Propane-1,2,3-triyl tris(hydrogen sulfate): A mild and efficient recyclable catalyst for the synthesis of biscoumarin derivatives in water and solvent-free conditions

Article abstract of DOI:10.1016/j.cclet.2013.10.033

A simple, efficient, and ecofriendly procedure has been developed using propane-1,2,3-triyl tris(hydrogen sulfate) as a catalyst for the synthesis of biscoumarin derivatives in water and solvent-free conditions. The significant features of the present protocol are simplicity, environmentally benign, high yields, no chromatographic separation, and recyclability of the catalyst.

Full text of DOI:10.1016/j.cclet.2013.10.033

Chinese Chemical Letters 25 (2014) 183–186
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Propane-1,2,3-triyl tris(hydrogen sulfate): A mild and efficient
recyclable catalyst for the synthesis of biscoumarin derivatives in
water and solvent-free conditions
a,
a
b
Ramin Rezaei *, Fatemeh Moezzi , Mohammad Mahdi Doroodmand
a
Department of Chemistry, Firoozabad Branch, Islamic Azad University, Firoozabad 74715-117, Iran
b
Department of Chemistry, College of Sciences, & Nanotechnology Research Center, Shiraz University, Shiraz 71454, Iran
A R T I C L E I N F O
A B S T R A C T
A simple, efficient, and ecofriendly procedure has been developed using propane-1,2,3-triyl
Article history:
Received 26 June 2013
tris(hydrogen sulfate) as a catalyst for the synthesis of biscoumarin derivatives in water and
solvent-free conditions. The significant features of the present protocol are simplicity, environmentally
benign, high yields, no chromatographic separation, and recyclability of the catalyst.
ß 2013 Ramin Rezaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Received in revised form 4 October 2013
Accepted 22 October 2013
Available online 22 November 2013
Keywords:
Biscoumarin
Aldehyde
4
-Hydroxycoumarin
Propane-1,2,3-triyl tris(hydrogen sulfate)
Homogeneous catalyst
1
. Introduction
Glycerol is a non-toxic, biodegradable, and recyclable liquid
that is highly inert, stable and also able to dissolve organic
0
a,a
-(Benzylidene)-bis-(4-hydroxycoumarin), commonly known
compounds that are poorly miscible in water. It combines the
advantages of water (low toxicity, low price, and wide availability)
and ionic liquids (highly boiling point and low vapor pressure).
These advantages make it ideal for use as a sustainable solvent in
organic synthesis [22,23]. Chemically modified glycerols are
generally made by treating glycerol with agents that can react
with hydroxyl groups. Such glycerols have physicochemical
properties that differ significantly from the parent glycerol, thus
widening their usefulness in many applications such as in biodiesel
industries [24] and other industrial processes, so some reviews
have appeared recently dealing with the use of glycerol as a source
of commodity chemicals [25].
as biscoumarin, and its derivatives are of considerable interest due
to their biological activities, e.g., anticoagulant activity [1], pre-
vention and treatment of thrombosis [2], urease inhibitors [3]. Also,
a number of coumarin derivatives showed HIV inhibitory activity
[
4]. To date, available synthesis methods of biscoumarins include
Pechmann, Perkin, Knoevenagel, Reformatsky, and Wittig reactions.
Among these, the Knoevenagel reaction is the most commonly
applied one, in which different types of acid catalysts such as
sulfuric acid, phosphorus pentoxide, aluminum chloride, iodine, and
trifluoroacetic acid are employed [5–7]. Other procedures use
microwaves [8] and ultrasound [9]. Given the importance of this
reaction, many attempts to reduce its environmental impact have
been made by using catalysts such as molecular iodine [10], 1,8-
We report herein a green approach for the synthesis of some
biscoumarin derivatives from aldehydes and 4-hydroxycoumarin
catalyzed by propane-1,2,3-triyl tris(hydrogen sulfate) [PTTH] in
water and solvent-free conditions for the first time (Scheme 1).
diazabicyclo[5.4.0]undec-7-ene (DBU) [11], MnCl
dimethylformamide (DMF) [13], Et AlCl [14], SO
ionic liquids [15], [bmim][BF ] [16], tetrabutylammonium bromide
TBAB) [17], Zn(Proline) [18], sodium dodecyl sulfate (SDS) [19],
tris(hydrogensulfato) boron [20], and sulfated titania [21].
2
[12], POCl
3
in dry
2
3
3
H functionalized
4
(
2
2. Experimental
All chemicals and analytical grade solvents were purchased
from Merck or Fluka. Melting points of all products were
determined in open glass capillaries on a Mettler 9100 melting
point apparatus. Infrared (IR) spectra were recorded using a 4300
*
Corresponding author.
1
E-mail address: rezaieramin@yahoo.com (R. Rezaei).
Shimadzu FT-IR spectrometer. H NMR spectra were recorded on a
1
001-8417/$ – see front matter ß 2013 Ramin Rezaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.10.033

1
84
R. Rezaei et al. / Chinese Chemical Letters 25 (2014) 183–186
OH
O
OH
R
OH
O
HO SO
OSO H
3
3
3
OSO H
+
RCHO
2
o
8
0 C, Water or Solvent-free
O O
O
O
Scheme 1. Synthesis of biscoumarin.
O
HO
OH
+
3 Cl
S
OH
HO SO
OSO H
+ 3HCl
3
3
OH
O
OSO H
3
Scheme 2. Synthesis of propane-1,2,3-triyl tris(hydrogen sulfate).
Bruker 400 MHz spectrometer. Elemental analysis was performed
on a Horeaus CHN Rapid analyzer. All products were characterized
by comparison of their melting points, IR, and H NMR spectra with
mentioned in Table 1. After completion of the reaction as
monitored by TLC, the reaction mixture was extracted with ethyl
acetate (10 mL). The organic layer was dried over anhydrous
sodium sulfate and evaporated to dryness. A crude solid was
obtained. The pure product was obtained through crystallization
from ethanol.
1
those of authentic samples.
2.1. Preparation of propane-1,2,3-triyl tris(hydrogen sulfate)
Method B: In another procedure, the components as mentioned
above were mixed thoroughly and heated in an oil bath maintained
at 80 8C under solvent-free conditions for the appropriate time.
After completion of the reaction as monitored by TLC, ethyl acetate
(10 mL) and water (5 mL) were added to the mixture and the
reaction was worked up as described in method A.
In order to recover the catalyst totally, the separated aqueous
layer (after extraction of the reaction mixture with EtOAc)
containing the catalyst was washed with diethyl ether
A
250 mL suction flask charged with glycerol (8.30 g,
9
0.22 mmol) was equipped with a gas inlet tube for conducting
HCl gas over an adsorbing solution i.e. water. Chlorosulfonic acid
(
ꢀ20.0 mL, ꢀ300 mmol) was added in small portions over a period
of 30 min at 0 8C. HCl gas evolved from the reaction vessel
immediately (Scheme 2). After completion of the addition of
chlorosulfonic acid, the mixture was shaken for 30 min; mean-
while, the residual HCl was exhausted by suction. Then, the
mixture was concentrated under vacuum, washed with ether
(3 ꢂ 5 mL) and concentrated under vacuum conditions.
1
(
10 mL) three times, and dried under vacuum. PTTH (8.77 g,
The structures of all products 3a–l were confirmed by IR,
H
2
6.40 mmol) was obtained as yellow oil, which was stored in a
NMR and elemental analysis.
ꢁ
1
0
capped bottle. IR: 3374, 2944, 1657, 1510, 1110, 1043 cm
.
a
,
a
-(4-Cholorobenzylidene)-bis-(4-hydroxycoumarin) (entry 2):
ꢁ1
1
According to the results, the efficiency of the coupling of glycerol
was estimated to be ꢀ88% via spectrophotometric analysis. Also,
according to the Boehm back-titration analysis, the percentage of
three sulfur atom presented in the propane-1,2,3-triyl tris(hydro-
gen sulfate), as the proposed catalyst synthesized according to the
recommended procedure, was estimated to be 87.67%.
IR (KBr, cm ): 3427, 3030, 1670, 1605, 1563, 1351, 765; H NMR
(400 MHz, DMSO-d ): 6.40 (s, 1H, CH), 7.32–8.40 (m, 12H, ArH),
6
d
11.33 (s, 1H, OH), 11.57 (s, 1H, OH), Anal. Calcd. for C25H15ClO
6
(445.68): C, 67.20; H, 3.38. Found: C, 67.0; H, 3.30.
0
a
,a
-(2-Cholorobenzylidene)-bis-(4-hydroxycoumarin) (entry 3):
ꢁ
1
1
IR (KBr, cm ): 3435, 2925, 1651, 1618, 1060, 762; H NMR
400 MHz, DMSO-d ): 6.14 (s, 1H, CH), 7.24–8.03 (m, 12H, ArH),
10.92 (s, 1H, OH), 11.63 (s, 1H, OH), Anal. Calcd. for C25 15ClO
6
(
6
d
2.2. General procedure for the synthesis of biscoumarin derivatives
H
(
445.68): C, 67.20; H, 3.38. Found: C, 67.15; H, 3.35.
0
Method A: mixture of 4-hydroxycoumarin (2.0 mmol),
A
a
,a
-(3-Nitrobenzylidene)-bis-(4-hydroxycoumarin) (entry 5): IR
ꢁ1
1
aldehyde (1.0 mmol), PTTH (0.1 g, 0.03 mol%), and 5 mL of water
(KBr, cm ): 3420, 2926, 1656, 1616, 1346, 760; H NMR
was stirred magnetically at 80 8C for the appropriate time as
(400 MHz, DMSO-d
6
):
d
6.13 (s, 1H, CH), 7.26–8.17 (m, 12H,
Table 1
Synthesis of biscoumarin.
Entry
R
Product
Method A
Method B
Mp (8C)
Time (min)
Yield (%)
Time (min)
Yield (%)
Found
Reported [9,19,20]
1
2
3
4
5
6
7
8
9
C
6
H
5
3a
3b
3c
3d
3e
3f
10
7
90
90
85
95
95
85
90
85
85
85
80
80
8
5
7
5
5
7
5
8
8
7
–
8
90
80
80
90
90
80
80
80
80
80
–
228–230
254–25
233–234
258–259
–
4-ClC
2-ClC
6
H
H
4
4
6
10
8
218–220
232–234
122–124
242–244
266–268
218–220
228–230
260–262
290–292
198–200
4-NO
3-NO
2
C
C
6
H
4
238–240
128–130
249–250
270–272
222–224
230–232
265–267
–
2
6
H
4
8
4-CH
4-CH
3
OC
6
H
4
10
8
3
C
6
H
4
3g
3h
3i
4-HOC
6
H
4
10
10
10
8
–CH5CH–C
6
H
4
1
1
1
0
1
2
3,4-(CH
H
3
O)
2
C
6
H
3
3j
3k
3l
2-Furanyl
10
75
202

R. Rezaei et al. / Chinese Chemical Letters 25 (2014) 183–186
185
O
O
O
O
O
S
S
O
SO H
3
O
O
OH
O
H
H
O
O
O
C
H
-H O
2
R
+
R
S
O
O
O
O
O
O
S
O
O
SO H
3
O
O
H
H
R
O
OH
O
OH
O
R
+
O
O
O
O
O O
R
O
R
OH
OH
OH
O
O
H
O
O
O
O
O O
O
Scheme 3. Proposed mechanism.
0
ArH), 11.58 (s, 2H, OH), Anal. Calcd. for C25
5.65; H, 3.31; N, 3.06. Found: C, 65.69; H, 3.30; N, 2.90.
’-(2-Styrylpropaane-1,3-diyl)-bis-(4-hydroxycoumarin) (en-
H
15NO
8
(458.43): C,
80 8C. Ninety percent yield of
a,a
-(benzylidene)-bis-(4-hydroxy-
6
coumarin)3a was obtained by simplerecrystallizationfromethanol.
