Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-diones from 8-formyl-7-hydroxy-4-methylcoumarin

Article abstract of DOI:10.1016/j.tetlet.2013.07.047

We report the synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-dione based scaffolds by the reaction of 8-formyl-7-hydroxy-4-methylcoumarin with various active methylene compounds. A mechanism of a tandem Knoevenagel condensation and cyclisation reaction is proposed. The structure of all compounds was established on the basis of ¹H and ¹³C NMR data, high resolution mass spectrometry and elemental analysis.

Full text of DOI:10.1016/j.tetlet.2013.07.047

Accepted Manuscript
Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-diones from 8-formyl-7-
hydroxy-4-methylcoumarin
Ahmed Al-Kawkabani, Baya Boutemeur-Kheddis, Malika Makhloufi-Chebli,
Maamar Hamdi, Oualid Talhi, Artur M.S. Silva
PII:
S0040-4039(13)01186-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.07.047
TETL 43245
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
2 June 2013
3 July 2013
8 July 2013
Please cite this article as: Al-Kawkabani, A., Boutemeur-Kheddis, B., Makhloufi-Chebli, M., Hamdi, M., Talhi, O.,
Silva, A.M.S., Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-diones from 8-formyl-7-hydroxy-4-
methylcoumarin, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.07.047
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Graphical Abstract
Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-
diones from 8-formyl-7-hydroxy-4-methylcoumarin
Leave this area blank for abstract info.
Ahmed Al-Kawkabani, Baya Boutemeur-Kheddis, Malika
Makhloufi-Chebli, Maamar Hamdi, Oualid Talhi, Artur M. S. Silva
CH3
CH3
Activated methylene
O
O
O
HO
O
O
Knoevenagel
Cyclysation
Hydrolysis
O
O
R
.

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-diones from 8-formyl-7-
hydroxy-4-methylcoumarin
Ahmed Al-Kawkabani,a Baya Boutemeur-Kheddis,a,* Malika Makhloufi-Chebli,b Maamar Hamdi,a Oualid
Talhi,c Artur M. S. Silvac,*
aLaboratoire de Chimie Organique appliquée (groupe hétérocycles), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediène BP 32,
El-Alia, 16111Bab-Ezzouar, Alger, Algeria.
bUniversité Mouloud Mammeri, Faculté des sciences, département de chimie, TiziOuzou, 15000, Algérie.
cDepartment of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We report the synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-dione based scaffolds by the
reaction of 8-formyl-7-hydroxy-4-methylcoumarin with various active methylene compounds. A
mechanism of a tandem Knoevenagel condensation and cyclisation reaction is proposed. The
structure of all compounds was established on the basis of 1H and 13C NMR data, high resolution
mass spectrometry and elemental analysis.
Available online
2013 Elsevier Ltd. All rights reserved.
Keywords:
Coumarin
Pyran-2-one
Formylation
Knoevenagel reaction
Translactonisation
Heterocyclisation
1. Introduction*
TAL) 3a (Scheme 2).19-21 Herein, we report an efficient synthetic
procedure of 8-formyl-7-hydroxy-4-methylcoumarin 2 in view of
Coumarins and pyran-2-ones form an exceptional class of
oxygen containing heterocyclic compounds playing a key role in
the medicinal area due to their structural diversity and pharma-
ceutical properties. They are exemplified in a large number of
natural products displaying a broad spectrum of medicinal bene-
fits. Various synthetic coumarin derivatives constitute one of the
most widely used groups of anti-HIV,1 anti-inflammatory2-4 and
antioxidant5,6 agents. They have been extensively investigated for
decades to exert other valuable biological effects such as the
anticancer,7-10 and the antiviral activities.11 In light of these po-
tential biological findings, a huge amount of researches on cou-
marin derivatives have been conducted to develop a plethora of
synthetic procedures mostly by using Perkin or Knoevenagel
reactions.12-18 However, further scientific efforts are still on de-
mand to seek for more adequate and flexible synthetic method-
ologies of novel coumarin based scaffolds. Taking into consid-
eration the referred biological outcome due to pyran-2-ones, our
interest is particularly focused on the chemical transformations
related to triacetic lactone (4-hydroxy-6-methylpyran-2-one,
investigating its reactivity towards the above mentioned pyran-2-
one 3a and other active methylene compounds such as, ethyl
acetoacetate 3b, malononitrile 3c and ethyl cyanoacetate 3d. The
use of the key starting material 2 in the current study provides a
facile access to a novel series of 2H,8H-pyrano[2,3-f]chromene-
2,8-dione based scaffolds 4a-d via a Knoevenagel condensation /
cyclisation tandem process. Synthetic pyranobenzopyranone
derivatives have recently been described as photoreagents to-
wards DNA and present some antimicrobial activity in the dark.22
2. Results and discussion
A large number of investigations have been carried out on the
formylation of 7-hydroxy-4-methylcoumarin 1 which usually
proceeds in the presence of hexamine in refluxing acetic acid
lasting for more than 6 hours of reaction time. Nevertheless, the
reported strategies have not escaped criticism since this reaction
is mostly offering 8-formyl-7-hydroxy-4-methylcoumarin 2 in
very low yields,23-27 and many difficulties are faced in the purifi-
cation of this product 2. However, successful attempts have been
described by Panel et al28 and Wei et al29 affording up to 60%
yield of 2. The synthesis of 2 was repeated by us following ex-
actly the reported operating conditions,28,29 but only 25 % yield is
reached after 8 hours of reaction time.30 Moreover, the final
product requires further steps of purification. These operative
problems drive us to study the formylation reaction of 7-
———
*
Corresponding author. Tel.: +213 21247950, +351 234370714;
fax: +213 21247311, +351 234370084. E-mail address: bayakhed-
dis@hotmail.com (B. Boutemeur-Kheddis) and artur.silva@ua.pt
(Artur M. S. Silva).

2
hydroxy-4-methylcoumarin 1 under the same conditions but
using microwave irradiation as an alternative source of heating.
By applying a power of 300 W for 7 min and 200 W after addi-
tion of HCl (20%) for 4 min, compound 2 was obtained in 40%
yield.31 The structure of 2 was confirmed on the basis of physico-
chemical and literature data (Scheme 1).28,29
to the carbonyl groups C-11 and C-13 of the acetoacetyl enolic
form. It is also possible to observe both signals of the carbonyl
groups C-8 and C-2 of the pyran-2-one rings appearing at 158.9
and 156.9 ppm. A careful analysis of the HSQC spectrum helped
us to assign all the protonated carbons, while the connectivities
encountered in the HMBC spectrum confirm without ambiguity
the structure of compound 4a allowing the assignment of all
carbonyl groups and quaternary carbons (Figure 1).
H
O
O
O
O
O
O
H
H
H
H3C
CH3
H3C
CH3
H
OH
O
OH
O
Scheme 1. Synthesis of compound 2: (i) AcOH, MW, reflux, (ii)
HCl (20%), MW, 80 °C.
O
O
In our previous work, we reported that the condensation of
triacetic lactone (TAL) 3a with salicylaldehydes produces 3-
acetoacetylcoumarin compounds following a successive Kno-
evenagel condensation and an intramolecular trans-
lactonisation.19-22 In this undertaken study, a similar approach
was used to selectively synthesize 4-methyl-9-(3-oxobutanoyl)-
2H,8H-pyrano[2,3-f]chromene-2,8-dione 4a through the reaction
of TAL 3a with 8-formyl-7-hydroxy-4-methylcoumarin 2. The
reaction proceeds at room temperature in a mixture of etha-
nol:toluene as solvent using a catalytic amount of triethylamine
as base (Scheme 2).
Figure 1. HMBC connectivities of compound 4a.
The structure of 4a is undoubtedly showing that the reaction
of 2 with TAL 3a involves a first Knoevenagel condensation
affording the intermediate 5 which is ready for a subsequent
intramolecular translactonisation causing the pyran-2-one ring
opening of the attached TAL unit (Scheme 2).
