An efficient one-pot solvent-free synthesis and photophysical properties of 9-aryl/alkyl-octahydroxanthene-1,8-diones

Article abstract of DOI:10.1016/j.tet.2011.03.078

A facile and efficient protocol for the synthesis of 9-aryl/alkyl-3,3,6,6- tetramethyl-1,2,3,4,5,6,7,8-octahydroxanthene-1,8-diones has been developed by one-pot reaction of dimedone with aldehydes in the presence of InCl₃ or P₂O

Full text of DOI:10.1016/j.tet.2011.03.078

Tetrahedron 67 (2011) 3698e3704
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient one-pot solvent-free synthesis and photophysical properties
of 9-aryl/alkyl-octahydroxanthene-1,8-diones
*
Girijesh K. Verma, Keshav Raghuvanshi, Rajiv K. Verma, Pratibha Dwivedi, M.S. Singh
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and efficient protocol for the synthesis of 9-aryl/alkyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octa-
hydroxanthene-1,8-diones has been developed by one-pot reaction of dimedone with aldehydes in the
presence of InCl3 or P2O5 under solvent-free conditions. The optical behaviors of the xanthenediones
have been investigated by UVevis and fluorescence spectroscopy. The present approach offers the ad-
vantages of simple methodology, clean and mild reaction, high atom-economy, short reaction time, low
environmental impact, wide substrate scope, high yield, and excellent purity.
Received 15 January 2011
Received in revised form 7 March 2011
Accepted 22 March 2011
Available online 30 March 2011
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
One-pot synthesis
Tetramethyloctahydroxanthene-1,8-diones
Dimedone
Aldehydes
Indium trichloride
P2O5
Solvent-free condition
Optical behavior
1. Introduction
and in photodynamic therapy.8 Furthermore, these compounds can
be used as dyes,9 in laser technologies,10 and as pH sensitive fluo-
There are a number of environmental implications of the use of
a large volume of organic solvents since they are utilized in larger
quantities than the solutes they carry, and are wasted into the
environment through evaporation and leakage. Because of the in-
creasing concern for the harmful effects of organic solvents on the
environment and human body, organic reactions that are operated
without conventional organic solvents have aroused attention of
organic chemists. Many organic reactions have been reported to
proceed efficiently under solvent-free conditions and sometimes
show enhanced selectivity1 also. Therefore, more and more
chemist’s synthetic endeavors are devoted toward nature friendly
synthesis2a to reduce drastic prerequisites for reactions. Among the
proposed solutions, solvent-free conditions hold a leading position.
So, it is now often claimed that ‘the best solvent is no solvent’.2b
Xanthenes are important classes of organic compounds of a large
number of naturally occurring as well as synthetic derivatives, and
occupy a prominent position in medicinal chemistry.3 They are im-
portant biologically active heterocyclic compounds possessing an-
tiviral,4 anti-inflammatory,5 and antibacterial6 activities. These are
being utilized as antagonists for paralyzing action of zoxazolamine7
rescent materials for visualization of biomolecules.11 In particular,
xanthenediones constitute a key structural motif in a number of
natural products,12 and have been used as versatile synthons be-
cause of the inherent reactivity of the inbuilt pyran ring.13 Synthesis
of xanthenediones is a continuing hot topic because these moieties
are privileged pharmacophores as well as valuable reactive in-
termediates for both synthetic and medicinal chemists.
Several elegant strategies for the synthesis of xanthenediones
involving different types of catalysts have been reported.1j,14e20 The
above methods show varying degrees of successes as well as lim-
itations, such as prolonged reaction times, low yields, use of toxic
and costly reagents/catalysts, harsh reaction conditions, and com-
plex work-up procedures. Keeping in view the disadvantages as-
sociated with reported protocols as well as increasing importance
of xanthenediones in pharmaceutical and industrial chemistry,
there still remains a high demand for the development of more
general, efficient, and eco-friendly protocol to assemble such scaf-
folds. Indium trichloride has emerged as a highly efficient and ef-
fective potential Lewis acid catalyst imparting high regio- and
chemo-selectivity in various chemical transformations,21 due to its
low toxicity, air and water compatibility, operational simplicity, and
remarkable ability to suppress side reactions in acid sensitive
substrates. A literature survey shows that P2O5 is a mild and
* Corresponding author. Fax: þ91 542 2368127; e-mail address: mssinghbhu@
yahoo.co.in (M.S. Singh).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.078

G.K. Verma et al. / Tetrahedron 67 (2011) 3698e3704
3699
selective catalyst, easy to handle and readily biodegradable, and has
been utilized widely in various organic transformations,22 and
given many advantages in several organic synthesis.23
P2O5 showed maximum yield in minimum time at 100 ꢀC (Table 1,
entry 13). A further increasing of catalyst loading did not affect the
yield (Table 1, entry 14). Herein, the reaction temperature was cru-
cial in terms of the reaction rate and product yield. The above model
reaction was carried out at different temperatures (60, 70, 80, and
100 ꢀC) with 15 mol % of InCl3 and 20 mol % of P2O5 loading sepa-
rately. It was found that the desired compound 4b was obtained in
excellent yield at 100 ꢀC (Table 1, entries 10e13). Further increase of
the temperature (120 ꢀC) neither increased the yield nor shortened
the reaction time. The time taken for complete conversion (moni-
tored by TLC) and the isolated yields at different temperatures are
recorded in Table 1 for both the catalysts.
