Abstract: A rapid, efficient and green methodology has been developed for the synthesis of 3,3&apos;-arylmethylene-bis-4-hydroxycoumarins by microwave assisted condensation of aromatic aldehydes and 4-hydroxycoumarin without use of any solvent, catalyst or solid surface

Asok K Mondal

Das Arpita

Mallik

Rina Samanta

Swati Gupta

CiteSeerX

Chem Sci Trans., 2013, 2(2), 524-528              Chemical Science Transactions 
DOI:10.7598/cst2013.388                  ISSN/E-ISSN: 2278-3458/2278-3318 
A Rapid, Efficient and Green Method for Synthesis of  
3,3'-Arylmethylene-bis-4-hydroxycoumarins without  
Use of any Solvent, Catalyst or Solid Surface 
ARPITA DAS GUPTA, SWATI SAMANTA, RINA MONDAL and ASOK K. MALLIK* 
Department of Chemistry, Jadavpur University, Kolkata-700 032, India 
mallikak52@yahoo.co.in  
Received 18 September 2012 / Accepted 20 October 2012 
Abstract: A rapid, efficient and green methodology has been developed for the synthesis of                  
3,3'-arylmethylene-bis-4-hydroxycoumarins by microwave assisted condensation of aromatic 
aldehydes and 4-hydroxycoumarin without use of any solvent, catalyst or solid surface. 
Keywords: 3,3'-Arylmethylene-bis-4-hydroxycoumarins, Solvent-free synthesis, Catalyst-free 
synthesis, 4-Hydroxycoumarin 
Introduction 
4-Hydroxycoumarin and its derivatives are known for their anticoagulant1, antibacterial2, 
antifungal2, antibiotic3, antitumor3,4 and anti-HIV5 activities. They are also used as 
agrochemicals6 and analytical reagents7. 3,3'-Arylmethylene-bis-4-hydroxycoumarins (3), 
commonly known as  biscoumarins, are the bridge substituted dimers of 4-hydroxycoumarin. 
They have enormous potential as anticoagulants1,8,9 and antioxidants6 and some of them 
have also been found to be urease inhibitors10. The compound 3,3′ -methylene-bis-4-
hydroxycoumarin, commonly known as dicoumarol, occurs naturally in moldy clover11. It is 
the hemorrhagic agent responsible for the sweet clover disease of cattle and has also been 
employed for the prevention and treatment of thrombosis12. 3,3'-Arylmethylene-bis-4-
hydroxycoumarins (3) are usually synthesized by condensing 4-hydroxycoumarin (1) with 
various aldehydes (aromatic, heterocyclic and α,β-unsaturated) (2) using different catalysts 
and media8-10,13-19. Some of these methods require long reaction time, use of expensive 
catalysts and organic solvents and tedious work up8,10. The current literature shows that there 
has been a growing trend towards green synthesis of these compounds13-19. However, in such 
reported green methods use of catalysts, solid surfaces, solvents etc. could not be avoided. 
The current trend towards development of catalyst-free and solvent-free reaction conditions 
for organic synthesis20-23 encouraged us to study the same reaction under microwave 
irradiation condition without using any solvent, catalyst or solid surface. The remarkable 
success in this endeavor is presented herein. 
 RESEARCH ARTICLE 
Chem Sci Trans., 2013, 2(2), 524-528                  525 
 
 
 
 
 
