Reactions of 2-methylchromones with cyanoacetamides and ethyl cyanoacetate. synthesis of 6-(2-hydroxyaryl)-4-methyl-2-oxo-1,2-dihydropyridine-3- carbonitriles and 7-hydroxy-6-imino-9-methyl-6h-benzo[c]chromene-8-carbonitriles

Article abstract of DOI:10.1002/jhet.1601

Although 2-methylchromones react with cyanoacetamide and N-methyl cyanoacetamide in the presence of sodium ethoxide in refluxing ethanol to produce 6-(2-hydroxyaryl)-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitriles, their reactions with ethyl cyanoaceta

Full text of DOI:10.1002/jhet.1601

September 2013 Reactions of 2-Methylchromones with Cyanoacetamides and Ethyl
Cyanoacetate. Synthesis of 6-(2-Hydroxyaryl)-4-methyl-2-oxo-1,
2-dihydropyridine-3-carbonitriles and 7-Hydroxy-6-imino-9-methyl-
6H-benzo[c]chromene-8-carbonitriles
1005
a
a
a
b
*
Vyacheslav Ya. Sosnovskikh, Viktor A. Anufriev, Alexander V. Safrygin, and Oleg S. Eltsov
aDepartment of Chemistry, Ural State University, 620083 Ekaterinburg, Russia
bDepartment of Chemistry, Ural Federal University, 620002 Ekaterinburg, Russia
*
E-mail: Vyacheslav.Sosnovskikh@usu.ru
Received September 2, 2011
DOI 10.1002/jhet.1601
Published online 16 July 2013 in Wiley Online Library (wileyonlinelibrary.com).
Me
Me
O
O
CN
O
CN
OH
R
NCCH2CONHR'
NCCH2CO2Et
R
R
N
R'
OH
Me
O
NH
R = H, Me, Cl, Br; R' = H, Me
Although 2-methylchromones react with cyanoacetamide and N-methyl cyanoacetamide in the presence
of sodium ethoxide in refluxing ethanol to produce 6-(2-hydroxyaryl)-4-methyl-2-oxo-1,2-dihydropyridine-
3-carbonitriles, their reactions with ethyl cyanoacetate under the same conditions took an entirely different
course and gave 7-hydroxy-6-imino-9-methyl-6H-benzo[c]chromene-8-carbonitriles.
J. Heterocyclic Chem., 50, 1005 (2013).
INTRODUCTION
cyanoacetate in the presence of sodium ethoxide, leading
to isolation of 2-pyridones 3 and 2-pyrones 4, was reported
[14]. Contrary to a previous report [10], the reaction
proceeded via nucleophilic 1,4-addition with concomitant
opening of the pyrone ring and subsequent intramolecular
cyclization (Scheme 1). In view of these contradictory
literature reports and our continued interest in the chemistry
of chromones [15], we repeated the reaction of 2-methyl-
chromones 1 with active methylene compounds following
the literature method [10,14].
Chromones are naturally occurring oxygen-containing
heterocyclic compounds that perform important biological
functions in nature [1]. Although 2-methylchromones 1
constitute a small family of naturally occurring compounds,
their synthesis and transformations into other biologically
active compounds have been exploited [2,3]. It is known
that the pyrone ring of 1 is susceptible to ring opening under
the action of N-nucleophiles such as amines [4], hydrazines
[5,6], hydroxylamine [6,7], and thiourea [8]. However, only
a handful of papers describing some examples of reactions
with C-nucleophiles is present in the literature. In almost
all cases, the reactions with active methylene compounds
proceeded without cleavage of the pyrone ring, and only
1,2-addition (Knoevenagel condensation) at the carbonyl
group took place to give the corresponding methylidene
derivatives [9,10], including compound 2 [10] (Scheme 1).
In addition, 1,4-dianion generated from acetophenone oxime
and phenyl magnesium bromide reacts with 1 at C-4 to give
the spiroisoxazoline derivative [11] and 2-methyl-4-phenyl-
chromen-4-ol [12], respectively.
