BF3?OEt2-Promoted Annulation for Substituted 2-Arylpyridines as Potent UV Filters and Antibacterial Agents

Article abstract of DOI:10.1002/adsc.201701137

A simple and efficient BF₃?OEt₂ mediated methodology for the construction of diverse 2-phenylpyridines bearing benzophenone moieties from readily available 3-formylchromones and phenylacetylenes in wet acetonitrile was developed. The nitrogen source for the pyridine construction was derived from acetonitrile. This one-pot protocol proceeds via [3+2+1] annulation through cascade nucleophilic addition, hydrolysis, Michael-type addition, ring opening, and elimination reactions. The synthesized compounds may have applications as UV filters and exhibit potent antibacterial activities. (Figure presented.).

Full text of DOI:10.1002/adsc.201701137

Title: BF3•OEt2-Promoted Annulation for Substituted 2-Arylpyridines
as Potent UV Filters and Antibacterial Agents
Authors: Sabera Sultana, Shizuka Mei Bautista Maezono, Muhammad
Saeed Akhtar, Jae-Jin Shim, Young-Jung Wee, Sung Hong
Kim, and Yong Rok Lee
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of the final Version of Record (VoR). This work is currently citable by
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701137
Link to VoR: http://dx.doi.org/10.1002/adsc.201701137

10.1002/adsc.201701137
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
BF3∙OEt2-Promoted Annulation for Substituted 2-Arylpyridines
as Potent UV Filters and Antibacterial Agents
Sabera Sultanaa, Shizuka Mei Bautista Maezonoa, Muhammad Saeed Akhtara, Jae-Jin
Shima, Young-Jung Weeb, Sung Hong Kimc and Yong Rok Leea*
a
School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea. E-mail:
yrlee@yu.ac.kr; Fax: +82-53-810-4631; Tel: +82-53-810-2529
Department of Food Science and Technology, Yeungnam University, Gyeongsan 38541, Republic of Korea
Analysis Research Division, Daegu Center, Korea Basic Science Institute, Daegu 702-701, Republic of Korea
b
c
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A simple and efficient BF3∙OEt2 mediated addition, ring opening, and elimination reactions. The
methodology for the construction of diverse 2- synthesized compounds may have applications as UV
phenylpyridines bearing benzophenone moieties from readily filters and exhibit potent antibacterial activities.
available 3-formylchromones and phenylacetylenes in wet
acetonitrile was developed. The nitrogen source for the
pyridine construction was derived from acetonitrile. This
one-pot protocol proceeds via [3+2+1] annulation through
cascade nucleophilic addition, hydrolysis, Michael-type
Keywords: BF3∙OEt2; 2-phenylpyridines; [3+2+1]
annulation; UV filters; Antibacterial
with ammonium acetate,[7] cyclocondensation of 3-
chloro-1-phenyl-pro-2-enone with 3-amino-1-phenyl-
pro-2-enone,[8] and reaction of ethyl acetoacetate with
phenyl-2-propyn-1-one and ammonium acetate.[9]
Importantly, the nitrogen source for 2-arylpyridine
formation was derived from 1,3-diaminopropane,
lithium hexamethyldisilazide, oxime carboxylate,
ammonium acetate, and ammonia.
Introduction
2-Arylpyridines are key skeletons in pharmaceuticals
and bioactive materials (Figure 1).[1] In addition, they
are also used as starting materials or building blocks
in the synthesis of valuable ligands for metal
complexes[2]
and
in
important
organic
transformations.[3] Owing to the importance of 2-
arylpyridines, several synthetic approaches have been
reported based on transition-metal catalyzed or metal-
free conditions. Typical methods for the synthesis of
2-arylpyridines include copper-catalyzed C-N bond
Although a number of approaches for the synthesis
of 2-arylpyridines have been developed,[10] a more
facile and efficient one-pot synthetic protocol is still
desirable. Recently, we reported an organocatalyzed
oxidative N-annulation for the synthesis of pyridines
from ketones with α,β-unsaturated aldehydes and
ammonium acetate (method a, Scheme 1).[11] We also
described a catalyst- and solvent-free thermal
multicomponent cascade of 4-oxo-4H-chromene-3-
carbaldehydes with cyanoacetates and anilines for the
activation
of
acetophenones
with
1,3-
diaminopropane,[4] nucleophilic addition of a dithiane
Figure 1. Selected bioactive molecules bearing 2-
arylpyridine moieties.
anion to an α,β-unsaturated carbonyl followed by the
metallacycle-mediated union of allylic alcohols with
pre-formed
trimethylsilane-imines,[5]
copper-
Scheme 1. Our reported synthetic strategies for pyridines.
catalyzed coupling of oxime carboxylates to
vinylboronic acids,[6] condensation of enaminones
1
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
synthesis of 2-aminopyridines (method b, Scheme
2).[12]
produced and
starting materials were recovered
(entries 21-22). Importantly, the reaction was also
carried out in dry acetonitrile, desired product 3a was
not obtained, instead, intractable mixture was
produced (Scheme 4). The structures of 3a and 4a
Recently, metal-mediated or catalyzed [2+2+2]
cycloaddition of two alkynes with nitriles has become
one of the most powerful strategies for the
construction of substituted pyridines (method a,
Scheme 2).[13] In these cases, nitriles were used as an
active reagent for the formation of pyridine ring. To
date, there are no reports on [3+2+1] annulations for
the synthesis of 2-arylpyridines using acetonitrile as a
nitrogen source. As part of our ongoing interest in
this area, we report a novel BF3∙OEt2 mediated
[3+2+1] annulation of commercially available 3-
formylchromones, aryl acetylenes, and acetonitrile
for the construction of diverse 2-arylpyridines
(method b, Scheme 2). Interestingly, in this reaction,
the nitrogen source for the 2-arylpyridine
construction is from acetonitrile, rather than
ammonium acetate or the amine.
1
were confirmed by spectroscopic analyses. The H
NMR spectrum of 3a showed a characteristic -OH
peak at δ = 11.89 ppm as a singlet and one aromatic
peak on the pyridine moiety at δ = 8.97 ppm (J = 2.4
Hz) as a doublet due to long range coupling.
Compound 4a showed a characteristic vinylic proton
peak on the chromenone ring at 8.19 ppm as a singlet
and two trans-vinylic protons at δ = 8.66 ppm (J =
15.0 Hz) and 7.47 ppm (J = 15.0 Hz) as two doublets.
The structure of 3a was further confirmed by X-ray
crystallographic analysis of related compound 3e.
Table 1. Optimization of reaction conditions for the
synthesis of 3a.[a]
Scheme 2. Strategy for the construction of 2-arylpyridines.
Results and Discussion
The reaction of 3-formylchromone (1a) with
phenylacetylene (2a) in wet nitriles was first
investigated using several Brønsted and Lewis acids
(Table 1). Initial attempts with Brønsted acids such as
p-TsOH and TFA in wet acetonitrile at room
temperature for 12 h did not furnish the desired
product (entries 1 and 2). Several Lewis acids such as
AgOTf, Cu(OTf)2, In(OTf)3, InCl3, Fe(OTf)3,
Y(OTf)3, TiCl4, SnCl4, AlCl3, FeCl3 and BF3∙OEt2
were next screened (entries 3-13). Among these,
BF3∙OEt2 (1.0 equiv.) gave 3a in 58% isolated yield
(entry 13). With other Lewis acids, only starting
material 1a was recovered. Decreasing the amount of
BF3∙OEt2 to 0.5 equivalent did not improve the yield
(entry 14). When the amount of BF3∙OEt2 was
increased to 2.0 equivalent, product 3a was obtained
in 79% yield (entry 15). However, when the reaction
was screened with other nitriles, two products 3a and
4a were isolated. For example, treatment of 1a with
2a in wet propionitrile provided 3a in 28% yield with
trace amount of 4a (entry 16). With other nitriles
[a]Reaction conditions: 1a (0.6 mmol), 2a (0.66 mmol), and
solvent (1 mL). [b]Isolated yield.*[c],[d] = without nitrogen
source
Next, the generality of the reaction was explored
using diverse 3-formylchromones 1b-1h with
phenylacetylene (2a) under the optimized conditions
(Table 2). For example, treatment of 1b-1d bearing
electron-donating groups (6-Me, 6-Et, and 6-iPr) with
2a in wet acetonitrile at room temperature for 1 h
provided the desired products 3b-3d in 79%, 76%,
and 75% yields, respectively, whereas 1e-1g bearing
electron-withdrawing groups (6-Br, 6-Cl, and 6-F)
afforded 3e-3g in 72%, 72%, and 68% yields,
respectively. Notably, 3-formylchromone 1h bearing
both electron-donating and electron-withdrawing
groups on the aromatic ring were also transformed
into desired product 3h in 70% yield.
such
as
valeronitrile,
methoxypropionitrile,
benzonitrile, and phenylacetonitrile, both 3a (31-41%)
and 4a (trace-18%) were produced (entries 17-20). In
other solvents having no nitrogen source such as 1,2-
dichloroethane and ethanol, no products were
2
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
Table 2. Substrate scope of 3-formylchromones 1b-1h in
formation of 2-phenylpyridines 3b-3h.
Table 3. Substrate scope of phenylacetylenes 2b-2j
in formation of 2-arylpyridines 5a-5i.
To demonstrate the versatility of the developed
reaction, various arylacetylenes were tested (Table 3).
The reactions proceeded smoothly to provide the
corresponding products in good yields. For example,
when 3-formylchromone (1a) was treated with
arylacetylenes 2b-2e bearing electron-donating
groups such as 3-methyl, 4-methyl, 4-n-propyl, and
4-n-pentyl in acetonitrile, the desired products 5a-5d
were obtained in 70-78% yields. Similarly, with
arylacetylenes 2f-2h bearing electron-withdrawing
groups 4-Br, 4-CF3, and 3,5-CF3 on the benzene ring,
5e, 5f, and 5g were isolated in 73%, 69%, and 68%
yields, respectively. The reaction of 1a with 1,4-
diethynylbenzene (2i) in wet acetonitrile gave 5h in
71% yield without concomitant formation of the
bispyridine. With 1-ethynylnaphthalene (2j), 5i
bearing a naphthyl ring was formed in 70% yield.
The scope of the substrates was further extended
by employing substituted 3-formylchromones (1b-1c
and 1e-1i) and substituted phenylacetylenes (2c-2i
and 2k-2l) (Table 4). Treatment of 6-methyl-3-
formylchromone (1b) with 1-ethynyl-4-methoxy-2-
Table 4. Substrate scope of 3-formylchromones 1b-1c,
1e-1i and arylacetylenes 2c-2i and 2k-2l in formation of 2-
arylpyridines 6a-6l.
methylbenzene
(2k)
or
1-ethynyl-3,5-
bis(trifluoromethyl)benzene (2h) in wet acetonitrile at
room temperature for 1 h gave 6a and 6b in 76% and
68% yields, respectively; the reaction of 1c with 2c
provided 6c in 75% yield. Similarly, halogen-
substituted
3-formylchromones
1e-1g
with
substituted phenylacetylenes 2c-2g and 2l provided
the corresponding products 6d-6i in 69-75% yields.
In addition, the combination of dichloride-substituted
3-formylchromones 1i with 2c or 2i afforded products
6j and 6k in 74% and 71% yields, respectively. 3-
Formylchromone 1h with 2g was also transformed
into 6l in 70% yield. This methodology provides a
rapid route towards diverse 2-arylpyridines bearing
benzophenones.
3
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
Having seen the generality and versatility of the
reaction, the possibility of use of aliphatic alkyne was
next examined. For example, the reaction of 1a with
1-hexyne (7) in the presence of 2 equivalents of
BF3∙OEt2 in wet acetonitrile did not provide the
desired product 3a, instead compound 8 was isolated
in 46% yield (Scheme 3).
furnishes intermediate 14. Elimination of acetic acid
from 14 finally affords product 3a.
Scheme 3. Reaction of 1a with 1-hexyne (7).
To gain insight into the mechanism, some control
experiments were carried out (Scheme 4). The
reaction of compound 4a was carried out under
standard conditions, desired cycloadduct 3a was not
formed and only starting material 4a was recovered
(eq. a, Scheme 4). When the reaction was performed
under argon atmosphere with anhydrous acetonitrile,
intractable mixture was obtained (eq. b, Scheme 4).
Further reaction between 1a with 2a in anhydrous
acetonitrile with excessive D2O was performed,
deuterium exchanged compound 9a was obtained,
Scheme 5. Proposed mechanism for the formation of 3a.
The optical and chemical properties of the
compounds bearing benzophenone moieties have
important implications in photochemistry.[15] As such,
the potential of the synthesized 2-arylpyridines
bearing benzophenone skeletons as UV filters was
explored in vitro. Although benzophenones have been
widely used as potent ingredients in sunscreen, the
development of new UVA/UVB filters is required
owing to the prevalence of allergic reactions and free
radical damage by benzophenone derivatives.[15b,16]
Therefore, the UV absorption of 3a, 3b, 3f, 3h, 5a, 5e,
5f, 6b, 6g, and 6j were evaluated to determine their
viability and performance as UV filters (Figure 2).
Specifically, the molar extinction coefficient (ε),
UVA/UVB ratio, and critical wavelength were
determined.
1
which is detected in crude H NMR (method c,
Scheme 4). However, after purification by column
chromatography, only compound 3a was isolated in
64% yield. These observations showed that
compound 4a is
a side product instead of
intermediate and that water is preferentially necessary
to produce the desired product 3a.
2,5
2
3a
3b
3f
3h
5a
5e
5f
6b
6g
6j
1,5
1
0,5
0
Scheme 4. Control Experiments.
280 300 320 340 360 380 400 420
Wavelength/nm
On the basis of above mentioned control
experiments and results,[14] a possible mechanism for
the formation of 3a is depicted in Scheme 5. In the
.
presence of BF3 OEt2, 3-formylchromone (1a) gives
Figure 2. Absorbance vs. wavelength of 3a, 3b, 3f, 3h, 5a,
5e, 5f, 6b, 6g, and 6j in EtOH.
complex 1a'. The addition of acetonitrile to 2a
followed by nucleophilic addition to 1a' affords
intermediate 10. Hydrolysis of nitrile group followed
by keto-enol tautomerization of 11 generates
intermediate 12. Intramolecular Michael-type
addition of the nitrogen on amide moiety gives 13
which undergoes retro Michael-type ring opening
The molar extinction coefficient (ε), which is an
important variable that describes the light absorbance
strength of a substance at a given wavelength per
molar concentration, was computed using Beer-
Lambert’s law. The UVA/UVB ratio and critical
4
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
wavelength (λc) were determined using the method
described by Diffey (Table 5).[17] According to
previous studies, the prerequisite for broad-spectrum
UVA/UVB protection labeling is satisfied when the
critical wavelength is greater than 370 nm.[18]
modified version of the Kirby-Bauer disk diffusion
method.[20] The bacterial strains were obtained from
the Korean Collection for Type Cultures (KCTC).
The bacterial strains were cultivated in 10 mL of
fresh DifcoTM broth for 24 h. The optical density of
the newly cultivated bacterial suspension was 0.7 at
595 nm. 100 µL aliquots from the bacterial
suspension were then spread over the DifcoTM
nutrient broth (prepared via the method described
above). Filter paper disks with 8 mm diameters,
previously autoclaved and saturated with 20 µL of the
test sample, were placed on the agar plate and
incubated for 20-36 h at 37 °C. After the incubation
period, the zones of inhibition were measured.
Standard discs of ciprofloxacin were used as positive
controls. Filter paper discs impregnated with DMSO
were used as negative controls. Notably, the depth of
the agar in the plate must be considered in the disc
diffusion method.
Table 5. UV absorption properties of synthesized
compounds.
The antibacterial activities of the compounds are
recorded in Table 6. When filter paper discs
impregnated with the chemical compounds were
placed on the agar medium, the chemical compounds
diffused into the agar. The solubility of the chemical
compound and its molecular mass determines the
infiltration area. When bacteria are placed on the agar
plate, they will not grow in the area around the disc if
the chemical compound present on the disc has
antibacterial activity. The area (diameter) of no
growth around the disc is known as the zone of
inhibition. A few of the compounds viz. 3h, 5f, 5g, 6b,
and 6e were selectively active against gram positive
and gram negative bacteria. Compounds 3h, 5f, 5g,
6b, and 6e appeared to be moderately active against
most of the strains as compared to the reference
antibiotic (ciprofloxacin). Compound 5g exhibited a
zone of inhibition with a diameter of 12 mm against
P. aeruginosa, 15 mm against E. coli, 10 mm against
S. aureus, and 15 mm for B. cereus. Furthermore,
compound 6b cast zones of inhibition with diameters
of 10, 12, 11, and 14 mm for P. aeruginosa, E. coli, S.
aureus, and B. cereus, respectively, indicating that
the synthesized compounds bearing strong electron
withdrawing groups on the phenyl ring showed better
antibacterial activities than other compounds.
[a]The concentration of tested sample was 50 μM in EtOH.
Although 3a, 3f, 3h, 5a, 5e, 5f, 6b, 6g, and 6j
showed a broad spectrum in the UVB region, only 3b
exhibited a critical wavelength (371 nm) to be
classified as a broad-spectrum protection agent. In
terms of the UVA/UVB ratio, which is based on the
mean absorbance in the UVA region divided by the
mean absorbance in the UVB region,[19] compounds
5a, 5e, and 5g showed the highest values of 0.53,
0.53, and 0.51, respectively, indicating good UVA-
coverage compared to UVB-coverage. Shifts in the
absorbance towards the blue or red region could have
been caused by the substituents present on the phenyl
group attached to the pyridine ring of the compounds.
For instance, compounds 3b, 3h, 5f, and 6b showed
hypsochromic (blue) shifts, while compounds 5e and
Table 6. Antibacterial activity of tested compounds against
several standard bacterial strains.
6g exhibited bathochromic (red) shifts in their λmax
which were all based on 3a (Figure 2).
,
Since pyridine moieties have central roles in many
biological activities, the antibacterial activities of
some selected synthetic compounds (3h, 5f, 5g, 6b,
and 6e) were screened against gram-negative bacteria
E. coli (KCTC-1924) and P. aeruginosa (KCTC-
2004), as well as gram-positive bacteria S. aureus
(KCTC-1916) and B. cereus (KCTC-1012) using a
Conclusion
In conclusion, we have developed a facile and
efficient methodology for the construction of
5
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
(2-Hydroxy-5-methylphenyl)(6-phenylpyridin-3-yl)
methanone (3b). The title compound (3b) was prepared
according to the general procedure. The product was
substituted 2-arylpyridines bearing benzophenone
moieties starting from commercially available 3-
formylchromones and arylacetylenes in acetonitrile
with good yields. This protocol offers mild reaction
conditions and a convenient one-pot procedure.
Moreover, many functional groups on the benzene
rings are tolerated. The synthesized compounds were
found to have applications as UV protecting materials,
especially compound 3b, which exhibited the most
potential with a critical wavelength of 371 nm. As for
the antibacterial applications, the tested compounds
o
obtained as a brown solid, mp 89-90 C. Yield: 78% (135
1
mg). H NMR (600 MHz, CDCl3)  11.71 (1H, s), 8.97
(1H, d, J = 4.4 Hz), 8.08-8.06 (3H, m), 7.87 (1H, d, J = 3.9
Hz), 7.51-7.45 (3H, m), 7.38 (1H, s), 7.34 (1H, dd, J = 9.0,
2.4 Hz), 6.99 (1H, d, J = 8.4 Hz), 2.25 (3H, s); 13C NMR
(150 MHz, CDCl3)  198.9, 161.1, 159.9, 149.9, 137.9,
137.8, 137.7, 132.5, 131.9, 130.0, 128.9, 128.2, 127.3,
119.9, 118.7, 118.4, 20.4; IR (ATR) 2919, 1626, 1585,
1475, 1384, 1294, 1224, 1141, 1020, 858, 770 cm-1;
HRMS m/z (M+) calcd for C19H15NO2: 289.1103. Found:
289.1102.
showed
moderate
activities,
and
further
(5-Ethyl-2-hydroxyphenyl)(6-phenylpyridin-3-yl)metha
none (3c). The title compound (3c) was prepared
according to the general procedure. The product was
improvements may be possible.
o
obtained as a yellow solid, mp 115-117 C. Yield: 76%
1
(138 mg). H NMR (600 MHz, CDCl3)  11.71 (1H, s),
Experimental Section
8.98 (1H, d, J = 4.4 Hz), 8.10-8.07 (3H, m), 7.89 (1H, d, J
= 3.9 Hz), 7.52-7.46 (3H, m), 7.40-7.38 (2H, m), 7.02 (1H,
d, J = 8.4 Hz), 2.56 (2H, q, J = 7.8 Hz), 1.17 (3H, t, J = 7.8
Hz); 13C NMR (150 MHz, CDCl3)  198.9, 161.3, 159.9,
149.9, 137.9, 137.8, 136.9, 134.8, 131.9, 131.5, 130.1,
128.9, 127.4, 120.1, 118.8, 118.5, 27.9, 15.8; IR (ATR)
2964, 2918, 2858, 1585, 1478, 1411, 1386, 1338, 1133,
1109, 778 cm-1; HRMS m/z (M+) calcd for C20H17NO2:
303.1259. Found: 303.1256.
General remarks:
All experiments were carried out in open air. Merck
precoated silica gel plates (Art. 5554) with a fluorescent
indicator were used for analytical TLC. Flash column
chromatography was performed using silica gel 9385
(Merck). The melting points are uncorrected and were
determined using micro-cover glasses on a Fisher-Johns
1
apparatus. H NMR spectra were recorded on a Varian-
(2-Hydroxy-5-isopropylphenyl)(6-phenylpyridin-3-yl)m
ethanone (3d). The title compound (3d) was prepared
according to the general procedure. The product was
VNS (600 MHz) spectrometer using the chemical shift of
the solvent at  = 7.24 ppm for CDCl3 or  = 0.00 ppm for
TMS as a reference. 13C NMR spectra were recorded on a
Varian-VNS (150 MHz) spectrometer using the chemical
shift of the solvent at  = 77.0 ppm for CDCl3 as a
reference. Chemical shifts (δ) are expressed in units of
ppm and J values are given in Hz. Multiplicities are
abbreviated as follows: s = singlet, d = doublet, t = triplet,
q = quartet, br s = broad singlet, dd = doublet of doublets,
td = triplet of doublets, quint = quintet, sept = septet, and
m = multiplet. IR spectra were recorded on a FTIR (BIO-
RAD) and high-resolution mass spectra were obtained on a
JEOL JMS-700 spectrometer at the Korea Basic Science
Institute.
o
obtained as a yellow solid, mp 155-157 C. Yield: 75%
1
(142 mg). H NMR (600 MHz, CDCl3)  11.72 (1H, s),
8.99 (1H, d, J = 1.2 Hz), 8.10-8.08 (3H, m), 7.89 (1H, d, J
= 7.8 Hz), 7.53-7.46 (3H, m), 7.44-7.42 (2H, m), 7.03 (1H,
d, J = 8.4 Hz), 2.83 (1H, sept, J = 7.2 Hz), 1.19 (6H, d, J =
7.2 Hz); 13C NMR (150 MHz, CDCl3)  198.9, 161.4,
160.1, 149.9, 139.5, 138.0, 137.8, 135.4, 131.9, 130.2,
130.1, 128.9, 127.4, 120.1, 118.7, 118.5, 33.3, 23.9; IR
(ATR) 2917, 2849, 1622, 1575, 1473, 1329, 1298, 1236,
1145, 1105, 1068, 1004, 813, 753 cm-1; HRMS m/z (M+)
calcd for C21H19NO2: 317.1416; Found: 317.1412.
(5-Bromo-2-hydroxyphenyl)(6-phenylpyridin-3-yl)meth
anone (3e). The title compound (3e) was prepared
according to the general procedure. The product was
obtained as a yellow solid and crystallized in ethanol, mp
157-159 C. Yield: 72% (152 mg). H NMR (600 MHz,
CDCl3)  11.77 (1H, s), 8.98 (1H, d, J = 1.8 Hz), 8.09 (3H,
dd, J = 8.4, 1.8 Hz), 7.91 (1H, d, J = 8.4 Hz), 7.72 (1H, d,
J = 2.4 Hz), 7.61 (1H, dd, J = 9.0, 2.4 Hz), 7.53-7.47 (3H,
m), 7.00 (1H, d, J = 9.0 Hz); 13C NMR (150 MHz, CDCl3)
 197.9, 162.1, 160.5, 149.9, 139.5, 137.8, 137.7, 134.7,
131.1, 130.3, 129.0, 127.4, 120.7, 120.3, 120.1, 110.7; IR
(ATR) 3062, 1626, 1586, 1460, 1381, 1319, 1289, 1154,
1081, 1020, 939, 831, 691 cm-1; HRMS m/z (M+) calcd for
C18H12BrNO2: 353.0051. Found: 353.0048.
