Expeditious Pechmann condensation by using biodegradable cellulose sulfuric acid as a solid acid catalyst

Article abstract of DOI:10.1080/00397910903419860

A facile synthesis of coumarins was performed in excellent yields via Pechmann condensation by using different type of phenols and ethylacetoacetates under solvent-free media using both conventional method and microwave irradiation in short reaction times is described. The reaction workup is very simple, and the catalyst can be easily separated from the reaction mixture and reused several times in subsequent reactions. Copyright

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Expeditious Pechmann Condensation by
Using Biodegradable Cellulose Sulfuric
Acid as a Solid Acid Catalyst
B. Suresh Kuarm a , J. Venu Madhav a , S. Vijaya Laxmi a , B. Rajitha
a , Y. Thirupathi Reddy b , P. Narsimha Reddy b & Peter A. Crooks b
a Department of Chemistry, National Institute of Technology,
Warangal, India
b Department of Pharmaceutical Sciences, College of Pharmacy,
University of Kentucky, Lexington, Kentucky, USA
Published online: 15 Oct 2010.
To cite this article: B. Suresh Kuarm , J. Venu Madhav , S. Vijaya Laxmi , B. Rajitha , Y. Thirupathi
Reddy , P. Narsimha Reddy & Peter A. Crooks (2010): Expeditious Pechmann Condensation by Using
Biodegradable Cellulose Sulfuric Acid as a Solid Acid Catalyst, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:22, 3358-3364
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Synthetic Communications1, 40: 3358–3364, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903419860
EXPEDITIOUS PECHMANN CONDENSATION BY
USING BIODEGRADABLE CELLULOSE SULFURIC
ACID AS A SOLID ACID CATALYST
B. Suresh Kuarm,1 J. Venu Madhav,1 S. Vijaya Laxmi,1
B. Rajitha,1 Y. Thirupathi Reddy,2 P. Narsimha Reddy,2 and
Peter A. Crooks2
1Department of Chemistry, National Institute of Technology,
Warangal, India
2Department of Pharmaceutical Sciences, College of Pharmacy, University of
Kentucky, Lexington, Kentucky, USA
A facile synthesis of coumarins was performed in excellent yields via Pechmann conden-
sation by using different type of phenols and ethylacetoacetates under solvent–free media
using both conventional method and microwave irradiation in short reaction times is
described. The reaction workup is very simple, and the catalyst can be easily separated from
the reaction mixture and reused several times in subsequent reactions.
Keywords: Cellulose sulfuric acid; coumarins; Pechmann condensation; solvent-free conditions
INTRODUCTION
In recent years, there has been extensive effort to synthesize coumarins and
their derivatives. The coumarin molecule has had a wide variety of applications in
organic and medicinal chemistry for many years as a large number of natural pro-
ducts contain this heterocyclic nucleus and they are widely used as additives in food,
perfumes, agrochemicals, cosmetics, pharmaceuticals,[1] and in the preparations of
insecticides, optical brightening agents, and dispersed fluorescent and laser dyes.[2]
They have various bioactivities, such as inhibition of platelet aggregation,[3] antibac-
terial[4] and anticancer activities[5] inhibition of steroid 5a-reductase,[6] and inhibition
of HIV-1 protease.[7] Coumarins can be synthesized by various methods such as
Pechmann,[8] Perkin,[9] Knoevenagel,[10] and Witting,[11] reactions. However, because
of its simplicity and relatively inexpensive starting materials, the Pechmann reaction
was widely used for the synthesis of coumarins and its derivatives. This method
involves the reaction between phenol with b-keto ester in the presence of acidic
catalysts such as polyphosphoric acid (PPA),[12] InCl3,[13] ZrCl4,[14] Yb(OTf)3,[15–18]
p-TsOH,[19] BiCl3,[20] I2 or AgOTf,[21] and Sm(NO3)3,[22] as well as chloroaluminate
Received August 4, 2009.
Address correspondence to B. Rajitha, Department of Chemistry, National Institute of Technology,
Warangal, India. E-mail: rajithabhargavi@ymail.com
3358

EXPEDITIOUS PECHMANN CONDENSATION
3359
ionic liquids.[23,24] The main disadvantages of the processes using these catalysts are
longer reaction time, large amount of the catalyst, and tedious purification process
after completion of the reaction. Some of the catalysts are highly expensive; some
of the existing methods destroy the catalysts in the workup procedure and they can-
not be recovered or reused. These shortcomings surely indicate demand for a safe,
ecofriendly, and efficient method. Hence, it is essential to develop biodegradable,
ecofriendly, green synthesis of coumarins.
Cellulose is one of the most abundant natural biopolymers and has been stud-
ied during the past several decades because it is a biodegradable material and a
renewable resource. Its unique properties make it an attractive alternative to conven-
tional organic or inorganic supports in catalytic applications. Recently, the approach
has been shifting more toward ecofriendly and reusable catalysts. Recently, cellulose
sulfuric acid has emerged as a solid acid-catalyst for acid catalyzed reactions,
such as synthesis of a-aminonitriles,[25] imidazoazines,[26] quinolines,[27] aryl-14H-
dibenzo[a.j]xanthenes,[28] and 3,4-dihydropyrimidine-2(1H)-ones.[29] Cellulose sulfu-
ric acid can be easily prepared by the reaction of inexpensive cellulose with
chlorosulfonic acid.
RESULTS AND DISCUSSION
It is an established fact in the literature that the Pechmann reaction proceeds
through trans esterification and intramolecular hydroxyalkylation, followed by
dehydration. These three steps are all typical acid-catalyzed reactions. Therefore,
the outcome of the Pechmann reaction depends on an acid catalyst. We now report
a new and efficient method for the synthesis of coumarin. Recently, cellulose sulfuric
acid has emerged as attractive alternative catalyst in terms of acidic strength and
environmentally benign character for various reactions. Presently, thermally driven
organic transformations take place by one of two ways: conventional heating and
microwave (MW) irradiation. Comparatively, MW irradiation is more advantageous
than the conventional method because in the conventional heating method reactants
are slowly activated by a conventional external heat source. Heat is driven into
the substance, passing first through the walls of the vessel to reach the solvent and
reactants. This is a slow and inefficient method for transferring energy into the react-
ing system. In the MW irradiation method, MWs couple directly with the molecules
of the entire reaction mixture, leading to a rapid rise in temperature. Because the
process is not limited by the thermal conductivity of the vessel, the result is an instan-
taneous localized superheating of any substance that will respond to either dipole
reaction or ionic conduction—the two fundamental mechanisms for transferring
energy from microwaves to the substance(s) being heated. When the reaction was
carried out in MW irradiation (method A), phenol and b-ketoester were irradiated
in the presence of cellulose sulfuric acid (catalytic amount) without using any solvent
at 300-W power levels affords the corresponding coumarin in 1–3 min. In the
conventional method (method B), phenol and b-ketoester were stirred at r.t. in the
presence of cellulose sulfuric acid (catalytic amount) under solvent-free conditions,
which afforded the corresponding coumarin in 15–35 min (Scheme 1).
To illustrate the need of the cellulose sulfuric acid for these reactions, an
experiment was conducted in the absence of cellulose sulfuric acid. The yields

3360
B. S. KUARM ET AL.
Scheme 1. Synthesis of coumarins by using cellulose sulfuric acid as a solid acid catalyst.
Table 1. Effect of catalysts on yield
Entry
Catalyst
Yielda (%)
1
2
3
4
5
Cellulose sulfuric acid
Silica sulfuric acid
97
92
85
55
15
p-Toluene sulfonic acid
Sulfuric acid in acetic acid
No catalyst
aYields refer to the pure isolated recovered catalyst.
obtained are very poor, side products are formed, and reactants are not involved
completely in this reaction. Obviously, cellulose sulfuric acid is an important
component of the reaction.
The efficiency of the cellulose sulfuric acid compared to various sulfur-analog
acidic catalysts was also examined (Table 1). In this study, it was found that cellulose
sulfuric acid is a more efficient and superior catalyst over other acidic catalysts with
respect to reaction time and yield. It was also observed that the yield was only 15% in
the absence of the cellulose sulfuric acid catalyst.
EXPERIMENTAL
General Procedure: Method A (Microwave Irradiation)
A mixture of the phenol 1 (1 mmol), b-ketoester 2 (1 mmol), and cellulose
sulfuric acid (0.1 g) was inserted in a microwave oven (BPL, 800 T model) on a
silica-gel solid support and irradiated at 300 W for the appropriate time (Table 2).
Progress of the reaction was checked by thin-layer chromatography (TLC). The
reaction mass was cooled to room temperature, water (5 ml) was added, and it
was stirred for 1–2 min, filtered, and recrystallized from ethanol to afford expected
products 3 in excellent yields.
Method B (Conventional Method)
A mixture of the phenol 1 (1 mmol), b-ketoester 2 (1 mmol), and cellulose
sulfuric acid (0.1 g) was stirred at room temperature for the appropriate
time according to Table 2. Completion of the reaction was confirmed by (TLC).
After completion of the reaction, water (5 ml) was added to the reaction mixture,
and it was stirred for 2 min, filtered, and recrystallized from ethanol to afford

EXPEDITIOUS PECHMANN CONDENSATION
3361
Table 2. Cellulose sulfuric acid–catalyzed synthesis of coumarins

3362
B. S. KUARM ET AL.
Table 3. The effect of reusability of catalyst on yield
Run
Cycle
Yielda (%)
1
2
3
4
0
1
2
3
97
96
92
86
Note. Reaction conditions: Phenol 1 (1 mmol), b-ketoester 2
(1 mmol), and cellulose sulfuric acid (0.1 g) were stirred at room
temperature.
aYields refer to the pure isolated recovered catalyst.
corresponding products in good yields. After filtration, the filtrate (water) containing
the catalyst could be evaporated under reduced pressure to give a white solid.
The recovered catalyst was washed with CH2Cl2, dried in an oven at 60 ꢀC for 5 h
under high pressure prior to use in the other reaction. The recovered catalyst can
be reused at least three additional times in subsequent reactions without significant
loss in product yield (Table 3).
CONCLUSION
In summary, we have successfully developed a facile economic and green
method for construction of coumarins by employing phenols and b-ketoester under
solvent-free conditions in the presence of cellulose sulfuric acid. The notable factors
of this reaction are (a) reasonably good yields, (b) fast reaction, and (c) easy recovery
of catalyst, cellulose sulfuric acid. Thus we believe our procedure will find important
application in the synthesis of coumarin.
ACKNOWLEDGMENT
Financial assistance from the council of Scientific and Industrial Research
(Grant No. 01(2061)=06=EMR-II), New Delhi, is greatly acknowledged.
REFERENCES
1. O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applications, and Mode of Action;
John Wiley and Sons: Chichester, 1997.
2. Murray, R. D.; Mendez, J.; Brown, S. A. The Natural Coumarins: Occurrence, Chemistry,
and Biochemistry; John Wiley & Sons: New York, 1982.
3. Cavettos, G.; Nano, G. M.; Palmisano, G.; Tagliapietra, S. An asymmetric approach to
coumarin anticoagulants via hetero-Diels–Alder cycloaddition. Tetrahedron: Asymmetry
2001, 12, 707.
4. Kayser, O.; Kolodziej, H. Antibacterial activity of extracts and constituents of
Pelargonium sidoides and Pelargonium reniforme. Planta Med. 1997, 63, 508.
5. Wang, C. J.; Hsieh, Y. J.; Chu, C. Y.; Lin, Y. L.; Tseng, T. H. Inhibition of cell cycle
progression in human leukemia HL-60 cells by esculetin. Cancer Lett. 2002, 183, 163.

EXPEDITIOUS PECHMANN CONDENSATION
3363
6. Fan, G. J.; Mar, W.; Park, M. K.; Wook Choi, E.; Kim, K.; Kim, S. A novel class of
inhibitors for steroid 5a-reductase: Synthesis and evaluation of umbelliferone derivatives.
Bioorg. Med. Chem. Lett. 2001, 11, 2361.
7. Kirkiacharian, S.; Thuy, D. T.; Sicsic, S.; Bakhchinian, R.; Kurkjian, R.; Tonnaire, T.
Structure–activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1
protease inhibitors. Farmaco 2002, 57, 703.
8. Sethna, S. M.; Phadke, R. The Pechmann reaction. Org. React. 1953, 7, 1.
9. Donnelly, B. J.; Donnelly, D. M. X.; Sullivan, A. M. O. Dalbergia species—VI: The
occurrence of melannein in the genus Dalbergia. Tetrahedron 1968, 24, 2617.
10. (a) Jones, G. Knoevenagel condensation. Org. React. 1967, 15, 204; (b) Bigi, F.; Chesini,
L.; Maggi, R.; Sartori, G. Montmorillonite KSF as an inorganic, water stable, and
reusable catalyst for the Knoevenagel synthesis of coumarin-3-carboxylic acids. J. Org.
Chem. 1999, 64, 1033.
11. Yavari, I.; Hekmat-Shoar, R.; Zonuzi, A.
A new and efficient route to 4-
carboxymethylcoumarins mediated by vinyltriphenylphosphonium salt. Tetrahedron
Lett. 1998, 39, 2391.
12. Nadkarni, A. J.; Kudav, N. A. Convenient synthesis of 8-methoxy-4-methyl-coumarin.
Ind. J. Chem. 1981, 20B, 719–720.
13. Bose, D. S.; Rudradas, A. P.; Babu, M. H. The indium(III) chloride-catalyzed von
Pechmann reaction: A simple and effective procedure for the synthesis of 4-substituted
coumarins. Tetrahedron Lett. 2002, 43, 9195.
14. Smitha, G.; Reddy, C. S. ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins
under solvent-free conditions. Synth. Commun. 2004, 34, 3997.
15. Wang, L.; Xia, J.; Tian, H.; Qian, C.; Ma, Y. Synthesis of coumarin by Yb(OTf)3-
catalyzed Pechmann reaction under the solvent-free conditions. Ind. J. Chem. 2003,
42B, 2097.
16. Woods, L. L.; Sapp, J. A new one-step synthesis of substituted coumarins. J. Org. Chem.
1962, 27, 3703.
17. Zagotto, G.; Gia, O.; Baccichetti, F.; Uriarte, E.; Palumbo, M. Synthesis and photobio-
logical properties of 4-hydroxymethyl-40-methylpsoralen derivatives. Photochem.
Photobiol. 1993, 58, 486–491.
18. Khaikin, M. S.; Petrova, N. L.; Kukhtin, V. A. Chlorination of dihydroxy coumarins. Zh.
Obshch. Khim. 1963, 33, 3941.
19. Sugino, T.; Tanaka, K. Solvent-free coumarin synthesis. Chem. Lett. 2001, 2, 110.
20. Sachin, B. P.; Ramakrishna, P. B.; Vivek, P. R.; Shriniwas, D. S. Ultrasound-assisted
pechmann condensation of phenols with b-ketoesters to form coumarins, in the presence
of bismuth(III) chloride catalyst. Synth. Commun. 2006, 36, 525.
21. Jie, W.; Tianning, D.; Wei, S.; Yizhe, L. Expeditious approach to coumarins via
Pechmann reaction catalyzed by molecular iodine or AgOTf. Synth. Commun. 2006, 36,
2949.
22. Sushilkumar, S. B.; Devanand, B. S. Samarium(III)-catalyzed one-pot construction of
coumarins. Tetrahedron Lett. 2004, 45, 7999.
23. Mahesh, P. K.; Swapnil, M. S.; Manikrao, S. M. Coumarin syntheses via Pechmann
condensation in Lewis acidic chloroaluminate ionic liquid. Tetrahedron Lett. 2001, 42,
9285–9287.
24. Amit, K. C.; Bhushan, K. M. Pechmann reaction in chloroaluminate ionic liquid. Synlett
2002, 152.
25. Ahmad, S.; Ali, M. Cellulose sulfuric acid as a bio-supported and recyclable solid acid
catalyst for the one-pot three-component synthesis of a-amino nitriles. Appl. Catal. A:
Gen. 2007, 331, 149.

3364
B. S. KUARM ET AL.
26. Ahmad, S.; Ali, M.; Jafar, M. R.; Ebrahim, S. Cellulose sulfuric acid catalyzed one-pot
three-component synthesis of imidazoazines. Chem. Pharm. Bull. 2007, 55, 957.
27. Ahmad, S.; Abbas, R.; Zahra, B. Sulfonated cellulose and starch: New biodegradable
and renewable solid acid catalysts for efficient synthesis of quinolines. Catal. Commun.
2008, 9, 13.
28. Venu Madhav, J.; Thirupathi Reddy, Y.; Narsimha Reddy, P.; Nikhil Reddy, M.; Suresh,
K.; Crooks, P. A.; Rajitha, B. Cellulose sulfuric acid: An efficient biodegradable and
recyclable solid acid catalyst for the one-pot synthesis of aryl-14H-dibenzo [a.j] xanthenes
under solvent-free conditions. J. Mol. Catal. A 2009, 304, 85–87.
29. Narsimha Reddy, P.; Thirupathi Reddy, Y.; Nikhil Reddy, M.; Rajitha, B.; Crooks, P. A.
Cellulose sulfuric acid: An efficient biodegradable and recyclable solid acid catalyst for
the one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-ones. Synth. Commun. 2009, 39,
1257.