Studies on the Chemical Reactions of Some 3-Substituted-6,8-dimethylchromones with Nucleophilic Reagents

Article abstract of DOI:10.1002/jhet.3291

A variety of 3-substituted-6,8-dimethylchromones have been synthesized and characterized. The chemical reactivity of 3-substituted-6,8-dimethylchromones was studied towards some nucleophiles, namely, S-benzyldithiocarbazate, o-phenylenediamine, and cyanoacetamide, and a diversity of products were efficiently synthesized. Reactions of 3-substituted-6,8-dimethylchromones (except 3-formyl-6,8-dimethylchromone), with nucleophilic reagents, usually proceed through nucleophilic attack at C-2 position followed by different types of heterocyclization depending on the functional group present at C-3 position. Structures of the newly synthesized products have been established based on elemental analysis and spectral data.

Full text of DOI:10.1002/jhet.3291

Month 2018
Studies on the Chemical Reactions of Some 3-Substituted-6,8-
dimethylchromones with Nucleophilic Reagents
*
Magdy A. Ibrahim,
Al-Shimaa Badran, Nasser M. El-Gohary, and Salsabeel H. Hashiem
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt
*E-mail: magdy_ahmed1977@yahoo.com
Received April 14, 2018
DOI 10.1002/jhet.3291
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A variety of 3-substituted-6,8-dimethylchromones have been synthesized and characterized. The chemical
reactivity of 3-substituted-6,8-dimethylchromones was studied towards some nucleophiles, namely,
S-benzyldithiocarbazate, o-phenylenediamine, and cyanoacetamide, and a diversity of products were
efficiently synthesized. Reactions of 3-substituted-6,8-dimethylchromones (except 3-formyl-6,8-
dimethylchromone), with nucleophilic reagents, usually proceed through nucleophilic attack at C-2 position
followed by different types of heterocyclization depending on the functional group present at C-3 position.
Structures of the newly synthesized products have been established based on elemental analysis and spectral
data.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
corresponding
five-membered
and
six-membered
heterocycles. This domino-transformation usually
involves initial nucleophilic addition on the 2-position
of the chromone skeleton with subsequent γ-pyrone ring
opening followed by the formation of new heterocyclic
systems. These types of transformations are facilitated
by the electron-withdrawing group present at the 3-
position [21–24].
Substituted chromones represent one of the major
classes of naturally occurring compounds [1,2].
Chromones have shown diverse biological activities
including antimicrobial [3], anti-inflammatory [4],
antioxidant [5,6], anticancer [7,8], antitumor [9,10],
neuroprotective [11], and human immunodeficiency virus
inhibitory [12]. Quantum chemical studies, density
functional theory calculations, electronic absorption
spectra, and optical properties of some chromone
derivatives were studied [13–16]. 3-Substituted
chromones possess an activated endocyclic olefinic bond,
three electrophilic centers (C-2, C-4 as C¼O, and the
carbon atom of the functional group present at C-3 of the
γ-pyrone ring). C-2 is more electrophilic than the other
carbon atoms. The chemistry of 3-substituted chromones
is more varied, and their chemical behavior depends
widely on the type of the functional group present at C-3
position [17–20]. Chromones bearing electron-
withdrawing substituents in the 3-position react with 1,2-
dinucleophiles and 1,3-dinucleophiles delivering the
RESULTS AND DISCUSSION
The present work aimed to synthesize a variety of 3-
substituted-6,8-dimethylchromones and study their
chemical behavior towards selected nucleophiles, namely,
S-benzyldithiocarbazate,
o-phenylenediamine,
and
cyanoacetamide.
6,8-Dimethylchromone-3-carboxaldehyde (1) [25] and
6,8-dimethylchromone-3-carbonitrile (2) [26] were
prepared as previously reported. Herein, treating
carboxaldehyde 1 with N-bromosuccinimide (NBS) in
carbon tetrachloride under irradiation using 200-W
© 2018 Wiley Periodicals, Inc.

M. A. Ibrahim, A.-S. Badran, N. M. El-Gohary, and S. H. Hashiem
Vol 000
tungsten lamp followed by quenching with water afforded
6,8-dimethylchromone-3-carboxylic acid (3) (Scheme 1).
Quenching the reaction medium in the previous reaction
with aqueous ammonia, instead of water, produced 6,8-
dimethylchromone-3-carboxamide (4) in moderate yield
(Scheme 1) [27].
Condensation reaction of carboxaldehyde 1 with
cyanoacetic acid in boiling pyridine furnished E-
chromonylacrylonitrile derivative 5, via condensation
followed by decarboxylation under the reaction
conditions (Scheme 1). The IR spectrum of compound 5
revealed characteristic absorption bands at ν 2216 and
1637 cmꢀ1 attributable to (CꢁN) and (C¼Oγ-pyrone),
respectively. The 1H-NMR spectrum of compound 5
showed two characteristic doublets at δ 6.93 and 7.33
with high coupling constant (J = 16.4 Hz) assigned to
vinyl protons, indicating trans configuration around the
double bond. Further, the mass spectrum of compound 5
revealed the molecular ion peak at m/z 225 and confirms
the structure.
Also, the mass spectra of compounds 8 and 9 showed
their molecular ion peaks, at m/z 343 and 345, which
agree well with the assigned molecular formulas and
confirm the suggested structures.
Then,
heating
carboxaldehyde
1
with
o-
phenylenediamine in 95% ethanol for 1 min produced
orange crystals in high yield. Inspection of the spectral
data confirms the formation of addition product 10,
throughout addition of amino group into the formyl
group (1,2-addition) with addition of water molecule at
C2–C3 double bond (1,2-addition) during the reaction
(Scheme 3). The mass spectrum of compound 10 showed
the molecular ion peak, as the base peak, at m/z 328,
which agrees well with the proposed structure.
Repeating the previous reaction under reflux for 2 h
furnished the annulated benzochromenodiazepine
derivative 11 as pale yellow crystals, via the formation of
compound 10 followed by elimination of two molecules
of water with subsequent dehydrogenation (Scheme 3)
[29,30]. In this reaction, the orange crystals formed after
1 min was dissolved under reflux, indicating the
formation of compound 11 throughout compound 10
(as isolable intermediate). The 1H-NMR spectrum of
compound 11 showed characteristic singlets at δ 7.58
(H-2), 7.86 (H-4), and 9.34 (H-6diazepine), in addition to
D2O-exchangeable signal attributable to NH proton at δ
11.93. Structure of compound 11 was deduced from its
mass spectrum, which showed the molecular ion peak at
m/z 290, as the base peak, and supports the assigned
structure.
