Synthesis of Fused Oxazolocoumarins from o-Hydroxynitrocoumarins and Benzyl Alcohol Under Gold Nanoparticles or FeCl3 Catalysis

Article abstract of DOI:10.1002/jhet.2842

Synthesis of fused oxazolocoumarins has been achieved from the one-pot tandem reactions of o-hydroxynitrocoumarins with benzyl alcohol in toluene under catalysis in a sealed tube at 150°C. The catalysis was performed by gold nanoparticles supported on TiO

Full text of DOI:10.1002/jhet.2842

Month 2017 Synthesis of Fused Oxazolocoumarins from o-Hydroxynitrocoumarins and
Benzyl Alcohol Under Gold Nanoparticles or FeCl3 Catalysis†
a
b
a
*
Evangelia-Eirini N. Vlachou, Gerasimos S. Armatas, and Konstantinos E. Litinas
aLaboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki
54124, Greece
bDepartment of Materials Science and Technology, University of Crete, Vassilika Vouton, Heraklion 71003, Greece
*
E-mail: klitinas@chem.auth.gr
†Preliminary communications presented at the 12th Chemistry Congress of Greece-Cyprus, Thessaloniki, Greece, May 2015, CD Abstrs., slides, pdf 73;
IXth Joint Meeting in Medicinal Chemistry, Athens, Greece, June 2015, Abstrs. P51.
Received May 12, 2016
DOI 10.1002/jhet.2842
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
Synthesis of fused oxazolocoumarins has been achieved from the one-pot tandem reactions of
o-hydroxynitrocoumarins with benzyl alcohol in toluene under catalysis in a sealed tube at 150°C. The
catalysis was performed by gold nanoparticles supported on TiO2 (0.4 mol% Au) or FeCl3 (5%) or silver
nanoparticles supported on TiO2 (1.7 mol% Ag).
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
at 140°C. The other is the condensation of
o-aminophenols with either carboxylic acids in the
presence of Lawesson’s reagent under microwaves [20]
or the condensation of aromatic aldehydes under 2-
Iodoxybenzoic acid (IBX) oxidation [21] or under Ir-
catalyzed hydrogen transfer reactions [22]. Very recently
[23] the Ag/TiO2 NPs were applied for an analogous
synthesis from aldehydes and carboxylic acids derivatives
in water. Recently 2-arylbenzoxazoles were synthesized
in a one-pot tandem procedure from o-nitrophenols and
benzyl alcohols under dppf catalysis [24] or catalysis by
gold NPs supported on titanium oxide [25].
In continuation to our interest in this field [3,15,26,27],
we wish to apply the catalysis [26] with NPs Au/TiO2 or
with FeCl3 [27], as well as the catalysis with NPs
Ag/TiO2 for the first time in the synthesis of fused
oxazolocoumarins in a one-pot tandem procedure using
the o-hydroxynitrocoumarins as starting materials along
with benzyl alcohol. The reactions studied and the
products obtained are depicted in Scheme 1.
Coumarin derivatives, natural or synthetic, represent a
class of compounds with important biological activities
[1–5], such as anticoagulant, antibiotic, antiiflammatory,
antivirus, or anticancer. Fused coumarin derivatives
possess also a wide range of biological effects. Especially,
furocoumarins are used as photochemotherapeutics [6,7].
Fused oxazolocoumarins have been studied for
photosensitizing [8], antibacterial [9], anti-inflammatory
[9,10], and antimicrobial [11] activities or as
agonists/antagonists of the benzodiazepine receptor [12].
There are few synthetic methods for the preparation
of fused oxazolocoumarins starting from the heating
on a steam bath of a mixture of 6-hydroxy-4-methyl-
5-nitrocoumarin acetate with iron powder, CH3COONa,
and (CH3CO)2O in acetic acid [13]. The reactions of
o-aminohydroxycoumarins with acids [12,14], anhydrides
[9], or aromatic aldehydes [9,11,12,14] led also to
oxazolocoumarins. The condensations of 7-methoxyimino-
4-methylchromen-2,8-dione with methylarenes, arylacetic
esters, benzylchloride, or phosphorus ylides gave the
corresponding title compounds [15]. Another procedure
was by anodic oxidation of 7-hydroxycoumarin in a
solution of MeCN and LiClO4 [16].
