Br?nsted acidic ionic liquid as an efficient and reusable catalyst for one-pot synthesis of 1-amidoalkyl 2-naphthols under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2009.07.116

A mild and efficient method has been developed for the preparation of amidoalkyl naphthols from condensation of aldehydes with amides or urea and 2-naphthol in the presence of a catalytic amount of Br?nsted acidic ionic liquid ([TEBSA][HSO₄]) u

Full text of DOI:10.1016/j.tetlet.2009.07.116

Tetrahedron Letters 50 (2009) 5649–5651
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Tetrahedron Letters
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Brønsted acidic ionic liquid as an efficient and reusable catalyst for
one-pot synthesis of 1-amidoalkyl 2-naphthols under solvent-free conditions
b
b
a
Abdol R. Hajipour a,b, , Yosof Ghayeb , Nafisehsadat Sheikhan , Arnold E. Ruoho
*
a Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
b Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Islamic Republic of Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild and efficient method has been developed for the preparation of amidoalkyl naphthols from con-
densation of aldehydes with amides or urea and 2-naphthol in the presence of a catalytic amount of
Brønsted acidic ionic liquid ([TEBSA][HSO4]) under thermal solvent-free conditions. High yields, short
reaction time, easy work-up and reusability of the catalyst are advantages of this procedure.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 31 March 2009
Revised 17 July 2009
Accepted 17 July 2009
Available online 24 July 2009
Keywords:
Brønsted acidic ionic liquid
Amidoalkyl naphthols
Solvent-free
One-pot
Multicomponent reaction
Multicomponent reactions (MCRs) are very important and
attractive subjects in organic synthesis due to formation of
carbon–carbon and carbon–hetero atom bonds in one pot.1–4
Simple procedures, high bond forming efficiency, time and energy
saving and low expenditures are advantages of these reactions.5
Therefore, researchers have made great efforts to find and develop
new MCRs.
eco-friendly catalysts with high catalytic activity and short reac-
tion times for the production of 1-amidoalkyl 2-naphthols have
gained considerable attention.
Ionic liquids (ILs) have attracted extensive research interest as
environmentally benign solvents due to their specific properties
such as undetectable vapour pressure, non-inflammability, wide
liquid range, reusability and high thermal stability.24,25 Ionic
liquids have been widely applied in many reactions as catalysts
or dual catalyst-solvents including the Mannich reaction26 and
esterification.27
Brønsted acidic ionic liquids consist of the useful characteristics
of solid acids and mineral liquid acids and are designed to replace
traditional mineral liquid acids such as sulfuric acid and hydro-
chloric acid in chemical procedures.28,29 N-(4-sulfonic acid) butyl
triethyl ammonium hydrogen sulfate ([TEBSA][HSO4]) has been
synthesized and used as an efficient and reusable catalyst for nitra-
tion of aromatic compounds30 and esterification of various alcohols
by different acids.31 In a continuation of our investigations on the
development of new synthetic methodologies,32–35 herein we re-
port a new, convenient, mild and efficient procedure for one-pot
three-component synthesis of amidoalkyl naphthol derivatives
from various aryl aldehydes, 2-naphthol and different amides
(acetamide, benzamide and urea) in the presence of [TEBSA][HSO4]
as an effective and recoverable catalyst under solvent-free condi-
tions (Scheme 1).36,37
Compounds containing 1,3-amino-oxygenated functional
groups are frequently found in biologically active natural prod-
ucts and potent drugs such as nucleoside antibiotics and HIV pro-
tease inhibitors.6–9 Furthermore, 1-amidoalkyl 2-naphthols can be
converted to useful and important biological building blocks and
to 1-amino methyl 2-naphthols by an amide hydrolysis reaction,
since compounds exhibit depressor and bradycardia effects in
humans.10,11 1-Amidoalkyl 2-naphthols can be prepared by
multicomponent condensation of aldehydes, 2-naphthols and
acetonitrile or different amides in the presence of Lewis or
Brønsted acids such as p-TSA,12 montmorillonite K10,13
Ce(SO4)2,14 Iodine,15 Fe(HSO4)3,16 Sr(OTf)2,17 K5CoW12O40.3H2O,18
sulfamic acid,19,20 molybdophosphoric acid,21 cation-exchange
resins22 and silica sulfuric acid.23 However some of the reported
methods suffer from disadvantages such as prolonged reaction
time, low yield of products, toxic and corrosive reagents and
the use of additional microwave or ultrasonic irradiation. There-
fore, the discovery of clean procedures and the use of green and
Initially to optimize the amount of ionic liquid, the reaction of
2-naphthol (1 mmol), 4-chloro benzaldehyde (1 mmol) and acet-
amide (1.2 mmol) was performed under solvent-free conditions
* Corresponding author. Tel.: +98 3113913262; fax: +98 3113912350.
E-mail address: haji@cc.iut.ac.ir (A.R. Hajipour).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.116

5650
A. R. Hajipour et al. / Tetrahedron Letters 50 (2009) 5649–5651
R1
NHCOR2
OH
OH
5 mol% IL
R1CHO
2
R2CONH2
3
+
+
120 °C, solvent-f ree, 10 min
4
1
+
-
R1 = Ph and Aryl
R2 = CH3, Ph and NH2
IL = (CH3CH2)3NCH2(CH2)2CH2SO3H HSO4
Scheme 1.
at 120 °C in the presence of different quantities of [TEBSA][HSO4]
(Table 1). As shown in Table 1, the yields of product 4c using high
amounts of [TEBSA][HSO4] were low and the reaction time was
long (Table 1, entries 1–3). No improvement in the reaction rate
was observed by decreasing the amount of ionic liquid from 17
to 1 mmol but the yield of product 4c in the presence of 0.05 mmol
of [TEBSA][HSO4] was higher than the others (Table 1, entries 4–8).
Therefore 5 mol % of ionic liquid was chosen as the optimal quan-
tity of [TEBSA][HSO4].
Thus, we employed 5 mol % ionic liquid for one-pot synthesis of
amidoalkyl naphthols from various aldehydes, amides or urea and
2-naphthol under solvent-free conditions at 120 °C (Table 2, en-
tries 1–21). Aromatic aldehydes reacted with amides or urea and
2-naphthol to produce the corresponding 1-amidoalkyl 2-naph-
thols in 73–91% yields. It was shown that aromatic aldehydes with
electron-donating (e.g., entries 9, 10, 17 and 20) or electron-with-
drawing substituents (e.g., entries 6, 7, 11, 12, 14 and 20) were
converted to amidoalkyl naphthols in 76–91% yields and in short
reaction time (10 min).
Table 1
The effect of different amounts of [TEBSA][HSO4] on the reaction of 2-naphthol,
acetamide and 4-chlorobenzaldehyde
Entry
[TEBSA][HSO4] (mmol)
Time (min)
Yield of 4ca (%)
1
2
3
4
5
6
7
8
3
1
0.5
0.17
0.09
0.05
0.03
0.01
45
40
30
10
10
10
10
10
0
60
65
80
84
85
75
63
a
Isolated yields.
Table 2
The one-pot three-component reaction of 2-naphthol, urea/amides and aryl alde-
hydes in the presence of ionic liquid under solvent-free conditions at 120 °C and
10 mina
Entry
Aldehyde R1
Urea/amide R2
Product
Yieldb (%)
Mp
As shown in Scheme 2, the reaction of 2-naphthol with aromatic
aldehydes in the presence of acid catalyst is known to provide
ortho-quinone methides (o-QMs).12,18 The o-QMs were reacted
with amides or urea to produce 1-amidoalkyl-2-naphthol deriva-
tives (Scheme 2).
In comparison with other catalysts employed for the synthesis
of N-[(3-nitro phenyl)-(2-hydroxy-naphthalen-1-yl)-methyl]-acet-
amide from 3-nitro benzaldehyde, acetamide and 2-naphthol at
different conditions, [TEBSA][HSO4] showed more catalytic reactiv-
ity than the others in terms of short reaction time and simplified
conditions (Table 3, entries 1–9).
The reusability of the [TEBSA][HSO4] was also determined.
After each run, water was added to the reaction mixture and
the product was filtered and the containing ionic liquid was ex-
tracted with CH2Cl2 (3 Â 10 ml) to remove non-ionic organic
impurities. Then the water was evaporated and the catalyst was
dried at 65 °C under reduced pressure for 2 h and reused in the
reaction of 3-nitro benzaldehyde, acetamide and 2-naphthol un-
der solvent-free conditions at 120 °C (Table 3, entries 9–12).
The results show that the catalyst can be employed four times,
although the activity of the catalyst gradually decreased. This
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
C6H5
2-ClC6H4
4-ClC6H4
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
NH2
NH2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4a
4b
4c
4d
4e
4f
4g
4h
4i
87
90
85
90
87
89
88
84
83
84
87
91
73
76
86
83
87
79
83
81
86
218–220
192–194
229–230
223–224
229–231
238–240
222–223
214–216
218–220
228–230
232–234
225–227
176–178
192–193
234–236
182–184
214–216
209–211
180–182
233–235
238–240
2,6-Cl2C6H3
4-Br C6H4
3-O2NC6H4
4-O2NC6H4
4-MeC6H4
3-MeOC6H4
2,5-(MeO)2C6H3
4-NCC6H4
4-CH3OCOC6H4
C6H5
3-O2NC6H4
C6H5
4-Br C6H4
3-MeOC6H4
4-MeC6H4
4-ClC6H4
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
3-O2NC6H4
2,5-(MeO)2C6H3
4u
a
Aldehyde/urea or amide/2-naphthol/IL = 1:1.2:1:0.05.
Yields refer to isolated products and all synthesized amidoalkyl naphthols were
b
characterized by spectral data (IR, 1H and 13C NMR) and melting points and com-
parison with authentic samples.
R1
H
R1
NHCOR2
OH
OH
O
R2CONH2
IL
R1CHO
IL
o-QMs
Scheme 2.

A. R. Hajipour et al. / Tetrahedron Letters 50 (2009) 5649–5651
5651
Table 3
Acid-catalyzed synthesis of N-[(3-nitro phenyl)-(2-hydroxy-naphthalen-1-yl)-methyl]-acetamide via reaction of 3-nitro benzaldehyde (1 mmol), 2-naphthol (1 mmol) and
acetamide (1.2 mmol) under different conditions
Entry
Catalyst (mol %)
Solvent
Conditions
Time
Yield (%)
References
1
2
3
4
5
6
7
8
9
Fe(HSO4)3 (5)
—
DCE
—
85 °C
)))) 28–30 °C
125 °C
125 °C
rt
rt
125 °C
rt
120 °C
120 °C
120 °C
120 °C
25 min
90 min
30 min
3 h
12 h
10 h
5 h
7 h
10 min
10 min
10 min
10 min
97
93
96
78
89
85
81
82
89
87
85
80
16
20
13
18
18
15
15
19
—
Sulfamic acid (0.05 g)
Montmorillonite K10 (0.1 g)
K5CoW12O40Á3H2O (1)
K5CoW12O40Á3H2O (1)
Iodine (5)
Iodine (5)
Sulfamic acid (10)
[TEBSA][HSO4] (5) (first run)
[TEBSA][HSO4] (5) (2nd run)
[TEBSA][HSO4] (5) (3nd run)
[TEBSA][HSO4] (5) (4nd run)
—
DCE
DCE
—
DCE
—
—
—
—
10
11
12
—
—
—
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catalyst for the preparation of amidoalkyl naphthols was
recyclable.
In conclusion, we have developed a facile, convenient and sol-
vent-free method for the one-pot synthesis of amidoalkyl naph-
thols derivatives by coupling various aromatic aldehydes with
amides or urea and 2-naphthol using N-(4-sulfonic acid) butyl tri-
ethyl ammonium hydrogen sulfate ([TEBSA][HSO4]) as an efficient
catalyst. The advantages of this method, in which a relatively non-
toxic (halogen-free) and reusable Brønsted acidic ionic liquid is
employed as an effective catalyst, are high catalytic efficiency,
short reaction time, high yields, a straightforward work-up and
environmental benignancy.
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Acknowledgements
We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT), IR Iran
(A.R.H.), and Grants GM 033138, MH 065503 and NS 033650
(A.E.R.) from the National Institutes of Health. Further financial
support from Center of Excellency in Sensor and Green Chemistry
Research (IUT) is gratefully acknowledged.
33. Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org. Chem. 2002, 67, 8622.
34. Hajipour, A. R.; Adibi, H.; Ruoho, A. E. J. Org. Chem. 2003, 68, 4553.
35. Hajipour, A. R.; Mirjalili, B. B. F.; Zarei, A.; Khazdooz, L.; Ruoho, A. E. Tetrahedron
Lett. 2004, 45, 6607.
Supplementary data
Supplementary data (1H and 13C NMR, EMS and IR of com-
pounds) associated with this article can be found, in the online ver-
sion, at doi:10.1016/j.tetlet.2009.07.116.
36. Preparation of ionic liquid: 1,4-butane sultone (10 mmol, 1.0 mL), triethyl amine
(10 mmol, 1.4 mL) and acetonitrile (5 mL) were charged in a 100 mL round-
bottomed flask. Then, the mixture was refluxed for 10 h. The white solid
zwitterions were filtered and washed with ethyl acetate to remove non-ionic
residues and were dried in vacuum (2.0 g, 85% yield). Then, a stoichiometric
amount of concentrated sulfuric acid (96%, 0.5 mL) was added dropwise to
zwitterions and the mixture was stirred for 6 h at 80 °C to produce the
Brønsted acidic ionic liquid. 1H NMR (400 MHz, DMSO-d6) d 1.16 (br s, 9H),
1.59–1.73 (m, 4H), 2.53 (t, J = 7.6 Hz, 2H), 3.09–3.25 (m, 8H), 6.46 (S, 2H); 13C
NMR (100 MHz, DMSO-d6) d 7.60, 20.27, 22.23, 50.67, 52.48, 56.15.
37. General procedure for the preparation of amidoalkyl naphthols: a mixture of
aldehyde (1 mmol), 2-naphthol (1 mmol), urea or amide (1.2 mmol) and
[TEBSA][HSO4] (0.05 mmol) was stirred at 120 °C in oil bath. The completion of
the reaction was monitored through TLC (ethyl acetate/cyclohexane, 1:3), after
10 min, water (10 mL) was added and the product was filtered and then
recrystallized from ethyl alcohol. The products were characterized by spectral
data (IR, 1H NMR and 13C NMR) and comparison of their physical data with the
literature data.
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