An efficient one-pot synthesis of tetrahydrobenzo xanthen-11-one derivatives catalyzed by P2O5 under solvent free conditions

Article abstract of DOI:10.14233/ajchem.2018.21018

The present study highlights the catalytic activity of P2O5 for the one pot synthesis of tetrahydrobenzoxanthen-11-one derivatives from dimedone and various aromatic aldehydes under solvent free conditions. The present methodology offers several advantage

Full text of DOI:10.14233/ajchem.2018.21018

Asian Journal of Chemistry; Vol. 30, No. 4 (2018), 804-806
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21018
An Efficient One-Pot Synthesis of Tetrahydrobenzo Xanthen-11-one
Derivatives Catalyzed by P2O5 under Solvent Free Conditions
1,*
1
1
1,2
KRISHNA KANTH GARLAPATI , SIVA SANKAR BABU , N. SRINIVASU and T. MURTHY CHAVALI
1Division of Chemistry, Department of Sciences and Humanities, Vignan’s Foundation for Science, Technology and Research, Vadlamudi,
Guntur-522 213, India
2Centre of Excellence forAdvanced Materials, Manufacturing, Processing and Characterization, Vignan's Foundation for Science, Technology
and Research University, Vadlamudi, Guntur-522 213, India
*Corresponding author: E-mail: krishnakanthgarlapati@gmail.com
Received: 1 September 2017;
Accepted: 23 November 2017;
Published online: 28 February 2018;
AJC-18788
The present study highlights the catalytic activity of P2O5 for the one pot synthesis of tetrahydrobenzoxanthen-11-one derivatives from
dimedone and various aromatic aldehydes under solvent free conditions. The present methodology offers several advantages such as clean
and mild reaction, short reaction time, low environmental impact, wide substrate scope, high yield and purity.
Keywords: P2O5, One-pot synthesis, Solvent free conditions, Xanthene.
ultrasonic irradiation [15], ionic liquids [16], Ambedrlyst-1s
[17], NaHSO4-SiO2 or silica chloride [18], phosphomolybdic
acid supported on silica gel [19], nano-sized MCM-41-SO3H
under ultrasonic irradiation [20], sulfonic acid on silica gel
[21], Dowex-50W ion exchange resin under solvent-free condi-
tions [22] HClO4-SiO2 [23], ZnO and ZnO-acetyl chloride [24]
and heteropoly acid supported MCM-41 [25].
However, the methods reported serve their best but they
still suffer from certain drawbacks such as long reaction times,
low yields, use of toxic transition metals as catalysts, use of
hazardous organic solvents and tedious workup procedures.
Keeping the above facts in mind and as a part of our ongoing
research, herein we report the first time use P2O5 for the effi-
cient synthesis of tetrahydrobenzo xanthen-11-one derivatives.
This method offers advantages such as short reaction time,
easy to work-up procedure and excellent yields (Scheme-I).
INTRODUCTION
Xanthene derivatives are very important class of organic
molecules because they have a wide range of biological and
pharmaceutical properties such as antibacterial [1], antiviral
[2], antiinflammatory [3], antidepressant, antimalarial agents
and these are being utilized as antagonists [4] for paralyzing
action of zoxazolamine [5] and in photodynamic therapy [6].
Furthermore, these compounds can be used as dyes in laser
technologies [7] and pH sensitive fluorescent materials for
visualization of biomolecules [8]. In particular, xanthene diones
constitute a key structural motif in a number of natural products
[9] and have been used as versatile synthons because of inherent
reactivity of inbuilt pyran ring [10]. Synthesis of xanthene diones
is a continuing hot topic because these moieties are active
pharmaceutical ingredients (API’s) and also valuable reactive
intermediates for both synthetic and medicinal chemists.
A survey of the literature reveals that various methods
have been reported for the preparation of xanthenes and substi-
tuted xanthenes. The classical method for the synthesis of tetra-
hydrobenzo xanthen-11-one derivatives involves the conden-
sation of appropriate active methylene compounds with various
substituted aromatic aldehydes. For this purpose, two molecules
of dimedone (5,5-dimethylcyclohexane-1,3-dione) was reacted
with various aromatic aldehydes [11] by using different Lewis
acid catalysts such as triethyl benzyl ammonium chloride [12],
p-dodecylbenzenesulfonic acid [13], diammonium hydrogen
phosphate [14] under various conditions, sulfonic acid under
EXPERIMENTAL
Synthesis of tetrahydrobenzo xanthen-11-one deriva-
tives: A mixture of 5,5-dimethyl-1,3-cyclohexanediones,
substituted aromatic aldehyde, 2-naphthol and P2O5 as catalyst
was stirred at 120 °C in the oil bath. The reaction was monitored
by TLC. The reaction was cooled to room temperature after
completion of the reaction. The solid product was filtered,
washed with hot water and finally recrystallized from ethanol.
All the synthesized products were characterized by IR, NMR
and mass spectroscopic data for their structure and their melting
points were compared with authentic samples.

Vol. 30, No. 4 (2018)
An Efficient One-Pot Synthesis of Tetrahydrobenzo Xanthen-11-one Derivatives Catalyzed by P2O5 805
R
CHO
O
OH
P2O5
O
+
+
120 °C
Solvent free
O
R
3
1
2
O
4a-j
Scheme-I: Synthesis of xanthenes catalyzed by P2O5 under solvent free conditions
Spectral data for selected compounds
3148, 3110, 1728; 1H NMR (DMSO-d6): δ 2.05-2.14 (s, 4H,
2CH2), δ 4.30 (s, 1H), 6.5-7.5 (m, 12H,Ar-H), 2.8 (s, 6H, 4CH3),
3.2 (d, 6H, 2CH3), 3.5 (q, 1H, CH), MS (m/z): 397 [M+].
9,10-Dihydro-9,9-dimethyl-12-phenyl-8H-benzo[a]-
xanthen-11(12H)-one (4a): IR (KBr, νmax, cm–1): 3148, 3110,
1728; 1H NMR (DMSO-d6): δ 2.05-2.14 (s, 4H, 2CH2), δ 4.30
(s, 1H), 6.5-7.5 (m, 12H, Ar-H), 2.8 (s, 6H, 2CH3), MS (m/z):
354 [M+].
9,10-Dihydro-9,9-dimethyl-12-p-tolyl-8H-benzo[a]-
xanthen-11(12H)-one (4b): IR (KBr, νmax, cm–1): 3146, 3112,
1732; 1H NMR (DMSO-d6): δ 2.15-2.27 (s, 4H, 2CH2), δ 4.82
(s, 1H), 6.5-7.5 (m, 12H, Ar-H), 2.9 (s, 9H, 3CH3), MS (m/z):
369 [M+].
RESULTS AND DISCUSSION
Literature survey revealed that there are few reports on
the use of P2O5 as a catalyst in the synthesis of tetrahydrobenzo-
xanthen-11-one derivatives under solvent-free reaction [26,27].
In continuation of our interest in the area of clean synthesis
under solvent-free conditions for the development of new
synthetic methodologies herein, we reported a simple, efficient
and one-pot reaction of dimedone, 2-naphthol and aldehydes
using P2O5 at 120 °C for the preparation of tetrahydrobenzo-
xanthen-11-one derivatives (4a-j) in high yields (Scheme-I).
The different reaction time carried out in presence of P2O5
catalyst, percentage of the yield and melting points are presen-
ted in Table-1.
9,10-Dihydro-9,9-dimethyl-12-(4-hydroxyphenyl)-8H-
benzo[a]xanthen-11(12H)-one (4c): IR (KBr, νmax, cm–1):
1
3251, 3136, 3112, 1722; H NMR (DMSO-d6): δ 2.25-2.27
(s, 4H, 2CH2), δ 4.26 (s, 1H), 6.4-7.5 (m, 12H, Ar-H), 2.9 (s,
9H, 3CH3), 11.2 (s, 1H, OH), MS (m/z): 371 [M+].
9,10-Dihydro-9,9-dimethyl-12-(4-methoxyphenyl)-8H-
benzo[a]xanthen-11(12H)-one (4d): IR (KBr, νmax, cm–1):
3138, 3110, 1728; 1H NMR (DMSO-d6): δ 2.05-2.14 (s, 4H,
2CH2), δ 4.30(s, 1H), 6.5-7.5 (m, 12H,Ar-H), 2.8 (s, 9H, 3CH3),
MS (m/z): 384 [M+].
TABLE-1
REACTION OF DIFFERENT SUBSTRATE
UNDER OPTIMIZED CONDITION
Entry
4a
4b
4c
4d
4e
R
H
-CH3
-OH
-OCH3
-NMe2
-NEt2
-Br
Time (min)
Yield (%)
m.p. (°C)
202-204
215-217
220-222
230-232
224-226
224-226
230-232
223-225
219-221
238-239
9,10-Dihydro-9,9-dimethyl-12-[4-(dimethylamino)-
phenyl]-8H-benzo[a]xanthen-11(12H)-one (4e): IR (KBr,
5
95
85
90
80
90
90
91
92
95
88
15
30
30
15
15
20
12
15
25
ν
max, cm–1): 3248, 3112, 1726; 1H NMR (DMSO-d6): δ 2.15-
2.24 (s, 4H, 2CH2), δ 4.30(s, 1H), 6.6-7.7 (m, 12H, Ar-H),
2.28 (s, 12H, 4CH3), MS (m/z): 398 [M+].
4f
9,10-Dihydro-9,9-dimethyl-12-[4-(diethylamino)-
phenyl]-8H-benzo[a]xanthen-11(12H)-one (4f): IR (KBr,
4g
4h
4i
-F
ν
max, cm–1): 3148, 3110, 1728; 1H NMR (DMSO-d6): δ 2.05-
-NO2
CH(CH3)2
2.14 (s, 8H, 4CH2), δ 4.30(s, 1H), 6.5-7.5 (m, 12H, Ar-H), 2.8
(s, 12H, 4CH3), MS (m/z): 426 [M+].
4j
9,10-Dihydro-9,9-dimethyl-12-(4-bromophenyl)-8H-
benzo[a]xanthen-11(12H)-one (4g): IR (KBr, νmax, cm–1):
3138, 3110, 1728; 1H NMR (DMSO-d6): δ 2.05-2.14 (s, 4H,
2CH2), δ 4.32(s, 1H), 6.5-7.5 (m, 12H,Ar-H), 2.8 (s, 6H, 2CH3),
MS (m/z): 434 [M+].
9,10-Dihydro-9,9-dimethyl-12-(4-fluorophenyl)-8H-
benzo[a]xanthen-11(12H)-one (4h): IR (KBr, νmax, cm–1):
3158, 3130, 1725; 1H NMR (DMSO-d6): δ 2.25-2.64 (s, 4H,
2CH2), δ 4.38 (s, 1H), 6.5-7.5 (m, 12H, Ar-H), 2.8 (s, 6H,
2CH3), MS (m/z): 372 [M+].
9,10-Dihydro-9,9-dimethyl-12-(4-nitrophenyl)-8H-
benzo[a]xanthen-11(12H)-one (4i): IR (KBr, νmax, cm–1):
3148, 3110, 1728; 1H NMR (DMSO-d6): δ 2.05-2.14 (s, 4H,
2CH2), δ 4.30 (s, 1H), 6.5-7.5 (m, 12H, Ar-H), 2.8 (s, 6H,
2CH3), MS (m/z): 414 [M+].
Initially, a blank reaction with benzaldehyde, dimedone
and 2-naphthol (mol ratio 1:1:1) at 120 °C without P2O5 was
performed in order to establish the real effectiveness of the
catalyst and the results showed that the desired product was
not formed even after 12 h of heating. We then focused on
optimizing the catalyst loading percentage. In order to evaluate
the most appropriate catalytic percentage, a model reaction
using benzaldehyde and dimedone (mole ratio 1:2) was carried
out using 0, 5, 10, 15 and 20 mol % of P2O5 at different tempe-
ratures under solvent-free conditions (Table-2). It was found
that 15 mol % of P2O5 showed a maximum yield in minimum
time at 120 °C (Table-3).
Conclusion
In the present work, it is found that P2O5 is the most efficient
catalyst with respect to the reaction time and temperature and
exhibited broad applicability in terms of yields.
9,10-Dihydro-9,9-dimethyl-12-(4-isopropylphenyl)-
8H-benzo[a]xanthen-11(12H)-one (4j): IR (KBr, νmax, cm–1):

806 Garlapati et al.
Asian J. Chem.
10. C.N. O’Callaghan and T.B.H. McMurry, J. Chem. Res. (S)., 214 (1995).
11. M.Anary-Abbasinejad,A. Hassanabadi and K. Charkhati, Synth. Commun.,
39, 4289 (2009);
https://doi.org/10.1080/00397910902898643.
12. X.S. Wang, D.Q. Shi,Y.L. Li, H. Chen, X.Y. Wei and Z.M. Zong, Synth.
Commun., 35, 97 (2005);
https://doi.org/10.1081/SCC-200046510.
13. T.S. Jin, J.S. Zhang, J.C. Xiao, A.Q. Wang and T.S. Li, Synlett, 866 (2004);
https://doi.org/10.1055/s-2004-820022.
14. F. Darviche, S. Balalaie, F. Chadegani and P. Salehi, Synth. Commun.,
37, 1059 (2007);
https://doi.org/10.1080/00397910701196520.
15. T.S. Jin, J.S. Zhang, A.Q. Wang and T.S. Li, Ultrason. Sonochem., 13,
220 (2006);
https://doi.org/10.1016/j.ultsonch.2005.04.002.
16. M. Dabiri, M. Baghbanzadeh and E. Arzroomchilar, Catal. Commun., 9,
939 (2008);
TABLE-2
EFFECT OF TEMPERATURE ON RATE OF REACTION
Entry
Temperature ( 5 °C)
Yield (%)
1
2
3
4
40
60
80
10
49
76
96
120
Reaction conditions: 2-Naphthol (20 mmol); dimedone (20 mmol);
benzaldehyde (20 mmol); P2O5 = 10 % weight of substrate; time = 15
min).
TABLE-3
EFFECT OF CATALYST ON SYNTHESIS OF
TETRAHYDROBENZO XANTHEN-11-ONE DERIVATIVES
Entry
Catalyst (%)
Yield (%)
Time (min)
https://doi.org/10.1016/j.catcom.2007.09.023.
17. B. Das, P. Thirupathi, I. Mahender, V.S. Reddy andY.K. Rao, J. Mol. Catal.
Chem., 247, 233 (2006);
https://doi.org/10.1016/j.molcata.2005.11.048.
18. B. Das, P. Thirupathi, K.R. Reddy, B. Ravikanth and L. Nagarapu, Catal.
Commun., 8, 535 (2007);
https://doi.org/10.1016/j.catcom.2006.02.023.
19. P. Srihari, S.S. Mandal, J.S.S. Reddy, R.S. Rao and J.S.Yadav, Chin. Chem.
Lett., 19, 771 (2008);
1
2
3
4
5
0
5
10
15
20
0
24 h
18
15
16
20
89
96
95
94
Reaction conditions: 2-Naphthol (20 mmol); dimedone (20 mmol);
benzaldehyde (20 mmol); temp. = 120 °C, time = 15-30 min (reaction
completion on TLC)
https://doi.org/10.1016/j.cclet.2008.05.005.
20. S. Rostamizadeh,A.M.Amani, G.H. Mahdavinia, G.Amiri and H. Sepehrian,
Ultrason. Sonochem., 17, 306 (2010);
https://doi.org/10.1016/j.ultsonch.2009.10.004.
21. G.H. Mahdavinia, M.A. Bigdeli and Y.S. Hayeniaz, Chin. Chem. Lett.,
20, 539 (2009);
REFERENCES
1. T. Hideo, Jpn. Tokkyo Koho JP 56,005,480 (1981); Chem. Abstr., 95,
80922b (1981).
2. R.W. Lambert, J.A. Martin, J.H. Merrett, K.E.B. Parkes and G.J. Thomas,
PCT Int.Appl. WO 9,706,178 (1997); Chem. Abstr., 126, 212377y (1997).
3. A.G. Banerjee, L.P. Kothapalli, P.A. Sharma, A.B. Thomas, R.K. Nanda,
S.K. Shrivastava and V.V. Khatanglekar, Arab. J. Chem., 9 Suppl. 1, S480
(2016);
https://doi.org/10.1016/j.cclet.2008.12.026.
22. G.I. Shakibaei, P. Mirzaei andA. Bazgir, Appl. Catal. A, 325, 188 (2007);
https://doi.org/10.1016/j.apcata.2007.03.008.
23. S. Kantevari, R. Bantu and L. Nagarapu, J. Mol. Catal. Chem., 269, 53
(2007);
https://doi.org/10.1016/j.arabjc.2011.06.001.
4. N.P. Buu-Hoi, G. Saint-Ruf, A. De and H.T. Hieu, Bull. Chim. Ther., 7,
83 (1972).
5. G. Saint-Ruf, Huynh-Trong-Hieu and J.-P. Poupelin, Naturwissenschaften,
62, 584 (1975);
https://doi.org/10.1007/BF01166986.
6. R.-M. Ion, Prog. Catal., 2, 55 (1997).
7. M. Ahmad, T.A. King, D.-K. Ko, B.H. Cha and J. Lee, J. Phys. D Appl.
Phys., 35, 1473 (2002);
https://doi.org/10.1016/j.molcata.2006.12.039.
24. M.T. Maghsoodlou, S.M. Habibi-Khorassani, Z. Shahkarami, N. Maleki
and M. Rostamizadeh, Chin. Chem. Lett., 21, 686 (2010);
https://doi.org/10.1016/j.cclet.2010.02.005.
25. G. Karthikeyan andA. Pandurangan, J. Mol. Catal. Chem., 311, 36 (2009);
https://doi.org/10.1016/j.molcata.2009.06.020.
26. A. Hassankhani, E. Mosaddegh and S.Y. Ebrahimipour, E-J. Chem., 9,
786 (2012);
https://doi.org/10.1155/2012/930251.
https://doi.org/10.1088/0022-3727/35/13/303.
8. C.G. Knight and T. Stephens, Biochem. J., 258, 683 (1989);
https://doi.org/10.1042/bj2580683.
27. A. Akbari and A. Hosseini-Nia, J. Saudi Chem. Soc., 21, S7 (2017)
https://doi.org/10.1016/j.jscs.2013.09.009.
9. S. Hatakeyma, N. Ochi, H. Numata and S. Taka S. Hatakeyama, N. Ochi,
H. Numata and S. Takanono, J. Chem. Soc. Chem. Commun., 1202 (1988);
https://doi.org/10.1039/C39880001202.