Zirconyl triflate as an efficient and reusable catalyst for one-pot synthesis of 1-amidoalkyl-2-naphthols under solvent-free conditions

Article abstract of DOI:10.1007/s13738-012-0208-y

In the present work, the preparation of 1-amidoalkyl-2-naphthols via one-pot three-component condensation of amides, aldehydes, and β-naphthol in the presence of catalytic amounts of zirconyl triflate, as a highly efficient, low toxic, stable and non-hygr

Full text of DOI:10.1007/s13738-012-0208-y

J IRAN CHEM SOC (2013) 10:745–750
DOI 10.1007/s13738-012-0208-y
ORIGINAL PAPER
Zirconyl triflate as an efficient and reusable catalyst
for one-pot synthesis of 1-amidoalkyl-2-naphthols
under solvent-free conditions
•
Hajar Hashemi Ali Reza Sardarian
Received: 25 June 2012 / Accepted: 12 December 2012 / Published online: 17 January 2013
Ó Iranian Chemical Society 2013
Abstract In the present work, the preparation of
1-amidoalkyl-2-naphthols via one-pot three-component
condensation of amides, aldehydes, and b-naphthol in the
presence of catalytic amounts of zirconyl triflate, as a
highly efficient, low toxic, stable and non-hygroscopic
catalyst under solvent-free conditions is reported. This low-
cost procedure offers several other advantages such as short
reaction times and good to excellent yields.
activities including antibiotic [11–13], antitumor [14–16],
analgesic [17, 18], anticonvulsant [19], antipsychotic [20],
antimalarial [21], antianginal [22], antihypertensive [23],
and antirheumatic properties [24]. 1-Amidoalkyl 2-naph-
thols can be prepared by multicomponent condensation of
aldehydes, 2-naphthols, and amides in the presence of
different Lewis or Brønsted acids such as p-TSA [25],
ZrOCl2 [26], FeCl3ꢀSiO2 [27], montmorillonite K10 [28],
I2 [29], Ce(SO4)2 [30], Fe(HSO4)3 [31], Sr(OTf)2 [32],
([TEBSA][HSO4]) [33], thiamine hydrochloride [34], P2O5
[35], Yb(OTf)3/[Bmim]BF4 [36], Cu1.5PMo12O40 [37],
polymer-supported sulfonic acid [38], NaHSO4ꢀH2O [39],
K5CoW12O40ꢀ3H2O [40], sulfamic acid [41, 42], molyb-
dophosphoric acid [43], cation-exchange resins [44], silica
sulfuric acid [45], silica gel-supported polyphosphoric acid
(PPA-SiO2) [46], oxalic acid [47], and Al(HSO4)3 [48],
dodecylphosphonic acid [49].
Keywords b-Naphthol ꢀ Zirconyl triflate ꢀ Solvent-free ꢀ
1-Amidoalkyl-2-naphthol
Introduction
Multicomponent reactions (MCRs) are a powerful and
useful synthetic tool to produce complex molecules from
simple precursors by a one-pot procedure [1]. These reac-
tions are performed without isolation of any intermediate
which reduces the reaction times and saves both energy and
raw materials [2]. Therefore, the design of novel MCRs has
attracted a great deal of attention in the field of medicinal
chemistry, drug discovery, and materials science [3].
Biginelli [4], Ugi [5], and Manich [6] reactions are some
examples of MCRs.
Zirconium (IV) salts have recently attracted much
attention because of their low cost, high catalytic activ-
ity, easy availability, and low toxicity. A variety of Zr
(IV) salts have been used for several organic transforma-
tions [50].
In 2008, the synthesis of the zirconyl triflate [ZrO(OTf)
2] as a super catalyst was explored [51] and applied in
trimethylsilylation of alcohols and phenols with hexam-
ethyldisilazane (HMDS) [51], acetylation and benzoylation
of alcohols, phenols, amines and thiols with acetic and
benzoic anhydrides [52], aminolysis of epoxides [53],
acetalization of carbonyl compounds [54], preparation of
benzoxanthenes [55], and ring opening of epoxides [56].
Here, we report a novel, convenient, mild and efficient
method for one-pot synthesis of 1-amidoalkyl-2-naphthol
derivatives from various aldehydes, amides and b-naphthol
in the presence of zirconyl triflate under solvent-free
conditions (Scheme 1).
1-Amidoalkyl-2-naphthol derivatives are of significant
importance since they have been frequently applied as
hypotensive and bradycardiac agents [7–9]. 1-Amidoalkyl-
2-naphthols can be converted to 1,3-oxazine derivatives
[10]. 1,3-Oxazines have potentially different biological
H. Hashemi ꢀ A. R. Sardarian (&)
Department of Chemistry, College of Sciences,
Shiraz University, Shiraz 75454, Iran
e-mail: sardarian@susc.ac.ir
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J IRAN CHEM SOC (2013) 10:745–750
R1
NHCOR2
OH
Scheme 1 Preparation of
1-amidoalkyl-2-naphthol
derivatives
OH
+
ZrO(OTf)2
neat 80oC
R2CONH2
R1CHO
+
R1 =aryl or alky
R2 = CH3, Ph
Experimental
(Table 1, entries 2–4). Running the same reaction using
lesser amount of the catalyst, 2 mol %, led to lower yield,
80 %, and higher amount of the catalyst, 10 mol %, did not
show pronounced effect on the efficiency of the reaction
(Table 1, entries 10 and 11). Therefore, 5 mol % of
ZrO(OTf)2 was chosen as the most efficient amount of
catalyst in the rest of study.
General
All chemicals were purchased from Merck or Fluka
Chemical Companies. The known products were identified
by comparison of their melting points, spectral data, and
CHN analysis with those reported in the literature. NMR
spectra were recorded on a Bruker Avance DPX-250 (1H
NMR 250 MHz and 13C NMR 63 MHz), spectrometer in
DMSO-d6, using TMS as an internal standard. IR spectra
were obtained using a Shimadzu FT-IR 8300 spectropho-
tometer. Mass spectra were determined on a Shimadzu
GCMS-QP 1000 EX instruments at 70 or 20 eV and CHN
data were measured on a Flash EA instrument. Melting
points were determined in open capillary tubes in a Bu¨chi-
545 circulating oil melting point apparatus. ZrO(OTf)2 was
prepared according to the reported procedure [51].
For studying the effect of solvent, the reaction was
examined in petroleum ether, ethyl acetate, toluene, etha-
nol, and water under reflux conditions.
According to the results shown in Table 1 (Entries
5–9),we decided to examine generality and versatility of
ZrO(OTf)2 as a catalyst in the synthesis of 1-amidoalkyl-2-
naphthols from various benzaldehydes, benzamide and
2-naphthol under solvent-free conditions at 85 °C. In these
reactions, the corresponding 1-amidoalkyl-2-naphthols were
produced in 65–98 % yields (Table 2, entries 1–12). As can
be seen from Table 2, aromatic and aliphatic aldehydes were
converted to the corresponding 1-amidoalkyl-2-naphthols in
good to excellent yields. In the case of aromatic aldehydes,
the nature of substituents (electron-donating and electron-
withdrawing) has no significant effect on the yields and
reaction times. Polyaromatic aldehydes, including phenan-
threne-9-carbaldehyde and pyrene-1-carbaldehyde, were
General procedure for the preparation of 1-amidoalkyl-
2- naphthols under solvent-free
Zirconyl triflate (5 mol %) was added to a mixture of
b-naphthol (1 mmol), aldehyde (1 mmol), and amide
(1.2 mmol). The mixture was stirred at 80 °C for the corre-
sponding time and the reaction was followed by TLC. After
completion of the reaction, the reaction mixture was washed
with water (3 9 5 mL) and the residue was recrystallized
from EtOH–H2O to give pure product in 65–98 % yield.
Table 1 Optimization of reaction parameters for preparation of
1-amidoalkyl-2- naphthols using of ZrO(OTf) as a catalyst
2
Entry Catalyst
(mol %)
Solvent
Temp.
(oC)
Time
(min)
Yield
(%)
1
2
3
4
5
5
5
5
5
5
Solvent-free R.T
Solvent-free 60
Solvent-free 80
Solvent-free 90
120
5
–
78
98
98
50
Results and discussion
2
2
For optimization of the reaction parameters, the reaction of
2-naphthol (1 mmol) with benzaldehyde (1 mmol) and
benzamide (1.2 mmol) was chosen, as model, in the pres-
ence of ZrO(OTf)2 (5 mol %) under solvent-free condi-
tions at room temperature. TLC monitoring showed no
progress in the reaction even after 2 h. The model reaction
was also carried out under solvent-free conditions at 60, 80,
and 90 °C and the corresponding 1-amidoalkyl-2-naphthol
was formed in 78, 98, and 98 % after 5, 2, and 2 min,
respectively, in the presence of 5 mol % of ZrO(OTf)2
Petroleum
ether
Reflux
60
6
5
Ethyl
Reflux
60
50
acetate
7
5
5
Toluene
EtOH
H2O
Reflux
Reflux
Reflux
60
60
60
5
70
20
20
80
98
8
9
5
10
11
2
Solvent-free 80
Solvent-free 80
10
5
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747
Table 2 Synthesis of 1-amidoalkyl-2-naphthols in the presence of catalytic amounts of ZrO(OTf)2 under solvent-free conditions
Entry
1
Aldehyde
Amide
Product
Time (min)
3
Yield (%)a
M.p (oC) (Lit.)
Ref.
[42]
PhCONH2
98
240–241 (239–241)
H
H
O2N
NHCOPh
OH
O
O
O2N
O2N
2
PhCONH2
3
98
239–241 (240–242)
[43]
NO2
NHCOPh
OH
3
4
PhCONH2
PhCONH2
2
5
98
85
234–235 (235–237)
196–198 (197–199)
[20]
[38]
H
NHCOPh
OH
O
H3CO
H
NHCOPh
O
OH
H3CO
5
PhCONH2
2
95
210–211 (210)
[49]
H
O
NHCOPh
OH
6
7
PhCONH2
PhCONH2
1.5
90
229–231 (228–230)
[37]
[49]
H
Br
NHCOPh
O
H
OH
Br
3
65b
157–159 (158)
NHCOPh
OH
O
O
8
9
PhCONH2
PhCONH2
7
70b
233–234 (234)
251–253 (251)
[49]
[49]
H
NHCOPh
OH
10
85b
O
H
NHCOPh
OH
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J IRAN CHEM SOC (2013) 10:745–750
Table 2 continued
Entry
10
Aldehyde
Amide
Product
Time (min)
5
Yield (%)a
82b
M.p (oC) (Lit.)
245–246 (246)
Ref.
[49]
PhCONH2
H
O
NHCOPh
OH
11
12
13
PhCONH2
PhCONH2
CH3CONH2
2
98
70
90
167–168 (166)
[49]
[49]
[24]
O
O
NHCOPh
OH
10
10
H
10
5
226–227 (226)
NHCOPh
OH
H
230–231 (228–230)
H
NHCOCH3
OH
O
14
15
CH3CONH2
7
8
72b
173–175 (174–175)
[38]
[49]
H
NHCOCH3
O
OH
CH3CONH2
70b
271–274 (273)
O
H
NHCOCH3
OH
16
CH3CONH2
8
5
85
87
203–205 (204)
110–111 (110)
[49]
[49]
H
Br
NHCOCH3
OH
O
Br
O
17
CH3CONH2
NHCOCH3
OH
10
10
H
a
Isolated yields
b
Isolated with column chromatography
also transformed to the desired products in good yields when
treated with b-naphthol and benzamide in the presence of
ZrO(OTf)2 under solvent-free conditions in 5 min (Table 2,
entries 9 and 10).
formed in longer reaction times under solvent-free condi-
tions (Table 2, entries 13–17).
The reaction of urea (1.2 mmol), in the place of benz-
amide, with b-naphthol (1 mmol) and benzaldehyde
(1 mmol) in the presence of ZrO(OTf)2 (5 mol %) under
solvent-free condition did not proceed after 2 h and the
starting material remained intact.
When acetamide was utilized instead of benzamide in
the preparation of the title compounds, the similar results
were observed although the corresponding products were
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J IRAN CHEM SOC (2013) 10:745–750
749
Table 3 Comparison among of the efficiency of various acid catalysts used in the synthesis of N-[(2-hydroxynaphthalen-1-yl) (phenyl) methyl]
benzamide with ZrO(OTf)2
Entry
Catalyst (mol %)
Conditions
Time
Yield (%)
Ref.
1
2
3
4
5
6
7
8
p-TSA (10 %)
Solvent-free (125 °C)
EtOH
6 h
89
88
79
90
87
83
88
98
[24]
Thiamine.HCl (10 %)
ZrOCl2 (10 %)
4 h
[33]
ClCH2CH2Cl (R.T)
Solvent-free (125 °C)
Solvent-free (125 °C)
Solvent-free (85 °C)
Solvent-free (90 °C)
Solvent-free (80 °C)
11 h
2 h
[25]
K5CoW12O40.3H2O (1 %)
I2 (5 %)
[39]
4.5 h
65 min
20 min
2 min
[28]
Fe (HSO4)2 (5 %)
Dodecylphosphonic acid (10 mol %)
ZrO(OTf)2 (5 %)
[30]
[49]
Present work
low toxic and efficient catalyst under solvent-free condi-
tions. This method offers several advantages such as high
conversions, short reaction times, clean reaction profiles,
simple experimental and work-up procedures. Finally,
recovery and recyclability of ZrO(OTf)2 is another
advantage for this method.
Table 4 Reusability of ZrO(OTf)2 in solvent-free conditions for the
synthesis of N-[(2-hydroxynaphthalen-1-yl)(phenyl)methyl]benzamide
Entry
No. of recycles
Yield (%)
1
2
3
4
5
0
1
2
3
4
98
96
86
87
80
Acknowledgments We gratefully acknowledge the support of this
work by Shiraz University Research Council.
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