Synthesis and spectral characterization of some new 4-(2,6-Diarylpyridin-4- yl)- 2H -chromen-2-ones

Article abstract of DOI:10.1080/00397911.2013.864772

Some new 4-(2,6-diarylpyridin-4-yl)-2H-chromen-2-one derivatives 5a-l have been synthesized by reacting 4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-ones 3a-c with appropriate 1-(2-oxo-2-arylethyl)pyridinium bromide salt 4a-d in the presence of ammonium aceta

Full text of DOI:10.1080/00397911.2013.864772

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Synthesis and Spectral Characterization
of Some New 4-(2,6-Diarylpyridin-4-
yl)-2H-chromen-2-ones
Anil K. Patel a , Niraj H. Patel a , Mehul A. Patel a , Chirag V. Patel a
& Dinker I. Brahmbhatt a
a Department of Chemistry , Sardar Patel University , Gujarat , India
Accepted author version posted online: 04 Apr 2014.Published
online: 29 May 2014.
To cite this article: Anil K. Patel , Niraj H. Patel , Mehul A. Patel , Chirag V. Patel & Dinker I.
Brahmbhatt (2014) Synthesis and Spectral Characterization of Some New 4-(2,6-Diarylpyridin-4-yl)-2H-
chromen-2-ones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 44:13, 1881-1887, DOI: 10.1080/00397911.2013.864772
To link to this article: http://dx.doi.org/10.1080/00397911.2013.864772
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Synthetic Communications1, 44: 1881–1887, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.864772
SYNTHESIS AND SPECTRAL CHARACTERIZATION OF
SOME NEW 4-(2,6-DIARYLPYRIDIN-4-YL)-2H-
CHROMEN-2-ONES
Anil K. Patel, Niraj H. Patel, Mehul A. Patel, Chirag V. Patel,
and Dinker I. Brahmbhatt
Department of Chemistry, Sardar Patel University, Gujarat, India
GRAPHICAL ABSTRACT
Abstract Some new 4-(2,6-diarylpyridin-4-yl)-2H-chromen-2-one derivatives 5a–l have
been synthesized by reacting 4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-ones 3a–c with
appropriate 1-(2-oxo-2-arylethyl)pyridinium bromide salt 4a–d in the presence of
ammonium acetate in refluxing glacial acetic acid. The newly synthesized compounds have
been characterized by elemental and spectral analysis.
Keywords 2H-Chromen-2-ones; coumarins; Krohnke’s reaction; pyridyl coumarins;
Wittig reactions
INTRODUCTION
2H-Chromen-2-ones (coumarins) are present in significant amounts in natural
products. Many natural and synthetic chromenones have attracted considerable
interest because of their numerous biological activities, namely anticoagulant,[1]
antimicrobial,[2] antibacterial,[3] anticancer,[4] and anti-HIV activity.[5] The interest-
ing biological activities of the chromenones make them attractive targets in organic
synthesis.
The incorporation of the heterocyclic ring onto the chromenone nucleus can
bring about an extensive modification in the biological activities of the parent com-
pound as well as make them valuable targets in organic synthesis. A large number of
chromenones that have heterocyclic moieties such as benzimidazole, triazole,
diazole, diazine, and thiadiazole as substituent groups either in the lactone ring
Received September 1, 2013.
Address correspondence to Dinker I. Brahmbhatt, Department of Chemistry, Sardar Patel
University, Vallabh Vidyanagar 388 120, Gujarat, India. E-mail: drdib317@gmail.com
Color versions of one or more of the figures in the article can be found online at www.tandfonline.
com/lsyc.
1881

1882
A. K. PATEL ET AL.
or in the benzene ring of chromenone are used as dyes or whitening agents.[6]
Chromenones having nuclei with pyridine, indole, triazole, and oxazine as substitu-
ent groups possess a variety of biological activities.[7]
Among the heterocyclic substituted chromenones, pyridyl chromenones have a
special importance because of their diverse physiological actions. A number of chro-
menone derivatives having pyridine substitution mainly at 3- or 4-positions possess
varied activity such as CNS depressant,[8] antifungal,[8] bactericidal,[9] analgesic,[10]
anti-inflammatory,[11] and moth-proofing activities.[12] The literature survey reveals
that the methods used for the synthesis of 3- or 4- pyridine-substituted chromenones
mainly involve Perkin or modified Perkin,[8,12,13] Knoevenagel,[8] and Pechmann
reactions.[8] However, these methods incorporate pyridine rings in chromenones at
3- or 4-positions; they do not provide further substitution in the pyridine ring. To
overcome this problem, we had developed a new method for synthesizing pyridyl-
substituted chromenones in such a way that it provided further substitution in the
pyridine ring, and the method was able to build up the pyridine nucleus not only
at 3- or 4-positions of chromenone but at any suitable positions in chromenones.
The method was based on Krohnke’s synthesis and a variety of chromenone deriva-
tives having pyridine or modified pyridine substitutions at 3-, 6-, and 8-positions
were synthesized from our laboratory.[14] In continuation of our work on synthesiz-
ing newer pyridyl-substituted chromenones, herein we report the synthesis of various
chromenone derivatives having pyridine substitution at the 4-position.
In the present work the synthesis of various 4-(2,6-diarylpyridin-4-yl)-2H-
chromen-2-ones 5a–l have been carried out by reacting 4-(3-oxo-3-aryl-prop-
1-enyl)-2H-chromen-2-ones 3a–c with appropriate 1-(2-oxo-2-arylethyl)pyridinium
bromide salt 4a–d under Krohnke’s reaction condition. The newly synthesized com-
pounds were characterized by elemental and spectral analysis.
RESULTS AND DISCUSSION
The synthetic routes adopted to obtain the title compounds 4-(2,6-diarylpyridin-
4-yl)-2H-chromen-2-ones 5a–l are shown in Scheme 1. The required intermediates
4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-ones 3a–c were prepared by Wittig
reaction in which 7-methoxy-4-formyl-2H-chromen-2-one 1 was reacted with appropriate
triphenylphosphine aroyl methylenes 2a–c in refluxing tetrahydrofuran (THF). The
intermediates 3a–c were obtained in excellent yield and were fully characterized by
analytical and spectral data. The intermediates 4-(3-oxo-3-arylprop-1-enyl)-2H-
chromen-2-ones 3a–c were then further reacted with appropriate aroyl methyl
pyridinium salts 4a–d in the presence of ammonium acetate and acetic acid to give
the title compounds 4-(2,6-diarylpyridin-4-yl)-2H-chromen-2-ones 5a–l. The reaction
proceeded smoothly and the compounds 5a–l were obtained in moderate to good
yields (Table 1).
The formation of compounds 5a–l involves Kro¨hnke’s reaction mechanism,[15]
in which Michael addition of aroyl methyl pyridinium salts 4a–d to 4-(3-oxo-
3-arylprop-1-enyl)-2H-chromen-2-ones 3a–c give rise to 1,5-dionyl intermediate,
which in situ gets cyclized into 4-(2,6-diarylpyridin-4-yl)-7-methoxy-2H-chromen-2-
ones 5a–l in the presence of ammonium acetate and acetic acid (Scheme 2).

SYNTHESIS OF 4-PYRIDYL-2H-CHROMEN-2-ONES
1883
Scheme 1. Reagents and conditions: (a) THF, reflux, 8 h; (b) NH4OAc, AcOH, reflux, 8 h.
Table 1. Physical data (mp and yield) of synthesized compounds 5a–l
Compound
R
R1
Mp (ꢁC)
Yield (%)
5a
5b
5c
5d
5e
5f
H
CH3
OCH3
H
H
H
235
68
67
70
66
71
69
72
70
71
68
70
68
200–201
168–169
200–201
201–202
202
H
CH3
CH3
CH3
OCH3
OCH3
OCH3
Br
CH3
OCH3
H
5g
5h
5i
168–169
202
CH3
OCH3
H
166–167
197–198
239–240
196–198
5j
5k
5l
CH3
OCH3
Br
Br
The structures of all the synthesized compounds 5a–l were established on the basis of
analytical and spectral data.
In infrared (IR) spectra, compounds 5a–l showed a strong band between 1725
and 1718 cmꢀ1 for d-lactone carbonyl (C O) stretching vibrations. The strong bands
=
=
=
for aromatic C C and C N stretching vibrations were observed between 1615 and
1610 and between 1560 and 1544 cmꢀ1 respectively. The aromatic C-H stretching
vibrations were observed between 3015 and 3000 cmꢀ1 in the form of a medium band.
1
In the H NMR spectra of compounds 5a–l, the aromatic protons signals
except C6-H and C8-H were observed as a multiplet in the region d 7.06–8.22. In
all the compounds the signal for C6-H was observed as an ortho and meta coupled
doublet of a doublet in the region d 6.84–6.87 whereas the C8-H signal was observed
as a meta coupled doublet in the region d 6.95–6.96. In all the compounds the C3-H
signal appeared as a singlet in the region d 6.34–6.36.
The 13C NMR spectra of compound 5a–l showed expected signals for nonequi-
valent carbons present in the compounds. The most downfield signal appeared in the

1884
A. K. PATEL ET AL.
Scheme 2. Plausible mechanism for the formation of compounds 5a–l.
range of d 163.2–163.4 and can be assigned to the carbonyl carbon of the d-lactone
ring of chromenone. The differentiations of quaternary and tertiary carbons were
done by the help of DEPT-90 spectra.
The mass spectrum of selected compound 5a showed Mþ peak at m=z 405
(100%) along with other fragment peaks. The appearance of molecular ion peak at
405 mass unit supports the structure of compound 5a. An analytical and spectral
data of all compounds 5a–l are in full agreement with the proposed structures.
EXPERIMENTAL
All the melting points reported are uncorrected. All the IR spectra (KBr disc)
were recorded on a Shimadzu FT-IR 8400-S spectrometer. 1H NMR and 13C
NMR spectra were recorded on a Bruker Avance 400 spectrometer operating at
400 MHz for 1H NMR and 100 MHz for 13C NMR. The chemical shift (d) is
reported in parts per million (ppm) using chloroform-d as a solvent and calibrated
standard solvent signal. Elemental analysis was carried out with a Hareaus CHNO
analyzer. Mass spectrum of compound 5a was recorded on Shimadzu QP 2010
spectrometer. All solvents and reagent were obtained from commercial sources
and used without any additional purification. Thin-layer chromatography (TLC)
was performed on precoated silica gel on aluminium sheets (Kieselgel 60, F254
Merck). TLC plates were visualized with ultraviolet (UV) light (254 nm) and=or in
,
an iodine chamber.

SYNTHESIS OF 4-PYRIDYL-2H-CHROMEN-2-ONES
1885
The required starting materials 7-methoxy-2-oxo-2H-chromene-4-carbaldehyde
1,[16] triphenyl phosphine aroyl methylenes 2a–c,[17] and aryl methyl pyridinium
salts 4a–d[18] were prepared according to literature procedures.
7-Methoxy-4-(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-one (3a–c):
General Procedure
A mixture of appropriate triphenyl phosphine aroyl methylenes 2a–c (10 mmol)
and 7-methoxy-2-oxo-2H-chromene-4-carbaldehyde 1 (10 mmol) in tetrahydrofuran
(THF, 50 ml) was heated to reflux for 8 h and then allowed to cool down to ambient
temperature. The excess THF was removed by distillation under reduced pressure
and the reaction mixture was quenched in cold water (100 ml). The resulting
crude yellow solid was filtered out, washed with water, and dried. The crude product
was subjected to column chromatography using silica gel (60–120 mesh) and
chloroform–petroleum ether (60–80) (6:4) as an eluent to give light yellow product
3a–c in 84–87% yield.
7-Methoxy-4-(3-oxo-3-phenylprop-1-enyl)-2H-chromen-2-one (3a)
Yield: 2.60 g (85%). Mp 168–169 ꢁC. IR: 3060, 1713, 1663, 1613, 745, 695 cmꢀ1
.
1H NMR (400 MHz, CDCl3): d 3.91 (s, 3H, OCH3), 6.53 (s, 1H, C3-H), 6.89–6.94 (m,
=
2H, C6-H and C8-H), 7.54–7.69 (m, 5H, Ar-H, C5-H and a-H of -CO-CH CH-),
8.01–8.07 (m, 3H, Ar-H and b-H of –CO-CH CH-). 13C NMR (100 MHz, CDCl3):
=
d 55.9 (OCH3), 101.4 (CH), 109.9 (CH), 111.6 (C), 112.7 (CH), 125.7 (CH), 128.7
(CH), 129.0 (CH), 129.7 (CH), 133.8 (CH), 136.5 (CH), 137.0 (C), 148.8 (C), 155.7
(C), 161.0 (C), 163.2 (C), 188.9 (C). Anal. calcd. for C19H14O4: C, 74.50; H, 4.61%.
Found: C, 74.41; H, 4.69%.
General Procedure for the Synthesis of 4-(2,6-Diaryllpyridin-4-yl)-
7-methoxy-2H-chromen-2-ones (5a–l)
Ammonium acetate (30 mmol) and a solution of appropriate 7-methoxy-4-
(3-oxo-3-arylprop-1-enyl)-2H-chromen-2-one 3a–c (3 mmol) in acetic acid (15 ml)
were added to a solution of the appropriate aroyl methyl pyridinium salt 4a–d
(3 mmol) in acetic acid (15 ml), at room temperature, and the reaction mixture was stir-
red for 30 min. Then the reaction mixture was refluxed for 8 h, allowed to cool to room
temperature, and poured into ice-cold water (75 ml). The resultant crude solid material
was extracted with chloroform (3 ꢂ 30 ml). The combined chloroform extract was
washed with 5% sodium bicarbonate solution (3 ꢂ 20 ml) and brine (2 ꢂ 20 ml) and
dried over anhydrous sodium sulfate. The removal of chloroform under reduced press-
ure gave the crude product, which was further purified by column chromatography
using silica gel (60–120 mesh) and ethyl acetate–petroleum ether (60–80) (3:7) as an
eluent. The compounds were recrystallized from chloroform–hexane.
4-(2,6-Diphenylpyridin-4-yl)-7-methoxy-2H-chromen-2-one (5a)
Yield: 0.827 g (68%). Mp 235 ꢁC. IR: 3003, 1718, 1613, 1544, 782, 703 cmꢀ1. 1H
NMR (400 MHz, CDCl3): d 3.92 (s, 3H, OCH3), 6.37 (s, 1H, C3-H), 6.85 (dd, J ¼ 8.8

1886
A. K. PATEL ET AL.
and 2.4 Hz, 1H, C6-H), 6.96 (d, J ¼ 2.4 Hz, 1H, C8-H), 7.40 (d, J ¼ 8.8 Hz, 1H, C5-H),
0
0
7.48–7.57 (m, 6H, Ar-H), 7.75 (s, 2H, C3 -H and C5 -H of pyridine ring), 8.20–8.22
(m, 4H, Ar-H). 13C NMR (100 MHz, CDCl3): d 55.9 (OCH3), 101.5 (CH), 111.8 (C),
112.2 (CH), 112.7 (CH), 117.7 (CH), 127.2 (CH), 127.5 (CH), 128.9 (CH), 129.7
(CH), 138.6 (C), 145.1 (C), 153.7 (C), 156.2 (C), 157.7 (C), 160.6 (C), 163.3 (C). Anal.
calcd. for C27H19NO3: C, 79.98; H, 4.72; N, 3.45%. Found: C, 79.87; H, 4.81; N,
3.54%. MS: m=z 405 (Mþ).
CONCLUSION
In conclusion, we have synthesized some new 4,4-pyridyl substituted chrome-
none derivatives using Krohnke’s reaction. The methodology used in the present
synthesis requires easily available starting materials and gives the products with good
yields.
SUPPORTING INFORMATION
Spectral and analytical data of synthesized compounds along with copies of
1H NMR and 13C NMR spectra of compound 3a–c and 5a–l can be accessed on the
publisher’s website.
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SYNTHESIS OF 4-PYRIDYL-2H-CHROMEN-2-ONES
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