Synthesis of two novel flavonoid derivatives with extended φ-system: Possible UV-B and UV-A sunscreens

Article abstract of DOI:10.14233/ajchem.2017.20430

Two novel flavonoid derivatives 5 and 6 were synthesized and characterized by IR, ¹H, ¹³C NMR spectroscopy and mass spectrometry. The core structure of the two flavonoids was constructed by applying Baker-Venkataraman rearrangement on 2-Acylphenyl ester intermediate. The two compounds exhibited remarkable UV-visible absorption activities compared to flavone. Flavonoid 5 showed a bathochromic shift of 75.6 nm when the size of the cinnamic acid was increased by phenylbutadienyl group and hence it is a good UVA sunscreen. The 4-nitrostyryl group introduced in the cinnamic acid subchromophore of flavonoid 6 causes the compound to absorb at 308.3 and at 345.8 nm which will make it a broad-spectrum sunscreen.

Full text of DOI:10.14233/ajchem.2017.20430

Asian Journal of Chemistry; Vol. 29, No. 5 (2017), 1103-1107
ASIAN JOURNAL OF CHEMISTRY
https://doi.org/10.14233/ajchem.2017.20430
Synthesis of Two Novel Flavonoid Derivatives with Extended
π-System: Possible UV-B and UV-A Sunscreens
*
SALEH N. AL-BUSAFI , ASMA M. AL-BURAIKI and MONTHER H. AL-QARNI
Department of Chemistry, College of Science, Sultan Qaboos University, Box 36, Al-Khodh 123, Sultanate of Oman
*Corresponding author: Fax: +968 24141469; Tel: +968 24142305; E-mail: saleh1@squ.edu.om
Received: 30 November 2016;
Accepted: 2 February 2017;
Published online: 10 March 2017;
AJC-18308
Two novel flavonoid derivatives 5 and 6 were synthesized and characterized by IR, 1H, 13C NMR spectroscopy and mass spectrometry.
The core structure of the two flavonoids was constructed by applying Baker-Venkataraman rearrangement on 2-acylphenyl ester intermediate.
The two compounds exhibited remarkable UV-visible absorption activities compared to flavone. Flavonoid 5 showed a bathochromic
shift of 75.6 nm when the size of the cinnamic acid was increased by phenylbutadienyl group and hence it is a good UVA sunscreen. The
4-nitrostyryl group introduced in the cinnamic acid subchromophore of flavonoid 6 causes the compound to absorb at 308.3 and at 345.8
nm which will make it a broad-spectrum sunscreen.
Keywords: Flavonoids, Baker-Venkataraman rearrangement, UV-visible absorption, Sunscreens, Bathochromic shit.
Given the adverse effect of UVR on the skin, several
physical and chemical sunscreens have been developed and
used to provide effective photoprotection against harmful UV
radiation [12]. The principle of photoprotection in physical
sunscreens such as titanium dioxide (TiO2) is based on reflec-
tion of UVA and UVB rays away from the skin [13]. Chemical
sunscreens, on the other hand, are organic aromatic compounds
conjugated with carbonyl group capable of absorbing UVA
and UVB radiations and hence protecting the skin from their
harmful effects [14]. One of the earliest organic sunscreen
developed was p-aminobenzoic acid. This synthetic sunscreen
was found to cause photocontact allergies and degrades
under sunlight into carcinogenic nitrosamine product [15].
Many other commercial synthetic organic compounds such
as oxybenzone, octocrylene and avobenzone found their way
into the market and became widely used as body sunscreens
[16-18]. Unlike their physical counterparts, chemical sunscreens
are invisible on the skin surface and therefore they are more
commercially desired. However, several reports in the literature
have shown that synthetic organic sunscreens, in general, cause
skin irritation and phototoxic reactions. Moreover, under
extensive UV irradiation, organic sunscreens tend to degrade
into toxic radical species that can interact with biological
molecules [19].
INTRODUCTION
Ultraviolet radiation (UVR) reaching the earth surface
composed of about 95 % of UVA (aging rays, 320-400 nm)
and 5 % of UVB (burning rays, 290-320 nm) [1]. This UV
radiation causes a wide range of chronic types of skin damage
such as sunburn, wrinkling, immunosuppression and photo-
carcinogenesis [2]. The shortest wavelength radiation, UVC
(200-290 nm), is far more harmful to the skin than UVA and
UVB, but fortunately, it is completely absorbed by ozone and
molecular oxygen in the earth’s atmosphere [3]. Prolong UVA
exposure can cause significant damage in areas of the dermis
layer and cause early aging, sagging and dry appearance of
the skin [4]. Furthermore, chronic UVA exposure produces
chemical alteration of DNA which leads to development of
skin cancer [5]. It has been documented that about 67 % of
malignant melanoma is attributed to UVA radiation [6,7]. UVA
radiation triggers the release of melanin dye in the epidermis
layer which causes the darkening of the skin [7]. Exposure to
UVB radiation causes oxidative damage to the epidermal layer
which leads to reddening and sunburn of the skin [8]. UVB
radiation can harm the skin directly by inducing inflammation
and proliferation or indirectly by depleting the antioxidants
in the skin and producing reactive oxygen species (ROS)
[9,10]. The most common type of human skin cancer, non-
melanoma cancer (NMSC), is attributed to prolong exposure
to UVB rays [11].
New trend has emerged of using naturally occurring
substances to protect against UV radiation. Several natural
compounds such as sulforaphane, ascorbic acid, β-carotene

1104 Al-Busafi et al.
Asian J. Chem.
and resveratrol have demonstrated their UV-shielding pro-
perties [20]. Curcumin, a yellow spice collected from Curcuma
longa has been shown to provide effective photoprotection
against UVB radiation [21]. Flavonoids are a class of secondary
plant metabolites distributed widely in the leaves, seeds, bark
and flowers [22]. They are responsible for the wonderful
colours of flowers and provide protection for the plants against
harmful UV radiation [23]. Flavonoids exhibit a wide range
of pharmaceutical application such as antioxidant, anti-
inflammatory, antitumor and cardioprotective properties [24-
27]. Due to their highly conjugated aromatic structure, many
flavonoids have been utilized to protect against UV radiation
[28]. For instance, flavone showed an efficient pro-tection for
zebrafish from UV induced damage [29]. Quercitrin, a
common flavonoid in nature, functions as an antioxidant
against UVB irradiation-induced oxidative damage to skin
[30]. Flavonoids naringenin and rutin prevented the accumu-
lation of DNA damage after irradiated with UVB light [31].
The basic structure of flavonoids can be viewed as a combi-
nation of two main fragments: the benzoyl sub-chromophore
and the cinnamic acid sub-chromophore (Fig. 1). The
absorption behaviour of flavonoids can be tuned according to
particular needs by adjusting the substitution pattern on these
two subchromofores. In this regard, when the cinnamic acid
fragment in flavone 1 was extended by inserting a vinyl group,
the absorption maximum has shifted from 289 to 330 nm in
flavonoid 2 [32]. Such bathochromic shift makes flavonoid 2
a UVA sunscreen and hence can be used to protect against
photoaging. In addition, when hydroxyl group (an electron-
releasing) attached to the benzoyl subchromophore of flavone
1 a hypsochromic shift was observed from 289 to 265 nm in
flavonoid 3 which will make it a good UVC sunscreen (Fig.
1) [33].
fragments with p-nitrostyryl group in compound 5 and with
1-phenylbutadienyl group in compound 6 (Fig. 2) and to study
their UV absorption activities.