 
Scheme 1. Synthesis of 3,3'-arylmethylene-bis-4-hydroxycoumarins (3) 
Experimental  
Melting points were recorded on a Köfler block. IR spectra were recorded on a Perkin Elmer 
FT-IR spectrophotometer (Spectrum BX II) in KBr pellets. 1H and 13C NMR spectra were 
recorded in CDCl3 on a Bruker AV-300 (300 MHz) spectrometer. Analytical samples were 
routinely dried in vacuo at room temperature. Microanalytical data were recorded on a 
Perkin-Elmer 2400 Series II C, H, N analyzer. The FAB-MS of 3j was recorded on a Jeol 
the M Station JMS.700 spectrometer. Column chromatography was performed with silica 
gel (100-200 mesh) and TLC with silica gel G made of SRL Pvt. Ltd. Petroleum ether had 
the boiling range 60-80 °C.  
General procedure for synthesis of 3,3'-arylmethylene-bis-4-hydroxycoumarins (3)  
In a typical experiment, an intimate mixture of 4-hydroxycoumarin (1, 4 mmole) and an 
aromatic aldehyde (2, 2 mmole) was taken in a pyrex beaker (100 mL) and it was irradiated 
with microwave for 2.5-3.5 min within which the reaction was complete (Table 1) [An 
unmodified domestic household microwave oven (LG, DMO, Model No.-556P, 900 watt) 
was used. The MW oven was operated at reduced MW-power level of 60% (540 watt).]. The 
reaction mixture was then cooled and crystallized from CH2Cl2 - petroleum ether, which 
gave 3 in perfectly pure state.  
 All the thirteen compounds of the series 3 synthesized by us have been found to be 
previously known. The analytical and spectral data of some selected compounds are given 
below:    
3,3′-Phenylmethylene-bis-4-hydroxycoumarin (3a) 
Colourless crystalline solid, IR (KBr, ν cm-1): 3069, 1660 (C=O), 1616, 1568, 1496, 1337, 
1266, 1199 (OH), 1093, 902, 800, 757; 1H NMR (300 MHz, CDCl3): δ = 6.11 (s, 1H, Ar-
CH<),7.21-7.43 (m, 9H), 7.63 (dt, 2H, J =7.9 and 1.5 Hz), 8.01(br. d, 1H, J = 6.7 Hz), 8.07 
(br.d, 1H, J = 6.6 Hz), 11.30 (br. s, 1H, OH), 11.53 (br. s, 1H, OH); Anal. Calcd. for 
C25H16O6  C, 72.81; H, 3.91%; found  C, 72.63 ; H, 4.02%. 
3,3'-(4-Methoxyphenylmethylene)-bis-4-hydroxycoumarin (3c) 
Colourless crystalline solid, IR (KBr, ν cm-1): 3440 (OH), 3072, 3002, 1668 (C=O), 1604, 
1565, 1510, 1454, 1353, 1258, 1180 (OH), 1094, 907, 828, 768; 1H NMR (300 MHz, 
CDCl3): δ =3.80 (s, 3H, OCH3), 6.05 (s, 1H, Ar-CH<), 6.85 ( d, 2H, J = 8.7 Hz), 7.13 (d, 
2H, J = 8.7 Hz), 7.30 -7.42 ( m, 4H), 7.63 (br. t, 2H, J = 8.2 Hz) , 8.03 (dd, 2H, J = 8.4 Hz), 
11.29 (br. s, 1H, OH), 11.51 (br. s, 1H, OH) ; Anal. Calcd. for C26H18O7  C, 70.58; H, 
4.10%; found  C, 70.37; H, 4.22%. 
 
ArCHO+
O O
OH
MW Irradiation
O O
OH
OO
OHAr
2.5-3.5 min
2
31 2
526       Chem Sci Trans., 2013, 2(2), 524-528  
3,3’-(4-Chlorophenylmethylene)-bis-4-hydroxycoumarin (3d) 
Colourless crystalline solid, IR (KBr, ν cm-1):3072, 2684, 2609, 1668 (C=O), 1617, 1603, 
1490, 1454, 1351, 1311, 1266, 1182 (OH), 1094, 920, 908, 821, 790, 706; 1H NMR (300 
MHz, CDCl3): δ = 6.04 (s, 1H, Ar-CH<), 7.15 (d, 2H, J = 8.4 Hz), 7.29 (d, 2H, J = 8.6 Hz), 
7.38-7.43 (m, 4H), 7.64 (dt, 2H, J = 8.0 and 1.5  Hz), 8.00 (br. D, 1H, J = 7.3 Hz), 8.07 (br. 
D, 1H, J =7.2 Hz), 11.31 (br. S, 1H, OH), 11.53 (br. S, 1H, OH); Anal. Calcd. For 
C25H15ClO6; C, 67.20; H, 3.38 %; found C, 66.96; H, 3.52%. 
3,3’-(4-Bromophenylmethylene)-bis-4-hydroxycoumarin (3e) 
Colourless crystalline solid, IR (KBr, ν cm-1): 3446 (OH), 3071, 2729, 2610, 2361, 1668 
(C=O), 1618, 1604, 1561, 1488, 1351, 1309, 1266, 1182 (OH), 1094, 908, 820, 766; 1H 
NMR (300 MHz, CDCl3): δ = 6.01 (s, 1H, Ar-CH<), 7.10 (d, 2H, J = 8.2 Hz), 7.32-7.45 (m, 
6H), 7.64 (dt, 2H, J = 8.0 and 1.5  Hz), 7.99 (br. D, 1H, J = 7.7 Hz), 8.06 ( br. D, 1H, J =7.8 
Hz), 11.31 (br. S, 1H, OH),  11.54(br. S, 1H, OH); Anal. Calcd. For C25H15BrO6; C, 61.12; 
H, 3.08%; found C, 61.21; H, 3.24%. 
3,3’-(4-Nitrophenylmethylene)-bis-4-hydroxycoumarin (3h) 
Colourless crystalline solid, IR (KBr, ν cm-1): 3440 (OH), 3072, 2361, 1660(C=O), 1618, 
1601, 1566, 1519, 1494, 1348, 1309, 1265, 1182 (OH), 1109, 909, 826, 765; 1H NMR (300 
MHz, CDCl3): δ = 6.12 (s, 1H, Ar-CH<), 7.40-7.45 (m, 6H), 7.67(br. T, 2H, J = 7.8 Hz), 
8.01(br. D, 1H, J = 7.6 Hz), 8.11 (br. D, 1H, J = 7.2 Hz), 8.19 (d, 2H, J = 8.9 Hz), 11.37       
(s, 1H, OH), 11.57 (s, 1H, OH); Anal. Calcd. For C25H15NO8; C, 65.65; H, 3.31; N, 3.06% 
found C, 65.38; H, 3.22; N, 3.20%. 
3,3’-(4-Hydroxy-3-methoxyphenylmethylene)-bis-4-hydroxycoumarin (3j) 
Colourless crystalline solid, IR (KBr, ν cm-1): 3457 (OH), 2360, 1668 (C=O), 1616, 1604, 
1515, 1451, 1352, 1270, 1212, 1187 (OH), 1093, 909, 799, 766; 1H NMR (300 MHz, 
CDCl3): δ 3.75 (s, 3H, OCH3), 5.58 (br. S, 1H, OH), 6.06 (s, 1H, Ar-CH<), 6.67 (1H, s), 
6.72 (d, 1H, J =8.4Hz), 6.86 (d, 1H, J = 8.3Hz), 7.36-7.42 (m, 4H), 7.63 (br. T, 2H, J = 7.6 
Hz), 8.03 ( br. Peak, 2H, w1/2= 23.9 Hz ), 11.28 (br. S, 1H, OH), 11.51 (br. S, 1H, OH); 13C 
NMR (300 MHz, CDCl3) δ 146.70, 144.56, 132.83, 126.85, 124.89, 124.36, 119.51, 116.64, 
114.46, 109.44, 56.10 (OCH3), 35.79 (Ar-CH<); FABMS: 458.3 (M+); Anal. Calcd. For 
C26H18O8; C, 68.12; H, 3.96%; found C, 67.95; H, 4.11%. 
3,3’-(2- Thiophenyl)-bis-4-hydroxycoumarin (3l) 
Greenish crystalline solid, IR (KBr, ν cm-1): 3069, 1655, 1616, 1602, 1568, 1358, 1309, 
1268, 1098, 903, 810, 761, 720, 707.  1H NMR (500 MHz, CDCl3): δ 6.20 (s, 1H), 6.85-6.86 
(m, 1H), 6.94-6.96 (m, 1H), 7.21-7.22 (m, 1H), 7.40-7.41 (m, 4H), 7.61-7.65 (m, 2H), 8.04 
(br. S, 2H, w1/2= 32 Hz), 11.27 (s, 1H, OH), 11.79 (s, 1H, OH); Anal. Calcd. For C23H14O6S; 
C, 66.02; H, 3.37%; found C, 66.29; H, 3.58%. 
Results and Discussion 
Our present method involves subjecting of a mixture of an aldehyde and 4-hydroxy-
coumarin in 1:2 mole ratio directly to microwave irradiation. A range of structurally diverse 
aldehydes belonging to the categories aromatic, heterocyclic and α,β-unsaturated aldehydes 
were taken. To our delight, the target compounds were obtained in excellent yield in the 
above mentioned method for all the combinations. The yields of the products by the method 
have been presented in Table 1. 
Chem Sci Trans., 2013, 2(2), 524-528                  527 
Table 1. Synthesis of 3,3'-Arylmethylene-bis-4-hydroxycoumarins (3) from 4-hydroxycoumarin 
(1) by MW Irradiation 
 
 
 
 
Entry Aldehyde (2) Ar 
Time, 
min 
Yield of 3, 
% † [3a-m] mp, 
o C [Lit. Value] 
1 2a C6H5- 3.5 91 231-232 [230-232]13 
2 2b 4-Me-C6H4- 3.5 93 265-266 [266-268]13 
3 2c 4-MeO-C6H4- 3.5 95 244-245 [246-248]13 
4 2d 4-Cl-C6H4- 2.5 95 257-258 [256-258]13 
5 2e 4-Br-C6H4- 3.5 92 268-270 [265-267]13 
6 2f 4-Me2N-C6H4- 3.5 91 225-227 [222-224]13 
7 2g 3-O2N-C6H4- 3.5 94 233-234 [234-236]13 
8 2h 4-O2N-C6H4- 3.5 97 234-235 [232-234]13 
9 2i 
 
 
 
3.5 93 258-259 [260]13 
10 2j 
 
 
 
3.5 92 227-228
¶ 
 
11 2k 2-Furyl 2.5 94 204-205 [202]13 
12 2l 2-Thienyl 3.5 93 213-214 [210]13 
13 2m E-C6H5CH=CH- 3.5 89 232-233 [230-232]13 
†Pure product obtained after crystallization. ¶The compound has been reported in ref. 25, but its mp 
has not been given there. 
 In the method being reported it was a common observation that the reactions were very 
clean and no side product was formed in any run. In fact, the crude products obtained were 
of high purity (> 95% by 1H NMR) and did not require any chromatographic separation. 
Their crystallization from CH2Cl2 - petroleum ether provided analytically pure samples. 
More significantly, the whole operation did not require any solvent, organic or inorganic, at 
any stage. Furthermore, the reaction condition has been found to be mild enough to tolerate 
a variety of functionalities such as NO2, Cl, OH, OMe, conjugated C-C double bond and 
heterocyclic moieties. It is very likely that in our experiments 4-hydroxycoumarin itself or a 
carboxylic acid formed by aerial oxidation of the aldehyde used acts as acid catalyst and so 
addition of any external catalyst does not become necessary.  
Conclusion 
We have developed a very simple, efficient and environmentally benign method for 
synthesis of 3,3'-arylmethylene-bis-4-hydroxycoumarins (3) without use of any catalyst, 
solvent, surfactant or solid support. We feel that this protocol being a good addition to the 
currently reported methods24,25 is in fact better than many others referred herein. 
Acknowledgement 
Financial assistance from the UGC-CAS and DST-PURSE programs, Department of Chemistry 
is gratefully acknowledged. The authors also acknowledge the  DST-FIST program to the 
O
O
HO
MeO
ArCHO+
O O
OH
MW Irradiation
O O
OH
OO
OHAr
2
31 2
528       Chem Sci Trans., 2013, 2(2), 524-528  
Department of Chemistry, Jadavpur University for providing the NMR spectral data. AD 
and SS are thankful to the CSIR and RM to the UGC, New Delhi for their Research 
Fellowships. 
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A Rapid, Efficient and Green Method for Synthesis of 3,3&apos;-Arylmethylene-bis-4-hydroxycoumarins without Use of any Solvent, Catalyst or Solid Surface

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A Rapid, Efficient and Green Method for Synthesis of 3,3'-Arylmethylene-bis-4-hydroxycoumarins without Use of any Solvent, Catalyst or Solid Surface

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A Rapid, Efficient and Green Method for Synthesis of 3,3&apos;-Arylmethylene-bis-4-hydroxycoumarins without Use of any Solvent, Catalyst or Solid Surface

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A Rapid, Efficient and Green Method for Synthesis of 3,3'-Arylmethylene-bis-4-hydroxycoumarins without Use of any Solvent, Catalyst or Solid Surface