Efficient synthesis of 14-substituted-14-H-dibenzo[a,j]xanthenes using silica supported sodium hydrogen sulfate or amberlyst-15 catalyst

Article abstract of DOI:10.1002/jhet.151

(Chemical Equation Presented) Silica supported sodium hydrogen sulfate (NaHSO₄·SiO₂) or amberlyst-15 acts as an efficient heterogeneous catalyst for the preparation of 14-alkyl and aryl-14-H-dibenzo[a, j]xanthenes with various aldehy

Full text of DOI:10.1002/jhet.151

September 2009 Efficient Synthesis of 14-Substituted-14-H-Dibenzo[a,j]xanthenes
Using Silica Supported Sodium Hydrogen Sulfate or
Amberlyst-15 Catalyst
997
Chebolu Naga Sesha Sai Pavan Kumar,a Chiguru Srinivas,a
Partha Sarathi Sadhu,a Vaidya Jayathirtha Rao,a* and Srinivasan Palaniappanb
aOrganic Chemistry Division-II, Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500007, Andra Pradesh, India
bOrganic Coatings and Polymers Division, Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500007, Andra Pradesh, India
*E-mail: jrao@iict.res.in
Received March 11, 2008
DOI 10.1002/jhet.151
Published online 1 September 2009 in Wiley InterScience (www.interscience.wiley.com).
Silica supported sodium hydrogen sulfate (NaHSO4ꢀSiO2) or amberlyst-15 acts as an efficient hetero-
geneous catalyst for the preparation of 14-alkyl and aryl-14-H-dibenzo[a,j]xanthenes with various alde-
hydes and b-naphthol in dichloroethane solvent in excellent yields. Synthesis of three new compounds
are reported using this methodology. Recyclable nature of the amberlyst-15 catalyst was also studied
and the catalyst can be reused.
J. Heterocyclic Chem., 46, 997 (2009).
INTRODUCTION
have used silica supported sodium hydrogen sulfate
(NaHSO4ꢀSiO2) or amberlyst-15, an efficient heterogene-
ous acid catalyst for the preparation of 14-Alkyl and
Aryl-14-H-dibenzo[a,j]xanthenes with various aldehydes
and b-naphthol in dichloroethane solvent (Scheme 1).
Recyclable nature of the amberlyst-15 catalyst was also
studied.
Xanthenes and Benzoxanthenes are important class of
heterocyclic compounds and they possess diverse range
of biological properties such as antiviral [1], antibacte-
rial [2], anti-inflammatory [3] activities, as well as in
photodynamic therapy [4]. Benzoxanthenes have also
been investigated for agricultural bactericide activity for
antagonism of the paralyzing action of zoxazolamine
[5]. In addition, these compounds have wide applica-
tions in dyes [6] and in laser technologies [7] because
of their useful spectroscopic properties. These com-
pounds can also be employed as pH sensitive fluorescent
materials for visualization of biomolecules [8].
RESULTS AND DISCUSSION
Product was not obtained when benzaldehyde
(1 mmol) was reacted with b-naphthol (2 mmol) in 1,2-
dichloroethane (5 mL) under reflux conditions for 24 h.
However, with the use of Amberlyst-15 (20 wt % with
respect to aldehyde) as catalyst yielded dibenzoxanthene
in 93% yield in 2 h. Almost same yield (92%) was
obtained with the use of silica supported sodium hydro-
gen sulfate as catalyst. Both catalysts are not soluble in
organic solvents and act as heterogeneous catalysts. We
have also examined this condensation reaction using dif-
ferent catalysts such as Amberlite IR-120 (Hþ form),
Montmorillonite K-10, and Indion-236. However, very
low yield (<15%) was obtained even for longer reaction
time. This may be because of the acidic nature of these
catalysts, i.e. these catalysts show less acidic character
for this reaction. To evaluate the efficiency of this meth-
odology, the catalytic activity of Amberlyst-15 and
silica supported sodium hydrogen sulfate was studied
Many synthetic routes have been developed for the
synthesis of xanthenes and benzoxanthenes, such as c-
alkylations to the heteroatom [9], trapping of benzynes
by phenols [10], cyclocondensation between 2-hydroxy
aromatic aldehydes, 2-tetralone [11], intramolecular phe-
nyl carbonyl coupling reactions of benzaldehydes and
acetophenones [12], reaction of b-naphthol with form-
amide [13], carbon monoxide [14], and 2-naphthol-1-
methanol [15].
The reaction procedure has been improved by reacting
b-naphthol with aldehydes under microwave irradiation
[16] and using various acid catalysts [17]. Recently, our
group reported using polyaniline based solid acid cata-
lyst for the preparation of dodecahydroxanthenes [18].
In continuation of our research work, in this article we
C
V
2009 HeteroCorporation

998
C. N. S. S. P. Kumar, C. Srinivas, P. S. Sadhu, V. J. Rao, and S. Palaniappan
Vol 46
Scheme 1
solvent was evaporated by reduced pressure. The crude prod-
ucts were subjected to column chromatography (silica gel 5%
EtOAc in hexane) to afford the pure products. All products
were characterized by 1H NMR, mass spectral data and com-
pared with the reported spectral and physical data for known
compounds (entry numbers 1–9, 11–13).
The recovered catalyst (Amberlyst-15) was reused (after
treatment with HCl) four more times for the condensation
reaction between benzaldehyde and b-naphthol following the
above procedure for 2 h in each case the corresponding prod-
uct furnishes with an yield of 93, 92, 92, and 91%.
for various aldehydes with b-naphthol and the yields are
reported in Table 1.The products were obtained within 2
to 4 h in excellent yields and generally, both catalysts
provided almost the same yield (Table 1).
Selected analytical data of three new representative diben-
zoxanthenes are given below.
We observed that the reactivity of aromatic aldehydes
with b-naphthol is higher when compared with the ali-
phatic aldehydes in terms of yields and reaction time
(Table 1). Furfural undergoes condensation smoothly
with b-naphthol in 2.5 h with good yield (entry no. 15,
Table 1). 4-Dimethylaminobenzaldehyde and pyridine-4-
carbaldehyde did not react to give dibenzoxanthenes and
it may be due to the presence of basic nitrogen in the
system (Table 1). Amberlyst-15 can be recovered by
simple filtration and can be reused after activation by
treatment with HCl.
14-(3,4-dimethoxyphenyl)-14H-ibenzo[a,j]xanthene (entry
10). Wheatish solid; mp 186–188ꢁC. IR (KBr): 3065, 1681,
1
1590, 1269, 1239, 1135, 1019, 815, 746 cmꢂ1. H NMR (300
MHz, CDCl3): d ¼ 8.35 (d, 2H), 7.35–7.81 (m, 10H), 7.08
(dd, 1H), 6.83 (d, 1H), 6.62 (d, 1H), 6.4 (s, 1H), 3.68 (s, 3H),
3.64 (s, 3H); 13C NMR (300 MHz, CDCl3): d 154.36, 148.95,
148.6,147.45, 137.58, 131.32, 130.98, 128.68, 128.64, 126.64,
126.56, 124.10, 122.6, 122.25, 117.78, 117.30, 111.68, 110.77,
55.85, 55.51, 37.29; HRMS (ESI) Calcd for C29H23O3 [Mþ
H]þ 419.1647, found 419.1633; Anal. Calcd for C29H23O3: C,
83.23; H, 5.30; Found: C, 83.17; H, 5.38.
14-Heptyl-14H-dibenzo[a,j]xanthene (entry 14). Off-white
solid; mp 74–76ꢁC. IR (KBr): 2922, 2850, 1589, 1458, 1397,
In conclusion, we have described a simple, clean, effi-
cient, and environmental friendly method for the synthe-
sis of biologically active heterocyclic compound, diben-
zoxanthenes using two different inexpensive and nonha-
zardous catalysts NaHSO4ꢀSiO2 and Amberlyst-15. We
feel that this method is a valid contribution to the exist-
ing methodologies.
1
1241, 810, 741 cmꢂ1. H NMR (300 MHZ, CDCl3): d ¼ 8.25
(d, 2H), 7.9 (d, 2H), 7.75 (d, 2H), 7.6 (t, 2H), 7.42 (t, 2H), 7.3
(d, 2H), 5.55 (s, 1H), 2.02 (m, 2H), 1.1–0.85 (m, 10 H), 0.7 (t,
3H); 13C NMR (300 MHZ, CDCl3): d 149.9, 131.4, 131.0,
128.8, 128.1, 126.5, 124.0, 122.4, 117.5, 116.7, 35.9, 31.7,
31.0, 29.7, 29.0, 24.8, 22.4, 14.0. HRMS (ESI) Calcd for
C28H29O [Mþ H]þ 381.2218, found 381.2217; Anal. Calcd for
C28H29O: C, 88.38; H, 7.42; Found: C, 88.41; H, 7.35.
EXPERIMENTAL
All chemicals were of research grade and were used as
obtained from Aldrich and Fluka. The reactions were carried
out in a round-bottomed flask of 25 mL capacity at reflux tem-
perature in an efficient fume hood. Analytical thin layer chro-
matography was performed with E. Merck silica gel 60F glass
plates and flash chromatography using E. Merck silica gel
(60–120 mesh). Melting points were determined on a MEL-
TEMP II melting point apparatus and were uncorrected. NMR
spectra were recorded of Gemini 200 MHz Varian instrument
and Avance 300 MHz Bruker UX 300 FT NMR. All NMR
data were obtained in CDCl3 solution and chemical shifts (d)
were given in ppm relative to TMS and are compared with the
reported literature values. Mass spectra were recorded on VG
Micromass 7070 H (EI), VG Autospec (FAB) using Csþ ion
gun, MNBA as a matrix, Applied Biosystems QSTAR XL
High resolution mass spectrometer, Thermofinnigan ESI ion
trap mass spectrometer and GC-MS instruments. Elemental
analyses were performed using a Vario-EL elemental analyzer.
Typical procedure for the preparation of di-
benzoxanthenes. In a typical procedure, a mixture of aldehyde
(1 mmol), b-naphthol (2 mmol), 1,2-dichloroethane (5 mL),
and NaHSO4.SiO2 (100 mg) (Method A) or amberlyst-15 (20
wt % with respect to aldehyde) (method B) was stirred at
reflux for the appropriate time according to Table 1. The pro-
gress of the reaction was monitored by TLC. After completion
of the reaction, the catalyst was filtered off and the organic
Table 1
Synthesis of dibenzoxanthene derivatives using
heterogeneous catalysts.
Yielda (%)
Entry
R
Time(h) Method A Method B
1
2
C6H5
4-ClC6H4
4-FC6H4
2
1.5
2
92
91
96
92
91
92
81
85
87
85
91
80
90
82
81
–
93
90
94
94
90
93
82
83
88
86
90
82
90
83
84
–
3
4
5
4-BrC6H4
3
3
4-O2NC6H4
4-H3CC6H4
H3CCH2CH2
(CH3)2CHCH2
CH3(CH2)3CH2
3,4-(OCH3)2C6H2
3-O2NC6H4
4-OHC6H4
6
7
2
4
8
9
2
4
10
11
12
13
14
15
16
17
4
2.5
4
4-H3COC6H4
H3C(CH2)5CH2
2-C4H3O
4-C5H4N
4-N(CH3)2C6H4
3
4
2.5
24
24
–
–
Method A ¼ NaHSO4ꢀSiO2; Method B ¼ Amberlyst-15.
a Isolated yields.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2009
Efficient Synthesis of 14-Substituted-14-H-Dibenzo[a,j]xanthenes Using Silica
Supported Sodium Hydrogen Sulfate or Amberlyst-15 Catalyst
999
[8] Knight, C. G.; Stephens, T. Biochem J 1989, 258, 683.
14-(2-Furyl)-14H-dibenzo[a,j]xanthene (entry 15). Reddish
solid; mp 217–219ꢁC. IR (KBr): 3059, 2923, 1621, 1590,
[9] (a) Vazquez, R.; De la Fuente, M. C.; Castedo, L.; Domi-
nguez, D. Synlett 1994, 433; (b) Ishibashi, H.; Takagoki, K.; Imada,
N.; Ikeda, M. Synlett 1994, 49.
1245, 1146, 813, 737 cmꢂ1 1H NMR (300 MHz, CDCl3): d
.
¼ 8.33 (d, 2H), 7.82–7.39 (m, 10H), 7.13 (d, 1H), 6.6 (s, 1H),
6.03 (m, 1H), 5.75 (d, 1H); 13C NMR (300 MHz, CDCl3): d
156.8, 149.2, 141.2, 129.2, 128.6, 126.8, 126.2, 124.6, 124.4,
122.8, 118.0, 114.2, 110.3, 106.6, 31.6; HRMS: (ESI) Calcd
for C25H17O2 [Mþ H]þ 349.1228, found 349.1230; Anal.
Calcd for C25H17O2: C, 86.19; H, 4.63; Found: C, 86.26; H,
4.61.
[10] (a) Knight, D. W.; Little, P. B. Synlett 1998, 1141; (b)
Knight, D. W.; Little, P. B. J Chem Soc Perkin Trans 1 2001,
1771.
[11] Jha, A.; Beal, J. Tetrahedron Lett 2004, 45, 8999.
[12] Kuo, C. W.; Fang, J. M. Synth Commun 2001, 31, 877.
[13] Papini, P.; Cimmarusti, R. Gazz Chim Ital 1947, 77, 142.
[14] Ota, K.; Kito, T. Bull Chem Soc Jpn 1976, 49, 1167.
[15] Sen, R. N.; Sarkar, N. J Am Chem Soc 1925, 47, 1079.
[16] (a) Rajitha, B.; Sunil kumar, B.; Thirupathi Reddy, Y.; Nar-
simha Reddy, P.; Sreenivasulu, N. Tetrahedron Lett 2005, 46, 8691;
(b) Khoramabadi-zad, A.; Akbari, S.; Shiri, A.; Veisi, H. J Chem Res
Synop 2005, 5, 277; (c) Bhattacharya, A. K.; Rana, K. C. Mendeleev
Commun 2007, 17, 247; (d) Selvam, N. P.; Shanthi, G.; Perumal, P. T.
Can J Chem 2007, 85, 989.
Acknowledgments. The authors thank CSIR and UGC, New
Delhi, for fellowship.
REFERENCES AND NOTES
[1] Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E.
B.; Thomas, G. J. PCT Int Appl WO 9706178 (1997).
[2] Hideo, T. Jpn. Kokai. Tokkyo Koho 56005480 (1981).
[3] Poupelin, J. P.; Saint-Rut, G.; Foussard-Blanpin, O.; Nar-
cisse, G.; Uchida-Ernouf, G.; Lacroix, R. Eur J Med Chem 1978, 13,
67.
[17] (a) Khosropour, A. R.; Khodaei, M. M.; Moghannian, H.
Synlett 2005, 955; (b) Das, B.; Ravikanth, B.; Ramu, R.; Laxminar-
ayana, K.; Rao, B. V. J Mol Catal A: Chem 2006, 255, 74; (c) Pasha,
M. A.; Jayashankara, V. P. Bioorg Med Chem Lett 2007, 17, 621; (d)
Sarma, R. J.; Baruah, J. B. Dyes Pigm 2005, 64, 91; (e) Buu-Hoi, PH.;
Xuong, D.; Khoi, H. J Chem Soc 1951, 255; (f) Das, B.; Kumar, D.
N.; Laxminarayana, K.; Ravikanth, B. Helv Chim Acta 2007, 90,
1330; (g) Rogow Chem Ber 1900, 33, 3536; (h) Dilthey, Q. Chem Ber
1936, 69, 1575; (i) Patil, S. B.; Bhat, R. P.; Samant, S. D. Synth.
Commun. 2006, 36, 2163; (j) Ko, S.; Yao, C. Tetrahedron Lett 2006,
47, 8827; (k) Nagarapu, L.; Baseeruddin, M.; Kumari, N. V.; Srinivas;
K.; Rudradas, A. P. Synth Commun 2007, 37, 2519; (l) Dabiri, M.;
Baghbanzadeh, M.; Nikcheh, M. S.; Arzroomchilar, E.; Bioorg Med
Chem Lett 2008, 18, 436.
[4] (a) Ion, R. M. Progr Catal 1997, 2, 55; (b) Ion, R. M.;
Frackowiak, D.; Planner, A.; Wiktorowicz, K. Acta Biochim Pol 1998,
45, 833.
[5] Saint-Ruf, G.; Hieu, H. T.; Poupelin, J. P. Naturwissen-
schaften 1975, 62, 584.
[6] (a) Banerjee, A.; Mukherjee, A. K. Stain Technol 1981, 56,
83; (b) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen, W.;
Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M. U. S. Pat.
6,583,168 (2003).
[18] John, A.; Yadav, P. J. P.; Palaniappan, S. J Mol Catal A:
Chem 2006, 248, 121.
[7] Sirkeeioglu, O.; Talini, N.; Akar, A. J Chem Res Synop
1995, 12, 502.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet