Facile synthesis of octahydroxanthenes by one-pot reaction under solvent-free condition

Article abstract of DOI:10.14233/ajchem.2016.19746

Synthesis of 1,8-dioxo-octahydroxanthenes by cyclocondensation of 5,5-dimethyl-1,3-cyclohexanedione and aromatic aldehydes using catalytic amount of CuCl₂·2H₂O under solvent free condition is reported. Structures of ten compounds are

Full text of DOI:10.14233/ajchem.2016.19746

Asian Journal of Chemistry; Vol. 28, No. 7 (2016), 1528-1530
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19746
Facile Synthesis of Octahydroxanthenes by One-Pot Reaction under Solvent-Free Condition
1,*
2
2
2
L. RONIBALA DEVI , L. VARTIMA CHANU , I. HARIMALA CHANU and O. MUKHERJEE SINGH
1
2
Department of Basic Science and Humanities, National Institute of Technology Manipur, Langol-795 004, India
Department of Chemistry, Manipur University, Canchipur-795 003, Manipur, India
*
Corresponding author: E-mail: laisroni@gmail.com
Received: 26 November 2015; Accepted: 16 February 2016;
Published online: 31 March 2016;
AJC-17843
Synthesis of 1,8-dioxo-octahydroxanthenes by cyclocondensation of 5,5-dimethyl-1,3-cyclohexanedione and aromatic aldehydes using
catalytic amount of CuCl
analytical data.
2
·2H O under solvent free condition is reported. Structures of ten compounds are characterized by spectral and
2
Keywords: Tetramethyl-1,8-dioxo-octahydroxanthenes, CuCl
2
·2H O, 5,5-Dimethyl-1,3-cyclohexendione, Solvent-free.
2
pyrroles and dihydrofuran [14]. In continuation of our work
on the application of cupric chloride in the synthesis of organic
compounds [15], here we report the synthesis of 1,8-dioxo-
INTRODUCTION
1
,8-Dioxo-octahydroxanthenes are well known hetero-
cyclic compounds possessing xanthene units in their structural
frameworks. Xanthene derivatives constitute an important class
of organic compounds containing naturally occurring and
synthetic heterocycles and occupy a prominent position in
medicinal chemistry [1]. Xanthene-based compounds have also
been investigated for agricultural bactericide activity [2], anti-
inflammatory effect [3] and antiviral activity [4]. Xanthene-
diones constitute a structural unit in a number of natural
products [5] and have been used as versatile synthons because
of the inherent reactivity of the inbuilt pyran ring [6]. Thus,
the synthesis of these heterocyclic compounds is interesting
for both organic synthesis and medicinal chemistry. Many
methods are reported for the synthesis of xanthenes. Among
these methods, the condensation of aldehydes with 1,3-cyclo-
hexanedione or 5,5-dimethyl-1,3-cyclohexanedione to the
corresponding xanthenes were found to be conducted success-
fully in the presence of strong protonic acids [7], Lewis acids
octahydroxanthenes catalyzed by CuCl
free condition (Scheme-I).
2
·2H
2
O under solvent
CHO
O
O
CuCl ·2H O
2
2
2
+
R
9
0 °C
O
O
O
R
Scheme-I
EXPERIMENTAL
Reagents were used without further purification. Commer-
cial solvents were used after distillation. Melting points were
determined on a “Veego MP-I” capillary melting point appa-
ratus and are uncorrected. The IR spectra were recorded on
and Shimadzu IR 408 spectrometers. Infrared spectra were
recorded as thin films on KBr plates with νmax in cm . Column
chromatography was performed on Merck Silica Gel 60 (230-
400 mesh) using analytical reagent grade hexane and ethyl
acetate as eluents.
Synthesis of octahydroxanthene derivatives:Aromatic
aldehyde (2) (0.5 mol), 1,3-cyclohaxenedione (1) (1 mol) and
such as InCl
3
·4H
2
O [8], FeCl
3
.8H
2
O [9], NaHSO
4
[10], p-
dodecylbenzenesulphonic acid [11], acidic ionic liquid [12],
3+
Fe montmorilonite [13]. However, most of these methods
often suffer from the drawbacks of long reaction times, harsh
reaction conditions, toxicity and difficulty in product separation.
In recent years, copper compounds have been used as
catalyst in organic synthesis because these compounds are
easy to handle, low cost and good stability. Among these,
–1
CuCl
2
·2H O has emerged as medium and as well as catalyst in
2
various organic transformations like carbonylation of
alkylamines and heterocyclization to pyrrolidinone, pyridinones,
CuCl
2
·2H
2
O (0.4 mmol) were heated at 90 °C with stirring
for 30-45 min. Then water was added and the product was

Vol. 28, No. 7 (2016)
Facile Synthesis of Octahydroxanthenes by One-Pot Reaction under Solvent-Free Condition 1529
13
extracted with chloroform. After the organic layer was dried
over sodium sulphate and evaporated, the residue was recrysta-
llized by ethanol and chloroform to products 3. In cases where
further purification was required, the crude products were
4H), 2.45 (s, 4H), 4.67 (s, 1H), 7.11-7.27 (m, 4H); C NMR
(75.5 MHz, CDCl , δ ppm) 27.1, 30.5, 33.9, 43.6, 51.6, 116.3,
127.2, 128.5, 130.7, 135.1, 143.2, 157.7, 165.3. Anal. calcd.
Cl: C, 71.77; H, 6.45. Found: C, 71.83; H, 7.23.
3
for C23
H
25
O
3
subjected to column chromatography on SiO
amounts of ethyl acetate in hexanes as eluent.
,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-phenyl-2H-
2
, using increasing
9-(2-Bromophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3h): White solid;
–1
1
3
IR (KBr, νmax, cm ): 3027, 2982, 1684, 1670, 1621; H NMR
(300 MHz, CDCl , δ ppm): 1.03 (s, 6H), 1.11 (s, 6H) 2.06 (q,
4H), 2.45 (s, 4H), 4.56 (s, 1H), 7.21-7.34 (m, 4H); C NMR
(75.5 MHz, CDCl , δ ppm) 27.3, 30.6, 31.3, 44.6, 51.6, 114.3,
126.2, 127.4, 128.5, 131.8, 134.5, 144.7, 159.7, 166.7. Anal.
xanthene-1,8(5H,9H)-dione (3a): White solid; IR (KBr, νmax
,
, δ
3
–1
1
13
cm ): 3030, 2933, 1661, 1586; H NMR (300 MHz, CDCl
3
ppm): 0.98 (s, 6H) 1.65 (s, 6H), 2.24 (dd, 4H), 2.44 (dd, 4H),
3
1
3
4
.89 (s, 1H), 7.22-7.34 (m, 5H); C NMR (75.5 MHz, CDCl
δ ppm) 20.2, 27.1, 31.5, 36.9, 116.8, 126.4, 128.0, 128.3, 144.3,
63.9, 196.5,Anal. calcd. for C23 : C,78.3, H,7.47. Found:
C, 78.32; H, 7.3.
,4,6,7-Tetrahydro-3,3,6,6-tetramethyl-9-p-tolyl-2H-
3
calcd. for C23
7.23.
H
25
3
O Br: C, 71.77; H, 6.45. Found: C, 71.83; H,
1
H
26
O
3
9-(2,4-Dichlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-
3
hexahydro-1H-xanthene-1,8-(2H)-dione (3i): White solid;
–1
1
xanthene-1,8(5H,9H)-dione (3b):White solid; IR (KBr, νmax
,
, δ
IR (KBr, νmax, cm ): 3031, 2984, 1683, 1672, 1625; H NMR
(300 MHz, CDCl , δ ppm): 1.02 (s, 6H), 1.13 (s, 6H) 2.26 (q,
4H), 2.46 (s, 4H), 7.20 (s, 1H), 7.34 (d, 2H); C NMR (75.5
MHz, CDCl , δ ppm) 27.4, 30.3, 30.7, 44.6, 51.2, 114.3, 126.2,
128.4, 128.7, 130.8, 134.5, 146.7, 157.7, 167.3. Anal. calcd.
Cl : C, 65.88; H, 5.77. Found: C, 65.83; H, 5.63.
–1
1
cm ): 3028, 2931, 1665, 1560; H NMR (300 MHz, CDCl
3
3
13
ppm): 1.62 (s, 6H), 1.92 (s, 6H), 2.26 (dd, 4H), 2.34 (s, 3H),
1
3
2
.47 (dd, 4H), 4.77 (s, 1H), 7.0-7.19 (aro., 4H); C NMR (75.5
MHz, CDCl , δ ppm) 20.2, 21.0, 27.1, 31.1, 36.9, 117.0, 128.2,,
28.8, 135.9, 141.48, 163.7, 196.6. Anal. calcd. for C24
C, 79.09; H7.74. Found: C, 79.05; H, 7.81.
,4,6,7-Tetrahydro-9-(4-methoxyphenyl)-3,3,6,6-
tetramethyl-2H-xanthene-1,8(5H,9H)-dione (3c): White
3
3
1
H
28
O
3
:
for C23
H
24
O
3
2
9-(3-Nitrophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-
3
hexahydro-1H-xanthene-1,8-(2H)-dione (3j): White solid;
–1
1
IR (KBr, νmax, cm ): 3027, 2982, 1684, 1670, 1621; H NMR
(300 MHz, CDCl , δ ppm): 0.96 (s, 6H), 1.01 (s, 6H) 1.86 (q,
4H), 2.85 (s, 4H), 3.96 (s, 1H), 7.14-7.33 (m, 4H); C NMR
(75.5 MHz, CDCl , δ ppm) 27.7, 30.4, 32.5, 44.6, 51.3, 113.4,
119.2, 125.4, 128.6, 133.7, 143.4, 148.7, 155.7, 169.3. Anal.
–1
1
solid; IR (KBr, νmax, cm ): 3025, 2987, 1684, 1661; H NMR
300 MHz, CDCl , δ ppm): 1.01 (s, 6H) 1.92 (s, 6H), 3.7 (s,3H),
.7 (s, 1H), 6.74-7.22(aro.,4H); C NMR (75.5 MHz, CDCl
δ ppm) 20.9, 27.1, 30.7, 32.0, 31.1, 36.9, 117.0, 128.2, 128.8,
35.9, 141.48, 163.7, 196.6. Anal. calcd. for C24
5.76; H,7.41. Found: C, 75.62; H, 7.45.
3
13
(
4
3
13
3
,
3
1
7
H
28
O
4
: C,
calcd. for C23
6.23.
H
25NO : C, 69.86; H, 6.37. Found: C, 69.83; H,
5
9
-(4-Chlorophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetra-
RESULTS AND DISCUSSION
methyl-2H-xanthene-1,8(5H,9H)-dione (3d): White solid;
IR (KBr, νmax, cm ): 3028, 2987, 1680, 1660, 1620; H NMR
–1
1
Initially, benzaldehyde (1a) was selected as the represen-
tative arylaldehyde to investigate the optimized reaction
conditions and the results are listed in Table-1. Obviously,
catalyst had important effects on the reaction. The reaction in
(
(
300 MHz, CDCl
dd, 4H), 2.44 (dd, 4H), 7.22-7.34 (m, 5H); C NMR (75.5
, δ ppm) 20.9, 27.1, 30.7, 31.1, 36.9, 117.0, 128.2,
28.8, 135.9, 141.48, 163.7, 196.6.Anal. calcd. for C23 Cl:
C, 71.77; H,6.55. Found: C, 71.78; H, 6.45.
,3,6,6-Tetramethyl-9-(4-nitrophenyl)-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3e): White solid;
3
, δ ppm): 0.98 (s, 6H) 1.23 (s, 6H), 2.45
13
MHz, CDCl
3
1
H
25
O
3
presence of catalytic amount of CuCl
the addition of a catalytic amount of BiCl
product with high yield but with longer time (Table-1). How-
ever, the addition of a catalytic amount of CuCl ·2H O resulted
in the product 3a-e with maximum yield of 80-95 % at 80-
0 °C within 30-50 min. Thus we optimized experimental
conditions at 90 °C using CuCl ·2H O as catalyst under solvent-
2
gives low yield product;
3
resulted in the
3
2
2
–1
1
IR (KBr, νmax, cm ): 3024, 2977, 1689, 1666, 1632; H NMR
300 MHz, CDCl ): δ 0.99 (s, 6H), 1.11 (s, 6H), 2.18 (dd,
H), 2.49 (s, 4H), 4.82 (s, 1H), 7.47(d, 2H), 7.47 (d, 2H); C
NMR (75.5 MHz, CDCl , δ ppm) 21.9, 26.1, 31.7, 32.2, 33.9,
19.1, 127.2, 128.9, 136.9, 140.28, 161.7, 195.2. Anal. calcd.
: C, 69.86; H,6.37. Found: C, 69.78; H, 6.45.
-(4-Hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3f): White solid;
(
4
3
9
13
2
2
3
free condition and extended to various aldehydes (2). Under
these optimized reaction conditions, the scope and efficiency
of this reaction was explored for the synthesis of a wide variety
of octahydroxanthenes (10) and results are summarized in
Table-2. As can be seen from Table-2, aromatic aldehydes
containing electron donating groups (such as methyl, methoxy)
were found reacting smoothly and give higher yield.
1
for C23
H25NO
5
9
–1
1
IR (KBr, νmax, cm ): 3030, 2965, 1677, 1669, 1643; H NMR
(
(
(
1
C
300 MHz, CDCl
s, 4H), 4.67 (s, 1H), 6.61 (d, 2H), 7.11 (d, 2H); C NMR
75.5 MHz, CDCl , δ ppm) 26.1, 31.7, 32.2, 33.9, 44.6, 51.6,
19.1, 127.2, 128.9, 136.9, 140.28, 161.7. Anal. calcd. for
: C, 69.86; H,6.37. Found: C, 75.38; H, 7.15.
-(2-Chlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-
hexahydro-1H-xanthene-1,8-(2H)-dione (3g): White solid;
3
, δ ppm): 1.09 (s, 12H), 2.21 (q, 4H), 2.45
13
3
TABLE-1
CONDENSATION REACTION OF BENZALDEHYDE
AND DIMETHYL-1,3-CYCLOHEXANEDIONE UNDER
DIFFERENT REACTION CONDITIONS
23
H
26
O
4
9
Entry
Catalyst
Time (min)
30-40
Yield (%)
80-95
70-80
1
2
3
CuCl2
–1
1
IR (KBr, νmax, cm ): 3027, 2982, 1684, 1670, 1621; H NMR
300 MHz, CDCl , δ ppm): 1.03 (s, 6H), 1.11 (s, 6H) 2.34 (q,
BiCl3
120-240
1-2
(
3
SnCl
2
60-70

1
530 Devi et al.
Asian J. Chem.
TABLE-2
conversions, simplicity in operation, solvent-free conditions
and use of low cost and commercially available copper(II)
chloride as catalyst.
SYNTHESIS OF 9-ARYL SUBSTITUTED 1,8-DIOXO-
OCTAHYDROXANTHENES USING CuCl ·2H O
2
2
Time
Yield
(%)
m.p.
(°C)
Entry
R
Product
(
min)
35
30
40
38
45
35
40
43
47
45
ACKNOWLEDGEMENTS
1
2
3
4
5
6
7
8
9
C H5
6
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
90
84
70
69
75
72
73
68
69
203-204
217-219
240-241
228-230
223-224
243-244
202-203
207-208
203-204
201-202
One of the authors (O.M.S.) is thankful to Department of
Biotechnology, New Delhi, India for financial assistance (Project
No.BT/278/TBP/2011).
4-MeC H4
6
4-MeOC H4
6
4-ClC H4
6
4-NO C H
4
2
6
4-OHC H4
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–1
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1
13
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1
1. J.P. Poupelin, G.S. Ruf, O.F. Blandpin, G. Narcisse, G.U. Ernouf and
1
13
1
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3
, δ ppm) 0.98 (s, 6H), 1.65 (s, 6H), 2.24 (d, 4H), 2.44
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13
(
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3
1
8
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1
28,3, 144.3, 163.9, 196.5.
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2
is proved to be an efficient catalyst
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for the synthesis of 1,8-dioxooctahydroxanthene derivatives
by condensation of aldehydes with 1,3-cyclohexanedione. This
method is bestowed with several unique merits, such as high