2. Results and discussion
Our literature survey at this stage revealed that there are no re-
ports on the use of InCl3 or P2O5 as catalyst in the synthesis of
octahydroxanthene-1,8-diones under solvent-free conditions. Our
main strategy in this work is to develop a solvent-free organic re-
action enhancement methodology, which is extremely fast and
cleaner than conventional reactions, and lead to higher atom
economy. In continuation of our interest in the area of clean syn-
thesis under solvent-free conditions using InCl3 or P2O5 as efficient
and effective catalysts for the development of useful synthetic
methodology24 herein, we report a simple, efficient, and one-pot
reaction of dimedone and aldehydes using InCl3 or P2O5 at 100 ꢀC for
the preparation of 9-aryl/alkyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-
octahydroxanthene-1,8-diones in high yields (Scheme 1).
With the optimized condition in hand, to explore the scope and
generality of the reaction, we extended our study with other struc-
turally varied aromatic, heteroaromatic, and aliphatic aldehydes to
prepare
a series of 9-aryl/heteroaryl/alkyl-3,3,6,6-tetramethyl-
1,2,3,4,5,6,7,8-octahydroxanthene-1,8-diones(Table2, entries1e25).
This protocol tolerates well aromatic aldehydes containing both
electron-donating and electron-withdrawing substituents. The
electronic effects and the nature of the substituents on the aldehydes
show some obvious effects in terms of yields and reaction times. The
aromatic aldehydes with electron-withdrawing groups as substrates
reacted very well at faster rate and the reaction time is shorter
compared with aromatic aldehydes with electron-donating groups.
Though meta- and para-substituted aromatic aldehydes gave almost
equally good results. However, ortho-substituted aromatic aldehydes
turned out to be reluctant to undergo smooth reaction probably be-
cause of steric hindrance. Thus, longer reaction time is required for
ortho-substituted aromatic aldehydes to get the corresponding
products in high yields (Table 2, entries 3, 8, 12, and 17e22).
O
O
R
O
InCl3 or P2O5
+
RCHO
solvent-free
100 0C
O
O
2
4
1
25 Examples
No chromatographic separation
Scheme 1. InCl3 and P2O5 promoted synthesis of 9-substituted tetramethyloctahy-
droxanthene-1,8-diones.
Initially, a blank reaction using 4-nitrobenzaldehyde and dime-
done (mole rate 1:2) at 100 ꢀC without InCl3 or P2O5 was performed
in order to establish the real effectiveness of the catalyst. We did not
found the trace amount of desired product even after 12 h of heating.
We then focused on optimizing the catalyst and its percentage
loading. In order to evaluate the most appropriate catalyst loading,
a model reaction using 4-nitrobenzaldehyde and dimedone (mole
rate 1:2) was carried out using 5 mol %, 10 mol %, 15 mol %, and
20 mol % of InCl3, and 10 mol %, 15 mol %, 20 mol %, and 25 mol % of
P2O5 separately at different temperatures under solvent-free con-
ditions (Table 1). It was found that 15 mol % of InCl3 and 20 mol % of
Table 2
Synthesis of tetramethyloctahydroxanthene-1,8-diones (4aey)
Entry
R
Product
Time (min)
InCl3/P2O5
Yielda (%)
InCl3/P2O5
1
2
3
4
5
6
7
8
C6H5
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
36/40
15/20
42/45
27/32
35/40
45/48
35/40
60/63
55/58
32/36
42/47
55/60
50/55
35/40
45/48
55/60
65/70
60/65
65/70
70/74
55/60
50/55
25/30
65/70
55/60
83/80
98/96
78/75
87/82
85/81
83/79
90/88
80/76
82/79
88/85
83/81
79/78
74/72
82/79
90/88
87/86
80/78
83/80
90/87
77/73
87/81
78/76
70/68
60/58
58/56
p-NO2$C6H4
o-NO2$C6H4
m-NO2$C6H4
p-Me$C6H4
p-Cl$C6H4
m-Cl$C6H4
o-Cl$C6H4
p-Br$C6H4
p-F$C6H4
p-OMe$C6H4
o-OMe$C6H4
4-Me2N$C6H4
2,4-Cl2$C6H3
p-OH$C6H4
m-OH$C6H4
o-OH$C6H4
5-Bre2-OH$C6H3
5-NO2e2-OH$C6H3
2-OH$C10H6
2-OHe3-OEt$C6H3
2-OHe3-OMe$C6H3
2-C4H3S
9
Table 1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Optimization of the catalyst on model reactiona
O
O
R
O
InCl3 or P2O5
solvent-free
2
+
O
RCHO
O
4
2
1
Entry
Temp (ꢀC)
Method A (InCl3)
Method B (P2O5)
4s
4t
time/loading (%)/yieldb (%)
time/loading (%)/yieldb (%)
4u
4v
4w
4x
4y
1
2
100
60
12 h/no catalyst/0
2.0 h/5/87
12 h/no catalyst/0
2.5 h/10/90
3
70
1.5 h/5/90
2 h/10/88
(CH3)2CH
C6H5CH]CH
4
5
6
7
8
9
10
11
12
13
14
80
100
60
70
80
100
60
70
80
100
100
80 min/5/92
70 min/5/94
1.5 h/10/88
1.5 h/10/89
80 min/10/92
1.75 h/15/87
1.5 h/15/85
70 min/15/90
45 min/15/92
85 min/20/82
65 min/20/84
40 min/20/91
20 min/20/96
23 min/25/96
a
Yields of isolated pure products.
75 min/10/87
60 min/10/91
40 min/10/93
75 min/15/88
60 min/15/90
30 min/15/92
15 min/15/98
20 min/20/98
In order to further investigate the scope of this reaction with
aliphatic (isobutyraldehyde), heteroaromatic (thiophene-2-alde-
hyde), and
actions of dimedone were examined and found to produce the
products in somewhat lower yields than those with aromatic al-
dehydes (Table 2, entries 23e25). However, furfuraldehyde under
this protocol gave very poor yield of the expected product, which
might be attributed toward the decomposition/polymerization of
a,b-unsaturated aldehyde (cinnamaldehyde) the re-
a
Reaction of 4-nitrobenzaldehyde (1 mmol) and dimedone (2 mmol) under sol-
vent-free condition.
b
Isolated pure yields.

3700
G.K. Verma et al. / Tetrahedron 67 (2011) 3698e3704
furfuraldehyde under the reaction condition. Also, acyclic ketone,
such as 2,4-dioxopentane when treated with benzaldehyde/p-ani-
saldehyde failed to give the expected products under this protocol.
The products were easily isolated in almost pure state simply by
aqueous washing and extraction with ethyl acetate. The octahy-
droxanthene-1,8-diones, thus isolated were homogeneous on TLC
and pure enough (ꢁ97% by 1H NMR) for all practical purposes.
Finally, in order to show the accessibility of the present work we
compared this method with the reported results in the literature
(Table 3), which showed that InCl3 and P2O5 are the most efficient
catalysts with respect to the reaction time and temperature and
exhibited broad applicability in terms of yields. The reason for the
efficiency of the current procedure might be due to an enhanced
second-order reaction rate resulting from ultimately high concen-
trations of reactants in the absence of solvent.
active methylene of the second molecule of dimedone reacted with
intermediate A via conjugate Michael addition to generate the in-
termediate 3, which undergoes intramolecular cyclodehydration to
give the octahydroxanthene-1,8-diones (4). P2O5 is not only a cat-
alyst but also acts as a water scavenger, which plays an important
role in acceleration of the reaction.
InCl3
InCl3
R
O
O
O
O
HO
H
R
H
OH
2
O
O
O
R
H
O
OH
R
O
H2O
InCl3
3
O
InCl3
O
1
A
O
R
O
O
R
O
O
H
Table 3
O
H2O
Comparison of the efficiency of InCl3 and P2O5 with reported catalysts for the syn-
OH
4
thesis of octahydroxanthene-1,8-diones
Scheme 2. Mechanism for the formation of octahydroxanthene-1,8-diones.
Entry Catalyst
Temp (ꢀC) Time
Yield (%) Ref.
1
2
3
4
5
6
7
8
p-DBSA
CH3SO3H
100
120
80
rt
100
80
6e8 h
1e1.5 h
1e2.5 h
48 h
89e92
90e95
87e96
88e92
84e94
83e95
82e93
88e95
88e94
54e82
88e96
80e94
88e97
88e94
78e91
85e93
88e95
72e84
75e90
84e90
80e93
14a
14b
14c
1j
3. Photophysical properties
p-TSA
TiO2/SO42ꢂ
Fe3þ-montmorillonite
InCl3$4H2O in IL
([Hmim]TFA)
[TMPSA]-HSO4/IL
6 h
15a
15c
15d
15e
16a
16b
16c
17a
17b
17c
17d
18
The hydroxanthenes or xanthenedione derivatives are supposed
to exhibit optical behavior because of extended conjugation with
inbuilt pyran ring. Therefore, we further extended our study to
understand the optical behavior of synthesized hydroxanthene
derivatives containing variable chromophores and auxochromes at
different positions. In general, the UVevis absorption spectra of
some of the derivatives containing either electron-donating group
like eOH, eOCH3, and eN(CH3)2 or electron-withdrawing groups
like eNO2, eCl, eBr, etc. have been recorded in different solvents,
such as cyclohexane (Fig. 2), acetonitrile (Fig. 4), methanol (Fig. 6),
and THF (Fig. 8) and their absorption bands are given in Table 4. In
acetonitrile and tetrahydrofuran UVevis absorption spectra
appeared around 254e314 nm range and in polar protic solvent,
such as MeOH, absorption bands appeared around 270e275 nm
range. Comparatively in non-polar solvent like cyclohexane, xan-
thene derivatives containing eNO2, eCl, and eOH substituents at
ortho- and para-positions exhibited relatively higher absorption
than the meta-substituted derivatives. However, in case of polar
aprotic and protic solvents no such consistent effects of sub-
stituents were observed.
Similarly, the fluorescence behaviors of all the xanthene de-
rivatives were investigated in different non-polar, polar-aprotic and
polar-protic solvents (Table 4). In a non-polar aprotic solvent, such
as cyclohexane (Fig. 1) relatively high fluorescence intensity at
around 360 nm (Stokes shift 3539.79e6425.77 cmꢂ1) was ob-
served. In acetonitrile (Fig. 3) upon excitation at the respective
wavelengths, high energy band was observed at around
275e283 nm range. However, in the case of derivatives 4c, 4h, and
4y, a broad low energy band was observed at around 333e345 nm
range due to the presence of electron-withdrawing group at ortho-
position, which extended conjugation in the skeleton of the xan-
thenes. However, in polar-protic solvent, such as methanol (Fig. 5)
nitro-substituted derivative has shown a low energy band at
around 365 nm due to interaction of substituents with xanthene-
dione ring. In case of THF (Fig. 7) beside high energy emission
bands, a significant low intensity emission bands at around 402 and
423 nm were observed in the case of derivative 4t that contains
a naphthalene ring at position 9 of the xanthenedione skeleton. The
observed low energy band may be attributed due to the formation
of non-structured excimer fluorescence (Fig. 9), since upon in-
creasing the concentration of probe the intensity of excimer fluo-
rescence rises. The above behavior shows their potential
application as new fluorescent probes or luminescence material.
4e10 h
3e4 h
1e2 h
1213 h
1012 h
46 h
0.52 h
12.5 h
3e3.5 h
2e4 h
1e1.5 h
1 h
8e10 h
2e4 h
1.5e2.5 h
1.0e1.5 h
15e60 min 89e98
1.5e2.0 h 84e92
80
100
9
NaHSO4$SiO2 or Silica chloride 100
PPA/SiO2
PMA/SiO2
Amberlyst-15
SiO2/H2SO4
TBAHS
Dowex-50W
SbCl3/SiO2
TCT
TMSCl
BiCl3
InCl3 (5 mol %)
InCl3 (10 mol %)
InCl3 (15 mol %)
P2O5 (10 mol %)
P2O5 (15 mol %)
P2O5 (20 mol %)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
140
90
125
80
110
100
120
120
100
80
100
100
100
100
100
100
19a
19b
20
d
d
d
d
45e95 min 82e93
20e70 min 88e97
d
d
In 1H NMR spectra of compounds 4, the four methyl groups form
two sets of axial and equatorial methyl groups, hence appear dif-
ferentlygiving rise totwosinglets each with six hydrogens at around
0.99 ppm and at 1.12 ppm, respectively. Due to the possibility of free
rotation and conformational considerations, the four methyl groups
are not becoming equivalent and appear as two singlets at different
chemical shifts in all the compounds showing axial and equatorial
positions. The two methylene protons in the four positions are not
equivalent due to adjacent substituents and ring conformation. They
are located as axial and equatorial therefore, are non-equivalent and
give rise to two doublets in the region 2.13e2.28 ppm (J¼14.0 Hz).
The proton at the bridge between the two dimedone rings appears
normally in the region 4.6e4.8 ppm, and is not much affected by its
neighboring substituents except in compounds 4t and 4w, in which
it appears at somewhat lower fields at 5.25 ppm and 5.14 ppm, re-
spectively. In 13C NMR the two dimedone portion’s carbon atoms
were symmetrical and give rise to one signal for each set of carbons.
The carbon at the bridge between the two dimedone rings appears
around 40.1 ppm. The carbonyl carbons appear in the expected re-
gion around 195.3e200.9 ppm.
A mechanistic rationale portraying the probable sequence of
events is given in Scheme 2. One molecule of dimedone 1 was firstly
condensed with an aromatic aldehyde 2 to afford intermediate A,
which can be regarded as a fast Knoevenagel addition. Then the

Table 4
UVevis and fluorescence data of all the derivatives of xanthene-1,8-dione (4)
abs
em
Compound (4) R¼
l
(nm)
l
(nm)
e
(Mꢂ1 cmꢂ1
)
Dn (cmꢂ1
CH3CN CH3OH c-C6H12 THF
17,000 5300 84,000 4795.51 2901.10 5028.09
)
4fa
max
max
c-C6H12 THF CH3CN CH3OH c-C6H12 THF
CH3CN CH3OH c-C6H12 THF
CH3CN
CH3OH
c-C6H12 THF
CH3CN CH3OH
C6H5 (4a)
307
291
ND
302 294
296 281
302 253
298 268
302 294
301 293
277 ND
277 294
302 294
298 285
301 296
304 296
314 272
299 286
313 247
274
275
274
275
281
274
276
274
274
275
275
274
274
276
272
272
277
268
268
282
ND
360
330
ND
331
314
331
312
331
330
309
310
332
326
330
334
345
328
348
ND
345
330
343
ND
345
344
ND
347
345
328
347
344
352
331
283
ND
304
312
312
313
305
304
304
303
304
304
307
304
305
305
304
306
313
304
306
306
ND
7400
40,600
ND
ND
9400
14,200
9900
22,600
7200
8300
18,500
9300
3601.61 0.90
4312.35 0.018
0.19
0.095
0.01
p-NO2$C6H4 (4b)
o-NO2$C6H4 (4c)
m-NO2$C6H4 (4d)
p-Cl$C6H4 (4f)
m-Cl$C6H4 (4g)
o-Cl$C6H4 (4h)
11,100 16,000 44,500 4061.23 1936.65 5284.16
0.168 0.04
0.052 0.186
0.135 ND
0.37
7800
7200
2100
2100
8300
11,300 18,900 ND
13,200 54,100 ND
2901.10 10371.17 4445.06 ND
1505.76 ND
0.145
0.033
0.09
ND
ND
4414.75 ND
2800.30 0.896
3601.61 0.009
307
295
305
285
295
310
306
310
313
295
305
313
316
311
359
364
359
344
356
361
359
361
352
359
360
361
366
361
363
358
361
364
5700
9500
ND
11,700 4718.13 2901.10 5028.09
0.19
0.19
0.089
0.064
5800
7500
6425.77 2919.56 5059.92
4931.73 3738.62 ND
0.20
3337.1
0.876
0.114 ND
0.16
p-Br$C6H4(4i)
p-F$C6H4 (4j)
16,200 5000
14,300 6017.95 3843.01 5195.16
9600 5808.41 2992.10 5028.09
22,000 4557.23 2882.20 4599.91
3493.05 0.216
3601.61 0.91
3468.89 0.952
3790.34 0.431
3601.61 0.967
3709.46 0.019
3444.99 0.215
3869.96 0.254
4084.96 0.89
4152.00 0.89
4418.69 0.55
4633.69 0.63
2781.25 0.47
0.055 0.095
0.08
2300
3400
9000
5700
9500
0.16
0.16
0.086
0.072
0.069 0.431
0.26 0.084
0.043 0.014
0.103
0.047
0.017
0.077
0.034
0.073
0.044
0.056
0.08
p-OMe$C6H4 (4k)
4-Me2N$C6H4 (4m)
2,4-Cl2$C6H3 (4n)
p-OH$C6H4 (4o)
m-OH$C6H4 (4p)
o-OH$C6H4 (4q)
5-Bre2-OH$C6H3(4r)
2-OH$C10H6 (4t)
2-OHe3-OEt$C6H3 (4u)
14,300 51,200 4824.58 2919.56 4965.33
13,700 4557.23 4954.61 4714.06
44,200 34,100 3539.79 2861.62 8355.61
14,000 5700
28,300
22,100
28,600
8800
7400
4500
2700
ND
8500
6200
ND
14,700 6043.15 2957.01 4753.55
24,400 5009.10 3213.24 5150.14
0.12
0.23
ND
0.06
0.05
0.77
0.078
0.234
ND
ND
ND
17,600 4248.05 ND
ND
316 269
304 257
276 262
300 285
302 290
300 231
405, 427 359
7500
14,100 17,400 28,300 4323.16 8335.54 9319.56
0.03
333
310
329
331
329
283
283
329
344
343
15,200
13,200
14,700
2400
8300
1100
1100
400
19,500 19,300 4453.50 2864.70 3574.81
18,300 20,700 4298.92 3973.81 2832.24
0.121
0.139
0.415 0.075
0.92 0.122
0.056 0.056
0.053
0.056
0.094
ND
2-OHe3-OMe$C6H3 (4v) 314
2-C4H3S (4w)
(CH3)2CH (4x)
C6H5CH]CH (4y)
299
316
315
7600
5900
10,900 5511.85 2938.19 4692.58
ND 3944.73 2901.10 5412.99
4273.50 2938.19 14135.52 ND
ND
0.94
0.91
ND
ND
3900
2600
26,400 ND
ND
4f¼Quantum yield.
abs
l
l
¼Absorbance maxima.
¼Fluorescence maxima.
max
em
max
e
¼Molar absorptivity.
Dn¼Stoke’s shift.
a
Quantum yield was calculated with respect to naphthalene in CH3CN.

3702
G.K. Verma et al. / Tetrahedron 67 (2011) 3698e3704
4A
200
500
400
300
200
100
0
4A
4B
4F
4I
4B
4F
4I
150
100
50
4K
4N
4O
4T
4V
4W
4X
4Y
4K
4N
4O
4T
4V
4W
0
300
350
400
450
500
300
350
400
450
500
550
Wavelength (nm)
Wavelength (nm)
Fig. 5. Fluorescence spectra of some selected xanthenediones in methanol solution
Fig. 1. Fluorescence spectra of some selected xanthenediones in cyclohexane solution
abs
abs
(10ꢂ5 M) were collected using their corresponding
l
.
(10ꢂ5 M) were collected using their corresponding
l
.
max
max
4A
4B
4F
4I
1.0
0.8
0.6
0.4
0.2
0.0
0.5
0.4
0.3
0.2
0.1
0.0
4A
4B
4F
4K
4N
4O
4T
4V
4W
4K
4N
4O
4T
4V
4W
4X
4Y
275
300
325
350
300
350
400
450
Wavelength (nm)
Wavelength (nm)
Fig. 6. UVevis spectra of xanthenedione derivatives in methanol solution (10ꢂ5 M).
Fig. 2. UVevis spectra of xanthenedione derivatives in cyclohexane solution (10ꢂ5 M).
120
4A
4A
400
4B
4F
4I
4B
4F
4I
4K
90
4N
4O
4T
4V
300
4K
4N
4O
60
4W
4T
200
Excimer band
4X
4Y
4V
4W
4X
30
0
4Y
100
0
300
350
400
450
500
300
350
400
450
Wavelength (nm)
Wavelength (nm)
Fig. 7. Fluorescence spectra of some selected xanthenediones in THF solution (10ꢂ5 M)
abs
Fig. 3. Fluorescence spectra of some selected xanthendiones in CH3CN solution
were collected using their corresponding
l
.
max
abs
(10ꢂ5 M) were collected using their corresponding
l
.
max
4A
4B
4F
4I
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
4A
4B
4F
4I
0.5
0.4
0.3
0.2
0.1
0.0
4K
4N
4O
4T
4V
4W
4X
4Y
4K
4N
4O
4T
4V
4W
4X
4Y
240
280
320
360
400
300
325
350
375
400
Wavelength (nm)
Wavelength (nm)
Fig. 4. UVevis spectra of xanthendione derivatives in acetonitrile solution (10ꢂ5 M)
abs
were collected using there corresponding
l
.
Fig. 8. UVevis spectra of xanthenedione derivatives in THF solution (10ꢂ5 M).
max

G.K. Verma et al. / Tetrahedron 67 (2011) 3698e3704
3703
the reaction mixture was cooled to room temperature, water
(25 mL) was added and extracted with ethyl acetate (3ꢃ20 mL). The
combined organic extract was washed with water (2ꢃ15 mL), brine
(1ꢃ25 mL), and dried over anhydrous Na2SO4. The solvent was
evaporated under vacuum to give the desired product, which was
recrystallized from ethanol to afford the pure product. All products
were characterized by elemental and spectral studies, and com-
parison of their physical and spectral data with those of reported
ones. The spectral data of some representative and new octahy-
droxanthene-1,8-diones are given below.
45
30
15
0
4t-5
4t-4
4t-3
5.2.1. 9-Phenyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (4a). White solid. Mp 204e205 ꢀC. IR (KBr):
2954,1664,1364, 1199 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d 7.27e7.09
(m, 5H, ArH), 4.74 (s, 1H, CH), 2.46 (s, 4H, 2CH2), 2.19 (q, J¼16.5 Hz,
4H, 2CH2), 1.10 (s, 6H, 2CH3), 0.98 (s, 6H, 2CH3). 13C NMR (75 MHz,
CDCl3): d 196.2, 162.3, 143.8, 128.4, 127.6, 115.2, 50.6, 40.7, 32.0, 31.6,
325
375
425
475
29.3, 27.2. EIMS (m/z): 350 (Mþ). Anal. Calcd for C23H26O3: C, 78.83;
Wavelength (nm)
H, 7.47. Found: C, 78.96; H, 7.40.
Fig. 9. Excimer fluorescence spectra of xanthenedione derivative 4t in THF of 10ꢂ3 M,
10ꢂ4 M and 10ꢂ5 M solution.
5.2.2. 9-(4-Nitrophenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahy-
droxanthene-1,8-dione (4b). White solid. Mp 223e224 ꢀC. IR (KBr):
2958, 1670, 1650, 1520, 1362, 1206, 870 cmꢂ1. 1H NMR (300 MHz,
4. Conclusion
CDCl3):
4.82 (s,1H, CH), 2.49 (s, 4H, 2CH2), 2.21 (q, J¼16.2 Hz, 4H, 2CH2),1.12
(s, 6H, 2CH3), 0.99 (s, 6H, 2CH3). 13C NMR (75 MHz, CDCl3):
196.1,
162.9, 151.3, 146.6, 129.4, 123.5, 114.5, 50.5, 40.8, 32.3, 32.1, 29.6,
29.2, 27.2. EIMS (m/z): 395 (Mþ). Anal. Calcd for C23H25NO5: C,
69.85; H, 6.37; N, 3.54. Found: C, 69.96; H 6.49; N, 3.43.
d
8.09 (d, J¼8.0 Hz, 2H, ArH), 7.46 (d, J¼8.0 Hz, 2H, ArH),
In conclusion we have developed a convenient and atom-
efficient protocol for the synthesis of 3,3,6,6-tetramethyl-9-aryl/
heteroaryl/alkyl-1,2,3,4,5,6,7,8-octahydroxanthene-1,8-diones. The
remarkable catalytic activity of InCl3 and P2O5 are superior to the
reported other catalytic methods with respect to reduced reaction
times. The pure products were obtained simply by aqueous wash-
ing and extraction with ethyl acetate. The higher yields, mild re-
action condition, easy isolation and purification, and economic
availability of the catalyst make the eco-friendly procedure an at-
tractive alternative to the existing methods for the synthesis of
octahydroxanthene-1,8-diones. Furthermore, the screening for
optical properties showed that some products may have a good
future as new luminescence materials or fluorescence probes.
d
5.2.3. 9-(4-Methylphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahy-
droxanthene-1,8-dione (4e). White solid. Mp 213e215 ꢀC. IR (KBr):
3030, 2980, 1685, 1660, 1620, 1490, 1365, 1200, 1135, 1000, 850,
840 cmꢂ1.1H NMR (300 MHz, CDCl3):
d
7.16 (d, J¼8.0 Hz, 2H, ArH), 7.01
(d, J¼8.0 Hz, 2H, ArH), 4.70 (s, 1H, CH), 2.45 (s, 4H, 2CH2), 2.23 (s, 3H,
CH3), 2.19 (q, J¼16.3 Hz, 4H, 2CH2), 1.09 (s, 6H, 2CH3), 0.99 (s, 6H,
2CH3).13CNMR(75MHz, CDCl3):
d196.4, 162.1, 141.1, 135.7, 128.7, 128.1,
115.7, 50.7, 40.8, 32.1, 31.3, 29.2, 27.3, 20.9. EIMS (m/z): 364 (Mþ). Anal.
5. Experimental section
5.1. General
Calcd for C24H28O3: C, 79.09; H, 7.74. Found: C, 79.16; H 7.49.
5.2.4. 9-(4-Hydroxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octa-
hydroxanthene-1,8-dione (4o). White solid. Mp 249e251 ꢀC. IR
(KBr): 3324, 2959, 1652, 1617, 1363 cmꢂ1 1H NMR (300 MHz,
.
All reagents were commercial and purchased from Merck, Aldrich
and Fluka, and were used as received. All 1H and 13C NMR spectra
were recorded on JEOL AL 300 FT NMR spectrometer. Chemical shifts
CDCl3):
d
7.10 (d, J¼8.4 Hz, 2H, ArH), 6.60 (d, J¼8.4 Hz, 2H, ArH), 5.72
(s, 1H, OH, D2O exchangeable), 4.67 (s, 1H, CH), 2.45 (s, 4H, 2CH2),
are given as d value with reference to tetramethylsilane (TMS) as the
2.20 (q, J¼16.2 Hz, 4H, 2CH2), 1.09 (s, 6H, 2CH3), 0.99 (s, 6H, 2CH3).
13C NMR (75 MHz, CDCl3):
d 195.8, 162.5, 140.7, 135.5, 128.2, 128.0,
internal standard. The IR spectra were recorded on Varian 3100 FT-IR
spectrophotometer. The UVevis absorption spectra were recorded
on Shimadzu 1700 spectrophotometer using a quartz cuvette of 1 cm
path length. Mass spectra were recorded at 70 eV ionizing voltage on
a JEOL-D300 MS instrument. The C, H, and N analyses were per-
formed with an Exeter Analytical Inc. ‘Model CE-400 CHN Analyzer’.
All the reactions were monitored by TLC using precoated sheets of
silica gel G/UV-254 of 0.25 mm thickness (Merck 60 F254) using UV
light (254 nm/365 nm) for visualization. The fluorescence spectra
were recorded at. Cary Eclipse fluorescence spectrophotometer.
115.2, 50.6, 40.1, 32.4, 31.2, 29.1, 27.2. EIMS (m/z): 366 (Mþ). Anal.
Calcd for C23H26O4: C, 75.38; H, 7.15. Found: C, 75.16; H 7.29.
5.2.5. 9-(2-Hydroxynaphthyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-oc-
tahydroxanthene-1,8-dione (4t). White solid. Mp 232e233 ꢀC. IR
(KBr): 3324, 2959, 1687, 1652, 1617, 1490, 1363, 1200, 1135, 1012,
854 cmꢂ1 1H NMR (300 MHz, CDCl3):
. d 10.65 (s, 1H, OH, D2O ex-
changeable), 7.77e7.33 (m, 6H, ArH), 5.25 (s, 1H, CH), 2.60 (q,
J¼18.0Hz, 2H,CH2),2.38(s, 4H,2CH2),1.87(q, J¼16.8Hz, 2H, CH2),1.15
(s, 3H, CH3), 1.06 (s, 3H, CH3), 0.93 (s, 3H, CH3), 0.70 (s, 3H, CH3). 13
C
€
Melting points were determined with Buchi B-540 melting point
apparatus and are uncorrected.
NMR (75 MHz, CDCl3): d 200.9, 196.8, 170.2, 168.9, 148.7, 131.1, 130.8,
128.4, 128.3, 126.6, 124.5, 122.7, 117.5, 116.4, 116.0, 110.9, 50.6, 43.1,
41.2, 32.3, 30.5, 29.8, 26.9, 26.3, 25.2, 21.0, 14.1. EIMS (m/z): 416 (Mþ).
Anal. Calcd for C27H28O4: C, 77.86; H, 6.78. Found: C, 77.74; H, 6.62.
5.2. General procedure for the synthesis of 9-substituted-
tetramethyloctahydroxanthene-1,8-diones (4)
To a nicely ground mixture of dimedone (2 mmol) and aldehyde
(1 mmol), InCl3 (15 mol %) or P2O5 (20 mol %) was added and the
reaction mixture was heated at 100 ꢀC for the appropriate period of
time (Table 2). After completion of the reaction (monitored by TLC),
5.2.6. 9-(2-Hydroxy-3-methoxyphenyl)-3,3,6,6-tetramethyl-
1,2,3,4,5,6,7,8-octahydroxanthene-1,8-dione (4v). White solid. Mp
197e199 ꢀC. IR (KBr): 3336, 2963, 1656, 1627, 1369 cmꢂ1. 1H NMR
(300 MHz, CDCl3): d 10.41 (s, 1H, OH, D2O exchangeable), 6.96e6.91

3704
G.K. Verma et al. / Tetrahedron 67 (2011) 3698e3704
5. Poupelin, J. P.; Saint-Ruf, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf,
G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67e71.
6. Hideo, T. Jpn. Tokkyo Koho JP 56,005,480, 1981; Chem. Abstr. 1981, 95, 80922b.
7. (a) Buu-Hoi, N. P.; Saint-Ruf, G.; De, A.; Hieu, H. T. Bull. Chim. Ther. 1972, 7,
83e86; (b) Saint-Ruf, G.; Hieu, H. T.; Poupelin, J. P. Naturwissenschaften 1975, 62,
584e585.
8. (a) Ion, R.-M. Prog. Catal. 1997, 2, 55e76; (b) Ion, R. M.; Frackowiak, D.; Planner,
A.; Wiktorowicz, K. Acta Biochim. Pol. 1998, 45, 833e845.
9. (a) Banerjee, A.; Mukherjee, A. K. Stain Technol. 1981, 56, 83e85; (b) Menchen, S.
M.; Benson, S. C.; Lam, J. Y. L.; Zhen, J. Y. L.; Sun, W.; Rosenblum, D.; Khan, B. B.;
Taing, S. H.; U.S. M. Patent 6,583,168, 2003.
(m, 1H, ArH), 6.75 (d, J¼8.1 Hz, 1H, ArH), 6.58 (d, J¼7.5 Hz, 1H, ArH),
4.65 (s, 1H, CH), 3.88 (s, 3H, OCH3), 2.61 (q, J¼17.4 Hz, 2H, CH2), 2.36
(s, 2H, CH2), 2.32 (s, 2H, CH2), 1.96 (q, J¼4.2 Hz, 2H, CH2), 1.02 (s, 6H,
2CH3), 0.99 (s, 6H, 2CH3). 13C NMR (75 MHz, CDCl3):
d 195.3, 162.9,
140.4, 135.7, 128.3, 128.1, 114.9, 55.1, 50.2, 41.1, 32.6, 31.6, 29.3, 27.1.
EIMS (m/z): 396 (Mþ). Anal. Calcd for C24H28O5: C, 72.70; H, 7.12.
Found: C, 72.74; H, 7.69.
5.2.7. 9-(2-Thienyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
10. Ahmad, M.; King, T. A.; Ko, D.-K.; Cha, B. H.; Lee, J. J. Phys. D: Appl. Phys. 2002, 35,
1473e1476.
11. Knight, C. G.; Stephens, T. Biochem. J. 1989, 258, 683e687.
anthene-1,8-dione (4w). White solid, Mp 161e162 ꢀC. IR (KBr):
2956, 2895, 1658, 1622, 1496, 1199 cmꢂ1 1H NMR (300 MHz,
.
12. (a) Hatakeyma, S.; Ochi, N.; Numata, H.; Takano, S. J. Chem. Soc., Chem. Commun.
1988, 1202e1204 and references therein; (b) Cingolani, G. M.; Gualtieri, F.;
Pigini, M. J. Med. Chem. 1969, 12, 531e532; (c) Ahadi, S.; Khavasi, H. R.; Bazgir, A.
Chem. Pharm. Bull. 2008, 56, 1328e1330.
13. O’Callaghan, C. N.; McMurry, T. B. H. J. Chem. Res., Synop. 1995, 214e218.
14. (a) Jin, T. S.; Zhang, J. S.; Xiao, J. C.; Wang, A. Q.; Li, T. S. Synlett 2004, 866e870;
(b) Shen, Y.-B.; Wang, G.-W. ARKIVOC 2008, xvi, 1e8; (c) Khosropour, A. R.;
Khodaei, M. M.; Moghannian, H. Synlett 2005, 955e958.
15. (a) Song, G.; Wang, B.; Luo, H.; Yang, L. Catal. Commun. 2007, 8, 673e676; (b)
Fan, X. S.; Li, Y. Z.; Zhang, X. Y.; Hu, X. Y.; Wang, J. J. Chin. Chem. Lett. 2005, 16,
897e899; (c) Fan, X.; Hu, X.; Zhang, X.; Wang, J. Can. J. Chem. 2005, 83, 16e20;
(d) Dabiri, M.; Baghbanzadeh, M.; Arzroomchilar, E. Catal. Commun. 2008, 9,
939e942; (e) Fang, D.; Gong, K.; Liu, Z.-L. Catal. Lett. 2009, 127, 291e295; (f) Ma,
J.-J.; Wang, C.; Wu, Q.-H.; Tang, R.-X.; Liu, H.-Y.; Li, Q. Heteroat. Chem. 2008, 19,
609e611.
16. (a) Das, B.; Thirupathi, P.; Reddy, K. R.; Ravikanth, B.; Nagarapu, L. Catal. Com-
mun. 2007, 8, 535e538; (b) Kantevari, S.; Bantu, R.; Nagarapu, L. J. Mol. Catal. A:
Chem. 2007, 269, 53e57; (c) Srihari, P.; Mandal, S. S.; Reddy, J. S. S.; Rao, R. S.;
Yadav, J. S. Chin. Chem. Lett. 2008, 19, 771e774.
CDC13):
d
7.01 (d, J¼4.8 Hz, 1H, ArH), 6.96 (d, J¼3.3 Hz, 1H, ArH),
6.83e6.81 (m, 1H, ArH), 5.14 (s, 1H, CH), 2.45 (s, 4H, 2CH2), 2.26 (s,
4H, 2CH2), 1.11 (s, 6H, 2CH3), 1.05 (s, 6H, 2CH3). 13C NMR (75 MHz,
CDCl3):
d 196.1, 162.6, 148.0, 126.6, 125.2, 123.3, 115.2, 50.7, 40.8,
32.0, 29.2, 27.3, 26.3. EIMS (m/z): 356 (Mþ). Anal Calcd for
C21H24O3S: C, 70.78; H, 6.74. Found: C, 70.68; H, 6.63.
5.2.8. 9-Isopropyl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydrox-
anthene-1,8-dione (4x). White solid. Mp 146e147 ꢀC. IR (KBr):
2950, 1690, 1645, 1612, 1460, 1370, 1210, 1145, 1022, 844 cmꢂ1. 1H
NMR (300 MHz, CDCl3):
d
3.81 (d, J¼3.0 Hz, 1H, CH) 2.41e2.27 (m,
8H, 4CH2), 1.84e1.79 (m, 1H, CH), 1.13 (s, 6H, 2CH3), 1.11 (s, 6H,
2CH3), 0.75 (d, J¼6.9 Hz, 6H, 2CH3). 13C NMR (75 MHz, CDCl3):
d
198.9, 160.1, 113.5, 51.4, 44.1, 31.50, 30.2, 26.9, 25.6, 21.1, 15.8. EIMS
(m/z): 316 (Mþ). Anal. Calcd for C20H28O3: C, 75.91; H, 8.92. Found:
17. (a) Das, B.; Thirupathi, P.; Mahender, I.; Reddy, V. S.; Rao, Y. K. J. Mol. Catal. A:
Chem. 2006, 247, 233e239; (b) Seyyedhamzeh, M.; Mirzaei, P.; Bazgir, A. Dyes
Pigm. 2008, 76, 836e839; (c) Karade, H. N.; Sathe, M.; Kaushik, M. P. ARKIVOC
2007, xiii, 252e258; (d) Shakibaei, G. I.; Mirzaei, P.; Bazgir, A. Appl. Catal., A
2007, 325, 188e192.
C, 75.74; H, 8.72.
Acknowledgements
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V. S. Eur. J. Org. Chem. 2010, 591e605; (b) Fringuelli, F.; Piermatti, O.; Pizzo, F.;
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Mini-Rev. Org. Chem. 2004, 1, 1e7; (d) Zhang, Z.-H. Synlett 2005, 711e712; (e)
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1719e1723.
This work was carried out under financial support from Council
of Scientific and Industrial Research (Grant 01(2260)/08/EMR-II)
and Department of Science and Technology (Grant SR/S1/OC-66/
2009), New Delhi. G. K. V. is thankful to University Grants Com-
mission (UGC), New Delhi for junior research fellowship. R.K.V. and
P.D. are grateful to Council of Scientific and Industrial Research
(CSIR), New Delhi for senior research fellowships. Generous help
from Dr. Arvind Misra and Dr. Satyen Saha regarding optical studies
is gratefully acknowledged.
References and notes
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