RESULTS AND DISCUSSION
The reaction of 6-hydroxy-5-nitrocoumarin (2a) [28]
with excess of benzyl alcohol (1) in the presence of
catalytic amount (0.4 mol% Au) of 1% Au/TiO2 NPs
(Method A, Table 1, entry 1) in refluxing toluene
for 8 days resulted to the corresponding 2-phenyl-7
H-chromeno[5,6-d][1,3]oxazol-7-one (3a) in 55% yield,
Among the conventional methods for the synthesis of
benzoxazoles, there are usually two approaches. One is
the use of o-haloanilides by intramolecular cyclization
with CuO nanoparticles (NPs) [17] or FeCl3 [18]
catalyzed cross coupling or base-mediated in DMSO [19]
© 2017 Wiley Periodicals, Inc.

E.-E. N. Vlachou, G. S. Armatas, and K. E. Litinas
Vol 000
Scheme 1. Reagents and conditions: (i) Method A: (0.4 mol% Au) of 1% Au/TiO2 NPs, (Ar atmosphere, toluene, reflux) or (sealed tube, 150°C); Method
B: 5% FeCl3 (Ar atmosphere, toluene, reflux) or (sealed tube, 150°C); Method C: (1.7 mol% Ag) 4% Ag/TiO2 NPs (Ar atmosphere, toluene, reflux) or
(sealed tube, 150 °C); 4 (from Method B, MW, 120°C); 7 (from Method C).
while 13% of the starting coumarin recovered. The MS
spectrum of the new compound 3a gave the expected
molecular ion at m/z 264 [M + H]+ In the 1H–NMR
spectrum, there is a doublet at 8.42 ppm (d, 1H,
J = 9.6 Hz) for the 4-H of the coumarin moiety,
deprotected from the fused oxazole ring, and a peak at
8.28 ppm (dd, 2H, J1 = 2.0 Hz, J2 = 7.6 Hz) for the o-H
of phenyl ring, while in the 13C–NMR spectrum, there
are only aromatic and C = O carbons. We investigated
next the suitable conditions for the synthesis of fused
oxazolocoumarins by using the aforementioned coumarin
2a as the representative reactant. Different catalysts and
solvents were screened under different temperatures
(Table 1). The analogous reaction between 2a and 1 in
the presence of 5% FeCl3 (Method B, Table 1, entry 2)
as the catalyst led to the oxazolocoumarin 3a in 46%
yield with 25% unreacted coumarin 2a. The use of 4%
Ag/TiO2 NPs (Method C, Table 1, entry 3) in this
reaction for the first time as a catalyst (1.7 mol% Ag) in
analogous reactions, according to our knowledge, gave
only 18% of 3a. A blank experiment without the use of
any catalyst had no results (Method D, Table 1, entry 4).
When the reaction of 2a and 1 was performed in toluene
in a sealed tube at 150°C for 24 h under Method A, the
Table 1
Optimization for the conditions of the synthesis of 2-phenyl-7H-chromeno[5,6-d][1,3]oxazol-7-one (3a) from 6-hydroxy-5-nitrocoumarin (2a) with
benzyl alcohol (1).
Entry
Method
Conditions
Products (yield %)
1
2
3
4
A: Au/TiO2 (0.4 mol% Au)
B: FeCl3 (5%)
C: Ag/TiO2 (1.7 mol% Ag)
Toluene, Ar, reflux, 8 days
Toluene, Ar, reflux, 2 days
Toluene, Ar, reflux, 9 days
Toluene, Ar, reflux, 24 h
3a (55), 2a (13)
3a (46), 2a (25)
3a (18), 2a (49)
2a (100)
D: No catalyst
5
6
7
8
A
B
C
A
B
C
A
A
Toluene, sealed tube, 150°C, 24 h
Toluene, sealed tube, 150°C, 2 days
Toluene, sealed tube, 150°C, 3 days
Toluene, MW, 110°C, 4 min
Toluene, MW, 120°C, 4 min
Toluene, MW, 110°C, 4 min
H2O, Ar, reflux, 7 days
3a (95)
3a (93)
3a (48), 2a (24)
3a (5), 2a (70)
3a (24), 4 (40), 2a (35)
2a (100)
2a (100)
3a (traces), 2a (95)
2a (100)
9
10
11
12
13
DCE, Ar, reflux, 6 days
Toluene, Ar, reflux, 5 days
E: CF3SO3Ag
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Fused Oxazolocoumarins from o-Hydroxynitrocoumarins and Benzyl Alcohol
yield of the product 3a was increased to 95% (Table 1,
entry 5). The similar reaction under Method B resulted to
93% of 3a (Table 1, entry 6), while under Ag/TiO2 NPs
(Method C) led to 48% of 3a (Table 1, entry 7). The
reaction of 2a and 1 under Method A and microwave
(MW) irradiation gave only 5% of the product 3a
(Table 1, entry 8), while under Method B and MW
irradiation, the 3a was received in 24% yield along with the
unexpected nitrate 4 (40%) (Table 1, entry 9). The
analogous reaction under Method C in microwaves was
unsuccessful (Table 1, entry 10). By changing the solvent to
H2O or 1,2-dichloroethane (DCE) (Method A), the starting
coumarin 2a was almost recovered (Table 1, entries 11,12).
The use of CF3SO3Ag in the place of silver NPs had not
any outcome for the reaction (Method E, Table 1, entry 13).
After the examination of suitable reaction conditions,
different o-nitrohydroxycoumarins were reacted with
benzyl alcohol in the presence of the aforementioned
catalysts (Table 2). The reactions of 6-hydroxy-4-methyl-
5-nitrocoumarin (2b) [13] with excess of benzyl alcohol
(1) in a sealed tube at 150°C in the presence of Au/TiO2
NPs (Method A) or FeCl3 (Method B) or Ag/TiO2 NPs
(Method C) resulted to oxazolocoumarin 3b [14] in 55%,
49%, or 33% yield, respectively (Table 2, entries 1–3).
The yields are lower than in the case of 3a (Table 1,
entries 5–7) possibly because of steric reasons from the
4-CH3 group.
and gave the oxazolocoumarin 6b [30] in good enough
yields (Methods A,B) (Table 2, entries 7–9). In the cases
of the reactions of 1 with the 7-hydroxy-8-nitrocoumarins
8a,b [9,28], the products 9a,b received in better yields
under Method B (Table 2, entries 10–16). Furthermore,
the reaction of 4-hydroxy-3-nitrocoumarin (10) [31]
resulted to oxazolocoumarin 11 [12] in lower yields
(Table 2, entries 16–18).
In the proposed mechanism for these reactions
under the use of gold or silver NPs (Scheme 2), in
analogy to previous reports [23–25], benzaldehyde (A)
is formed by oxidation of benzyl alcohol (1), while
metal-hydride species [32–36] are generated. The
study for the oxidation of 1 by Au NPs is well
established [34,37], while with Ag NPs is limited [35,36].
o-Nitrohydroxycoumarin 5a is reduced next in situ from
the metal-hydride species to the o-aminohydroxycoumarin
B in a hydrogen transfer process. Hydrogenations of
nitrobenzenes have been studied for both Au [38] and Ag
[39] NPs. The next step is the reaction of A and B to
give the imine C. The imine C is cyclized to the
dihydrooxazolocoumarin D, which is oxidized to the final
product, the oxazolocoumarin 6a. This oxidation could be
attributed to the M-NPs especially in the cases of
refluxing toluene under Ar atmosphere (Table 1, entries
1–3). In the cases of sealed tubes, the yields were better
possibly because of the amount of air presented in the tubes
(Table 1, entries 5–7). When Ag NPs were used, a reduction
in the imine C led to benzylaminocoumarin 7. This event
could be explain by the lower yields of Method C
(Tables 1 and 2).
The analogous reactions of 7-hydroxy-6-nitrocoumarin
(5a) [28,29] with benzyl alcohol (1) under all the referred
catalysts earlier led to the oxazolocoumarin 6a in
moderate yields (Table 2, entries 4–6). In the case of
Method C, the 6-benzylamino-7-hydroxycoumarin (7)
A similar plausible mechanism could be followed in the
case of FeCl3 catalysis in analogy to the Fe–catalyzed
synthesis of benzoxazoles [24].
was
also
isolated.
The
7-hydroxy-4-methyl-6-
nitrocoumarin (5b) [28] reacted also with 1 (Scheme 1)
Table 2
Reactions of o-nitrohydroxycoumarins with benzyl alcohol (1) in toluene in a sealed tube at 150°C.
Entry
o-Nitrohydroxycoumarin
Conditions
Products (yield %)
1
2
3
4
5
6
7
8
2b
2b
2b
5a
5a
5a
5b
5b
5b
8a
8a
8a
8b
8b
8b
10
10
10
Method A, 7 days
Method B, 6 days
Method C, 9 days
Method A, 6 days
Method B, 44 h
Method C, 7 days
Method A, 3 days
Method B, 3 days
Method C, 6 days
Method A, 2 days
Method B, 3 days
Method C, 6 days
Method A, 2 days
Method B, 3 days
Method C, 9 days
Method A, 24 h
Method B, 24 h
3b [14] (55), 2b (15)
3b (49), 2b (22)
3b (33), 2b (35)
6a (30), 5a (33)
6a (40), 5a (27)
6a (26), 5a (42), 7 (5)
6b [30] (71)
6b (57), 5b (16)
6b (25), 5b (43)
9a (45), 8a (26)
9a (48), 8a (22)
9a (36), 8a (29)
9b [11] (38), 8b (34)
9b (60)
9
10
11
12
13
14
16
17
18
19
9b (31), 8b (29)
11 [12] (33), 10 (31)
11 (25), 10 (46)
11 (25), 10 (35)
Method C, 48 h
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E.-E. N. Vlachou, G. S. Armatas, and K. E. Litinas
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Scheme 2. Conditions: (i) Oxidation (dehydrogenation) of 1; (ii) reduction (hydrogen transfer; (iii) imine formation (condensation); (iv) cyclisation; and
(v) oxidation (dehydrogenation).
In conclusion, the one-pot tandem catalyzed synthesis of
fused oxazolocoumarins from o-hydroxynitrocoumarins
and benzyl alcohol is herein reported. The catalysis is
performed with gold or silver NPs supported on TiO2 or
with FeCl3. The catalysis with Ag/TiO2 NPs is the first
ever reported for the synthesis of the benzoxazole moiety
from an o-hydroxynitrobenzene and alcohol. The
synthesis of coumarinyl nitrates in the presence of FeCl3
is under further investigation.
electrospray ionization (ESI) conditions. Microanalyses
were performed on a Perkin-Elmer 2400-II Element
analyzer. Silica gel No60, Merck A.G., was used for
column chromatography. The MW experiments were
performed in a Biotage (Initiator 2.0) scientific MW oven.
General Procedure. Nitration of 6-hydroxycoumarin by
the nitrating agent.
A solution of 6-hydroxycoumarin
(0.5 g, 3.1 mmol) in concentrated H2SO4 (4.16 mL) was
cooled in an ice-bath at 0°C. A cooled at 0°C solution of
concentrated H2SO4 (0.63 mL) and concentrated HNO3
(0.2 mL) was then added dropwise maintaining the
temperature at 0°C. The stirring was continued for 1 h at
0°C till the consumption of the starting compound. The
mixture was poured on ice (~50 g). The precipitate was
filtered, washed with H2O, and dried under vacuum to
give 2a (0.56 g, 89% yield).
EXPERIMENTAL
General. Melting points were determined on a Kofler
hot-stage apparatus and are uncorrected. IR spectra were
obtained with a Perkin-Elmer 1310 spectrophotometer as
KBr pellets. NMR spectra were recorded on a Bruker
AM 300 (300 MHz and 75 MHz for 1H and 13C,
respectively) or an Agilent (Varian) 500/54 (500 MHz
6-Hydroxy-5-nitrocoumarin (2a).
Yellow solid, mp
159–161°C (EtOH) (lit. [28] mp 158–160°C).
6-Hydroxy-4-methyl-5-nitrocoumarin (2b). (96% yield),
yellow solid, mp 215–217°C (EtOH) (lit. [13] mp 208–
1
and 125 MHz for H and 13C, respectively) using CDCl3
as solvent and TMS as an internal standard. J values are
reported in Hz. Mass spectra were determined on an
LCMS-2010 EV Instrument (Shimadzu) under
215°C).
7-Hydroxy-8-nitrocoumarin (8a).
(94% yield), yellow
solid, mp 220 °C (dec) (EtOH) [lit. [28] mp 218°C (dec)].
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Fused Oxazolocoumarins from o-Hydroxynitrocoumarins and Benzyl Alcohol
7-Hydroxy-4-methyl-6-nitrocoumarin (5b).
from 7-hydroxy-4-methylcoumarin) yellow solid, mp
248–250°C (EtOH) (lit. [28] mp 252–254°C).
7-Hydroxy-4-methyl-8-nitrocoumarin (8b).
from 7-hydroxy-4-methylcoumarin) pale orange solid, mp
253–255°C (EtOH) (lit. [9] mp 255–256°C).
(42% yield
concentrated under reduced pressure. The residue was
subjected to column chromatography [silica gel, hex-
ane : ethyl acetate (2:1)] to give 3a (15 mg, 24% yield),
followed by the nitrate 4 (20 mg, 40%) and coumarin
2a (17.5 mg, 35%).
(51% yield
c Method C.
General procedure for the catalyzed reactions of
o-nitrohydroxycoumarins with benzyl alcohol.
i Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 mL, 0.784 g, 7.26 mmol), 4% Ag/TiO2 [11 mg
(0.44 mg Ag, 0.00407 mmol)], and toluene (1 mL) were
added in a sealed tube. The resulted mixture was stirred
at 150°C for 3 days. After cooling, the catalyst was re-
moved by filtration, and the solvent was concentrated
under reduced pressure. The residue was subjected to
column chromatography [silica gel, hexane/ethyl ace-
tate (2:1)] to give 3a (30 mg, 48% yield), followed by
coumarin 2a (12 mg, 24%).
a Method A.
i Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 ml, 0.784 g, 7.26 mmol), 1% Au/TiO2 [19 mg
(0.19 mg Au, 0.00096 mmol)], and toluene (1 mL) were
added in a sealed tube. The resulted mixture was stirred at
150°C for 24 h. After cooling, the catalyst was removed
by filtration, and the solvent was concentrated under re-
duced pressure. The residue was subjected to column
chromatography [silica gel, hexane : ethyl acetate (2:1)]
to give 3a (60 mg, 95% yield).
ii 3a was received in only 18% yield (11 mg), when the
aforementioned procedure was repeated under reflux in
Ar atmosphere for 9 days.
ii The earlier procedure was repeated under reflux in Ar
atmosphere for 8 d and led to 3a (35 mg, 55% yield).
iii Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 mL, 0.784 g, 7.26 mmol), 1% Au/TiO2 [19 mg
(0.19 mg Au, 0.00096 mmol)], and toluene (1 mL) were
added in a vial for MW oven and irradiated under mi-
crowaves at 110°C for 4 min (monitoring by TLC).
After cooling, the catalyst was removed by filtration,
and the solvent was concentrated under reduced pres-
sure. The residue was subjected to column chromatog-
raphy [silica gel, hexane : ethyl acetate (2:1)] to give 3a
(3 mg, 5% yield), followed coumarin 2a (35 mg, 70%).
iv The same procedure in H2O (1 mL) under reflux for
7 days left unchanged the coumarin 2a, while the reflux
in DCE (1 mL) for 6 days gave only traces of 3a.
iii Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 mL, 0.784 g, 7.26 mmol), 4% Ag/TiO2 [11 mg
(0.44 mg Ag, 0.00407 mmol)], and toluene (1 mL) were
added in a vial for MW oven and irradiated under MW
at 110°C for 4 min. TLC examination indicated only
unchanged starting coumarin 2a.
d Method D.
A solution of coumarin 2a (50 mg,
0.24 mmol) and benzyl alcohol (1) (0.75 mL, 0.784 g,
7.26 mmol) in toluene (1 mL) was refluxed for 24 h.
TLC examination indicated only unreacted coumarin 2a.
e Method E. CF3SO3Ag (11 mg, 0.043 mmol) was added
to the solution of coumarin 2a (50 mg, 0.24 mmol) and
benzyl alcohol (1) (0.75 mL, 0.784 g, 7.26 mmol) in
toluene (1 mL), and the resulted mixture was heated
under reflux for 5 days. TLC examination indicated only
b Method B.
the starting coumarin 2a.
2-Phenyl-7H-chromeno[5,6-d][1,3]oxazol-7-one (3a). Light
i Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 mL, 0.784 g, 7.26 mmol), FeCl3 (2 mg,
yellow solid, mp 214–216°C (MeOH), IR (KBr): 3071,
1
1729, 1619, 1602, 1547, 1477 cmÀ1; H–NMR (CDCl3,
0.012 mmol), and toluene (1 mL) were added in a sealed
tube. The resulted mixture was stirred at 150°C for
2 days. After cooling, the catalyst was removed by fil-
tration, and the solvent was concentrated under reduced
pressure. The residue was separated by column chro-
matography [silica gel, hexane : ethyl acetate (2:1)] to
give 3a (59 mg, 94% yield).
500 MHz) δ 6.57 (d, 1H, J = 9.6 Hz), 7.32 (d, 1H,
J
= 8.9 Hz), 7.53–7.59 (m, 3H), 7.70 (d, 1H,
J = 8.9 Hz), 8.28 (dd, 2H, J1 = 2.0 Hz, J2 = 7.6 Hz),
8.42 (d, 1H, J = 9.6 Hz); 13C–NMR (CDCl3, 125 MHz)
δ 111.1, 113.3, 113.7, 117.0, 126.6, 127.7, 129.1, 132.2,
138.5, 139.0, 146.9, 151.6, 160.8, 165.3; MS (ESI): m/z
264 [M + H]+., 318 [M + Na + MeOH]+ Anal. Calcd for
C16H9NO3: C, 73.00; H, 3.45; N, 5.32. Found: C, 72.92;
H, 3.60; N, 5.29.
ii The earlier procedure was repeated under reflux in Ar
atmosphere for 2 days (monitoring by TLC) and gave
the 3a (29 mg, 46% yield).
iii Coumarin 2a (50 mg, 0.24 mmol), benzyl alcohol (1)
(0.75 ml, 0.784 g, 7.26 mmol), FeCl3 (2 mg,
2-Oxo-2H-chromen-6-yl nitrate (4).
Yellow oil, IR
(KBr): 3015, 1717, 1613 cmÀ1
;
1H–NMR (CDCl3,
0.012 mmol), and toluene (1 mL) were added in a vial
for MW oven and irradiated under MW at 120°C for
4 min (monitoring by TLC). After cooling, the catalyst
was removed by filtration, and the solvent was
500 MHz) δ 6.28 (d, 1H, J = 9.4 Hz), 7.05 (dd, 2H,
J1 = 1.9 Hz, J2 = 8.6 Hz), 7.32 (d, 1H, J = 1.9 Hz),
7.36 (d, 1H, J = 8.6 Hz), 7.64 (d, 1H, J = 9.4 Hz);
13C–NMR (CDCl3, 125 MHz) δ 107.1, 113.5, 113.8,
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E.-E. N. Vlachou, G. S. Armatas, and K. E. Litinas
Vol 000
117.1, 128.2, 143.4, 153.3, 159.1, 161.2; MS (ESI): m/z
208 [M + H]+., 206 [M-H]À. Anal. Calcd for C9H5NO5:
C, 52.19; H, 2.43; N, 6.76. Found: C, 52.11; H, 2.49; N,
Method B; 16 mg, 25% yield, Method C), light yellow
solid, mp 191–193°C (MeOH) (lit. [12] mp 189–190°C).
6.68.
9-Methyl-2-phenyl-7H-chromeno[5,6-d][1,3]oxazol-7-one
(3b). [55% yield (Method A), 49% yield (Method B),
REFERENCES AND NOTES
and 33% yield (Method C)] light yellow solid, mp
208–210°C (MeOH) (lit. [14] mp 211–212°C).
2-Phenyl-6H-chromeno[6,7-d][1,3]oxazol-6-one (6a). (19 mg,
30% yield, Method A; 25 mg, 40% yield, Method B;
[1] Murray, D. H.; Mendez, J.; Brown, S. A. In The Natural
Coumarins: Occurrence, Chemistry and Biochemistry; John Wiley &
Sons: New York, 1982; p 1.
[2] O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applica-
tions and Mode of Action; John Wiley & Sons: Chichester, 1997; p 1.
[3] Fylaktakidou, K. C.; Hadjipavlou-Litina, D. J.; Litinas, K. E.;
Nicolaides, D. N. Curr Pharm Des 2004, 10, 3813.
[4] Borges, F.; Roleira, F.; Milhazes, N.; Santana, L.; Uriarte, E.
Curr Med Chem 2005, 12, 887.
[5] Kostova, I.; Raleva, S.; Genova, P.; Argirova, R. Bioinorg
Chem Appl 2006. DOI: 10.1155/BCA/2006/68274.
16.5 mg, 26% yield, Method C), yellow solid, mp 207–
209°C (MeOH), IR (KBr): 3053, 1720, 1610, 1575 cmÀ1
;
1H–NMR (CDCl3, 300 MHz) δ 6.43 (d, 1H, J = 9.6 Hz),
7.54 (s, 1H), 7.55–7.57 (m, 3H), 7.82 (s, 1H), 7.83 (d,
1H, J = 9.6 Hz), 8.25 (dd, 2H, J1 = 1.9 Hz, J2 = 7.6 Hz);
13C–NMR (CDCl3, 75 MHz) δ 99.5, 115.3, 116.5,
118.1, 126.3, 127.8, 129.1, 132.3, 139.2, 143.9, 152.3,
152.6, 160.5, 164.8; MS (ESI): m/z 264 [M + H]+., 302
[M + K]+, 318 [M + Na + MeOH]+ Anal. Calcd for
C16H9NO3: C, 73.00; H, 3.45; N, 5.32. Found: C, 73.07;
H, 3.53; N, 5.39.
[6] Dall’Acqua, F.; Vedaldi, D. In CRC Handbook of Organic
Photochemistry and Photobiology; Horspool, W. M.; Song, P. S. Eds.;
CRC Press: Boca Raton, FL, 1995; pp 1341–1350.
[7] Kitamura, N.; Kohtani, S.; Nakagaki, R.
Photobiol C Photchem Rev 2005, 6, 168.
J Photochem
[8] Pathak, M. A.; Fellman, J. H.; Kaufman, K. D. J Invest
Dermatol 1960, 35, 165.
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Biol 2012, 2, 899.
[10] Kontogiorgis, C.; Hadjipavlou-Litina, D. J. Enz Inh Med
Chem 2003, 18, 63.
[11] Prasanna, B.; Sandeep, A.; Revathi, T. World J Pharm Pharm
Sci 2014, 3, 404.
6-(Benzylamino)-7-hydroxy-2H-chromen-2-one (7). (3 mg,
5% yield, Method C), light yellow solid, mp 180–182°C
(MeOH), IR (KBr): 3424, 3212, 3057, 2924, 2848, 1724,
1
1606, 1562 cmÀ1; H–NMR (CDCl3, 300 MHz) δ 5.04
[12] Colotta, V.; Catarzi, D.; Varano, F.; Cecchi, L.; Filacchioni,
G.; Martini, C.; Giusti, L.; Lucacchini, A. Il Farmaco 1998, 53, 375.
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1965, 30, 4344.
[14] Reddy, S. J Indian Chem Soc 1981, 58, 599.
[15] Bezergiannidou-Balouctsi, C.; Litinas, K. E.; Malamidou-
Xenikaki, E.; Nicolaides, D. N.; Mentzafos, D.; Terzis, A. Tetrahedron
1993, 49, 9127.
(s, 2H), 6.37 (d, 1H, J = 9.6 Hz), 6.79 (s, 1H), 7.36–738
(m, 6H), 7.60 (d, 1H, J = 9.6 Hz); 13C–NMR (CDCl3,
75 MHz) δ 46.5, 112.5, 115.4, 115.7, 117.6, 127.9,
129.2, 132.3, 140.9, 143.0, 143.7, 155.9, 160.2, 161.6;
MS (ESI): m/z 268 [M
C16H13NO3: C, 71.90; H, 4.90; N, 5.42. Found: C, 71.85;
+
H]+ Anal. Calcd for
H, 4.79; N, 5.34.
8-Methyl-2-phenyl-6H-chromeno[6,7-d][1,3]oxazol-6-one
(6b). [71% yield (Method A), 57% yield (Method B)
and 25% yield (Method C)] light yellow solid, mp
231–232 °C (MeOH) (lit. [30] mp 232–233°C).
2-Phenyl-8H-chromeno[8,7-d][1,3]oxazol-8-one (9a). (28 mg,
45% yield, Method A; 30 mg, 48% yield, Method B;
[16] Abdelghani, S.; Abd El-Aal, A.; Shehab, W.; El-Mobayed, M.
Synthesis 2003 1373.
[17] Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.; Paul, R.;
Punniyamurthy, T. J Org Chem 2009, 74, 8719.
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Chen, C. Org Biomol Chem 2011, 9, 1225.
[20] Sejas, J.; Vazquez-Tato, M.; Carballido-Reboredo, M.;
Crecente-Campo, J.; Romar-Lopez, L. Synlett 2007, 313.
[21] Chen, F.; Shen, C.; Yang, D. Tetrahedron Lett 2011, 52, 2128.
[22] Blacker, A. J.; Farah, M. M.; Hall, M. I.; Mrsden, S. P.; Saidi,
O.; Williams, J. M. J. Org Lett 2009, 11, 2039.
[23] Maleki, B.; Baghayeri, M.; Vahdat, S. M.; Mohammadzadeh,
A.; Akhoondi, S. RSC Adv 2015, 5, 46545.
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14, 2722.
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2013, 69, 4612.
[27] Symeonidis, T. S.; Hadjipavlou-Litina, D. J.; Litinas, K. E.
J Heterocyclic Chem 2014, 51, 642.
22 mg, 36% yield, Method C), light yellow solid, mp 197–
199°C (MeOH), IR (KBr): 3071, 1729, 1657 cmÀ1; H–
1
NMR (CDCl3, 300 MHz) δ 6.45 (d, 1H, J = 9.6 Hz), 7.49
(d, 1H, J = 8.5 Hz), 7.54–7.58 (m, 3H), 7.82 (d, 1H,
J = 8.5 Hz), 7.86 (d, 1H, J = 9.6 Hz), 8.29 (dd, 2H,
J1 = 1.7 Hz, J2 = 7.6 Hz); 13C–NMR (CDCl3, 75 MHz) δ
99.5, 107.4, 115.4, 118.1, 126.6, 128.1, 129.1, 132.2, 139.2,
139.7, 143.9, 150.8, 160.5, 164.6; MS (ESI): m/z 264
[M
+
H]+., 296 [M
+
H
+
MeOH]+., 318
[M + Na + MeOH]+ Anal. Calcd for C16H9NO3: C, 73.00;
H, 3.45; N, 5.32. Found: C, 72.87; H, 3.51; N, 5.22.
6-Methyl-2-phenyl-8H-chromeno[8,7-d][1,3]oxazol-8-one
(9b). [38% yield (Method A), 60% yield (Method B),
and 31% yield (Method C)] light yellow solid, mp
232–234°C (MeOH) (lit. [11] mp 232–234°C).
2-Phenyl-4H-chromeno[3,4-d][1,3]oxazol-4-one (11).
(20.5 mg, 33% yield, Method A; 16 mg, 25% yield,
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985.
[29] Lin, S.-T.; Yang, F.-M.; Yang, H.-J.; Huang, K.-F. J Chem
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Herrera, M.; Sevenand, D. V.; Villinger, A.; Ghochikyan, T. V.;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Fused Oxazolocoumarins from o-Hydroxynitrocoumarins and Benzyl Alcohol
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet