CFL light promoted one-pot synthesis of pyrano[3,2-c]chromen-5(4H)-ones

Article abstract of DOI:10.1080/00397911.2018.1426101

An eco-friendly synthesis of pyrano[3,2-c]chromen-5(4H)-one derivatives was conducted by the condensation of 4-hydroxycoumarins, aromatic aldehydes, and acetophenones. Clean profile, excellent yield, ambient temperature, and use of visible light intensity

Full text of DOI:10.1080/00397911.2018.1426101

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
CFL light promoted one-pot synthesis of
pyrano[3,2-c]chromen-5(4H)-ones
Ankusab Noorahmadsab Nadaf & Kalegowda Shivashankar
To cite this article: Ankusab Noorahmadsab Nadaf & Kalegowda Shivashankar (2018): CFL light
promoted one-pot synthesis of pyrano[3,2-c]chromen-5(4H)-ones, Synthetic Communications, DOI:
10.1080/00397911.2018.1426101
To link to this article: https://doi.org/10.1080/00397911.2018.1426101
View supplementary material
Published online: 27 Feb 2018.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

SYNTHETIC COMMUNICATIONS®
https://doi.org/10.1080/00397911.2018.1426101
CFL light promoted one-pot synthesis of pyrano[3,2-c]
chromen-5(4H)-ones
Ankusab Noorahmadsab Nadaf and Kalegowda Shivashankar
P. G. Department of Chemistry, Bangalore University, Bangalore, Karnataka, India
ABSTRACT
ARTICLE HISTORY
Received 6 November 2017
An eco-friendly synthesis of pyrano[3,2-c]chromen-5(4H)-one
derivatives was conducted by the condensation of 4-hydroxycoumar-
ins, aromatic aldehydes, and acetophenones. Clean profile, excellent
yield, ambient temperature, and use of visible light intensity instead of
catalyst are the attractive features of this method.
KEYWORDS
CFL light; coumarins;
photoorganic;
pyranocoumarins; pyrans;
visible light
GRAPHICAL ABSTRACT
Introduction
Unique chemical,[1] biological,[2] and physical properties[3] associated with pyran derivatives
have found broad applications as agrochemical and drugs. Pyran derivatives are widespread
in nature. They are core skeletons in numerous natural products such as Frutinone A and
[4]
Frutinone C (Polygala fruticosa) and Isoethulia-coumarin C (Ethulia conyzoides) (Fig. 1).
[
5]
[6]
The presence of pyran architectures in nature with antimicrobial,
anticancer,
antidyslipidemic,[7] antihyperglycemic, anti-HIV, antioxidant,
[8]
[9]
[10]
antiallergic,
[11]
xan-
[
12]
[13]
thine oxidase inhibitory,
acetylcholinesterase, and butyrylcholinesterase inhibitory,
Src kinase inhibitory activities[14] made it a privileged structure.
Extensive research efforts have been focused on development of various strategies-
[
15,16]
for the synthesizing pyran derivatives. Few general methods are (i) one-pot
condensation of aromatic aldehydes, malanonitrile/ethylcyanoacetate, and α-hydroxy
[
17]
C–H acids
(ii) four-component reactions of arylamine, acetylenedicarboxylate,
[
18]
aromatic aldehydes, and cyclic 1,3-diketones
(iii) intramolecular alkoxycarbonylative
[
19]
annulation
(iv) one-pot synthesis of pyran-based heterocycles from benzyl halides as
Even though synthesis of pyran derivatives using variety of catalysts such
[
20]
key reagents.
[
21]
[22]
[23]
[24]
as ZnFe O ,
cellulose–perchloric acid,
meglumine,
gold(III),
nickel
2
4
CONTACT Kalegowda Shivashankar
shivashankark@gmail.com
P. G. Department of Chemistry, Central College
Campus, Bangalore University, Bangalore, Karnataka 560 001, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
©
2018 Taylor & Francis

2
A. N. NADAF AND K. SHIVASHANKAR
Figure 1. A few natural products embedded with pyranocoumarin core skeleton.
nanoparticles,[25] DBU,[26] Fe(HSO ) ,
[27]
Ce(SO ) .4H O,
[28]
and ionic liquid[29] have
4
3
4 2
2
made tremendous progress in the past years, this reaction still has limitations including
nongeneralization, use of excess amount of expensive catalysts, harsh reaction condition,
low yields, and long reaction time. Therefore, an ideal protocol would install the desired
pyran scaffolds in a time-efficient and one-pot procedure.
Results and discussion
Initially, 4-hydroxycoumarin (1a), 4-bromoacetophenone (2b), and 4-nitrobenzaldehyde
(
(
(
3f) were selected as model substrates for the reaction discovery and optimization
Scheme 1). When the model reaction was conducted under the visible light intensity
CFL, 20 W) in DMF at room temperature for 4h, the pyrano[3,2-c]chromen-5(4H)-
one (4f) was obtained in 50% yield. In the absence of visible light intensity, no reaction
was observed.
The effect of solvent on the reaction was examined and ethanol is the best choice. When
the model reaction was conducted in ethanol, 94% yield of (4f) was generated (Table 1).
Other solvents such as dioxane, THF, DMF, DMSO, acetonitrile, methanol, toluene, and
dichloromethane showed less reactivity providing (4f) in 42–78% yields. On varying the
visible light intensity from 8 to 32 W, the best yield of (4f) was obtained in 22 W at room
temperature.
With the optimal condition for the synthesis of pyranocoumarins on hand, we studied
the scope of this multicomponent process (Table 2). Various aromatic aldehydes and acet-
ophenones containing electron-donating and electron-withdrawing substituents at ortho,
Scheme 1. Synthesis of pyranocoumarin derivatives under visible light condition at ambient temperature.

SYNTHETIC COMMUNICATIONS®
3
Table 1. Optimization of visible light intensity and solvent screen for the synthesis of (4f).
Entry
Solvent
Visible light intensity (W)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Dioxane
THF
20
20
20
20
20
20
20
20
20
22
5.5
5
4.0
5.5
4
3.5
4.5
4.0
2.3
3
3.5
4.2
3
78
62
50
42
68
72
60
48
78
94
DMF
DMSO
Acetonitrile
Methanol
Toluene
2 2
CH Cl
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
10
11
12
13
15
8
32
77
43
89
Bold values represents the best results.
Table 2. Synthesis of pyranocoumarin derivatives under visible light condition.
No.
R
1
R
2
R
3
Product
Time (h)
Yield (%)
89
1
H
H
4a
3.0
2
3
H
H
4-Br
4-Br
4b
4c
3.4
3.3
88
87
4
5
H
H
4-Br
4-Br
4d
4e
3.5
3.3
90
92
6
7
H
H
4-Br
4-Br
4f
3.0
3.2
94
96
4g
8
9
H
H
3-CH
3
, 4-OH
4h
4i
3.5
3.4
92
96
2-Cl, 4-Cl
(Continued)

4
A. N. NADAF AND K. SHIVASHANKAR
Table 2. Continued.
No.
R
1
R
2
R
3
Product
Time (h)
3.2
Yield (%)
90
10
H
4-NO
2
4j
1
1
2
H
2-NO
3-NO
2
2
4k
4l
3.3
3.2
90
91
1
Cl
1
3
4
Cl
Cl
3-NO
2
4m
4n
3.0
3.2
89
91
1
2-Cl, 4-Cl
meta, and para positions exhibited equal ease towards the product formation in excellent
yields ranging from 87 to 96%. Heteroaromatic aldehydes such as imidazole and indole
could also be accepted in the reaction. 5-Chloro-4-hydroxycoumarin was applied in the
reaction instead of 4-hydroxycoumarin that successfully led to the corresponding pyrano
[
3,2-c]chromen-5(4H)-ones in high yields.
On the basis of the above mentioned experimental results, a plausible reaction mech-
anism (Scheme 2) is proposed for the formation of pyranocoumarin derivatives.[30–34]
Aldehydes (3a–j) undergo condensation with acetophenones (2a–i) to afford a chalcones.
Michael addition of 4-hydroxycoumarins (1a–b) with chalcones produces the intermediate
that on intramolecular cyclization gives the pyranocoumarins (4a–n).
To know, whether the reaction takes place in a radical pathway or ionic pathway, the
same model reaction was performed in the presence of hydroquinone which is a radical
[
35]
inhibitor.
The result indicated that only a trace amount of (4f) was produced. This
experiment clearly demonstrated that the reaction proceeds in a radical pathway.
Conclusion
In conclusion, we have developed a one-pot methodology for the efficient synthesis of
pyranocoumarin derivatives under visible light condition. Excellent yields, easy workup,
ambient temperature, and short reaction time are the key advantages of this protocol.
General information
The melting points were determined using electric melting point apparatus with a
1
calibrated thermometer. H -NMR spectra were recorded using a Bruker/Jeol spectro-
1
3
photometer operating at 400 MHz and C -NMR spectra were recorded at 100 MHz.
The spectra were measured in CDCl /DMSO-d relative to tetramethylsilane (TMS)
3
6
(0.00 ppm). HRMS spectra were recorded using Waters Model: Synapt G2. The elemental

SYNTHETIC COMMUNICATIONS®
5
Scheme 2. Proposed radical pathway for the formation of pyranocoumarin derivatives under visible
light condition.
analyses were determined on Elemental Vario Micro Cube CHN Rapid Analyzer. CFL
bulbs manufactured by Philips company were used for reaction conditions.
Typical procedure for the synthesis of 2-(phenyl)-4-(phenyl)pyrano[3,2-c]
chromen-5(4H)-one (4a)
A 100 ml beaker was charged with 4-hydroxycoumarin (1a) (1 mmol), acetophenone (2a)
(
1 mmol) and benzaldehyde (3a) (1 mmol) in ethanol (10 mL). A glowing CFL bulb (22 W)
was put inside the beaker but above the surface of the reaction mixture that was stirred
under ambient condition for 3 h. The reaction progress and completion were monitored
by TLC (Eluent: EtoAc and n-hexane). The organic layer was concentrated under reduce
pressure. The residue was purified by recrystallization.
2
-(Phenyl)-4-(phenyl)pyrano[3,2-c]chromen-5(4H)-one (4a)
1
A white solid, 313.3778 mg (89% yield). Mp 176–178 °C. H NMR (DMSO-d 400 MHz): δ
6
13
6
.30 (s, 1H, CH) 7.07–7.84 (m, 15H, 14Ar-H & 1 Pyran-H) ppm. C NMR (CDCl 100 MHz):
3
δ 62.1, 110.7, 111.0, 116.7, 122.3, 123.3, 123.5, 124.1, 124.5, 125.1, 129.0, 129.2, 129.5, 130.1,
1
32.6, 138.2, 144.0, 144.2, 144.5, 144.7, 155.7, 155.9 (2C), 168.9 ppm. HRMS: [M] ¼ m/z
3
53.1645; Anal. Calcd for C H O : C, 81.80; H, 4.58; found: C, 81.60; H, 4.55%.
24 16 3

6
A. N. NADAF AND K. SHIVASHANKAR
Associated content
Supporting information
1H NMR, 13C NMR, HRMS spectra, elemental analyses data, and experimental details for
the compounds (4b-n).
Funding
This work is generously supported by the Department of Science and Technology-Science and
Engineering Research Board (DST-SERB), New Delhi, India under the Fast Track Young Scientist
Scheme (Grant No: SB/FT/CS-028/2013 dated: 09.06.2014, 24.09.2015, and 12.09.2016) in the form
of major research project.
References
[
[
[
1] Vekariya, R. H.; Patel, H. D. Synth. Commun. 2014, 44, 2756.
2] Dar, A. M.; Shamsuzzaman. Eur. Chem. Bull. 2015, 4, 249.
3] Kaur, C.; Dhiman, S.; Singh, H.; Kaur, M.; Bhagat, S.; Gupta, M.; Sharma, S.; Bedi, P. M. S.
Asian J. Biochem. Pharm. Res. 2015, 7, 127.
[
[
[
4] Murray, R. D. H. Fortchemie 1991, 35, 1.
5] Makawana, J. A.; Patel, M. P.; Patel, R. G. Arch. Pharm. Chem. Life Sci. 2012, 345, 314.
6] Emmadi, N. R.; Atmakur, K.; Chityal, G. K.; Pombala, S. J.; Nanubolu, B. Bioorg. Med. Chem.
Lett. 2012, 22, 7261.
[
7] Kumar, A.; Maurya, R. A.; Sharma, S. A.; Ahmad, P.; Singh, A. B.; Bhatia, G.; Srivastava, A. K.
Bioorg. Med. Chem. Lett. 2009, 19, 6447.
[
[
8] Wang, H.; Lu, J.; Zhang, Z. Monatsh Chem. 2010, 141, 1107.
9] Mansoor, S. S.; Logaiya, K.; Aswin, K.; Sudhan, P. N. J. Taibah Univ. Sci. 2015, 9, 213.
[
[
[
[
[
10] Symeonidis, T.; Chamilos, M.; Litina, D. J. H.; Kallitsakis, M.; Litinas, K. E. Bioorg. Med. Chem.
Lett. 2009, 19, 1139.
11] Coudert, P.; Couquelet, J. M.; Bastide, J.; Marion, Y.; Fialip, J. Ann. Pharm. Fr.
1
988, 46, 91.
12] Kaur, R.; Naaz, F.; Bedi, P. M. S.; Sharma, S.; Nepali, K.; Mehndiratta, S.; Gupta, M. K. Med.
Chem. Res. 2015, 24, 3334.
13] Khoobi, M.; Alipour, M.; Sakhteman, A.; Nadri, H.; Moradi, A.; Emami, S.; Foroumadi, A.;
Shafiee, A. Eur. J. Med. Chem. 2013, 68, 260.
14] Rafinejad, A.; Fallah-Tafti, A.; Tiwari, R.; Shirazi, A. N.; Mandal, D.; Shafiee, A.; Parang, K.;
Foroumadi, A.; Akbarzadeh, T. DARU J. Pharm. Sci. 2012, 20, 1.
[
[
15] Gu, Y.; Jerome, F. Chem. Soc. Rev. 2013, 42, 9550.
16] Virdi, H. S.; Sharma, S.; Mehndiratta, S; Bedi, P. M. S.; Nepali, K. J. Enzyme Inhib. Med. Chem.
2
015, 30, 730.
[
[
[
[
[
[
[
17] Shaterian, H. R.; Honarmand, M. Synth. Commun. 2011, 41, 3573.
18] Sun, J.; Xia, E. Y.; Wu, Q.; Yan, C. G. ACS Comb. Sci. 2011, 13, 421.
19] Li, Z.; Gao, Y.; Jiao, Z.; Wu, N.; Wang, D. Z.; Yang, Z. Org. Lett. 2008, 10, 5163.
20] Beerappa, M.; Shivashankar, K. RSC Adv. 2015, 5, 30364.
21] Das, P.; Dutta, A.; Bhaumikb, A.; Mukhopadhyay, C. Green Chem. 2014, 16, 1426.
22] Khan, T.; Siddiqui, Z. N. New J. Chem. 2014, 38, 4847.
23] Guo, R. Y.; An, Z. M.; Mo, L. P.; Wang, R. Z.; Liu, H. X.; Wang, S. X.; Zhang, Z. H. ACS Comb.
Sci. 2013, 15, 557.
[
[
[
[
24] Liu, Y.; Zhu, J.; Qian, J.; Jiang, B.; Xu, Z. J. Org. Chem. 2011, 76, 9096.
25] Khurana, J. M.; Vij, K. Synth. Commun. 2013, 14, 2294.
26] Saluja, P.; Aggarwal, K.; Khurana, J. M. Synth. Commun. 2013, 43, 3239.
27] Eshghi, H.; Damavandi, S.; Zohuri, G. H. Synth. React. Inorg. Met.-Org. Chem. 2011,
41, 1067.

SYNTHETIC COMMUNICATIONS®
7
[
[
[
[
[
28] Islami, M. R.; Mosaddegh, E. Phosphorus Sulfur Silicon 2009, 184, 3134.
29] Wen, L. R.; Xie, H. Y.; Li, M. J. Heterocycl. Chem. 2009, 46, 954.
30] Haas, Y. Photochem. Photobiol. Sci. 2004, 3, 6.
31] Hoffmann, N. Chem. Rev. 2008, 108, 1052.
32] Tiwari, J.; Saquib, M.; Singh, S.; Tufail, F.; Singh, M.; Singh, J.; Singh, J. Green Chem. 2016, 18,
3
221.
[
[
[
33] Hari, D. P.; Konig, B. Org. Lett. 2011, 13, 3852.
34] Yadav, S.; Srivastava, M.; Rai, P.; Singh, J.; Tiwari, K. P.; Singh, J. New J. Chem. 2015, 39, 4556.
35] Zhang, M.; Fu, Q. Y.; Gao, G.; He, H. Y.; Zhang, Y.; Wu, Y. S.; Zhang, Z. H. ACS Sustainable
Chem. Eng. 2017, 5, 6175.