Treatment of carboxaldehyde 1 with cyanoacetamide in
boiling ethanol containing few drops of piperidine
produced pyridine-3-carbonitrile derivative 12 in good
yield (Scheme 3). Compound 12 gave red color with
FeCl3 solution, indicating the presence of phenolic OH
group and confirms the γ-pyrone ring opening. Mass
spectrum of compound 12 revealed the molecular ion
peak at m/z 268, which is in agreement with the assigned
molecular formula (C15H12N2O3). Its IR spectrum
showed characteristic absorption bands at ν 3208 (OH),
3137 (NH), 2238 (CꢁN), and 1694 cmꢀ1 (C¼Opyridone).
The 1H-NMR spectrum of compound 12 showed
Next, stirring carbonitrile 2 with 2M sodium hydroxide
solution at 70°C for
2
h
gave 2-amino-6,8-
dimethylchromone-3-carboxaldehyde (6), throughout ring
opening following by ring closure (Scheme 1) [28].
Condensation of carboxaldehyde
1
with S-
benzyldithiocarbazate in ethanol under stirring afforded
the corresponding hydrazone 7 (Scheme 2). Repeating the
reaction in boiling ethanol in the presence of piperidine
yielded piperidinylcarbonothioylpyrazole derivative 8,
throughout nucleophilic substitution of SCH2Ph group
with piperidinyl group (intermediate A) with concomitant
γ-pyrone ring opening (Scheme 2). Similarly, using
morpholine, instead of piperidine, in the previous reaction
yielded morpholinylcarbonothioylpyrazole derivative 9,
via intermediate B (Scheme 2). Compounds 8 and 9 give
red color with FeCl3 solution, indicating the presence of
1
free phenolic OH group. H-NMR spectra of compounds
8 and 9 showed the absence of phenyl protons indicating
elimination of SCH2Ph group during the reaction. The
13C-NMR spectrum of compound 9 showed specific
signals assignable to N (CH2)2, O (CH2)2, C¼O, and
C¼S at δ 52.2, 65.6, 176.8, and 191.1, respectively.
Scheme 1. Synthesis of 3-substituted-6,8-dimethylchromones.
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3-Substituted-6,8-dimethylchromones
Scheme 2. Reaction of carboxaldehyde 1 with and S-benzyldithiocarbazate.
compound 14 showed specific singlet at δ 8.36 attributed to
azomethine proton. The 13C-NMR spectrum of compound
14 revealed characteristic signals δ 37.7, 91.9, 173.8, and
196.7 attributable to CH2, C-3chromone, C¼O, and C¼S,
respectively.
Scheme 3. Reaction of carboxaldehyde 1 with o-phenylenediamine and
cyanoacetamide.
Interestingly, boiling carbonitrile
benzyldithiocarbazate in acetic
2
acid
with S-
afforded
chromeno[4,3-c]pyrazol-4(1H)-one derivative 15, which
was obtained authentically from the reaction of
carbonitrile 2 with hydrazine hydrate in boiling acetic
acid (Scheme 4). IR spectrum displayed characteristic
absorption bands at ν 1710 (C¼Oα-pyrone) and 1602 cmꢀ1
(C¼N). 1H-NMR spectrum consists of three singlet
signals attributed to H-7, H-9, and H-3pyrazole at δ 6.78,
7.38, and 8.44, respectively. The mass spectrum of
compound 15 recorded the molecular ion peak at m/z
214, as the base peak, corresponding to the formula
weight (214.22) and confirms the suggested structure.
Reaction of carbonitrile 2 with o-phenylenediamine
in boiling dimethylformamide (DMF) afforded
benzochromenodiazepine derivative 11 (co-identical mp,
mmp, and spectral data with that prepared from the reaction
of aldehyde 1 with the same reagent) (Scheme 5) [31].
characteristic singlets at δ 8.15 and 8.29 attributed to
H-4pyridine and H-6pyridine, respectively, in addition to
D2O-exchangeable signal at δ 10.30 attributable to NH
and OH protons.
Next, the chemical behavior of 6,8-dimethylchromone-3-
carbonitrile (2) was studied towards S-benzyldithiocarbazate
under different reaction conditions. Treatment of
carbonitrile 2 with S-benzyldithiocarbazate in boiling
ethanol furnished pyrazole derivative 13, via γ-pyrone ring
opening (intermediate C) followed by addition into the
nitrile function (intermediate D) as shown in Scheme 4.
Carrying out the latter reaction in benzene as a solvent
containing triethylamine furnished hydrazone derivative 14,
After that, reaction of carbonitrile
2
with
cyanoacetamide in boiling ethanol containing few drops
of piperidine gave chromeno[2,3-b] pyridine 16 in good
yield (Scheme 5). The mass spectrum presented the
molecular ion peak at m/z 283 (100%) as the base peak,
corresponding to the molecular formula (C15H13N3O3).
1H-NMR spectrum of compound 16 showed
characteristic singlet at δ 8.84 assigned to H-4pyridine
.
1
via (intermediates C and E) (Scheme 5). The H-NMR
Next, the chemical transformations of 6,8-
dimethylchromone-3-carboxamide (4) were studied
towards the previous nucleophilic reagents. Treating
spectrum of compound 13 showed specific singlet at δ 8.08
attributed to H-3pyrazole, while 1H-NMR spectrum of
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M. A. Ibrahim, A.-S. Badran, N. M. El-Gohary, and S. H. Hashiem
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Scheme 4. Reaction of carbonitrile 2 with S-benzyldithiocarbazate. TEA, triethylamine.
derivative 17, as Z isomer (Scheme 6). The 1H-NMR
spectrum of compound 17 showed characteristic doublet
(J = 15.2 Hz) exchanged to singlet in D2O, at δ 7.57,
which was assigned to the exocyclic vinyl proton, in
addition to D2O-exchangeable doublet assigned to the
NH proton at δ 13.45. The structure of compound 17 was
further deduced from its mass spectrum, which revealed
the molecular ion peak at m/z 308 and the base peak at
m/z 307 assigned to M+ after loss of hydrogen as a radical.
Scheme 5. Reaction of carbonitrile 2 with o-phenylenediamine and
cyanoacetamide. DMF, dimethylformamide.
