Efficient green procedure for the synthesis of coumarin derivatives by a one-pot, three-component reaction under solvent-free conditions

Article abstract of DOI:10.1080/00397910601031553

A simple, efficient, and general method has been developed for the synthesis of coumarin derivatives through a one-pot reaction of aromatic aldehydes, 2,2-dimethyl-1,3-dioxane-4,6-dione and 5,5-dimethyl-1,3- cyclohexanedione, in the presence of TEBA under solvent-free conditions using grinding methods. The mild reaction conditions, simple protocol, high yields, and cleaner reaction make this protocol practical and economically attractive. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601031553

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Efficient Green Procedure for the Synthesis
of Coumarin Derivatives by a One‐Pot,
Three‐Component Reaction under
Solvent‐Free Conditions
Liangce Rong a b , Xiaoyue Li a , Haiying Wang a , Daqing Shi a b , Shujiang Tu
a b & Qiya Zhuang a b
a Department of Chemistry, Xuzhou Normal University, Xuzhou, Jiangsu,
China
b Key Laboratory of Biotechnology for Medicinal Plant, Xuzhou, Jiangsu,
China
Published online: 25 Jul 2007.
To cite this article: Liangce Rong , Xiaoyue Li , Haiying Wang , Daqing Shi , Shujiang Tu & Qiya Zhuang (2007):
Efficient Green Procedure for the Synthesis of Coumarin Derivatives by a One‐Pot, Three‐Component Reaction
under Solvent‐Free Conditions, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 37:2, 183-189
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Synthetic Communicationsw, 37: 183–189, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601031553
Efficient Green Procedure for the Synthesis
of Coumarin Derivatives by a One-Pot,
Three-Component Reaction under Solvent-
Free Conditions
Liangce Rong
Department of Chemistry, Xuzhou Normal University, Xuzhou, Jiangsu,
China and Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, China
Xiaoyue Li and Haiying Wang
Department of Chemistry, Xuzhou Normal University, Xuzhou, Jiangsu,
China
Daqing Shi, Shujiang Tu, and Qiya Zhuang
Department of Chemistry, Xuzhou Normal University, Xuzhou, Jiangsu,
China and Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, China
Abstract: A simple, efficient, and general method has been developed for the synthesis
of coumarin derivatives through a one-pot reaction of aromatic aldehydes, 2,2-
dimethyl-1,3-dioxane-4,6-dione and 5,5-dimethyl-1,3-cyclohexanedione, in the
presence of TEBA under solvent-free conditions using grinding methods. The mild
reaction conditions, simple protocol, high yields, and cleaner reaction make this
protocol practical and economically attractive.
Keywords: coumarin, grinding method, solvent-free conditions, TEBA
Received February 14, 2006
Address correspondence to Liangce Rong, Department of Chemistry, Xuzhou
Normal University, Xuzhou, Jiangsu 221116, China. E-mail: lcrong2005@yahoo.com
183

184
L. Rong et al.
The increasing demands of environmental legislation have been prompting the
chemical industry to minimize or preferably eliminate waste production in
chemical manufacture. Environmentally benign processes are requested for
primary prevention of pollution, and enviroeconomic factors will become
the driving force behind new products and processes.[1]
To minimize the amount of harmful organic solvents used in chemical
processes, much attention has been devoted to the use of alternative
reaction media.[2] Besides the use of supercritical fluids, water, and ionic
liquids, the possibility of performing chemical processes in the absence of
solvent (solvent-free conditions) has been receiving more attention.[2b,3] For
historical and cultural reasons, organic reactions have generally been
developed in solution, although a higher chemical efficiency would be
expected if there were no medium interposed between the reactants. The
examples reported demonstrate that no-solvent reactions are generally
faster, give higher selectivities and yields, and usually require easier
workup procedures and simpler equipment.[3,4] Some solvent-free reactions
could be completed by grinding; many articles about solvent-free reactions
under grinding have been reported, such as the Grignard reaction,[5] Refor-
matsky reaction,[6] aldol condensations,[7] Dieckmann condensations,[8]
phenol coupling reaction,[9] reduction reaction,[10] and other reactions.[11]
Coumarins have been widely studied and used but still generate much
interest. Coumarins are well known as natural products and many exhibit
high levels of biological activity.[12] Coumarins are also used as food
additives, in cosmetics,[13] and as optical brightening agents[14] and
dispersed fluorescent and laser dyes.[15] In addition, some coumarins are of
interest because of their toxicity,[16] carcinogenity,[17] and photodynamic
effects.[18] Coumarins also act as intermediates for the synthesis of furocou-
marins, chromenes, coumarones, and 2-acylresorcinols.[19] It is therefore of
importance that the synthesis of coumarin and its derivatives should be
achieved by an effective method.
Coumarins can be synthesised by various methods including the Perkin,[20]
Pechmann,[21] Knoevenagel,[22] Reformatsky,[23] and Wittig[24] reactions. In
some methods, various acids[25] and several hours or even days are required
to complete the reaction even when heated to temperatures greater than
1508C. Undesired by-products such as chromones are sometimes formed.[26]
Recently, cation exchange resins[27] and solid acid catalysts[28] have been
used; however, such reactions require either a reaction temperature of about
1508C or more or long reaction times and in some cases give low yields.
More recently, there have been reports on the use of microwave irradiation[29]
for accelerated synthesis of different coumarins, but it has limitations in that it
can be only carried out in the laboratory and is difficult to apply in the industrial
process, until now. In view of the current emphasis on solid-state synthesis[30]
and green chemistry,[31] herein we report a novel, efficient, green procedure
for the synthesis of coumarin derivatives by grinding, starting material at
room temperature, under mild and solvent-free conditions.

Synthesis of Coumarin Derivatives
185
As the part of our study, first of all, we investigated the amounts of
catalyst (TEBA) used in the reaction. We found different amounts of
catalyst could give different reaction results. The optimum amounts of
catalyst were selected. The amounts of TEBA used are listed in Table 1.
With this result in hand, we further investigated the reaction. The three
components 1, 2,2-dimethyl-1,3-dioxane-4,6-dione 2, and 5,5-dimethyl-1,3-
cyclohexanedione 3 were added to a mortar, with triethylbenzyl ammonium
chloride (TEBA) as catalyst. The mixture was ground with a pestle at room
temperature; the reaction was completed in 5–7 min, allowing the one-pot
formation of 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocomarins 4 in
high yields (Scheme 1). The results of reaction are listed in Table 2.
In summary, we have found an efficient and versatile method for the prep-
aration of a series of 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocou-
marins in excellent isolated yields at room temperature in short reaction
times under solvent-free conditions. We find TEBA is a virtual and necessary
catalyst in this protocol, and the reaction could not be carried out without it.
To our knowledge, TEBA was used as efficient catalyst in solvent-free
synthesis for the first time. Although we could not know the detailed
mechanism of this reaction, we think the possible reason is as follow:
because TEBA is easily deliquescent, during the reaction, ground by a pestle,
the mixture of reactants blends uniformly and turns into liquid quickly; it
reacts in organic solvent, so the reaction could be carried out rapidly. We
believe that the present methodology addresses the current interest in green
chemistry because of the easy workup procedure, mild reaction conditions,
and ready access to the starting materials.
EXPERIMENTAL
All the reagents and aromatic aldehydes were obtained from suppliers and
were not purified. Melting points were determined on XT-5 microscopic
melting-point spectrometer and are uncorrected. 1H NMR spectra were
obtained for solution in CDCl3 with Me4Si as internal standard using an
Table 1. Optimizing the amounts of catalyst
Amounts of catalyst
(mmol)
Yields of 4a
(%)
Entry
Catalyst
1
2
3
4
5
TEBA
TEBA
TEBA
TEBA
TEBA
2
3
4
5
7
51
80
91
91
92

186
L. Rong et al.
Scheme 1.
Inova-400 spectrometer. Microanalyses were carried out using a Perkin-Elmer
2400 II analyzer. IR spectra were recorded on an FTIR-8101 spectrometer in
KBr.
General Procedure
Aromatic aldehyde 1 (2 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione
2
(2 mmol), 5,5-dimethyl-1,3-cyclohexanedione 3 (2 mmol), and triethylbenzyl-
ammonium chloride (TEBA) (4 mmol) were added to a mortar. The mixture
was grounded with a pestle at room temperatures (258C); the reaction was
completed within 5–7 min (the reaction was monitored by thin-layer chrom-
atography, TLC) and poured into water. The product was filtered, dried, and
recrystallized from 95% ethanol.
Data
4a: mp 166–1688C (lit.[32] 169–1708C); IR (KBr) n: 2965, 1772, 1657, 1490,
1417, 1371, 1313, 1185, 1164, 1107, 1034, 1013, 972, 861, 828 cm21
;
1H NMR d: 1.09 (3H, s, CH3), 1.15 (3H, s, CH3), 2.33 (2H, s, C8-H), 2.53
(2H, s, C6-H), 2.87–2.95 (2H, m, C3-H), 4.26–4.29 (1H, m, C4-H), 7.08–
7.28 (4H, m, ArH); anal. calcd. for C17H17ClO3: C, 66.99; H, 5.62; found
C, 67.07; H, 5.46%.
Table 2. Synthesis of coumarin derivatives under solvent-free
conditions
Entry
Ar
4-ClC6H4
4-FC6H4
Time (min)
Yield (%)
4a
4b
4c
4d
4e
4f
7
5
5
5
6
7
5
5
91
95
96
97
92
91
94
94
4-CH3OC6H4
4-(CH3)2NC6H4
2,4-Cl2C6H3
3,4-OCH2OC6H3
2,4-(CH3O)2C6H3
4-HO-3-CH3OC6H3
4g
4h

Synthesis of Coumarin Derivatives
187
4b: mp 165–1668C (lit.[32] 167–1688C); IR (KBr) n: 2965, 1773, 1654, 1601,
1510, 1475, 1418, 1373, 1220, 1180, 1158, 1110, 1037, 975, 862, 845 cm21
;
1H NMR d: 1.09 (3H, s, CH3), 1.15 (3H, s, CH3), 2.33 (2H, s, C8-H), 2.53 (2H,
s, C6-H), 2.87–2.97 (2H, m, C3-H), 4.28–4.30 (1H, m, C4-H), 6.94–7.14 (4H,
m, ArH); anal. calcd. for C17H17FO3: C, 70.82; H, 5.94; found C, 70.94;
H, 5.73%.
4c: mp 127–1298C; IR (KBr) n: 2965, 1770, 1650, 1508, 1465, 1412, 1352,
1
1225, 1167, 1137, 1112, 1035, 965, 855, 824 cm21; H NMR d: 1.11 (3H,
s, CH3), 1.14 (3H, s, CH3), 2.31 (2H, s, C8-H), 2.53 (2H, s, C6-H), 2.90–
2.93 (2H, m, C3-H), 3.75 (3H, s OCH3), 4.25–4.29 (1H, m, C4-H), 6.69–
7.07 (4H, m, ArH); anal. calcd. for C18H20O4: C, 71.98; H, 6.71; found
C, 72.08; H, 6.63%.
4d: mp 177–1798C (lit.[32] 176–1778C); IR (KBr) n: 2963, 1786, 1650, 1616,
1520, 1375, 1318, 1239, 1161, 1100, 1036, 1006, 858, 815 cm21; 1H NMR d:
1.10 (3H, s, CH3), 1.14 (3H, s, CH3), 2.31 (2H, s, C8-H), 2.51 (2H, s, C6-H),
2.80–2.94 (8H, m, (CH3) N þ C3-H), 4.11–4.29 (1H, m, C4-H), 6.63–7.02
2
(4H, m, ArH); anal. calcd. for C19H23NO3: C, 72.81; H, 7.33; N, 4.46;
found C, 73.05; H, 7.17; N, 4.52%.
4e: mp 174–1768C (lit.[32] 173–1748C); IR (KBr) n: 2965, 2873, 1772, 1673,
1656, 1581, 1560, 1465, 1420, 1371, 1305, 1180, 1101, 1046, 967, 858,
1
832 cm21; H NMR d: 1.18 (6H, s, 2 ꢀ CH3), 2.33 (2H, s, C8-H), 2.61 (2H,
s, C6-H), 2.91–2.94 (2H, m, C3-H), 4.58–4.70 (1H, m, C4-H), 6.83–7.45
(3H, m, ArH); anal. calcd. for C17H16Cl2O3: C, 60.19; H, 4.75; found C,
60.45; H, 4.50%.
4f: mp 151–1538C (lit.[32] 154–1558C); IR (KBr) n: 2960, 2895, 1784, 1650,
1488, 1443, 1420, 1361, 1290, 1237, 1111, 1030, 975, 935, 885, 854, 801,
1
765 cm21; H NMR d: 1.11 (3H, s, CH3), 1.15 (3H, s, CH3), 2.32 (2H, s,
C8-H), 2.52 (2H, s, C6-H), 2.85–2.92 (2H, m, C3-H), 4.21–4.23 (1H, m,
C4-H), 5.93 (2H, s, OCH2O), 6.58–6.70 (3H, m, ArH); anal. calcd. for
C18H18O5: C, 68.77; H, 5.77; found C, 68.94; H, 5.53%.
4g: mp 147–1488C (lit.[32] 145–1468C); IR (KBr) n: 2965, 1786, 1643,
1614, 1585, 1505, 1475, 1375, 1288, 1210, 1164, 1135, 1081, 1036, 915,
1
853, 793 cm21; H NMR d: 1.05 (3H, s, CH3), 1.13 (3H, s, CH3), 2.36
(2H, s, C8-H), 2.46 (2H, s, C6-H), 2.79–2.88 (2H, m, C3-H), 3.72 (3H, s,
CH3O), 3.78 (3H, s, CH3O), 4.28–4.31 (1H, m, C4-H), 6.37–7.05 (3H,
m, ArH); anal. calcd. for C19H22O5: C, 69.07; H, 6.71; found C, 69.36;
H, 6.46%.
4h: mp 184–1868C (lit.[32] 186–1878C); IR (KBr) n: 3345, 2956, 2870, 1785,
1650, 1515, 1460, 1374, 1282, 1255, 1143, 1107, 1035, 846 cm21; 1H NMR d:

188
L. Rong et al.
1.10 (3H, s, CH3), 1.14 (3H, s, CH3), 2.33 (2H, s, C8-H), 2.51 (2H, s, C6-H),
2.89–2.95 (2H, m, C3-H), 3.84 (3H, s, CH3O), 4.20–4.26 (1H, m, C4-H), 5.57
(1H, s, OH), 6.60–6.81 (3H, m, ArH); anal. calcd. for C18H20O5: C, 68.34;
H, 6.37; found C, 68.53; H, 6.45%.
ACKNOWLEDGMENTS
We are grateful to the Natural Science Foundation (04XLB14) of Xuzhou
Normal University for financial support.
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