General procedure:
To a mixture of 3-formylchromone (1) (0.6 mmol) and
phenylacetylene (2) (0.66 mmol, 1.1 equiv.) in acetonitrile
(1 mL) was added boron trifluoride etherate (0.6 mmol, 1
equiv.) at room temperature; the mixture was stirred for 1 h.
The progress of the reaction was monitored by TLC. After
the completion of the reaction, the solvent was removed on
a rotary evaporator and the product was extracted with
ethyl acetate (2 × 10 mL) and then washed with brine (5
mL). The organic layer was dried over Na2SO4 and
evaporated to give the crude product, which was purified
by short column chromatography over silica gel
(EtOAc/hexane = 1:9) to give the desired products.
o
1
X-Ray crystallographic data of compound 3e: Empirical
Formula- C23H22N2O4, M = 354.20, Monoclinic, Space
group P21/c, a = 6.2873(3) Å, b = 16.9635(8) Å, c =
13.8579(7) Å, V = 1448.39(12) Å3, Z = 4, T = 223(2) K,
ρcalcd = 1.624 Mg/m3, 2Өmax. = 28.357o, Refinement of 200
parameters on 3622 independent reflections out of 46289
collected reflections (Rint = 0.0422) led to R1 = 0.0299 [I
>2σ(I)], wR2 = 0.0738 (all data) and S = 1.076 with the
largest difference peak and hole of 0.584 and -0.615 e. Å-3
respectively. The crystal structure has been deposited at the
Cambridge Crystallographic Data Centre (CCDC 1570166).
The data can be obtained free of charge via the Internet at
www.ccdc.cam.ac.uk/data_request/cif.
Characterization data of synthesized compounds:
(2-Hydroxyphenyl)(6-phenylpyridin-3-yl)methanone
(3a). The title compound (3a) was prepared according to
the general procedure. The product was obtained as a
o
1
yellow solid, mp 119-121 C. Yield: 79% (130 mg). H
NMR (600 MHz, CDCl3)  11.90 (1H, s), 8.97 (1H, d, J =
2.4 Hz), 8.08-8.05 (3H, m), 7.86 (1H, d, J = 7.8 Hz), 7.61
(1H, d, J = 8.4 Hz), 7.54-7.45 (4H, m), 7.08 (1H, d, J = 8.4
Hz), 6.90 (1H, t, J = 7.8 Hz); 13C NMR (150 MHz, CDCl3)
 199.0, 163.2, 160.0, 149.9, 137.9, 137.6, 136.8, 132.9,
131.6, 130.0, 128.9, 127.3, 119.8, 119.0, 118.9, 118.6; IR
(ATR) 3023, 1737, 1619, 1583, 1477, 1445, 1385, 1304,
1242, 1209, 1140, 1016, 786 cm-1; HRMS m/z (M+) calcd
for C18H13NO2: 275.0946. Found: 275.0948.
(5-Chloro-2-hydroxyphenyl)(6-phenylpyridin-3-yl)meth
anone (3f). The title compound (3f) was prepared
according to the general procedure. The product was
o
obtained as a brown solid, mp 171-173 C. Yield: 70%
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701137
Advanced Synthesis & Catalysis
1
(129 mg). H NMR (600 MHz, CDCl3)  11.75 (1H, s),
(3H, s); 13C NMR (150 MHz, CDCl3)  198.9, 163.1, 160.0,
149.9, 140.4, 137.6, 136.7, 135.1, 132.9, 131.4, 129.7,
119.9, 119.5, 119.1, 118.9, 118.6, 21.3; IR (ATR) 2935,
1619, 1587, 1467, 1445, 1389, 1343, 1309, 1247, 1137,
1032, 765 cm-1; HRMS m/z (M+) calcd for C19H15NO2:
289.1103. Found: 289.1101.
8.98 (1H, d, J = 2.4 Hz), 8.09 (3H, dd, J = 8.4, 1.8 Hz),
7.90 (1H, d, J = 8.4 Hz), 7.58 (1H, d, J = 3.0 Hz), 7.53-
7.47 (4H, m), 7.05 (1H, d, J = 9.6 Hz); 13C NMR (150
MHz, CDCl3)  198.0, 161.6, 160.5, 149.9, 137.8, 137.7,
136.7, 131.7, 131.1, 130.3, 129.0, 127.4, 123.8, 120.4,
120.1, 119.7; IR (ATR) 3074, 1627, 1587, 1461, 1384,
1320, 1208, 946, 834, 694 cm-1; HRMS m/z (M+) calcd for
C18H12ClNO2: 309.0557. Found: 309.0556.
(2-Hydroxyphenyl)(6-(4-propylphenyl)pyridin-3-yl)met
hanone (5c). The title compound (5c) was prepared
according to the general procedure. The product was
o
(5-Fluoro-2-hydroxyphenyl)(6-phenylpyridin-3-yl)meth
anone (3g). The title compound (3g) was prepared
according to the general procedure. The product was
obtained as a yellow solid, mp 85-87 C. Yield: 72% (136
1
mg). H NMR (600 MHz, CDCl3)  11.91 (1H, s), 8.95
(1H, d, J = 8.4, 1.8 Hz), 8.05 (1H, dd, J = 8.4, 1.8 Hz),
7.99 (2H, d, J = 7.8 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.62 (1H,
dd, J = 7.8, 1.8 Hz), 7.52 (1H, td, J = 7.2, 1.8 Hz), 7.31
(2H, d, J = 8.4 Hz), 7.08 (1H, d, J = 7.2 Hz), 6.90 (1H, td,
J = 8.4, 1.2 Hz), 2.64 (2H, t, J = 7.8 Hz), 1.60 (2H, q, J =
7.8 Hz), 0.95 (3H, t, J = 7.0 Hz); 13C NMR (150 MHz,
CDCl3)  198.9, 163.1, 160.1, 149.9, 145.1, 137.7, 136.7,
135.3, 132.9, 131.4, 129.1, 127.2, 119.5, 119.1, 118.9,
118.6, 37.8, 24.3, 13.7; IR (ATR) 2957, 2927, 2867, 1623,
1581, 1478, 1440, 1382, 1329, 1299, 1245, 1219, 1143,
1112, 934, 800, 753 cm-1; HRMS m/z (M+) calcd for
C21H19NO2: 317.1416. Found: 317.1413.
o
obtained as a yellow solid, mp 161-163 C. Yield: 68%
1
(119 mg). H NMR (600 MHz, CDCl3)  11.61 (1H, s),
8.99 (1H, s), 8.09-8.07 (3H, m), 7.90 (1H, d, J = 3.9 Hz),
7.53-7.47 (3H, m), 7.31-7.27 (2H, m), 7.07 (1H, dd, J =
9.0, 4.2 Hz); 13C NMR (150 MHz, CDCl3)  198.1, 160.5,
159.3, 154.7 (d, J = 237.9 Hz), 149.9, 137.8, 137.7, 131.2,
130.3, 129.0, 127.4, 124.5 (d, J = 24.1 Hz), 120.0 (d, J =
8.1 Hz), 120.0, 118.5, 117.6 (d, J = 24.1 Hz); IR (ATR)
3079, 1635, 1582, 1477, 1419, 1329, 1280, 1219, 1131,
1019, 970, 774 cm-1; HRMS m/z (M+) calcd for
C18H12FNO2: 293.0852. Found: 293.0850.
(5-Chloro-2-hydroxy-4-methylphenyl)(6-phenylpyridin-
3-yl)methanone (3h). The title compound (3h) was
prepared according to the general procedure. The product
(2-Hydroxyphenyl)(6-(4-pentylphenyl)pyridin-3-yl) met
hanone (5d). The title compound (5d) was prepared
according to the general procedure. The product was
o
o
was obtained as a yellow solid, mp 136-138 C. Yield:
obtained as a yellow solid, mp 85-88 C. Yield: 70% (144
1
1
70% (135 mg). H NMR (600 MHz, CDCl3)  11.78 (1H,
mg). H NMR (600 MHz, CDCl3)  11.92 (1H, s), 8.95
s), 8.97 (1H, d, J = 1.8 Hz), 8.08 (3H, dd, J = 8.4, 1.8 Hz),
7.90 (1H, d, J = 8.4 Hz), 7.57 (1H, s), 7.53-7.47 (3H, m),
6.98 (1H, s), 2.40 (3H, s); 13C NMR (150 MHz, CDCl3) 
197.6, 161.6, 160.3, 149.8, 146.4, 137.7, 132.2, 131.4,
130.2, 129.0, 127.4, 124.5, 120.7, 120.1, 117.9, 20.9; IR
(ATR) 2920, 1629, 1587, 1470, 1382, 1290, 1221, 1134,
1019, 859, 780 cm-1; HRMS m/z (M+) calcd for
C19H14ClNO2: 323.0713. Found: 323.0710.
(1H, d, J = 4.4 Hz), 8.04 (1H, dd, J = 8.4, 2.4 Hz), 7.99
(2H, d, J = 7.8 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.61 (1H, dd,
J = 7.8, 1.8 Hz), 7.52 (1H, td, J = 8.4, 1.8 Hz), 7.31 (2H, d,
J = 7.8 Hz), 7.08 (1H, d, J = 7.2 Hz), 6.90 (1H, td, J = 8.4,
1.8 Hz), 2.66 ( 2H, t, J = 7.8 Hz), 1.64 (2H, quint, J = 7.8
Hz), 1.35-1.31 (4H, m), 0.88 (3H, t, J = 7.2 Hz); 13C NMR
(150 MHz, CDCl3)  198.9, 163.1, 160.1, 149.9, 145.4,
137.6, 136.7, 135.3, 132.9, 131.3, 129.0, 127.2, 119.5,
119.1, 118.9, 118.6, 35.7, 31.4, 30.9, 22.5, 13.9; IR (ATR)
2924, 2855, 1623, 1582, 1476, 1440, 1383, 1329, 1299,
1245, 1144, 935, 753 cm-1; HRMS m/z (M+) calcd for
C23H23NO2: 345.1729. Found: 345.1728.
(E)-3-(3-Oxo-3-phenylprop-1-en-1-yl)-4H-chromen-4-
one (4a). The title compound (4a) was prepared according
to the general procedure. The product was obtained as a
o
1
yellow solid, mp 134-136 C. Yield: 15% (25 mg). H
NMR (600 MHz, CDCl3)  8.66 (1H, d, J = 15.0 Hz), 8.30
(1H, dd, J = 7.8, 1.2 Hz), 8.18 (1H, s), 8.09-8.08 (2H, m),
7.71-7.68 (1H, m), 7.57-7.55 (1H, m), 7.49-7.47 (3H, m),
7.47-7.44 (2H, m); 13C NMR (150 MHz, CDCl3)  190.6
176.3, 158.9, 155.4, 137.9, 135.3, 134.1, 132.9, 128.7,
128.6, 126.3, 125.9, 125.8, 124.3, 119.6, 118.2; IR (ATR)
3080, 3026, 2817, 1664, 1651, 1570, 1496, 1450, 1309,
1287, 1215, 1177, 1078, 989 cm-1; HRMS m/z (M+) calcd
for C18H12O3: 276.0786. Found: 276.0783.
(6-(4-Bromophenyl)pyridin-3-yl)(2-hydroxyphenyl)me
thanone (5e). The title compound (5e) was prepared
according to the general procedure. The product was
o
obtained as a brown solid, mp 150-152 C. Yield: 73%
1
(154 mg). H NMR (600 MHz, CDCl3)  11.85 (1H, s),
8.96 (1H, d, J = 1.8 Hz), 8.08 (1H, dd, J = 7.8, 1.8 Hz),
7.95 (2H, d, J = 8.4 Hz), 7.85 (1H, d, J = 7.8 Hz), 7.63 (2H,
d, J = 8.4 Hz), 7.59 (1H, dd, J = 8.4, 1.8 Hz), 7.54 (1H, td,
J = 8.4, 1.8 Hz), 7.09 (1H, d, J = 8.4 Hz), 6.91 (1H, t, J =
7.8 Hz) ;13C NMR (150 MHz, CDCl3)  198.9, 163.2,
158.8, 150.0, 137.8, 136.9, 136.8, 132.9, 132.2, 132.1,
128.8, 124.8, 119.6, 119.1, 119.0, 118.7; IR (ATR) 3065,
1620, 1582, 1465, 1385, 1325, 1280, 1150, 1181, 1021,
834, 754 cm-1; HRMS m/z (M+) calcd for C18H12BrNO2:
353.0051. Found: 353.0049.
(2-Hydroxyphenyl)(6-(m-tolyl)pyridin-3-yl)methanone
(5a). The title compound (5a) was prepared according to
the general procedure. The product was obtained as a
1
brown solid, mp 66-67 oC. Yield: 77% (133 mg). H NMR
(600 MHz, CDCl3)  11.88 (1H, s), 8.97 (1H, s), 8.07 (1H,
dd, J = 9.0, 2.4 Hz), 7.91 (1H, s), 7.86 (1H, d, J = 8.4 Hz),
7.84 (1H, d, J = 7.8 Hz), 7.61 (1H, d, J = 7.8 Hz), 7.53 (1H, (2-Hydroxyphenyl)(6-(4-(trifluoromethyl)phenyl)pyrd
t, J = 7.8 Hz), 7.39 (1H, t, J = 7.8 Hz), 7.28 (1H, d, J = 7.2
Hz), 7.08 (1H, d, J = 8.4 Hz), 6.91 (1H, t, J = 7.8 Hz), 2.44
in-3-yl)methanone (5f). The title compound (5f) was
prepared according to the general procedure. The product
(3H, s); 13C NMR (150 MHz, CDCl3)  199.0, 163.2, 160.3, was obtained as a yellow solid, mp 155-157 C. Yield:
o
1
149.9, 138.7, 137.9, 137.7, 136.8, 132.9, 131.6, 130.9,
128.8, 127.9, 124.4, 119.9, 119.1, 118.9, 118.6, 21.5; IR
(ATR) 2920, 1617, 1583, 1477, 1440, 1379, 1333, 1304,
1240, 1141, 1030, 761 cm-1; HRMS m/z (M+) calcd for
C19H15NO2: 289.1103. Found: 289.1100.
69% (142 mg). H NMR (600 MHz, CDCl3)  11.85 (1H,
s), 9.00 (1H, d, J = 1.2 Hz), 8.19 (2H, d, J = 8.4 Hz), 8.11
(1H, dd, J = 7.8, 1.2 Hz), 7.91 (1H, d, J = 8.4 Hz), 7.67
(2H, d, J = 7.8 Hz), 7.59 (1H, d, J = 8.4 Hz), 7.54 (1H, t, J
= 7.2 Hz), 7.09 (1H, d, J = 9.0 Hz), 6.91 (1H, t, J = 7.2
Hz); 13C NMR (150 MHz, CDCl3)  198.8, 163.3, 158.4,
150.1, 141.3, 137.8, 137.1, 132.9, 132.6, 131.7 (q, J = 32.1
Hz), 127.6, 125.9 (q, J = 4.5 Hz), 123.1, 120.2, 119,1,
118.9, 118.8; IR (ATR) 3005, 1620, 1579, 1483, 1437,
1380, 1312, 1239, 1160, 1106, 1064, 1013, 798, 759 cm-1;
HRMS m/z (M+) calcd for C19H12F3NO2: 343.0820. Found:
343.0819.