RESULTS AND DISCUSSION
We found that 2-methylchromones 1a–d react with
cyanoacetamide and N-methyl cyanoacetamide in the presence
of sodium ethoxide in absolute ethanol (reflux, 10 h), affording
6-(2-hydroxyaryl)-4-methyl-2-oxo-1,2-dihydropyridine-3-car-
bonitriles 3a–h in 47–76% yields. This reaction is earlier
known transformation of 2-methylchromones 1a,b [14],
which should be regarded as nucleophilic 1,4-addition of
cyanoacetamides with the formation of a new C–C bond
(intermediate A) followed by cyclodehydration into the
On the other hand, there are only two reports on the
reactions of 2-methylchromones 1 with C-nucleophiles
leading to the products, which can result from the initial
nucleophilic 1,4-addition. The use of methylcopper-BF3
provided 2,2-dimethylchroman-4-ones via conjugate addition
to the double bond in the g-pyrone system [13]. Recently, the
reaction of 1 with malononitrile, cyanoacetamide, and ethyl
1
products 3 (Scheme 2). All the signals in the H and 13C
NMR spectra of compound 3b were assigned on the basis
1
of 2D H–13C HSQC and HMBC experiments. Besides
the signals expected for the aromatic protons, the 1H
NMR spectrum of 3b in DMSO-d6 showed four singlets
because of the Me and MeN groups (d 2.38 and 3.23), H-
© 2013 HeteroCorporation

1006
V. Y. Sosnovskikh, V. A. Anufriev, A. V. Safrygin, and O. S. Eltsov
Vol 50
Scheme 1
Scheme 2
Me
Me
Me
O
NC
CN
CN
O
CN
CN
O
R
R
N
H
OH
R
N
R'
O
O
Me
2
3
OH
3a-h
OH
4
ref. 10 NCCH2CN,
R = H EtONa
X = CN, CONH2
ref. 14
X
-H2O X = NHR'
X = OEt
COX
O
O
Me
CN
O
O
O
CN
Me
NCCH2X,
R
R
R
R
EtONa
NCCH2COX
EtONa
ref. 14
X
O
Me
OH
Me
OH
A
1a-d
A
1 (R = H, Me)
X = OEt
-EtOH
X = CO2Et
NCCH2CO2Et
CF3
Me
NC
CO2Et
O
CN
CN
O
O
EtO2C
CN
CN
O
R
R
NC
OH
NH
O
R
R
Me
Me
O
OH
-H2O
5
4
OH
OH
B
C
-EtOH
-CO2
H2O
5 proton (d 6.30), and phenolic hydroxyl (d 10.27). In
addition, the choice between 4-Me- and 6-Me-2-pyridones
was made in favor of the former on the basis of the 2D
HMBC spectrum for 3b. The most informative cross-peaks
are as follows: Me/C3, Me/C5, Me/CN, Me/C4. Note that
in the case of 6-Me-2-pyridone, cross-peaks Me/C3 and
Me/CN could not be observed.
Me
Me
9
CN
O
CN
8
10
1
10a
7
10b
4a
R
R
OH
2
3
6a
CN
6
O
H
O
NH
4
6a-d
D
As mentioned earlier, the previous workers [14] reported
that the reaction of 1a,b with ethyl cyanoacetate leads
to compounds 4 (R═H, Me), and their claim has been
favorably reviewed [2]. However, the 2-pyrone ring forma-
tion was not firmly established, and in light of the known
behavior 2-(trifluoromethyl)chromones in reaction with
ethyl cyanoacetate, which afforded 7-hydroxy-6-imino-9-
3
a
b
c
d
R
H
R'
3
e
f
R
R'
1, 6
a
R
H
H
Me
H
Cl
Cl
Br
Br
H
Me
H
H
b
Me
Cl
Br
Me
Me
g
h
c
Me
Me
d
(trifluoromethyl)-6H-benzo[c]chromene-8-carbonitriles
5
(Scheme 1) [16], it was anticipated that the process would
follow a 1:2 instead of a 1:1 stoichiometry and proceed
by double nucleophilic attack of the base-activated ethyl
cyanoacetate to the chromone system. We therefore decided
to repeat the condensation of chromones 1a–d with ethyl
cyanoacetate as originally reported [14].
It was found that the reaction of 1a with ethyl cyanoace-
tate (2 equiv.) in the presence of sodium ethoxide in
refluxing absolute ethanol gave a 61% yield of high melt-
ing solid with low solubility in solvents such as DMSO,
DMF, ethanol, acetone, and toluene. This compound was
described by Ibrahim et al. [14] as the a-pyrone 4
(R═H). However, in contrast with this structure, its com-
position corresponded to a 1:2 adduct, C15H10N2O2, which
was assigned the structure 7-hydroxy-6-imino-9-methyl-
6H-benzo[c]chromene-8-carbonitrile (6a) on the basis of
elemental analysis, 1H NMR, 13C NMR, IR spectroscopies,
and comparison of the spectroscopic data with the data
reported for related systems [16]. In particular, the aromatic
protons of compound 6a at d 7.37 (H-4), 7.40 (H-2), 7.61
(H-3), and 8.26 (H-1) compare well with those of trifluoro-
methylated analog, 7-hydroxy-6-imino-9-(trifluoromethyl)-
6H-benzo[c]chromene-8-carbonitrile (5, R═H, d 7.41, 7.43,
7.67, and 8.38, respectively). In addition, the Me group and
H-10 appeared as two singlets at d 2.53 and 7.52 ppm; the
broad signal at d 7.70 (2H) is due to the resonances of OH
and NH protons. The Ibrahim group attributed the 1H
NMR aromatic signals at d 7.37–8.29ppm to the phenolic
protons of 4 (R═H), although they are more befitting of a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2013 Reactions of 2-Methylchromones with Cyanoacetamides and Ethyl Cyanoacetate
1007
internal standard (only for 1H NMR spectra). IR spectra were
recorded on a Bruker Alpha FTIR instrument with the appliance
of disturbed total internal reflection (ZnSe crystal). Elemental
analyses were performed at the Microanalysis Services of the
Institute of Organic Synthesis, Ural Branch, Russian Academy
of Sciences. Melting points were uncorrected. All solvents used
were dried and distilled per standard procedures.
coumarin system. Consequently, structure 4 should be revised
to 6 (Scheme 2).
Similar reactions of 1b–d with ethyl cyanoacetate gave
7-hydroxy-6-imino-9-methyl-6H-benzo[c]chromene-8-
carbonitriles 6b–d in 62–78% yields as the sole products
after recrystallization from DMF. It should be noted that
these 1:2 adducts were obtained even from the reaction of
1 with 1 equiv. of ethyl cyanoacetate, albeit in a lower
yield. It was also found that formation of the tricyclic com-
pounds 6 was encouraged by prolonged heating (12–16h).
Unfortunately, the low solubility of 6a–d (mp >300ꢀC)
in suitable solvents made it difficult to obtain good 13C
NMR spectra; however, rather satisfactory 13C NMR spectra
obtained for compounds 6a,c at 50ꢀC supported the
aforementioned structures. Additional support for 6 is
provided by the IR spectra, in which a highly characteristic
nitrile absorption at 2208–2216 cm–1 and C═NH and OH
bands at 1678–1698, 3321–3326, and 3420–3428 cm–1
was observed.
Thus, the reaction of 1 with ethyl cyanoacetate took an
entirely different course as compared with the reaction of
cyanoacetamides. Clearly, the most significant difference
between these reactions is the failure of cyanoacetamides
to form 1:2 adducts. This failure may be attributed to the
readiness with which 1:1 adducts undergo ring closure
involving the amide group to form 2-pyridones 3. In this
process, ethyl cyanoacetate may be regarded as a synthetic
equivalent of 1,3-dicyanoacetone, which is not a readily
available compound. It should be noted that the products
of type 2, which can result from the initial nucleophilic
1,2-addition, were not observed at all.
General procedure for the synthesis of 6-(2-hydroxyaryl)-
4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitriles (3a–h).
A
solution of sodium ethoxide (69 mg, 3.0 mmol sodium in 5 mL
of absolute ethanol) was added with the corresponding
2-methylchromone 1 (3.0 mmol) in absolute ethanol (5 mL) and
cyanoacetamide or N-methyl cyanoacetamide (3.0 mmol). The
mixture was refluxed for 10 h. Then, the orange reaction mixture
was poured onto dilute hydrochloric acid (2N, 25 mL), and
the yellow solid so formed was filtered and washed with ethanol
to give compound 3 in an analytically pure state without
recrystallization.
6-(2-Hydroxyphenyl)-4-methyl-2-oxo-1,2-dihydropyridine-3-
carbonitrile (3a). Yield 55%, light-brown crystals, mp >300ꢀC
(lit. [14] mp >300ꢀC); IR (ATR) 3182, 2222, 1645, 1597,
1531 cmꢁ1 1H NMR (400 MHz, DMSO-d6) 2.40 (s, 3H, Me),
;
6.60 (br s, 1H, H-5), 6.92 (t, 1H, H-50, J = 7.4 Hz), 6.98 (d, 1H,
H-30, J = 7.8 Hz), 7.34 (ddd, 1H, H-40, J = 8.2, 7.0, 1.7 Hz), 7.46
(br s, 1H, H-60), 10.55 (br s, 1H, OH), 12.15 (br s, 1H, NH).
6-(2-Hydroxyphenyl)-1,4-dimethyl-2-oxo-1,2-dihydropyridine-3-
carbonitrile (3b).
Yield 56%, light-brown crystals, mp 260–
263ꢀC; IR (ATR) 3115, 2221, 1623, 1599, 1568, 1549 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6) 2.38 (s, 3H, Me), 3.23 (s, 3H,
MeN), 6.30 (s, 1H, H-5), 6.95 (td, 1H, H-50, J = 7.4, 0.8 Hz),
6.99 (d, 1H, H-30, J = 8.2 Hz), 7.23 (dd, 1H, H-60, J = 7.6,
1.7 Hz), 7.38 (ddd, 1H, H-40, J = 8.2, 7.2, 1.7 Hz), 10.27 (s, 1H,
OH); 13C NMR (100 MHz, DMSO-d6) d 20.8 (Me), 33.6
(Me), 100.7 (C-3), 110.7 (C-5), 116.2 (C-30), 116.5 (CN), 119.9
(C-50), 121.9 (C-10), 130.1 (C-60), 132.2 (C-40), 152.9 (C-6),
154.8 (C-20), 158.8 (C-4), 160.8 (C-2). Anal. Calcd for
C14H12N2O2: C, 69.99; H, 5.03; N, 11.66. Found: C, 69.87; H,
4.91; N, 11.47.
For the formation of products 6, a plausible mechanism
depicted in Scheme 2 can be proposed. The initial nucleo-
philic attack of the base-activated methylene compound at
C-2 (intermediate A) followed by Claisen condensation
(intermediate B, the initial Claisen self-condensation of
the starting ester could not be excluded), intramolecular
cyclization and dehydration (intermediate C), and then
aromatization (intermediate D, after hydrolysis and decar-
boxylation) leads to benzo[c]coumarins 6 through involve-
ment of the phenolic hydroxy group.
6-(2-Hydroxy-5-methylphenyl)-4-methyl-2-oxo-1,2-
dihydropyridine-3-carbonitrile (3c).
crystals, mp >300ꢀC (lit. [14] mp >300ꢀC); IR (ATR) 3139,
2324, 2218, 1634, 1604, 1583 cmꢁ1 1H NMR (400MHz,
Yield 47%, light-brown
;
DMSO-d6) 2.24 (s, 3H, Me-50), 2.40 (s, 3H, Me-4), 6.56 (br s,
1H, H-5), 6.87 (d, 1H, H-30, J = 8.3 Hz), 7.15 (dd, 1H, H-40,
J = 8.3, 1.7 Hz), 7.28 (br s, 1H, H-60), 10.27 (br s, 1H, OH), 12.10
(br s, 1H, NH). Anal. Calcd for C14H12N2O2: C, 69.99; H, 5.03;
N, 11.66. Found: C, 70.02; H, 5.15; N, 11.76.
In conclusion, we have shown that the condensation of
2-methylchromones with active methylene compounds in
the presence of sodium ethoxide affords two types of
products: 6-(2-hydroxyaryl)-3-cyano-4-methyl-2-pyridones with
cyanoacetamides and 7-hydroxy-6-imino-9-methyl-6H-benzo[c]
chromene-8-carbonitriles with ethyl cyanoacetate. The latter
reaction represents a one-pot, multistep transformation and
can be employed to obtain functionalized 6H-benzo[c]-
chromen-6-ones.
6-(2-Hydroxy-5-methylphenyl)-1,4-dimethyl-2-oxo-1,2-
dihydropyridine-3-carbonitrile (3d).