Moreover, treatment of carboxamide
4
with
cyanoacetamide in sodium ethoxide under reflux
produced the pyridine derivative 18. The reaction
proceeds via deprotonation of cyanoacetamide followed
by nucleophilic attack at C-2 position (intermediate F)
and γ-pyrone ring opening (intermediate G) with
concomitant cycloaddition (intermediate H) and proton
transfer as depicted in Scheme 7.
In the current study, the chemical transformation of
carboxylic acid 3 and acrylonitrile 5 was concised
towards cyanoacetamide. Therefore, treatment of
carboxylic acid 3 with cyanoacetamide in ethanol
containing few drops of triethylamine as a catalyst
carboxamide 4 with S-benzyldithiocarbazate in DMF under
reflux afforded chromenopyrazole derivative 15
(Scheme 6) (co-identical spectral data with that from the
reaction of carbonitrile 2 with the same reagent in acetic
acid).
Boiling carboxamide 4 with o-phenylenedimine in
refluxing DMF afforded the chromane-2,4-dione
Scheme 6. Conversion of carboxamide 4 into coumarines 15 and 17.
DMF, dimethylformamide.
afforded
6-(2-hydroxy-3,5-dimethylphenyl)-2-oxo-1,2-
dihydropyridine-3-carbonitrile (19) (Scheme 8). The mass
spectrum revealed the molecular ion peak at m/z 240,
which is consistent with the proposed molecular formula
C14H12N2O2.
Finally, treatment of (2E)-3-(6,8-dimethylchromon-3-yl)
acrylonitrile (5) with cyanoacetamide in boiling ethanol
containing few drops of piperidine afforded 5-(cyanomethyl)-
7,9-dimethyl-2-oxo-1,5-dihydro-2H-chromeno[4,3-b]pyridine-
3-carbonitrile (20), via a non-isolable intermediates J and
K, as described in Scheme 9. Structure of compound 20
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3-Substituted-6,8-dimethylchromones
Scheme 7. Reaction of carboxamide 4 with cyanoacetamide.
Scheme 8. Reaction of carboxylic acid 3 with cyanoacetamide. TEA, triethylamine.
Scheme 9. Reaction of acrylonitrile 5 with cyanoacetamide.
was deduced from its mass spectrum, which revealed the
molecular ion peak at m/z 291 and the base peak at m/z
251, and assigned to the molecular ion after loss of
CH2CN moiety. The 1H-NMR spectrum showed
characteristic doublet and triplet at δ 2.99 and 5.45
attributable to (CH2CN) and (H-5), respectively, and
supports the identity of the assigned structure.
the synthesis of different heterocyclic systems. 3-
Substituted 6,8-dimethylchromones possess three electron
deficient centers: C-2, C-4, and carbon atom of the
functional group present at position 3. In all reactions of
3-substituted-6,8-dimethylchromones (except 3-formyl-
6,8-dimethylchromone), with nucleophilic reagent, it was
found that the nucleophile usually attack the chromone
ring at C-2 position followed by different types of
heterocyclization depending on the functional group
present at C-3 position. In case of 3-formyl-6,8-
dimethylchromone, the nucleophiles reacted with the
aldehyde function with subsequent γ-pyrone ring opening
leading to a diversity of nitrogen heterocyclic systems.
CONCLUSION
A variety of 3-substituted-6,8-dimethylchromones were
efficiently synthesized and found as a good precursors for
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M. A. Ibrahim, A.-S. Badran, N. M. El-Gohary, and S. H. Hashiem
Vol 000
EXPERIMENTAL
DMSO-d6): 2.22 (s, 3H, CH3), 2.40 (s, 3H, CH3), 7.55
(s, 1H, H-7), 7.77 (s, 1H, H-5), 8.56 (s, 2H, NH2
exchangeable with D2O), 8.99 (s, 1H, H-2). Mass
spectrum, m/z (Ir %): 217 (100), 201 (38), 174 (42), 148
(12), 120 (12), 91 (37), 77 (18), 65 (21). Anal. Calcd for
C12H11NO3 (217.22): C, 66.35; H, 5.10; N, 6.45%.
Found: C, 66.25; H, 5.00; N, 6.29%.
General. Melting points were determined on a digital
Stuart SMP3 apparatus (Büchi, Flawil, Switzerland).
Infrared spectra were measured on PerkinElmer 293
spectrophotometer (cmꢀ1) (Thermo Fisher Scientific,
1
Waltham, MA), using KBr disks. H-NMR spectra were
(2E)-3-(6,8-Dimethylchromon-3-yl)acrylonitrile (5).
A
measured on Mercury-300BB/400BB (300 and
400 MHz) (Bruker, Rheinstetten, Germany), using
DMSO-d6 as a solvent and tetramethylsilane (δ) as the
internal standard. 13C-NMR spectra were measured on
Mercury400BB (75 and 100 MHz), using DMSO-d6 as
a solvent and tetramethylsilane (δ) as the internal
standard. Mass spectra were obtained using GC-2010
Shimadzu gas chromatography instrument mass
spectrometer (70 eV) (Manchester, England). Elemental
microanalyses were performed on a PerkinElmer CHN-
mixture of carboxaldehyde 1 (2.02 g, 10 mmol) and
cyanoacetic acid (0.85 g, 10 mmol) in pyridine (10 mL)
was heated under reflux for 1 h. The pale yellow crystals
obtained after cooling were filtered and crystallized from
MeOH to give compound 5 as white crystals, yield
1.48 g (66%), mp 221–222°C. IR (KBr, cmꢀ1): 3105
(CHolefinic), 3079 (CHarom.), 2935, 2920 (CHaliph.), 2216
(CꢁN), 1637 (C¼Oγ-pyrone), 1615 (C¼C). 1H-NMR
(400 MHz, DMSO-d6): 2.36 (s, 3H, CH3), 2.39 (s, 3H,
CH3), 6.93 (d, 1H, J = 16.4 Hz, Holefinic), 7.33 (d, 1H,
J = 16.4 Hz, Holefinic), 7.49 (s, 1H, H-7), 7.68 (s, 1H, H-
5), 8.72 (s, 1H, H-2). 13C-NMR (75 MHz, DMSO-d6):
15.5 (CH3), 20.1 (CH3), 91.5, 116.8, 121.0, 124.2, 126.9,
128.7, 130.2, 133.4, 137.0, 153.2, 155.4, 175.2 (C¼O).
