Cellulose sulfuric acid: An efficient biodegradable and recyclable solid acid catalyst for the synthesis of 1-oxo-hexahydroxanthene

Article abstract of DOI:10.1080/00397911.2010.492076

A series of 1-oxo-hexahydroxanthene derivatives was synthesized at room temperature in solid state from substituted salicylaldehydes and substituted 1,3-hexanediones in the presence of a catalytic amount of cellulose sulfuric acid. The results showed that

Full text of DOI:10.1080/00397911.2010.492076

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Cellulose Sulfuric Acid: An Efficient
Biodegradable and Recyclable Solid Acid
Catalyst for the Synthesis of 1-Oxo-
hexahydroxanthene
a
a
a
B. Suresh Kuarm , J. Venu Madhav , S. Vijaya Laxmi , B. Rajitha
a
b
b
b
,
Y. Thirupathi Reddy , P. Narsimha Reddy & Peter A. Crooks
a
Department of Chemistry, National Institute of Technology,
Warangal, India
b
Department of Pharmaceutical Sciences, College of Pharmacy,
University of Kentucky, Lexington, Kentucky, USA
Version of record first published: 29 Apr 2011
To cite this article: B. Suresh Kuarm, J. Venu Madhav, S. Vijaya Laxmi, B. Rajitha, Y. Thirupathi
Reddy, P. Narsimha Reddy & Peter A. Crooks (2011): Cellulose Sulfuric Acid: An Efficient Biodegradable
and Recyclable Solid Acid Catalyst for the Synthesis of 1-Oxo-hexahydroxanthene, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:12, 1719-1724
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1
Synthetic Communications , 41: 1719–1724, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.492076
CELLULOSE SULFURIC ACID: AN EFFICIENT
BIODEGRADABLE AND RECYCLABLE SOLID ACID
CATALYST FOR THE SYNTHESIS OF
1-OXO-HEXAHYDROXANTHENE
1
B. Suresh Kuarm, J. Venu Madhav, S. Vijaya Laxmi,
1
1
2
1
2
B. Rajitha, Y. Thirupathi Reddy, P. Narsimha Reddy, and
2
Peter A. Crooks
1
Department of Chemistry, National Institute of Technology,
Warangal, India
2
Department of Pharmaceutical Sciences, College of Pharmacy,
University of Kentucky, Lexington, Kentucky, USA
GRAPHICAL ABSTRACT
Abstract A series of 1-oxo-hexahydroxanthene derivatives was synthesized at room
temperature in solid state from substituted salicylaldehydes and substituted 1,3-hexane-
diones in the presence of a catalytic amount of cellulose sulfuric acid. The results showed
that the reaction performed under solid-state conditions was benign to the environment, with
higher yields and more convenient workup.
Keywords Cellulose sulfuric acid; 1,3-hexanedione; 1-oxo-hexahydro xanthene;
substituted salicylaldehydes; solid state
INTRODUCTION
-Oxo-hexahydroxanthene and their derivatives have drawn much attention in
1
the field of medicinal chemistry. These oxygen-containing heterocycles have been
reported to exert various biological and pharmacological properties, such as anti-
[
1]
[2]
estrogenic activity, antimicrobial activity, insulin-sensitizing activities, selective
[3]
[4]
[5]
thrombin (THR) inhibitory activity, hypoglycemic activity, and antibacterial
[
activity. Particularly, xanthenediones constitute a structural unit in a number of
6]
[7]
natural products and have been used as versatile synthons because of the inherent
Received January 20, 2010.
Address correspondence to B. Rajitha, Department of Chemistry, National Institute of
Technology, Warangal, AP, India. E-mail: rajithabhargavi@ymail.com
1
719

1720
B. SURESH KUARM ET AL.
Scheme 1. Synthesis of 1-oxo-hexahydroxanthene using cellulose sulfuric acid.
reactivity of the inbuilt pyran ring. Thus, the synthesis of a variety of benzopyran
heterocyclic molecules is desirable. Recently, benzopyran derivatives have been
synthesized by the reaction of substituted salicyaldehydes with dimedone catalyzed
[
8]
[9]
[10]
by KF-Al O , triethylbenzylammonium chloride (TEBA), ([Hmim]TFA),
3
2
[11]
and Amberlyst-15.
Unfortunately, some of these methods suffer from severe
drawbacks, including use of large amounts of expensive reagents and catalysts, poor
yields, use of toxic solvents and catalysts, longer reaction times, and tedious workup
procedures, which necessitate the development of an alternative route for the syn-
thesis of these biologically active molecules.
Cellulose is one of the most abundant natural biopolymers in the world and
has been widely studied during the past several decades because it is a biodegradable
material and a renewable resource. Its unique properties make it an attractive alter-
native as a conventional organic or inorganic support in catalytic applications.
Recently, the direction of science and technology has been shifting more toward eco-
friendly and reusable catalysts in organic synthesis. Thus, natural biopolymers are
[
12]
attractive candidates in the search for such solid-support catalysts.
cellulose sulfuric acid (CSA) has emerged as a promising biopolymeric solid-support
Recently,
[
13]
acid catalyst for acid-catalyzed reactions, such as the synthesis of a-aminonitriles,
imidazoazines, quinolines, aryl-14H-dibenzo[a.j]xanthenes, 3,4-dihydropyri-
midine-2(1H)-ones, Pechmanncondensation, andthiadiazolobenzimidazoles.
In continuation of our investigation on new catalysts, we report the solid-state
[14]
[15]
[16]
[17]
[18]
[19]
[
20]
synthesis
stituted 1,3-hexanediones by using cellulose sulfuric acid as a solid acid catalyst
Scheme 1).
of 1-oxo-hexahydroxanthene with substituted salicylaldehyde and sub-
(
RESULTS AND DISCUSSION
Cellulose sulfuric acid is one of the important catalysts for the selective
construction of heterocyclic ring systems, especially in the synthesis of 1-oxo-
hexahydroxanthene. The catalyst decreases the production of chemical waste
without using some highly toxic reagents in the synthesis of these products. All
the reactions were carried out at room temperature by the addition of cellulose
sulfuric acid to the mixture of substituted salicylaldehyde and substituted 1,3-
hexanediones and by grinding the mixture in a mortar. The process was monitored
by thin-layer chromatography (TLC). The results showed that the reactions were
completed within 20–30 min of grinding, and the desired products were obtained
in excellent yields (Table 1).

SYNTHESIS OF 1-OXO-HEXAHYDROXANTHENE
1721
Table 1. Synthesis of 1-oxo-hexahydroxanthene derivatives using cellulose sulfuric acid
a
Entry
Aldehydes
R
1
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
2-Hydroxybenzaldehyde
CH
CH
CH
CH
CH
CH
CH
CH
CH
H
3
3
3
3
3
3
3
3
3
20
25
23
25
28
30
25
20
20
22
28
30
25
30
30
96
91
87
93
95
92
93
94
96
92
94
94
91
93
95
2-Hydroxy3-methoxybenzaldehyde
2-Hydroxy5-methylbenzaldehyde
2-Hydroxy5-chlorobenzaldehyde
2-Hydroxy5-bromobenzaldehyde
2-Hydroxy5-nitrobenzaldehyde
2-Hydroxy3,5-dichlorobenzaldehyde
2-Hydroxy3,5-bromobenzaldehyde
2-Hydroxy-naphthalene-1- carbaldehyde
2-Hydroxybenzaldehyde
1
1
1
1
1
1
0
1
2
3
4
5
2-Hydroxy5-chlorobenzaldehyde
2-Hydroxy5-bromobenzaldehyde
2-Hydroxy3,5-dichlorobenzaldehyde
2-Hydroxy3,5-bromobenzaldehyde
2-Hydroxy-naphthalene-1-carbaldehyde
H
H
H
H
H
a
Yields refer to pure solid products; all products were reported in the literature and were characterized
by comparison of their physical and spectral data with those previously reported.
We then investigated the efficiency of the cellulose sulfuric acid compared
to various sulfur analog acidic catalysts. The results are summarized in Table 2.
Cellulose sulfuric acid was found to be the most effective catalyst based on the
product yield. The reaction did not proceed in the absence of catalyst (yield less
than 10%).
We examined the effect of the amount of catalyst in this reaction. The best
results were obtained using 0.08 g of catalyst (96%). Using lower amounts of catalyst
resulted in lower yields, and in the absence of catalyst the yield of the product was
found to be very low (Table 3).
The reusability of the catalyst was checked by separating the cellulose sulfuric
acid from the reaction mixture by simple filtration, washing with CH Cl , and drying
2
2
ꢀ
in a vaccum oven at 60 C for 5 h prior to reuse in subsequent reactions. The recov-
ered catalyst can be reused at least three additional times in subsequent reactions
without significant decrease in product yield (Table 4).
a
Table 2. Effect of catalysts on yield
b
Entry
Catalyst
Yield (%)
1
2
3
4
5
Cellulose sulfuric acid
Methane sulfonic acid
Silica sulfuric acid
Sulfuric acid in acetic acid
No catalyst
96
92
86
59
10
a
Mixture of salicylaldehyde (1 mmol), 1,3-hexanedione (2 mmol), and various cat-
alysts such as cellulose sulfuric acid (0.08 g), methane sulfonic acid (0.1 mmol), silica
sulfuric acid (0.08 g), and sulfuric acid in acetic acid (0.1 mmol) was used.
b
Isolated yield.

1722
B. SURESH KUARM ET AL.
a
Table 3. Influence of the catalytic amounts of cellulose sulfuric acid
b
Entry
Catalyst (g)
Time (min)
Yield (%)
1
2
3
4
5
6
None
0.01
0.03
0.05
0.08
0.08
60
20
20
20
40
20
Trace
28
51
79
96
96
a
Mixture of salicylaldehyde (1 mmol), 1,3-hexanedione (2 mmol), and cellulose sul-
furic acid was used, but we observed variation in catalyst loading: 0.01 g, yield 28%;
0
.03 g, yield 51%; 0.05 g, yield 79%; 0.08 g, yield 96%.
b
isolated yield.
a
Table 4. Results of recyclability of the catalyst
b
Run
Cycle
Yield (%)
1
2
3
4
0
1
2
3
96
93
87
72
a
Mixture of salicylaldehyde (1 mmol), 1,3-hexanedione
2 mmol), and cellulose sulfuric acid (0.08 g) was ground with
a pestle in a mortar.
(
b
Isolated yield.
EXPERIMENTAL
A mixture of salicylaldehyde (1 mmol) and 1,3-hexanedione (2 mmol) was
taken in a mortar. Cellulose sulfuric acid (0.08 g) was added to this and ground with
a pestle at room temperature until the reaction was completed (progress of the reac-
tion was observed by TLC) (Table 1). After completion of the reaction, the crude
reaction mass was extracted with EtOAc, the organic layer was washed with brine
solution and dried (anhydrous Na SO ), and the solvent was evaporated under
2
4
reduced pressure. The resulting product was purified by column chromatography,
ethyl acetate þ hexane (2:8), to afford the pure compound.
CONCLUSION
In conclusion, we have developed a novel and efficient method for the synthesis
of 1-oxo-hexahydroxanthene in excellent yields employing cellulose sulfuric acid as a
solid acid catalyst. The application of an inexpensive, easily available, and reusable
catalyst makes this method simple, clean, practical, and economically viable. We
believe this methodology is superior to existing methodologies for the synthesis of
1
-oxo-hexahydroxanthene.

SYNTHESIS OF 1-OXO-HEXAHYDROXANTHENE
1723
ACKNOWLEDGMENT
Financial assistance from the Council of Scientific and Industrial Research
Grant No. 01(2061)=06=EMR-II), New Delhi, is gratefully acknowledged.
(
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