A one-pot synthesis of 1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one derivatives catalyzed by perchloric acid supported on silica (HClO 4/SiO2) in the absence of solvent

Article abstract of DOI:10.1007/bf03246067

1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one derivatives were synthesized in high yields using a facile and one-pot condensation of 2-naphthol, aromatic aldehydes and urea catalyzed by perchloric acid supported on silica under thermal solventfree co

Full text of DOI:10.1007/bf03246067

J. Iran. Chem. Soc., Vol. 7, No. 3, September 2010, pp. 770-774.
JOURNAL OF THE
Iranian
Chemical Society
A One-Pot Synthesis of 1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one Derivatives
Catalyzed by Perchloric Acid Supported on Silica (HClO /SiO ) in the Absence of
4
2
Solvent
a
b,
a
a
H. Abbastabar Ahangar , G.H. Mahdavinia *, K. Marjani and A. Hafezian
Faculty of Chemistry, Teacher Training University, P.O. Box 15614, Tehran, Iran
Young Research Club & Department of Chemistry, Islamic Azad University-Marvdasht Branch, Marvdasht, Iran
a
b
(Received 25 October 2008, Accepted 12 November 2009)
1
,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one derivatives were synthesized in high yields using a facile and one-pot
condensation of 2-naphthol, aromatic aldehydes and urea catalyzed by perchloric acid supported on silica under thermal solvent-
free conditions.
Keywords: One-pot, HClO -SiO , Heterogeneous catalyst, Naphthoxazine-3-one, Solvent-free reaction
4
2
INTRODUCTION
heterogeneous catalysts have attracted special attention in
recent years due to economic and environmental
considerations. These catalysts are generally inexpensive and
easily available. They can conveniently be handled and
removed from the reaction mixture, thus making the
experimental procedure simple and eco-friendly. The leading
contenders for environmentally acceptable processes are
supported reagents. The use of silica-supported reagents in
one-pot multi-component construction of heterocycles has
received considerable attention in organic synthesis [10]. In
particular, perchloric acid adsorbed on silica gel (HClO /SiO )
Multicomponent reactions (MCRs) constitute an especially
attractive synthetic strategy due to the fact that the products
are formed in a single step while diversity can be promoted
simply by varying the reacting components [1]. Moreover,
multicomponent reactions (MCRs) by virtue of their
convergence, productivity, ease of execution and generally
high yields of products have attracted considerable attention in
the field of combinatorial chemistry [2]. The first MCR was
described by Strecker in 1850 for the synthesis of amino acids
4
2
[
3]. However, in the past decade, there have occurred
[11] has emerged as an extremely useful catalyst in various
organic transformations including acylation of alcohols [11],
acylation of aldehydes [12], 1,3-dithiolane/dithiane formation
[13], tetrahydropyranylation [14], thio-acetalization [14],
Ferrier rearrangement [15], Michael addition [16], cleavage of
ketals and benzylidene acetals [17], the Hantzsch condensation
[18], synthesis of bis-indolylmethanes [19], glycosylation of
sugars [20] N-tert-butoxycarbonylation of amines [21],
synthesis of tetrasubstituted imidazoles [22], synthesis of poly-
substituted quinolines [23] and synthesis of benzoxanthenes
tremendous developments in three- and four-component
reactions and great efforts are continually being made to
develop new MCRs [4-8].
Solid-phase organic synthesis is a subject of recent interest
in the context of generating libraries of molecules for the
discovery of biologically active leads and also for the
optimization of potent drug candidates [9]. Moreover,
*
Corresponding author. E-mail: hmahdavinia@gmail.com

Abbastabar Ahangar et al.
[
24].
Aromatic-condensed oxazinone derivatives are an
was kept at room temperature for a while and the solid product
was collected by filtration. The product was found to be pure
and no further purification was necessary.
important class of heterocyclic compounds, since many of
these heterocyclic systems exhibit biological activities [25].
For example, naphthalene-condensed 1,3-oxazin-3-ones have
been reported to act as antibacterial agents [26]. This class of
compounds has also been used as precursors in the preparation
of phosphinic ligands for asymmetric catalysis [27]. However,
to the best of our knowledge, only few experiments on the
synthesis of naphthalene-condensed oxazinone derivatives are
reported in the literature [26,28]. Recently, some syntheses of
naphthalene-condensed 1,3-oxazin-3-ones derivatives have
been reported using condensation of amino alkylnaphthols as
precursors with phosgene in the presence of triethylamine [29]
and carbonyl diimidazol instead of phosgene [30]. However,
in these methods, either expensive reagents and solvents are
required or the reagents used are highly toxic and hazardous.
Furthermore, for the preparation of starting materials such as
amino alkylnaphtol, a multi-step reaction using harsh
conditions is needed. Therefore, the development of new,
simple, green and one-pot methods for the synthesis of
naphthoxazinone derivatives are of prime importance.
Recently, Bazgir and co-workers reported a one-pot
synthesis of 1,2-dihydro-1-aryl- naphtho[1,2-e][1,3]oxazine-3-
one derivatives [31] wherein they make use of MW irradiation
to achieve good yields, but in thermal conditions no high
yields were produced.
1
13
The Spectral (IR, H NMR, C NMR) and Analytical
Data of New Compounds
1,2-Dihydro-1-(2-chlorophenyl)naphtho[1,2-e][1,3]
oxazine-3-one (4e). IR(KBr): 3237, 3124, 1727, 1396, 1233
-
1 1
cm ; H NMR (300 MHz, DMSO-d ): ꢀ = 6.50 (d, 1H, J =
6
2.94, CH), 7.18-8.01 (m, 10H, Ar-H), 8.89 (sbr, 1H, NH); 13
C
NMR (75 MHz, DMSO-d ): ꢀ = 52.46, 114.13, 117.43,
6
123.58, 124.23, 125.68, 126.32, 128.06, 129.17, 129.32
129.76, 130.13, 130.24, 130.37, 133.09, 143.25, 147.15,
149,08; Calcd. for C H ClNO : C, 70.04; H, 4.04; N, 4.63.
1
8
12
2
Found: C, 69.80; H, 3.90; N, 4.52.
1,2-Dihydro-1-(3-bromophenyl)naphtho[1,2-e][1,3]
oxazine-3-one (4f). IR(KBr): 3269, 3163, 1746, 1710, 1221
-
1
1
cm ; H NMR (300 MHz, DMSO-d ): ꢀ = 6.25 (d, 1H, J =
6
2.97, CH), 7.17-8.01 (m, 10H, Ar-H), 8.91 (d, 1H, J = 2.97,
NH); 13C NMR (75 MHz, DMSO-d ): ꢀ = 53.02, 113.29,
6
116.91, 122.01, 123.05, 125.24, 125.87, 127.57, 128.71,
128.78 129.93, 130.42, 130.55, 130.98, 131.34, 145.35,
147.56, 149,14; Calcd. for C H BrNO : C, 61.04; H, 3.41; N,
3.95. Found: C, 61.66; H, 3.58; N, 4.02.
1,2-Dihydro-1-(3-methoxyphenyl)naphtho[1,2-e][1,3]
oxazine-3-one (4i). IR(KBr): 3211, 3135, 1748, 1597, 1263
18
12
2
-
1
1
cm ; H NMR (300 MHz, DMSO-d ): ꢀ = 6.15 (d, 1H, J =
6
In this article, we present a one-pot, three-component
method for the preparation of 1,2-dihydro-1-arylnaphtho[1,2-
e][1,3]oxazine-3-one derivatives under thermal, solvent-free
conditions.
2.96, CH), 6.75-7.99 (m, 10H, Ar-H), 8.85 (d, 1H, J = 2.96,
NH); 13C NMR (75 MHz, DMSO-d ): ꢀ = 53.02, 55.04,
6
113.29, 116.91, 122.01, 123.05, 125.24, 125.87, 127.57,
128.71, 128.78 129.93, 130.55, 130.98, 131.34, 145.35,
1
47.56, 149,14, 159.2; Calcd. for C H NO : C, 74.32; H,
19
15
3
EXPERIMENTAL
4.97; N, 4.50. Found: C, 74.74; H, 4.95; N, 4.59.
,2-Dihydro-1-(2-thiophen)naphtho[1,2-e][1,3]oxazine-
3-one (4k). IR (KBr): 3772, 3266, 1747, 1710, 1516, 1278,
1
General Experimental Procedure
-
1
1
A mixture of an aldehyde (1 mmol), 2-naphtol (1 mmol),
1222, 1178, 806, 728 cm ; H NMR (300 MHz, DMSO-d ):
6
urea (1.3 mmol) and HClO -SiO (40 mg, 0.02 mmol, 2
ꢀ = 6.56 (d, 1H, J = 2.92 Hz, CH), 6.92-7.99 (m, 8H, Ar-H),
9.05 (d, 1H, J = 2.92 Hz, NH); 13C NMR (75 MHz, DMSO-
d6): ꢀ = 48.79, 114.52, 116.84, 123.03, 125.20, 125.68, 126.20,
126.96, 127.47, 128.62 128.79, 130.37, 130.43, 146.83,
147.09, 149.49; Calcd. for C H NO S: C, 68.312; H, 3.94;
4
2
mol%) was heated at 150 °C with stirring for one hour. After
the completion of the reaction (monitored by TLC), the
mixture was cooled to room temperature and the reaction
mixture was diluted with ethanol (5 ml) and stirred for 5 min
at 80 °C. The catalyst was separated by filtration. The residue
16
11
2
N, 4.98. Found: C, 67.87; H, 3.88; N, 4.87.
7
71

A One-Pot Synthesis of 1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
RESULTS AND DISCUSSION
derivatives were conducted. The results are summarized in
Table 1. Benzaldehyde and other aromatic aldehydes
containing electron-withdrawing groups (halide groups) or
electron-donating groups (such as hydroxy, alkoxyl groups)
were employed which were found to react well to give the
corresponding 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-
3-ones in good yields.
In continuation of our previous work on the synthesis of
heterocyclic compounds [24,32-34], herein, we wish to report
a novel, one-pot, three-component method for the preparation
of
1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
derivatives under thermal, solvent-free conditions (Scheme 1).
Following a typical, general experimental procedure, a
solution of an aromatic aldehyde, ꢁ-naphtol and urea under
neat conditions, in the presence of a catalytic amount of
HClO /SiO (2 mol%), and in the appropriate period of time,
The catalyst plays a crucial role in the success of the
reaction in terms of the rate and the yields. For example, 4-
chlorobenzaldehyde reacted with ꢁ-naphtol and urea in the
presence of 0.5 mol% HClO /SiO to give the product 4c in
4
2
4
2
the reaction took place. The resulting crude 1,2-dihydro-1-
arylnaphtho[1,2-e][1,3]oxazine-3-ones was purified by
recrystallization from EtOH to afford the pure product.
To examine the generality of the process, several
experimental trials illustrating this method for the synthesis
modest yield (45%) under neat conditions after one hour of
reaction time. Increasing the molar amounts of the catalyst to
1 mol%, 2 mol% and 3 mol% resulted in increasing the
reaction yields to 65%, 89% and 89.2%, respectively. The use
of just 2 mol% of HClO /SiO under solvent-free conditions
4
2
of
1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
was sufficient to proceed the reaction. Higher amounts of the
H
Ar
N
O
O
OH
O
HClO /SiO2
4
ArCHO
+
NH2
+
H N
2
1
50°C,
solvent-free
1
2
3
4a-k
Scheme 1
Table 1. Reaction of ꢁ-Naphthol with Aldehydes and Urea under Thermal Solvent-Free Conditions
Reported M.p.
Entry
Ar
Product
Yield (%)
M.p. (°C)
(
°C)
1
2
3
4
5
6
7
8
9
C
6
H
5
4a
4b
4c
4d
4e
4f
85
90
88
92
90
89
85
85
84
75
92
218-220
206-207
212-214
218-220
250-252
232-235
169-171
191-193
202-204
185(dec.)
208-210
218-220
202-204
208-210
220-223
-
4-FC
4-ClC
4-BrC
2-ClC
3-BrC
4-MeC
6
H
4
H
6
4
6
H
4
6
H
4
6
H
4
-
H
4g
4h
4i
166-168
185-188
-
6
4
4-MeOC
3-MeOC
6
H
4
4
6
H
1
1
0
1
4-OHC
6
H
4
4j
180(dec.)
-
2-Thiophen
4k
7
72

Abbastabar Ahangar et al.
catalyst did not improve the results of the reaction to a
Table 2. The Reaction of 4-Chlorobenzaldehyde with ꢁ-
noticeable extent. The yields were in general high, regardless
of the structural variations in aromatic aldehydes. Under the
identical conditions, the rate of the reaction was affected by
the presence of HClO /SiO and the yields were 70%, 89%
Naphthol and Urea Catalyzed by HClO /SiO at
Reflux Conditions
4
2
4
2
Entry
Solvent
Time (h)
Yield (%)
and 89.5% after different time intervals of 0.5 h, 1 h, 2 h,
respectively. Thus, 2 mol% of HClO /SiO was chosen as the
4
2
1
2
3
4
5
6
Ethanol
DMF
2
2
2
2
2
1
0
10
0
suitable amount of the catalyst for these reactions. The catalyst
could be reused 5 times for the synthesis of 4c without
significant loss of its activity. This reaction was also examined
CH CN
3
in the presence of SiO at 150 ꢀC. As we noticed earlier, the
2
Water
0
reaction failed under this condition.
CHCl3
0
We further examined the effect of the solvents upon the
reaction of 4-chlorobenzaldehyde with ꢁ-naphtol and urea
catalyzed by HClO /SiO (2 mol%) in various solvents the
Solvent-free
88
4
2
results of which are summarized in Table 2. The yields refer to
the isolated products. The results show that the solvent-free
condition is a more suitable one for the reactions.
We propose the following possible mechanism to account
for the reaction. The reaction could be mechanistically
considered to proceed through the acylimine intermediate
by IR, 1H NMR, 13C NMR and elemental analyses.
Replacement of ꢁ-naphtol with ꢂ-naphtol under these
conditions produced no product.
In conclusion, we have described a highly efficient one-pot
synthesis for the preparation of naphthoxazine-3-one
derivatives in three-component cyclo-condensation reaction of
ꢁ-naphtol, aromatic aldehydes and urea under solvent-free
thermal conditions. Easy work-up, low cost, ready availability
of the catalyst make the procedure an attractive alternative to
the existing methods for the synthesis of naphthoxazine-3-one
derivatives.
(
formed in situ by reaction of the aldehyde with urea) [35] or
ortho-quinone methides (O-QMs) intermediate (formed in situ
by reaction of the aldehyde with ꢁ-naphtol) [36]. The
subsequent addition of the ꢁ-naphtol to the acylimine or
addition of the urea to the O-QMs, followed by cyclization
affords the corresponding products 4a-k and ammonia
(Scheme 2). The structures of the products were characterized
O
O
Ar
H N
NH2
ArCHO
+
+
2
N
NH2
OH
OH
O
H
N
H
N
Ar
Ar
O
Ar
O
NH2
OH
O
O
H N
NH2
2
-
NH3
Scheme 2
7
73

A One-Pot Synthesis of 1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
Lett. 47 (2006) 3573.
REFERENCES
[
18] M. Maheswara, V. Siddaiah, G.L.V. Damu, C.V. Rao,
ARKIVOC (2006) 201.
[
1]
A. Domiling, I. Ugi, Angew. Chem. Int. Ed. 39 (2000)
168.
L.Weber, K. Illegen, M. Almstetter, Synlett (1999) 366.
A. Strecker, Liebigs. Ann. Chem. 75 (1850) 27.
D. Pizzirani, M. Roberti, M. Recanatini, Tetrahedron
Lett. 48 (2007) 7120.
3
[19] V.T. Kamble, K.R. Kadam, N.S. Joshi, D.B. Muley,
Catal. Commun. 8 (2007) 498.
[20] Y. Du, G. Wei, S. Cheng, Y. Hua, R.J. Linhardt,
Tetrahedron Lett. 47 (2006) 307.
[21] A.K. Chakraborthi, S.V. Chankeshwara, Org. Biomol.
Chem. 4 (2006) 2769.
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
R.S. Kumar, S. Perumal, Tetrahedron Lett. 48 (2007)
7
164.
D. Dallinger, N.Y. Gorobets, C.O. Kappe, Org. Lett. 5
2003) 1205.
U. Bora, A. Saikia, R.C. Boruah, Org. Lett. 5 (2003)
35.
[22] S. Kantevari, S.V.N. Vuppalapati, D.O. Biradar, L.
Nagarapu, J. Mol. Catal. A: Chem. 266 (2006) 109.
[23] M. Narasimhulu, T.S. Reddy, K.C. Mahesh, P.
Prabhakar, C.B. Rao, Y. Venkateswarlu, J. Mol. Catal.
A: Chem. 266 (2006) 114.
(
4
A. Shaabani, R. Ghadari, A. Rahmati, A.H. Rezayan, J.
Iran. Chem. Soc. 6 (2009) 710.
[24] M.A. Bigdeli, M.M. Heravi, G.H. Mahdavinia, J. Mol.
Catal. A: Chem. 275 (2007) 25.
M.A. Zolfigol, I. Mohammadpoor-Baltork, M. Shiri, J.
Iran. Chem. Soc. 5 (2008) 90 and references cited
therein.
[25] A.S. Girgis, Pharmazie (2000) 466.
[26] N. Latif, N. Mishriky, F.M. Assad, Aust. J. Chem. 35
(1982) 1037.
[
[
[
10] A. Corma, H. Garcia, Adv. Synth. Catal. 348 (2006)
391.
11] A.K. Chakraborthi, R. Gulhane, Chem. Commun.
2003) 1896.
12] a) V.T. Kamble, V.S. Jamode, N.S. Joshi, A.V. Biradar,
R.Y. deshmukh, Tetrahedron Lett. 47 (2006) 5573; b)
A.T. Kahan, L.H. Choudhury, S. Ghosh, J. Mol. Cat. A:
Chem. 255 (2006) 230.
[27] Y. Wang, X. Li, K. Ding, Tetrahedron: Asymmetry 13
(2002) 1291.
[28] K. Ikeda, T. Morimoto, M. Sekia, Chem. Pharm. Bull.
(1980) 1178.
[29] I. Szatmari, A. Hetenyi, L. Lazar, F. Fulop, J.
Hetrocyclic Chem. 41 (2004) 367.
[30] C. Cimarelli, G. Palmieri, E. Volpini, Can. J. Chem. 82
(2004) 1341.
1
(
[
[
[
13] S. Rudrawar, R.C. Besra, A.K. Chakraborti, Synthesis
[31] M. Dabiri, A.S. Delbari, A. Bazgir, Synlett (2007) 821.
[32] M.A. Bigdeli, M.M. Heravi, G.H. Mahdavinia, Catal.
Commun. 8 (2007) 1595.
[33] M.A. Bigdeli, S. Jafari, G.H. Mahdavinia, H.
Hazarkhani, Catal. Commun. 8 (2007) 1641.
[34] M.A. Bigdeli, A. Rahmati, H. Abbasi-Ghadim, G.H.
Mahdavinia, Tetrahedron Lett. 48 (2007) 4575.
[35] C.O. Kappe, J. Org. Chem. 62 (1997) 7201.
[36] S.R. Angle, J.D.Rainer, Z. Woytowiez, J. Org. Chem.
62 (1997) 5884.
(
2006) 2767.
14] A.T. Khan, T. Pravin, L.H. Choudhury, Synthesis
2006) 2497.
15] a) A. Agarwal, Y.D. Vankar, Carbohydrate Res. 340
2005) 1661; b) A. Agarwal, S. Rani, Y.D. Vankar, J.
(
(
Org. Chem. 69 (2004) 6137.
[
[
16] A.T. Khan, S. Ghosh, L.H. Choudhury, Eur. J. Org.
Chem. (2006) 2226.
17] a) G. Agnihotri, A.K. Misra, Tetrahedron Lett. 47
(2006) 3653; b) P. Tiwari, A.K. Misra, Tetrahedron
7
74