Mass spectrum, m/z (Ir %): 225 (51), 199 (38), 171 (32),
148 (100), 120 (22), 77 (45), 65 (13). Anal. Calcd for
C14H11NO2 (225.24): C, 74.65; H, 4.92; N, 6.22%.
Found: C, 74.60; H, 4.70; N, 6.00%.
2400 analyzer (Leco, St. Joseph, MI).
6,8-Dimethylchromone-3-carboxylic acid (3). A mixture
of carboxaldehyde 1 (2.02 g, 10 mmol) and NBS (2.14 g,
12 mmol) in carbon tetrachloride (50 mL) was stirred
under illumination from 200-W tungsten lamp for
40 min. The solvent was evaporated under vacuum, and
the residue was cooled in an ice bath followed by
addition of distilled water (10 mL) with continuous
stirring. The solid obtained was filtered, washed with
water, then diethyl ether, and crystallized from acetic acid
to give compound 3 as white crystals, mp 210–211°C,
yield 1.23 g (56%). IR (KBr, cmꢀ1): 3100 (br, OH), 3056
(CHarom), 2925, 2887 (CHaliph.), 1763 (C¼Ocarboxylic acid),
2-Amino-6,8-dimethylchromene-3-carboxaldehyde (6).
A
mixture of carbonitrile 2 (1.99 g, 10 mmol) and 2M
sodium hydroxide solution (20 mL) was stirred at 70°C
for 2 h. Water was added (40 mL), and the solid obtained
was filtered and crystallized from AcOH to give
compound 6 as yellow crystals, yield 1.44 (72%), mp
255–256°C. IR (KBr, cmꢀ1): 3258 (br, NH2), 3074
(CHarom.), 2998, 2918, 2885 (CHaliph.), 2756 (C–
Haldehyde), 1675 (C¼Oaldehyde), 1636 (C¼Oγ-pyrone), 1602
(C¼C). 1H-NMR (400 MHz, DMSO-d6): 2.33 (s, 3H,
CH3), 2.34 (s, 3H, CH3), 7.38 (s, 1H, H-7), 7.61 (s, 1H,
H-5), 9.45 (s, H, NH exchangeable with D2O), 9.51 (s,
H, NH, exchangeable with D2O), 10.04 (s, 1H, CHO).
13C-NMR (75 MHz, DMSO-d6): 14.6 (CH3), 20.1 (CH3),
94.7 (C-3), 122.3, 126.1, 128.3, 129.9, 132.7, 135.0,
135.9, 153.1, 168.4, 174.6 (CH¼O), 189.1 (CH¼O).
Mass spectrum, m/z (Ir %): 217 (100), 189 (26), 174 (17),
148 (66), 121 (36), 91 (14), 77 (46), 64 (11). Anal. Calcd
for C12H11NO3 (217.22): C, 66.35; H, 5.10; N, 6.45%.
Found: C, 66.14; H, 4.80; N, 6.24%.
1
1651 (C¼Oγ-pyrone), 1624 (C¼C). H-NMR (400 MHz,
DMSO-d6): 2.38 (s, 3H, CH3), 2.41 (s, 3H, CH3), 7.59
(s, 1H, H-7), 7.74 (s, 1H, H-5), 9.10 (s, 1H, H-2), 13.29
(bs, 1H, COOH, exchangeable with D2O). 13C-NMR
(75 MHz, DMSO-d6): 15.6 (CH3), 19.9 (CH3), 107.3,
115.7, 121.6, 123.4, 129.6, 133.0, 150.7, 156.2, 171.5
(C-4 as C¼O), 188.2 (C¼Oacid). Mass spectrum, m/z (Ir
%): 218 (3), 217 (16), 199 (100), 174 (7), 149 (15), 120
(19), 91 (27), 77 (18), 65 (18). Anal. Calcd for C12H10O4
(218.21): C, 66.05; H, 4.62%. Found: C, 65.70; H, 4.50%.
6,8-Dimethylchromone-3-carboxamide (4). A mixture of
carboxaldehyde 1 (2.02 g, 10 mmol) and NBS (2.14 g,
12 mmol) in carbon tetrachloride (50 mL) was stirred
under illumination from 200-W tungsten lamp for
40 min. The solvent was evaporated under vacuum, and
the residue was cooled in an ice bath followed by
addition of ammonia (5 mL) with continuous stirring.
The reaction mixture was neutralized with 10% acetic
acid. The solid obtained was filtered, washed with water,
and crystallized from DMF/H2O to give compound 4 as
white crystals, mp 268–269°C, yield 1.18 g (54%), mp
268–269°C. IR (KBr, cmꢀ1): 3336, 3143 (NH2), 3082
(CHarom), 2922, 2880 (CHaliph.), 1684 (C¼Oamide), 1647
(C¼Oγ-pyrone), 1601 (C¼C). 1H-NMR (400 MHz,
Benzyl
2-[(6,8-dimethylchromon-3-yl)methylidene]
hydrazinecarbodithioate (7).
To
a hot solution of
carboxaldehyde 1 (0.61 g, 3 mmol) in absolute ethanol
(15 mL), S-benzyldithiocarbazate (0.58 g, 3 mmol) in
absolute ethanol (10 mL) was added with continuous
stirring, and the reaction mixture was heated under reflux
for 1 min. The white crystals obtained during heating
were filtered off and crystallized from DMF/EtOH to
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Month 2018
3-Substituted-6,8-dimethylchromones
give compound 7 as white crystals, mp 230–231°C, yield
0.89
(77%). IR (KBr, cmꢀ1): 3165 (NH),
exchangeable with D2O). 13C-NMR (75 MHz,
DMSO-d6): 15.1 (CH3), 19.8 (CH3), 52.2 (NCH2), 65.6
(OCH2), 119.5, 122.4, 126.1, 127.5, 128.3, 137.0, 137.3,
142.2, 157.0, 176.8 (C¼O), 191.1 (C¼S). Mass
spectrum, m/z (Ir %): 345 (26), 250 (4), 231 (30), 202
(7), 148 (10), 130 (70), 120 (8), 86 (100), 77 (12), 65 (7).
Anal. Calcd for C17H19N3O3S (345.42): C, 59.11; H,
5.54; N, 12.17; S, 9.28%. Found: C, 58.80; H, 5.44; N,
11.80; S, 9.15%.
g
3036 (CHarom.), 2997, 2920, 2890 (CHaliph.), 1634
(C¼Oγ-pyrone), 1605 (C¼N), 1577 (C¼C). 1H-NMR
(400 MHz, DMSO-d6): 2.18 (s, 3H, CH3), 2.23 (s, 3H,
CH3), 4.61 (s, 2H, CH2), 7.25–7.47 (m, 5H, Ar–H), 7.51 (s,
1H, H-7), 7.69 (s, 1H, H-5), 8.43 (s, 1H, CH¼N), 9.06 (s,
1H, H-2), 11.39 (s, 1H, NH, exchangeable with D2O). Mass
spectrum, m/z (Ir %): 382 (21), 216 (7), 200 (11), 148 (7),
120 (6), 105 (6), 91 (100), 77 (13), 65 (20). Anal. Calcd for
C20H18N2O2S2 (382.49): C, 62.80; H, 4.74; N, 7.32; S,
3-{[(2-Aminophenyl)amino](hydroxy)methyl}-2-hydroxy-6,8-
dimethyl-2,3-dihydro-4H-chromen-4-one (10).
To a hot
solution of carboxaldehyde 1 (0.61 g, 3 mmol) in 95%
ethanol (20 mL), o-phenylenediamine (0.33 g, 3 mmol)
was added and stirred for 1 min. The resulting orange
crystals were filtered off and crystallized from EtOH to
give compound 10 as orange crystals, mp 205°C, yield
0.78 g (79%). IR (KBr, cmꢀ1): 3446 (br, NH2, NH, OH),
2922, 2860 (CHaliph.), 1638 (C¼Oγ-pyrone), 1597 (C¼C).
1H-NMR (400 MHz, DMSO-d6): 2.13 (s, 3H, CH3),
2.19–2.22 (m, 1H, NCHO), 2.35 (t, 1H, H-3), 2.43 (s,
3H, CH3), 5.52 (bs, 2H, NH2 exchangeable with D2O),
6.56 (s, 1H, H-2), 6.84–6.95 (m, 2H, Ar–H), 7.14–7.19
(m, 1H, Ar–H), 7.40 (s, 1H, H-7), 7.45 (d, 1H, Ar–H),
7.57 (s, 1H, H-5), 7.64 (bs, 1H, OH exchangeable with
D2O), 9.33 (bs, 1H, NH exchangeable with D2O), 9.67
(d, 1H, OH exchangeable with D2O). 13C-NMR
(75 MHz, DMSO-d6): 14.0 (CH3), 20.1 (CH3), 60.9,
61.6, 71.3, 117.1, 118.2, 120.7, 124.6, 126.0, 131.4,
133.3, 133.7, 136.5, 140.1, 150.5, 151.4, 164.9. Mass
spectrum, m/z (Ir %): 328 (100), 291 (71), 283 (15), 263
(16), 247 (8), 200 (16), 159 (6), 119 (25), 105 (16), 91
(64), 77 (52), 65 (74). Anal. Calcd for C18H20N2O4
(328.36): C, 65.84; H, 6.14; N, 8.53%. Found: C, 65.55;
H, 6.02; N, 8.26%.
16.77%. Found: C, 62.75; H, 4.55; N, 7.10; S, 16.49%.
4-(2-Hydroxy-3,5-dimethylbenzoyl)-1-(piperidin-1-
ylcarbonothioyl)-1H-pyrazole (8).
To a hot solution of
carboxaldehyde 1 (0.61 g, 3 mmol) in absolute ethanol
(15 mL), S-benzyldithiocarbazate (0.58 g, 3 mmol) in
absolute ethanol (10 mL) containing piperidine (0.1 mL)
was added with continuous stirring. The solid formed
after 1 min was dissolved after 20 min. The reaction
mixture was refluxed for another 2 h. The yellow crystals
obtained after cooling were filtered off and crystallized
from EtOH to give compound 8 as pale yellow crystals,
mp 157–158°C, yield 0.75 g (73%). IR (KBr, cmꢀ1):
3400 (OH), 3080 (CHarom.), 2949, 2860 (CHaliph.), 1635
(C¼Obenzoyl), 1589 (C¼N), 1547 (C¼C). 1H-NMR
(400 MHz, DMSO-d6): 1.67 (t, 6H, 3CH2), 2.18 (s, 3H,
CH3), 2.26 (s, 3H, CH3), 3.59 (s, 4H, 2NCH2), 7.29 (s,
1H, Ar–H), 7.53 (s, 1H, Ar–H), 8.25 (s, 1H, Hpyrazole),
8.81 (s, 1H, Hpyrazole), 11.68 (bs, 1H, OH, exchangeable
with D2O). 13C-NMR (75 MHz, DMSO-d6): 15.3 (CH3),
19.6 (CH3), 25.1 (CH2), 29.4 (CH2), 52.0 (NCH2), 119.2,
122.5, 125.8, 127.3, 128.1, 136.8, 136.9, 142.7, 157.4,
177.2 (C¼O), 190.9 (C¼S). Mass spectrum, m/z (Ir %): 343
(23), 248 (5), 231 (25), 202 (17), 148 (6), 128 (100), 112
(10), 91 (13), 84 (30), 77 (8), 69 (77), 65 (5). Anal. Calcd
for C18H21N3O2S (343.44): C, 62.95; H, 6.16; N, 12.23; S,
1,3-Dimethyl-12H-benzo[b]chromeno[2,3-e][1,4]diazepin-5-
one (11).
Method A. A mixture of carboxaldehyde 1 (0.61 g,
9.34%. Found: C, 62.71; H, 6.10; N, 12.11; S, 9.05%.
4-(2-Hydroxy-3,5-dimethylbenzoyl)-1-(morpholin-4-
3 mmol) and o-phenylenediamine (0.33 g, 3 mmol) in
95% ethanol (20 mL) was heated under reflux for 2 h.
After cooling, the resulting yellow solid was filtered off
and crystallized from DMF/EtOH to give compound 11
as white crystals, mp 283–284°C, yield 0.63 g (77%).
ylcarbonothioyl)-1H-pyrazole (9).
