Reactivity of 6-methylchromone-3-carbonitrile towards some nitrogen nucleophilic reagents

Article abstract of DOI:10.3987/COM-18-13874

The chemical reactivity of 6-methylchromone-3-carbonitrile (1) was studied towards a variety of nitrogen nucleophiles. A variety of products was obtained from the reaction of carbonitrile 1 with hydrazine hydrate, S-benzyl dithiocarbazate, isonicotinic acid hydrazide and cyanoacetohydrazide. A diversity of Schiff bases bearing 2-amino-6-methylchromone linked variable heterocyclic systems was efficiently synthesized. Reaction of carbonitrile 1 with guanidine and cyanoguanidine resulted in ring conversion producing chromeno[4,3d]pyrimidines. Reaction of carbonitrile 1 was also studied towards some 1,4-binucleophiles.

Full text of DOI:10.3987/COM-18-13874

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HETEROCYCLES, Vol. 96, No. 4, 2018
HETEROCYCLES, Vol. 96, No. 4, 2018, pp. 690 - 706. © 2018 The Japan Institute of Heterocyclic Chemistry
Received, 6th February, 2018, Accepted, 23rd February, 2018, Published online, 6th March, 2018
DOI: 10.3987/COM-18-13874
REACTIVITY
OF
6-METHYLCHROMONE-3-CARBONITRILE
TOWARDS SOME NITROGEN NUCLEOPHILIC REAGENTS
Nasser M. El-Gohary, Magdy A. Ibrahim,* and Sara Said
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy
11711, Cairo, Egypt. E-mail address: magdy_ahmed1977@yahoo.com
Abstract – The chemical reactivity of 6-methylchromone-3-carbonitrile (1) was
studied towards a variety of nitrogen nucleophiles. A variety of products was
obtained from the reaction of carbonitrile 1 with hydrazine hydrate, S-benzyl
dithiocarbazate, isonicotinic acid hydrazide and cyanoacetohydrazide. A diversity
of Schiff bases bearing 2-amino-6-methylchromone linked variable heterocyclic
systems was efficiently synthesized. Reaction of carbonitrile 1 with guanidine and
cyanoguanidine resulted in ring conversion producing chromeno[4,3-
d]pyrimidines. Reaction of carbonitrile 1 was also studied towards some 1,4-
binucleophiles.
INTRODUCTION
Chromone derivatives represent an important class of oxygen containing heterocyclic compounds, which
are widely spread in plants1-3 and exhibit wide range of biological and pharmacological activities
including anti-inflammatory,4 anti-HIV,5 anticancer,6 antibacterial,7 antimalarial,8 antitumor,9 as well as
treatment of Alzheimer’s disease.10 The presence of the electron-withdrawing cyano group at the position
3 of the chromone system changes crucially the chemical reactivity of the γ-pyrone ring with respect to
nucleophiles, and provides a broad synthetic potential of chromone-3-carbonitriles.11-14 They have the
ability to undergo a nucleophilic 1,4-attack followed by additional transformations related to γ-pyrone
ring opening and heterocyclizations at the C-4 atom and/or at the cyano group.15-19 Herein, we aimed to
study the chemical transformations of 6-methylchromone-3-carbonitrile (1) towards some nitrogen
nucleophiles.
RESULTS AND DISCUSSION
The present work aimed to study the chemical reactivity of 6-methylchromone-3-carbonitrile (1) towards

HETEROCYCLES, Vol. 96, No. 4, 2018
691
a variety of nitrogen nucleophiles under different reaction conditions. Treatment of carbonitrile 1 with
hydrazine hydrate (1:1 molar ratio) in boiling acetic acid afforded 8-methylchromeno[4,3-c]pyrazol-
4(1H)-one (2). The proposed mechanism is depicted in Scheme 1, the reaction may proceed through
nucleophilic attack at C-2 with ring opening (intermediate A). Free rotation around the single bond
(intermediate B) with concomitant cycloaddition reactions produced intermediate C which underwent
dehydration followed by hydrolysis to produce the final product 2. The IR spectrum of compound 2
1
showed characteristic absorption bands at 3192 (NH), 1706 (C=Oα-pyrone) and 1632 cm-1 (C=N). Its H
NMR spectrum showed two doublets assigned to H-6 and H-7 at δ 7.24 and 7.29, two singlets at δ 7.73
and 8.42 assigned to H-9 and H-3, respectively, in addition to D2O-exchangeable signal at δ 14.20
attributed to the NH proton. Furthermore, the mass spectrum is a strong evidence for elucidation of
structure 2 which revealed the molecular ion peak, as the base peak, at m/z 200, which agrees well with
the proposed molecular formula (C11H8N2O2).
..
O
H2N
O
O
NH
N
Me
CN
Me
NH2NH2•H2O
Me
AcOH
NH2
O
OH
N
H
OH
N
1
A
B
EtOH
O
O
NC
OH
Me
NH2
Me
HN
O
NH
OH
Me
O
HN
HO
C
N
1
HO
Me
NH
N
NH
NH
D
E
-H2O
+H2O
57%
Me
N
HN
Me
O
Me
OH
N
O
O
O
O
i) cycloaddition
2
OH
Me
O
HN
NH2
ii) proton transfer
55%
OH
O
N
N
NH
N
NH
Me
F
3
Scheme 1

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HETEROCYCLES, Vol. 96, No. 4, 2018
Interestingly, reaction of carbonitrile 1 with hydrazine hydrate in boiling ethanol showed different
o
behavior producing a yellow crystalline product with high melting point (above 300 C). After
interpretation of the spectral data, this product was identified as 2-amino-3-[({4-[(2-hydroxy-5-
methylphenyl)carbonyl]-1H-pyrazol-3-yl}imino)methyl]-6-methylchromone (3) (Scheme 1). The reaction
may occur through the formation of intermediate A followed by the cycloaddition of the NH2 group onto
the nitrile function producing intermediate D which reacted with another molecule of carbonitrile 1
producing the target compound 3, via γ-pyrone ring opening (intermediate E) with rotation around the
single bond (intermediate F) followed by cycloaddition of the hydroxyl group on the nitrile group with
concomitant proton transfer. The IR spectrum of compound 3 showed characteristic absorption bands at
3390, 3224, 3090 (NH2, NH, OH), 1652 (C= Oγ-pyrone) and 1609 cm-1 (C=Obenzoyl and C=N). The 1H NMR
spectrum of compound 3 consists of two upfield signals attributable to 2CH3 protons at δ 2.08 and 2.39,
four doublets assignable to aromatic protons at δ 6.84, 7.10, 7.29 and 7.48, in addition to four singlets at δ
7.05 (Ar-H), 7.78 (H-5pyrazole), 8.06 (H-5chromone) and 8.76 (CH=N). The spectrum also revealed
D2O-exchangeable signals at δ 7.21 (NH2) and 9.04 (NH). The OH proton was not observed in the
spectrum and this may attributed to the strong hydrogen bonding between the hydroxyl and carbonyl
groups. The mass spectrum of compound 3 confirms the suggested structure, which recorded the
molecular ion peak at m/z 402 and the base peak at m/z 135.
Next, the chemical transformations of 6-methylchromone-3-carbonitrile (1) were studied toward some
hydrazides namely; cyanoacetohydrazide, isonicotinic acid hydrazide and S-benzyl dithiocarbazate, in
different solvents. Therefore, reaction of carbonitrile 1 with cyanoacetohydrazide and isonicotinic acid
hydrazide in boiling ethanol afforded the corresponding hydrazones 4 and 5, respectively (Scheme 2).
1
The H NMR spectra of compounds 4 and 5 showed characteristic singlets attributed to CH=N at δ 8.61
and 8.95, respectively.
O
O
O
O
H2N
H
Me
N
H
R
Me
N
R
CN
N
O
EtOH
O
NH2
1
4; R= CH2CN (61%)
5; R= 4-pyridyl (60%)
Scheme 2
On the other hand, S-benzyl dithiocarbazate showed different behavior upon treating with carbonitrile 1 in
boiling ethanol producing the unexpected; benzyl 5-amino-4-[(2-hydroxy-5-methylphenyl)carbonyl]-1H-
pyrazole-1-carbodithioate (6), another expected product; benzyl 2-[(2-amino-6-methylchromon-3-
yl)methylidene]hydrazine-carbodithioate (7) was ruled out based on the spectral data (Scheme 3).
Compound 7 was prepared alternatively from the condensation reaction of 2-amino-6-methylchromone-3-

HETEROCYCLES, Vol. 96, No. 4, 2018
693
carboxaldehyde (8) with S-benzyl dithiocarbazate, in boiling ethanol (Scheme 3). Compound 6 gave deep
red color with FeCl3 solution, indicating the presence of free phenolic OH group. Formation of compound
6 may occur via nucleophilic attack at C-2 position with concomitant γ-pyrone ring opening leading to
intermediate G, which underwent intramolecular cyclization through addition of NH group onto the
nitrile function (intermediate H) followed by proton transfer producing the final product 6. Another
reaction pathway leading to hydrazone 7, via intermediate I, was excluded.
S
O
O
O
N
H2N
Me
Me
CN
N
H
S
Ph
H
N
S
Ph
EtOH
OH
G
N
H
S
1
O
O
O
H
N
O
NH
Me
Me
S
Ph
Me
S
N
O
H
N
S
OH
S
NH2
NH
N
OH
Ph
8
I
H
55%
S
H2N
EtOH
O
O
O
NH2
N
S
Ph
H
N
H
Me
S
Me
S
Ph
N
N
73%
S
S
N
NH2
OH
Ph
7
6
Scheme 3
Next, reactions of carbonitrile 1 with the above hydrazides were repeated in boiling acetic acid. Treatment
of carbonitrile 1 with isonicotinic acid hydrazide and S-benzyl dithiocarbazate, in boiling acetic acid,
gave one product which was found to be identical with 8-methylchromeno[4,3-c]pyrazol-4(1H)-one (2),
via the nonisolable intermediate J (Scheme 4).20

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HETEROCYCLES, Vol. 96, No. 4, 2018
:
H2O
R
X
X
N
HN
O
O
O
N
N
H2N
Me
Me
N
R
Me
CN
H
AcOH
O
O
O
2
1
J
X= O, R= 4-pyridyl (45%)
X= S, R= SCH2Ph (48%)
Scheme 4
Interestingly, reaction of carbonitrile 1 with cyanoacetohydrazide in boiling acetic acid proceeds in a
different mechanism leading to unexpectedly, 3-hydroxy-9-methylchromeno[4,3-b]pyrazolo[4,3-e]-
pyridin-5(1H)-one (9) (Scheme 5). Under these reaction conditions cyanoacetohydrazide acted as carbon
nucleophile, and the ring transformation of carbonitrile 1 into the annulated system 9 may initially
proceeds via nucleophilic attack at C-2 position with γ-pyrone ring opening to produce intermediate K,
which underwent cycloaddition reactions including addition of phenolic OH into the C≡N group, two
consecutive cycloaddition reactions through addition of NH2 into the C≡N group followed by addition to
the C=O group, generating intermediate L. Dehydration of the latter intermediate gave intermediate M
which hydrolyzed under the reaction conditions producing the final product 9 as depicted in Scheme 5.
The IR spectrum of compound 9 showed characteristic absorption bands at 3196 (OH and NH), 1694
(C=Oα-pyrone) and 1608 cm-1 (C=N). The mass spectrum is a strong evidence for elucidation of structure 9
which revealed the molecular ion peak at m/z 267, as the base peak, which agrees well with the proposed
molecular formula (C14H9N3O3).
H2N
NH
N
O
O
O
O
Me
CN
NH2
AcOH
65%
Me
HN
N
+
H
CN
O
OH
N
1
K
N
HN
NH
HN
N
OH
O
N
N
O
OH
H
N
O
HO
Me
+H2O
-H2O
Me
Me
O
O
NH
NH
9
L
M
Scheme 5

HETEROCYCLES, Vol. 96, No. 4, 2018
695
Due to the interesting behavior of cyanoacetohydrazide, the reaction of carbonitrile 1 was studied towards
N`-acetyl-2-cyanoacetohydrazide and 2-cyano-N'-[(3,4-dimethoxyphenyl)methylidene]acetohydrazide.
Thus, reaction of carbonitrile 1 with N'-acetyl-2-cyanoacetohydrazide afforded N'-acetyl-2-amino-7-
methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carbohydrazide (10), via the nonisolable intermediate N
(Scheme 6).17 The 1H NMR spectrum of compound 10 revealed four singlet signals at δ 1.89 (CH3), 2.37
(CH3), 7.77 (H-6), 8.56 (H-4pyridine), two doublets at δ 7.31 (H-9), 7.47 (H-8), in addition to D2O-
exchangeable signals at δ 9.02, 9.49 (NH2), 10.95 (NH) and 11.28 (NH). The mass spectrum of
compound 10 revealed the molecular ion peak at m/z 326 and confirms the suggested structure.
O
O
O
O
O
O
O
Me
CN
H
H
H
Me
N
Me
Me
N
Me
Me
N
N
+
N
EtOH/DBU
70%
N
H
H
H
O
O
CN
O
O
N
NH2
OH
N
N
1
10
N
Scheme 6
On the other hand, reaction of carbonitrile 1 with 2-cyano-N'-[(3,4-dimethoxyphenyl)methylidene]-
acetohydrazide (11) in boiling ethanol containing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) yielded
2-amino-5-cyano-N'-[(3,4-dimethoxyphenyl)methylidene]-8-methyl-6-oxo-1-benzoxocine-3-carbohydra-
zide (12).17,18 The expected product from the latter reaction, 2-amino-N'-[(3,4-dimethoxyphenyl)-
methylidene]-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carbohydrazide (13), was excluded based
on the spectral data (Scheme 7). The expansion of carbonitrile 1 into benzoxocine derivative 12 may
occur via the formation of intermediate O followed by an intramolecular nucleophilic addition of the
hydroxyl group onto the nitrile function leading to the final product 12 as shown in Scheme 7. Another
reaction pathway leading to compound 13, via intermediate P, was ruled out. The IR spectrum of
compound 12 showed characteristic absorption bands at 3384 (br, NH2, NH), 2231 (C≡N), 1669
(C=Oamide and C=Ooxocine) and 1615 cm–1 (C=N).
O
CN
OMe
Me
O
OMe
O
O
OMe
EtOH/DBU
OMe
OMe
Me
H
O
CN
N
OMe
Me
CN
52%
N
O
N
N
O
N
H
+
N
O
N
OH
NH2
CN
H
1
11
12
O
OMe
OMe
OMe
O
O
O
OMe
Me
O
O
N
N
H
Me
N
N
H
N
NH2
CN
CN
OH
13
P
Scheme 7

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HETEROCYCLES, Vol. 96, No. 4, 2018
An alternative route was utilized to synthesize chromeno[2,3-b]pyridine derivative 13 from condensation
reaction of 2-amino-6-methylchromone-3-carboxaldehyde (8) with cyanoacetohydrazide derivative 11
(Scheme 8). The IR spectrum of compound 13 showed characteristic absorption bands at 3399, 3289,
1
3154 (NH2, NH), 1671 (C=Oamide and C=Oγ-pyrone) and 1608 cm–1 (C=N). Its H NMR spectrum showed
characteristic singlets at δ 8.50s and 8.61 attributed CH=N and H-4pyridine, respectively. The spectrum also
revealed broad D2O-exchangeable signals at δ 9.32 (NH2) and 11.44 (NH). Furthermore, the mass
spectrum of compound 13 is a strong evidence for elucidation of structure 13 which revealed the
molecular ion peak at m/z 432, which agrees well with the proposed formula weight (432.43).
OMe
OMe
OMe
O
O
O
O
O
OMe
O
Me
N
Me
CHO
NH2
EtOH/DBU
71%
N
N
H
N
+
H
N
NH2
CN
13
8
11
Scheme 8
Then, the chemical reactivity of carbonitrile 1 was studied towards some hydrazones. Therefore,
treatment of carbonitrile 1 with salicylaldehyde hydrazone 14 and isatin hydrazone 15 in boiling ethanol
furnished the corresponding unsymmetrical Schiff bases 16 and 17, respectively (Scheme 9). The IR
spectra of compounds 16 and 17 showed characteristic absorption bands at 1651/1652 (C=Oγ-pyrone),
1625/1609 cm-1 (C=N). The 1H NMR spectrum of compound 16 showed two singlet signals attributed to
1
two CH=N protons at δ 8.98 and 9.02, while the H NMR spectrum of compound 17 showed singlet
signal corresponding to CH=N at δ 8.99.
N
H2N
H2N
N
O
O
HO
O
O
O
O
N
H
O
Me
CN
Me
HO
N
O
Me
N
N
N
15
14
N
NH2
EtOH
67%
EtOH
69%
NH2
16
H
1
17
Scheme 9
In the same manner, reaction of carbonitrile 1 with 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-
3-carbonitrile (18),20 and 3-amino-2-phenylquinazolin-4(3H)-one (19),21 afforded Schiff bases 20 and 21,
respectively, in which 2-amino-6-methylchromone linked pyridine and quinazoline moities in one
molecular frame (Scheme 10). The IR spectra of compounds 20 and 21 showed characteristic absorption

HETEROCYCLES, Vol. 96, No. 4, 2018
697
bands at 3250, 3130/3293, 3219 (NH2), 1655/1652 (C=Oγ-pyrone), 1614/1607 cm-1 (C=N), respectively, in
addition the spectrum of compound 20 showed absorption band assigned to C≡N at 2213 cm-1, while the
spectrum of compound 21 showed absorption band attributed to C=Oquinazoline at 1669 cm-1. The 1H NMR
spectra of compounds 20 and 21 showed characteristic singlet signals attributed to H-5 and CH=N at δ
7.80/8.06 and 8.84/8.97, respectively. The spectrum of compound 20 showed distinctive singlet at δ 6.03
assigned to H-5pyridone
.
CN
O
O
H2N
Ph
CN
Me
N
Me
H2N
N
O
Me
O
N
O
O
O
O
O
N
Me
CN
Me
Me
N
Me
N
19
N
N
18
Ph
EtOH
58%
EtOH
70%
O
NH2
NH2
1
20
21
Scheme 10
Next, the conversion of carbonitrile 1 into chromeno[4,3-d]pyrimidines 22 and 23, was achieved through
the ring opening/ring closure (RORC) reactions of carbonitrile 1 with guanidine hydrochloride and
cyanoguanidine in ethanolic potassium hydroxide solution (Scheme 11). The IR spectra of compounds 22
and 23 revealed characteristic absorption bands attributed to C=Oα-pyrone at 1720 and 1695 cm-1,
1
respectively. Their H NMR spectra showed characteristic singlet attributed to H-4pyrimidine at δ 8.94.
Structures of compounds 22 and 23 were deduced from their mass spectrum which revealed their
molecular ion peaks at m/z 227 (base peak) and 252 (92%), respectively.
CN
N
NH2
CN
HN
N
NH
O
O
HCl
NH2
N
O
N
Me
CN
N
O
H2N
NH2
Me
H2N
Me
5% KOH/EtOH
67%
5% KOH/EtOH
73%
O
O
1
22
23
Scheme 11
After that, carbonitrile 1 was allowed to react with some 1,4-binucleophiles. Reaction of carbonitrile 1
with o-phenylenediamine in boiling ethanol afforded chromeno[2,3-b][1,5]benzodiazepine 24 as shown in
Scheme 12. The reaction may proceed via intermediate Q followed by an intamolecular cyclization with
loss of ammonia molecule. The IR spectrum of compound 24 showed characteristic absorption bands
1
assigned to NH, C=Oγ-pyrone and C=N at 3303, 1642 and 1614 cm-1, respectively. Its H NMR spectrum
showed characteristic singlet attributed to CH=N at δ 9.35, in addition to an exchangeable signal

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HETEROCYCLES, Vol. 96, No. 4, 2018
attributed to NH proton at δ 12.62. Structure of compound 24 was further deduced from its mass spectrum
which revealed the molecular ion peak, as the base peak, at m/z 276 and confirms the suggested structure.
H2N
O
O
H2N
Me
-NH3
Me
N
N
H
59%
O
NH2
O
O
O
N
O
Q
NH
H
Me
CN
24
EtOH
H2N
H2N
CN
Ar
N
OMe
CN
1
O
NC
25
O
Me
N
N
CN
Ar = C6H4-p-OMe
NH2
O
NH2
26
63%
Scheme 12
On the other hand, reaction of carbonitrile 1 with 1,6-diamino-4-(4-methoxyphenyl)-2-oxo-
1,2-dihydropyridine-3,5-dicarbonitrile (25)22 in boiling ethanol afforded the Schiff base 26 (Scheme 12).
The IR spectrum of compound 26 showed absorption bands at 3458, 3396, 3305, 3150 (2NH2), 2218
1
(2C≡N), 1671 (C=Oγ-pyrone and C=Opyridone) and 1612 cm-1 (C=N). Its H NMR spectrum showed
characteristic singlet attributed to H-5 and CH=N at δ 7.79 and 10.05, respectively, in addition to an
exchangeable signal attributed to NH2 and 2NH protons at δ 8.39, 9.49 and 9.55.
Finally, reaction of carbonitrile 1 with o-aminothiophenol in boiling ethanol gave 2-amino-
3-(1,3-benzothiazol-2-yl)-6-methylchromone (27), via the nonisolable intermediate R followed by
cycloaddition of SH group onto the azomethine function with concomitant dehydrogenation, under the
reaction conditions (Scheme 13). The IR spectrum of compound 27 showed characteristic absorption
bands at 3447, 3290 (NH2), 1654 (C=Oγ-pyrone) and 1613 cm-1 (C=N). The mass spectrum of compound 27
did not record the molecular ion peak, but the molecule splits into two parts corresponding to
benzothiazole fragment, as the base peak at m/z 135, and 2-amino-6-methylchromone fragment at m/z 175,
with high relative intensity (91%).
HS
HS
O
O
O
N
O
O
Me
Me
Me
-H2
CN
H2N
S
N
H
O
NH2
EtOH
53%
NH
1
27
R
Scheme 13

HETEROCYCLES, Vol. 96, No. 4, 2018
699
EXPERIMENTAL
General: Melting points were determined on a digital Stuart SMP3 apparatus. Infrared spectra were
measured on FTIR Nicolet IS10 spectrophotometer (cm-1), using KBr disks. 1H NMR (300 MHz) and 13C
NMR (75 MHz) spectra were measured on Mercury-300BB (300 MHz), using DMSO-d6 as a solvent and
TMS (δ) as the internal standard. Mass spectra were obtained using GC-2010 Shimadzu Gas
chromatography instrument mass spectrometer (70 eV). Elemental microanalyses were performed on a
Perkin–Elmer CHN-2400 analyzer. 6-Methylchromone-3-carbonitrile (1) and 2-amino-6-methyl-
chromone-3-carboxaldehyde (8) were prepared according to the published methods.23
8-Methylchromeno[4,3-c]pyrazol-4(1H)-one (2). Method A: A mixture of carbonitrile 1 (0.55 g, 3
mmol) and hydrazine hydrate (0.15 g, 3 mmol) in acetic acid (10 mL) was heated under reflux for 2 h.
After cooling, the reaction mixture was poured onto crushed ice. The solid so formed was filtered and
crystallized from EtOH/H2O to give compound 2 as white crystals. mp 186-187 ºC, yield (0.34 g, 57%).
Method B: A mixture of carbonitrile 1 (0.55 g, 3 mmol) and isonicotinic acid hydrazide or S-benzyl
dithiocarbazate (3 mmol) in acetic acid (10 mL) was heated under reflux for 4 h. After cooling, the
reaction mixture was poured onto crushed ice (~20 g). The solid so formed was filtered and crystallized
from EtOH/H2O to give compound 2 as white crystals, mp 186-187 ºC, yield (45-48%). IR (KBr, cm-1):
1
3192 (NH), 3034 (CHarom.), 2919 (CHaliph.), 1706 (C=Oα-pyrone), 1632 (C=N), 1583 (C=C). H NMR
(DMSO-d6, δ): 2.32 (s, 3H, CH3), 7.24 (d, 1H, J = 7.8 Hz, H-6), 7.29 (d, 1H, J = 7.8 Hz, H-7), 7.73 (s, 1H,
H-9), 8.42 (s, 1H, H-3), 14.20 (bs, 1H, NH exchangeable with D2O). 13C NMR (DMSO-d6, δ): 20.9, 114.6,
118.9, 122.4, 123.6, 124.9, 136.3, 145.7, 154.3, 158.4, 175.1. Mass spectrum (m/z, I%): 200 (100), 171
(17), 144 (15), 115 (16), 89 (10), 77 (6), 63 (7). Anal. Calcd for C11H8N2O2 (200.19): C, 66.00; H, 4.03;
N, 13.99%. Found: C, 65.91; H, 4.01; N, 13.79%.
2-Amino-3-[({4-[(2-hydroxy-5-methylphenyl)carbonyl]-1H-pyrazol-3-yl}imino)methyl]-6-methyl-
chromone (3). A mixture of carbonitrile 1 (0.55 g, 3 mmol) and hydrazine hydrate (0.15 g, 3 mmol) in
absolute EtOH (20 mL) was heated under reflux for 2 h. The yellow crystals obtained during heating were
filtered and crystallized from DMF/EtOH to give compound 3 as yellow crystals. mp >300 ºC, yield (0.33
g, 55%). IR (KBr, cm-1): 3390, 3224, 3090 (NH2, NH, OH), 1652 (C=Oγ-pyrone), 1609 (C=Obenzoyl and
C=N), 1559 (C=C). 1H NMR (DMSO-d6, δ): 2.08 (s, 3H, CH3), 2.39 (s, 3H, CH3), 6.84 (d, 1H, J = 7.5 Hz,
Ar-H), 7.05 (s, 1H, Ar-H), 7.10 (d, 1H, J = 8.7 Hz, Ar-H), 7.21 (bs, 2H, NH2 exchangeable with D2O),
7.29 (d, 1H, J = 8.1 Hz, H-8chromone), 7.48 (d, 1H, J = 8.4 Hz, H-7chromone), 7.78 (s, 1H, H-5pyrazole), 8.06 (s,
1H, H-5chromone), 8.76 (s, 1H, CH=N), 9.04 (bs, 1H, NH exchangeable with D2O). Mass spectrum (m/z,
I%): 402 (16), 386 (13), 367 (6), 217 (19), 201 (72), 185 (20), 170 (18), 135 (100), 115 (15), 106 (28), 91
(16), 77 (39), 65 (11). Anal. Calcd for C22H18N4O4 (402.40): C, 65.66; H, 4.51; N, 13.92%.

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HETEROCYCLES, Vol. 96, No. 4, 2018
Found: C, 65.26; H, 4.31; N, 13.77%.
N'-[(2-Amino-6-methylchromon-3-yl)methylidene]-2-cyanoacetohydrazide (4).
A
mixture of
carbonitrile 1 (0.55 g, 3 mmol) and cyanoacetohydrazide (0.30 g, 3 mmol) in EtOH (15 mL) was heated
under reflux for 2 h. The pale yellow crystals obtained during heating were filtered and crystallized from
DMF/EtOH to give compound 4 as yellow crystals, mp >300 ºC, yield (0.52 g, 61%). IR (KBr, cm-1):
3284, 3196, 3113 (NH2, NH), 3063 (CHarom.), 2958, 2921 (CHaliph.), 2254 (C≡N), 1680 (C=Oamide), 1636
1
(C=Oγ-pyrone), 1616 (C=N), 1571 (C=C). H NMR (DMSO-d6, δ): 2.38 (s, 3H, CH3), 4.22 (s, 2H, CH2),
7.30 (d, 1H, J = 8.7 Hz, H-8), 7.47 (d, 1H, J = 8.7 Hz, H-7), 7.78 (s, 1H, H-5), 8.61 (s, 1H, CH=N), 9.22
(bs, 1H, NH exchangeable with D2O), 9.32 (bs, 1H, NH exchangeable with D2O), 11.69 (bs, 1H, NH
exchangeable with D2O). Anal. Calcd for C14H12N4O3 (284.27): C, 59.15; H, 4.25; N, 19.71%. Found: C,
59.01; H, 4.13; N, 19.55%.
N'-[(2-Amino-6-methylchromon-3-yl)methylidene]pyridine-4-carbohydrazide (5). A mixture of
carbonitrile 1 (0.55 g, 3 mmol) and isonicotinic acid hydrazide (0.41 g, 3 mmol) in EtOH (15 mL) was
heated under reflux for 2 h. The yellow crystals obtained during heating were filtered and crystallized
from DMF/H2O to give compound 5 as yellow crystals, mp 304-305 ºC, yield (0.58 g, 60%). IR (KBr,
cm-1): 3395, 3295, 3137 (NH2, NH), 1652 (C=Oamide and C=Oγ-pyrone), 1604 (C=N), 1588 (C=C). 1H NMR
(DMSO-d6, δ): 2.41 (s, 3H, CH3), 7.35 (d, 1H, J = 8.4 Hz, H-8), 7.51 (d, 1H, J = 8.7 Hz, H-7), 7.85 (d, 2H,
J = 5.7 Hz, H-3pyridine and H-5pyridine), 8.78 (d, 2H, J = 6.3 Hz, H-2pyridine and H-6pyridine), 8.95 (s, 1H,
CH=N), 9.22 (bs, 1H, NH exchangeable with D2O), 9.60 (bs, 1H, NH exchangeable with D2O), 12.03 (bs,
1H, NH exchangeable with D2O). Mass spectrum (m/z, I%): 322 (9), 218 (10), 201 (100), 188 (20), 135
(53), 123 (15), 106 (24), 91 (9), 78 (40), 64 (7). Anal. Calcd for C17H14N4O3 (322.32): C, 63.35; H, 4.38;
N, 17.38%. Found: C, 63.14; H, 4.25; N, 17.09%.
Benzyl 5-amino-4-[(2-hydroxy-5-methylphenyl)carbonyl]-1H-pyrazole-1-carbodithioate (6). A
mixture of carbonitrile 1 (0.55 g, 3 mmol) and S-benzyl dithiocarbazate (0.59 g, 3 mmol) in EtOH (20
mL) was heated under reflux for 30 min. The white crystals obtained during heating were filtered and
crystallized from EtOH to give compound 6 as white crystals, mp 172 ºC, yield (0.63 g, 55%). IR (KBr,
cm-1): 3405, 3282 (OH, NH2), 3022 (CHarom.), 2920, 2870 (CHaliph.), 1634 (C=Obenzoyl), 1615 (C=N), 1577
1
(C=C), 1282 (C=S). H NMR (DMSO-d6, δ): 2.25 (s, 3H, CH3), 4.48 (s, 2H, CH2), 6.86 (d, 1H, Ar-H),
7.17-7.22 (m, 2H, Ar-H), 7.28-7.31 (m, 2H, Ar-H), 7.44 (s, 1H, H-3pyrazole), 7.46-7.48 (m, 2H, Ar-H), 8.90
(bs, 2H, NH2 exchangeable with D2O), 10.13 (bs, 1H, OH exchangeable with D2O). 13C NMR (DMSO-d6,
δ): 20.7, 44.2, 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, I%): 383 (26), 307 (6), 244 (13), 203 (13), 135 (27), 107 (6),
105 (3), 91 (100), 77 (17). Anal. Calcd for C19H17N3O2S2 (383.49): C, 59.51; H, 4.47; N, 10.96; S,
16.72%. Found: C, 59.45; H, 4.36; N, 10.71; S, 16.39%.

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701
Benzyl 2-[(2-amino-6-methylchromon-3-yl)methylidene]hydrazine-carbodithioate (7). A mixture of
2-amino-6-methylchromone-3-carboxaldehyde (8) (0.41 g, 2 mmol) and S-benzyl dithiocarbazate (0.40 g,
2 mmol) in EtOH (10 mL) was heated under reflux for 1 h. The yellow crystals obtained during heating
were filtered and crystallized from DMF/EtOH to give compound 7 as yellow crystals, mp 299-300 ºC,
yield (0.56 g, 73%). IR (KBr, cm-1): 3442, 3270, 3126 (NH2, NH), 2963, 2925 (CHaliph.), 1641
(C=Oγ-pyrone), 1607 (C=N), 1573 (C=C), 1287 (C=S). 1H NMR (DMSO-d6, δ): 2.39 (s, 3H, CH3), 4.55 (s,
2H, CH2), 7.21-7.48 (m, 6H, Ar-H), 7.51 (d, 1H, J = 8.4 Hz, Ar-H), 7.79 (s, 1H, H-5), 8.69 (bs, 1H, NH
exchangeable with D2O), 8.77 (s, 1H, CH=N), 9.42 (bs, 1H, NH exchangeable with D2O), 13.35 (bs, 1H,
NH exchangeable with D2O). Mass spectrum (m/z, I%): 383 (40), 343 (7), 307 (7), 244 (9), 217 (3), 203
(8), 173 (11), 135 (20), 91 (100), 77 (11), 65 (12). Anal. Calcd for C19H17N3O2S2 (383.49): C, 59.51; H,
4.47; N, 10.96; S, 16.72%. Found: C, 59.25; H, 4.21; N, 10.68; S, 16.47%.
3-Hydroxy-9-methylchromeno[4,3-b]pyrazolo[4,3-e]pyridin-5(1H)-one (9). A mixture of carbonitrile
1 (0.55 g, 3 mmol) and cyanoacetohydrazide (0.30 g, 3 mmol) in AcOH (10 mL) was heated under reflux
for 2 h. The solid obtained after cooling was filtered and crystallized from AcOH/H2O to give compound
9 as pale yellow crystals, mp >300 ºC, yield (0.52 g, 65%). IR (KBr, cm-1): 3196 (OH and NH), 2920
(CHaliph.), 1694 (C=Oα-pyrone), 1608 (C=N), 1588 (C=C). 1H NMR (DMSO-d6, δ): 2.38 (s, 3H, CH3), 7.23
(d, 1H, J = 7.5 Hz, H-7), 7.38 (d, 1H, J = 8.1 Hz, H-8), 8.12 (s, 1H, H-10), 8.85 (s, 1H, H-4pyridine), 11.59
(bs, 1H, NH exchangeable with D2O), 12.79 (bs, 1H, OH exchangeable with D2O). 13C NMR (DMSO-d6,
δ): 20.3, 104.6, 117.2, 125.9, 128.0, 128.7, 129.0, 129.8, 133.5, 135.0, 145.4, 154.0, 188.9, 200.9. Mass
spectrum (m/z, I%): 267 (100), 239 (18), 210 (10), 195 (3), 154 (6), 127 (9), 105 (5), 91 (4), 77 (13), 64
(8). Anal. Calcd for C14H9N3O3 (267.25): C, 62.92; H, 3.39; N, 15.72%. Found: C, 62.85; H, 3.28; N,
15.60%.
N'-Acetyl-2-amino-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carbohydrazide (10). A mixture
of carbonitrile 1 (0.55 g, 3 mmol) and N'-acetyl-2-cyanoacetohydrazide (0.43 g, 3 mmol) in absolute
EtOH (20 mL) containing piperidine (0.2 mL) was heated under reflux for 30 min. The yellow crystals
obtained during heating were filtered and crystallized from DMF/H2O to give compound 10 as white
crystals, mp >300 ºC, yield (0.69 g, 70%). IR (KBr, cm-1): 3226 (br, NH2, 2NH), 1652, 1625 (C= Oacetyl
and 2C=Oamide), 1610 (C=N), 1567 (C=C). 1H NMR (DMSO-d6, δ): 1.89 (s, 3H, CH3), 2.37 (s, 3H, CH3),
7.31 (d, 1H, J = 8.0 Hz, H-9), 7.47 (d, 1H, J = 8.4 Hz, H-8), 7.77 (s, 1H, H-6), 8.56 (s, 1H, H-4), 9.02 (bs,
1H, NH exchangeable with D2O), 9.49 (bs, 1H, NH exchangeable with D2O), 10.95 (bs, 1H, NH
exchangeable with D2O), 11.28 (bs, 1H, NH exchangeable with D2O). Mass spectrum (m/z, I%): 326 (2),
313 (2), 259 (14), 218 (6), 201 (100), 188 (14), 135 (40), 107 (10), 91 (6), 77 (13). Anal. Calcd for
C16H14N4O4 (326.31): C, 58.89; H, 4.32; N, 17.17%. Found: C, 58.64; H, 4.30; N, 17.00%.
2-Amino-5-cyano-N'-[(3,4-dimethoxyphenyl)methylidene]-8-methyl-6-oxo-6H-1-benzoxocine-3-

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HETEROCYCLES, Vol. 96, No. 4, 2018
carbohydrazide (12). A mixture of carbonitrile 1 (0.55 g, 3 mmol) and N`-[(3,4-dimethoxyphenyl)-
methylidene]-2-cyanoacetohydrazide (11) (0.62 g, 3 mmol) in absolute EtOH (20 mL) containing DBU
(0.1 mL) was heated under reflux for 45 min. The yellow crystals obtained during heating were filtered
and crystallized from DMF/EtOH to give compound 12 as yellow crystals, mp >300 ºC, yield (0.68 g,
52%). IR (KBr, cm-1): 3384 (br, NH2, NH), 2930, 2863 (CHaliph.), 2231 (C≡N), 1669 (C=Oamide and
1
C=Ooxocine), 1615 (C=N), 1590 (C=C). H NMR (DMSO-d6, δ): 2.25 (s, 3H, CH3), 3.82 (s, 3H, OCH3),
3.86 (s, 3H, OCH3), 7.18 (d, 1H, J = 8.7, Ar-H), 7.23 (d, 1H, J = 8.7, Ar-H), 7.43 (d, 1H, J = 8.4, Ar-H),
7.58 (d, 1H, J = 7.4, Ar-H), 7.69 (s, 1H, H-7), 8.59 (bs, 2H, NH2 exchangeable with D2O), 8.66 (s, 1H,
13
Ar-H), 8.77 (s, 1H, CH=N), 9.84 (bs, 1H, NH exchangeable with D2O). C NMR (DMSO-d6, δ): 21.4,
50.6 (C-5), 61.6, 62.2, 105.3, 106.2, 110.9, 114.7, 117.8, 119.8, 121.8, 129.9, 144.5, 146.4, 147.0, 147.6,
148.3, 149.0, 154.6, 165.1, 172.4, 175.4, 196.8. Anal. Calcd for C23H20N4O5 (432.43): C, 63.88; H, 4.66;
N, 12.96%. Found: C, 63.78; H, 4.50; N, 12.80%.
2-Amino-N'-[(3,4-dimethoxyphenyl)methylidene]-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-
carbohydrazide (13). A mixture of 2-amino-6-methylchromone-3-carboxaldehyde (8) (0.41 g, 2 mmol)
and N'-[(3,4-dimethoxyphenyl)methylidene]-2-cyanoacetohydrazide (11) (0.42 g, 2 mmol) in absolute
EtOH (20 mL) containing piperidine (0.2 mL) was heated under reflux for 30 min. The solid obtained
during heating was filtered and crystallized from DMF/H2O to give compound 13 as yellow crystals, mp
>300 ºC, yield (0.61 g, 71%). IR (KBr, cm-1): 3399, 3289, 3154 (NH2, NH), 2914, 2858 (CHaliph.), 1671
(C=Oamide and C=Oγ-pyrone) and 1608 (C=N), 1582 (C=C). 1H NMR (DMSO-d6, δ): 2.39 (s, 3H, CH3), 3.75
(s, 3H, OCH3), 4.23 (s, 3H, OCH3), 7.30-7.35 (m, 3H, Ar-H), 7.48-7.51 (m, 2H, Ar-H), 7.78 (s, 1H, H-6),
8.50 (s, 1H, CH=N), 8.61 (s, 1H, H-4pyridine), 9.32 (bs, 2H, NH2 exchangeable with D2O), 11.44 (bs, 1H,
NH exchangeable with D2O). Mass spectrum (m/z, I%): 432 (29), 416 (20), 401 (16), 385 (22), 370 (45),
341 (17), 328 (31), 313 (17), 286 (15), 253 (95), 225 (15), 201 (35), 185 (22), 175 (18), 151 (55), 135
(100), 105 (31), 91 (30), 77 (84), 65 (32). Anal. Calcd for C23H20N4O5 (432.43): C, 63.88; H, 4.66; N,
12.96%. Found: C, 63.50; H, 4.30; N, 12.70%.
2-Amino-3-{(2-hydroxybenzylidene)hydrazinylidene}methyl}-6-methylchromone (16). A mixture of
carbonitrile 1 (0.55 g, 3 mmol) and salicylaldehyde hydrazone (14) (0.41 g, 3 mmol) in absolute EtOH
(20 mL) was heated under reflux for 2 h. The solid obtained after cooling was filtered and crystallized
from AcOH/H2O to give compound 16 as white crystals, mp >300 ºC, yield (0.66 g, 69%). IR (KBr,
cm-1): 3222 (br, NH2 and NH), 3079 (CHarom.), 2914 (CHaliph.), 1651 (C=Oγ-pyrone), 1625 (C=N), 1566
1
(C=C). H NMR (DMSO-d6, δ): 2.39 (s, 3H, CH3), 6.94-6.97 (m, 3H, Ar-H), 7.33-7.41 (m, 2H, Ar-H),
7.66 (d, 1H, J = 8.4 Hz, H-7), 7.81 (s, 1H, H-5), 8.98 (s, 1H, CH=N), 9.02 (s, 1H, CH=N), 9.30 (bs, 1H,
NH exchangeable with D2O), 9.45 (bs, 1H, NH exchangeable with D2O), 11.08 (bs, 1H, NH
13
exchangeable with D2O). C NMR (DMSO-d6, δ): 20.8, 92.7 (C-3), 116.9, 118.6, 118.8, 120.0, 121.5,

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703
125.3, 131.2, 132.9, 133.6, 134.8, 135.0, 151.4, 158.5, 158.8, 161.4, 163.2. Mass spectrum (m/z, I%):
321 (36), 285 (7), 236 (6), 201 (100), 185 (5), 175 (6), 147 (9), 135 (41), 121 (20), 91 (20), 77 (29), 65
(23). Anal. Calcd for C18H15N3O3 (321.33): C, 67.28; H, 4.71; N, 13.08%. Found: C, 66.80; H, 4.55; N,
12.75%.
3-{[(2-Amino-6-methylchromon-3-yl)methylidene]hydrazinylidene}-1,3-dihydro-2H-indol-2-one
(17). A mixture of carbonitrile 1 (0.55 g, 3 mmol) and isatin hydrazone (15) (0.45 g, 3 mmol) in absolute
EtOH (20 mL) was heated under reflux for 2 h. The yellow crystals obtained during heating were filtered
and crystallized from DMF to give compound 17 as yellow crystals, mp >300 ºC, yield (0.70 g, 67%). IR
(KBr, cm-1): 3227 (br, NH2 and NH), 3070 (CHarom.), 1716 (C=Oisatine), 1652 (C=Oγ-pyrone), 1609 (C=N),
1566 (C=C). 1H NMR (DMSO, δ): 2.36 (s, 3H, CH3), 7.03 (d, 1H, J = 8.4 Hz, Ar-H), 7.21-7.30 (m, 4H,
Ar-H), 7.47 (t, 1H, J = 6.4 Hz, Ar-H), 7.70 (s, 1H, H-5), 8.85 (bs, 2H, NH2 exchangeable with D2O), 8.99
(s, 1H, CH=N), 10.42 (bs, 1H, NH exchangeable with D2O). Anal. Calcd for C19H14N4O3 (346.34): C,
65.89; H, 4.07; N, 16.18%. Found: C, 65.66; H, 4.04; N, 15.90%.
1-{[(2-Amino-6-methylchromon-3-yl)methylidene]amino}-4,6-dimethyl-2-oxo-1,2-dihydropyridine-
3-carbonitrile (20). A mixture of carbonitrile 1 (0.55 g, 3 mmol) and 1-amino-4,6-dimethyl-2-oxo-
1,2-dihydropyridine-3-carbonitrile (18) (0.49 g, 3 mmol) in absolute EtOH (20 mL) was heated under
reflux for 2 h. The yellow crystals obtained after cooling were filtered and crystallized from DMF/EtOH
to give compound 20 as yellow crystals, mp >300 ºC, yield (0.73 g, 70%). IR (KBr, cm-1): 3250, 3130
1
(NH2), 3011 (CHarom.), 2928 (CHaliph.), 2213 (C≡N), 1655 (C=Oγ-pyrone), 1614 (C=N), 1578 (C=C). H
NMR (DMSO, δ): 2.29 (s, 3H, CH3), 2.33 (s, 3H, CH3), 2.42 (s, 3H, CH3), 6.03 (s, 1H, H-4pyridine), 7.33 (d,
1H, J = 8.4 Hz, H-8), 7.53 (d, 1H, J = 8.4 Hz, H-7), 7.80 (s, 1H, H-5), 8.84 (s, 1H, CH=N), 9.03 (bs, 1H,
NH exchangeable with D2O), 9.12 (bs, 1H, NH exchangeable with D2O). 13C NMR (DMSO-d6, δ): 19.0,
19.6, 20.6, 92.7 (C-3), 108.2, 110.0, 113.2, 115.5, 117.1, 118.9, 121.8, 125.2, 128.4, 135.3, 144.6, 158.4,
162.2, 171.1, 188.4. Anal. Calcd for C19H16N4O3 (348.35): C, 65.51; H, 4.63; N, 16.08%. Found: C,
65.29; H, 4.41; N, 15.87%.
3-{[(2-Amino-6-methylchromon-3-yl)methylidene]amino}-2-phenylquinazolin-4(3H)-one (21).
A
mixture of carbonitrile 1 (0.55 g, 3 mmol) and 3-amino-2-phenylquinazolin-4(3H)-one (19) (0.71 g, 3
mmol) in absolute EtOH (20 mL) was heated under reflux for 2 h. The yellow crystals obtained during
heating were filtered and crystallized from MeOH to give compound 21 as yellow crystals, mp >300 ºC,
yield (0.74 g, 58%). IR (KBr, cm-1): 3293, 3219 (NH2), 1669 (C=Oquinazoline), 1652 (C=Oγ-pyrone), 1607
1
(C=N), 1559 (C=C). H NMR (DMSO-d6, δ): 2.39 (s, 3H, CH3), 7.12-7.27 (m, 2H, Ar-H), 7.34 (d, 1H,
Ar-H), 7.40-7.45 (m, 3H, Ar-H), 7.58-7.61 (m, 4H, Ar-H), 7.83 (d, 1H, J = 8.4 Hz, Ar-H), 7.89 (bs, 2H,
NH2 exchangeable with D2O), 8.06 (s, 1H, H-5), 8.97 (s, 1H, CH=N). 13C NMR (DMSO-d6, δ): 20.7, 91.3
(C-3), 105.4, 115.8, 116.5, 116.9, 117.0, 117.6, 118.3, 122.2, 123.1, 124.5, 125.6, 129.1, 129.2, 133.9,

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HETEROCYCLES, Vol. 96, No. 4, 2018
134.8, 136.5, 152.8, 153.2, 161.0, 162.4, 165.6, 166.0, 174.4. Anal. Calcd for C25H18N4O3 (422.44): C,
71.08; H, 4.29; N, 13.26%. Found: C, 70.70; H, 4.10; N, 13.00%.
2-Amino-9-methyl-5H-chromeno[4,3-d]pyrimidin-5-one (22). To a solution of carbonitrile 1 (0.55 g, 3
mmol) in absolute EtOH (15 mL), guanidine hydrochloride (0.29 g, 3 mmol) in aqueous potassium
hydroxide (5%, 15 mL) was added. The reaction mixture was heated under reflux for 2 h. After cooling,
the reaction mixture was poured onto crushed ice (~ 20 g) and neutralized with conc. HCl. The solid so
formed was filtered and crystallized from AcOH/H2O to give compound 22 as yellow crystals, mp >300
ºC, yield (0.49 g, 73%). IR (KBr, cm-1): 3381, 3329 (NH2), 2920 (CHaliph.), 1720 (C=Oα-pyrone), 1659
1
(C=N), 1610 (C=C). H NMR (DMSO-d6, δ): 2.39 (s, 3H, CH3), 7.26 (d, 1H, J = 8.4 Hz, H-7), 7.48 (d,
1H, J = 8.8 Hz, H-8), 7.90 (bs, 2H, NH2 exchangeable with D2O), 8.05 (s, 1H, H-10), 8.94 (s, 1H, H-4).
Mass spectrum (m/z, I%): 227 (100), 199 (25), 185 (10), 170 (6), 157 (8), 129 (7), 111 (6), 97 (9), 77 (7).
Anal. Calcd for C12H9N3O2 (227.22): C, 63.43; H, 3.99; N, 18.49%. Found: C, 63.20; H, 3.70; N, 18.40%.
(9-Methyl-5-oxo-5H-chromeno[4,3-d]pyrimidin-2-yl)cyanamide (23). To a solution of carbonitrile 1
(0.55 g, 3 mmol) in absolute EtOH (15 mL), cyanoguanidine (0.26 g, 3 mmol) in aqueous potassium
hydroxide (5%, 15 mL) was added. The reaction mixture was heated under reflux for 2 h. After cooling,
the reaction mixture was poured onto crushed ice and neutralized with conc. HCl. The solid so formed
was filtered and crystallized from AcOH/H2O to give compound 23 as yellow crystals, mp >300 ºC, yield
(0.52 g, 67%). IR (KBr, cm-1): 3307 (NH), 2926 (CHaliph.), 2201 (C≡N), 1695 (C=Oα-pyrone), 1652 (C=N),
1
1610 (C=C). H NMR (DMSO-d6, δ): 2.37 (s, 3H, CH3), 7.28 (d, 1H, J = 8.0 Hz, H-7), 7.50 (d, 1H, J =
8.0 Hz, H-8), 7.97 (s, 1H, H-10), 8.94 (s, 1H, H-4), 10.05 (bs, H, NH exchangeable with D2O). 13C NMR
(DMSO-d6, δ): 20.4, 106.5, 117.4, 121.7, 122.6, 128.2, 130.8, 131.8, 134.2, 135.4, 150.6, 157.3, 172.4.
Mass spectrum (m/z, I%): 252 (92), 227 (40), 224 (23), 211 (6), 199 (15), 182 (13), 171 (6), 157 (11),
134 (100), 117 (10), 106 (41), 91 (11), 77 (33), 63 (13). Anal. Calcd for C13H8N4O2 (252.23): C, 61.90; H,
3.20; N, 22.21%. Found: C, 61.80; H, 3.15; N, 22.01%.
9-Methyl-7-oxo-7,13-dihydrochromeno[2,3-b][1,5]benzodiazepine (24). A mixture of carbonitrile 1
(0.55 g, 3 mmol) and o-phenylenediamine (0.32 g, 3 mmol) in absolute EtOH (20 mL) was heated under
reflux for 30 min. The solid obtained during heating was filtered and crystallized from DMF/EtOH to
give compound 24 as yellow crystals, mp 256-257 ºC, yield (0.49 g, 59%). IR (KBr, cm-1): 3303 (NH),
3048 (CHarom.), 2915, 2880 (CHaliph.), 1642 (C=Oγ-pyrone), 1614 (C=N), 1575 (C=C). 1H NMR (DMSO-d6,
δ): 2.45 (s, 3H, CH3), 7.18-7.24 (m, 2H, Ar-H), 7.63-7.72 (m, 4H, Ar-H), 8.05 (s, 1H, H-8), 9.35 (s, 1H,
CH=N), 12.62 (bs, 1H, NH exchangeable with D2O). 13C NMR (DMSO-d6, δ): 20.7, 113.7, 117.0, 118.7,
121.1, 122.2, 125.2, 125.6, 130.5, 135.2, 137.6, 138.7, 151.6, 153.6, 159.7, 164.5, 165.8. Mass spectrum
(m/z, I%): 276 (100), 248 (5), 220 (15), 134 (4), 119 (17), 105 (8), 91 (15), 77 (11), 64 (10). Anal. Calcd
for C17H12N2O2 (276.29): C, 73.90; H, 4.38; N, 10.14%. Found: C, 73.73; H, 4.21; N, 10.11%.

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6-Amino-1-{[(2-amino-6-methylchromon-3-yl)methylidene]amino}-2-oxo-4-(4-methoxyphenyl)-1,2-
dihydropyridine-3,5-dicarbonitrile (26). A mixture of carbonitrile 1 (0.55 g, 3 mmol) and
1,6-diamino-4-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (25) (0.84 g, 3 mmol) in
absolute EtOH (20 mL) was heated under reflux for 4 h. The yellow crystals obtained after cooling were
filtered and crystallized from AcOH to give compound 26 as yellow crystals, mp 297-298 ºC, yield (0.88
g, 63%). IR (KBr, cm-1): 3458, 3396, 3305, 3150 (2NH2), 2218 (2C≡N), 1671 (C=Oγ-pyrone and
C=Opyridone), 1612 (C=N), 1577 (C=C). 1H NMR (DMSO, δ): 2.38 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 7.07
(d, 2H, J = 8.8 Hz, Ar-H), 7.28 (d, 1H, J = 8.4 Hz, H-8), 7.43 (d, 2H, J = 8.8 Hz, Ar-H), 7.52 (d, 1H, J =
8.4 Hz, H-7), 7.79 (s, 1H, H-5), 8.39 (bs, 2H, NH2 exchangeable with D2O), 9.49 (bs, 1H, NH
exchangeable with D2O), 9.55 (bs, 1H, NH exchangeable with D2O). 10.05 (s, 1H, CH=N). Mass
spectrum (m/z, I%): 466 (2), 451 (3), 437 (3), 423 (4), 409 (3), 367 (6), 313 (12), 299 (6), 285 (6), 236
(7), 203 (21), 187 (12), 160 (34), 134 (22), 91 (9), 77 (29), 64 (9). Anal. Calcd for C25H18N6O4 (466.45):
C, 64.37; H, 3.89; N, 18.02%. Found: C, 64.20; H, 3.65; N, 18.04%.
2-Amino-3-(1,3-benzothiazol-2-yl)-6-methylchromone (27). A mixture of carbonitrile 1 (0.55 g, 3
mmol) and o-aminothiophenol (0.38 g, 3 mmol) in absolute EtOH (20 mL) was heated under reflux for 30
min. The solid obtained during heating was filtered and crystallized from DMF/MeOH to give compound
27 as yellow crystals, mp 291-292 ºC, yield (0.49 g, 53%). IR (KBr, cm-1): 3447, 3290 (NH2), 3058
(CHarom.), 2917 (CHaliph.), 1654 (C=Oγ-pyrone), 1613 (C=N), 1557 (C=C). 1H NMR (DMSO, δ): 2.37 (s, 3H,
CH3), 5.44 (bs, 2H, NH2 exchangeable with D2O), 6.44 (t, 1H, J = 7.2 Hz, Ar-H), 6.74 (d, 1H, J = 7.8 Hz,
Ar-H), 7.01-7.12 (m, 2H, Ar-H), 7.26 (d, 1H, J = 8.4 Hz, Ar-H), 7.40 (d, 1H, J = 8.4 Hz, Ar-H), 7.77 (s,
13
1H, H-5). C NMR (DMSO-d6, δ): 20.8, 93.5 (C-3), 111.7, 113.6, 116.8, 118.5, 121.9, 125.0, 129.4,
129.6, 133.9, 134.5, 136.0, 145.8, 151.1, 162.0, 173.1. Mass spectrum (m/z, I%): 308 (M+, not recorded),
175 (91), 135 (100), 106 (28), 91 (10), 77 (28), 63 (10). Anal. Calcd for C17H12N2O2S (308.35): C, 66.22;
H, 3.92; N, 9.08%. Found: C, 66.05; H, 3.78; N, 8.90%.
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