O
O
4
λ
max=320 nm , (UVA sunscreen)
O
NO2
O
5
O
O
6
Fig. 2. UV absorption of flavonoid 4 and proposed flavonoid derivatives 5
and 6
EXPERIMENTAL
O
All the reagents and solvents used in this study were
obtained from Sigma-Aldrich Chemical Company (USA) and
used without further purification. Melting points were deter-
mined using GallenKamp-MPA350 melting point apparatus
(UK). Column chromatography was performed using Merck
silica gel 60 (40-63 µm). IR spectra were determined on a
Perkin-Elmer FTIR-881 spectrometer (Perkin Elmer, USA)
using KBr pellets.
Proton magnetic resonance (1H NMR) spectra were recor-
ded using 400 or 700 MHz Bruker spectrometer (Bruker Corp.,
UK). Carbon Magnetic Resonance (13C NMR) spectra were
recorded at 100.4 or 176 MHz Bruker spectrometer (Bruker
Corp., UK). Chemical shifts (δc) are quoted in parts per million
(ppm) to the nearest 0.1 and 0.01 and are referenced to the
solvent peaks (CDCl3/DMSO-d6). The NMR data have been
processed using Topspin 3.2 software program.
benzoyl
subchromophore
cinnamic acid
subchromophore
O
O
O
O
O
O
OH
O
2
1
3
max=265 nm, (UVC sunscreen)
λ
max=330 nm, (UVA sunscreen)
λ
Fig. 1. Structure of flavonoids and UV absorptions of flavonoids derivative
2 and 3
We have reported the synthesis of a novel flavonoid
derivative 4 with extended π-system in the cinnamic acid sub-
chromophore through the addition of a styryl group [34].
Flavonoid 4 showed a bathochromic shift from 294 to 320 nm
compared to flavonoid 1. This shift in the absorption maxima
causes compound 4 to absorb at the borderline between UVB
and UVA light regions. In continuation of our effort to explore
the relationship between the structure of flavonoids and their
UV absorption aptitudes we report herein the synthesis of two
novel flavonoids 5 and 6 by extending the cinnamic acid
Mass spectra were obtained using Quattro Ultima Pt
tandem quadruple mass spectrometer (Waters Corp. MA, USA)
instrument. High resolution mass spectra were obtained using
Waters LCT Premier XE Mass Spectrometer instrument
(determined at the University of Sheffield, UK). UV study
was performed on a Shimadzu UV-visible spectrophotometer
(multispec-1501, Shimadzu, Japan).

Vol. 29, No. 5 (2017)
Synthesis of Two Novel Flavonoid Derivatives with Extended π-System 1105
Ultraviolet-visible absorption study: A series of stock
solutions were prepared by dissolving 1 mg of each flavone
derivative (flavonoids 1, 4, 5 and 6) in 10 mL acetonitrile.
From each of the stock solutions, series of diluted solutions
were formed by taking 0.3 mL of each stock solution and
diluted by acetonitrile to 10 mL. UV-visible measurements
were taken against acetonitrile as blank.
NMR (100.6 MHz, CDCl3): δ (ppm): 30.12, 124.30, 126.55
(2C), 126.84, 127.04, 128.04, 128.48 (2C), 129.09, 129.16,
129.87, 130.66 (2C), 131.17 (2C),131.78,132.78, 133.80,
135.37, 137.37, 143.27, 149.85, 165.30, 198.04. ESI-MS (M+)
calcd. for C25H20O3: 368.14, found: 368.02.