To a hot solution of
carboxaldehyde 1 (0.61 g, 3 mmol) in absolute ethanol
(15 mL), S-benzyldithiocarbazate (0.58 g, 3 mmol) in
absolute ethanol (10 mL) containing morpholine (0.1 mL)
was added with continuous stirring. The solid formed
after 1 min was dissolved after 20 min. The reaction
mixture was refluxed for another 2 h. The yellow crystals
obtained after cooling were filtered off and crystallized
from EtOH to give compound 9 as pale yellow crystals,
mp 189–190°C, yield 0.71 g (69%). IR (KBr, cmꢀ1):
3090 (CHarom.), 2972, 2921, 2855 (CHaliph.), 1647
(C¼Obenzoyl), 1624 (C¼N), 1588 (C¼C).1H-NMR
(400 MHz, DMSO-d6): 2.18 (s, 3H, CH3), 2.26 (s, 3H,
CH3), 3.71 (s, 4H, 2 NCH2), 4.18 (s, 4H, 2 OCH2), 7.30
(s, 1H, Ar–H), 7.48 (s, 1H, Ar–H), 8.27 (s, 1H, H-
3pyrazole), 8.82 (s, 1H, H-5pyrazole), 11.65 (bs, 1H, OH,
Method B.
A mixture of carbonitrile 2 (0.60 g,
3 mmol) and o-phenylenediamine (0.33 g, 3 mmol) in
DMF (10 mL) was heated under reflux for 2 h. After
cooling, the reaction mixture was poured onto ice
(~30 g), and the resulting solid was filtered off and
crystallized from DMF/EtOH to give compound 11 as
white crystals, mp 283–284°C, yield 0.56 g (71%). IR
(KBr, cmꢀ1): 3220 (NH), 3087 (CHarom.), 2970, 2937
(CHaliph.), 1646 (C¼Oγ-pyrone), 1624 (C¼N), 1601
(C¼C). 1H-NMR (400 MHz, DMSO-d6): 2.43 (s, 3H,
CH3), 2.45 (s, 3H, CH3), 7.17 (d, 2H, J = 6.4 Hz, Ar–H),
7.58 (s, 1H, H-2), 7.65 (d, 2H, J = 6.4 Hz, Ar–H), 7.86
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. A. Ibrahim, A.-S. Badran, N. M. El-Gohary, and S. H. Hashiem
Vol 000
(s, 1H, H-4), 9.34 (s, 1H, Hdiazepine), 11.93 (bs, 1H, NH
exchangeable with D2O). 13C-NMR (75 MHz,
DMSO-d6): 17.0 (CH3), 20.7 (CH3), 113.7, 118.8, 121.1,
125.6, 130.5, 135.2, 137.6, 138.7, 145.7, 149.2, 153.6,
159.7, 164.5, 168.9, 176.6, 199.1. Mass spectrum, m/z (Ir
%): 290 (100), 261 (4), 233 (12), 145 (6), 120 (4), 105
(4), 91 (12), 77 (4), 65 (5). Anal. Calcd for C18H14N2O2
(290.32): C, 74.47; H, 4.86; N, 9.65%. Found: C, 74.20;
H, 4.50; N, 9.45%.
from DMF/EtOH to give compound 14 as yellow
crystals, mp 250–251°C, yield 0.71 g (60%). IR (KBr,
cmꢀ1): 3403, 3210, 3143 (NH2, NH), 2979, 2955, 2920
(CHaliph.), 1631 (C¼O), 1606 (C¼N), 1571 (C¼C). H-
1
NMR (400 MHz, DMSO-d6): 2.32 (s, 3H, CH3), 2.34 (s,
3H, CH3), 4.46 (s, 2H, CH2), 7.23–7.47 (m, 5H, Ar–H),
7.58 (s, 1H, H-7), 7.69 (s, 1H, H-5), 8.36 (s, 1H,
CH¼N), 8.63 (bs, 1H, NH exchangeable with D2O), 9.39
(bs, H, NH exchangeable with D2O), 13.33 (s, 1H, NH
exchangeable with D2O). 13C-NMR (75 MHz,
DMSO-d6): 14.8 (CH3), 20.4 (CH3), 37.7 (CH2), 91.9 (C-
3), 117.3, 120.9, 123.0, 125.4, 127.5, 128.6, 135.2,
136.7, 139.7, 144.7, 154.4, 162.5, 173.8 (C¼O), 196.7
(C¼S). Mass spectrum, m/z (Ir %): 397 (32), 320 (19),
215 (65), 171 (9), 148 (33), 121 (15), 91 (100), 77 (49),
64 (8). Anal. Calcd for C20H19N3O2S2 (397.51): C,
60.43; H, 4.82; N, 10.57; S, 16.13%. Found: C, 60.20; H,
4.45; N, 10.30; S, 15.85%.
5-(2-Hydroxy-3,5-dimethylbenzoyl)-2-oxo-1,2-
dihydropyridine-3-carbonitrile (12).
A
mixture of
carboxaldehyde 1 (0.61 g, 3 mmol) and cyanoacetamide
(0.26 g, 3 mmol) in absolute ethanol (20 mL) containing
piperidine (0.1 mL) was heated under reflux for 30 min.
The yellow crystals obtained during heating were filtered
off and crystallized from DMF/EtOH to give compound
12 as yellow crystals, mp 288–289°C, yield 0.68 g
(85%). IR (KBr, cmꢀ1): 3208 (OH), 3137 (NH), 3072
(CHarom.), 2935, 2875 (CHaliph.), 2238 (CꢁN), 1694
(C¼Opyridone), 1674 (C¼Obenzoyl), 1623 (C¼N), 1592
(C¼C). 1H-NMR (400 MHz, DMSO-d6): 2.17 (s, 3H,
CH3), 2.21 (s, 3H, CH3), 7.12 (s, 1H, Ar–H), 7.20 (s, 1H,
Ar–H), 8.15 (s, 1H, H-4pyridine), 8.29 (s, 1H, H-6pyridine),
10.30 (bs, 2H, NH, OH, exchangeable with D2O). Mass
spectrum, m/z (Ir %): 268 (43), 148 (63), 120 (100), 91
(56), 77 (31), 65 (17). Anal. Calcd for C15H12N2O3
(268.27): C, 67.16; H, 4.51; N, 10.44%. Found: C, 66.80;
H, 4.30; N, 10.21%.
6,8-Dimethylchromeno[4,3-c]pyrazol-4(1H)-one (15).
Method A.
A mixture of carbonitrile 3 (0.60 g,
3 mmol) and S-benzyldithiocarbazate (0.58 g, 3 mmol) in
acetic acid (15 mL) was heated under reflux for 2 h.
After cooling, the reaction mixture was poured onto
crushed ice (~25 g). The solid deposited was filtered off
and crystallized from EtOH to give compound 15 as
white crystals, mp 233–234°C, yield 0.39 g (61%).
Method B.