Yield 63%, colorless
crystals, mp 283ꢁ285ꢀC; IR (ATR) 3162, 2220, 1624, 1612,
1597, 1567, 1549, 1512cmꢁ1 1H NMR (400MHz, DMSO-d6)
;
2.24, 2.38 (both s, 3H, Me), 3.23 (s, 3H, MeN), 6.30 (s, 1H, H-5),
6.88 (d, 1H, H-30, J = 8.3 Hz), 7.04 (d, 1H, H-60, J = 2.0 Hz), 7.18
(dd, 1H, H-40, J = 8.3, 2.0 Hz), 10.02 (s, 1H, OH). Anal. Calcd for
C15H14N2O2: C, 70.85; H, 5.55; N, 11.02. Found: C, 70.66; H,
5.78; N, 11.13.
6-(5-Chloro-2-hydroxyphenyl)-4-methyl-2-oxo-1,2-
dihydropyridine-3-carbonitrile (3e). Yield 69%, pale-yellow
crystals, mp >330ꢀC; IR (ATR) 3153, 3108, 2390, 2221, 1638,
EXPERIMENTAL
1
1616, 1585, 1540 cmꢁ1; H NMR (400MHz, DMSO-d6) 2.44 (s,
1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded
on a Bruker Avance II spectrometer in DMSO-d6 with TMS as an
3H, Me), 6.56 (br s, 1H, H-5), 6.95 (d, 1H, H-30, J = 8.7 Hz), 7.25
(dd, 1H, H-40, J = 8.7, 2.7Hz), 7.48 (br s, 1H, H-60), 10.63 (br s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1008
V. Y. Sosnovskikh, V. A. Anufriev, A. V. Safrygin, and O. S. Eltsov
Vol 50
1H, OH), 12.10 (br s, 1H, NH). Anal. Calcd for C13H9ClN2O2: C,
59.90; H, 3.48; N, 10.75. Found: C, 59.74; H, 3.63; N, 10.97.
6-(5-Chloro-2-hydroxyphenyl)-1,4-dimethyl-2-oxo-1,2-
dihydropyridine-3-carbonitrile (3f). Yield 67%, light-brown
crystals, mp 274ꢁ277ꢀC; IR (ATR) 3078, 2580, 2230,
2-Chloro-7-hydroxy-6-imino-9-methyl-6H-benzo[c]chromene-
8-carbonitrile (6c).
Yield 78%, pale-yellow crystals, mp
>300ꢀC; IR (KBr) 3422, 3321, 2216, 1687, 1612, 1598,
1
1574 cmꢁ1; H NMR (400 MHz, DMSO-d6, 50ꢀC) d 2.55 (s, 3H,
Me), 7.37 (d, 1H, H-4, J = 8.9 Hz), 7.53 (s, 1H, H-10), 7.55
(dd, 1H, H-3, J = 8.9, 2.4 Hz), 7.6–7.9 (br s, 1H, OH), 8.17 (s, 1H,
NH), 8.29 (d, 1H, H-1, J = 2.4 Hz); 13C NMR (100 MHz, DMSO-
d6, 50ꢀC) d 21.7 (Me), 95.9 (C), 111.4 (CH), 116.3 (CN), 119.4
(C), 119.6 (CH), 124.7 (CH), 129.7 (C), 132.1 (C), 132.2 (CH),
138.7 (C), 151.0 (C), 152.6 (C), 154.3 (C), 161.3 (C). Anal. Calcd
for C15H9ClN2O2: C, 63.28; H, 3.19; N, 9.84. Found: C, 63.26;
H, 3.19; N, 9.82.
1601, 1561, 1493 cmꢁ1 1H NMR (400 MHz, DMSO-d6) 2.40
;
(s, 3H, Me), 3.28 (s, 3H, MeN), 6.21 (s, 1H, H-5), 6.96 (d, 1H,
H-30, J= 8.7 Hz), 7.19 (d, 1H, H-60, J= 2.7 Hz), 7.30 (dd, 1H, H-
40, J= 8.7, 2.7 Hz), 10.44 (s, 1H, OH). Anal. Calcd for
C14H11ClN2O2: C, 61.21; H, 4.04; N, 10.20. Found: C, 60.93; H,
4.33; N, 10.25.
6-(5-Bromo-2-hydroxyphenyl)-4-methyl-2-oxo-1,2-dihydropyridine-
3-carbonitrile (3g).
>330ꢀC; IR (ATR) 3155, 2500, 2220, 1640, 1616, 1591,
1539cmꢁ1 1H NMR (400MHz, DMSO-d6) 2.42 (s, 3H, Me),
Yield 76%, light-yellow crystals, mp
2-Bromo-7-hydroxy-6-imino-9-methyl-6H-benzo[c]chromene-
8-carbonitrile (6d).
Yield 71%, pale-yellow crystals, mp
;
>300ꢀC; IR (KBr) 3424, 3324, 2213, 1687, 1611, 1595,
1
6.52 (br s, 1H, H-5), 6.91 (d, 1H, H-30, J = 8.7 Hz), 7.42 (dd, 1H,
H-40, J = 8.7, 2.5 Hz), 7.56 (br s, 1H, H-60), 10.65 (br s, 1H, OH),
12.13 (br s, 1H, NH). Anal. Calcd for C13H9BrN2O2ꢂ0.25H2O: C,
50.43; H, 3.09; N, 9.05. Found: C, 50.23; H, 2.83; N, 8.91.
6-(5-Bromo-2-hydroxyphenyl)-1,4-dimethyl-2-oxo-1,2-
dihydropyridine-3-carbonitrile (3h). Yield 68%, brown crystals,
mp 272ꢁ273ꢀC; IR (ATR) 3138, 2221, 1624, 1590, 1571,
1575cmꢁ1; H NMR (400MHz, DMSO-d6) d 2.55 (s, 3H, Me),
7.31 (d, 1H, H-4, J = 8.8Hz), 7.54 (s, 1H, H-10), 7.68 (dd, 1H,
H-3, J = 8.8, 2.3Hz), 7.6–7.9 (br s, 1.5H, OH), 8.17 (s, 0.5H,
NH), 8.41 (d, 1H, H-1, J =2.3 Hz). Anal. Calcd for C15H9BrN2O2:
C, 54.74; H, 2.76; N, 8.51. Found: C, 54.46; H, 2.69; N, 8.44.
1547 cmꢁ1 1H NMR (400 MHz, DMSO-d6) 2.39 (s, 3H, Me),
;
3.26 (s, 3H, MeN), 6.24 (s, 1H, H-5), 6.92 (d, 1H, H-30,
J = 8.7 Hz), 7.34 (d, 1H, H-60, J = 2.6 Hz), 7.45 (dd, 1H, H-40,
J = 8.7, 2.6 Hz), 10.50 (s, 1H, OH). Anal. Calcd for
C14H11BrN2O2ꢂ0.25H2O: C, 51.96; H, 3.58; N, 8.66. Found: C,
51.69; H, 3.08; N, 8.53.
REFERENCES AND NOTES
[1] (a) Ellis, G. P. Chromenes, Chromanones, and Chromones, in
The Chemistry of Heterocyclic Compounds; Wiley: New York, 1977;
Vol. 31; (b) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem Rev
2003, 103, 893.
General procedure for the synthesis of 7-hydroxy-6-imino-
[2] Chosh, C. K. J Heterocycl Chem 2006, 43, 813.
[3] Ibrahim, M. A.; Ali, T. E.; Alnamer, Y. A.; Gabr, Y. A.
Arkivoc 2010, (i), 98.
9-methyl-6H-benzo[c]chromene-8-carbonitriles (6a–d).
A
solution of sodium ethoxide (69 mg, 3.0 mmol sodium in
5 mL of absolute ethanol) was added with the corresponding 2-
methylchromone 1 (3.0 mmol) in absolute ethanol (5 mL) and
ethyl cyanoacetate (680 mg, 6.0 mmol). The red-orange reaction
mixture was refluxed for 12–16 h, cooled, and acidified with
dilute hydrochloric acid (6N, 25 mL). The solid obtained was
filtered off and crystallized from DMF to give compound 6.
7-Hydroxy-6-imino-9-methyl-6H-benzo[c]chromene-8-
carbonitrile (6a). Yield 61%, pale-yellow crystals, mp >300ꢀC
(lit. [14] mp >300ꢀC); IR (ATR) 3428, 3326, 2211, 1698, 1599,
[4] Zagorevskii, A. V.; Orlova, E. K.; Tsvetkova, I. D.; Vinokurov, G.
V.; Troitskaya, V. S.; Rozenberg, S. G. Chem Heterocycl Compd 1971, 7, 675.
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[6] Morin, C.; Beugelmans, R. Tetrahedron 1977, 33, 3183.
[7] Eiden, F.; Löwe, W. Tetrahedron 1972, 28, 3295.
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Chem Soc Pak 1996, 18, 226.
[9] (a) Eiden, F.; Engelhardt, A. Arch Pharm 1967, 300, 211; (b)
Mahmoud, M. R.; Amine, M. S.; Guirgius, D. B. Indian J Chem 1993,
32B, 427; (c) Al Naimi, I. S.; Hussain, B. A. Qatar Univ Sci J 1992, 12, 73.
[10] Zeid, I.; El-Bary, H. A.; Yassin, S.; Zahran, M. Liebigs Ann
Chem 1984, 186.
1
1581cmꢁ1; H NMR (400 MHz, DMSO-d6, 50ꢀC) d 2.53 (s, 3H,
Me), 7.37 (d, 1H, H-4, J = 8.3Hz), 7.40 (t, 1H, H-2, J = 7.5 Hz),
7.52 (s, 1H, H-10), 7.61 (t, 1H, H-3, J = 7.8 Hz), 7.70 (br s, 2H,
NH, OH), 8.26 (d, 1H, H-1, J = 7.5 Hz); 13C NMR (100 MHz,
DMSO-d6, 50ꢀC) d 21.1 (Me), 95.7 (C), 101.1 (C), 110.3
(CH), 115.7 (C), 116.8 (CH), 116.9 (CN), 124.5 (CH), 124.7
(CH), 131.9 (CH), 139.2 (C), 150.0 (C), 151.1 (C), 153.7 (C),
160.9 (C). Anal. Calcd for C15H10N2O2: C, 71.99; H, 4.03; N,
11.19. Found: C, 71.68; H, 3.99; N, 11.32.
[11] Sosnovskikh, V. Y.; Usachev, B. I.; Sizov, A. Y.; Kodess,
M. I. Tetrahedron Lett 2004, 45, 7351.
[12] Elkaschef, M. A. F.; Abdel-Megid, F. M. E.; Mokhtar,
K. E. M. Acta Chim Acad Sci Hung 1975, 84, 319.
[13] (a) Wallace, T. W. Tetrahedron Lett 1984, 25, 4299; (b)
Clarke, P. D.; Fitton, A. O.; Suschitzky, H.; Wallace, T. W.; Dowlatshahi,
H. A.; Suschitzky J. L. Tetrahedron Lett 1986, 27, 91.
[14] Ibrahim, S. S.; El-Shaaer, H. M.; Hassan, A. Phosphorus
Sulfur and Silicon 2002, 177, 151.
[15] (a) Sosnovskikh, V. Y. Uspekhi Khimii 2003, 72, 550; Russ
Chem Rev 2003, 72, 489; (b) Sosnovskikh, V. Y.; Sevenard, D. V.; Usa-
chev, B. I.; Röschenthaler, G.-V. Tetrahedron Lett 2003, 44, 2097; (c)
Sosnovskikh, V. Y.; Usachev, B. I.; Sevenard, D. V.; Röschenthaler, G.-
V. J Org Chem 2003, 68, 7747; (d) Sosnovskikh, V. Y.; Usachev, B. I.;
Sizov, A. Y.; Barabanov, M. A. Synthesis 2004, 942; (e) Sosnovskikh,
V. Y.; Usachev, B. I.; Sevenard, D. V.; Röschenthaler, G.-V. Tetrahedron
2003, 59, 2625.
7-Hydroxy-6-imino-2,9-dimethyl-6H-benzo[c]chromene-8-
carbonitrile (6b).
>300ꢀC (lit. [14] mp >300ꢀC); IR (ATR) 3420, 3322, 2208,
1678, 1583 cmꢁ1 1H NMR (400 MHz, DMSO-d6) d 2.44 (s,
Yield 62%, pale-yellow crystals, mp
;
3H, Me-2), 2.55 (s, 3H, Me-9), 7.22 (d, 1H, H-4, J = 8.3 Hz),
7.38 (br d, 1H, H-3, J = 8.3 Hz), 7.44 (s, 1H, H-10), 7.6–8.0
(br s, 1.6H, NH, OH), 8.01 (br s, 1H, H-1), 8.19 (s, 0.4H,
NH). Anal. Calcd for C16H12N2O2: C, 72.72; H, 4.58; N,
10.60. Found: C, 72.78; H, 4.54; N, 10.64.
[16] Sosnovskikh, V. Y.; Safrygin, A. V.; Anufriev, V. A.; Eltsov,
O. S.; Iaroshenko, V. O. Tetrahedron Lett 2011, 52, 6271.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet