A New, Highly Efficient and Green Protocol for the Synthesis of Pyranochromenes

Full text of DOI:10.1080/00304948.2020.1779003

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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A New, Highly Efficient and Green Protocol for the
Synthesis of Pyranochromenes
Leila Zare Fekri , Mohammad Nikpassand & Sakineh Pourmirzajani
To cite this article: Leila Zare Fekri , Mohammad Nikpassand & Sakineh Pourmirzajani (2020):
A New, Highly Efficient and Green Protocol for the Synthesis of Pyranochromenes, Organic
Preparations and Procedures International, DOI: 10.1080/00304948.2020.1779003
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2020.1779003
EXPERIMENTAL PAPER
A New, Highly Efficient and Green Protocol for the
Synthesis of Pyranochromenes
Leila Zare Fekria, Mohammad Nikpassandb, and Sakineh Pourmirzajania
b
aDepartment of Chemistry, Payame Noor University, Tehran, Iran; Department of Chemistry, Rasht
Branch, Islamic Azad University, Rasht, Iran
ARTICLE HISTORY Received 16 July 2019; Accepted 22 March 2020
Pyranochromenes make up a class of important heterocycles with a wide range of
pharmaceutical and biological properties such as anti-coagulant, spasmolytic, analgesic,
myorelaxant, anti-cancer, cytotoxic, anti-HIV, anti-microbial, anti-tuberculosis, diuretic,
and anti-anaphylactic activity.1–11 So far, only a few methods have been reported for the
synthesis of pyrano[3,2-c]chromen-5(4H)-ones.12–16
Ionic liquids (ILs) have attracted recent attention as green solvents and catalysts.
Their unique properties include non-flammability, non-volatility, desirable solubility
and polarity, as well as high thermal and chemical stabilities.17–19 Therefore, multi-com-
ponent reactions (MCRs) combined with IL assisted synthesis of pyranochromenes
could potentially reduce costs and the generation of by-products, shorten reaction times
and give higher yields. For these reasons and in continuation of our studies for the
green synthesis of organic materials,20–28 we now report our initial investigations on the
synthesis of pyrano[3,2-c]chromen-5(4H)-ones using the ionic liquid 1,4-diazabicy-
clo[2.2.2]octanium diacetate (DABCO-diacetate) in a multicomponent reaction.
The MCR of benzaldehydes, acetophenones and 4-hydroxycoumarin, simple in
nature, is essentially a condensation reaction. The reaction can be assisted by activating
the carbonyl group of aldehydes with an acidic species or by improving the nucleophilic
property of 4-hydroxycoumarin in basic media. We describe here the use of the acidic
bis-ionic liquid DABCO-diacetate as a green medium for the synthesis of pyrano[3,2-
c]chromen-5(4H)-ones (Scheme 1).
Initially, we observed that the reaction among 4-nitrobenzaldehyde, 4-hydroxycou-
marin and acetophene in the DABCO-diacetate could be a suitable choice for the syn-
thesis of pyranochromene 4b. This protocol proceeds smoothly at room temperature to
afford product 4b in fairly high yield. We have also carried out the sample reaction in
the neutral ionic liquids [BMIM]Br and [BMIM]BF4 or in the absence of ionic liquids.
It was interesting that the reaction did not occur in either of the above imidazolium
ionic liquids or in the absence of them, confirming the functional role of DABCO-diac-
etate in catalysis of the reaction. To optimize the amount of ionic liquid media for this
reaction, we performed the sample reaction using different quantities of the ionic liquid.
The best results were obtained with 0.5 mmol of bis-ionic liquid DABCO-diacetate per
CONTACT Leila Zare Fekri
chem_zare@yahoo.com
Department of Chemistry, Payame Noor University, P.O. Box
19395-3697, Tehran, Iran
ß 2020 Taylor & Francis Group, LLC

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L. ZARE FEKRI ET AL.
Scheme 1. Multicomponent synthesis of pyrano[3,2-c]chromen-5(4H)-ones using DABCO-diacetate.
1 mmol of substrate. Further, we reacted 4-nitrobenzaldehyde, acetophenone and
4-hydroxycoumarin in the presence of a catalytic amount of DABCO-diacetate at differ-
ent temperatures. By increasing the temperature to 80 ꢀC pyrano[3,2-c]chromen-5(4H)-
one 4b was obtained in 98%. The results are summarized in Table 1.
To check the generality of this method, various derivatives of benzaldehyde and ace-
tophenone were subjected to the reaction with 4-hydroxycoumarin. The results are sum-
marized in Table 2. Yields were uniformly high (mean 95%), and the reaction was
tolerant of a number of different substituent groups within the aromatic series explored.
All of the compounds synthesized were characterized by IR, NMR and elemental ana-
lysis and by comparison with authentic samples. Applications of the method to aliphatic
aldehydes and ketones may be the subject of future investigations.
1
The H NMR spectrum of 4b exhibited a chiral C-H moiety that resonated at 5.4 ppm.
3
Although this proton should appear as a doublet, it seems the J protons in this series of
compounds have an angle nearly 90ꢀ. For this reason, based on the Karplus curve, the cou-
pling between them is zero and this chiral C-H shows as a singlet.
We compared the efficiency of this method with recently reported methods (Table 3).
In conclusion, we have made a preliminary investigation of DABCO-diacetate as a
mild and efficient catalyst for the synthesis of pyrano[3,2-c]chromen-5(4H)-ones. This
method could be very useful from an industrial point of view because it is a high yield-
ing and time saving process. DABCO-diacetate is an inexpensive, non-toxic and easy-
handling green medium.
Experimental section
Melting points were measured on an Electrothermal 9100 apparatus. Chemicals were
1
purchased from Merck and Fluka and used as purchased. H NMR and 13C NMR spec-
tra were obtained on a Bruker DRX 500 Avance spectrometer in CDCl3 and DMSO-d6
as solvents and with TMS as internal standard. FT-IR spectra were recorded on a
Shimadzu FT-IR-8400S spectrometer. Elemental analyses were recorded on a Carlo-Erba

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
3
Table 1. Optimization of reaction conditions.
Entry
Catalyst
Catalyst amount
Reaction conditions
Time (min)
Yield (%)
1
2
3
4
5
6
7
–
–
Reflux in EtOH
Stir, rt
Stir, rt
Stir, rt
Stir, rt
720
720
720
25
40
25
–
11
7
86
81
87
98
[BMIM]Br
[BMIM]BF4
DABCO-diacetate
DABCO-diacetate
DABCO-diacetate
DABCO-diacetate
0.5 mmol
0.5 mmol
0.5 mmol
0.3 mmol
0.7 mmol
0.5 mmol
Stir, rt
Heat, 80 ꢀC
10
Table 2. Synthesis of pyrano[3,2-c]chromen-5(4H)-ones using DABCO-diacetate.
Entry
Product
Time (min)
Yield (%)a,b
Mp ꢀC, Found
Mp ꢀC, Reported
Ref.
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
10
10
15
12
15
10
10
15
10
10
95
98
93
95
90
94
95
93
97
96
123-124
230
167-169
166-167
142
238-240
190-192
152-154
179-180
145-147
122-123
230-231
165-166
170-171
143-144
239-241
189-190
150-152
176-177
149-151
14
13, 15
16
29,12–15
29, 16
12, 15
16
16
13, 14
12, 14
10
4j
aAll the isolated products were characterized on the basis of their physical properties and IR, 1H and 13C NMR spectral
analysis and by direct comparison with authentic materials.
bIsolated yields.
Table 3. Comparison of present method for the synthesis of 4d with some previous methods.
Entry
Condition
Time (min)
Yield (%)
Ref.
1
2
3
4
MWI, 60 ꢀC
15
50
360
240
92
98
78
92
29
I2, AcOH, 100 ꢀC
14a
15a
13a
AuCl3, AgOTf (3mol%), reflux
Ca(OTf)2, BuNPF6, 120 ꢀC
aThis pyranochromene was synthesized in a two step protocol: synthesis of the chalcone followed by reaction with
4-hydroxycoumarin.
EA1110CNNO-S analyzer. Thin layer chromatography (TLC) was carried out with ethyl
acetate: n-hexane 1:4 on TLC Silica gel 60 F254
.
Synthesis of ionic liquid DABCO-diacetate
20,21,23,24
This ionic liquid was synthesized as described by Zare Fekri, et al.
General procedure for preparation of pyrano[3,2-c]chromen-5(4H)-ones (4a-j)
A mixture of aldehyde (1.0 mmol), acetophenone derivative (1.0 mmol), 4-hydroxycou-
marin (1.0 mmol) and 0.5 mL of DABCO-diacetate was heated at 80 ꢀC for the required
reaction time according to Table 2. After completion of the reaction, as indicated by
TLC, the reaction mixture was placed in 20 mL of H2O. The product was separated by
filtration, recrystallized from EtOH and dried to afford powdery compounds 4a-j. The
fluid portion was dried in a vacuum evaporator to recover the ionic liquid for subse-
quent use. All of the synthesized compounds were characterized by their physical con-
stants, IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The

4
L. ZARE FEKRI ET AL.
pyranochromenes are known and were compared with authentic samples, matching
melting points (Table 2) and spectra. For the sake of completeness, some representative
data are provided below.
4-(3-Nitrophenyl)-2-phenylpyrano[3,2-c]chromen-5(4H)-one (4a)
White solid, mp 123-125 ꢀC, FT-IR: (cmꢁ1) 3077, 2938, 1707 (C ¼ O), 1613, 1510, 1495,
1
1388 (NO2), 1237 (C-O). H NMR (DMSO-d6): d 5.41 (s, 1H), 7.05-7.92 (m, 14H) ppm.
13C NMR (DMSO-d6): d 162.09, 154.75, 151.54, 147.87, 145.83, 142.49, 139.72, 137.63,
135.87, 130.29, 127.72, 121.92, 119.38, 119.03, 115.82, 114.72, 111.74, 111.62, 109.28,
105.65, 103.34, 34.34 ppm.
Anal. Calc for C24H15NO5: C, 72.54; H, 3.80; N, 3.52. Found: C, 72.51; H, 3.83;
N, 3.55.
4-(4-Nitrophenyl)-2-phenylpyrano[3,2-c]chromen-5(4H)-one (4b)
White solid, mp 228-230 ꢀC, FT-IR (cmꢁ1) 2918, 1663 (C ¼ O), 1600, 1523, 1356 (NO2),
1
1400, 1233 (C-O). H NMR (DMSO-d6): d 5.42 (s, 1H), 7.23-7.97 (m, 14H) ppm. 13C
NMR (DMSO-d6) d 162.24, 154.73, 151.38, 147.48, 145.27, 142.80, 139.48, 137.82,
133.72, 130.59, 121.62, 119.82, 116.04, 115.04, 111.19, 111.98, 109.54, 105.92,
103.60, 37.82 ppm.
Anal. Calc for C24H15NO5: C, 72.54; H, 3.80; N, 3.52. Found: C, 72.53; H, 3.81;
N, 3.54.
4-(4-Hydroxyphenyl)-2-phenylpyrano[3,2-c]chromen-5(4H)-one (4c)
White solid, mp 167-169 ꢀC, FT-IR (cmꢁ1) 3239, 3069, 2930, 1707 (C ¼ O), 1572, 1486,
1
1237 (C-O). H NMR (DMSO-d6) d 5.4 (s, 1H), 6.88-7.92 (m, 14H), 9.8 (s, 1H, phenolic
O-H) ppm. 13C NMR (DMSO-d6) d 160.48, 154.48, 151.58, 149.62, 143.64, 142.756,
139.05, 137.72, 133.83, 130.21, 121.97, 119.24, 116.50, 115.84, 111.37, 111.04, 109.72,
105.78, 103.56, 37.63 ppm.
Anal. Calc for C24H16O4: C, 78.25; H, 4.38. Found: C, 78.21; H, 4.40.
2,4-Diphenylpyrano[3,2-c]chromen-5(4H)-one (4d)
White solid, mp 166-168 ꢀC, FT-IR (cmꢁ1) 3099, 2987, 1665 (C ¼ O), 1609, 1487, 1234
(C-O). 1H NMR (DMSO-d6) d 5.41 (s, 1H), 6.78-7.64 (m, 15H) ppm. 13C NMR
(DMSO-d6) d 165.41, 153.98, 151.09, 147.16, 145.67, 145.12, 143.91, 142.09, 135.87,
128.14, 126.76, 121.45, 115.03, 114.78, 111.38, 111.13, 109.11, 105.21, 36.71ppm.
Anal. Calc for C24H16O3: C, 81.80; H, 4.58. Found: C, 81.81; H, 4.56.
4-(4-Methoxyphenyl)-2-phenylpyrano[3,2-c]chromen-5(4H)-one (4e)
White solid, mp 143-144 ꢀC, FT-IR (cmꢁ1) 2938, 1666 (C ¼ O), 1495, 1388, 1261 (C-O),
1
1102. H NMR (DMSO-d6) d 3.50 (s, 3H), 5.59 (s, 1H), 7.19-8.17 (m, 14H) ppm. 13C

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
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NMR (DMSO-d6) d 163.09, 153.49, 152.41, 151.87, 145.43, 145.63, 143.84, 142.38,
135.87, 129.87, 125.87, 123.74, 115.24, 114.62, 111.83, 111.27, 109.09, 105.82, 103.27,
54.58, 36.65 ppm.
Anal. Calc for C25H18O4: C, 78.52; H, 4.74. Found: C, 78.51; H, 4.71.
2,4-bis(4-Chlorophenyl)pyrano[3,2-c]chromen-5(4H)-one (4f)
White solid, mp 238-240 ꢀC, FT-IR (cmꢁ1) 2934, 1675 (C ¼ O), 1605, 1495, 1221 (C-O),
1
1098, 1016. H NMR (DMSO-d6) d 6.10 (s, 1H), 7.07-8.09 (m, 13H) ppm. 13C NMR
(DMSO-d6) d (ppm) 161.32, 152.32, 151.09, 148.38, 145.63, 143.63, 143.21, 142.40,
135.62, 129.04, 123.93, 123.29, 115.05, 113.49, 111.38, 111.06, 109.71, 105.47,
103.72, 36.80 ppm.
Anal. Calc for C24H14Cl2O3: C, 68.43; H, 3.35. Found: C, 68.41; H, 3.37.
4-(4-Chlorophenyl)-2-(3-nitrophenyl)pyrano[3,2-c]chromen-5(4H)-one (4g)
White solid, mp 189-190 ꢀC, FT-IR (cmꢁ1) 3065, 2934, 1667 (C ¼ O), 1609, 1572, 1392,
1
1245 (C-O), 1171 (C-Cl). H NMR (DMSO-d6) d 5.64 (s, 1H), 7.37-8.09 (m, 10H), 8.32
(s, 1H), 8.58 (s, 1H), 8.83 (s, 1H) ppm. 13C NMR (DMSO-d6) d 162.51, 154.05, 151.48,
147.72, 145.38, 144.93, 142.28, 139.85, 137.43, 133.72, 131.32, 130.04, 121.92, 119.61,
116.03, 115.41, 111.38, 111.39, 109.76, 105.48, 103.72, 36.29 ppm.
Anal. Calc for C24H14ClNO5: C, 66.75; H, 3.27; N, 3.24. Found: C, 66.71; H, 3.29;
N, 3.27.
2-(3-Nitrophenyl)-4-p-tolylpyrano[3,2-c]chromen-5(4H)-one (4h)
White solid, mp 152-154 ꢀC, FT-IR (cmꢁ1) 3089, 2922, 1675 (C ¼ O), 1604, 1527,1495,
1
1347, 1216 (C-O). H NMR (DMSO-d6) d 2.31 (s, 3H), 5.61 (s, 1H), 7.11-8.11 (m, 8H),
8.25 (d, J ¼ 8.2 Hz, 1H), 8.53-8.59 (m, 1H), 8.79 (s, 1H) ppm. 13C NMR (DMSO-d6) d
161.82, 154.21, 151.73, 147.59, 145.63, 142.72, 139.29, 137.68, 133.69, 133.28, 131.73,
130.28, 121.76, 119.98, 116.28, 113.87, 111.48, 111.49, 109.72, 105.78, 103.40,
37.58, 31.29 ppm.
Anal. Calc for C25H17NO5: C, 72.99; H, 4.16; N, 3.40. Found: C, 72.98; H, 4.19;
N, 3.41.
Acknowledgment
Financial support from the Research Council of Payame Noor University of Rasht and Roodsar
branch is sincerely acknowledged.
References
1. M. M. Heravi, B. Alimadadi Jani, F. Derikvand, F. F. Bamoharram, and H. A. Oskooie,
Catal. Commun., 10, 272 (2008). doi:10.1016/j.catcom.2008.08.023
2. L. Bonsignore, G. Loy, D. Secci, and A. Calignano, Eur. J. Med. Chem., 28, 517 (1993). doi:
10.1016/0223-5234(93)90020-F

6
L. ZARE FEKRI ET AL.
3. G. Cingolani, F. Gualtieri, and M. Pigini, J. Med. Chem. 12, 531 (1969). doi:10.1021/
jm00303a616
4. J. Y. –C. Wu, W. –F. Fong, J. –X. Zhang, C. –H. Leung, H. –L. Kwong, M. –S. Yang, D. Li,
and H. –Y. Cheung, Eur. J. Pharmacol., 473, 9 (2003). doi:10.1016/S0014-2999(03)01946-0
5. F. W. Perrella, S. –F. Chen, D. L. Behrens, R. F. Kaltenbach, and S. P. Seitz, J. Med. Chem.,
37, 2232 (1994). doi:10.1021/jm00040a016
6. N. R. Emmadi, K. Atmakur, G. K. Chityal, S. Pombala, and J. B. Nanubolu, Bioorg. Med.
Chem. Lett., 22, 7261 (2012). doi:10.1016/j.bmcl.2012.09.018
7. Y. Kashman, K. R. Gustafson, R. W. Fuller, J. H. Cardellina, J. B. Mcmahon, M. J. Currens,
R. W. Buckheit, S. H. Hughes, G. M. Cragg, and M. R. Boyd, J. Med. Chem., 35, 2735
(1992). doi:10.1021/jm00093a004
8. A. D. Patil, A. J. Freyer, D. S. Eggleston, R. C. Haltiwanger, M. F. Bean, P. B. Taylor, M. J.
Caranfa, A. L. Breen, and H. R. Bartus, J. Med. Chem., 36, 4131 (1993). doi:10.1021/
jm00078a001
9. D. C. Mungra, M. P. Patel, D. P. Rajani, and R. G. Patel, Eur. J. Med. Chem., 46, 4192
(2011). doi:10.1016/j.ejmech.2011.06.022
10. M. Zabradnik, “The Production and Application of Fluorescent Brightening Agents”, Vol.1,
p.15, John Wiley and Sons, New York, NY, 1992.
11. R. D. Murray, J. Mendez and S. A. Brown, “The Natural Coumarins: Occurrence, Chemistry
and Biochemistry”, Vol.7, p. 430, John Wiley and Sons, New York, NY, 1982.
12. M. Gohain, H. T. Johannes, and C. B. B. Barend, Tetrahedron Lett., 54, 3773 (2013). doi:10.
1016/j.tetlet.2013.05.008
13. Y. Srinivasarao, S. Pyare Lal, and G. Singh, Tetrahedron Lett., 56, 1649 (2015). doi:10.1016/j.
tetlet.2015.02.023
14. A. Naseem and B. Venkata Babu, Synth. Commun., 43, 3044 (2013). doi:10.1080/00397911.
2012.763099
15. L. Yunkui, Z. Jie, Q. Jianqiang, B. Jiang, and X. Zhenyuan, J. Org. Chem., 76, 9096 (2011).
doi:10.1021/jo201342m
16. L. Zare Fekri, M. Nikpassand, S. Pourmirzajani, and B. Aghazadeh, RSC Adv., 8, 22313
(2018). doi:10.1039/C8RA02572J
17. T. Welton, Chem. Rev., 99, 2071 (1999). doi:10.1021/cr980032t
18. M. Nikpassand, L. Zare Fekri, P. Farokhian, Synth. Commun., 45, 2303 (2015). doi:10.1080/
00397911.2015.1077256
19. L. Z. Fekri, M. Nikpassand, Russ. J. Gen. Chem., 84, 1825 (2014). doi:10.1134/S107036321409031X
20. L. Zare Fekri, M. Nikpassand, Lett. Org. Chem., 14, 494 (2017).
21. L. Z. Fekri, S. Sarhandi, E. Vessally, Acta. Chim. Slov., 65, 246 (2018). doi:10.17344/acsi.2017.
3723
22. M. Nikpassand, L. Zare Fekri, and S. Sanagou, Dyes. Pig., 136, 140 (2017). doi:10.1016/j.dye-
pig.2016.08.044
23. L. Z. Fekri and H. S. Fard, Acta. Chim. Slov. 63, 263 (2016).
24. L. Z. Fekri, M. Nikpassand, and R. Maleki, J. Mol. Liq., 222, 77 (2016). doi:10.1016/j.molliq.
2016.07.009
25. L. Zare, N. Mahmoodi, A.Yahyazadeh, M. Mamaghani, and K. Tabatabaeian, J. Heterocycl.
Chem., 48, 864 (2011). doi:10.1002/jhet.649
26. L. Z. Fekri and R. Maleki, J. Heterocycl. Chem., 54, 1167 (2017). doi:10.1002/jhet.2686
27. M. Nikpassand, L. Z. Fekri, M. Gharib, and O. Marvi, Lett. Org. Chem., 9, 745 (2012). doi:
10.2174/157017812803901917
28. M. Nikpassand, L. Zare, and M. R. Mousavi, Lett. Org. Chem., 9, 375 (2012). doi:10.2174/
157017812801264719
29. M. Veeranarayana Reddy, B. Siva Kumar, K. Taek Lim, B. Gwon Cho, and Y. Tae Jeong,
Tetrahedron Lett., 57, 476 (2016). doi:10.1016/j.tetlet.2015.12.061