A mixture of carbonitrile 2 (0.60 g,
3 mmol) and hydrazine hydrate (0.15 g, 3 mmol) in
acetic acid (15 mL) was heated under reflux for 2 h.
After cooling, the reaction mixture was poured onto
crushed ice. The white solid so formed was filtered off
and crystallized from EtOH to give compound 15 as
white crystals, mp 233–234°C, yield 0.44 g (69%).
Benzyl
5-amino-4-(2-hydroxy-3,5-dimethylbenzoyl)-1H-
pyrazole-1-carbodithioate (13). A mixture of carbonitrile
2 (0.60 g, 3 mmol) and S-benzyldithiocarbazate (0.58 g,
3 mmol) in absolute ethanol (15 mL) was heated under
reflux for 2 h. The pale yellow crystals deposited after
cooling were filtered off and crystallized from EtOH to
give compound 13 as pale yellow crystals, mp 241–
242°C, yield 0.79 g (66%). IR (KBr, cmꢀ1): 3371 (OH),
3261, 3170 (NH2), 3040 (CHarom.), 2912, 2890 (CHaliph.),
1635 (C¼O), 1603 (C¼N), 1533 (C¼C). 1H-NMR
(400 MHz, DMSO-d6): 2.15 (s, 3H, CH3), 2.24 (s, 3H,
CH3), 4.46 (s, 2H, CH2), 7.17 (s, 1H, Ar–H), 7.27–7.51
(m, 5H, Ar–H), 7.69 (s, 1H, Ar–H), 8.08 (s, 1H, H-
3pyrazole), 8.99 (bs, 2H, NH2 exchangeable with D2O),
10.92 (bs, 1H, OH exchangeable with D2O). Mass
spectrum, m/z (Ir %): 397 (59), 321 (6), 258 (11), 217
(8), 173 (11), 149 (13), 120 (6), 91 (100), 77 (11), 65
(14). Anal. Calcd for C20H19N3O2S2 (397.51): C, 60.43;
H, 4.82; N, 10.57; S, 16.13%. Found: C, 60.20; H, 4.60;
N, 10.35; S, 16.00%.
Method C.
A mixture of carboxamide 4 (0.65 g,
3 mmol) and S-benzyldithiocarbazate in DMF (15 mL)
was heated under reflux for 2 h. After cooling, the
reaction mixture was poured onto crushed ice. The
yellow solid so formed was filtered off and crystallized
from ethanol to give compound 15 as white crystals, mp
233–234°C, yield 0.40 g (63%). IR (KBr, cmꢀ1): 3401
(NH), 3009 (CHarom.), 2940, 2885, 2825 (CHaliph.), 1710
(C¼Oα-pyrone), 1602 (C¼N), 1538 (C¼C). 1H-NMR
(400 MHz, DMSO-d6): 2.01 (s, 3H, CH3), 2.11 (s, 3H,
CH3), 6.78 (s, 1H, H-7), 7.38 (s, 1H, H-9), 8.44 (s, 1H,
H-3pyrazole). 13C-NMR (75 MHz, DMSO-d6): 14.7 (CH3),
20.4 (CH3), 113.5, 121.7, 126.7, 128.7, 130.0, 132.3,
137.6, 150.1, 155.5, 156.4. Mass spectrum, m/z (Ir %):
214 (100), 199 (40), 185 (6), 130 (10), 115 (8), 107 (12),
92 (13), 77 (13), 65 (11). Anal. Calcd for C12H10N2O2
(214.22): C, 67.28; H, 4.71; N, 13.08%. Found: C, 67.00;
H, 4.50; N, 12.80%.
Benzyl 2-[(2-amino-6,8-dimethylchromon-3-yl)methylidene]
hydrazine-carbodithioate (14). A mixture of carbonitrile 2
(0.60 g, 3 mmol) and S-benzyldithiocarbazate (0.58 g,
3 mmol) in dry benzene (30 mL) containing triethylamine
(0.1 mL) was heated under reflux for 4 h. The solid
deposited after cooling was filtered off and crystallized
2-Amino-7,9-dimethyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-
carboxamide (16). To a solution of carbonitrile 2 (0.60 g,
3 mmol) in absolute ethanol (15 mL), cyanoacetamide
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
3-Substituted-6,8-dimethylchromones
(0.26 g, 3 mmol) in absolute ethanol (10 mL) and
piperidine (0.1 mL) was added. The reaction mixture was
refluxed for 30 min. The yellow crystals obtained during
heating were filtered and recrystallized from DMF/H2O to
give compound 16 as yellow crystals, yield mp > 300°C,
yield 0.63 g (74%). IR (KBr, cmꢀ1): 3368, 3225, 3185
(2NH2), 2941 (CHaliph.), 1665 (C¼Oamide), 1655 (C¼Oγ-
NH2 exchangeable with D2O), 8.65 (bs, H, NH
exchangeable with D2O), 8.78 (s, 1H, H-4pyridine). Mass
spectrum, m/z (Ir %): 301 (59), 285 (41), 271 (80), 257
(61), 241 (47), 228 (22), 149 (100), 121 (49), 77 (14), 66
(55). Anal. Calcd for C15H15N3O4 (301.29): C, 59.79; H,
5.02; N, 13.95%. Found: C, 59.50; H, 4.80; N, 13.60%.
6-(2-Hydroxy-3,5-dimethylphenyl)-2-oxo-1,2-
1
pyrone), 1612 (C¼N), 1542 (C¼C). H-NMR (400 MHz,
dihydropyridine-3-carbonitrile (19).
A
mixture of
DMSO-d6): 2.28 (s, 3H, CH3), 2.30 (s, 3H, CH3), 7.21 (s,
1H, H-8), 7.96 (s, 1H, H-6), 8.84 (s, 1H, H-4), 11.87 (bs,
4H, 2NH2 exchangeable with D2O). 13C-NMR (75 MHz,
DMSO-d6): 14.2 (CH3), 20.4 (CH3), 103.4, 107.9, 118.5,
126.7, 128.4, 129.8, 133.4, 146.3, 151.6, 154.5, 159.2,
166.8, 179.1 (C¼O). Mass spectrum, m/z (Ir %): 283
(100), 266 (47), 238 (24), 209 (3), 91 (11), 77 (7), 65 (8).
