A new pathway to 3-hetaryl-2-oxo-2H-chromenes: On the proposed mechanisms for the reaction of 3-carbamoyl-2-iminochromenes with dinucleophiles

Article abstract of DOI:10.3390/51001146

The present account summarizes the author's studies to elucidate the mechanisms of the recently reported rearrangements resulting from inter- and/or intramolecular reactions of 2-imino-2H-chromene-3-carboxamides with different dinucleophiles.

Full text of DOI:10.3390/51001146

Molecules 2000, 5, 1146–1165
molecules
ISSN 1420-3049
http://www.mdpi.org
A New Pathway to 3-Hetaryl-2-oxo-2H-chromenes: On the
Proposed Mechanisms for the Reaction of 3-Carbamoyl-2-
iminochromenes with Dinucleophiles
Sergiy M. Kovalenko,* Igor E. Bylov, Konstantyn M. Sytnik, Valentyn P. Chernykh and
Yaroslav V. Bilokin
Department of Organic Chemistry, Ukrainian National Academy of Pharmacy, Kharkiv 61002,
Ukraine.
* Author to whom correspondence should be addressed; E-mail: kovalenko_sergey@ukrfa.kharkov.ua
Received: 30 July 2000 / Accepted: 19 September 2000 / Published: 31 October 2000
Abstract: The present account summarizes the author's studies to elucidate the mechanisms
of the recently reported rearrangements resulting from inter- and/or intramolecular reactions
of 2-imino-2H-chromene-3-carboxamides with different dinucleophiles.
Keywords: rearrangements, mechanisms, iminochromenes, nucleophiles.
Introduction
The coumarin (2H-chromen-2-one) moiety is often found in natural products [1]. In view of the
ubiquity of this fragment in a variety of biologically active compounds, the synthesis of various 2H-
chromen-2-one analogs is important in gauging their potential as a source of chemotherapeutics [2]. As
part of our investigations on the reactivity of 3-carbamoyl-2-imino-2H-chromenes [3], we recently
introduced a new method for synthesis of 3-hetaryl-2-oxo-2H-chromenes [4]. This method was based
on the rearrangements of 2-imino-2H-chromene-3-carboxamides into 3-hetaryl-2-oxo-2H-chromenes
under the action of dinucleophiles. In this account, results of our studies on clarification of the
mechanism of the above-mentioned rearrangements are summarized and exemplified by utilizing
anthranilic acid, its derivatives, and arylhydrazides as N-nucleophiles. In order to elucidate the
© 2000 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.

Molecules 2000, 5
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mechanisms of the applied rearrangements, a model system approach based on isolation of stable
reaction intermediates or their structural analogs was used.
Results and Discussion
Several methods for synthesis of quinazolinylcoumarin derivatives of type 7 have been reported.
For example, compounds of type 7 have been prepared by aminolysis of 4-oxo-2-(2-oxo-2H-chromen-
3-yl)-4H-3,1-benzoxazines with aqueous ammonia [5], ammonium acetate or formamide [6]. Various
O
O
O
NH
N
R
2
CO H
2
NH
2
NH
2
2
PhMe
reflux
NH
HN
O
NH
O
NH
OH
2
1a,b
H N
2
HO
4
HO
O
O
2
3
O
O
HO
H N
2
O
HO
N
O
NH
2
HN
O
R
N
N
– NH
– H O
2
NH
3
OH
2
O
O
O
5
6
7a,b
EtOH/HCl/H O
2
A
reflux
O
O
HN
N
R
R
piperidine/EtOH
rt
NH
O
CN
N
OH
9a,b
O
10a,b
NH
8
a: R = H
b: R = OMe
B
Scheme 1. Proposed mechanism for the transformations of 2-imino-2H-chromenes 1 into 3-
(quinazolin-2-yl)-2H-chromen-2-ones 7 by the action of anthranilic acid (2) under non-acidic
conditions

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7-diethylamino-3-(4-oxo-3H-quinazolin-2-yl)-2H-chromen-2-one dyes have been synthesized [7] by
the reactions of: (i) ethyl 7-diethylamino-2-oxo-2H-chromene-3-carboxylate with anthranilamides; (ii)
cyclization of 4-diethylamino-2-hydroxybenzaldehyde with 2-(cyanomethyl)quinazolin-4(3H)-ones;
(iii) 7-amino-2-oxo-2H-chromene-3-carboxamides with isatoic anhydride or of 4-diethylamino-2-
hydroxybenzaldehyde with acetanilides and subsequent cyclization of the product formed with
urethane and phosphorus pentoxide.
Kametani et al. reported [8] the synthesis of 3-substituted quinazolin-4(3H)-ones starting from a
sulfinamide anhydride, prepared from anthranilic acid (2) and thionyl chloride, and primary and
secondary amides. Our attempts to synthesize quinazolinylcoumarin 7a by simple heating of 2-oxo-
2H-chromene-3-carboxamide (25 [9], cf. Scheme 9) and anthranilic acid (2) without any additional
reagents failed. However, it was found that refluxing of compounds 1a,b and 2 in degassed toluene
afforded compounds 7a,b in moderate yields as the sole products (Scheme 1A). In the course of the
reaction, a strong liberation of ammonia was detected. In order to fully characterize compounds 7a,b,
they were also synthesized by an alternative method via Knoevenagel condensation of 2-(cyano-
methyl)quinazolin-4(3H)-one 8 [10] with salicylaldehydes 9a,b in ethanol and using piperidine as a
catalyst and subsequent acid hydrolysis of the formed imines 10 (Scheme 1B).
O
NH
NH
2
2
H
N
BuOH
reflux
N
O
NH
1a
O
O
O
H N NH
2
12
O
11
11: PhCONHNH
2
A
B
DMF/EtOH, 80 °C
S
NH
SMe
O
1. MeI/DMF, 0 °C
NH
2
2. Et N
3
O
O
O
14
13
Scheme 2. Synthesis of amide-hydrazone 12 under non-acidic conditions
A mechanism was postulated (Scheme 1A) for the formation of 2H-chromen-2-one and quinazolin-
4(3H)-one moieties via a rearrangement of 2-imino-2H-chromene-3-carboxamides 1 by the action of
anthranilic acid (2) as N-nucleophile [11] under non-acidic conditions. It may involve several
consecutive or concerted steps: (i) intermolecular nucleophilic attack of NH2 on C-2 of the

Molecules 2000, 5
1149
iminolactone ring (1 + 2 ! 3), (ii) iminolactone ring opening (3 ! 4), (iii) thermal E/Z isomerization
[12] of intermediate 4 (4 ! 5), iv) cyclization of intermediate 5 to amidine 6; and (v) subsequent
formation of 2H-chromen-2-one and pyrimidine fragments (6 " 7).
To prove the proposed mechanism, we directed our studies to isolation of intermediate amidines of
type 6. With this objective in view various heterocyclic systems, not prone to spontaneous cyclization,
were designed and synthesized. As an example, refluxing of iminocarboxamide 1a and benzohydrazide
(11) (Scheme 2A) in butan-1-ol afforded amide-hydrazone 12, which was also synthesized
independently (Scheme 2B) from chromenethiocarboxamide 13 [13] through the intermediacy of
carboximidothioate 14. Furthermore, amidines 16a,b were synthesized (Scheme 3) in moderate yields
employing the same rearrangement conditions.
O
O
CN
H N
2
R
NH
2
R
BuOH
reflux
N N
O
NH
O
O
1a,b
16a,b
H N
2
N
O
a: R = H
b: R = OMe
CN
15
Scheme 3. Synthesis of amidines 16 under non-acidic conditions
O
O
2
NHR
NH
2
NHR
1
R
B:
1
R
reflux
O
NH
B
O
1
B
NH
2
CN
O
– R NH , – B:
2
1
R
1
O
R
O
2
NHR
O
35
1
R = H, 7-NEt , benzo[f]
B: = basic aprotic solvents
(DMF, DMSO, pyridine, quinoline, and 1-formylpiperidine)
2
2
R = H, Me, Ph
Scheme 4. Proposed mechanism for the transformations of substituted 2-imino-2H-chromenes 1 in
basic aprotic solvents

Molecules 2000, 5
1150
It was also shown that 2-imino-2H-chromene-3-carboxamides of type 1 undergo transformation into
2-oxo-2H-chromene-3-carbonitriles 35 in basic aprotic solvents: DMF, DMSO, pyridine, quinoline
and N-formylpiperidine (Scheme 4) [14]. In contrast, the corresponding 2-oxo-2H-chromene-3-
carboxamides 1 did not undergo dehydration to afford 2-oxo-2H-chromene-3-carbonitriles even after
prolonged boiling for 3–4 h in the above-mentioned solvents. The reaction mechanism of this
transformation should be analogous to that presented in Scheme 1A. In this case, solvent acts as a
nucleophile and opens the iminolactone ring (1 + base) and then is eliminated with the formation of
nitrile group (1 " 35, Scheme 4).
In connection with this, a study on isomerization of chromen-2-imines in DMSO-d6 has to be
mentioned. O'Callaghan et al. revealed [15] that when unsubstituted 2-imino-2H-chromene-3-
carboxamide (1a) was dissolved in DMSO-d6, the NMR spectra showed that a mixture of both 2-
imino-2H-chromene-3-carboxamide and the isomeric 2-cyano-3-(2-hydroxyphenyl)-prop-2-enamide
(Figure 1) was present. Other chromen-2-imines behaved similarly, but the degree of isomerization
varied considerably, depending on the nature and position of the substituents.
OH
OH
CN
H
N
H
O
H
O
NC
N
H
Figure 1.
As shown in Scheme 5 (paths A and B), two distinct pathways leading to different products were
envisioned to be involved in the acid-catalyzed rearrangements of 2-imino-2H-chromene-3-
carboxamides 1. Thus, depending on reaction conditions, two types of products might be formed: (i)
under non-aqueous acidic conditions compounds, comprising 2H-chromen-2-one and quinazoline or
benzoxazine moieties 23 (1 " 19 " 23, Scheme 5, path A) or (ii) in aqueous acidic media, where H2O
acts as O-nucleophile, N-substituted 2-oxo-2H-chromene-3-carboxamides 28 (1 " 19 " 28, Scheme
5, path B). In this case, a competing reaction could be a simple hydrolysis (19 " 25), although a full
understanding of the factors controlling this competition has not been attained. General intermediates
for transformations presented in Scheme 5 are 2-(arylimino)-2H-chromenes of type 19. To verify our
assumption of two possible mechanisms of reaction between 2-imino-2H-chromene-3-carboxamides 1
and anthranilates in acidic media, we directed our studies to isolation of intermediate 2-(arylimino)-
2H-chromenes 19 and, starting from them, to the synthesis of 3-substituted 2H-chromen-2-ones of type
23 and 28.
A method for synthesis of 2-(arylimino)chromenes 19 was recently introduced in our laboratory and
it was shown that a variety of 2-(aryl- or alkylimino)-substituted 2H-chromen-2-ones of type 19 could
be prepared [3]. This method is based on aminolysis of cyclic imido esters and is similar to the

Molecules 2000, 5
1151
reaction of simple imidates with amines [16]. This type of reactions should also be similar to the acid
hydrolysis of 2-imino-2H-chromenes to 2H-chromen-2-ones which proceeds through the formation of
the corresponding benzopyrylium salts [17,18].
O
O
O
± H+
± NH3
± Ar–NH2
± H+
NH
NH
NH
2
2
2
NH
2
O
NH
O
NH
O
2
NH
1
17
18
X
X = NH ; OH; OMe
2
O
O
N
O
O
Path A:
NH
N
2
NH
± H+
NH
intramolecular
± H+
2
2
O
O
O
NH
Y
OH
21
X
X
20
O
O
Path B:
19
O
intermolecular
± H2O
± H+
O
Y
O
O
NH
2
O
N
NH
2
NH
X
NH
2
OH
CONH
O
2
– R–NH2
O
OH
26
O
O
OH
22
HN
25
X
– NH3
24
O
O
O
Y
X
O
O
O
N
H
if X = NH , Y = NH
2
N
N
H
if X = OH, Y = O
O
– NH3
NH
O
O
2
O
X
O
OH
27
28
23
Scheme 5. Proposed mechanism for the transformations of 2-imino-2H-chromenes 1 by the action of
nucleophiles under acidic conditions
The principal feature of the method for synthesis of 2-(arylimino)chromenes 19 is the use of either
amine hydrochloride [3,19,20] or benzopyrylium salts of type 17 [3]. Finally, we found a different
methodology [4] based on using glacial acetic acid for in situ formation of the corresponding salts,
their reaction and subsequent removal of the ammonia released.

Molecules 2000, 5
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O
O
N
O
N
NH
2
HN
O
NH
2
O
NH
AcOH
rt
AcOH
reflux
O
NH
2
1a
H N
2
O
O
H N
2
30
7a
O
29
Scheme 6. Synthesis and rearrangement of 2-(arylimino)chromene 30 into 3-(quinazolin-2-yl)-2H-
chromen-2-one (7a) under acidic anhydrous conditions
As shown in Schemes 6–10, syntheses of the desired 2-(arylimino)chromenes 30, 31, 39 and 41
were finally performed by adding equivalent amounts of the corresponding 2-iminochromene
derivatives 1 to a solution of anthranilates 29, 2, 38 or benzohydrazide (11) in glacial acetic acid. After
stirring the reaction mixture at room temperature, products were precipitated and subsequently
isolated, purified, characterized and used for further transformations.
O
O
O
NH
2
O
O
NH
2
O
NH
AcOH
rt
Ac O
2
N
O
N
OH
1a
H N
2
reflux
O
O
HO
31
32
O
2
EtOH/HCl/H O
2
A
B
reflux
O
O
O
piperidine/EtOH
rt
O
N
O
CN
N
OH
O
34
NH
33
9a
Scheme 7. Synthesis and rearrangement of 2-(arylimino)chromene 31 into 2-(2-oxo-2H-chromen-3-
yl)-4H-3,1-benzoxazin-4-one (32) under acidic anhydrous conditions
It was found that in acidic anhydrous media (glacial acetic acid or acetic anhydride), 2-(N-
substituted imino)chromenes 30 and 31 reacted intramolecularly (cf. Scheme 5, path A) to produce
expected derivatives 7a (Scheme 6) and 32 (Scheme 7A) in good yields.

Molecules 2000, 5
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O
N
AcOH, rt
NH
2
R = H
O
CO H
2
O
O
R
31
HO
H N
NH
2
AcOH/H O
2
O
NH
2
reflux
O
1a,b
2
AcOH/H O
2
R
N
H
reflux
CO H
2
O
36a,b
O
A
R
O
O
O
piperidine/EtOH
rt
N
H
OEt
OH
a: R = H
b: R = OMe
CO H
2
37
9a,b
B
Scheme 8. Synthesis of N-aryl-2-oxo-2H-chromene-3-carboxamides 36 in aqueous acidic media
The reaction between imines 1a,b and 2 in aqueous acidic media (80% acetic acid) (Scheme 8A)
proceeded differently. Refluxing in this solvent for 2 h gave N-(2-carboxyphenyl)-2-oxo-2H-
chromene-3-carboxamides 36a,b. A mechanism that accounts for the products is detailed in Scheme 5,
path B. To prove that mechanism, a reaction between 1a and 2 (Scheme 8A) was initially performed in
acetic acid at room temperature. It took place without iminolactone ring opening and furnished
expected intermediate 31, which was converted into compound 36a by further boiling in aqueous
acetic acid. For unambiguous structure elucidation, 2-(2-oxo-2H-chromen-3-yl)-4H-3,1-benzoxazin-4-
one 32 [21] and N-aryl-2-oxo-2H-chromene-3-carboxamides 36a,b were also prepared independently
from 2-(cyanomethyl)-4H-3,1-benzoxazin-4-one 33 [22] or ethyl 2'-carboxymalonanilate 37 [23] and
salicylaldehydes 9 as depicted in Schemes 7B and 8B.
Taking into consideration the results observed for synthesis of N-aryl-2-oxo-2H-chromene-3-
carboxamides 36 (Scheme 8A), we examined the possibility of rearrangement of 2-(arylimino)-2H-
chromene-3-carboxamide 39 into N-aryl-2-oxo-2H-chromene-3-carboxamide 40 by the action of water
as O-nucleophile (Scheme 9). However, compound 40 was not detected presumably due to simple
hydrolysis (cf. Scheme 5, path B), which took place to furnish the known 2-oxo-2H-chromene-3-
carboxamide 25 [9].

Molecules 2000, 5
1154
O
O
O
O
O
N
H
O
N
CO Me
2
NH
O
2
NH
2
AcOH
rt
40
O
NH
AcOH/H O
2
O
1a
H O
CO Me
H N
2
reflux
2
2
MeO
NH
2
39
O
O
38
25
Scheme 9. Attempted synthesis of N-aryl-2-oxo-2H-chromene-3-carboxamide 40 using H2O as O-
nucleophile
As a further development of the methodology outlined in Scheme 5, path A, a new approach to 2-
oxo-3-(5-aryl-1,3,4-oxadiazol-2-yl)-2H-chromenes of type 45 was elaborated [4e].
O
O
O
NH
2
AcOH
rt
PhNO
reflux
2
R
NH
2
NH
2
R
R
O
NH
O
O
N
O
HO
N
N
1a,c
H
NH
Ph
N
Ph
H N
2
Ph
O
11
41a,b
42a,b
N
Ph
N
O
N
N
O
NH
N
2
Ph
O
O
R
R
R
N
– NH
NH
3
O
2
O
O
OH
OH
43
Ph
45a,b
44
1a, 41–45a: R = H
R = H
1c, 41–45b: R = 6-n-C H
6
13
AcOH/H SO
2
4
7-OH
reflux
A
NH
2
H
N
N
O
O
O
B
12
Scheme 10. Synthesis and rearrangement of 2-(N-aroylhydrazono)-2H-chromene-3-carboxamides 41
into 1,3,4-oxadiazolylchromenes 45

Molecules 2000, 5
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As exemplified in Scheme 10 (path A), the procedure was based on the rearrangement of 2-(N-
aroylhydrazono)-2H-chromene-3-carboxamides 41, which are readily obtained by the reaction of 2-
imino-2H-chromene-3-carboxamides 1 with benzohydrazide (1 1 ) in an acidic medium.
Oxadiazolylchromene 45a was also synthesized separately from amide-hydrazone 12 (cf. Scheme 2)
by refluxing it in AcOH/H2SO4 mixture (Scheme 10, pat B). Furthermore, as part of our program on
structure-activity relationship studies of different heterocycles as potential tyrosine kinase inhibitors
[24], we were especially interested in a short and selective entry into heterocyclic compounds
comprising 2-imino- or 2-oxo-2H-chromene and tetrahydrobenzo[b]thiophene moieties. In our
synthetic approach to heterocycles of this type [4f,g] we also applied the approach summarized in
Scheme 5, path A.
Conclusion
The results obtained in the study of the rearrangements of 2-imino-2H-chromene-3-carboxamides
with different N-nucleophiles clearly indicate that the reactions studied follow the mechanisms
described in Schemes 1 and 5. Finally, this work opened a new avenue for the synthesis of a variety of
new 3-hetaryl substituted 2-oxo-2H-chromene derivatives.
Experimental
General
Melting points (°C) were measured on a Büchi melting point apparatus and are uncorrected. Thin
layer chromatography (TLC) was performed on aluminum sheets precoated with silica gel (Merck,
Kieselgel 60 F-254). 1H-NMR spectra were recorded on Bruker WP-100 SY, Bruker DPX-250, Bruker
AMX-400 or Varian WXR-400 spectrometers in DMSO-d6 or DMSO-d6–CDCl3 using TMS as an
internal standard (chemical shifts in ppm). Mass spectra (MS) were obtained with Finnigan MAT-
4615B spectrometer at an ionization potential of 70 eV. Combustion analyses of all compounds
synthesized gave satisfactory microanalytical data. Infrared spectra (IR) were recorded in KBr pellets
on Nicolet Protege 460 FT-IR or an IBM 486 computer-controlled Specord M-80 spectrometers.
2-Imino-2H-chromene derivatives 1a–c were prepared (1a (R = H; refs. [9,25]); 1b (R = 6-OCH3;
ref. [26]); 1c (R = 6-OH, 7-n-C6H13; ref. [4b]) by condensing cyanoacetamide with salicylaldehydes
9a–c in ethanol at room temperature using piperidine as a catalyst to form the expected imino
compounds 1a–c.
(4-Oxo-3,4-dihydroquinazolin-2-yl)acetonitrile (8) [10], 2-oxo-2H-chromene-3-thiocarboxamide
(13) [13], 1-amino-4,6-dimethyl-2(1H)-oxopyridine-3-carbonitrile (15) [27], (4-oxo-4H-3,1-
benzoxazin-2-yl)acetonitrile (33) [22], ethyl 2'-carboxymalonanilate 37 [23] and salicylaldehyde 9c
[28] were prepared by known literature procedures.

Molecules 2000, 5
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Solvents were purified by conventional methods [29]. Starting materials, anthranilic acid (2),
salicylaldehydes (9a,b), benzohydrazide (11), anthranilamide (29) and methyl anthranilate (38) were
purchased from Aldrich®.
2-(2-Oxo-2H-chromen-3-yl)quinazolin-4(3H)-one (7a):
Method A: A mixture of 1a (282 mg, 1.5 mmol) and anthranilic acid 2 (370 mg, 2.7 mmol) in dry and
degassed toluene (10 mL) was refluxed for 5-6 h (TLC monitoring) through a column equipped with a
Dean-Stark trap containing a thimble filled with 4Å molecular sieves which had been activated at 325
°C for 24 h. In the course of the reaction, ammonia was released. The mixture was cooled and a yellow
precipitate was filtered off and recrystallized from DMF/BuOH to afford 205 mg (47%) of 7a: M.p.
275-277 °C (lit. [5] m.p. 243 °C; lit. [6] m.p. 245 °C). 1H-NMR (400 MHz, DMSO-d6): 7.49 (dddd,
1H, J = 8.3, 7.8, 0.6, 0.4 Hz, ArH); 7.58 (m, 2H, ArH); 7.79 (m, 2H, ArH); 7.90 (m, 1H, ArH); 8.03
(ddd, 1H, J = 7.7, 1.6, 0.4 Hz, ArH); 8.18 (m, 1H, ArH); 8.97 (s, 1H, H-4); 12.07 (br s, 1H, NH). IR
(KBr), cm-1: 3254 (NH), 1706 (C=O, lactone), 1690 (C=O, amide), 1606, 1579, 1553, 1465. MS (EI,
70 eV) m/z (rel.%): 290 (M+·, 83), 262 (17), 145 (8), 119 (100), 92 (19), 76 (5), 53 (10). Anal. Calcd
for C17H10N2O3 (290.28): C, 70.34; H, 3.47; N, 9.65. Found: C, 70.29; H, 3.61; N, 9.79.
Method B: To a well stirred solution of quinazoline-2-acetonitrile 8 [10] (185 mg, 1 mmol) in propan-
2-ol (5 mL) was added the equivalent amount of salicylaldehyde 9a (0.1 mL) and a few drops of
piperidine as a catalyst. The reaction mixture was stirred at room temperature for 2 h. The precipitated
product was filtered off, washed with propan-2-ol and recrystallized from butan-1-ol to afford 214 mg
1
(74%) of 2-(2-imino-2H-chromen-3-yl)quinazolin-4(3H)-one (10a): M.p. 225-228 °C. H-NMR (100
MHz, DMSO-d6): 7.22-7.28 (m, 2H, ArH); 7.46 (dd, 1H, J = 8.3, 7.8 Hz, ArH); 7.52-7.73 (m, 4H,
ArH); 8.14 (d, 1H, J = 7.8 Hz, ArH); 8.96 (s, 1H, H-4); 8.98 (s, 1H, C=NH); 14.04 (br s, 1H, NH). IR
(KBr), cm-1: 3435 (NH), 3319 (NH), 3060, 1689 (C=O, amide), 1678 (C=N), 1655, 1599. MS (EI, 70
eV) m/z (rel.%): 289 (M+·, 76), 272 (100), 171 (10), 146 (30), 119 (62), 92 (19), 77 (6), 63 (9). A
solution of the corresponding 10a (189 mg, 0.65 mmol) in 10 mL of a mixture of ethanol/water/~32%
hydrochloric acid (30:1:1, v/v/v) was refluxed with vigorous stirring for 1 h. After cooling to room
temperature, the precipitated product was filtered off and recrystallized from DMF/BuOH to afford
169 mg (89%) of the title compound 7a.
Method C: A solution of 30 (309 mg, 1.0 mmol) in glacial (99.8%) acetic acid (5 mL) was refluxed for
30 min. The mixture was cooled, the yellow precipitate was filtered off, washed with water and
recrystallized from DMF/BuOH to afford 201 mg (70%) of 7a. According to 1H-NMR and IR spectral
data as well as the melting points, the products obtained by Methods A, B and C are identical.
2-(6-Methoxy-2-oxo-2H-chromen-3-yl)quinazolin-4(3H)-one (7b):

Molecules 2000, 5
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Method A: The reaction of 1b (327 mg, 1.5 mmol) was performed using the reaction conditions
described for preparation of 7a to give 187 mg (39%) of 7b: 1H-NMR (100 MHz, DMSO-d6): 3.87
(s, 3H, OCH3); 7.26-8.06 (m, 6H, ArH); 8.18 (d, 1H, J = 8.0 Hz, ArH); 8.99 (s, 1H, H-4); 12.00 (br s,
1H, NH). IR (KBr), cm-1: 3242 (NH), 3065, 3010, 2971, 1706 (C=O, lactone), 1683 (C=O, amide),
1566, 1491. MS (EI, 70 eV) m/z (rel.%): 320 (M+·, 100), 292 (23), 277 (28), 249 (6), 221 (8), 146 (13),
119 (95), 90 (21), 76 (17). Anal. Calcd for C18H12N2O4 (320.31): C, 67.50; H, 3.77; N, 8.74. Found: C,
67.71; H, 3.81; N, 8.69.
Method B: The synthesis of 10b was performed starting from 8 (185 mg, 1 mmol) and 9b (0.15 mL)
1
using the reaction conditions described for preparation of 10a to give 227 mg (71%) of 10b: H-NMR
(100 MHz, DMSO-d6): 3.79 (s, 3H, OCH3); 7.17 (s, 1H, ArH); 7.41-7.93 (m, 5H, ArH); 8.12 (d, 1H,
J = 7.7 Hz, ArH); 8.85 (s, 1H, H-4); C=NH and NH exchanged deuterium with the solvent. MS (EI, 70
eV) m/z (rel.%): 319 (M+·, 42), 302 (100), 276 (8), 259 (6), 222 (7), 160 (8), 146 (8), 119 (14).
Subsequent acid hydrolysis of 10b (160 mg, 0.5 mmol) employing the reaction conditions described
for hydrolysis of 10a afforded 130 mg (81%) of 7b. According to 1H-NMR, IR spectral data, and the
melting points, the compounds obtained by Methods A and B are identical.
N2-Benzoyl-2-oxo-2H-chromene-3-carbohydrazonamide (12):
Method A: A mixture of 1a (188 mg, 1 mmol) and benzohydrazide (11) (136 mg, 1 mmol) in butan-1-
ol (5 mL) was refluxed for 15–30 min (TLC monitoring) while ammonia was released. Then the
mixture was cooled, the precipitate was filtered off and washed with hot ethanol to afford 267 mg
(87%) of 12: M.p. 187-189 °C. 1H-NMR (100 MHz, DMSO-d6): 6.87 (br s, 2H, NH2); 7.40-7.90 (m,
9H, ArH); 8.57 (s, 1H, H-4); 10.09 (br s, 1H, CONH). IR (KBr), cm-1: 3418, 3181 (NH), 1704 (C=O,
lactone), 1682 (C=O, amide), 1658 (C=N). Anal. Calcd for C17H13N3O3 (307.30): C, 66.44; H, 4.26; N,
13.67. Found: C, 66.09; H, 4.51; N, 13.89.
Method B: To a cold (0 °C) solution of 2-oxo-2H-chromene-3-carbothioamide 13 [13] (2.05 g, 10
mmol) in DMF (25 mL) dry acetone (15 mL) followed by iodomethane (2 mL, 32 mmol) were added.
The mixture was kept for 24 h at a dark place. The hydroiodide precipitated was filtered off and
washed with ether. Hydroiodide (10 mmol) was suspended in 1,4-dioxane (50 mL) and triethylamine
(1.5 mL, 10 mmol) was added. After stirring for 1 h at room temperature, the solvent was removed
under reduced pressure and the residue was extracted with CHCl3 (2 x 10 mL). The extract was washed
with ice water, dried over Na2SO4 and the solvent was removed in vacuo to afford 899 mg (41%) of S-
1
methyl 2-oxo-2H-chromene-3-carboximidothioate (14) [30]: H-NMR (250 MHz, DMSO-d6): 2.47
(s, 3H, SCH3); 7.11-7.83 (m, 4H, ArH); 8.33 (s, 1H, H-4); 9.89 (s, 1H, NH). IR (KBr), cm-1: 3247
(NH), 1729 (C=O, lactone), 1612 (C=N), 1593. The crude 14 was used without any purification in the

Molecules 2000, 5
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following stage. The imidothioester 14 (440 mg, 2 mmol) and benzohydrazide (11) (275 mg, 2 mmol)
were dissolved in DMF/EtOH (3/1 mixture, 10 mL). The mixture was heated for 4 h at 80 °C until
evolving methanethiol was detected. The solvents were removed under reduced pressure and the
residue was washed with hot ethanol to afford 178 mg (29%) of 12. According to 1H-NMR, IR spectral
data as well as the melting points, the compounds obtained by Methods A and B are identical.
N-(3-Cyano-4,6-dimethyl-2(1H)-oxopyridin-1-yl)-2-oxo-2H-chromenes (16):
Amidines 16a,b were prepared from carbamoyliminochromenes 1a,b and 1-aminopyridone 15 [27]
using the reaction conditions described in Method A for the synthesis of 12.
1-[1-amino-1-(2-oxo-2H-chromen-3-yl)methylideneamino]-4,6-dimethyl-2(1H)-oxopyridine-3-
carbonitrile (16a):
1
Yield: 31%. M.p. 291-293 °C (dec.). H-NMR (400 MHz, DMSO-d6–CDCl3): 2.29 (s, 3H, CH3);
2.36 (s, 3H, CH3); 6.38 (s, 1H, CH-pyridone); 7.46 (br s, 2H, NH2); 7.48 (ddd, 1H, J = 7.7, 7.6, 1.0 Hz,
H-6); 7.55 (dd, 1H, J = 8.4, 1.0 Hz, H-8); 7.78 (ddd, 1H, J = 8.4, 7.6, 1.4 Hz, H-7); 8.00 (dd, J = 7.7,
1.4 Hz, H-5); 8.74 (s, 1H, H-4). Anal. Calcd for C18H14N4O3 (334.33): C, 64.66; H, 4.22; N, 16.76.
Found: C, 64.97; H, 4.34; N, 17.02.
1-[1-amino-1-(6-methoxy-2-oxo-2H-chromen-3-yl)methylideneamino]-4,6-dimethyl-2(1H)-
oxopyridine-3-carbonitrile (16b):
Yield: 27%. M.p. 312-314 °C. 1H-NMR (400 MHz, DMSO-d6): 2.28 (s, 3H, CH3); 2.37 (s, 3H, CH3);
3.85 (s, 3H, OCH3); 6.21 (s, 1H, CH-pyridone); 7.27 (dd, 1H, J = 9.1, 2.9 Hz, H-7); 7.34 (d, 1H, J =
2.9 Hz, H-5); 7.36 (d, 1H, J = 9.1 Hz, H-8); 7.46 (br s, 2H, NH2); 8.89 (s, 1H, H-4). Anal. Calcd for
C19H16N4O4 (364.35): C, 62.63; H, 4.43; N, 15.38. Found: C, 62.49; H, 4.58; N, 15.09.
2-(Phenylimino)-2H-chromene-3-carboxamides 30, 31 and 39:
General procedure
To a stirred solution of anthranilates 29, 2 or 38 (10 mmol) in glacial acetic acid (15 mL) was added an
equivalent amount of the corresponding 2-imino-2H-chromene derivatives 1a,b. The reaction mixture
was stirred at room temperature overnight. The precipitated products were filtered off, washed with
water, propan-2-ol (3 x 5 mL), and dried in air.
2-[(2-Carbamoylphenyl)imino]-2H-chromene-3-carboxamide (30):

Molecules 2000, 5
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1
Yield: 82%. M.p. 244-246 °C. H-NMR (250 MHz, DMSO-d6): 7.07-7.28 (m, 5H, CONH2+ArH);
7.40-7.64 (m, 3H, ArH); 7.75-7.78 (m, 2H, CONH2+ArH); 7.83 (br s, 1H, CONH2); 8.41 (s, 1H, H-4);
9.02 (br s, 1H, CONH2). IR (KBr), cm-1: 3392 (NH), 3168 (NH), 1640 (C=O+C=N), 1588. Anal.
Calcd for C17H13N3O3 (307.30): C, 66.44; H, 4.26; N, 13.67. Found: C, 66.21; H, 4.39; N, 13.89.
2-[(2-Carboxyphenyl)imino]-2H-chromene-3-carboxamide (31):
Yield: 62%. M.p. 191-192 °C. 1H-NMR (400 MHz, DMSO-d6): 6.98 (d, 1H, J = 8.1 Hz, ArH); 7.10-
7.22 (m, 3H, ArH); 7.41-7.48 (m, 2H, ArH); 7.62 (br s, 1H, CONH2); 7.64 (dd, 1H, J = 8.2, 0.6 Hz,
ArH); 7.90 (dd, 1H, J = 8.5, 0.6 Hz, ArH); 8.42 (s, 1H, H-4); 9.21 (s, 1H, CONH2). IR (KBr), cm-1:
3300 (NH2+OH), 3160 (NH), 1700 (C=O, acid), 1670 (C=O, amide). MS (EI, 70 eV) m/z (rel.%): 308
(M+·, 46), 291 (55), 264 (37), 248 (86), 220 (100), 189 (43), 173 (36), 145 (54), 119 (42), 89 (34), 65
(28), 44 (36). Anal. Calcd for C17H12N2O4 (308.30): C, 66.23; H, 3.92; N, 9.09. Found: C, 66.19; H,
4.01; N, 9.14.
2-{[(2-Methoxycarbonyl)phenyl]imino}-2H-chromene-3-carboxamide (39):
Yield: 68%. M.p. 214-217 °C. 1H-NMR (250 MHz, DMSO-d6): 3.71 (s, 3H, OCH3); 6.98 (d, 1H, J =
8.0 Hz, ArH); 7.17-7.26 (m, 3H, ArH); 7.45-7.52 (m, 2H, ArH); 7.73 (d, 1H, J = 8.2 Hz, ArH); 7.76
(br s, 1H, CONH2); 7.88 (d, 1H, J = 8.3 Hz, ArH); 8.52 (s, 1H, H-4); 9.17 (br s, 1H, CONH2). IR
(KBr), cm-1: 3424 (NH), 3272 (NH), 1716 (C=O, ester), 1688 (C=O, amide), 1608. Anal. Calcd for
C18H14N2O4 (322.31): C, 67.07; H, 4.38; N, 8.69. Found: C, 66.79; H, 3.99; N, 8.43.
2-(2-Oxo-2H-chromen-3-yl)-4H-3,1-benzoxazin-4-one (32):
Method A: A solution of 2-[(2-carboxyphenyl)imino]-2H-chromene-3-carboxamide (31) (310 mg, 1
mmol) in acetic anhydride (3 mL) was refluxed for 30 min. After completed reaction, the mixture was
cooled and the precipitate formed was filtered off, washed with water, cold propan-2-ol (2 x 5 mL) and
recrystallized from benzene to give 224 mg (77%) of 32: M.p. 203-204 °C (lit. [5] m.p. 197 °C; lit.
1
[21b] m.p. 195 °C). H-NMR (100 MHz, DMSO-d6): 7.38-7.43 (m, 2H, ArH); 7.65-7.74 (m, 3H,
ArH); 7.92-7.96 (m, 2H, ArH); 8.20 (d, 1H, J = 7.9 Hz, ArH); 8.86 (s, 1H, H-4). IR (KBr), cm-1:
3063, 1749 (C=O), 1599. Anal. Calcd for C17H9NO4 (291.26): C, 70.10; H, 3.11; N, 4.81. Found: C,
69.89; H, 3.34; N, 5.11.
Method B: 2-(2-Imino-2H-chromen-3-yl)-4H-3,1-benzoxazin-4-one (34) was synthesized from (4-oxo-
4H-3,1-benzoxazin-2-yl)-2-acetonitrile (33) [23] (190 mg, 1 mmol) and 2-hydroxybenzaldehyde (9a)
(0.1 mL) using the reaction conditions described in Method B for the synthesis of 10a to give 177 mg

Molecules 2000, 5
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(61%) of iminochromene 34. The compound 34 was used without any purification in the following
reaction. Acid hydrolysis of 34 (130 mg, 0.45 mmol) employing the reaction conditions described for
conversion of 10a into 7a afforded 77 mg (59%) of 32. 1H-NMR, IR spectral data, and melting points
confirm identity of the compounds obtained by Methods A and B.
N-aryl-2-oxo-2H-chromene-3-carboxamides 36a,b:
General procedures
Method A: A mixture of 1a or 1b (1.5 mmol) and anthranilic acid 2 (275 mg, 2 mmol) in aqueous
(80%) acetic acid (10 mL) was refluxed for 2 h. After the reaction finished, the mixture was cooled
and the precipitate was filtered off, washed with water and cold propan-2-ol (2 x 5 mL). The products
obtained were recrystallized from an appropriate solvent.
Method B: To a well stirred solution of ethyl 2'-carboxymalonanilate (37) [23] (4 mmol) in ethanol (10
mL) was added an equivalent amount of salicylaldehydes 9a or 9b and a few drops of piperidine as a
catalyst. The reaction mixture was stirred at room temperature for ca. 1 day and then poured into
water. The products precipitated were filtered off and recrystallized from an appropriate solvent.
N-(2-Carboxyphenyl)-2-oxo-2H-chromene-3-carboxamide (36a):
Yields: 82% (Method A) and 67% (Method B) (recrystallized from AcOH). M.p. 275-276 °C (lit.
[5,21b] m.p. 279 °C). 1H-NMR (400 MHz, DMSO-d6): 7.15 (dd 1H, J = 8.0, 8.0 Hz, ArH); 7.39 (m,
2H, ArH); 7.56 (dd, 1H, J = 8.0, 8.0 Hz, ArH); 7.73 (dd, 1H, J = 7.9, 7.9 Hz, ArH); 7.94 (d, 1H, J =
8.2 Hz, ArH); 8.05 (d, 1H, J = 8.2 Hz, ArH); 8.65 (d, 1H, J = 8.3 Hz, ArH); 8.85 (s, 1H, H-4); 13.52
(br s, 1H, NH). IR (KBr), cm-1: 3266 (NH), 3032 (CH), 1731 (C=O), 1696 (C=O), 1673 (C=O), 1608
(C=C). Anal. Calcd for C17H11NO5 (309.28): C, 66.02; H, 3.58; N, 4.53. Found: C, 66.32; H, 3.78; N,
4.72.
N-(2-Carboxyphenyl)-6-methoxy-2-oxo-2H-chromene-3-carboxamide (36b):
Yields: 69% (Method A) and 59% (Method B) (recrystallized from butan-1-ol). M.p. 124-125 °C. 1H-
NMR (400 MHz, DMSO-d6): 3.95 (s, 3H, OCH3); 7.14-7.32 (m, 4H, ArH); 7.42 (d, 1H, J = 8.2 Hz,
ArH); 8.01 (d, 1H, J = 8.0 Hz, ArH); 8.60 (d, 1H, J = 8.0 Hz, ArH); 8.89 (s, 1H, H-4); 13.20 (s, 1H,
NH). IR (KBr), cm-1: 3287 (NH), 2952 (CH), 1726 (C=O), 1694 (C=O), 1675 (C=O), 1614 (C=C).
Anal. Calcd for C18H13NO6 (339.31): C, 63.72; H, 3.86; N, 4.13. Found: C, 64.00; H, 4.03; N, 3.91.
2-Oxo-2H-chromene-3-carboxamide (25):

Molecules 2000, 5
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A solution of 39 (482 mg, 1.5 mmol) in aqueous (80%) acetic acid (10 mL) was refluxed for 2 h. After
the reaction was complete, the mixture was cooled and the precipitate was filtered off, washed with
water and cold propan-2-ol (5 mL). The product obtained was recrystallized from ethanol to give 228
mg (81%) of 25: M.p. 279-280 °C (lit. [9] m.p. 280-282 °C). 1H-NMR (400 MHz, DMSO-d6): 7.47
(ddd, 1H, J = 7.7, 7.7, 1.0 Hz, H-6); 7.53 (dd, 1H, J = 8.4, 1.0 Hz, H-8); 7.79 (ddd, 1H, J = 8.4, 7.7,
1.6 Hz, H-7); 7.96 (br s, 1H, CONH2); 8.00 (dd, J = 7.7, 1.6 Hz, H-5); 8.12 (br s, 1H, CONH2); 8.90 (s,
1H, H-4). Anal. Calcd for C10H7NO3 (189.17): C, 63.49; H, 3.73; N, 7.40. Found: C, 63.54; H, 3.71; N,
7.51.
2-oxo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2H-chromene (45a):
Method A: To a stirred solution of 2-imino-2H-chromene 1a (1.88 g, 10 mmol) in glacial acetic acid
(25 mL) was added an equivalent amount of benzohydrazide (11) (1.36 g, 10 mmol) and 2 drops of
H2SO4. The reaction mixture was warmed to 40 °C and stirred at room temperature for ca. 3 h. The
precipitated product was filtered off, washed with ethyl acetate (3 x 5 mL) and recrystallized from
propan-2-ol to yield 2.82 g (92%) of 2-(N-benzoylhydrazono)-2H-chromene 41a: M.p. 226-227 °C.
1H-NMR (100 MHz, DMSO-d6): 7.22-7.90 (m, 9H, ArH); 7.98 (s, 1H, CONH2); 8.23 (s, 1H, H-4);
9.16 (s, 1H, CONH2); 11.25 (s, 1H, CONH). IR (KBr), cm-1: 3305, 3238, 3110 (NH), 1698, 1678
(C=O), 1650 (C=N). A solution of benzoylhydrazonochromene 41a (1.54 g, 5 mmol) in dry and
degassed nitrobenzene (10 mL) was refluxed for 10–40 min. During the course of reaction, release of
ammonia was observed. After reaction was completed (monitoring by TLC), the mixture was cooled
and a precipitate was filtered off and recrystallized from benzene to give 1.13 g (78%) of 1,3,4-
1
oxadiazolylchromene 45a with m.p. 216-218 °C (lit. [31] m.p. 224 °C). H-NMR (100 MHz, DMSO-
-1
d6): 7.45-8.13 (m, 9H, ArH); 9.02 (s, 1H, H-4). IR (KBr), cm : 1744 (C=O). MS (EI, 70 eV) m/z
(rel.%): 290 (M+·, 26), 262 (5), 206 914), 189 (12), 173 (32), 105 (100). Anal. Calcd for C17H10N2O3
(290.27): C, 70.34; H, 3.47; N, 9.65. Found: C, 70.27; H, 3.62; N, 9.73.
Method B: Benzoylcarbohydrazonamide 12 (cf. Scheme 2) (154 mg, 0.5 mmol) was refluxed in a
mixture AcOH/H2SO4 (2 mL) for 15–30 min. After the reaction finished, the mixture was cooled and
neutralized with aqueous ammonia. The precipitate formed was filtered off, washed with water and
cold propan-2-ol (2 x 1 mL). The product obtained was recrystallized from an appropriate solvent to
1
afford 112 mg (78%) of 1,3,4-oxadiazolylchromene 45a. H-NMR, IR spectral data, and melting
points corroborate identity of the compounds obtained by Methods A and B.
6-n-Hexyl-7-hydroxy-2-oxo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2H-chromene (45b):

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1,3,4-Oxadiazolylchromene 45b was prepared from carbamoyliminochromene 1c [4b] and
benzohydrazide (11) using the reaction conditions described in Method A for the synthesis of 45a.
1
Yield: 68%. M.p. 241-242 °C. H-NMR (100 MHz, DMSO-d6):
0.86 (t, 3H, J = 7.0 Hz,
CH2(CH2)4CH3); 1.30 (m, 8H, CH2(CH2)4CH3); 1.56 (m, 2H, CH2(CH2)4CH3); 6.82 (s, 1H, H-8); 7.64
(m, 4H, ArH); 8.09 (m, 2H, ArH); 8.85 (s, 1H, H-4); 11.09 (br s, 1H, OH). IR (KBr), cm-1: 3088
(OH), 2851 (CHalkyl), 1744 (C=O), 1618 (C=C), 1570. Anal. Calcd for C23H22N2O4 (390.43): C, 70.75;
H, 5.68; N, 7.17. Found: C, 70.81; H, 5.80; N, 7.22.
References and Notes
1. Recent reviews on naturally occurred coumarins: (a) Malikov, V. M.; Saidkhodzhaev, A. I.
Coumarins. Plants, structure, properties. Khim. Prir. Soedin. 1998, 560-593. (b) Malikov, V. M.;
Saidkhodzhaev, A. I. Physical constants and spectral data of coumarins. Part 2. Coumarins: plants,
structure, properties. Khim. Prir. Soedin. 1998, 384-432. (c) Malikov, V. M.; Saidkhodzhaev, A. I.
Coumarins: plants, structure, properties. Part 1. Coumarin distribution in plants. Khim. Prir.
Soedin. 1998, 250-281; [Engl. Transl.: Chem. Nat. Compd. 1998, 34, 202-264]. (d) Estevez-
Braun, A.; Gonzalez, A. G. Coumarins. Nat. Prod. Rep. 1997, 14, 465-475. (e) Murray, R. D. H.
Naturally occurring plant coumarins. Prog. Chem. Org. Nat. Prod. 1997, 72, 1-119.
2. O'Kennedy, R.; Thornes, R. D. Coumarins: biology, applications, and mode of action. John Wiley
& Sons: Chichester; New York, 1997.
3. Zubkov, V. A.; Kovalenko, S. N.; Chernykh, V. P.; Ivkov, S. M. New derivatives of coumarin: 2-
(N-R-imino)-2H-1-benzopyrans. Khim. Geterotsikl. Soedin. 1994, 760-766; [Engl. Transl.: Chem.
Heterocycl. Compd. (N. Y.) 1994, 30, 665-670].
4. (a) Kovalenko, S. N.; Zubkov, V. A.; Chernykh, V. P.; Turov, A. V.; Ivkov, S. M. Recyclization
of 2-imino-2H-1-benzopyrans under the influence of nucleophilic reagents. 1. New approach to
the synthesis of 3-(1,3,4-oxadi-, thiadi-, and triazolyl-2)coumarins. Khim. Geterotsikl. Soedin.
1996, 186-192; [Engl. Transl.: Chem. Heterocycl. Compd. (N. Y.) 1996, 32, 163-168]. (b)
Kovalenko, S. N.; Chernykh, V. P.; Shkarlat, A. E.; Ukrainets, I. V.; Gridasov, V. I.; Rudnev, S.
A. Recyclization of 2-imino-2H-1-benzopyrans under the influence of nucleophilic reagents. 2.
Reaction of 2-iminocoumarin-3-carboxamides with o-aminobenzenesulfonamide. Khim.
Geterotsikl. Soedin. 1998, 916-920; [Engl. Transl.: Chem. Heterocycl. Compd. (N. Y.) 1998, 34,
791-795]. (c) Bilokin, Y. V.; Kovalenko, S. N.; Bylov, I. E.; Chernykh, V. P. Rearrangements of
2-imino-2H-1-benzopyran-3-carboxamides under action of anthranilic acid as N-nucleophile.
Heterocycl. Commun. 1998, 4, 257-260. (d) Kovalenko, S. N.; Vasil'ev, M. V.; Sorokina, I. V.;
Chernykh, V. P.; Turov, A. V.; Rudnev, S. A. Recyclization of 2-imino-2H-1-benzopyrans using
nucleophilic reagents. 3. Reaction of 2-iminocoumarin-3-carboxamides with o-phenylenediamines
and o-amino(thio)phenols. Khim. Geterotsikl. Soedin. 1998, 1664-1667; [Engl. Transl.: Chem.
Heterocycl. Compd. (N. Y.) 1998, 34, 1412-1415]. (e) Kovalenko, S. N.; Sytnik, K. M.;

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Nikitchenko, V. M.; Rusanova, S. V.; Chernykh, V. P.; Porokhnyak, A. O. Recyclization of 2-
imino-2H-1-benzopyrans by the action of nucleophilic reagents. 4. Use of 2-(N-aroylhydrazono)
coumarin-3-carboxamides for the synthesis of 3-(1,3,4-oxadiazol-2-yl)coumarins. Khim.
Geterotsikl. Soedin. 1999, 190-193; [Engl. Transl.: Chem. Heterocycl. Compd. (N. Y.) 1999, 35,
167-170]. (f) Vasylyev, M. V.; Bilokin, Y. V.; Branytska, O. V.; Kovalenko, S. M.; Chernykh, V.
P. A facile method for synthesis of heterocycles containing tetrahydrobenzo[4,5]thieno[2,3-
d]pyrimidine and coumarin moieties. Heterocycl. Commun. 1999, 5, 241-242. (g) Bilokin, Y. V.;
Vasylyev, M. V.; Branytska, O. V.; Kovalenko, S. M.; Chernykh, V. P. A novel and expedient
approach to new heterocycles containing benzothiophene, benzothieno[2,3-d ]pyrimidine and
coumarin moieties. Tetrahedron 1999, 55, 13757-13766. (h) Sytnik, K. M.; Kovalenko, S. M.;
Chernykh, V. P.; Goncharova, V. M. Synthesis and tuberculostatic activities of 2-(R-
thiosemicarbazono)coumarin-3-carboxamides. Fiziologichno Aktyvni Rechovyny 1999, (2), 50-53
(in Ukrainian with Engl abstr.). (i) Kovalenko, S. N.; Bylov, I. E.; Belokon, Ya. V.; Chernykh, V.
P. Recyclization of 2-imino-2H-1-benzopyrans under the action of nucleophilic reagents. 5.
Interaction of 2-imino-2H-1-benzopyran-3-carboxamide with anthranilic acid and its derivatives.
Khim. Geterotsikl. Soedin. 2000, 1175-1181.
5. Selim, M. R.; Aly, F. M.; Bedair, A. H.; Abu-Shanab, F. A. Synthesis of some benzoxazin-4-one
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688-690.
6. El-Hashash M. A.; Kaddah A. M.; El-Kady M.; Ammer M. M. Some reactions of 3[2'-(4'H,2',1')-
benzoxazin-4'-only]coumarins and 3(2'-quinazol-4'-onyl)coumarins. Pak. J. Sci. Ind. Res. 1982,
25, 104-108.
7. Enomoto, S.; Sato, K.; Suzuki, G. 3-(4-Oxo-3,4-dihydro-2-quinazolinyl)-7-diethylaminocoumarin
dyes. Ger. Offen. 2,005,933 (1970); Chem. Abstr. 1971, 74, 65585.
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Samples Availability: Available from the authors.
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