A modified reaction for the preparation of amidoalkyl naphthols

Article abstract of DOI:10.1016/j.tetlet.2007.12.093

An efficient synthesis of amidoalkyl naphthols using FeCl₃·SiO₂ as a heterogeneous catalyst is described. This thermal solvent-free procedure offers advantages such as shorter reaction times, simple work-up, excellent yields, and rec

Full text of DOI:10.1016/j.tetlet.2007.12.093

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1297–1300
A modified reaction for the preparation of amidoalkyl naphthols
Hamid Reza Shaterian *, Hossein Yarahmadi
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
Received 14 November 2007; revised 8 December 2007; accepted 19 December 2007
Available online 11 January 2008
Abstract
An efficient synthesis of amidoalkyl naphthols using FeCl3ÁSiO2 as a heterogeneous catalyst is described. This thermal solvent-free
procedure offers advantages such as shorter reaction times, simple work-up, excellent yields, and recovery and reusability of the catalyst.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: FeCl3ÁSiO2; Amidoalkyl naphthol; Multi-component reaction; Heterogeneous catalyst
Multi-component reactions (MCRs) have proved to be
remarkably successful in generating molecular complexity
in a single synthetic operation.1 In recent years, organic
reactions on silica-supported reagents2–4 have received con-
siderable attention in organic synthesis because of their
ease of handling, enhanced reaction rates, greater selectiv-
ity, simple workup, and recoverability of the catalysts.
Among various heterogeneous catalysts, FeCl3ÁSiO2 has
advantages of low cost, ease of preparation, and catalyst
recycling.3,4
and acetamide (1 equiv) was carried out under the condi-
tions of Method B using different quantities of catalyst at
120 °C under solvent-free conditions. The use of 25 mg of
catalyst resulted in the highest yield in 11 min (Fig. 1). A
slight excess of the acetamide was found to be advantageous,
therefore the molar ratio of 2-naphthol, aldehyde, and acet-
amide was kept at 1:1:1.2, respectively.
CHO
FeCl3.SiO2 (Catalyst)
OH
NH
R
+
The preparation of 1-amidoalkyl-2-naphthols can be
carried out by condensation of aryl aldehydes, 2-naphthol,
and acetonitrile or ethanamide in the presence of Lewis or
Brønsted acid catalysts such as Montmorillonite K10 clay,5
Ce(SO4)2,6 iodine,7 K5CoW12O40Á3H2O,8 p-TSA,9 sulfamic
acid,10 cation-exchanged resins,11 and silica-sulfuric acid.12
In continuation of our work13 on the application of
heterogeneous catalysts for the development of useful
synthetic methodologies, we now show that amidoalkyl-
2-naphthols can be produced using silica-supported ferric
chloride14 as an efficient heterogeneous catalyst (Scheme
1) via a Ritter15 type reaction (Method A)16 or under ther-
mal solvent-free conditions (Method B).17
Method (A, B)
OH
R
R = H, Cl, F, OMe, NO2, Me
O
H3C
Method A: CH3CN ( Ritter type reaction)
Method B: CH3CONH2 (Thermal Solvent-Free conditions)
Scheme 1. Three-component synthesis of amidoalkyl naphthols.
90
80
70
To determine the optimum quantity of FeCl3ÁSiO2,4i–m
the reaction of 2-naphthol (1 equiv), benzaldehyde (1 equiv),
10
25
50
100
200
300
Catalyst (mg)
*
Corresponding author. Tel.: +98 541 2446565; fax: +98 541 2431067.
Fig. 1. Optimization quantity of FeCl3ÁSiO2.
E-mail address: hrshaterian@hamoon.usb.ac.ir (H. R. Shaterian).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.093

1298
H. R. Shaterian, H. Yarahmadi / Tetrahedron Letters 49 (2008) 1297–1300
Table 1
Preparation of amidoalkyl-2-naphthol derivativesa (a–r) produced via
Scheme 1
OH
FeCl3.SiO2
CH3-C N
H
Ar
H2O
N C CH3
Entry
R
H
Method A time Method B time Mp [lit.]Ref.
II
(h)/yield (%)
(min)/yield (%)
(°C)
a
20/80
11/86
245–246
[241–243]6
222–223
248–250
123–125
[78–79]6
b
c
d
4-Me
4-NO2
4-NMe2
20/78
20/88
20/65
35/81
8/93
40/78
OH
NH
O
H
OH ArCHO
H
Ar
Ar
FeCl3.SiO2
OH
OH
Ar
I
O
H3C
(a-r)
o-QMs
e
f
4-Cl
20/79
20/77
20/75
20/84
7/87
7/89
24/80
8/94
223–225
[224–227]6
227–229
[228–230]5
183–185
[184–186]6
241–242
[182–184]6
248–249
230–232
[209–210]6
201–203
[198–199]6
251–253
213–215
[194–196]12
201–204
[203–205]5
179–182
[180–182]6
199–202
[200–202]12
235–237
[235–236]6
—
O
4-Br
H2N CH3
FeCl3.SiO2
g
h
4-OMe
3-NO2
Scheme 2. Suggested mechanism for the preparation of amidoalkyl
naphthols via a Ritter type reaction (Method A) and conjugated addition
(Method B).
i
j
3-F
4-F
20/75
20/72
8/89
10/86
As shown in Table 1, Method A, the three-component
reaction of 2-naphthol, aryl aldehyde, and acetonitrile
(reactant as well as solvent) was performed in the presence
of FeCl3ÁSiO2. In all cases, aromatic aldehydes with either
electron-donating or electron-withdrawing groups gave the
desired products via a Ritter type reaction in 65–88% yields
after 20 h. A mechanistic rationale for Method A is shown
in Scheme 2. It is suggested that the benzaldehyde first
reacted with 2-naphthol to give ortho-quinone methides
(o-QMs) I, which then reacted with acetonitrile to produce
intermediate II in a Ritter type reaction. Hydrolysis of II
then gave the desired 1-amidoalkyl-2-naphthol.
k
2,4-Cl2
20/79
8/90
l
2,5-(OMe)2 20/81
2-Cl
9/86
20/84
m
20/75
20/71
20/80
20/72
n
o
p
q
3-OMe
2-NO2
2-Me
17/81
25/87
30/77
3,4-(OMe)2 20/77
12/85
r
n-Heptanal 20/Trace
60/Trace
We also performed the reaction in the presence of acet-
amide under solvent-free conditions. In all cases, aromatic
aldehydes reacted successfully and gave the products in
high yields. It was shown that aromatic aldehydes with
electron-withdrawing groups reacted faster than those with
electron-releasing groups as expected (Table 1, Method B).
Sterically hindered aromatic aldehydes required longer
reaction times. The rate of reaction of these aldehydes
a
Yields refer to the pure isolated products. All known products have
been reported previously in the literature and were characterized by
comparison of IR and NMR spectra and melting points with authentic
samples.5–12
Thus, we prepared a range of amidoalkyl naphthols
under the optimized reaction conditions (Table 1).
Table 2
Comparison of FeCl3ÁSiO2 with Montmorillonite K10 clay,5 Ce(SO4)2,6 iodine,7 and K5CoW12O40Á3H2O8 in the synthesis of 1-amidoalkyl-2-naphthols
(entries a, h, and k from Table 1)
Entry
Catalyst
Aldehyde/2-naphthol/(catalyst mol %); conditions
Time
Yield (%)
(a)
Ce(SO4)2
I2
K-10 clay
K5CoW12O40Á3H2O
FeCl3ÁSiO2
1/1/(100 mol %); under reflux
1/1/(5 mol %); solvent-free, 125 °C
1/1/(0.1 g); solvent-free, 125 °C
1/1/(1 mol %); solvent-free, 125 °C
1/1/(0.025 g); Method B
36 h
72
87
89
90
86
4.5 h
1.5 h
2 h
11 min
(h)
(k)
Ce(SO4)2
I2
K-10 clay
K5CoW12O40Á3H2O
FeCl3ÁSiO2
Ce(SO4)2
I2
K-10 clay
K5CoW12O40Á3H2O
FeCl3ÁSiO2
1/1/(100 mol %); under reflux
1/1/(5 mol %); solvent-free, 125 °C
1/1/(0.1 g); solvent-free, 125 °C
1/1/(1 mol %); solvent-free, 125 °C
1/1/(0.025 g); Method B
16 h
5 h
0.5 h
3 h
65
76
96
78
94
8 min
1/1/(100 mol %); under reflux
1/1/(5 mol %); solvent-free, 125 °C
1/1/(0.1 g); solvent-free, 125 °C
1/1/(1 mol %); solvent-free, 125 °C
1/1/(0.025 g); Method B
36 h
6.5 h
1 h
3 h
8 min
56
82
84
82
90

H. R. Shaterian, H. Yarahmadi / Tetrahedron Letters 49 (2008) 1297–1300
1299
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the reaction mixtures by simple filtration. The recovered
catalyst was reused five times without any loss of activity.
In conclusion, a reliable, rapid, and environmentally
benign method for synthesizing 1-amidoalkyl-2-naphthols
has been developed, which involves the use of recyclable
silica-supported ferric chloride. In addition to the purity
of the products, the short reaction times and ease of
work-up make the method advantageous.
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benzaldehyde (1 mmol) in acetonitrile (5 mL, reactant as well as
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17. Typical experimental procedure for synthesis of amidoalkyl-2-naphthols
Acknowledgement
We are thankful to the Sistan and Baluchestan Univer-
sity Research Council for the partial support of this
research.
References and notes
(Method B): To
a mixture of 2-naphthol (1 mmol), aldehyde
´
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cooled to 25 °C and the solid residue was dissolved in EtOAc and the
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naphthols are given: N-[(3-Fluorophenyl)-(2-hydroxynapthalen-1-yl)-
methyl]-acetamide (i): [mp: 248–249 °C]; 1H NMR (500 MHz,
DMSO-d6): d = 1.98 (s, 3H), 6.98–6.92 (m, 3H), 7.12 (d, J = 8.3 Hz,
1H), 7.27–7.19 (m, 3H), 7.37 (t, J = 7.3 Hz, 1H), 7.76 (d, J = 8.6 Hz,
1H), 7.80 (d, J = 8.0 Hz, 1H), 7.84 (br d, 1H), 8.44 (d, J = 8.2 Hz,
1H), 10.01 (s, 1H) ppm; 13C NMR (125 MHz, DMSO-d6): 22.5, 47.5,
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2
112.5 (d, JC–F = 22.1 Hz), 112.7 (d, JC–F = 20.9 Hz), 118.3, 118.4,
4
122.1 (d, JC–F = 2.5 Hz), 122.4, 122.9, 126.4, 128.3, 128.5, 129.4,

1300
H. R. Shaterian, H. Yarahmadi / Tetrahedron Letters 49 (2008) 1297–1300
3
3
129.8 (d, JC–F = 8.1 Hz), 132.1, 145.9 (d, JC–F = 6.6 Hz), 153.1,
(s, 1H) ppm; 13C NMR (125 MHz, DMSO-d6): 22.5, 44.4, 55.2, 55.9,
111.1, 111.9, 115.7, 118.5, 118.9, 122.0, 123.2, 125.7, 128.1, 128.6,
131.7, 132.4, 150.7, 152.7, 153.1, 168.1 ppm; IR (KBr, cmÀ1): 3365,
3174, 3002, 2939, 1614, 1577, 1497, 1436, 1370, 1317, 1277, 1218,
1084, 1052, 819, 797, 727; MS (EI,70 eV) m/z = 351 (M+, 18%), 308
(6%), 276 (6%), 262 (36%), 261 (100%), 218 (17%), 205 (3%), 189 (5%),
164 (4%), 144 (7%), 115 (8%), 95 (2%), 77 (2%). Anal. Calcd for
162.0 (d, JC–F = 241.2 Hz), 169.3 ppm; IR (KBr, cmÀ1): 3410, 3160,
1
1640, 1589, 1545, 1484, 1439, 1335, 1280, 1064, 989, 814, 760, 743. MS
(EI, 70 eV) m/z = 310(M+1, 5%), 309 (M+, 21%), 266 (5%), 251 (9%),
250 (52%), 249 (100%), 231 (14%), 220 (16%), 202 (3%), 170 (3%), 145
(4%), 127 (4%), 122 (7%), 115 (9%), 95 (3%), 75 (2%). Anal. Calcd for
C
19H16FNO2: C, 73.77; H, 5.21; N, 4.53%. Found: C, 73.74; H, 5.25; N,
4.48%. N-[(2,5-Dimethoxyphenyl)-(2-hydroxynapthalen-1-yl)-methyl]-
acetamide (l): [mp: 251–253 °C]; 1H NMR (500 MHz, DMSO-d6):
d = 1.88 (s, 3H), 3.48 (s, 3H), 3.64 (s, 3H), 6.77–6.72 (m, 2H), 7.23–
7.10 (m, 4H), 7.39 (s, 1H), 7.73–7.66 (m, 2H), 8.27–8.15 (m, 2H), 9.75
C21H21NO4: C, 71.78; H, 6.02; N, 3.99%. Found: C, 71.73; H, 5.93; N,
4.08%.
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