Reaction with 0.05 g of catalyst required longer reaction time, while
reaction with 0.025 g of catalyst was incomplete even after 5 h and
only 30% of the product was obtained. To investigate the effect of
solvent, the model reaction was carried out in the various solvents
a,a
ꢁ
1
1
try 9): IR (KBr, cm ): 3325, 3025, 1725, 1670, 1614, 760;
NMR (400 MHz, DMSO-d ): 6.56 (d, 1H, CH), 6.68 (d, 1H, CH 55 ),
H
6
d
6
1
4
.75 (d, 1H, CH 55 ), 7.14–8.05 (m, 12H, 12 ꢂ CH); 11.42 (s, 1H, OH),
1.58 (s, 1H, OH); Anal. Calcd. for C27
H
18
O
6
(437.55): C, 73.97; H,
3
(water, ethanol, CH CN and THF) at different reflux temperatures;
.14. Found: C, 73.78; H, 4.08.
water was found to be the best medium for this reaction.
0
a
,
a
-(Methylene)-bis-(4-hydroxycoumarin) (entry 11): IR (KBr,
Subsequently, the condensation of a series of aromatic and
aliphatic aldehydes with 4-hydroxycoumarin was carried out
using PTTH as a catalyst under the conditions outlined above. As
can be seen from Table 1, aromatic aldehydes having electron-
donating as well as electron-withdrawing groups were trans-
formed into the corresponding biscoumarins in high to excellent
yields within 5–10 min (Table 1, entries 1–10). Additionally,
aliphatic aldehydes such as formaldehyde were also investigated,
and the corresponding biscoumarin was isolated in 80% yield
ꢁ
1
1
cm ): 3443, 2926, 1650, 1600, 1567, 1308, 1347, 762; H NMR
400 MHz, DMSO-d ): 3.85 (s, 2H, CH ), 7.26–8.01 (m, 8H, ArH),
1.32 (s, 2H,OH). Anal. Calcd. for C19 (336.29): C, 67.86; H,
(
6
d
2
1
3
12 6
H O
.60. Found: C, 67.82; H, 3.63.
3
. Results and discussion
PTTH was readily prepared by addition of chlorosulfonic acid to
(
Table 1, entry 11). In the case of aliphatic aldehydes, reactions
glycerol while keeping the temperature at 0 8C. The reaction is easy
and clean, and needs no special work-up procedure because HCl
gas is evolved from the reaction vessel immediately. This liquid
catalyst is safe and easy to handle (Scheme 2).
Initially, benzaldehyde and 4-hydroxycoumarin were chosen as
model substrates to optimize the reaction conditions. The reaction
was investigated in different conditions; according to the data the
best conversion was obtained by carrying out the reaction with a
were not performed under solvent-free conditions because of the
low boiling point of the aldehydes. A comparison of aqua mediated
synthesis with those performed under solvent-free conditions is
drawn in Table 1. It can be inferred from Table 1 that high yields of
biscoumarins were obtained by both methods, though, the
reaction times were slightly shortened in solvent-free conditions,
and the yields were also slightly lower.
Regarding the mechanism, the transformation involves
a Knoevenagel condensation of 4-hydroxycoumarin with the
1
:2 mol ratio of benzaldehyde and 4-hydroxycoumarinin the
presence of 0.1 g (0.03 mol%) of PTTH as the catalyst in water at
Table 2
Comparison results of PTTH with other catalysts reported in the literature.
Entry
Conditions
Catalyst
–
Time (min)
Yield (%)
Reference
1
2
3
4
5
6
7
8
H
H
2
O, MW
8–10
20–32
120–180
20–40
150–180
3–6
76–95
91–99
77–91
77–95
78–96
81–98
82–96
75–95
[8]
2
O, reflux
I
2
(10 mol%),
[10]
Solvent-free, 60–70 8C
[bmim][BF ] (4 mmol)
4
[16]
H
H
H
H
2
2
2
2
O, reflux
TBAB (10 mol%)
SDS (20 mol%)
[17]
O, 60 8C
O:EtOH (1:1), 70 8C
O, 80 8C
[19]
B(HSO
4
)
3
(0.3 mmol)
2
[20]
4ꢁ
TiO
2
/SO
(10 mol%)
12–30
5–12
[21]
Water/solvent-free, 80 8C
PTTH (0.03 mol%)
This work

1
86
R. Rezaei et al. / Chinese Chemical Letters 25 (2014) 183–186
6] J.S. Yadav, B.V.S. Reddy, A.K. Basak, et al., Phosphane-catalyzed Knoevenagel
[
aldehydes followed by a Michael addition with another molecule
of 4-hydroxycoumarin. The highly solving action of PTTH on the
reactants makes them readily available to interact, and the
carbonyl carbon of the aldehyde will be activated because of the
intermolecular hydrogen bonding with the hydroxyl groups of
PTTH. In addition, the formed intermediates could be stabilized by
several types of complexations and hydrogen bonding with the
hydroxyl groups of PTTH (Scheme 3).
condensation: a facile synthesis of a-cyanoacrylates and a-cyanoacrylonitriles,
Eur. J. Org. Chem. (2004) 546–551.
[7] A.V. Narsaiah, K. Nagaiah, An efficient Knoevenagel condensation catalyzed by
LaCl O in heterogeneous medium, Synth. Commun. 21 (2003) 3825–3832.
3
ꢃ7H
2
[
8] G.X. Gong, J.F. Zhou, L.T. An, X.L. Duan, S.J. Ji, Catalyst-free synthesis of a,a-bis(4-
hydroxycoumarin-3-yl)toluene in aqueous media under microwave irradiation,
Synth. Commun. 39 (2009) 497–505.
[9] X.R. Zhang, W. Chao, Y.T. Chuai, et al., A new N-type organic semiconductor
synthesized by Knoevenagel condensation of truxenone and ethyl cyanoacetate,
Org. Lett. 8 (2006) 2563–2566.
To show the merit of this work, we compared our results with
[
[
[
[
10] M. Kidwai, V. Bansal, P. Mothsra, et al., Molecular iodine: a versatile catalyst for
the synthesis of bis(4-hydroxycoumarin) methanes in water, J. Mol. Catal. A:
Chem. 268 (2007) 76–81.
11] H. Hagiwara, N. Fujimoto, T. Suzuki, M. Ando, Synthesis of methylenebis(4-
hydroxy-2-pyrone) or methylenebis(4-hydroxycoumarin) derivatives by organic
solid state reaction, Heterocycles 53 (2000) 549–552.
0
those from synthesis of
marin) derivatives by use of previously reported catalysts
Table 2). As it is clear from Table 2, the present method is more
a,a -(benzylidene)-bis-(4-hydroxycou-
(
efficient when all terms, including yields, reaction times, condi-
tions, and catalyst are taken into account.
12] J.N. Sangshetti, N.D. Kokare, D.B. Shinde, Water mediated efficient one-pot
synthesis of bis(4-hydroxycoumarin)methanes, Green Chem. Lett. Rev.
2009) 233–235.
2
(
13] M.H.A. Elgamal, N.M.M. Shalaby, N.M.M. Shaban, et al., Synthesis and spectro-
scopic investigation of some dimeric coumarin and furanocoumarin models,
Monatsh. Chem. 128 (1997) 701–712.
4
. Conclusion
We have developed an efficient and environmentally benign
2
[14] H. Hagiwara, S. Miya, T. Suzuki, et al., Et AlCl promoted coupling reactions of 4-
hydroxy-2-pyrone or 4-hydroxycoumarine with aldehydes: synthesis of methy-
lenebis-(4-hydroxy-2-pyrone) or methylenebis-(4-hydroxycoumarine) deriva-
tives, Heterocycles 51 (1999) 493–496.
strategy for the synthesis of biscoumarin derivatives using PTTH as
a catalyst. This method offers several advantages, including high
yield of products, short reaction time, low cost, cleaner reaction
profile, ease of preparation of catalyst, and ease of product
isolation. Also the catalyst was successfully recovered and recycled
for at least three runs without significant loss in activity.
