Three-component synthesis of amidoalkyl naphthols catalyzed by bismuth(III) nitrate pentahydrate

Article abstract of DOI:10.1016/j.cclet.2011.10.008

Bismuth(III) nitrate pentahydrate catalyzed the three-component condensation of β-naphthol, aldehydes and amines/urea under solvent-free conditions to afford the corresponding amidoalkyl naphthols in excellent yields.

Full text of DOI:10.1016/j.cclet.2011.10.008

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 65–68
www.elsevier.com/locate/cclet
Three-component synthesis of amidoalkyl naphthols
catalyzed by bismuth(III) nitrate pentahydrate
*
Min Wang , Yan Liang, Ting Ting Zhang, Jing Jing Gao
College of Chemistry, Chemical Engineering and Food Safety, Bohai University, Jinzhou 121000, China
Received 6 July 2011
Available online 9 November 2011
Abstract
Bismuth(III) nitrate pentahydrate catalyzed the three-component condensation of b-naphthol, aldehydes and amines/urea under
solvent-free conditions to afford the corresponding amidoalkyl naphthols in excellent yields.
#
2011 Min Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Amidoalkyl naphthols; Bismuth(III) nitrate; One-pot synthesis; Solvent-free conditions
Compounds bearing 1,3-amido oxygenated functional groups are ubiquitous to a variety of biologically important
natural products and potent drugs including a number of nucleoside antibiotics and HIV protease inhibitors such as
ritonavir, lipinavir, and the hypotensive [1]. In addition, the bradycardiac effects of these compounds have been
evaluated [2]. The importance of amidoalkyl naphthols for their synthesis has attracted renewed attention and various
improved procedures have been reported. These reported methods mainly include the one-pot three-component
condensation of b-naphthol, aldehydes and amine/CH CN, which employs catalysts such as p-toluene sulfonic acid
3
[
3], H NSO H [4], Al(H PO ) [5], Yb(OTf)3 [6], Sr(OTf)2 [7], I2 [8], Brønsted acidic ionic liquid [9],
2 3 2 4 3
K CoW O Á3H O [10], Indion-130 [11], Al O –HClO [12], montmorillonite K10 [13], and silica sulfuric acid [14].
5
12 40
2
2
3
4
Most of these methods suffer from drawbacks including long reaction time, expensive reagent, toxic and corrosive
solvent, high reaction temperature (>100 8C), high catalyst loading, strongly acidic conditions, and the use of
additional microwave or ultrasonic irradiation. Moreover, aliphatic aldehydes did not give satisfactory yields in earlier
reports. Therefore, the development of less expensive and high yielding catalytic method is desired.
Recently, the use of bismuth(III) nitrate as a catalyst or as a stoichiometric reagent in organic synthesis has
increased considerably [15–18]. The main reasons for this are their low cost, nontoxicity, commercial availability, ease
handling and resistant to air/moisture. That is why bismuth(III) compounds are termed as ‘‘green’’ reagents in organic
synthesis [19–21]. In continuation of our work on the development of useful synthetic methodologies, we herein
disclose the catalytic activity of bismuth(III) nitrate pentahydrate for the efficient three-component synthesis of
amidoalkyl naphthols 4 under solvent-free conditions (Scheme 1).
*
Corresponding author.
E-mail address: minwangszg@yahoo.com.cn (M. Wang).
1001-8417/$ – see front matter # 2011 Min Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.10.008

66
M. Wang et al. / Chinese Chemical Letters 23 (2012) 65–68
R1
NHCOR2
OH
OH
Bi(NO3)3 5H2O
+
1
R CHO
+
R CONH
2
2
o
8
0 C
solvent-free
1
2
3
4a-4r
Scheme 1. One-pot three-component synthesis of amidoalkyl naphthols.
1
. Experimental
General procedure for the synthesis of amidoalkyl naphthols (4): To a mixture of b-naphthol (10 mmol), an
aldehyde (10 mmol), and an amide (11 mmol), Bi(NO ) Á5H O (0.2 mmol) was added. The reaction mixture was
3
3
2
magnetically stirred on a preheated water bath at 80 8C. After completion of the reaction (monitored by TLC), the
reaction mixture was cooled to r.t., washed with H O/EtOH (v/v = 1/1), and the residue was recrystallized from EtOH.
1
2
13
The products were characterized by comparing their mp, IR, H NMR, C NMR and elemental analysis with those
reported for the authentic samples. Spectral data for some representative compounds.
À1
N-(1-(2-hydroxynaphthalen-1-yl)propyl)benzamide (4j). White solid. IR (KBr, cm ): 3405, 3184, 1635, 1532,
1
514, 1344, 1073, 816, 747, 707. H NMR (500 MHz, DMSO-d ): d 10.10 (s, 1H, OH), 8.62 (d, 1H, J = 8.0 Hz, NH),
1
8
7
0
1
4
6
.23 (d, 1H, J = 8.8 Hz, ArH), 7.82 (t, 3H, J = 7.2 Hz, ArH), 7.70 (d, 1H, J = 8.8 Hz, ArH), 7.53–7.44 (m, 4H, ArH),
.30 (t, 1H, J = 7.2 Hz, ArH), 7.20 (d, 1H, J = 8.8 Hz, ArH), 5.92 (q, 1H, J = 7.5 Hz, CH), 2.18–1.96 (m, 2H, CH ),
2
1
.93 (t, 3H, J = 7.3 Hz, CH3). C NMR (125 MHz, DMSO-d ): d 165.4, 152.9, 134.7, 132.1, 131.0, 128.5, 128.4,
3
6
28.3, 128.2, 126.9, 126.2, 122.5, 119.5, 118.6, 48.5, 26.9, 11.3. Anal. Calcd. for C H NO : C, 78.66; H, 6.27; N,
2
0
19
2
.58. Found: C, 78.54; H, 6.33; N, 4.52%.
N-(1-(2-hydroxynaphthalen-1-yl)propyl)acetamide (4p). White solid. IR (KBr, cm ): 3430, 3236, 2963, 1644,
À1
1
583, 1517, 1333, 1079, 814, 746, 709. H NMR (500 MHz, DMSO-d ): d 9.94 (s, 1H, OH), 8.08 (d, 1H, J = 8.6 Hz,
1
NH), 8.03 (s, 1H, ArH), 7.72 (d, 1H, J = 8.0 Hz, ArH), 7.64 (d, 1H, J = 8.8 Hz, ArH), 7.39 (t, 1H, J = 7.4 Hz, ArH),
6
7
1
1
5
.21 (t, 1H, J = 7.4 Hz, ArH), 7.13 (d, 1H, J = 9.1 Hz, ArH), 5.63 (q, 1H, J = 7.8 Hz, CH), 1.89–1.84 (m, 2H, CH ),
2
1
.81 (s, 3H, CH ), 0.77 (t, 3H, J = 7.4 Hz, CH ). C NMR (125 MHz, DMSO-d ): d 169.1, 153.5, 132.9, 129.0, 128.9,
3
3
3
6
28.7, 126.6, 123.1, 122.7, 120.0, 119.1, 48.0, 27.2, 23.2, 11.9. Anal. Calcd. for C H NO : C, 74.05; H, 7.04; N,
2
1
5
17
.75. Found: C, 74.17; H, 6.98; N, 5.68%.
N-(1-(2-hydroxynaphthalen-1-yl)butyl)acetamide (4q). White solid. IR (KBr, cm ): 3409, 3220, 2956, 1642,
À1
1
583, 1531, 1515, 1336, 1076, 816, 749, 705. H NMR (500 MHz, DMSO-d ): d 9.86 (s, 1H, OH), 8.13 (d, 1H,
1
6
J = 8.6 Hz, NH), 8.02 (s, 1H, ArH), 7.78 (d, 1H, J = 7.7 Hz, ArH), 7.68 (d, 1H, J = 8.8 Hz, ArH), 7.46 (t, 1H,
J = 7.2 Hz, ArH), 7.28 (t, 1H, J = 7.4 Hz, ArH), 7.18 (d, 1H, J = 8.8 Hz, ArH), 5.83 (q, 1H, J = 7.6 Hz, CH), 2.05–1.97
(
J = 7.4 Hz, CH3). C NMR (125 MHz, DMSO-d ): d 168.4, 152.9, 132.2, 128.4, 128.2, 128.1, 126.0, 122.1, 119.8,
m, 1H, CH ), 1.88–1.80 (m, 4H, CH and CH ), 1.40–1.30 (m, 1H, CH ), 1.22–1.13 (m, 1H, CH ), 0.88 (t, 3H,
2 2 3 2 2
1
3
6
1
N, 5.36%.
18.5, 45.5, 35.9, 22.7, 19.5, 13.7. Anal. Calcd. for C H NO : C, 74.68; H, 7.44; N, 5.44. Found: C, 74.79; H, 7.37;
16 19 2
À1
1
535, 1438, 1354, 1063, 814, 751, 698. H NMR (500 MHz, DMSO-d ): d 9.97 (s, 1H, OH), 7.83–7.75 (m, 3H, ArH),
-((2-Hydroxynaphthalen-1-yl)(phenyl)methyl)urea (4r). White solid. IR (KBr, cm ): 3447, 3212, 2932, 1651,
1
1
7
1
5
6
1
.40 (s, 1H, NH), 7.29–7.11 (m, 7H, ArH), 6.94 (s, 2H), 5.86 (s, 2H, NH2). C NMR (125 MHz, DMSO-d ): d 158.5,
3
6
52.9, 144.2, 128.9, 128.6, 127.8, 126.4, 125.8, 122.4, 120.2, 118.5, 48.1. Anal. Calcd. for C H N O : C, 73.95; H,
1
8 16 2 2
.51; N, 9.58. Found: C, 74.08; H, 5.59; N, 9.46%.
2
. Results and discussion
First, in order to optimize the reaction conditions, various reaction media were screened using the model reaction of
b-naphthol, benzaldehyde and benzamide in Table 1. It was found that the best results were obtained with 2 mol%
Bi(NO ) Á5H O under solvent-free conditions (Table 1, entry 9). The reaction was completed within 12 min and the
3
3
2
expected product was obtained in a 96% yield, while diminish the amount of catalyst would decrease the product yield
(Table 1, entry 10).

M. Wang et al. / Chinese Chemical Letters 23 (2012) 65–68
67
Table 1
Amidoalkylation reaction of b-naphthol, benzaldehyde and benzamide catalyzed by Bi(NO
a
3
)
3
2
Á5H O under various conditions.
Entry
Solvent
Amount of catalyst (mol%)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
CH
CH
2
Cl
COOC
2
2
2
2
2
2
2
2
2
2
1
2
11
25
36
49
64
64
77
86
96
75
3
2
H
5
2
Toluene
THF
2
2
H
2
O
2
EtOH
CH CN
2
3
2
Cyclohexane
None
2
0.2
0.3
1
0
None
a
Reaction conditions: b-naphthol 10 mmol, benzaldehyde 10 mmol, benzamide 11 mmol, the amount of solvent used for entries 1–8 was 3 mL.
Having established the reaction conditions, we extended the reaction to substituted aromatic aldehydes and
aliphatic aldehydes, which reacted with amides/urea and b-naphthol in Table 2. In all cases, amidoalkyl naphthols
were the sole products and no by-product was observed. Aromatic aldehydes carrying either electron-withdrawing or
electron-donating groups reacted successfully and gave the desired products in high yields. Aliphatic aldehydes also
underwent the transformation conveniently. However, the reactions of aliphatic aldehydes in most reported literatures
were sluggish and isolated no desired products [3–5,8,10–12]. In addition, urea and different amines such as
benzamide and acetamide worked equally, whereas the reaction was unsuccessful with thiourea.
In order to show the merit of Bi(NO ) Á5H O in comparison with other reported catalysts, we summarized some of
3
3
2
the results for the preparation of N-(1-(2-hydroxynaphthalen-1-yl)benzyl)benzamide (4a) in Table 3. The results
showed that Bi(NO ) Á5H O is a more efficient catalyst with respect to reaction temperature, catalyst load, reaction
3
3
2
time and yield than those reported ones.
We propose a reaction mechanism of the Bi(NO ) Á5H O-catalyzed condensation as shown in Scheme 2.
3
3
2
Bi(NO ) Á5H O act as a Lewis acid catalyst that facilitates the formation of o-QMs, which further react with a
3
3
2
nucleophile (amide/urea) to form the desired amidoalkyl naphthols [3,8].
From the results of the above study it can be concluded that the synthesis of amidoalkyl naphthols catalyzed by
Bi(NO ) Á5H O offers several significant advantages such as short reaction time (0.1–2.5 h), mild reaction condition,
3
3
2
simple work-up, excellent yields (79–97%), and extensive applicability.
Table 2
a
Synthesis of amidoalkyl naphthols in the presence of Bi(NO
3
)
3
2
Á5H O without solvent.
Entry
R
1
R
2
Time (h)
Product
Yield (%)
Mp (8C)
1
2
3
4
5
6
7
8
9
C
6
H
5
C
C
C
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
5
5
0.2
0.5
0.3
1.0
0.5
1.5
0.2
1.0
1.5
0.1
0.1
0.3
0.2
0.5
0.5
0.3
0.3
2.5
4a
4b
4c
4d
4e
4f
96
81
89
81
96
92
92
80
79
92
95
95
81
92
85
81
97
91
237–238 [9]
264–266 [22]
232–234 [9]
237–239 [23]
265–267 [24]
187–189 [7]
238–239 [24]
207–09 [9]
2-NO
3-NO
4-NO
2
2
2
C
C
C
6
6
6
H
H
H
4
4
4
2-ClC
6 4
H
4-ClC
6 4
H
2,4-Cl
2
C
6
H
3
4g
4h
4i
4-CH
4-CH
3
C
6
H
4
3
OC
6
H
4
208–210 [22]
246–248 [7]
240–242 [24]
239–240 [10]
255–257 [7]
208–210 [22]
218–220 [25]
179–180 [26]
224–226
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
CH
CH
3
CH
CH
2
4j
3
2
CH
2
4k
4l
C
6
H
5
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3-NO
2-ClC
4-CH
2
C
6
H
4
4m
4n
4o
4p
4q
4r
6 4
H
3 6
C H
4
CH
CH
3
CH
CH
2
3
2
CH
2
C
6
H
5
NH
2
177–179 [4]
a
Reaction conditions: b-naphthol 10 mmol, aldehyde 10 mmol, amide 11 mmol, Bi(NO
3
)
3
Á5H
2
O 0.2 mmol, 80 8C.

68
M. Wang et al. / Chinese Chemical Letters 23 (2012) 65–68
Table 3
a
Comparison of Bi(NO
3
)
3
Á5H
2
O with reported catalysts for synthesis of N-(1-(2-hydroxynaphthalen-1-yl)benzyl)benzamide.
Entry
Catalyst
Solvent/temp. (8C)
Catalyst load
Time (h)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
p-TSA
NSO
Al(H PO
Sr(OTf)
[TEBSA][HSO
CoW12
40Á3H
Indion-130
Al –HClO
Montmorillonite K10
Bi(NO
Á5H
Solvent-free/125
Solvent-free/28–30
Solvent-free/125
10 mol%
50 mol%
24 mol%
10 mol%
5 mol%
6.0
0.4
0.4
9.0
0.2
2.0
0.2
0.3
1.5
0.2
86
92
91
93
86
80
94
90
78
96
[3]
H
2
3
H
[4]
2
4
)
3
[5]
2
CHCl /reflux
3
[7]
4
]
Solvent-free/120
Solvent-free/125
Solvent-free/110
Solvent-free/125
Solvent-free/125
Solvent-free/80
[9]
K
5
O
2
O
1 mol%
[10]
[11]
[12]
[13]
This work
50 g/mol
100 g/mol
100 g/mol
2 mol%
2
O
3
4
1
0
3
)
3
2
O
a
Reaction conditions: molar ratio of b-naphthol/benzaldehyde/benzamide = 1:1:1.1–1.3.
O
R2
R1
OH
R1
H
O
OH
R1
NH
OH
Bi(NO3)3 5H2O
O
-H2O
R2CONH2
+
R1CHO
o-QM
4
Scheme 2. Proposed mechanism.
References
[
[
[
[
[
[
[
[
[
1] T. Dingermann, D. Steinhilber, G. Folkers, Molecular Biology in Medicinal Chemistry, Wiley-VCH, Weinheim, 2004.
2] A.Y. Shen, C.T. Tsai, C.L. Chen, Eur. J. Med. Chem. 34 (1999) 877.
3] M.M. Khodaei, A.R. Khosropour, H. Moghanian, Synlett (2006) 916.
4] S.B. Patil, P.R. Singh, M.P. Surpur, et al. Ultrason. Sonochem. 14 (2007) 515.
5] H.R. Shaterian, A. Amirzadeh, F. Khorami, et al. Synth. Commun. 38 (2008) 2983.
6] A. Kumar, M.S. Rao, I. Ahmad, et al. Can. J. Chem. 87 (2009) 714.
7] W.K. Su, W.Y. Tang, J.J. Li, J. Chem. Res. (2008) 123.
8] B. Das, K. Laxminarayana, B. Ravikanth, et al. J. Mol. Catal. A: Chem. 261 (2007) 180.
9] A.R. Hajipour, Y. Ghayeb, N. Sheikhan, et al. Tetrahedron Lett. 50 (2009) 5649.
[
[
[
[
[
[
[
[
[
[
[
[
[
[
[
[
[
10] L. Nagarapu, M. Baseeruddin, S. Apuri, et al. Catal. Commun. 8 (2007) 1729.
11] S.B. Patil, P.R. Singh, M.P. Surpur, et al. Synth. Commun. 37 (2007) 1659.
12] S. Hamid Reza, K. Fahimeh, A. Azita, et al. Chin. J. Chem. 27 (2009) 815.
13] S. Kantevari, S.V.N. Vuppalapati, L. Nagarapu, Catal. Commun. 8 (2007) 1857.
14] G. Srihari, M. Nagaraju, M.M. Murthy, Helv. Chim. Acta 90 (2007) 1497.
15] B.K. Banik, M. Cardona, Tetrahedron Lett. 47 (2006) 7385.
16] C. Mukhopadhyay, A. Datta, Catal. Commun. 9 (2008) 2588.
17] V.M. Alexander, R.P. Bhat, S.D. Samant, Tetrahedron Lett. 46 (2005) 6957.
18] P. Thirupathi, S.S. Kim, Tetrahedron 65 (2009) 5168.
19] N.M. Leonard, L.C. Wieland, R.S. Mohan, Tetrahedron 58 (2002) 8373.
20] R.M. Hua, Curr. Org. Chem. 5 (2008) 1.
21] J.M. Bothwell, S.W. Krabbe, R.S. Mohan, Chem. Soc. Rev. 40 (2011) 4649.
22] G.C. Nandi, S. Samai, R. Kumar, et al. Tetrahedron Lett. 50 (2009) 7220.
23] S.A.M.K. Ansari, J.N. Sangshetti, N.D. Kokare, et al. Indian J. Chem. Technol. 17 (2010) 71.
24] M. Wang, Y. Liang, Monatsh. Chem. 142 (2011) 153.
25] H.R. Shaterian, H. Yarahmadi, M. Ghashang, Bioorg. Med. Chem. Lett. 18 (2008) 788.
26] S.B. Sapkal, K.F. Shelke, B.R. Madje, et al. Bull. Korean Chem. Soc. 30 (2009) 2887.