New synthesis and reactivity of 3-bromoacetyl-4-hydroxy-6-methyl-2H-pyran- 2-one with binucleophilic amines

Article abstract of DOI:10.1002/jhet.507

3-(Bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo-DHAA with alkanediamines, phenylhydrazines, ortho-phenylenediamines, and ortho-aminobenzenethiol. The obtained new products 3-(2-N-substituted-acetyl)-4- hydroxy-6-methyl-2H-pyran-2-ones, 4-hydroxy-3-[1-hydroxy-2-(2-phenylhydrazinyl) vinyl]-6-methyl-2H-pyran-2-one, 1-(2,4-dinitrophenyl)-7-methyl-2,3-dihydro-1H- pyrano[4,3-c]pyridazine-4,5-dione, 3-(3,4-dihydroquinoxalin-2-yl)-4-hydroxy-6- methyl-2H-pyran-2-one/3-(3,4-dihydroquinoxalin-2-yl)-6-methyl-2H-pyran-2,4(3H) -dione, 6-methyl-3-(3,4-dihydroquinoxalin-2-yl)-2H-pyran-2,4(3H)-dione, and (E)-3-(2H-benzo[b][1,4]thiazin-3(4H)-ylidene)-6-methyl-2H-pyran-2,4(3H)-dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra.

Full text of DOI:10.1002/jhet.507

January 2011
New Synthesis and Reactivity of 3-Bromoacetyl-4-hydroxy-6-
methyl-2H-pyran-2-one with Binucleophilic Amines
63
Djamila Hikem-Oukacha,a Maamar Hamdi,a* Artur M. S. Silva,b
and Rachedi Yahiaa
a
´
Laboratoire de Chimie Organique Appliquee (Groupe heterocycles associe CRAPC),
Faculte de Chimie, Universite des Sciences et de la Technologie Houari Boumedienne,
´ ´
´
´
´
´
BP32, El-Alia 16111 Bab-Ezzouar, Alger, Algerie
bDepartment of Chemistry & QOPNA, University of Aveiro, Aveiro 3810-193 Portugal
*E-mail: prhamdi@gmail.com
Received December 26, 2009
DOI 10.1002/jhet.507
Published online 2 September 2010 in Wiley Online Library (wileyonlinelibrary.com).
3-(Bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one was synthesized by the reaction of dehydroace-
tic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized
from the reaction of bromo-DHAA with alkanediamines, phenylhydrazines, ortho-phenylenediamines,
and ortho-aminobenzenethiol. The obtained new products 3-(2-N-substituted-acetyl)-4-hydroxy-6-
methyl-2H-pyran-2-ones,
4-hydroxy-3-[1-hydroxy-2-(2-phenylhydrazinyl)vinyl]-6-methyl-2H-pyran-2-
one, 1-(2,4-dinitrophenyl)-7-methyl-2,3-dihydro-1H-pyrano[4,3-c]pyridazine-4,5-dione, 3-(3,4-dihydro-
quinoxalin-2-yl)-4-hydroxy-6-methyl-2H-pyran-2-one/3-(3,4-dihydroquinoxalin-2-yl)-6-methyl-2H-py-
ran-2,4(3H)-dione, 6-methyl-3-(3,4-dihydroquinoxalin-2-yl)-2H-pyran-2,4(3H)-dione, and (E)-3-(2H-
benzo[b][1,4]thiazin-3(4H)-ylidene)-6-methyl-2H-pyran-2,4(3H)-dione were fully characterized by IR,
1H and 13C NMR, and mass spectra.
J. Heterocyclic Chem., 48, 63 (2011).
INTRODUCTION
1 is an industrial available product and the chemistry of
this compound was extensively investigated [4–11]. For
this reason, we decided to investigate the bromination of
the acetyl DHAA group [12–19], since a-bromoketone 2
has been attracting our attention due to its high reactiv-
ity as building blocks for the preparation of several
classes of compounds and its selective transformations
with various nucleophiles. Therefore, DHAA has been
reported to generate a number of heterocyclic com-
pounds through ring opening and recyclization upon
treatment with a variety of binucleophiles [20,21].
2-Pyrones demonstrate a whole spectrum of bioactiv-
ity and have shown antibiotic, antifungal, cytotoxic,
neurotoxic, and phytotoxic activities. Simple change in
the substitution pattern on the 2-pyrone ring often leads
to compounds possessing new biological activity.
Indeed, some of the 4-hydroxy/alkyl/aryl/alkenyl-substi-
tuted-6-methyl-2-pyrones show remarkable biological
effects, such as antimicrobial activity, human chronic
myelogenous leukemia, and human ovarian carcinoma
inhibitory properties [1–3].
Inspection of the structure 2 suggests that it would be
susceptible for the attack of amines at five sites (A, B,
C, D, or E) leading to quite different products (Scheme
1). Transformations involving the three reactive sites of
The referred biological potential of 2-pyrones let us
to start a research program towards the synthesis of 3-
substituted-4-hydroxy-6-methyl-2-pyrones. 3-Acetyl-4-
hydroxy-6-methyl-2-pyrone (dehydroacetic acid, DHAA)
C
V
2010 HeteroCorporation

64
D. Hikem-Oukacha, M. Hamdi, A. M. S. Silva, and R. Yahia
Vol 48
Scheme 1
12.11–12.12 ppm due to the 6-CH3, H-5, and 4-OH pro-
tons of the 2-pyrone moiety. We also observed the sig-
nals from the 1,2-ethanediamine moiety, multiplets at d
1.35–2.83 ppm from methylene groups, and two three-
singlets at d 4.84–4.85, 7.70–7.72, and 8.90–8.92 ppm
due to the a-methylene, NH2, and NH protons. The exis-
tence of the 4-hydroxy-6-methyl-2-pyrone moiety was
also confirmed by 13C NMR, mainly by the carbonyl car-
bon resonances at d 165.9 (ester) and 196.4–196.5 (ke-
tone) ppm. All these spectroscopic features confirm the
generality of the reaction for aliphatic diamines.
the pyrone ring and the direct condensation in the bro-
moacetyl group, in particular with binucleophilic
reagents, offer a versatile approach to synthesize of a
plethora of 4-hydroxy-6-methyl-2H-pyran-2-one analogs
[22]. In that way, we decided to study the reactivity of
bromo-DHAA 2 with several binucleophilic amines.
Treatment of 2 with an equimolecular amount of hy-
drazine gave only one pure product. The analytical data
of this product indicate that the reaction took place with
the loss of one HBr molecule and keeping a 2-pyrone
skeleton. Its mass spectra [molecular ion at m/z 199
(MþH)þ and 221 (MþNa)þ] indicate the incorporation
1
of one hydrazine molecule. The H NMR spectrum of
RESULTS AND DISCUSSION
this compound presents three singlets at d 4.98 (CH2),
7.66 (NH), and 8.54 (NH2) ppm, typical signals of
the 3-(2-substituted-acetyl)-4-hydroxy-6-methyl-2-pyrone
moiety. Its spectrum 13C NMR also confirms the pres-
ence of 2-pyrone ring [d 165.2 (ester) and 183.8 (ke-
tone) ppm]. The referred spectroscopic data are only
compatible with the structure of 3-(2-hydrazinylacetyl)-
4-hydroxy-6-methyl-2H-pyran-2-one 4 (Scheme 3).
Then we investigated the reaction of phenylhydrazine
with 2, under similar conditions to those reported above,
but the transformation did not produce the analog of 4
but a new compound 5. The molecular ion at m/z 275
(MþH)þ and 297 (MþNa)þ suggests the formation of 5
by incorporation of one phenylhydrazine molecule and
the elimination of one HBr molecule. The 1H NMR
spectrum of 5 presents the typical three signals of 6-
CH3, H-5, and OH of the 2-pyrone moiety. Therefore,
other signals are observed at d 8.81, 9.28, 12.57, and
12.77 ppm, due to resonances of four exchangeable pro-
tons, then assigned to the two NH and OH protons,
respectively. The connectivities found in the HMBC
spectrum of 5 [H-5 (d 6.95 ppm)!C-6, C-7, and C-3;
OH-10 and H-20!C-10] allowed the unequivocal assign-
ments of some of their quaternary carbon resonances
and at the same time support the proposed structure 5.
Studies of Harris et al. [23] on the bromination of
DHAA under different experimental conditions describe a
method for the preparation of bromo-DHAA 2. We have
found some difficulties in reproducing this reaction, as
the bromination at the acetyl group gives a viscous oil;
render the method quite difficult to be scaled up. A modi-
fication of this method gives very good results. It
involves the treatment of DHAA with one equivalent of
bromine in refluxing glacial acetic acid to afford 2 in
70% yield. This method is superior to the one based on
the use bromine in an HBr-saturated solution [23].
We started our reactivity studies by refluxing 2 with an
equimolecular amount of 1,2-ethanediamine 2 in ethanol.
A large amount of product, whose structure was subse-
quently determined, was isolated on filtration the reaction
mixture. Two possibilities of the diamine attack without
pyrone ring opening may occur, but only one was
observed (Scheme 2). The elemental analysis and the
mass spectra of 3 [m/z at 227 (MþH)þ and 249
(MþNa)þ for 3a, m/z at 283 (MþH)þ and 305 [MþNa]þ
for 3b] indicate the absence of bromine in the structure
and that one molecule of 2 reacted with diamine. These
1
structures were also supported by its H NMR spectra,
especially by the singlets at d 2.36–2.38, 6.02, and
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011 New Synthesis and Reactivity of 3-Bromoacetyl-4-hydroxy-6-methyl-2H-pyran-2-one
with Binucleophilic Amines
65
Scheme 3
The reaction of
2
with 2,4-dinitrophenylhydrazine
nuated by the nucleophilicity of the NH2 groups. The
structure of the obtained products 9–11 was determined
by reference to the ring substituents and are a conse-
quence of the starting 1,2-phenylenediamines 7b–d.
When an electron-donating group is present (CH3, Cl),
the 1-NH2 reacts first, whereas for an electron-withdraw-
ing substituent (NO2), the 2-NH2 group reacts first, giv-
ing products 9–11 after a cyclocondensation reaction
[24–26]. The 13C NMR spectrum of 9 confirms a 4-
hydroxy-2-pyrone ring whereas in compounds 10 and
11, the presence of the methine group of a b-ketoester
system is amply confirmed using HSQC and HMBC
correlations (H-3!C-3 and C-20; H-30!C-3 and C-10;
NH!C-50).
(DNPH) in ethanol gave only one pure product 6
(Scheme 3). The mass spectrum of compound 6 and ele-
mental analysis indicates
a molecular formula of
C14H10N4O7, which are only compatible with the incor-
poration of one DNPH molecule and the elimination of
single HBr and water molecules relatively to the starting
material 2. The NMR spectra of 6, namely the singlets
at d 2.32 (7-CH3) and 6.06 (H-8) ppm, and those at d
161.7 (C-7), 165.7 (C-5), 173.9 (C-9), and 189.3 (C-4)
support the presence of a 2,3-dihydro-1H-pyrano[4,3-
c]pyridazine-4,5-dione ring. The connectivities found in
the HMBC spectrum of 6 (NH!C-3 and C-9) also sup-
port the proposed structure. The formation of this com-
pound would be explained through the formation of an
unstable intermediate (analog of the ketone form of 5)
and gives 6 after a cyclocondensation reaction.
To confirm the formation mechanism of 8–11 and
generalize this method of synthesis, we investigated the
condensation reaction of 2 with ortho-aminobenzene-
thiol. This transformation can afford the six-membered
heterocyclic compounds 12–15, resulting from the first
thiol or amino attack on the bromomethylenic group
(Scheme 5). The tlc analysis of the reaction mixture
showed that only a single product was formed. The
mass spectrum of this product reveals a molecular ion at
m/z 274 (MþH)þ and 296 (MþNa)þ, which is consist-
ent with the molecular formula C14H11NO3S. The 1H
Thereafter, we investigated the reaction of equimolar
amounts of 2 with 1,2-phenylenediamines 7a–d in
refluxing ethanol, which gave products 8–11 in excellent
yields (Scheme 4). The mass spectrum of the product 8
reveals a molecular ion at m/z 257 (MþH)þ and 279
(MþNa)þ indicating the incorporation of one 1,2-phen-
ylenediamine molecule and the elimination of HBr and
water molecules. This result would be explained through
the cyclocondensation of an a-haloketone. However, the
NMR spectra revealed the existence of a keto–enolic
equilibrium in a 30:70 ratio. The 1H NMR spectrum
showed three signals at d 15.20, 5.88, and 2.12/2.26
ppm corresponding to the expected 4-OH, H-5, and 6-
CH3 protons of a 2-pyrone moiety. The signal of the
major species at d 4.74 ppm is assigned to the methynic
group of the ketone system 8b. The 13C NMR spectrum
of 8 confirms all the carbon resonances of tautomers 8a
(enol form) and 8b (ketone form) (Scheme 4). The reac-
tion of 2 with 1,2-phenylenediamines 7b–d, bearing
CH3, Cl, and NO2 as substituents, yielded in each case a
single pure product 9–11 in high yields (confirmed by
Scheme 4
single resonances in the H and 13C NMR), even in the
1
case of electron-withdrawing NO2 group, which is atte-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

66
D. Hikem-Oukacha, M. Hamdi, A. M. S. Silva, and R. Yahia
Vol 48
tion (ꢀ10ꢁ5M) in 200 lL of 0.1% trifluoroacetic acid/methanol
solution. Nitrogen was used as nebulizer gas and argon as colli-
sion gas. The needle voltage was set at 3000 V, with the ion
source at 80ꢂC and desolvation temperature at 150ꢂC. Cone
voltage was 35 V]. Infrared spectra (KBr) were determined as
KBr pellets of the solids on a Magna-IR 550 series II Nicolet
apparatus. UV spectra were recorded on Cary 50 Scan UV-Visi-
ble spectrometer in acetonitrile solutions.
Scheme 5
3-(Bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (2). A
glacial acetic acid solution (10 mL) of bromine (0.80 g, 5
mmol) was added to a hot solution of the DHA (0.84, 5
mmol) in glacial acetic acid (20 mL) and refluxed for 2 h [23].
The reaction mixture was poured in a mixture of water (100
mL) and ice (50 g) and the obtained solid filtered off and
recrystallized from the 1:1 hexane–chloroform mixture. This
compound was obtained as yellow small crystals. Yield: 70%;
mp. 118–119ꢂC (mp. 111–114ꢂC); IR: 3160–3530, 1690–1735,
1717, 1641, 1350, 1260, 1240, 1180, 1150, 1070, 1020, 990
4
cmꢁ1
;
1H NMR (CDCl3): d 2.31 (d, 3H, J5–7 ¼ 0.6 Hz, 6-
CH3), 4.71 (s, 2H, H-20), 6.03 (s, 1H, H-5), 15.51 (s, 1H, OH);
13C NMR (CDCl3): d 20.8 (6-CH3), 35.2 (C-20), 99.4 (C-3),
101.3 (C-5), 160.6 (C-6), 170.1 (C-2), 180.9 (C-4), 197.2 (C-
10); ESI(þ)-MS: m/z 271 [(MþNa]þ, 81Br, 269 [(MþNa)þ,
79Br, 18), 249 [(MþH)þ, 81Br, 90), 247 [(MþH)þ, 79Br, 95),
167 [(M-Br)þ, 100]. Anal. calcd. for C8H7BrO4: C 38.89; H
2.86; Br 32.34. Found: C 39.10; H 2.80; Br 32.51.