(2-Hydroxyphenyl)(6-(p-tolyl)pyridin-3-yl)methanone
(5b). The title compound (5b) was prepared according to
the general procedure. The product was obtained as a
o
1
yellow solid, mp 116-117 C. Yield: 78% (135 mg). H
NMR (600 MHz, CDCl3)  11.89 (1H, s), 8.95 (1H, d, J =
2.4 Hz), 8.04 (1H, dd, J = 7.8, 1.8 Hz), 7.97 (2H, d, J =
7.8 Hz), 7.83 (1H, d, J = 8.4 Hz), 7.61 (1H, dd, J = 8.4, 1.8
Hz), 7.52 (1H, td, J = 8.4, 1.2 Hz), 7.30 (2H, d, J = 7.8 Hz), (6-(3,5-Bis(trifluoromethyl)phenyl)pyridin-3-yl)(2-hydr
7.08 (1H, t, J = 8.4 Hz), 6.90 (1H, td, J = 7.2, 0.6 Hz), 2.41
oxyphenyl)methanone (5g). The title compound (5g) was
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701137
Advanced Synthesis & Catalysis
prepared according to the general procedure. The product
(5-Ethyl-2-hydroxyphenyl)(6-(p-tolyl)pyridin-3-yl)meth
anone (6c). The title compound (6c) was prepared
according to the general procedure. The product was
o
was obtained as a yellow solid, mp 120-122 C. Yield:
1
68% (199 mg). H NMR (600 MHz, CDCl3)  11.82 (1H,
o
s), 9.02 (1H, d, J = 1.2 Hz), 8.56 (2H, s), 8.15 (1H, dd, J =
8.4, 6.6 Hz), 7.97 (2H, d, J = 7.8 Hz), 7.57-7.55 (2H, m),
7.11 (1H, d, J = 9.0 Hz ), 6.92 (1H, t, J = 7.8 Hz); 13C
NMR (150 MHz, CDCl3)  198.6, 163.4, 156.5, 150.2,
140.1, 138.1, 137.2, 133.2, 132.8, 132.4 (q, J = 33.4 Hz),
127.3 (q, J = 3.4 Hz), 123.4 (q, J = 3.45 Hz), 123.2 (q, J =
271.35 Hz), 120.1, 119.2, 118.9, 118.8; IR (ATR) 2925,
1580, 1485, 1383, 1337, 1275, 1163, 1125, 1071, 835, 790
cm-1; HRMS m/z (M+) calcd for C20H11F6NO2: 411.0694.
Found: 411.0694.
obtained as a yellow solid, mp 118-119 C. Yield: 75%
1
(142 mg). H NMR (600 MHz, CDCl3)  11.74 (1H, s),
8.96 (1H, d, J = 1.8 Hz), 8.06 (1H, dd, J = 8.4, 1.8 Hz),
7.98 (2H, d, J = 7.8 Hz), 7.85 (1H, d, J = 7.8 Hz), 7.41 (1H,
d, J = 1.8 Hz), 7.38 (1H, dd, J = 8.4, 1.8 Hz), 7.31 (2H, d,
J = 8.4 Hz), 7.01 (1H, d, J = 8.4 Hz), 2.56. (2H, q, J = 7.8
Hz), 2.41 (3H, s), 1.17 (3H, t, J = 7.2 Hz); 13C NMR (150
MHz, CDCl3)  198.9, 161.3, 160.0, 149.9, 140.3, 137.7,
136.7, 135.2, 134.7, 131.6, 131.5, 129.7, 127.2, 119.6,
118.8, 118.5, 27.9, 21.3, 15.8; IR (ATR) 2967, 2937, 2860,
1623, 1580, 1472, 1450, 1381, 1339, 1290, 1246, 1218,
1142, 1117, 807, 755 cm-1; HRMS m/z (M+) calcd for
C21H19NO2: 317.1416. Found: 317.1414.
(6-(4-Ethynylphenyl)pyridin-3-yl)(2-hydroxyphenyl)
methanone (5h). The title compound (5h) was prepared
according to the general procedure. The product was
obtained as a yellow solid, mp 130-133oC. Yield: 71%
(5-Bromo-2-hydroxyphenyl)(6-(4-propylphenyl)pyridin
1
(127 mg). H NMR (600 MHz, CDCl3)  11.85 (1H, s),
-3-yl)methanone (6d). The title compound (6d) was
8.97 (1H, d, J = 1.8 Hz), 8.08 (1H, dd, J = 8.4, 2.4 Hz),
prepared according to the general procedure. The product
o
8.05 (2H, d, J = 9.0 Hz), 7.87 (1H, d, J = 8.4 Hz), 7.62 (2H, was obtained as a yellow solid, mp 110-111 C. Yield:
1
d, J = 7.8 Hz), 7.59 (1H, dd, J = 7.8, 1.2 Hz), 7.55 (1H, td,
J = 8.4, 1.2 Hz), 7.09 (1H, d, J = 7.8 Hz), 6.91 (1H, td, J =
7.2, 0.6 Hz), 3.1 (1H, s); 13C NMR (150 MHz, CDCl3) 
198.9, 163.2, 158.9, 149.9, 138.1, 137.8, 136.9, 132.9,
132.7, 132.1, 127.2, 123.9, 119.9, 119.1, 119.0, 118.7, 83.2,
79.1; IR (ATR) 3224, 2921, 1619, 1580, 1474, 1442, 1378,
1335, 1300, 1239, 1147, 1030, 832, 758 cm-1; HRMS m/z
(M+) calcd for C20H13NO2: 299.0946. Found: 299.0946.
74% (175 mg). H NMR (600 MHz, CDCl3)  11.79 (1H,
s), 8.95 (1H, s), 8.05 (1H, dd, J = 8.4, 2.4 Hz), 8.00 (2H, d,
J = 8.4 Hz), 7.86 (1H, d, J = 8.4 Hz), 7.72 (1H, d, J = 2.4
Hz), 7.59 (1H, dd, J = 9.0, 2.4 Hz), 7.31 (2H, d, J = 8.4
Hz), 6.99 (1H, d, J = 8.4 Hz), 2.65 (2H, t, J = 8.4 Hz), 1.68
(2H, q, J = 7.2 Hz), 0.95 (3H, t, J = 7.8 Hz); 13C NMR
(150 MHz, CDCl3)  198.0, 162.1, 160.6, 150.0, 145.3,
139.4, 137.6, 135.3, 134.7, 130.7, 129.2, 127.3, 120.7,
120.3, 119.7, 110.6, 37.8, 24.3, 13.8; IR (ATR) 2955, 1617,
1584, 1461, 1371, 1329, 1288, 1210, 1153, 1104, 941, 821,
786 cm-1; HRMS m/z (M+) calcd for C21H18BrNO2:
395.0521. Found: 395.0523.
(2-Hydroxyphenyl)(6-(naphthalen-1-yl)pyridin-3-yl)me
thanone (5i). The title compound (5i) was prepared
according to the general procedure. The product was
o
obtained as a yellow solid, mp 117-119 C. Yield: 70%
1
(136 mg). H NMR (600 MHz, CDCl3)  11.92 (1H, s),
(5-Bromo-2-hydroxyphenyl)(6-(4-bromophenyl)pyridin
-3-yl)methanone (6e). The title compound (6e) was
prepared according to the general procedure. The product
9.08 (1H, d, J = 1.8 Hz), 8.15-8.13 (2H, m), 7.95 (1H, d, J
= 8.4 Hz), 7.93-7.92 (1H, m), 7.75 (1H, d, J = 7.8 Hz ),
7.70 (1H, dd, J = 8.4, 1.8 Hz), 7.67 (1H, dd, J = 6.6, 1.2
Hz), 7.59-7.50 (4H, m), 7.12 (1H, d, J = 8.4 Hz), 6.95 (1H,
td, J = 8.4, 1.2 Hz); 13C NMR (150 MHz, CDCl3)  199.2,
163.3, 162.3, 149.7, 137.3, 137.2, 136.9, 133.9, 133.1,
131.8, 130.8, 129.8, 128.5, 127.9, 126.9, 126.1, 125.3,
125.2, 124.6, 119.1, 119.0, 118.7; IR (ATR) 3046, 2921,
2934, 1584, 1483, 1332, 1304, 1239, 1146, 1025, 930, 758
cm-1; HRMS m/z (M+) calcd for C22H15NO2: 325.1103.
Found: 325.1101.
o
was obtained as a yellow solid, mp 134-136 C. Yield:
1
75% (193 mg). H NMR (600 MHz, CDCl3)  11.79 (1H,
s), 8.95 (1H, d, J = 1.8 Hz), 8.06 (1H, dd, J = 7.8, 1.8 Hz),
7.96 (2H, d, J = 8.4 Hz), 7.86 (1H, d, J = 8.4 Hz), 7.69 (1H,
d, J = 2.4 Hz), 7.63 (2H, d, J = 9.0 Hz), 7.61 (1H, dd, J =
9.0, 2.4 Hz), 7.00 (1H, d, J = 9.0 Hz); 13C NMR (150 MHz,
CDCl3)  197.9, 162.1, 159.3, 150.0, 139.6, 137.8, 136.7,
134.7, 132.2, 131.4, 128.8, 124.9, 120.8, 120.3, 119.8,
110.7; IR (ATR) 3084, 1616, 1579, 1457, 1376, 1323,
1285, 1216, 1149, 1074, 1005, 825, 784 cm-1; HRMS m/z
(M+) calcd for C18H11Br2NO2: 430.9157. Found: 430.9160.
(2-Hydroxy-5-methylphenyl)(6-(4-methoxy-3-methylph
enyl)pyridin-3-yl)methanone (6a). The title compound
(6a) was prepared according to the general procedure. The
(5-Chloro-2-hydroxyphenyl)(6-(p-tolyl)pyridin-3-yl)met
hanone (6f). The title compound (6f) was prepared
according to the general procedure. The product was
o
product was obtained as a yellow solid, mp 130-132 C.
Yield: 76% (151 mg). 1H NMR (600 MHz, CDCl3)  11.71
(1H, s), 8.96 (1H, d, J = 2.4 Hz), 8.05 (1H, dd, J = 7.8, 2.4
Hz), 7.55 (1H, d, J = 7.8 Hz), 7.46-7.44 (1H, m), 7.40 (1H,
s), 7.35 (1H, dd, J = 8.4, 2.4 Hz), 6.99 (1H, d, J = 7.8 Hz),
6.85-6.84 (2H, m), 3.84 (3H, s), 2.45 (3H, s), 2.27 (3H, s);
13C NMR (150 MHz, CDCl3)  199.1, 162.6, 161.2, 160.2,
149.4, 137.9, 137.8, 136.9, 132.6, 131.8, 131.4, 131.1,
128.2, 123.6, 118.7, 118.4, 116.5, 111.5, 55.3, 20.9, 20.5;
IR (ATR) 3023, 1619, 1583, 1477, 1445, 1385, 1304, 1242,
1209, 1140, 929, 745, 693 cm-1; HRMS m/z (M+) calcd for
C21H19NO3: 333.1365. Found: 333.1362.
o
obtained as a brown solid, mp 145-147 C. Yield: 74%
1
(143 mg). H NMR (600 MHz, CDCl3)  11.77 (1H, s),
8.95 (1H, s), 8.05 (1H, dd, J = 8.4, 1.2 Hz), 7.98 (2H, d, J
= 7.8 Hz), 7.86 (1H, d, J = 9.0 Hz), 7.58 (1H, d, J = 2.4
Hz), 7.46 (1H, dd, J = 9.0, 2.4 Hz), 7.31 (2H, d, J = 7.8
Hz), 7.04 (1H, d, J = 9.0 Hz), 2.41 (3H, s); 13C NMR (150
MHz, CDCl3)  198.1, 161.6, 160.5, 149.9, 140.6, 137.6,
136.6, 135.0, 131.7, 130.7, 129.7, 127.2, 123.8, 120.3,
119.7, 119.6, 21.4; IR (ATR) 3291, 3073, 1624, 1586,
1465, 1380, 1323, 1284, 1216, 1168, 1095, 946, 786 cm-1;
HRMS m/z (M+) calcd for C19H14ClNO2: 323.0713. Found:
323.0712.
(6-(3,5-Bis(trifluoromethyl)phenyl)pyridin-3-yl)(2-hydr
oxy-5-methylphenyl)methanone
(6b).
The
title
compound (6b) was prepared according to the general
(5-Chloro-2-hydroxyphenyl)(6-(3-ethynylphenyl)pyridi
n-3-yl)methanone (6g). The title compound (6g) was
prepared according to the general procedure. The product
procedure. The product was obtained as a yellow solid, mp
o
1
140-142 C. Yield: 68% (173 mg). H NMR (600 MHz,
CDCl3)  11.63 (1H, s), 9.00 (1H, d, J = 1.8 Hz), 8.56 (2H,
s), 8.15 (1H, dd, J = 8.4, 1.8 Hz), 7.98 (2H, dd, J = 11.4,
3.6 Hz), 7.37 (1H, dd, J = 9.0, 1.2 Hz), 7.32 (1H, s), 7.00
(1H, d, J = 4.5 Hz), 2.26 (3H, s); 13C NMR (150 MHz,
CDCl3)  198.5, 161.3, 156.4, 150.1, 140.0, 138.3, 138.1,
133.3, 132.4 (q, J = 33.4 Hz), 132.3, 128.4, 127.3 (q, J =
3.4 Hz), 123.3 (q, J = 3.4 Hz), 123.2 (q, J = 271.3 Hz),
120.2, 118.6, 20.5; IR (ATR) 2920, 1589, 1482, 1386,
1339, 1277, 1164, 1127, 1070, 830, 791 cm-1; HRMS m/z
(M+) calcd for C21H13F6NO2: 425.0850. Found: 425.0854.
o
was obtained as a yellow solid, mp 137-139 C. Yield:
1
69% (137 mg). H NMR (600 MHz, CDCl3)  11.74 (1H,
s), 8.97 (1H, d, J = 1.8 Hz), 8.21 (1H, s), 8.08 (2H, dd, J =
8.4, 2.4 Hz), 7.89 (1H, d, J = 7.8 Hz), 7.59 (1H, d, J = 8.4
Hz), 7.56 (1H, d, J = 3.0 Hz), 7.49-7.46 (2H, m), 7.05 (1H,
d, J = 9.0 Hz), 3.12 (1H, s); 13C NMR (150 MHz, CDCl3) 
198.0, 161.7, 159.4, 149.9, 138.1, 137.7, 136.8, 133.6,
131.7, 131.5, 131.0, 129.1, 127.7, 123.8, 123.0, 120.4,
120.0, 119.6, 83.1, 77.9; IR (ATR) 2912, 1575, 1463, 1396,
1325, 1285, 1214, 1149, 822, 783 cm-1; HRMS m/z (M+)
calcd for C20H12ClNO2: 333.0557. Found: 333.0555.
8
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10.1002/adsc.201701137
Advanced Synthesis & Catalysis
(5-Fluoro-2-hydroxyphenyl)(6-(4-pentylphenyl) pyridin
-3-yl)methanone (6h). The title compound (6h) was
prepared according to the general procedure. The product
1100, 1034, 1003, 782, 751 cm-1; HRMS m/z (M+) calcd
for C20H13ClF3NO2: 391.0587. Found: 391.0587.
o
was obtained as a yellow solid, mp 121-123 C. Yield:
(E)-3-(3-Oxohept-1-en-1-yl)-4H-chromen-4-one (8). The
title compound (8) was prepared according to the general
procedure. The product was obtained as a white solid, mp
114-120oC.Yield: 46% (70 mg). 1H NMR (600 MHz,
CDCl3)  8.23 (1H, dd, J = 6.6, 1.8 Hz), 8.12 (1H, s), 7.67
(1H, td, J = 7.2, 1.2 Hz), 7.56 (1H, d, J = 15.6 Hz), 7.45
(1H, d, J = 8.4 Hz), 7.42 (1H, t, J = 7.8 Hz), 7.28 (1H, d, J
= 16.2 Hz), 2.60 (2H, t, J = 7.2 Hz), 1.62 (2H, quint., J =
7.2 Hz), 1.33 (2H, sex., J = 7.8 Hz), 0.90 (3H, d, J = 7.2
Hz) ; 13C NMR (150 MHz, CDCl3)  201.1, 176.1, 157.7,
155.5, 134.0, 132.7, 128.9, 126.3, 125.9, 124.1, 119.4,
118.1, 41.9, 26.3, 22.4, 13.9; IR (ATR) 3050, 3027, 2813,
1660, 1645, 1575, 1490, 1435, 1319, 1288, 1213, 1165,
1071, 989, 780 cm-1; HRMS m/z (M+) calcd for C16H16O3:
256.1099. Found: 256.1096.
1
72% (156 mg). H NMR (600 MHz, CDCl3)  11.61 (1H,
s), 8.96 (1H, d, J = 1.8 Hz), 8.05 (1H, dd, J = 8.4, 2.4 Hz),
7.99 (2H, d, J = 8.4 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.32-
7.29 (3H, m), 7.28-7.24 (1H, m), 7.05 (1H, dd, J = 9.6, 4.8
Hz), 2.66 (2H, t, J = 7.8 Hz), 1.65 (2H, quint, J = 7.8 Hz),
1.36-1.31 (4H, m), 0.88 (3H, t, J = 7.2 Hz); 13C NMR (150
MHz, CDCl3)  198.1, 160.6, 159.3, 154.2 (d, J = 239.1
Hz), 149.9, 145.6, 137.5, 135.3, 130.8, 129.1, 127.2, 124.3
(d, J = 24.1 Hz), 120.0 (d, J = 6.9 Hz), 119.5, 118.5 (d, J =
6.9 Hz), 17.6 (d, J = 24.1 Hz), 35.7, 31.4, 30.9, 22.5, 13.9;
IR (ATR) 2924, 2856, 1633, 1581, 1475, 1418, 1384, 1331,
1277, 1220, 1129, 1016, 1065, 786 cm-1; HRMS m/z (M+)
calcd for C23H22FNO2: 363.1635. Found: 363.1633.
(5-Fluoro-2-hydroxyphenyl)(6-(4-(trifluoromethyl)phen
yl)pyridin-3-yl)methanone (6i). The title compound (6i)
was prepared according to the general procedure. The
Spectrophotometric Measurements:
o
product was obtained as a yellow solid, mp 133-135 C.
Yield: 75% (162 mg). 1H NMR (600 MHz, CDCl3)  11.56
(1H, s), 9.01 (1H, d, J = 1.8 Hz), 8.20 (2H, d, J = 7.8 Hz),
8.11 (1H, dd, J = 7.8, 1.8 Hz), 7.93 (1H, d, J = 8.4 Hz),
7.77 (2H, d, J = 8.4 Hz), 7.31-7.26 (2H, m), 7.08 (1H, dd,
J = 9.6, 4.8 Hz); 13C NMR (150 MHz, CDCl3)  197.9 (d, J
= 2.4 Hz) 159.5, 158.8, 155.5, 153.9, 149.9, 141.1, 137.8,
132.0, 131.7 (d, J = 30.6 Hz), 127.7, 125.9 (q, J = 3.4 Hz),
124.7 (q, J = 22.9 Hz), 123.1, 120.2 (d, J = 6.9 Hz), 118.4
(d, J = 5.7 Hz), 117.5 (d, J = 22.9 Hz); IR (ATR) 2922,
2854, 1578, 1582, 1476, 1411, 1319, 1220, 1167, 1109,
1065, 1015, 786 cm-1; HRMS m/z (M+) calcd for
C19H11F4NO2: 361.0726. Found: 361.0723.
A UV-Vis spectrophotometer (Optizen UV-3200) was
used to evaluate the absorbance spectra of the synthesized
compounds at 298K (room temperature). Commercially
available OBZ (Aldrich, analytical standard, ≥ 98% pure)
and synthesized compounds 3a, 3b, 3f, 3h, 5a, 5e, 5f, 6b,
6g, and 6j were all prepared at a concentration of 50 µM in
ethanol solvent (Sigma-Aldrich, ≥99.8% pure). For solvent
background, all data were corrected by setting the solvent
as blank through the instrument’s calibration. As the
absorption spectra for UV protecting materials
(UVA/UVB) is in the range of 290-400nm, the samples
absorption spectra were taken in the range of 200-550 nm.
With ethanol as a blank, samples were all prepared in 1 cm
quartz cell. The data were obtained in every 5 nm at each
point, charted by the data analysis The UVA/UVB-ratio is
an arithmetic term of the amount of UVA-coverage with
that of UVB-coverage. Another parameter used is critical
wavelength λc, it is defined as the 90% of the area of
absorbance spectrum under the approximate lower
wavelength limit of terrestrial sunlight (290 nm) to 400 nm.
(3,5-Dichloro-2-hydroxyphenyl)(6-(p-tolyl)pyridin-3-yl)
methanone (6j). The title compound (6j) was prepared
according to the general procedure. The product was
o
obtained as a yellow solid, mp 141-143 C. Yield: 74%
1
(158 mg). H NMR (600 MHz, CDCl3)  12.21 (1H, s),
8.96 (1H, s), 8.08 (1H, d, J = 7.8 Hz), 7.99 (2H, d, J = 7.8
Hz), 7.89 (1H, d, J = 7.8 Hz), 7.63 (1H, s), 7.53 (1H, d, J =
7.5 Hz), 7.32 (2H, d, J = 7.3 Hz), 2.42 (3H, s); 13C NMR
(150 MHz, CDCl3) 197.7, 160.8, 157.4, 149.9, 140.9,
137.9, 136.2, 134.7, 130.4, 130.3, 129.8, 127.3, 124.4,
123.7, 120.3, 119.8, 21.4; IR (ATR) 3287, 3173, 1620,
1576, 1475, 1382, 1327, 1280, 1217, 1169, 1099, 947, 789
cm-1; HRMS m/z (M+) calcd for C19H13Cl2NO2: 357.0323.
Found: 357.0323.
Preparation of agar plate for antibacterial studies:
The preparation of agar plate has been included in the
supporting information. For the preparation of agar plate,
water was added to the nutrient agar mixture powder
DifcoTM and the final volume was made up to 500ml in a
flask. The flask was covered with a piece of aluminum foil
and the contents inside was heated to boil for a 1 min with
constant stirring. The contents were then transferred to a 1
L pyrex jar and autoclaved for 20 minutes followed by
cooling to ~55 °C and pouring into a thin layer (5mm) of
~8mL into each plate. The plate was swirled in a circular
motion in order to distribute the agar on bottom surface
uniformly and cooled for about 20-25 min until it settled as
a stable gel. The plate was then flipped upside down so as
to avoid condensation on the agar medium.
(3,5-Dichloro-2-hydroxyphenyl)(6-(4-ethynylphenyl)py
ridin-3-yl)methanone (6k). The title compound (6k) was
prepared according to the general procedure. The product
o
was obtained as a yellow solid, mp 157-159 C. Yield:
1
71% (156 mg). H NMR (600 MHz, CDCl3)  12.19 (1H,
s), 8.98 (1H, d, J = 1.8 Hz), 8.09 (1H, dd, J = 8.4, 2.4 Hz),
8.06 (2H, d, J = 8.4 Hz), 7.91 (1H, d, J = 8.4 Hz), 7.63 (3H,
dd, J = 8.4, 2.4 Hz), 7.51 (1H, d, J = 2.4 Hz), 3.20 (1H, s);
13C NMR (150 MHz, CDCl3)  197.7, 159.8, 157.5, 150.0,
137.9, 137.8, 136.3, 132.8, 130.9, 130.3, 127.3, 124.4,
124.2, 123.7, 120.2, 120.1, 83.1, 79.3; IR (ATR) 2910,
1573, 1460, 1386, 1320, 1275, 1210, 1139, 820, 786 cm-1;
HRMS m/z (M+) calcd for C20H11Cl2NO2: 367.0167.
Found: 367.0167.
Acknowledgements
This study was supported by the 2016 Yeungnam University
Research Grant (216A345034).
(5-Chloro-2-hydroxy-4-methylphenyl)(6-(4 (trifluorome
thyl)phenyl)pyridin-3-yl)methanone (6l). The title
compound (6l) was prepared according to the general
procedure. The product was obtained as a yellow solid, mp
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o
1
151-153 C. Yield: 70% (164 mg). H NMR (600 MHz,
CDCl3)  11.73 (1H, s), 8.99 (1H, s), 8.20 (2H, d, J = 8.4
Hz), 8.10 (1H, dd, J = 8.4, 2.4 Hz), 7.93 (1H, d, J = 8.4
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3009, 1627, 1571, 1480, 1432, 1370, 1301, 1233, 1161,
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Advanced Synthesis & Catalysis
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FULL PAPER
BF3∙OEt2-Promoted Annulation for Substituted
2-Arylpyridines as Potent UV Filters and
Antibacterial Agents
Adv. Synth. Catal. Year, Volume, Page – Page
Sabera Sultanaa, Shizuka Mei Bautista Maezonoa,
Muhammad Saeed Akhtara, Jae-Jin Shima, Young-
Jung Weeb, Sung Hong Kimc and Yong Rok Leea*
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