3
[15] W. Li, Y. Wang, Z. Wang, L. Dai, Y. Wang, Novel SO H-functionalized ionic liquids
based on benzimidazolium cation: efficient and recyclable catalysts for one-pot
synthesis of biscoumarin derivatives, Catal. Lett. 141 (2011) 1651–1658.
16] J.M. Khurana, S. Kumar, Ionic liquid: an efficient and recyclable medium for the
synthesis of octahydroquinazolinone and biscoumarin derivatives, Monatsh.
Chem. 141 (2010) 561–564.
17] J.M. Khurana, S. Kumar, Tetrabutylammonium bromide (TBAB): a neutral and
efficient catalyst for the synthesis of biscoumarin and 3,4-dihydropyrano[c]chro-
mene derivatives in water and solvent-free conditions, Tetrahedron Lett. 50
[
[
Acknowledgment
(
2009) 4125–4127.
The authors are grateful to Firoozabad University Research
Council for the partial financial support.
[
[
18] Z. Siddiqui, F. Farooq, Zn(Proline) : a novel catalyst for the synthesis of dicou-
2
marols, Catal. Sci. Technol. 1 (2011) 810–816.
19] H. Mehrabi, H. Abusaidi, Synthesis of biscoumarin and 3,4-dihydropyrano[c]-
chromene derivatives catalysed by sodium dodecyl sulfate (SDS) in neat water, J.
Iran Chem. Soc. 7 (2010) 890–894.
References
[
20] Z. Karimi-Jaberi, M.R. Nazarifar, B. Pooladian, Tris(hydrogensulfato) boron as a
0
[
1] I. Manolov, C.M. Moessmer, I. Nicolova, N. Danchev, Synthesis and anticoagulant
activities of substituted 2,4-diketochromans, biscoumarins and chromanocou-
marins, Arch. Pharm. Chem. Life Sci. 339 (2006) 319–326.
solid heterogeneous catalyst for the rapid synthesis of a,a -benzylidene bis(4-
hydroxycoumarin) derivatives, Chin. Chem. Lett. 23 (2012) 781–784.
[21] B. Karmakar, A. Nayak, J. Banerji, Sulfated titania catalyzed water mediated
efficient synthesis of dicoumarols—a green approach, Tetrahedron Lett. 53
(2012) 4343–4346.
[22] Y. Gu, F. Jerome, Glycerol as a sustainable solvent for green chemistry, Green
Chem. 12 (2010) 1127–1138.
[
[
2] J. Lehmann, Thrombosis treatment and prevention with methylene-bis-(hydro-
xycoumarin), Lancet 241 (1943) 611–613.
3] K.M. Khan, S. Iqbal, M.A. Lodhi, et al., Biscoumarin: new class of urease inhibitors,
economical synthesis and activity, Bioorg. Med. Chem. 12 (2004) 1963–
1
968.
[23] K.P. Nandre, J.K. Salunke, J.P. Nandre, et al., Glycerol mediated synthesis of 5-
substituted 1H-tetrazole under catalyst free conditions, Chin. Chem. Lett. 23
(2012) 161–164.
[
[
4] R.D.R.S. Manian, J. Jayashankaran, R. Raghunathan, A rapid access to indolo[2,1-
a]pyrrolo[4 ,3 :4,5]pyrano[5,6-c]coumarin/[6,5-c]chromone derivatives by dom-
0
0
ino Knoevenagal intramolecular hetero Diels–Alder reactions, Tetrahedron Lett.
[24] S. Zhou, L. Liu, B. Wang, F. Xu, R.C. Sun, Biodiesel preparation from transester-
ification of glycerol trioleate catalyzed by basic ionic liquids, Chin. Chem. Lett. 23
(2012) 379–382.
[25] Y. Zheng, X. Chen, Y. Shen, Commodity chemicals derived from glycerol, an
important biorefinery feedstock, Chem. Rev. 108 (2008) 5253–5277.
4
8 (2007) 1385–1389.
5] G. Brufola, F. Ringuelli, O. Piermatti, F. Pizzo, Simple and efficient one-pot
preparation of 3-substituted coumarins in water, Heterocycles 43 (1996)
1
257–1266.