NMR spectrum showed the presence of one signal at d
16.12 ppm, which fits with a strongly deshielded che-
lated OH or NH proton. The 13C NMR spectrum gives
rise to only one resonance for each carbon atom, indi-
cating that only one species is observed in CDCl3 solu-
tion. The proton and carbon resonances at d 4.56 and
24.7 ppm confirms the presence of a thiomethylenic
group. Among the possible structures 12–14, only 13 is
confirmed by the connectivities found in their HMBC
spectrum (NH!C-3 and C-30).
General procedure for the synthesis of compounds 3–6,
8–12. A solution of 2 (2.47 g, 10 mmol) and the appropriate
binucleophile (10 mmol) in ethanol (30 mL) was refluxed with
stirring. After cooling at room temperature, the obtained solid
was filtered and recrystallized from ethanol.
3-[2-(2-Aminoethylamino)acetyl]-4-hydroxy-6-methyl-2H-py-
ran-2-one (3a). This compound was obtained as yellow pow-
der. Yield: 80%; mp. 132ꢂC; IR: 3300, 2930, 1735, 1662,
1600, 1280 cmꢁ1 1H NMR (CDCl3): d 2.36 (s, 3H, 6-CH3),
;
In summary, we have shown that the mechanism for
the reaction of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-
pyran-2-one 2 with binucleophilic amines involves an ini-
tial nucleophilic attack of the most reactive amino group
at the bromomethylenic carbon, followed by the attack
on the second amino group without opening of the py-
rone ring. This condensation reaction gives substituted 2-
pyrones in good yield. The results of biological study
have shown that compound 10 have an antifungal action.
2.71–2.74 (m, 2H, H-50), 2.81–2.83 (m, 2H, H-40), 4.84 (s, 2H,
H-20), 6.02 (s, 1H, H-5), 7.72 (s, 2H, NH2), 8.90 (s, 1H, NH),
12.11 (s, 1H, OH); 13C NMR (CDCl3): d 22.1 (6-CH3), 27.1
(C-50), 44.2 (C-40), 74.6 (C-20), 96.6 (C-3), 103.2 (C-5), 163.3
(C-6), 165.9 (C-2), 184.5 (C-4), 196.4 (C-10); ESI(þ)-MS: m/z
227 [(MþH)þ, 100], 249 [(MþNa)þ, 30]; UV: kmax 284 (-c
5.710), 352 (-c, 10.110) nm. Anal. calcd. for C10 H14N2O4: C,
53.09; H, 6.24. Found: C, 53.10; H, 6.26.
3-[2-(6-Aminohexylamino)acetyl]-4-hydroxy-6-methyl-2H-
pyran-2-one (3b). This compound was obtained as colored
powder. Yield: 84%; mp. 171ꢂC; IR: 3299, 2919, 1727, 1653,
EXPERIMENTAL
1
1601, 1255 cmꢁ1; H NMR (CDCl3): d 1.35 (m, 4H, H-60 and
H-70), 1.54–1.61 (m, 4H, H-50, and H-80), 2.38 (s, 3H, and 6-
CH3), 2.76–2.78 (m, 4H, H-40, and H-90), 4.85 (s, 2H, H-20),
6.02 (s, 1H, H-5), 7.70 (s, 2H, NH2), 8.92 (s, 1H, NH), 12.12
General remarks. Melting points were determined on a
Stuart scientific SPM3 apparatus fitted with a microscope and
are uncorrected. 1H and 13C NMR spectra were recorded in
CDCl3 or DMSO-d6 solutions on a Bruker Avance 300 (300.13
MHz for 1H and 75.47 MHz for 13C) spectrometer. Chemical
shifts are reported in ppm (d) using tetramethylsilane (TMS) as
internal reference and coupling constants (J) are given in Hz.
13C assignments were made using gradient selected heteronu-
clear single quantum coherence (gHSQC) and gradient selected
heteronuclear multiple quantum coherence (gHMBC) (delays
for one bond and long-range J C/H couplings were optimized
for 145 and 7 Hz, respectively) experiments. Positive-ion elec-
trospray ionization (ESI) mass spectra were acquired using a Q-
TOF 2 instrument [diluting 1 lL of the sample chloroform solu-
13
(s, 1H, OH); C NMR (CDCl3): d 22.1 (6-CH3), 25.4 (C-70),
25.9 (C-60), 26.9 (C-50), 27.0 (C-80), 38.7 (C-90), 43.7 (C-40),
74.8 (C-20), 96.6 (C-3), 103.2 (C-5), 163.3 (C-6), 165.9 (C-2),
184.5 (C-4), 196.3 (C-10); ESI(þ)-MS: m/z 283[(MþH)þ,
100], 305 [(MþNa)þ, 25]; UV: kmax 264 (-c 9.530), 369 (-c
11.550) nm. Anal. calcd. for C8H14N2O4: C 56.56; H 7.85.
Found: C 56.50; H 7.81.
3-(2-Hydrazinylacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one
(4). This compound was obtained as yellow powder. Yield:
80%; mp. 137ꢂC; IR: 3442, 2923, 1724, 1662, 1578, 1280
1
cmꢁ1; H NMR (CDCl3): d 2.11 (s, 3H, 6-CH3), 4.98 (s, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011 New Synthesis and Reactivity of 3-Bromoacetyl-4-hydroxy-6-methyl-2H-pyran-2-one
with Binucleophilic Amines
67
H-20), 5.61 (s, 1H, H-5), 7.67 (s, 2H, 40-NH), 8.54 (s, 1H, 30-
NH), 12.73 (s, 1H, 4-OH); 13C NMR (CDCl3): d 19.3 (6-CH3),
60.3 (C-20), 95.1 (C-3), 105.1 (C-5), 166.0 (C-2), 163.1 (C-6),
188.5 (C-4), 194.7 (C-10); ESI(þ)-MS: m/z 199 [(MþH)þ,
100], 221 [(MþNa)þ, 55]; UV: kmax 234 (-c 24.970), 313 (-c
17.920) nm. Anal. calcd. for C8H10N2O4: C 48.48; H 5.09.
Found: C 48.50; H 5.10.
MS: m/z 291 [(MþH)þ, 100], 313 [(MþNa)þ, 70]; UV: kmax
220 (-c 15.970), 313 (-c 11.980) nm. Anal. calcd. for
C14H11ClN2O3: C 57.84; H 3.81. Found: C 57.80; H 3.82.
6-Methyl-3-(7-methyl-3,4-dihydroquinoxalin-2-yl)-2H-pyran-
2,4(3H)-dione (10). This compound was obtained as colored
powder. Yield: 82%; mp. 167ꢂC; IR: 3462, 2925, 1712, 1642,
1549, 1270 cmꢁ1 1H NMR (DMSO-d6): d 2.11 (s, 3H, 6-
;
4-Hydroxy-3-[1-hydroxy-2-(2-phenylhydrazinyl)vinyl]-6-
methyl-2H-pyran-2-one (5). This compound was obtained as
colored powder. Yield: 85%; mp. 168ꢂC; IR: 3453, 1717,
CH3), 2.17 (s, 3H, 60-CH3), 4.71 (s, 1H, H-3), 4.92 (s, 2H, H-
30), 5.82 (s, 1H, H-5), 6.45–6.46 (m, 1H, H-50), 6.69 (s, 1H,
H-80), 6.93–6.96 (m, 1H, H-60), 11.33 (s, 1H, NH); 13C NMR
(DMSO-d6): d 19.5 (6-CH3), 21.0 (60-CH3), 55.8 (C-30), 87.7
(C-3), 99.4 (C-5), 114.2 (C-50), 118.7 (C-70), 120.5 (C-80),
134.0 (C-90), 137.4 (C-60), 143.3 (C-100), 164.1 (C-2), 164.2
(C-20), 173.9 (C-6), 188.6 (C-4); ESI(þ)-MS: m/z 271
[(MþH)þ, 100], 293 [(MþNa)þ, 73]; UV: kmax 218 (-c
26.190), 316 (-c 12.100) nm. Anal. calcd. for C15H14N2O3: C
66.66; H 5.22. Found: C 66.60; H 5.28.
1
1660, 1555, 1261 cmꢁ1; H NMR (CDCl3): d 2.09 (s, 3H, 6-
CH3), 5.75 (s, 1H, H-5), 6.95 (s, 1H, H-20), 7.30–7.32 (m, 5H,
Phenyl), 8.81 (s, 1H, 40-NH), 9.28 (s, 1H, 30-NH), 12.57 (s,
1H, 4-OH), 12.77 (s, 1H, 10-OH); 13C NMR (CDCl3): d 19.1
(6-CH3), 94.3 (C-3), 107.7 (C-5), 113.9 (C-70 and C-90), 121.9
(C-20), 128.3 (C-50), 129.3 (C-60, C-80, and C-100), 143.2 (C-
10), 162.2 (C-6), 165.2 (C-2), 183.8 (C-4); ESI(þ)-MS: m/z
275 [(MþH)þ, 100], 297 (MþNa)þ, 84]; UV: kmax 220 (-c
15.970), 313 (-c 11.980) nm. Anal. calcd. for C14H14N2O4: C
61.31; H 5.14. Found: C 61.30; H 5.12.
6-Methyl-3-(6-nitro-3,4-dihydroquinoxalin-2-yl)-2H-pyran-
2,4(3H)-dione (11). This compound was obtained as colored
powder. Yield: 78%; mp. 182ꢂC; IR: 3421, 2926, 1714, 1653,
;
1576, 1255 cmꢁ1 1H NMR (DMSO-d6): d 2.16 (s, 3H, 6-
1-(2,4-Dinitrophenyl)-7-methyl-2,3-dihydro-1H-pyrano[4,
3-c]pyridazine-4,5-dione (6). This compound was obtained
as colored powder. Yield: 78%; mp. 150ꢂC; IR: 3421, 2926,
;
1696, 1653, 1576, 1255 cmꢁ1 1H NMR (CDCl3): d 2.32 (s,
3H, 7-CH3), 5.02 (s, 2H, H-3), 6.06 (s, 1H, H-8), 7.51 (m, 1H,
H-60), 8.45 (m, 1H, H-50), 9.21 (s, 1H, H-30), 14.12 (s, 1H,
NH); 13C NMR (CDCl3): d 20.3 (7-CH3), 58.5 (C-3), 99.4 (C-
10), 101.6 (C-8), 114.8 (C-60), 123.7 (C-30), 129.7 (C-20),
130.1 (C-50), 138.2 (C-40), 143.0 (C-10), 161.7 (C-7), 165.7 (C-
5), 173.9 (C-9), 189.3 (C-4); ESI(þ)-MS: m/z 347 [(MþH)þ,
45], 369 [(MþNa)þ, 100]; UV: kmax 222 (-c 17.340), 312 (-c
16.050) nm. Anal. calcd. for C14H10N4O7: C 48.56; H 2.91.
Found: C 48.51; H 2.88.
CH3), 4.86 (s, 2H, H-30), 5.21 (s, 1H, H-3), 5.96 (s, 1H, H-5),
7.73–7.76 (m, 1H, H-80), 8.12–8.16 (m, 1H, H-70), 8.48 (s, 1H,
H-50), 11.66 (s, 1H, NH); 13C NMR (DMSO-d6): d 19.6 (6-
CH3), 56.9 (C-30), 88.1 (C-3), 100.2 (C-5), 111.4 (C-50), 114.9
(C-70), 118.4 (C-80), 143.1 (C-90), 148.7 (C-60), 154.9 (C-100),
163.4 (C-2), 164.0 (C-20), 170.6 (C-6), 187.1 (C-4); ESI(þ)-
MS: m/z 302 [(MþH)þ, 100], 324 [(MþNa)þ, 65]; UV: kmax
220 (-c 25.390), 312 (-c 17.780) nm. Anal. calcd. for
C14H11N3O5: C 55.82; H 3.68. Found: C 55.89; H 3.65.
(E)-3-(2H-Benzo[b][1,4]thiazin-3(4H)-ylidene)-6-methyl-
2H-pyran-2,4(3H)-dione (13). This compound was obtained
as yellow small crystals. Yield: 79%; mp. 177ꢂC; IR: 3500–
1
3300, 2925, 1730, 1640 cmꢁ1; H NMR (CDCl3): d 2.18 (s, 3H,
3-(3,4-Dihydroquinoxalin-2-yl)-4-hydroxy-6-methyl-2H-py-
ran-2-one (8a)/3-(3,4-dihydroquinoxalin-2-yl)-6-methyl-2H-
pyran-2,4(3H)-dione (8b). This compound was obtained as
colored powder. Yield: 79%; mp. 168ꢂC; IR: 3442, 2923, 1724,
6-CH3), 4.56 (s, 2H, H-30), 5.80 (s, 1H, H-5), 7.14–7.34 (m, 4H,
H-50, H-60, H-70, and H-80) 16.12 (s, 1H, NH); 13C NMR
(CDCl3): d 20.0 (6-CH3), 24.7 (C-30), 95.0 (C-3), 107.4 (C-5),
120.8 (C-80), 125.1 (C-100), 127.0 (C-60), 127.2 (C-70), 127.9 (C-
50), 133.4 (C-90), 162.9 (C-2), 163.4 (C-20), 164.0 (C-6), 185.5
(C-4); ESI(þ)-MS: m/z 274 [(MþH)þ, 100], 296 [(MþNa)þ,
45]; UV: kmax 247 (-c 25.120), 313 (-c 18.600) nm. Anal. calcd.
for C14H11N2O3: C 61.52; H 4.06. Found: C 61.50; H 4.00.
1662, 1578, 1280 cmꢁ1 1H NMR (DMSO-d6): d 2.12 (s, 3H,
;
6-CH3 ketone), 2.26 (s, 3H, 6-CH3 enol),4.70 (s, 2H, H-30 ke-
tone), 4.74 (s, 2H, H-30 enol), 5.22 (s, 1H, H-3 enol), 5.88 (s,
2H, H-5), 6.22–6.99 (m, 8H, Phenyl), 11.25 (s, 1H, NH ketone),
11.22 (s, 1H, NH enol), 15.20 (s, 1H, OH); 13C NMR (DMSO-
d6): d 19.6 (6-CH3 ketone), 20.7 (6-CH3 enol), 43.9 (C-30 ke-
tone), 55.1 (C-30 enol), 88.8 (C-3 ketone), 95.3 (C-3 enol),
101.2 (C-5 ketone), 99.4 (C-5 enol), 114.2 (C-50 ketone), 118.6
(C-70), 123.3 (C-80), 128.8 (C-60), 129.4 (C-90 enol), 130.4 (C-90
ketone), 139.3 (C-100), 162.4 (C-6), 162.7 (C-2), 161.9 (C-20
enol), 164.2 (C-20 ketone), 175.1 (C-4 ketone), 188.6 (C-4
enol). ESI(þ)-MS: m/z 257 [(MþH)þ, 100], 279 [(MþNa)þ,
40); UV: kmax 224 (-c 24.060), 313 (-c 18.120) nm. Anal. calcd.
for C14H12N2O3: C 65.62; H 7.72. Found: C 65.59; H 7.68.
3-(7-Chloro-3,4-dihydroquinoxalin-2-yl)-4-hydroxy-6-methyl-
2H-pyran-2-one (9). This compound was obtained as colored
powder. Yield: 84%; mp. 173ꢂC; IR: 3453, 2919, 1717, 1660,
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