Synthesis of flavonoid derivative (5): To a solution of
E,E-2-acetylphenyl-4-(4-phenylbuta-1,3-dienyl)benzoate (12)
(0.90 g, 2.44 mmol) in pyridine (2.8 mL) at 50 °C was added
potassium hydroxide (0. 21 g, mmol) and the mixture was
stirred for 15 min. Acetic acid solution (10 %, 4.3 mL) was
added to the cooled mixture and the solid intermediate was
collected by filtration. To a solution of the solid intermediate
in acetic acid (15 mL) was added concentrated sulfuric
acid (0.1 mL) and the mixture was refluxed for 1 h. The cooled
mixture was poured into ice and the product was collected by
suction filtration and washed with water. The product was
recrystallized from ethanol to yield flavonoid derivative 5 as
bright yellow crystals (0.46 g, 53.7 %). m.p.: 170-172 °C; IR
(KBr, νmax, cm–1): 3062, 1641, 1642, 1597, 1506; λmax, (nm)
(log ε) 289.6 (4.29), 364.6 (4.77); 1H NMR (400 MHz, CDCl3):
δ (ppm): 6.69 (1H, d, J = 15.3 Hz), 6.75 (1H, d, J = 15.3 Hz),
6.84 (1H, s), 6.97 (1H, dd, J = 10.6, J = 15.3 Hz), 7.08 (1H,
dd, J = 10.6, J = 15.3 Hz), 7.29 (1H, m), 7.35 (1H, m), 7.43
(2H, m), 7.46 (2H, m), 7.56 (2H, d, J = 8.3 Hz), 7.68 (1H, m),
7.71 (1H, m), 7.89 (2H, d, J = 8.3 Hz), 8.23 (1H, dd, J = 1.4,
J = 7.9 Hz); 13C NMR (100.6 MHz, CDCl3): δ (ppm): 107.56,
118.48, 124.40, 125.69, 125.63, 126.12, 127.00 (2C), 127.02
(2C), 127.22 (2C), 128.42 (2C), 129.15, 130.69, 131.51,
131.74, 132.04, 135.02, 137.41, 141.18, 156.63, 163.46, 178.9.
ESI-MS (M+ + 1) calcd. for C25H18O2: 351.13, found: 351.06.
Synthesis of E-4-(p-nitrostyryl)benzoic acid (11): 4-
Carboxybenzyltriphenylphosphonium bromide (9.0 g, 18.8
mmol) was suspended in dichloromethane (50 mL) in an
Erlenmeyer flask. 75 mL of aqueous solution of sodium
hydroxide (50 g) and 4-nitrobenzaldehyde (2.9 g, 18.8 mmol)
were added to the reaction mixture. The neck of the flask was
plugged with cotton wool and the yellow mixture stirred for
1 h. The reaction mixture was acidified to pH 1 using 1 M H2SO4.
The organic layer was separated and the aqueous layer was
extracted with (3 × 50 mL) dichloromethane. The combined
organic layer was dried over MgSO4, filtered and concentrated
under reduced pressure. The crude solid was recrystallized
from ethanol to yield bright yellow solid (3.11 g, 61.7 %).
m.p.: 120.2-125.4 C; IR (KBr, νmax, cm1): 3200-2400, 3061,
Synthesis of E,E-4-(4-phenylbuta-1,3-dienyl)benzoic
acid (10): 4-Carboxybenzyltriphenylphosphonium bromide
(18.06 g, 0.0378 mol) was suspended in dichloromethane
(100 mL) in an Erlenmeyer flask. 75 mL of aqueous solution
of sodium hydroxide (50 g) and trans-cinnamaldehyde (5 g,
0.0378 mol) were added to the reaction mixture. The neck of
the flask was plugged with cotton wool and the yellow mixture
stirred for 0.5 h. The organic layer was separated and the
aqueous layer was extracted with (2 × 20 mL) dichloromethane.
The combined organic layer was dried over MgSO4, filtered
and concentrated under reduced pressure. Petroleum ether (50
mL) and few crystals of iodine were added to the residue and
the mixture was refluxed for 3 h. The reaction mixture was
washed with 25 % sodium metabisulfite and the organic layer
was dried over MgSO4 and concentrated under reduced pressure
to give a yellow solid. The solid was recrystallized from ethanol
to yield yellow needles (6.15 g. 65 %). m.p.: 152.2-153.5 °C;
IR (KBr, νmax, cm–1): 3500-2496, 3051, 1670, 1608, 1556. 1H
NMR (400 MHz,CDCl3): δ (ppm) 6.81 (d, 1H, J = 10.5 Hz),
6.83 (d, 1H, J = 10.5 Hz), 7.12 (dd, 1H, J = 10.5, J = 15.4 Hz)
7.25 (dd, 1H, J = 10.4, 15.4 Hz), 7.28 (m, 2H), 7.36 (m, 1H),
7.55 (m, 2H), 7.61 (d, 2H, J = 8.3 Hz), 7.93 (d, 2H, J = 8.3
Hz); 13C NMR (100.4 MHz, CDCl3): δ (ppm) 127.10 (2C),
128.59, 129.36 (2C), 129.54, 129.54, 130.38, 130.39, 132.14
(2C), 132.49 (2C), 134.71, 137.27, 168.08. ESI-MS (M+) calcd.
for C17H14O2: 250.29, found: 250.55.
Synthesis of E,E-4-(4-phenylbuta-1,3-dienyl)benzoyl
chloride:A mixture of E,E-4-(4-phenylbuta-1,3-dienyl)benzoic
acid (10) (3.00 g, 11.99 mmol) and thionyl chloride (2.4 mL,
32.61 mmol) was heated under reflux for 1 h. Excess thionyl
chloride was removed under reduced pressure and the crude
solid was used for the next step.
Synthesis of E,E-2-acetylphenyl 4-(4-phenylbuta-1,3-
dienyl)benzoate (12): To a solution of 2-hydroxyacetophenone
(1.63 g, 11.99 mmol) in pyridine (2.3 mL) was added E,E-4-
(4-phenylbuta-1,3-dienyl)benzoyl chloride (3.22 g, 11.99
mmol). The reaction mixture was stirred briefly at room tempe-
rature. After cooling, the reaction mixture was poured into a
mixture of 60 mL HCl (3 %) and 30 g crushed ice. The product
was extracted with chloroform (3 × 10 mL) and the combined
organic layer was dried over MgSO4 and evaporated to give
yellowish solid. The product was purified by column chromato-
graphy on silica gel eluting with hexane: ethyl acetate (8:2) as
eluting solvent to give light yellow solid (2.52 g, 56.7 %).
m.p.: 124.2-125.4 °C; IR (KBr, νmax, cm–1): 3008, 2922, 1722,
1679, 1598, 1506. 1H NMR (400 MHz, CDCl3): δ (ppm): 2.55
(3H, s), 6.74 (1H, d, J = 15.3 Hz), 6.79 (1H, d, J = 15.3 Hz),
6.99 (1H, dd, J = 15.3, J = 10.6 Hz), 7.11 (1H, dd, J = 15.3, J
= 10.6 Hz), 7.23 (m, 1H)), 7.24 (1H, m), 7.28 (1H, m), 7.34
(m, 2H), 7.37 (2H, m), 7.47 (2H, d, J = 8.3 Hz), 7.56 (1H, m),
7.86 (1H, dd, J = 7.7, J = 1.4 Hz), 8.16 (2H, d, J = 8.3 Hz) 13C
1
1701, 1592, 1506, 1337, 1156, 1116; H NMR (700 MHz,
DMSO-d6): δ (ppm): 6.85 (d, 1H, J = 12.9 Hz), 6.92 (d, 1H, J
= 12.9 Hz), 7.32 (d, 2H, J = 9.0 Hz), 7.45 (d, 2H, J = 9.0 Hz),
7.86 (d, 2H, J = 9.0 Hz), 8.12 (d, 2H, J = 9.0 Hz); 13C NMR
(176 MHz, DMSO-d6): δ (ppm): 124.16 (C), 129.19 (2C),
129.16 (2C), 130.07 (C), 130.31 (C), 131.93 (2C), 131.99 (2C),
140.92 (C), 144.00 (C), 146.77 (C), 167.42 (C=O). ES-MS
(M+): calcd. for C15H11NO4: 269, found: 269.
Synthesis of E-4-(p-nitrostyryl)benzoyl chloride: A
mixture of E-4-(p-nitrostyryl)benzoic acid (11) (2.72 g, 10.10
mmol) and thionyl chloride (2.20 mL, 30.3 mmol) were heated
under reflux for 1 h. Excess thionyl chloride was removed
under reduced pressure and the crude solid was used for the
next step.

1106 Al-Busafi et al.
Asian J. Chem.
Synthesis of 2-acetylphenyl E-4-(p-nitrostyryl)benzoate
(13): To a solution of 2-hydroxy acetophenone (1.37 g, 10.10
mmol) in pyridine (15 mL) was added E-4-(p-nitrostyryl)-
benzoyl chloride (2.90 g, 10.10 mmol). The reaction mixture
was stirred briefly at room temperature. The temperature of
the reaction increased spontaneously. After cooling, the
reaction mixture was poured into a mixture of 20 mL HCl (3
%) and 30 g crushed ice. The product was extracted with
chloroform (3 × 10 mL) and the combined organic layer was
dried over MgSO4 and evaporated to give yellow oil. The
product was purified by column chromatography on silica gel
eluting with petroleum ether : ethyl acetate (7 : 3) to yield
light yellow solid (1.96 g, 50.6 %). m.p.: 175.3-177.5 °C; IR
(KBr, νmax, cm–1): 3071, 2918, 1735, 1686, 1598, 1513, 1339,
1260, 1175, 856; 1H NMR (700 MHz, CDCl3): δ (ppm): 2.52
(s, 3H), 6.94 (d, 1H, J = 12.0 Hz), 6.99 (d, 1H, J = 12.0 Hz),
7.44 (d, 2H, J = 7.0 Hz), 7.47 (m, H), 7.51 (d, 2H, J = 8.0),
7.71 (m, H), 8.02 (d, 2H, J = 7.0 Hz), 8.07 (m, 1H), 8.17 (d,
2H, J = 8.0 Hz), 8.59 (m, 1H); 13C NMR (176 MHz, CDCl3):
δ (ppm): 29.87 (CH3), 124.21 (C), 124.54 (C), 126.93 (C),
127.60 (2C),129.63 (2C),130.43 (2C), 130.67 (C), 130.96
(C),131.41 (C),132.73 (C),134.18 (C),142.63 (2C),143.93
(C),146.25 (C), 146.87 (C), 149.86 (C), 164.72 (C), 197.90
(CO). ES-MS (M+):Calculated for C23H17NO5: 387, found: 387.
Synthesis of flavonoid derivative (6): To a solution of
2-acetylphenyl E-4-(p-nitrostyryl)benzoate (0.70 g, 1.80
mmol) in pyridine (7 mL) at 70 °C was added potassium
hydroxide (0.6 g, 1.33 mmol) and the mixture was stirred for
15 min. Acetic acid solution (10 %, 11 mL) was added to the
cooled mixture and the solid intermediate was collected by
filtration. To a solution of the solid intermediate in acetic acid
(8 mL) was added concentrated sulfuric acid (0.25 mL) and the
mixture was refluxed for 1 h. The cooled mixture was poured
into ice and the product was collected by suction filtration
and washed with water. The product was recrystallized from
ethanol to give orange solid (0.37 g, 55.6 %); m.p.: 171.1-
175.2 °C. IR (KBr, νmax, cm–1): 3022, 1637, 1618, 1590, 1503,
1463, 1333, 899; λmax, (nm) (log ε) 308.3 (4.97), 345.8 (4.96);
1H NMR (700 MHz, DMSO-d6): δ (ppm): 6.90 (d, 1H, J =
12.0 Hz), 6.96 (d, 1H, J = 12.0 Hz), 7.13 (s, 1H), 7.53 (d, 2H,
J = 9.0 Hz), 7.64 (m, 1H), 7.85 (m, 1H), 7.89 (d, 2H, J = 9.0
Hz), 7.93 (d, 2H, J = 9.0 Hz), 8.07 (m, 1H), 8.18 (m, 1H),
8.27 (d, 2H, J = 9.0 Hz); 13C NMR (176 MHz, DMSO-d6): δ
(ppm): 107.40 (C), 119.05 (C), 124.26 (C), 124.56 (2C),
125.26 (C), 124.44 (C), 126.04 (C), 127.34 (2C), 128.13 (C),
128.14 (2C), 130.77 (C), 132.82 (C), 134.84 (C), 140.13 (C),
144.05 (C), 146.97 (C), 156.15 (C), 162.54 (C), 177.59 (C=O).
ES-MS (M)+: Calculated for C23H15NO4: 369, found: 369.
RESULTS AND DISCUSSION
Different synthetic methods have been employed to furnish
the structural skeleton of flavonoids such as cyclization of
chalcones, intramolecular Wittig reaction andAllan-Robinson
cyclization reaction [35]. Another favoured synthetic approach
towardsflavonoidstructuresisbyapplyingtheBaker-Venkataraman
rearrangement reaction on substituted ortho-acetylphenyl
benzoate ester [36]. Usually, the reaction commences from
acylation of ortho-hydroxyacetophenone with substituted
benzoyl chloride to form an ester which will undergo Baker-
Venkataraman rearrangement reaction in basic condition to
give 1,3-diketone intermediate. Cyclization of the diketone
intermediate to the required flavonoid derivative is achieved
by applying acid condition. In this regard, two new flavonoid
derivatives 5 and 6 were synthesized using Baker-Venkataraman
rearrangement starting from triphenylphosphonium bromide
7 (Scheme-I). The phophonium salt reacted viaWittig reaction
with either trans-cinnamaldehyde 8 or with 4-nitrobenzal-
dehyde 9 to give carboxylic acid 10 or 11, respectively, in the
presence of NaOH in H2O/CH2Cl2 solvent system. Carboxylic
acids (10 and 11) were purified by recrystallization from
hot ethanol to give yields of 65 % and 61.7 % respectively.
The coupling constants (J-values) of the two hydrogen atoms
in the new constructed double bonds are 15.4 Hz in carboxylic
acid 10 and 12.9 Hz in carboxylic acid 11 which indicate
formation of trans-double bonds. Thionyl chloride was used to
convert the carboxylic acids into their acid chloride counterparts
X
CH2PPh3 Br-
+
O
1. SOCl2
8
or
9
HOOC
O
NaOH/H2O/CH2Cl2
X
OH
12 or 13
2.
O
COOH
7
10 or 11
8:
9:
1- Pyridine/KOH
O
CHO
CHO
2- AcOOH, H2SO4
O N
2
X
O
O
6: X =
NO2
Or
5: X =
Scheme-I: Synthesis of flavonoid derivatives 5 and 6

Vol. 29, No. 5 (2017)
Synthesis of Two Novel Flavonoid Derivatives with Extended π-System 1107
15. B. Mackie and I. Mackie, Australasian J. Dermatol., 40, 51 (1999);
which were used without purification to react with 2-hydroxy
acetophenone in pyridine to form esters (12 and 13) in 56.7 %
and 50.6 %, respectively after recrystallization from ethanol.
Flavonoid derivatives (5 and 6) were prepared by applying
Baker-Venkataraman rearrangement reaction on esters 12 and
13 in a mixture of KOH and pyridine followed by acid treat-
ment. The overall percent yields of the two derivatives were
20 % for flavonoid 5 and 17.4 % for flavonoid 6.
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The structures of all the synthesized compounds except acid
chlorides were elucidated by combination of mass spectrometric
and IR, NMR spectroscopic methods. The singlet at δ 6.84 ppm
belongs to H-3 while the double bonds protons H-15 and H-
18 show doublet signals due to the coupling with H-16 and H-
17 at 6.75 ppm and 6.69 ppm, respectively. Protons H-16 and
H-17 exhibit doublet-of-doublet signals at 7.08 ppm and 6.97
ppm because they couple with each other in addition to their
coupling with H-15 and H-18. Other hydrogen atoms show
their signals as predicted.
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