Following our interest on the behaviour of pyran-2-one as a
cyclic active methylene, we attempt the reaction of 8-formyl-7-
hydroxy-4-methylcoumarin 2 with an equivalent amount of ethyl
acetoacetate 3b at room temperature in the presence of catalytic
amount of piperidine (Scheme 3). The reaction was monitored by
TLC which shows the formation of a unique product 4b in very
good yield (80%) after 2 hours of reaction time. The structure of
this product was confirmed by mass spectrometry, elemental
analysis and precisely elucidated by NMR as 9-acetyl-4-methyl-
2H,8H-pyrano[2,3-f]chromene-2,8-dione 4b.33 In this case, the
O
O
CH3
CH3
CH3
O
3a
HO
O
OH
O
O
HO
O
(i)
2
O
Knoevenagel
condensation
(Z)-5
O
H3C
O
Knoevenagel
condensation
of
8-formyl-7-hydroxy-4-
Intramolecular
methylcoumarin 2 on ethyl acetoacetate 3b can give rise to both
isomeric (E and Z)-forms of the intermediate olefin 6. However,
the occurring intramolecular transesterification reaction which
led to the final product 4b occurred via the (Z)-configured inter-
mediate (Z)-6 (Scheme 3).
translactonisation
CH3
CH3
5
4
4a
6
3
6a
O
O
O
O
O
O
2
10a 10b
10
In contrast, the reaction of 2 with malononitrile 3c has led, af-
ter a Knoevenagel reaction, to a spontaneous heterocyclisation of
the 7-hydroxy group on the cyano function in the intermediate 7
O
O
8
9
11
O
12
13
CH3
14
O
4a
delivering
8-imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-f]
O
CH3
HO
chromene-9-carbonitrile 4c in 80% yield.34 The hydrolysis of 4c
with hydrochloric acid (4 N) under microwave irradiation (at 300
W for 4 min) affords the mono-hydrolysed product 9.35 Using a
longer reaction time (9 min) in a more concentrated hydrochloric
acid (12 N), the 9-cyano group was also hydrolysed to a carbox-
ylic acid function in the product 1036 (85%, Scheme 3).
Scheme 2. Synthesis of compounds 4a: (i) NEt3, toluene/EtOH, r.t.
The analytical data of the obtained product 4a32 indicates that
a stoichiometric condensation reaction of TAL 3a with 8-formyl-
7-hydroxy-4-methylcoumarin 2 has taken place followed by
water elimination as revealed by the mass spectrum resulting the
molecular ion [M+Na]+ at m/z 335. This fact was further sup-
ported by elemental analysis of 4a to identify its exact molecular
formula C17H12O6. The 1H NMR spectrum of compound 4a
presents two signals as singlets at 2.29 and 2.50 ppm assigned to
the protons of the two methyl groups. Two doublet signals are
observed at 7.29 and 7.83 ppm which are attributed to adjacent
aromatic protons H-6 and H-5, respectively. Further characteris-
tic singlets appearing at 6.36, 6.98 and 9.20 ppm are due to
proton resonances of H-3 and H-10 related to both pyran-2-one
rings and the enolic proton H-12, respectively. Finally, the ap-
pearance of a hydroxyl proton at 15.73 ppm suggests the pre-
dominance of the enolic form in the acetoacetyl moiety (in
CDCl3 solution) and this high frequency value thereof explains
the strong intramolecular hydrogen bond with the oxygen of the
C-11 carbonyl group. The 13C NMR spectrum presents two
signals at 170.6 and 200.2 ppm which are respectively attributed
In order to study and compare the orientation of the trans-
esterification versus the iminocoumarin heterocyclisation arising
from both of the ethyl acetoacetate 3b and malononitrile 3c ac-
tion on 2, respectively, we treated 8-formyl-7-hydroxy-4-methyl-
coumarin 2 with ethyl cyanoacetate 3d under similar conditions
to those described above. The active methylene 3d is also ex-
pected to provide the Knoevenagel adduct as an intermediate of
two possible isomeric configuration (E)-8 and (Z)-8. According
to NMR and other analytical data, the iminocoumarin 4d37 was
the major isolated compound, which was formed through the (E)-
configured Knoevenagel adduct (E)-8. This result is completely
different from those obtained by Moskvina and Khilya38 in the
reaction of 8-formyl-7-hydroxy-4-phenylcoumarin (similar to our
starting material 2) with ethyl cyanoacetate 3d. We have used
organocatalytic conditions while they used an inorganic base
(NaHCO3) in the condensation of 8-formyl-7-hydroxy-4-
phenylcoumarin with 3d, followed by acidic transesterification to

3
selectively produce 2H,8H-pyrano[2,3-f]chromen-4-phenyl-9-
Acknowledgments
carbonitriles after acidic hydrolysis.
