Perchloric acid-silica (HClO4·SiO2)-catalyzed synthesis of 14-alkyl- or 14-aryl-14H-dibenzo[a,,j]xanthenes and N-[(2-hydroxynaphthalen-1-yl)methyl]amides

Article abstract of DOI:10.1002/hlca.200790134

The synthesis of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes 3 involving the treatment of naphthalen-2-ol (1) with arenecarboxaldehydes or alkanals 2 in the presence of HClO₄·SiO₂ as a heterogeneous catalyst was achieved (Table 1)

Full text of DOI:10.1002/hlca.200790134

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Helvetica Chimica Acta – Vol. 90 (2007)
Perchloric Acid – Silica (HClO4 · SiO2)-Catalyzed Synthesis of 14-Alkyl- or
14-Aryl-14H-dibenzo[a,j]xanthenes and N-[(2-Hydroxynaphthalen-1-
yl)methyl]amides1)
by Biswanath Das*, D. Nandan Kumar, Keetha Laxminarayana, and B. Ravikanth
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
The synthesis of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes 3 involving the treatment of
naphthalen-2-ol (1) with arenecarboxaldehydes or alkanals 2 in the presence of HClO4 · SiO2 as a
heterogeneous catalyst was achieved (Table 1), and this reaction was extended to the preparation of N-
[(2-hydroxynaphthalen-1-yl)methyl]amides 5 by a three-component reaction with urea (4a) or an amide
4b – d as a third reactant (Table 2).
Introduction. – The synthesis of xanthene derivatives, particularly of benzo-fused
xanthenes, has attracted considerable attention by chemists because of their biological
and pharmaceutical properties. These compounds possess anti-inflammatory [1],
antiviral [2], and antibacterial [3] activity. Furthermore, xanthene derivatives can be
utilized in photodynamic therapy [4] and as antagonism for the paralyzing action of
zoxazolamine [5]. The other useful applications of these compounds are as dyes [6],
fluorescent materials for visualization of biomolecules [7], and in laser technologies
[8]. It is also noteworthy that several polycyclic compounds containing the xanthene
skeleton have been reported from natural sources [9]. Thus, the synthesis of xanthene
derivatives is currently of great interest.
Various methods have been developed for the synthesis of xanthenes such as the
reactions of naphthalen-2-ol (1) with formamide [10], 2-hydroxynaphthalene-1-
methanol [11] and carbon monoxide [12], aryne cycloaddition to phenols [13],
cyclodehydration [14], and intramolecular coupling of aldehydes and ketones [15].
However, several of these methods suffer from harsh reaction conditions, long reaction
times, and poor yields. Consequently, there is a need for the development of a clean,
facile, and efficient process for the synthesis of xanthene derivatives.
Results and Discussion. – Heterogeneous catalysts have gained much importance in
recent years due to economic and environmental benefits [16]. These catalysts make
synthetic processes clean, safe, high yielding, and inexpensive. A tremendous interest
has sparked in various chemical transformations promoted by catalysts under
heterogeneous conditions. Recently HClO4 · SiO2 has been found to be an efficient
heterogeneous catalyst in various useful chemical transformations [17]. In continuation
1
)
Part 143 in the series, ꢁStudies on Novel Synthetic Methodologiesꢂ.
ꢀ 2007Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 90 (2007)
1331
of our work on the application of heterogeneous catalysts to the development of
simplified synthetic methodologies [18], we observed that HClO4 · SiO2 [19] can act as
an efficient catalyst for the synthesis of 14-aryl- or 14-alkyl-14H-dibenzo[a,j]xanthenes
3 by the condensation of naphthalen-2-ol (1) with aldehydes 2 (Table 1). Initially, we
carried out the reaction of 1 with 4-chlorobenzaldehyde (2b) in the presence of the
catalyst HClO4 · SiO2 by stirring the mixture for 3 h at 1008 in the absence of solvent.
We observed the formation of the desired xanthene derivative 3b (Table 1) in 91%
yield (isolated material). The same method applied to the conversion of 1 with other
aldehydes 2 proceeded within 3 – 6 h to form the products 3 in high yields (77 – 93%)
(Table 1). The reaction was equally effective with both aromatic and aliphatic
aldehydes. The aromatic aldehydes containing electron-donating as well as electron-
withdrawing groups underwent the conversion smoothly. We believe that in the present
transformations the xanthenes could be generated by ꢁin situꢂ formation of ꢁo-
quinomethaneꢂ intermediates [20] (Scheme).
Scheme
Table 1. Preparation of 14-Aryl- or 14-Alkyl-14H-dibenzo[a,j]xanthenes 3a)
Aldehyde
R
Product
Time [h]
Yield [%]b)
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
3.5
3.0
92
91
90
93
88
81
89
92
84
89
77
82
4-ClÀC6H4
4-FÀC6H4
3-CF3ÀC6H4
3-NO2ÀC6H4
4-MeÀC6H4
4-EtÀC6H4
4-OHÀC6H4
4-MeOÀC6H4
3-MeO,4-OHÀC6H3
Et
3.75
4.0
3.75
4.25
4.0
4.5
4.0
4.75
6.0
5.5
2j
2k
2l
3j
3k
3l
iPr
a) All the products were characterized by 1H-NMR and MS data. b) Yield of isolated material.

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Helvetica Chimica Acta – Vol. 90 (2007)
Encouraged by the above results, we extended this protocol to a three-component
coupling reaction involving urea (4a) or an amide (4b – d) as a third reactant to obtain
the corresponding N-[(2-hydroxynaphthalen-1-yl)methyl]amides 5 (Table 2). Here the
ꢁo-quinomethaneꢂ intermediates are trapped by urea or amides. The reaction was
conducted under neat conditions by heating the corresponding mixture at 1258. This
conversion proceeded within 5 – 9 h to form the products in good to high yields (68 –
93%). The aromatic aldehydes containing both electron-donating and electron-
withdrawing groups (see 2b – f) afforded the products in high yields. When the reaction
was conducted with aliphatic aldehydes, the products were formed in lower yields. The
reaction proceeded equally with urea (4a) or amides such as acetamide (4b),
benzamide (4c), and acrylamide (¼ prop-2-enamide; 4d). The structures of the
1
products were established by their H-NMR and MS data.
Table 2. Preparation of N-[(2-Hydroxynaphthalen-1-yl)methyl]amides 5a)
Aldehyde
R
Urea or Amide
R’
Product
Time [h]
Yield [%]b)
2a
2b
2m
2e
2n
2f
2o
2a
2h
2f
Ph
4a
4a
4a
4a
4a
4a
4a
4b
4b
4c
4c
4c
4d
4d
NH2
NH2
NH2
NH2
NH2
NH2
NH2
Me
Me
Ph
Ph
Ph
5aa
5ba
5ma
5ea
5na
5fa
5oa1
5ab
5hb
5fc
5
5.5
3
90
83
81
93
87
86
4-ClÀC6H4
2,4-Cl2ÀC6H3
3-NO2ÀC6H4
2-BrÀC6H4
4-MeÀC6H4
Naphth-1-yl
Ph
4-OHÀC6H4
4-MeÀC6H4
4-ClÀC6H4
Naphth-1-yl
4-MeÀC6H4
4-ClÀC6H4
5.75
6.0
5.25
77
6.5
5.5
7.75
9
82
78
75
68
73
77
76
2b
2o
2f
5bc
5oc
5fd
5bd
8.5
8.75
7.5
CH2¼CH
2b
CH2¼CH
a) All the products were characterized by 1H-NMR and MS data. b) Yield of isolated material.
In conclusion, we have developed a clean and simple method for the synthesis of
14H-dibenzo[a,j]xanthenes 3 and N-[(2-hydroxynaphthalen-1-yl)methyl]amides 5
under solvent-free conditions using HClO4 · SiO2 as a heterogeneous catalyst. The
mild reaction conditions, short reaction times, simplicity of the reaction, and high yields
are notable advantages of this protocol.
The authors thank CSIR, New Delhi, for financial assistance.

Helvetica Chimica Acta – Vol. 90 (2007)
1333
Experimental Part
14-Aryl- or 14-Alkyl-14H-dibenzo[a,j]xanthenes 3: General Procedure: A mixture of naphthalen-2-
ol (1; 1 mmol), aldehyde 2 (0.5 mmol), and HClO4 · SiO2 (100 mg; prepared as reported [19]) was heated
at 1008. After completion of the reaction (TLC monitoring) the mixture was filtered, the filtrate
concentrated, and the residue purified by column chromatography CC (silica gel, hexane): pure 14-aryl-
or 14-alkyl-14H-dibenzo[a,j]xanthene 3.
N-[(2-Hydroxynaphthalen-1-yl)methyl]amides 5: General Procedure: A mixture of naphthalen-2-ol
(1; 1 mmol), aldehyde 2 (1 mmol), urea (4a) or an amide 4b – d (1.4 mmol), and HClO4 · SiO2 (100 mg)
was heated at 1258. After completion of the reaction (TLC monitoring), the mixture was filtered, the
filtrate concentrated, and the residue purified by CC (silica gel, 30% AcOEt/hexane): pure N-[(2-
hydroxynaphthalen-1-yl)methyl]amide 5.
The 1H-NMR (d in ppm, J in Hz) and MS (in m/z) data of some representative products are given
below.
14-(3-Nitrophenyl)-14H-dibenzo[a,j]xanthene (3e): 1H-NMR (CDCl3, 200 MHz): 8.40 (s, 1 H); 8.25
(d, J ¼ 8.0, 2 H); 7.90 – 7.70 (m, 6 H); 7.63 – 7.21 (m, 7H); 6.50 ( s, 1 H). FAB-MS: 404 ([M þ H]þ).
1
14-(4-Methylphenyl)-14H-dibenzo[a,j]xanthene (3f): H-NMR (CDCl3, 200 MHz): 8.31 (d, J ¼ 8.0,
2 H); 7.85 – 7.71 (m, 3 H); 7.60 – 7.30 (m, 9 H); 6.90 (d, J ¼ 8.0, 2 H); 6.35 (s, 1 H); 2.10 (s, 3 H). FAB-MS:
373 ([M þ H]þ).
14-(4-Methoxyphenyl)-14H-dibenzo[a,j]xanthene (3i): 1H-NMR (CDCl3, 200 MHz): 8.30 (d, J ¼ 8.0,
2 H), 7.90 – 7.70 (m, 4 H); 7.60 – 7.30 (m, 8 H); 6.62 (d, J ¼ 8.0, 2 H); 6.35 (s, 1 H); 3.60 (s, 3 H). FAB-MS:
389 ([M þ H]þ).
14-Isopropyl-14H-dibenzo[a,j]xanthene (3l): 1H-NMR (CDCl3, 200 MHz): 8.26 (d, J ¼ 8.0, 2 H);
7.90 – 7.70 (m, 4 H); 7.61 – 7.40 (m, 2 H); 7.43 – 7.32 (m, 4 H); 5.42 (d, J ¼ 7.0, 1 H); 2.28 (m, 1 H); 0.81 (d,
J ¼ 7.0, 6 H). FAB-MS: 325 ([M þ H]þ).
N-[(2-Bromophenyl)(2-hydroxynaphthalen-1-yl)methyl]urea (5na): 1H-NMR (CDCl3/(D6)DMSO,
200 MHz): 9.28 (br. s, 1 H); 8.04 (d, J ¼ 8.0, 1 H); 7.74 – 6.78 (m, 13 H); 5.22 (br. s, 2 H). FAB-MS: 371,
373 ([M þ H]þ).
N-[(2-Hydroxynaphthalen-1-yl)(4-hydroxyphenyl)methyl]acetamide (5hb): 1H-NMR (CDCl3/
(D6)DMSO, 200 MHz): 9.64 (br. s, 1 H); 8.72 (br. s, 1 H); 8.14 (d, J ¼ 8.0, 1 H); 8.01 (d, J ¼ 8.0, 1 H);
7.42 – 6.98 (m, 8 H); 6.62 (d, J ¼ 8.0, 2 H); 2.04 (s, 3 H). FAB-MS: 296 ([M þ H]þ).
N-[(2-Hydroxynaphthalen-1-yl)naphthalen-1-ylmethyl]benzamide (5oc): 1H-NMR (CDCl3/
(D6)DMSO, 200 MHz): 10.01 (br. s, 1 H); 8.97( d, J ¼ 8.0, 1 H); 8.24 (d, J ¼ 8.0, 1 H); 7.98 – 7.16 (m,
18 H). FAB-MS: 404 ([M þ H]þ).
N-[(2-Hydroxynaphthalen-1-yl)(4-methylphenyl)methyl]prop-2-enamide (5fd): 1H-NMR (CDCl3/
(D6)DMSO, 200 MHz): 9.62 (br. s, 1 H); 8.25 (d, J ¼ 8.0, 1 H); 8.00 (d, J ¼ 8.0, 1 H); 7.78 – 7.62 (m, 2 H);
7.39 (t, J ¼ 8.0, 1 H); 7.28 – 6.90 (m, 10 H); 6.36 – 6.22 (m, 2 H); 5.61 (m, 1 H); 2.12 (s, 3 H). FAB-MS: 318
([M þ H]þ).
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Received March 16, 2007