ones, a
mixture of chroman-4-one, benzaldehyde and anhydrous barium hydroxide in a mortar was
ground well with pestle for 5 minutes. Colour of the reaction mixture turned to yellow,
indicating about the progress of reaction and was confirmed by TLC (Figure 1), when a new
product was found to have formed. For the completion of the reaction, reaction mixture was
left at room temperature and chroman-4-one was found to have reacted completely after 5
minutes. Reaction mixture on acidification in ice cold water gave a single solid product
which was identified as E-3-benzylidenechroman-4-one from its spectral data and melting
point comparison with literature value. Following this procedure differently substituted 3-
arylidenechroman-4-ones were obtained by reacting variously substituted chroman-4-ones
with aromatic aldehydes (Table 1).
Figure 1. Photographs of the reaction mixture in mortar showing color transition taking
place during reaction indicating the progress of reaction.

A Facile Solvent Free Synthesis of 3-arylidenechroman-4-ones 1255
The methods, reported so far make use of organic solvents either during
condensation reactions or during extraction processes. Some methods though are simple but
due to the prolonged refluxing are not widely accepted 14. In case of piperidine, 3-
arylidenechroman-4-ones formed initially undergo exo-endo double bond migration to give
a mixture of isomeric products 10. Here in this case, the reactions take place at room
temperature with enhanced rate and good selectivity. Use of toxic organic solvent was totly
eliminated as no extraction was required to obtain the product.
Chroman-4-ones required for the reaction has been obtained by a modified route involving
the polyphosphoric acid (PPA) catalysed cyclisation of phenoxypropanoic acid using
microwave irradiations.
Table 1. Physical data of the compounds synthesized.
Time
m.p.,0C
[Lit.]
%
Compounds
R
R1
R2
R3
[min]
(x+ y)a
-
yield
2a
2b
2c
3a
3b
3c
3d
3e
3f
H
CH3
Br
-
-
-
-
-
38-40 (38.5)20
35-36(35-36) 21
78-79 (77-79) 22
111-112 (112) 20
130-132 (133-134)23
103-104 (103-104)24
146-147 (147-148)25
126-28
78
75
77
89
87
85
87
83
88
92
91
88
86
89
-
-
-
-
-
-
H
H
H
H
5 + 5
5 + 5
5 + 10
5 + 10
5 + 10
5 + 10
5 + 10
5 + 10
5 + 10
5 + 10
5 + 15
H
H
H
OCH3
H
H
H
OCH3
H
CH3
CH3
CH3
Br
H
H
H
H
CH3
OCH3
H
H
H
108-10
3g
3h
3i
H
H
158-60
Br
H
H
OCH3
H
166-67
Br
H
OCH3
H
112-13
3j
Br
H
CH3
OCH3
156-58
3k
Br
OCH3
H
168-69
a x- Grinding time, y- time for which reaction mixture was kept at room temperature.
Conclusion
This appears to be a simple and highly efficient procedure for the synthesis of 3-
arylidenechroman-4-ones as it requires much shorter time for the completion of the reaction
and yields of the products are high. More over it is simple and eco-friendly protocol as it
avoids the use of solvent at any stage of reaction or isolation process.
Acknowledgements
The authors are grateful to CSIR (New Delhi) for providing financial support.

1256 Suresh Kumar
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