Thanks are due to the University of Aveiro, Fundação para a
Ciência e a Tecnologia (FCT, Portugal), the European Union,
QREN, FEDER, COMPETE, for funding the Organic Chemistry
Research Unit (QOPNA) (project PEst-C/QUI/UI0062/2013),
and the Portuguese National NMR Network (RNRMN). The
authors also thank Pr. Kirsch Gilbert for HRMS analysis.
The hydrolysis of 4d in hydrochloric acid 4 N under micro-
wave irradiation (at 100 W for 4 min) yields the product 11.39
When the reaction time was extended to 15 min in the presence
hydrochloric acid 12 N, the product 1036 was again obtained in a
different manner (Scheme 3).
CH3
CH3
CH3
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CH3
(i)
HO
EtO
O
O
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H3C
O
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(i)
(E)-6
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C
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N
7
CN
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CH3
O
CH3
O
(iii)
(ii)
O
O
O
O
O
O
O
O
22.
23.
24.
O
HN
10
9
COOH
4c
CN
CN
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8-Formyl-7-hydroxy-4-methylcoumarin 2: Under classical heating
conditions, a solution of 7-hydroxy-4-methylcoumarin 1 (5 g, 0.03
mol) and hexamethylenetetramine (10 g, 0.09 mol) in glacial acetic
acid (40 mL) was refluxed for 8 h. The hexamine adduct so formed
was hydrolysed with 20% HCl (75 mL) and the solution was heated
for another 30 min at 70-80 °C. After cooling, the reaction solution
was extracted with diethyl ether. The ether layer was evaporated and
the pale yellow coloured solution was poured to crushed ice to get
3. Conclusion
This paper has given an account on different chemical trans-
formations of 8-formyl-7-hydroxy-4-methylcoumarin upon
treatment with the cyclic triacetic lactone or several acyclic ac-
tive methylene compounds. These organic reactions have led to
the production of a novel series of functionalized 2H,8H-
pyrano[2,3-f]chromene-2,8-dione scaffolds through a tandem
process of a Knoevenagel condensation and stereoselective in-
tramolecular translactonisation, transesterification or heterocycli-
sation. In this synthetic work, we have also presented an experi-
mental improvement in the formylation reaction of 7-hydroxy-4-
methylcoumarin by using microwave irradiation in a short reac-
tion time.
27.
28.
29.
30.

4
the pale yellow solid of 8-formyl-7-hydroxy-4-methylcoumarin 2
which was recrystallized from a mixture of ethanol and 1,4-dioxane.
This compound was obtained as pale yellow small crystal 2. Yield:
25%; mp.174-176 °C (mp 174-176 °C).28,29
36.
4-Methyl-2,8-dioxo-2H,8H-pyrano[2,3-f]chromene-9-carboxylic
acid 10: The solution of 4-methyl-2,8-dioxo-2H,8H-pyrano[2,3-
f]chromene-9-carbonitrile 9 (2.53 g, 0.01 mol) with acid HCl 12 N
(10 mL) was stirred about 15 min under MW irradiation at 300 W.
After reaction completion the precipitate was filtrated and washed
with water to afford a pure white product 10 (80%), mp. 287 °C; UV
(λ): 310 cm-1; IR ( , cm-1): 3150, 3086, 1785, 1715, 1621, 1376,
1291, 1117; 1H NMR (DMSO-d6): δ 2.48 (s, 3H, 4-CH3), 6.49 (s,
1H, H-3), 8.12 (d, 1H, J = 9.0 Hz, H-5), 7.44 (d, 1H, J = 9.0 Hz, H-
6), 8.78 (s, 1H, H-10); 13C NMR (DMSO-d6): δ 18.9 (4-CH3), 107.6
(C-10a), 112.8 (C-6), 113.8 (C-3), 116.1 (C-4a), 118.9 (C-9), 131.3
(C-5), 141.0 (C-10), 150.9 (C-10b), 154.0 (C-4), 156.0 (C-6a), 156.8
(C-8), 159.2 (C-2), 164.0 (9-COOH). MS (ESI+): m/z found for
31.
8-Formyl-7-hydroxy-4-methylcoumarin 2: Under microwave irradia-
tion, a solution of 7-hydroxy-4-methylcoumarin 1 (5 g, 0.03 mol)
and hexamethylenetetramine (10 g, 0.09 mol) in glacial acetic acid
(40 mL) was heated on MW irradiation at 300 W for 7 min. The
hexamine adduct so formed was hydrolysed with 20% HCl (75 mL)
and the solution was heated for another 4 min on MW irradiation at
200 W. After cooling, the reaction solution was extracted with di-
ethyl ether. The ether layer was evaporated and the pale yellow col-
oured solution was poured to crushed ice to get the pale yellow solid
of 8-formyl-7-hydroxy-4-methylcoumarin 2 which was recrystallized
from a mixture of ethanol and 1,4-dioxane. This compound was ob-
tained as pale yellow small crystal 2. Yield: 40%; mp.174-176 °C
(mp 174-176 C°).28,29
[C14H8O6]+· 272. Anal. Calcd. for C14H8O6: C 61.77, H 2.96. Found:
C 61.90, H 3.12%.
8-Imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-f]chromene-9-
37.
carboxylate
4d.
A
solution
of
8-formyl-7-hydroxy-4-
32.
4-Methyl-9-(3-oxobutanoyl)-2H,8H-pyrano[2,3-f]chromene-2,8-
dione 4a. A solution of 8-formyl-7-hydroxy-4-methylcoumarin-2-
one 2 (2.04 g, 0.01 mol) in toluene (10 mL) and 4-hydroxy-6-
methyl-2H-pyran-2-one 3a (1.26 g, 0.01 mol) in ethanol (10 mL)
with some drops of NEt3 as a catalyst was stirred at room tempera-
ture for 2 h. After reaction completion the precipitate was filtrated
and recrystallized from DMF. This compound was obtained as
yellow powder 4a. Yield: 70%; mp. 252 °C; UV (λ): 360 cm-1; IR
methylcoumarin-2-one 2 (2.04 g, 0.01 mol) and ethyl cyanoacetate
3d (1.131 g, 0.01 mol) in ethanol (10 mL) with piperidine (0.25 mL)
as a catalyst was stirred for about 2 h at room temperature. After re-
action completion the precipitate was filtrated and recrystallized
from ethanol to afford a pure pink product 4d. Yield: 80%; mp. 190
°C; UV (λ): 310 cm-1; IR ( , cm-1): 3321, 1740, 1628, 1391, 1274,
1121, 1021; 1H NMR (DMSO-d6): δ 1.38 (t, 3H, J = 7.2 Hz, 3H,
CH2CH3), 2.50 (s, 3H, 4-CH3), 4.41 (q, 2H, J =7.2 Hz, CH2CH3),
6.40 (s, 1H, 3-H), 7.36 (d, 1H, J = 9.0 Hz, H-6), 7.90 (d, 1H, J = 9.0
Hz, H-5), 8.90 (s, 1H, H-10), 9.60 (s, 1H, NH); 13C NMR (DMSO-
d6): 14.2 (CH2CH3), 18.9 (4-CH3), 62.2 (CH2CH3), 107.2 (C-10a),
112.5 (C-6), 113.4 (C-3), 115.2 (C-4a and C-9), 129.4 (C-5), 134.6
(C-10), 150.6 (C-10b), 152.5 (C-4), 156.4 (C-6a), 158.1 (C-8), 159.5
(C-2), 163.6 (CO2Et). HRMS (ESI+): m/z calcd for [C16H13NO5+H]+
300.0872, found: 300.0851. Anal. Calcd. for C16H13NO5: C 64.21, H
4.38, N 4.68. Found: C 64.41, H 4.44, N 4.85%.
(
, cm-1): 3433, 3057, 2923, 1739, 1618, 1091; 1H NMR (CDCl3): δ
2.29 (s, 3H, H-14), 2.50 (s, 3H, 4-CH3), 6.36 (s, 1H, H-3), 6.98 (s, H,
H-12, enol), 7.30 (d, 1H, J = 9.0 Hz, H-6), 7.84 (d, 1H, J = 9.0 Hz,
H-5), 9.20 (s, H, H-10), 15.70 (s, 1H, 13-OH); 13C NMR (CDCl3): δ
18.9 (4-CH3), 27.7 (C-14), 101.8 (C-12), 108.4 (C-10a), 112.5 (C-6),
114.4 (C-3), 115.9 (C-4a), 120.9 (C-9), 129.1 (C-5), 138.8 (C-10),
150.8 (C-10b), 152.0 (C-4), 155.8 (C-6a), 156.9 (C-8), 158.9 (C-2),
170.6 (C-11), 200.2 (C-13). HRMS (ESI+): m/z calcd for
[C17H12O6+Na]+ 335.0532, found: 335.0535. Anal. Calcd. for
C17H12O6: C 65.39, H 3.87. Found: C 65.43, H 4.02%.
38.
39.
Moskvina, V. S.; Khilya, V. P. Chem. Nat. Compd. 2008, 44, 16-23.
Ethyl
4-methyl-2,8-dioxo-2H,8H-pyrano[2,3-f]chromene-9-
33.
9-Acetyl-4-methyl-2H,8H-pyrano[2,3-f]chromene-2,8-dione 4b. A
carboxylate 11. A solution of ethyl 8-imino-4-methyl-2-oxo-2H,8H-
pyrano[2,3-f]chromene-9-carboxylate 4d (2.99 g, 0.01 mol) with
acid HCl 4 N (10 mL) was stirred about 9 min under MW irradiation
at 300 W. After reaction completion the precipitate was filtrated and
washed with water to afford pure product 11. Yield: 88%; mp. 255
°C; UV (λ): 305 cm-1; IR ( , cm-1): 3086, 1781, 1741, 1621, 1390,
1121, 1027; 1H NMR (DMSO-d6): δ 1.36 (t, 3H, J = 7.3 Hz,
CH2CH3), 2.48 (s, 3H, 4-CH3), 4. 35(q, 2H, J = 7.3 Hz, CH2CH3),
6.49 (s, 1H, H-3), 8.11 (d, 1H, J = 9.0 Hz, H-5), 7.44 (d, 1H J = 9.0
solution of 8-formyl-7-hydroxy-4-methylcoumarin-2-one 2 (2.04 g,
0.01 mol) and ethyl acetoacetate 3b (1.3 g, 0.01 mol) in ethanol (10
mL) with piperidine (0.25 mL) as a catalyst was stirred for about 2 h
at room temperature. After reaction completion the obtained solid
was filtrated and then crystallized from ethanol to afford pure prod-
uct, as a white solid 4b. Yield: 80%; mp. 249 °C; UV (λ): 308 cm-1;
IR ( , cm-1): 3086, 1748, 1721, 1681, 1628, 1390, 1293, 1107, 1023;
1H NMR (DMSO-d6): δ 2.48 (s, 3H, CH3), 2.50 (s, 3H, 4-CH3), 6.47
(s, 1H, H-3), 7.46 (d, 1H J = 9.0 Hz, H-6), 8.10 (d, 1H, J = 9.0 Hz,
H-5), 8.69 (s, 1H, H-10), 13C NMR (DMSO-d6): δ 18.9 (4-CH3), 30.6
(CH3), 107.8 (C-10a), 113.9 (C-6), 114.4 (C-3), 116.2 (C-4a), 124.8
(C-9), 131.5 (C-5), 139.8 (C-10), 151.2 (C-10b), 154.0 (C-4), 156.7
(C-6a), 158.2 (C-8), 159.1 (C-2), 195.0 (9-COCH3). HRMS (ESI+):
m/z calcd for [C15H10O5+Na]+ 293.0426, found: 293.0449. Anal.
Calcd. for C15H10O5: C 66.67, H 3.73. Found: C 66.80, H 3.83%.
8-Imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-f]chromene-9-
Hz, H-6), 8.77 (s, 1H, H-10); 13C NMR (DMSO-d6):
δ 14.0
(CH2CH3), 18.3 (4-CH3), 61.6 (CH2CH3), 106.8 (C-10a), 112.3 (C-
6), 113.3 (C-3), 115.6 (C-4a), 117.6 (C-9), 131.0 (C-5), 141.0 (C-
10), 150.3 (C-10b), 153.4 (C-4), 155.0 (C-6a), 156.1 (C-8), 158.5
(C-2), 161.9 (CO2Et). HRMS (ESI+): m/z calcd for [C16H12O6+Na]+
323.0532, found: 323.0543. Anal. Calcd. for C16H12O6: C 64.00, H
4.03. Found: C 64.20, H 4.12%.
34.
carbonitrile
4c:
A
solution
of
8-formyl-7-hydroxy-4-
methylcoumarin-2-one 2 (2.04 g, 0.01 mol) and malononitrile 3c
(0.66 g, 0.01 mol) in ethanol (10 mL) with piperidine (0.25 mL) as a
catalyst was stirred for about 2 h at room temperature. After reaction
completion the obtained precipitate was filtrated and crystallized
from ethanol to afford a pure pink product 4c. Yield: 80%; mp. 229
°C; UV, λ. 310 cm-1, IR ( , cm-1): 3357, 2943, 2191, 1739, 1618,
1381, 1274; 1H NMR (DMSO-d6): δ 2.58 (s, 3H, 4-CH3), 6.32 (s,
1H, H-3), 6.95 (d, 1H, J = 9.0 Hz, H-6), 7.77 (d, 1H, J = 9.0 Hz, H-
5), 8.10 (s, 1H, NH), 8.37 (s, 1H, H-10); 13C NMR (DMSO-d6): δ
18.9 (4-CH3), 103.0 (CN), 107.1 (C-10a), 113.1 (C-6), 114.4 (C-3
and C-4a), 116.0 (C-9), 132.0 (C-5), 146.0 (C-10), 150.0 (C-10b),
153.0 (C-4), 156.3 (C-6a), 158.0 (C-8 and C-2). HRMS (ESI+): m/z
calcd for [C14H8N2O3+Na]+ 275.0433, found: 275.0399. Anal. Calcd.
for C14H8N2O3: C 66.67, H 3.20, N 11.11. Found: C 66.44, H 3.07, N
11.20%.
35.
4-Methyl-2,8-dioxo-2H,8H-pyrano[2,3-f]chromene-9-carbonitrile 9:
The solution of 8-imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-
f]chromene-9-carbonitrile 4c (2.52 g, 0.01 mol) with acid HCl 4 N
(10 mL) was stirred under MW irradiation at 300 W for 9 min. After
reaction completion the precipitate was filtrated and washed with
water to afford a pure yellow product 9 (85%); mp. 272 °C; UV (λ):
310 cm-1; IR ( , cm-1): 3380, 2915, 2236, 1739, 1627, 1579, 1381,
1274, 1H NMR (DMSO-d6): δ 2.50 (s, 3H, 4-CH3), 6.51 (s, 1H, H-3),
8.166 (d, 1H, J = 9.0 Hz, H-5), 7.44 (d, 1H, J = 9.0 Hz, H-6), 9.15 (s,
1H, H-10); 13C NMR (DMSO-d6): δ 18.3 (4-CH3), 102.7 (CN), 107.0
(C-10a), 112.7 (C-6), 113.7 (C-3), 114.1 (C-4a), 116.1 (C-9), 131.8
(C-10), 146.5 (C-5), 149.9 (C-10b), 153.3 (C-4), 155.5 (C-6a), 156.2
(C-8), 158.3 (C-2). MS (ESI+): m/z found for [C14H7NO4]+ 253.00.
Anal. Calcd. for C14H7NO4: C 66.41, H 2.79, N 5.53. Found: C
66.50, H 2.81, N 5.66%.