Synthesis of 14H-dibenzo xanthene derivatives using choline chloride/tin(II) chloride deep eutectic solvent and Fe3O4/?-carrageenan/Zn(II)

Article abstract of DOI:10.1007/s13738-016-0965-0

In this study, various xanthene derivatives have prepared efficiently through a simple method using choline chloride/tin(II) chloride (ChCl·2SnCl₂) deep eutectic solvent (DES), alone, or in the presence of Fe₃O₄/?-carragee

Full text of DOI:10.1007/s13738-016-0965-0

J IRAN CHEM SOC
DOI 10.1007/s13738-016-0965-0
ORIGINAL PAPER
Synthesis of 14H‑dibenzo xanthene derivatives using choline
chloride/tin(II) chloride deep eutectic solvent
and Fe3O4/ƛ‑carrageenan/Zn(II)
Dana Shahabi1 · Hossein Tavakol1
Received: 15 May 2016 / Accepted: 11 August 2016
© Iranian Chemical Society 2016
Abstract In this study, various xanthene derivatives have
prepared efficiently through a simple method using cho-
line chloride/tin(II) chloride (ChCl·2SnCl2) deep eutec-
tic solvent (DES), alone, or in the presence of Fe3O4/ƛ-
carrageenan/Zn(II) magnetic bionanocatalyst. In the
employed procedure, 2-naphthol derivatives have mixed
with aromatic or aliphatic aldehydes and the reactions have
been completed in the presence of DES at 90 °C in 1.5 h.
In addition, using DES/Fe3O4/ƛ-carrageenan/Zn(II), the
reaction time was reduced to 30 min. The employed DES
has been recycled four times without important loss of its
activity.
attention has been focused on developing different methods
for the synthesis of xanthene derivatives in the past dec-
ades. By reviewing the literatures, various methods, such as
cycloacylation of carbamates [8], trapping of benzynes by
phenols [9], condensation reaction between aryl oxymag-
nesium halides and triethyl ortho formate [10], reaction of
2-hydroxyaryl aldehydes with 2-tetralone [11], and many
other reaction [12–16], have been reported for the synthesis
of xanthene derivatives. Moreover, in these reactions, vari-
ous catalysts have been developed, such as p-toluene sul-
fonic acid [17], molecular iodine [18], K5CoW12O40 [19],
LiBr under microwave irradiation [20], amberlyst-15 [21],
cation-exchange resins [22], silica sulfuric acid [23], sul-
famic acid [24], AcOH-H2SO4 [25], silica perchloric acid
[26], heteropoly acids [27], cyanuric chloride [28], BF3.
SiO2 [29], Yb(OTf)3 [30], In(OTf)3 [31], P2O5/Al2O3 [32],
and Bu4NBr under microwave irradiation [33]. However,
the most of these methods suffer at least from one of some
disadvantages, such as a long reaction time, expensive
reagents, use of toxic solvents or catalysts, harsh reaction
conditions, environmental problems, undesirable wastes,
unsatisfactory yield, non-recyclable catalyst, and tedious
work-up procedures. Therefore, the synthesis of this class
of heterocyclic compounds is particularly significant for
researchers and in continuation of our previous works on
the use of DES in the synthesis of important compounds
[34–38], we have decided to develop a new method for syn-
thesis of xanthene derivatives.
Keywords Condensation · DES · Nanocomposite ·
Catalyst · Xanthene
Introduction
Xanthene derivatives are important organic compounds,
because they exhibit useful biological activities, such as
antibacterial [1], anti-inflammatory [2], and antiviral activi-
ties [3]. In addition, these compounds have widely been
used in the laser technology [4], functional materials for
visualization of biomolecular assemblies [5], photody-
namic therapy [6], and as antagonists [7]. Therefore, much
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-016-0965-0) contains supplementary
material, which is available to authorized users.
In this report, we hope to present a simple and efficient
method for the synthesis of xanthene derivatives by the
reaction between 2-naphthols and aromatic or aliphatic
aldehydes in the presence of DES, alone, or in the presence
of Fe3O4/ƛ-carrageenan/Zn(II) nanocatalyst. The proce-
dure of this synthesis and the obtained results will be dis-
cussed in the following sections.
* Hossein Tavakol
H_tavakol@cc.iut.ac.ir; h_tavakol@yahoo.com
1
Department of Chemistry, Isfahan University of Technology,
Isfahan 84156-83111, Iran
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R1
R1
R2
O
OH
Catalyst
2
R2
H
Optimized conditions
R1
O
1 (R=H, Br)
2
3a-3s
Scheme 1 General reaction for the synthesis of xanthene derivatives
Table 1 Optimization of reaction conditions for the model reaction
chloride with 1:2 ratio was heated with stirring until a clear
and colorless liquid was obtained.
Entry Cat. type
Cat (mol%) T (°C) Time (h) Yield (%)a
1
ChCl·2SnCl2 20
r.t.
60
90
90
90
90
120
90
90
90
90
90
5
0
20
25
45
94
94
94
94
94
96
35
67
Preparation of Fe3O4/ƛ‑carrageenan/Zn(II)
2
ChCl·2SnCl2 20
ChCl·2SnCl2 20
ChCl·2SnCl2 20
ChCl·2SnCl2 20
ChCl·2SnCl2 20
ChCl·2SnCl2 20
ChCl·2SnCl2 15
ChCl·2SnCl2 10
2
3
30 min
1
Fe3O4 nanoparticles were prepared by chemical co-pre-
cipitation of 2:1 of a molar ratio of FeCl3·6H2O (1 g) and
FeSO4·6H2O (0.65 g). Both iron salts were dissolved in
50 mL of deionized water and stirred to produce a clear
solution. This solution has been sonicated for 30 min.
Then, NH4OH solution (25 %) was added to the solution.
When the pH of the solution was reached to 10, a dark
solution was appeared, indicating the formation of mag-
netic nanoparticles. The solution was allowed to stir at
80 °C under N2 atmosphere for 2 h and the nanomagnetite
was separated by a magnet, washed with water and ace-
tone, and dried by air. Then, ƛ-carrageenan (0.25 g) was
dissolved into 50 mL of distilled water to get the homog-
enous solution, magnetite nanoparticles were added,
and the solution was stirred for 18 h at room tempera-
ture. The resulting coated nanomagnetite was separated
by a magnet, washed with water and acetone, and dried
by air. Finally, Fe3O4/ƛ-carrageenan (1 g) was added to
25 mL aqueous solution of ZnCl2·6 H2O (0.5 g) and the
mixture was gently stirred at room temperature for 24 h.
The resulting catalyst (Fe3O4/ƛ-carrageenan/Zn(II)) was
separated using external magnet, washed with water and
acetone, and dried by air. All characterization analyses on
this catalyst have been reported by our group in another
manuscript.
4
5
1.5
2
6
7
2
8
1.5
1.5
1.5
1.5
1.5
9
10
11
12
ChCl·2SnCl2
ChCl·2ZnCl2 20
ChCl·2Urea 20
5
The model reaction: 2-naphthol (2 mmol), benzaldehyde (1 mmol)
a
Isolated yield
Table 2 Optimization of reaction conditions for the model reaction
Entry Fe3O4/ƛ-Carrageenan/
T (°C) Time (min) Yield (%)a
Zn(II) (g)
1
2
3
4
5
6
0.1
r.t
120
30
30
30
30
30
0
35
96
75
60
50
0.1
60
90
120
90
90
0.1
0.1
0.05
0.01
The model reaction: 2-naphthol (2 mmol), benzaldehyde (1 mmol) in
the presence of DES (5 mol%)
a
General procedure for the synthesis of xanthene
derivatives
Isolated yield
2-Naphthol derivatives (2 mmol), aromatic or aliphatic
aldehyde (1 mmol), and ChCl·2SnCl2 (5 mol%) (in
some reactions, in the presence of 0.1 g of Fe3O4/ƛ-
carrageenan/Zn(II)) were mixed in a 25 mL round-bottom
flask equipped with a condenser on the top. The reac-
tion mixture has been stirred for 30 min, and during stir-
ring, it was warmed slowly on the oil bath to 90 °C. The
progress of the reaction was monitored by TLC (eluent
phase = n-hexane:EtOAc = 3:1). After completion of the
Experimental
Chemicals were purchased from Merckand Sigma-Aldrich
companies. Melting points were measured using Gallen
Kamp melting point instrument. IR spectra were recorded
1
with KBr pellets on JASCO FT-IR spectrophotometers. H
and 13C NMR spectra were recorded on a Bruker Ultrash-
ield 400 MHz spectrometer in CDCl3 solution. To prepare
the employed DES, a mixture of choline chloride/tin (II)
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J IRAN CHEM SOC
reaction, the mixture was diluted with water (5 mL) and
Et2O (2 × 5 mL) and shaken vigorously. The nanomagnetic
catalyst was separated with magnet. The organic layer was
separated from the aqueous layer (consisted of DES) by
simple liquid–liquid extraction. The deep eutectic solvent
was dried at 60–70 °C to remove water and reused. The
organic layer was dried over MgSO4 and its solvent was
evaporated. The crude product was recrystallized in etha-
nol to give the pure product. All products were known com-
pounds and their physical and spectroscopic data (mp, IR,
Table 3 Results for the
R1
R2
Product
Yield (%)a
96
mp (°C)
181–183
References
[39]
synthesis of xanthene
derivatives at optimized
conditions
a
b
c
d
H
C6H5
O
H
H
H
2-Cl–C6H4
3-Cl–C6H4
4-Cl–C6H4
90
91
96
213–215
209–211
290–292
[40]
[41]
[40]
Cl
O
Cl
O
Cl
O
e
H
3-NO2–C6H4
84
213–215
[40]
NO2
O
f
H
4-NO2–C6H4
85
310–312
[39]
NO2
O
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J IRAN CHEM SOC
Table 3 continued
R1
R2
Product
Yield (%)a
75
mp (°C)
239–240
References
[39]
g
H
4-CH3–C6H4
CH3
O
h
H
4-OCH3-C6H4
85
203–205
[40]
OCH3
O
i
H
C4H9
60
109–113
[42]
O
J
H
C5H11
63
102–104
[42]
O
O
O
k
Br
Br
Br
C6H5
88
85
81
247–250
218–220
266
[42]
[42]
[42]
Br
Br
l
2-Cl–C6H4
Cl
Br
Br
m
3-Cl–C6H4
Cl
Br
Br
O
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J IRAN CHEM SOC
Table 3 continued
R1
R2
Product
Yield (%)a
92
mp (°C)
296–299
References
[42]
n
Br
4-Cl–C6H4
Cl
O
Br
Br
o
Br
3-NO2–C6H4
80
159–161
[42]
NO2
Br
Br
Br
Br
O
p
Br
4-NO2–C6H4
81
303–305
[42]
NO2
Br
O
q
Br
4-CH3–C6H4
70
247–251
[42]
CH3
Br
O
r
Br
C4H9
58
138–140
[42]
Br
Br
O
s
Br
C5H11
56
Liquid
[42]
Br
Br
O
a
Isolated yield
1H NMR, 13C NMR) were compared with those of authen-
tic samples in the references [39–42]. The physical and
spectroscopic data for selected compounds are as follows.
14‑(4‑Chlorophenyl)‑14H‑dibenzo‑[a,j]‑xanthenes (3d) White
solid, mp = 295 °C, FT-IR (KBr): νmax (cm−1) = 3066, 1620,
1
1590, 1514, 1483, 1456, 1430, 1242, 1082, 960, 807, 743. H
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J IRAN CHEM SOC
N
SnCl3
O
H
O
OH
Fe3O4/lambda-Carrageenan/Zn2+
OH
R
H
R
H
OH
-H2O
-H
R
OH
H
OH
R
H
OH
OH
O
R
H
-H
HO
R
H H
O
-H2O
R
OH2
SnCl3
H
OH
OH
O
N
Scheme 2 Proposed mechanism for the synthesis of xanthenes catalyzed by ChCl·2SnCl2/Fe3O4/ƛ-carrageenan/Zn(II)
Table 4 Result of the reusability of the DES in the model reaction
νmax (cm−1) = 3071, 1590, 1509, 1458, 1398, 1248, 960,
1
809, 742. H NMR (400 MHz, CDCl3): δ (ppm) = 8.29
Entry
Cycle
Yield (%)
(d, 2H, J = 8 Hz), 7.73 (d, 2H,J = 8 Hz), 7.68 (d, 2H,
J = 8 Hz), 7.50 (t, 2H, J = 8 Hz), 7.30–7.46 (m, 6H), 6.57
(d, 2H, J = 8 Hz), 6.35 (s, 1H), 3.51 (s, 3H). 13C NMR
(125 MHz, CDCl3): δ (ppm) = 157.8, 148.7, 137.4, 131.4,
131.1, 129.2, 128.8, 128.7, 126.8, 124.2, 122.7, 118.0,
117.5, 113.8, 55.1, 37.1. Elemental analysis for C28H20O2:
C 86.60, H 5.15; found: C 82.03, H 4.54.
1
2
3
4
1st run
2nd run
3nd run
4nd run
94
90
89
86
NMR (400 MHz, CDCl3): δ (ppm) = 8.21 (d, 2H, J = 8 Hz),
7.75 (d, 2H, J = 8 Hz), 7.71 (d, 2H, J = 8 Hz),7.49 (t, 2H,
J = 8 Hz), 7.31–7.40 (m, 6H), 7.01 (d, 2H, J = 8 Hz), 6.37 (s,
1H).13C NMR (125 MHz, CDCl3): δ (ppm) = 148.7, 143.5,
131.3, 131.3, 131.1, 129.5, 129.1, 128.91, 128.6, 126.9, 124.4,
122.4, 118.0, 116.8, 37.4. Elemental analysis for C27H17OCl: C
82.56, H 4.33; found: C 81.80, H 3.82.
Results and discussion
Initially, we chose the model reaction between 2-naphthol
and benzaldehyde in the presence of catalyst (DES or DES
and nanomagnetic) to optimize the reaction parameters and
obtain the best conditions (Scheme 1).
Different reaction conditions, such as the type of DES
(ChCl·2SnCl2, ChCl·2ZnCl2 and ChCl·2Urea), the amount
of DES (5, 10, 15 and 20 mol%), reaction temperature (r.t,
14‑(4‑Methoxyphenyl)‑14H‑dibenzo‑[a.j]‑xanthene
(3h) Light pink solid, mp = 203–205 °C, FT-IR (KBr):
1 3

J IRAN CHEM SOC
60, 90, 120 °C), and the reaction time (15 min, 0.5, 1, 1.5,
2, 5 h), have employed to obtain the best reaction condi-
tions. The results were listed in Table 1 which showed that
the best yield of the product has observed in the reaction
at 90 °C in the presence of 5 mol% ChCl·2SnCl2 at 1.5 h.
Moreover, to determine the catalytic or synergic effect of
the prepared bionanocatalyst, different values of this cata-
lyst were added to the reaction at its optimized conditions
(Table 2) and the reaction time and its temperature has
reoptimized. The results showed that this catalyst reduces
the reaction time to 30 min.
The optimized conditions were employed for the syn-
thesis of other xanthene derivatives to show the versatil-
ity of this method. The details of these experiments were
shown in Table 3. According to this table, various aromatic
aldehydes-containing electron withdrawing and electron-
donating groups at different positions have used in addition
to the use of 2-naphthol and 6-bromo-2-naphthol as another
reactant.
References
1. A.N. Dadhania, V.K. Patel, D.K. Raval, C. R. Chim. 15, 378
(2012)
2. J.P. Poupelin, G.S. Ruf, O.F. Blanpin, G. Narcisse, G.U. Ernouf,
R. Lacroix, Eur. J. Med. Chem. 9, 67 (1978)
3. R. Tayebee, S. Tizabi, Chin. J. Catal. 33, 962 (2012)
4. S.M. Menchen, S.C. Benson, J.Y.L. Lam, W. Zhen, D. Sun,
B.B. Rosenblum, S.H. Khan, M. Taing, Tetrahedron Lett. 6, 583
(2003)
5. A. Bekaert, J. Andrieux, M. Plat, Tetrahedron Lett. 33, 2805
(1992)
6. R.M. Ion, D. Frackowiak, A. Planner, K. Wiktorowicz, Acta Bio-
chim. Pol. 45, 833 (1998)
7. G. Saint-Ruf, H.T. Hieu, J.P. Poupelin, Naturwissenschaen 62,
584 (1975)
8. D. Quintas, A. Garcia, D. Dominguez, Tetrahedron Lett. 44,
9291 (2003)
9. D.W. Knight, P.B. Little, J. Chem. Soc. 14, 1771 (2001)
10. G. Casiraghi, G. Casnati, M. Cornia, Tetrahedron Lett. 14, 679
(1973)
11. A. Jha, J. Beal, Tetrahedron Lett. 45, 8999 (2004)
12. T.S. Rivera, M.N. Blanco, L.R. Pizzio, G.P. Romanelli, Green
Chem. Lett. Rev. 5, 433 (2012)
The obtained yields show that the reactions with 2-naph-
tol have higher yields than those of 6-bromo-2-naphtol.
In addition, aromatic aldehydes give more yields than
aliphatic aldehydes and the best yields (96 %) have been
observed in the reaction of 2-naphtol with benzaldehyde
or 4-chlorobenzaldehyde. The role of employed catalyst is
shown in the proposed mechanism, in Scheme 2.
13. F. Shirini, M. Abedini, S. Akbari-Dadamahaleh, A. Rahmaninia,
J. Iran. Chem. Soc. 11, 791 (2014)
14. F. Shirini, M. Mamaghani, S.V. Atghia, J. Iran. Chem. Soc. 10,
415 (2013)
15. A. Khalafi-Nezhad, F. Panahi, S. Mohammadi, H.O. Foroughi, J.
Iran. Chem. Soc. 10, 189 (2013)
16. B. Maleki, S. Barzegar, Z. Sepehr, M. Kermanian, R. Tayebee, J.
Iran. Chem. Soc. 9, 757 (2012)
17. A.R. Khosropour, M.M. Khodaei, H. Moghannian, Synlett 6,
955 (2005)
18. B. Das, B. Ravikanth, R. Ramu, K. Laxminarayana, B.V. Rao, J.
Mol. Catal. A Chem. 55, 74 (2006)
19. L. Nagarapu, S. Kantevari, V.C. Mahankhali, Catal. Commun. 8,
1173 (2007)
20. A. Saini, S. Kumar, J.S. Sandhu, Synlett 12, 1928 (2006)
21. S. Ko, C.F. Yao, Tetrahedron Lett. 47, 8827 (2006)
22. B. Patil, R.P. Bhat, S.D. Samant, Synth. Commun. 36, 2163
(2006)
At the final step of this study, the reusability of the
employed DES has been explored in the model reaction.
The result were listed in Table 4 which showed that the
employed DES could be reused at least four times without
any significant loss in the yield.
Conclusion
23. H.R. Shaterian, M. Ghashang, A. Hassankhani, Dyes Pigments
76, 564 (2008)
In summary, an environmentally friend and green approach
has presented for the synthesis of xanthane derivatives via
the reaction between 2-naphthol derivatives and aromatic or
aliphatic aldehydes in the presence of ChCl2.SnCl2, alone,
or in the presence of Fe3O4/ƛ-carrageenan/Zn(II). This
method offers several advantages, including using DES
instead of toxic organic solvents or catalysts (or both), high
yields, short reaction times, simple work-up procedure, and
reusability of DES.
24. B. Rajitha, B. Sunil Kumar, Y. Thirupathi Reddy, P. Narsimha
Reddy, N. Sreeni-vasulu, Tetrahedron Lett. 46, 8691 (2005)
25. R.J. Sarma, J.B. Baruah, Dyes Pigments 64, 91 (2005)
26. M.A. Bigdeli, M.M. Heravi, G.H. Mahdavinia, J. Mol. Catal. A
Chem. 275, 25 (2007)
27. M.M. Amini, M. Seyyedhamzeh, A. Bazigir, Appl. Catal. A Gen.
323, 242 (2007)
28. A.B. Mohammad, M.H. Majid, H.M. Gholam, Catal. Commun.
8, 1595 (2007)
29. B.B.F. Mirjalili, A.H. Bamoniri, A. Akbari, Tetrahedron Lett. 49,
6454 (2008)
30. W. Su, D. Yang, C. Jin, B. Zhang, Tetrahedron Lett. 49, 3391
(2008)
Acknowledgments This work was supported the research council of
the Isfahan University of Technology.
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J IRAN CHEM SOC
31. S. Urinda, D. Kundu, A. Majee, A. Hajra, Heteroat. Chem. 20,
232 (2009)
37. F. Keshavarzipour, H. Tavakol, J. Iran. Chem. Soc. 13, 149
(2016)
32. A. Zarei, A.R. Hajipour, L. Khazdooz, Dyes Pigments 85, 133
(2010)
38. A. Heydari, M. Mehrdad, H. Tavakol, Synthesis 2003(13), 1962
(2003)
33. S. Kantevari, M.V. Chary, A.P.R. Das, S.V.N. Vuppalapati, N.
Lingaiah, Catal. Commun. 9, 1575 (2008)
34. H. Tavakol, S. Zakery, A. Heydari, J. Organomet. Chem. 692,
1924 (2007)
39. S. Nagarapu Kantevari, V.C. Mahankhali, S. Apuri, Catal. Com-
mun. 8, 1173 (2007)
40. L. Khazdooz, A. Zarei, A.R. Hajipour, N. Sheikhan, Iran. J.
Catal. 1, 1 (2011)
35. A. Heydari, H. Tavakol, J. Azarnia, N. Ahmadi, Synthesis
2005(5), 627 (2005)
36. F. Keshavarzipour, H. Tavakol, Catal. Lett. 145, 1062 (2015)
41. X. Wang, M. Chen, F. Xie, M. Zhang, RSC Adv. 4, 14744 (2014)
42. H. Eshghi, M. Bakavoli, H. Moradi, Org. Prep. Proc. Int. 43, 302
(2011)
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