Anal. Calcd for C15H13N3O3 (283.28): C, 63.60; H, 4.63;
N, 14.83%. Found: C, 63.35; H, 4.40; N, 14.60%.
carboxylic acid 3 (0.65 g, 3 mmol) and cyanoacetamide
(0.25 g, 3 mmol) in ethanol (15 mL) containing few
drops of triethylamine was refluxed on water bath for
30 min. The solid obtained after cooling was filtered and
crystallized from DMF to give compound 19 as pale
yellow crystals, mp > 300°C, yield 0.49 g (68%). IR
(KBr, cmꢀ1): 3302 (OH), 3216 (NH), 3077 (CHarom.),
2237 (CꢁN), 1652 (C¼O), 1620 (C¼C). 1H-NMR
(300 MHz, DMSO-d6, δ): 2.40 (s, 3H, CH3), 2.44 (s, 3H,
CH3), 7.26 (d, 1H, J = 9.0 Hz, Ar–H), 7.46 (d, 1H,
J = 8.4 Hz, Ar–H), 7.94 (s, 1H, Ar–H), 8.22 (s, 1H, Ar–
H), 9.46 (s, H, NH exchangeable with D2O). 13C-NMR
(100 MHz, DMSO-d6): 17.3 (CH3), 20.7 (CH3), 92.5 (C-
3), 117.1 (CꢁN), 121.3, 125.4, 135.1, 147, 150.9, 151.5,
164.5, 166.4, 171.8, 174.2. Mass spectrum, m/z (Ir %):
240 (46), 222 (18), 194 (12), 147 (15), 120 (100), 92
(39), 80 (85), 65 (45). Anal. Calcd for C14H12N2O2
(240.26): C, 69.99; H, 5.03; N, 11.66%. Found: C, 69.70;
H, 5.00; N, 11.40%.
(3Z)-3-{[(2-Aminophenyl)amino]methylidene}-6,8-
dimethyl-2H-chromane-2,4(3H)-dione (17).
A mixture of
carboxamide 4 (0.65 g, 3 mmol) and o-phenylenediamine
(0.33 g, 3 mmol) in DMF (15 mL) was heated under reflux
for 2 h. The pale yellow crystals obtained after cooling
were filtered off and recrystallized from DMF to give
compound 17 as yellow crystals, mp 231–232°C, yield
0.72 g (78%). IR (KBr, cmꢀ1): 3387, 3337, 3149 (NH2,
NH), 3081 (CHarom.), 2920, 2890 (CHaliph.), 1718 (C¼Oα-
1
pyrone), 1684 (C¼O), 1601 (C¼C). H-NMR (400 MHz,
DMSO-d6): 2.39 (s, 3H, CH3), 2.43 (s, 3H, CH3), 5.24
(bs, 2H, NH2 exchangeable with D2O), 6.75 (t, 1H,
J = 6.8 Hz, Ar–H), 6.91 (d, 1H, J = 7.2 Hz, Ar–H), 7.08 (t,
1H, J = 7.2 Hz, Ar–H), 7.38 (s, 1H, H–7), 7.46 (d, 1H,
J = 6.8 Hz, Ar–H), 7.57 (d, 1H, J = 15.2 Hz, Holefinic),
7.79 (s, 1H, H-5), 13.45 (d, 1H, J = 12.4 Hz, NH
exchangeable with D2O). Mass spectrum, m/z (Ir %): 308
(69), 307 (100), 290 (13), 263 (11), 159 (14), 149 (13),
119 (79), 105 (12), 91 (52), 77 (41), 65 (63). Anal. Calcd
for C18H16N2O3 (308.34): C, 70.12; H, 5.23; N, 9.09%.
Found: C, 69.80; H, 5.10; N, 8.70%.
5-(Cyanomethyl)-7,9-dimethyl-2-oxo-1,5-dihydro-2H-
chromeno[4,3-b]pyridine-3-carbonitrile (20). A mixture of
acrylonitrile 5 (0.66 g, 3 mmol) and cyanoacetamide
(0.26 g, 3 mmol) in absolute ethanol (20 mL) containing
piperidine (0.1 mL) was heated under reflux for 2 h. The
yellow crystals deposited during heating were filtered off,
and crystallized from EtOH to give compound 20 as
yellow crystals, yield 0.53 g (61%), mp > 300°C. IR
(KBr, cmꢀ1): 3420 (NH), 2950, 2862 (CHaliph.), 2235
(CꢁN), 2200 (CꢁN), 1652 (C¼O), 1617 (C¼C). 1H-
NMR (400 MHz, DMSO-d6): 2.16 (s, 3H, CH3), 2.34 (s,
3H, CH3), 2.99 (d, 2H, J = 5.6 Hz, CH2CN), 5.45 (t, 1H,
J = 6.4 Hz, H-5), 7.04 (s, 1H, H-8), 7.59 (s, 1H, H-10),
7.64 (s, 1H, H-4pyridine). 13C-NMR (DMSO-d6, δ): 15.7
(CH3), 20.4 (CH3), 23.1 (CH2), 71.3 (C-5), 110.4, 116.6
(CꢁN), 117.5 (CꢁN), 118.4, 123.1, 125.0, 132.3, 132.9,
135.7, 136.8, 143.9, 151.4, 162.3 (C-2). Mass spectrum,
m/z (Ir %): 291 (8), 251 (100), 223 (6), 179 (3), 104 (7),
98 (9), 85 (13), 77 (8), 71 (24), 65 (7). Anal. Calcd for
C17H13N3O2 (291.30): C, 70.09; H, 4.50; N, 14.42%.
Found: C, 69.80; H, 4.30; N, 14.10%.
2-Amino-5-(2-hydroxy-3,5-dimethylbenzoyl]-6-oxo-1,6-
dihydropyridine-3-carboxamide (18).
A
mixture of
carboxamide 4 (0.65 g, 3 mmol) and cyanoacetamide
(0.25 g, 3 mmol) in sodium ethoxide (prepared by
dissolving 0.2 g sodium in 20 mL absolute ethanol) was
heated under reflux for 2 h. After cooling, the reaction
mixture was poured onto crushed ice and neutralized with
concentrated HCl. The solid so formed was filtered off
and recrystallized from DMF/EtOH to give compound 18
as white crystals, mp > 300°C, yield 0.65 g (71%). IR
(KBr, cmꢀ1): 3373, 3249, 3161 (2NH2, NH, OH), 1683
(C¼Opyridone), 1648 (C¼Oamide), 1619 (C¼Obenzoyl),
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. A. Ibrahim, A.-S. Badran, N. M. El-Gohary, and S. H. Hashiem
Vol 000
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet