Synthesis and spectral study of novel benzopyrone and quinolinone derivatives

Article abstract of DOI:10.3184/174751913X13738962423671

A series of novel benzopyrones and quinolinone derivatives were prepared using the readily obtainable 6-nitrobenzo- 2-pyron-3-carboxylate through the reaction with nitrogen nucleophilic reagents such as cyclohexyl amine, p-aminoacetophenone, diamines, hydrazine hydrate, thiosemicarbazide, anthranilic acid and carbon nucleophile as malononitrile. The IR, ¹H NMR and mass spectra of the new synthesised compounds were discussed. Website

Full text of DOI:10.3184/174751913X13738962423671

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 535
SEPTEMBER, 535–541
Synthesis and spectral study of novel benzopyrone and quinolinone
derivatives
M.R. Mahmoud and F.S.M. Abu El-Azm*
Synthetic Lab of Organic Chemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo, Egypt
A series of novel benzopyrones and quinolinone derivatives were prepared using the readily obtainable 6-nitro-
benzo-2-pyron-3-carboxylate through the reaction with nitrogen nucleophilic reagents such as cyclohexyl amine,
p-aminoacetophenone, diamines, hydrazine hydrate, thiosemicarbazide, anthranilic acid and carbon nucleophile as
malononitrile. The IR, 1H NMR and mass spectra of the new synthesised compounds were discussed.
Keywords: benzopyrones, quinolinone, fused 1,3,4-thiadiazepine derivatives
The coumarin nucleus is widely available from plants and is an
important class of oxygen heterocycle.1–3 The useful medical
properties associated with these naturally occurring coumarins
have lead to the investigation of several synthetic analogues.
A large number of compounds containing coumarin have
been investigated because of their anti-inflammatory4, anti-
bacterial5, vasorelaxant6, antihepatitis-C virus agent7 and anti-
proliferative activities8. In view of this, and as continuation
of our effort9–15 to identify new, potent, selective and less toxic
antimicrobial agents, we aimed to synthesise a new coumarin
derivative that exhibits high therapeutic activity.
The EI fragmentation pattern of compound 1 is consistent
with the proposed structure. The C–O bond cleavage of the
molecular ion followed by a rearrangement through the γ-
hydrogen shift leads to the loss of the ethylene molecule and to
the formation of the ion [M+.-28] which loss CO2 to give the
base peak at m/z = 191 (100%).
It has been reported16 that the reaction of amines with 3-car-
boethoxy coumarin produced the corresponding 3-coumarin
carboxamide without fission of the heterocyclic ring. In the
present investigation, we aim to illustrate the effect of a nitro
group in 6-position on the reactivity of both α,β-unsaturated
δ-lactone and ester groups towards primary amines as nitrogen
nucleophiles. Thus, compound 1 reacted with cyclohexyl
amine in boiling ethanol and produced a semi-solid which was
triturated with ethanol to give soluble and insoluble fractions.
The soluble fraction (37%) after evaporation of the solvent and
purification was identified as 4-N-cyclohexylamino-6-nitro-3-
(N-cyclohexyl) carboxamido coumarin 2 (Scheme 1).
Results and discussion
Nitration of 3-carboethoxy coumarin in HNO3/AcOH mixture
afforded 3-carboethoxy-6-nitrocoumarin 1 as the sole product
(one spot in the TLC). The structure of 1 was characterised by
its analytical and spectroscopic data (IR, 1H NMR, MS). Thus,
the IR spectrum of 1 showed sharp bands at 1736 cm−1 (νC=O
of α,β-unsaturated δ-lactone), 1706 cm−1 (νC=O of ester group).
However, 1H NMR spectrum of 1 in CDCl3 showed the follow-
ing absorptions from low to high field: δ (ppm) 7.89–7.2 (m,
4Harom. + olefinic C4–H), 4.2 (q, 2H, CH2CH3, J = 6.7 Hz) and
1.2 (t, 3H, CH2CH3, J = 6.7 Hz).
The structure of 2 was substantiated from the analytical and
spectroscopic data. Thus, IR spectrum displayed the stretching
absorption bands at 3360,3300 cm−1 (νNH), 1758 cm−1 (νC=O
saturated δ-lactone), 1663 cm−1 (νC=O amide) and at 1600 (νC=C
which were consistent with the proposed structure. H NMR
)
1
Scheme 1
* Correspondent. E-mail: ftmsaber@yahoo.com

536 JOURNAL OF CHEMICAL RESEARCH 2013
spectrum (DMSO-d6) exhibited absorptions at δ (ppm) 8.9–8.6
(two s, 2H, exchangeable NH), 7.5 (s, 3Harom.), 3.0 (d, 1H,
C3–H, J = 4.2 Hz), 2.8 (t, 1H, C4–H, J = 5.5 Hz) and 2.0–1.2
(br, 22H, two cyclohexyl groups). The mass spectrum of com-
pound 2 displayed the correct molecular ion peak at m/z = 415
as the base peak. The insoluble fraction (58%) was crystallised
from dilute acetic acid to produce 6-nitro-3-(N-cyclohexyl)
carboxamidobenzo-2-pyrone 3 whose structure was deduced
from the following evidence: (i) Correct analytical data. (ii) Its
IR spectrum showed the stretching frequency of the NH group
at 3210 cm−1 besides the C=O absorption bands at 1726 cm−1
and 1658 cm−1 which are characteristic for α,β-unsaturated
δ-lactone and amide, respectively. (iii) The 1H NMR spectrum
(CDCl3) showed the signals at δ (ppm) 8.2 (br.s, 1H, exchange-
able NH), 7.4–7.2 (br.s, 4Harom. + C4–H) and 2.0–1.2 (m, 11H,
C6H11). (iv) The EI fragmentation pattern of 3 was completely
in accord with the proposed structure, which show the correct
molecular ion at m/z = 316 together with the base peak at m/z
= 146 attributable for the coumarin moiety.
protons and olefinic proton at C4-position. The ethyl protons
appeared as quartet for 2H at δ 4.28 ppm and triplet for 3H at
δ 1.27 ppm with equal coupling constant (J = 6.7 Hz). Further-
more, a singlet appears at δ 2.4 ppm representing the methyl
group. The mass spectrum of 6 was in accord with the assigned
structure.
The structure of the 3-substituted quinolin-2(H)-one deriva-
tive 7 was inferred from the analytical and spectroscopic data
1
1
(IR, HNMR, MS). HNMR (DMSO-d6) spectrum exhibited
two singlets at δ 10.3, 8.9 ppm which disappeared in D2O
representing the two NH together with multiplet integrated for
8H at δ 8.2–7.1 ppm corresponding to aromatic protons with
olefinic proton at C4.The methyl protons appeared as singlet
integrated for 3H at δ 2.4 ppm. Furthermore, the fragmentation
pattern of the mass spectrum displayed the molecular ion peak
at m/z = 351 which is the base peak.
The proclivity of compound 1 towards diamines was also
investigated. 6-Nitro-3-(benzimidazol-2-yl)benzo-2-pyrone 9
was obtained upon heating compound 1 with o-phenylene
diamine in an oil-bath at 190 °C (Scheme 1). Structure 9 was
established from the analytical and spectroscopic data. The IR
spectrum lacked the νC=O characteristic for the ester group and
exhibited νC=O at 1726 cm−1 (α,β-unsaturated δ-lactone), νC=N at
Refluxing compound 1 with 4-aminoacetophenone in boil-
ing ethanol in the presence of acetic acid afforded 6-nitro-3-
N-(4-acetylphenyl) carboxamidobenzo-2-pyrone 4 as the sole
product (Scheme 1). The assigned structure of 4 was consistent
with the study of its IR spectrum which displayed νNH (br)
at 3380 cm−1, νC=O (δ-lactone) at 1730 cm−1, νC=O (ketone) at
1675 cm−1 and νC=O (amide) at 1648. Both the mass spectrum
1
1632 cm−1, and νNH at 3345 cm−1. Furthermore, the H NMR
spectrum (CDCl3) showed a singlet at δ 9.1 ppm for one proton
which is characteristic for NH and multiplet for (8H) at δ 7.8–
7.2 ppm attributable for aromatic protons and C4–H. The mass
spectrum showed the radical cation peak at m/z = 307 (41.3%)
which represent the molecular ion peak upon loss of benzimid-
azolyl moiety yielded the base peak at m/z = 190 (100%).
Treatment of 1 with benzidine in boiling ethanol furnished
6-nitro-3N-(4′-aminobiphenyl) carboxamidobenzo-2-pyrone
10 as the sole product. The structure 10 was substantiated
1
and H NMR spectrum of 4 (CDCl3) revealed signals which
agree with the proposed structure. Formation of 4 had probably
occurred through the nucleophilic addition of the amino group
to the positively polarised carbonyl of the carboxylate group
through the AAC2 mechanism.
Furthermore, the structure of 4 was substantiated from the
following evidence.
1
First, compound 4 was stirred with 3,4,5-trimethoxybenzal-
dehyde in the presence of ethanolic sodium hydroxide (10%)
to give the corresponding chalcone 5 whose structure was con-
firmed by the elemental analysis and IR spectrum which exhib-
ited νC=O (δ-lactone) at 1738 cm−1, νC=O (α,β-unsaturated ketone)
at 1676 cm−1, νC=O (amide) at 1656 cm−1. Second, compound 4
was fused with ethyl cyanoacetate in the presence of ammo-
nium acetate in an oil bath at 160–170 °C. The resulting semi-
solid contained two products (TLC, two spots, Rf = 0.3, Rf =
0.42). This mixture was separated by fractional crystallisations
(see exp.) and gave 6 (32%) and 7 (19.1%) (Scheme 1).
The formulation assigned for compound 6 was established
by analytical and spectroscopic data. Thus, the IR spectrum
of 6 displayed νC≡N at 2226 cm−1, νC=O (ester) at 1708 cm−1,
νC=O (amide) at 1660, 1654 cm−1 with olefinic absorption at
1612 cm−1. There was an indication of hydrogen bonded –OH
absorption at 3300–3500 cm−1ponting to an enolisable system
(lactam lactim) and laking for the νC=O (unsaturated δ-lactone)
and νC=O of ketone. Furthermore, compound 6 failed to react
with phenyl hydrazine, 2,4-dinitrophenyl hydrazine or hydrox-
ylamine hydrochloride indicating the absence of free ketonic
group. Thus, Michael adduct 8 was rejected.
exclusively from IR, HNMR and mass spectral data. IR
spectrum of 10 exhibited the stretching frequencies of NH as
doublet at 3440, 3370 cm−1, νC=O (δ-lactone) at 1730 cm−1 and
νC=O (amide) at 1668 cm−1 and the 1HNMR spectrum (CDCl3)
of 10 displayed signals at δ (ppm) 9 (s, 1H, NH, exchangeable
with D2O), 7.9–7.1 (m, 12Harom. + C4–H) and broad singlet at
δ 4.6 ppm for 2H exchangeable with D2O corresponding to
NH2 protons. The highest recorded peak at m/z = 399 attributed
to the M+.-2 peak. The base peak (m/z = 184) represented the
benzidine radical cation which is obtained by α-cleavage.
Diazotization of 10 and coupling with alkaline β-naphthol
gave the red dye 12 which is a good evidence for the presence
of a primary aromatic amino group.
Compound 10 upon recrystallisation with acetic acid
produced the N-acetyl derivative 11 whose the structure was
substantiated from the elemental analysis and molecular
weight determination, the IR spectrum showed additional νC=O
at 1670 cm−1 which is attributable to the acetamido group and
1HNMR spectrum (DMSO-d6) of 11 showed a singlet at δ 2.36
attributable for CH3CO group besides the characteristic signals
for aromatic and olefinic protons.
It has been reported that the reaction of coumarins with
hydrazine hydrate affects the fission of heterocyclic ring17.
In the present investigation, the study of behaviour of 3-
carboethoxy-6-nitrocoumarin 1 towards hydrazine hydrate has
Moreover, the 1H NMR spectrum of compound 6 displayed
signals at δ (ppm) 10.3 and 8.6 as two singlets each integrating
for one proton which disappeared using D2O and two multiplet
in range 8.3–7.1 integrates for 8H representing for aromatic

JOURNAL OF CHEMICAL RESEARCH 2013 537
been extended. Compound 1 contains two possible sites for
nitrogen nucleophiles. Thus, compound 1 reacted with hydra-
zine hydrate to give a mixture of two products (two spots in
TLC, Rf = 4.15, 3.16).
The azine derivative 13 could be isolated in pure crystalline
form by trituration of the crude mixture with benzene
(Scheme 2).
One possible approach to explain the formation of the azine
13 involves the hydrazinolysis of δ-lactone through 1,4-addi-
tion followed by ring fission of the heterocyclic ring and also
the hydrazinolysis of the ester group (Scheme 3).
Compound 14 (soluble fraction in benzene) was obtained
in pure crystalline form after slow evaporation of benzene.
The structure 14 was confirmed by microanalytical and
spectroscopic data. The formation of 14 could be visualised as
in Scheme 4.
It has been reported18 that 4-alkyl-3-carboethoxybenzo-2-
pyrone undergoes cyclocondensation with thiosemicabazide
and yielded 3-[1,2,4-triazol-3-yl]benzo-2-pyrone derivative.
This reaction was reinvestigated with compound 1. Thus,
treatment of 1 with thiosemicabazide in refluxing n-butanol,
resulted in the formation of the product with molecular
formula C11H8N4O5S (M+. = 308). This formula indicates the
removal of ethanol molecule during the reaction pathway from
the two reactants. Three possible structures were assumed for
this product 15–17.
Scheme 2
Scheme 3

538 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 4
recorded peak in the mass spectrum of compound 18 at m/z =
452 represent the molecular ion peak. The conversion of 15
to 18 could be explained on the basis of acid-catalysed ring
opening followed by elimination of H2S gas to give the 1,3,4-
oxadiazole derivative A and finally simple condensation
reaction (Scheme 5).
Ample evidence for the postulated mechanism is obtained
by refluxing compound 15 with acetic acid which afforded
the N-acetylamino derivative 19 which is a good support for
1
the formation of intermediate A. The IR and H NMR were
consistent with the assigned structure 19.
The behaviour of 3-carboxy-6-nitrobenzo-2-pyrone towards
anthranilic acid has been further investigated in the present
study.19 The treatment of 1 with anthranilic acid in refluxing
n-butanol afforded 6-nitro-3-[3,1-benzoxazin-4-oxo-2-yl]
benzo-2-pyrone 20 (Scheme 6).
The structure assigned for 20 was consistent with the ana-
lytical data. Its IR spectrum displayed well defined absorption
bands at 1763 cm−1 (νC=O of benzoxazinone ring), 1732 cm−1
(νC=O of δ-lactone). On the other hand, the mass spectrum
exhibited peak at m/z = 336 (27.9%) attributable for the parent
molecular ion.
The IR and 1HNMR of the product revealed a pattern com-
pletely different from that expected for structures 16 and 17
and can only be intelligibly interpreted in terms of structure 15
since the IR spectrum of the product showed absorption bands
corresponding to the amino groups (3390 and 3280 cm−1),
NH group (3190 cm−1), saturated δ-lactone (1742 cm−1), cyclic
amide (1680 cm−1), 1614 cm−1 (C=N) and lacked νC=S. The
1H NMR spectrum (CDCl3) showed signals characteristic for
3NH protons at δ 9.1, 8.8 as two singlet with ratio (2:1) and
multiplet for aromatic protons together with two doublets each
integrated for one proton. The EI fragmentation pattern for
compound 15 showed peak at m/z = 310 (M+.+2). Furthermore,
compound 15 was condensed with 3,4,5-trimethoxybenzalde-
hyde in the presence of catalytic amount of dilute acetic acid,
H2S gas was released during the reaction time and the product
formed was investigated. This product lacked sulfur in ordi-
nary element test and elemental analysis, N% = 12.64. The
IR spectrum exhibited νC=O at 1730 cm−1(unsat. δ-lactone) and
νC=N at 1648 cm−1 and its believed that the assigned structure 18
was in accord with the above results (Scheme 3). The highest
Compound 1 reacted with malononitrile in the presence of
NaOEt/EtOH under Michael conditions and yielded 21 as the
sole product. Compound 21 was soluble in sodium bicarbonate
solution and its IR spectrum displayed broad absorption band
at 3460–2960 cm−1 (νNH2, OH), νC≡N at 2226 cm−1, νC=O at 1732
cm−1 (unsat. δ-lactone), νC=O at 1693 cm−1 (unsaturated acid),
1
νC=C at 1615 cm−1. Moreover, the H NMR spectrum showed
the absence of signals characteristic for ethyl protons and
only deshielded acidic proton appeared at δ 11.4 ppm which
indicates the hydrolysis of the ester group during the reaction
conditions. The formation of Michael adduct 21 possibly takes
place via the formation of malononitrile dimer followed by
carbanion 1,4-addition (Scheme 7).

JOURNAL OF CHEMICAL RESEARCH 2013 539
Scheme 5
Scheme 7
Scheme 6
volume of conc. HNO3 and glacial acetic acid (20 mL) was refluxed
for 3h. After cooling, the reaction mixture was quenched by adding
crushed ice. The yellow solid product obtained was filtered, washed
several times with H2O, dried and then recrystallised from ethanol
to give 1 as yellow crystals, m.p. 160–163 °C (yield 86%). IR (KBr):
1736 cm−1 (νCO α,β-unsaturated δ-lactone), 1706 cm−1 (νCO α,β-unsatu-
rated ester), 1605 cm−1 (νC=C). 1H NMR (CDCl3): δ (ppm) 7.89–7.2 (m,
4Harom. + C4–H), 4.2 (q, 2H, J = 6.7 Hz), 1.2 (t, 3H, J = 6.7 Hz). MS
(m/z): 263 (M+., 23.3), 235 (M-C2H4, 33.85), 218 (M-OEt, 30.11), 191
(100), 163 (23.76), 144 (22.63), 117 (31.7), 89 (37). Anal. Calcd for
C12H9NO6 (263): C, 54,75; H, 3.42; N, 5.32. Found: C, 54,55; H, 2.98;
N, 5.6%.
Conclusion
1,3,4-Oxadiazolyl-3,1-benzoxazinyl-, benzimidazolyl-, 1,3,4-
thiadiazapine benzopyran-2-one and other novel 3-substituted
benzopyran-2-one and quinolone-2-one derivative were pre-
pared using the easily accessible starting material 6-nitro ben-
zopyran-3-carboxylate via the reaction with different amines,
diamine, anthranilic acid, hydrazine, thiosemicarbazide and
carbon nucleophile. The synthesised compounds were obtained
in good yields.
Experimental
(2) and (3): A solution of 3-carboethoxy-6-nitro benzo-2-pyrone 1
(2.63 g, 0.01 mol) in absolute ethanol and (50 mL) was treated with
cyclohexylamine (2 mL, 0.02 mol) and the mixture was heated under
reflux for 3h. After concentration and cooling, the semi-solid product
obtained was refluxed with ethanol to give soluble and insoluble frac-
tions. The soluble fraction, after evaporation of the solvent and purifi-
cation with benzene left 2 as pale yellow crystals, m.p. 120–122 °C
(yield 37%). IR (KBr): 3360, 3300 cm−1 (νNH), 1758 cm−1 (νCO satu-
rated δ-lactone), 1663 cm−1 (νCO amide). 1H NMR (CDCl3): δ (ppm) 8.9
(s, 1H, NH, exchangeable with D2O), 8.6 (s, 1H, NH, exchangeable
with D2O), 7.5 (s, 3Harom.), 3.0 (d, 1H, C3-H, J = 4.2 Hz), 2.8 (t, 1H,
C4–H, J = 5.5 Hz), 2.0–1.2 (m, 22H, cyclohexyl protons). MS (m/z):
Melting points were determined on a Biotius hot-stage microscope
and are uncorrected. The IR spectra were recorded on a Pye-Unicam
SP 1200 spectrophotometer using the KBr Wafer technique. The H
NMR spectra were determined on Varian A-60 and Joel NMR EX-270
MHz spectrometers using TMS as an internal standard. The mass
spectra were carried out on an MS QP 1000 EX schimdzu spectrom-
eter, Japan EI 70 eV, ionisation chamber 250 °C. Microanalysis was
performed by Microanalytical units, Cairo and Ain Shams Universi-
ties. The homogeneity of the synthesised products was controlled by
TLC.
1
Ethyl-6-nitrobenzo-2-pyrone-3-carboxylate (1): A mixture of 3-
carboethoxy benzo-2-pyrone20–22 (2.17 g, 0.01 mol) and an equal

540 JOURNAL OF CHEMICAL RESEARCH 2013
415 (100), 323 (62.6), 295 (16.6), 202 (37.9), 92 (66.2). Anal. Calcd
for C22H29N3O5 (415): C, 63.61; H, 6.98; N, 10.12. Found: C, 63.9; H,
6.73; N, 9.9%. The insoluble fraction was recrystallised from dilute
acetic acid to give 6-nitro-3-N-(cyclohexyl)carboxamido benzo-2-
pyrone 3 as orange crystals, m.p. 220–222 °C (yield 58%). IR (KBr):
3210 cm−1 (νNH), 1726 cm−1 (νCO), 1658 cm−1 (νCO). 1H NMR (CDCl3):
δ (ppm) 8.2 (s, 1H, NH, exchangeable with D2O), 7.4–7.2 (br.s, 4Harom.
+ C4–H), 2.0 (m, 11H, C6H11). MS (m/z): 316 (M+., 22.8), 190 (76.3),
162 (8.6), 146 (100), 117 (76.1), 101 (9.2), 89 (56.2), 77 (10.1). Anal.
Calcd for C16H16N2O5 (316): C, 60.76; H, 5.06; N, 8.86. Found: C,
60.87; H, 5.31; N, 8.77%.
dried and recrystallised from benzene to give 10 as red crystals, m.p.
188–190 °C (yield 61%). IR (KBr): 3440, 3370 cm−1 (νNH2), 1730
(νCO), 1668 cm−1 (νCO amide). 1H NMR (CDCl3): δ (ppm) 9 (s, 1H, NH,
exchangeable with D2O), 7.9–7.1 (m, 12Harom. + C4–H), 4.6 (br.s, 2H,
NH2, exchangeable with D2O). MS (m/z): 399 (M+. - 2, 13.9), 356
(27.3), 234 (16.2), 218 (26.1), 190 (70.2), 184 (100), 146 (30.1), 117
(77.6), 89 (40.0). Anal. Calcd for C22H15N3O5 (401): C, 65.83; H, 3.74;
N, 10.47. Found: C, 65.88; H, 3.67; N, 10.22%. Recrystallisation of
11 with glacial acetic acid deposited a yellow crystals 11, m.p. 192–
194 °C (yield 86%). IR (KBr): 3379, 3197 cm−1 (νNH), 1736 cm−1 (νCO),
1
1670, 1665 cm−1. H NMR (DMSO-d6): δ (ppm) 9.6 (s, 1H, NH,
(4): A mixture of compound 1 (2.63 g, 0.01 mol) and p-aminoace-
tophenone (1.35 g, 0.01 mol) was dissolved in ethanol (20 mL) and
heated under reflux for 2h (TLC). After concentration and cooling, the
solid product obtained was triturated with methanol, filtered off, dried
and recrystallised from a mixture of benzene–light petroleum ether
(60–80 °C) to give 4 as orange crystals, m.p. 160–162 °C (yield 46%).
IR (KBr): 3380 cm−1 (νNH), 1730 (νCO δ-lactone), 1675 cm−1 (νCO ketone),
1648 cm−1 (νCO amide). 1H NMR (CDCl3): δ (ppm) 9 (s, 1H, NH,
exchangeable with D2O), 7.9–7.2 (m, 7Harom. + C4–H), 2.4 (s, 3H,
MeCO). MS (m/z): 352 (M+., 16.8), 190 (56.3), 146 (100), 135 (20.3),
120 (25.1), 117 (53.4), 92 (11.4), 89 (33.1), 77 (6.8). Anal. Calcd for
C18H12N2O6 (352): C, 61.36; H, 3.4; N, 7.95. Found: C, 61.61; H, 3.53;
N, 8.0%
exchangeable with D2O),8.3 (br.s, 1H, NH, exchangeable with D2O),
7.9–7.3 (m, 12Harom. + C4–H), 2.36 (s, 3H, COMe). MS (m/z): 401
(M- CH2=C=O, 31.2), 234 (22.7), 218 (11.3), 190 (97.3), 184 (100),
146 (52.6), 117 (23.6). Anal. Calcd for C24H17N3O6 (443): C, 65.01; H,
3.83; N, 9.48. Found: C, 65.32; H, 3.66; N, 9.51%.
Hydrazinolysis of (1): (13) and (14): A solution of compound 1
(2.63 g, 0.01 mol) in absolute ethanol (50 mL) was treated with hydra-
zine hydrate (0.03 mol) and the mixture was heated under reflux for
5h (TLC). The solid separated after concentration was filtered off,
washed with dilute HCl, then with water, and finally dried and
triturated with benzene. The insoluble fraction was crystallised from
benzene to give 13 as pale yellow crystals, m.p. 170–172 °C (yield
41.7%). IR (KBr): 3530–3150 (br.) cm−1 (νOH), 1626 cm−1 (νC=N). MS
(m/z): 330 (M+., 17.2), 285 (100), 192 (50.0), 165 (37.9), 164 (87.6),
137 (44.2), 120 (21.6), 93 (66.1), 65 (30.2).Anal. Calcd for C14H10N4O6
(330): C, 50.9; H, 3.03; N, 16.96. Found: C, 51.81; H, 3.29; N, 16.66%.
Evaporation of benzene left a crude product which recrystallised
from light petroleum ether (b.p. 80–100 °C) to give 14 as pale yellow
crystals, m.p. 106–108 °C (yield 23%). IR (KBr): 3262 cm−1 (νNH),
1663 cm−1 (νC=O),1622 cm−1 (νC=N). MS (m/z): 230 (M+.-1, 21.9),
203(M-N2, 16.7), 188 (100), 186 (50.4), 139 (30.1), 93 (70.2), 65
(66.1). Anal. Calcd for C10H5N3O4 (231): C, 51.94; H, 2.16; N, 18.18.
Found: C, 52.07; H, 2.41; N, 18.33%.
(Z)-2-Amino-10-nitro-4H-chromeno[3,4-f][1,3,4]thiadiazepine-
5,6(5aH,11bH)-dione (15): A mixture of 1 (0.01 mol), thiosemicarba-
zide (0.01 mol) and n-butanol (30 mL) was stirred in an oil-bath at
180 °C for 6h. The solid which separated after trituration with ethanol
was filtered off, washed with cold ethanol, and recrystallised from
ethanol to give 15 as pale yellow crystals, m.p. 135–140 °C (yield 45%).
IR (KBr): 3390, 3280 cm−1 (νNH2), 3190 (νNH), 1742 (νCO sat.δ lactone), 1680
cm−1 (νCO amide). 1H NMR (CDCl3): δ (ppm) 9.1 (br.s, 2H, NH2,
exchangeable with D2O), 8.8 (s, 1H, NH, exchangeable with D2O),
7.8 (m, 3Harom.), 3.1 (d, 1H, C6-H, J = 4.8 Hz), 2.8 (d, 1H, C7-H,
J = 3.3 Hz). MS (m/z): 310 (M + 2, 17.6), 269 (19.6), 235 (30.2), 191
(70.7), 146 (100), 102 (33.6). Anal. Calcd for C11H8N4O5S (308): C,
42.85; H, 2.59; N, 18.18. Found: C, 42.56; H, 2.7; N, 17.76%.
3-(5-(3,4,5-Trimethoxy benzylideneamino)-1,3,4-oxadiazol-2-yl)-6-
nitro-2H-chromen-2-one (18): Compound 15 (0.01 mol) was dissolved
in acetic acid (20 mL). 3,4,5-trimethoxybenzaldehyde (0.01 mol) in
acetic acid (10 mL) was gradually added while stirring for 30 min.
The reaction mixture was refluxed for 2h. H2S gas was released during
the reaction time. The reaction mixture was diluted with water, and
the solid separated was filtered off and crystallised from methanol to
give 18 as orange crystals, m.p. 125–127 °C (yield 51%). IR (KBr):
1730 cm−1 (νCO unsat.δ lactone), 1648 cm−1 (νC=N). 1H NMR (CDCl3): δ (ppm)
9.1 (s, 1H, N=CH), 8.3–7.4 (m, 4Harom+C4-H.), 6.9 (s, 2Harom), 3.87
(s, 6H, OMe), 3.8 (s, 3H, OMe). MS (m/z): 452 (M+., 100), 259
(M-ArCN, 44.2), 191 (27.9), 146 (50.1). Anal. Calcd for C21H16N4O8
(452): C, 55.75; H, 3.53; N, 12.38. Found: C, 55.67; H, 3.43; N,
12.64%.
(5): Compound 4 (3.5 g, 0.01 mol) was dissolved in ethanolic
sodium hydroxide solution (20 mL, 10%). A solution of 3,4,5-trime-
thoxy benzaldehyde (1.96 g, 0.01 mol) in 15 ml ethanol was gradually
added while stirring in an ice bath for 1h. The solid that separated was
filtered off, washed several times with H2O, dried and recrystallised
from ethanol to give 5 as brick-red crystals, m.p. 85–87 °C (yield
76.7%). IR (KBr): 3271 cm−1 (νNH), 1738 (νCO δ-lactone), 1676 cm−1
(νCO amide), 1656 cm−1 (νCO α,β-unsaturated ketone). 1H NMR (CDCl3):
δ (ppm) 8.7 (s, 1H, NH, exchangeable with D2O), 7.8–7.3 (m, 8Harom.
+ C4–H), 6.9 (s, 2Harom.), 6.6 (d, 2H, J = 11.3 Hz), 3.85 (s, 6H, 2OMe),
3.8 (s, 3H, OMe). MS (m/z): 530 (M+., 70.3), 337 (100), 221 (22.1),
218 (67.2), 191 (90.3), 146 (46.6). Anal. Calcd for C28H22N2O9 (530):
C, 63.39; H, 4.15; N, 5.28. Found: C, 63.61; H, 3.98; N, 5.08.
(6) and (7): A mixture of compound 4 (0.01 mol), ethylcyanoace-
tate (0.01 mol) and ammonium acetate (0.3 mol) was stirred in an
oil-bath at 160–170 °C for 6h (TLC). The reaction mixture was poured
onto water. The brown solid that separated was filtered off, washed
several times with H2O, dried and treated with benzene/drops of
methanol to give 6 as light brown crystals, m.p. 270–272 °C (yield
32%). IR (KBr): 3500–3300 cm−1 (νNH,OH), 2226 (νC≡N), 1708 (νCO
ester), 1660 cm−1 (νCO amide). 1H NMR (DMSO-d6): δ (ppm) 10.3 (s, 1H,
NH, exchangeable with D2O), 8.6 (s, 1H, NH, exchangeable with
D2O), 8.3–7.1 (m, 8Harom. + C4–H), 4.28 (q, 2H, J = 6.7 Hz), 2.4 (s, 3H,
Me), 1.27 (t, 3H, J = 6.7 Hz). MS (m/z): 446 (M+., 30.2), 230 (100),
217 (80.2), 202 (36.1), 190 (22.9), 185 (42.3), 158 (16.8), 157 (27.1),
145 (40.4). Anal. Calcd for C23H18N4O6 (446): C, 61.88; H, 4.03; N,
12.55. Found: C, 62.03; H, 4.11; N, 12.34%. The remaining solid was
crystallised from methanol to give 7 as brown crystals, m.p. >300 °C
(yield 19.1%). IR (KBr): 3550–3000 cm−1 (νNH,OH), 1695 (νCO ketone),
1
1660 cm−1 (νCO amide), 1654 (νCO). H NMR (DMSO-d6): δ (ppm) 10.3
(s, 1H, NH, exchangeable with D2O), 8.9 (s, 1H, NH, exchangeable
with D2O), 8.2–7.1 (m, 8Harom. + C4–H), 2.4 (s, 3H, Me). MS (m/z):
351 (M+., 100), 217 (42.6), 189 (13.6), 144 (21.9), 135 (77.3), 120
(33.1), 92 (28.3). Anal. Calcd for C18H13N3O5 (351): C, 61.54; H, 3.7;
N, 11.96. Found: C, 61.77; H, 3.75; N, 11.68%.
Reaction of 1 with diamine
(A) With o-phenylenediamine gives 6-nitro-3-(benzimidazol-2-yl)
benzo-2-pyrone (9): A mixture of 1 (0.01 mol) and o-phenylenedi-
amine (0.01 mol) was heated in an oil-bath at 170 °C for 12h. The
reaction mixture was triturated with dilute methanol, filtered off,
and recrystallised from methanol to give 9 as light brown crystals,
m.p. 190–195 °C (yield 62%). IR (KBr): 3345 cm−1 (νNH), 1726 (νCO
α,β-unsaturated δ-lactone), 1632 cm−1 (νC=N). 1H NMR (CDCl3):
δ (ppm) 9.1 (s, 1H, NH, exchangeable with D2O), 7.8–7.2 (m, 8Harom.
+ C4–H). MS (m/z): 307 (M+., 41.3), 190 (100), 163 (11.2), 146 (7.8).
Anal. Calcd for C16H9N3O4 (307): C, 62.54; H, 2.93; N, 13.68. Found:
C, 62.32; H, 2.77; N, 13.61%.
(B) With benzidine gives 6-nitro-3-N-(4-aminobiphenyl)carbox-
amido benzo-2-pyrone (10) and its N-acetylated derivative (11): A
mixture of 1 (2.63 g, 0.01 mol) and benzidine (1.84 g, 0.01 mol) in
abs. ethanol (50 mL) was refluxed for 3h (TLC). The reaction mixture
was concentrated, cooled and the solid separated was filtered off,
N-(5-(6-Nitro-2-oxo-2H-chromen-3-yl)-1,3,4-oxadiazol-2-yl)acet-
amide (19): A solution of compound 15 (0.5 g, mol) in glacial acetic
acid (20 mL) was refluxed for 3h. After cooling, the reaction mixture
was diluted with water. The deposited solid was filtered off, dried
and recrystallised from dioxane to give 19 as yellow crystals, m.p.
166–168 °C (yield 47.5%). IR (KBr): 3212 cm−1 (νNH), 1734 cm−1
(νCO), 1679 cm−1 (νCO). 1H NMR (DMSO-d6): δ (ppm) 9.6 (s, 1H, NH,
exchangeable with D2O), 7.7–7.4 (m, 4Harom+C4-H.), 2.1 (s, 3H,
MeCO). MS (m/z): 316 (M+., 100), 274 (82.6), 191 (26.6), 188 (43.3),
92 (63.4). Anal. Calcd for C13H8N4O6 (316): C, 49.36; H, 2.53; N,
17.72. Found: C, 49.71; H, 2.6; N, 17.53%.
3-(3,1-Benzoxazin-4-oxo-2-yl)benzo-2-pyrone (20):
A solution
of 3-carboethoxy-6-nitro benzo-2-pyrone 1 (0.01 mol) in n-butanol

JOURNAL OF CHEMICAL RESEARCH 2013 541
3
4
P.K. Bose, J. Ind. Chem. Soc., 1958, 35, 367.
(20 mL) was treated with anthranilic acid (0.01 mol) then refluxed
for 8h. The solid that separated after cooling was collected, washed
several times with water, dried and crystallised from benzene to
give 20 as yellow crystals, m.p. 153–155 °C (yield 63%). IR (KBr):
1763 cm−1 (νCObenzoxazinone), 1732 cm−1 (νCO unsat.δ lactone). MS (m/z): 336
(M+, 27.9), 190 (33.1), 146 (100), 118 (20.1). Anal. Calcd for
C17H8N2O6 (336): C, 60.71; H, 2.38; N, 8.33. Found: C, 61.06; H,
2.51; N, 8.0%.
Michael adduct (21): The carboethoxy benzo-2-pyrone 1 (0.01 mol)
was dissolved in a minimum amount of absolute ethanol and treated
with an alcoholic solution of sodium ethoxide (0.01 mol). The
malononitrile (0.01 mol) was then added and the mixture was kept
overnight then refluxed on water-bath for 6h. The cold mixture was
acidified with dilute acetic acid, and the deposited solid was filtered
off and crystallised from methanol to give 21 as pale yellow crystals,
m.p. 170–173 °C (yield 36.3%). IR (KBr): br. 3460–2960 cm−1
(νNH2,OH), 2226 (νC≡N), 1732 cm−1 (νCO unsat.δ lactone), 1693 cm−1 (νCO unsat. acid).
1H NMR (CDCl3): δ (ppm) 11.4 (s, 1H, COOH, exchangeable with
D2O), 7.7 (m, 3Harom), 5.1 (br.s, 2H, NH2, exchangeable with D2O),
4.1 (s, 1H). MS (m/z): 365 (M+., 11.3), 235 (72.3), 190 (100), 146
(40.2), 118 (16.3), 71 (52.7). Anal. Calcd for C16H7N5O6 (365): C,
52.6; H, 1.91; N, 19.17. Found: C, 52.43; H, 2.13; N, 18.77%.
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Received 20 May 2013; accepted 20 June 2013
Paper 1301957 doi: 10.3184/174751913X13738962423671
Published online: 6 September 2013
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