Synthesis of 1-amidoalkyl-2-naphthols based on a three-component reaction catalyzed by boric acid as a solid heterogeneous catalyst under solvent-free conditions

Article abstract of DOI:10.4314/bcse.v26i3.18

An efficient method for the preparation of 1-amidoalkyl-2-naphthols has been described using a multi-component, one-pot condensation reaction of 2-naphthol, aldehydes and amides in the presence of boric acid under solvent-free conditions.

Full text of DOI:10.4314/bcse.v26i3.18

Bull. Chem. Soc. Ethiop. 2012, 26(3), 473-478.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v26i3.18
ISSN 1011-3924
 2012 Chemical Society of Ethiopia
SHORT COMMUNICATION
SYNTHESIS OF 1-AMIDOALKYL-2-NAPHTHOLS BASED ON A THREE-
COMPONENT REACTION CATALYZED BY BORIC ACID AS A SOLID
HETEROGENEOUS CATALYST UNDER SOLVENT-FREE CONDITIONS
*
Zahed Karimi-Jaberi and Hadi Fakhraei
Department of Chemistry, Firoozabad Branch, Islamic Azad University, Firoozabad, Fars, Iran
(Received December 09, 2011; revised June 18, 2012)
ABSTRACT. An efficient method for the preparation of 1-amidoalkyl-2-naphthols has been described using a
multi-component, one-pot condensation reaction of 2-naphthol, aldehydes and amides in the presence of boric
acid under solvent-free conditions.
KEY WORDS: 1-Amidoalkyl-2-naphthols, Boric acid, 2-Naphthol, Solvent-free synthesis
INTRODUCTION
One-pot, multi-component processes have recently gained considerable economic and
ecological interest as they have proved to be remarkably successful in generating molecular
complexity in a single synthetic operation [1]. The use of heterogeneous catalysts in different
areas of the organic synthesis has now reached significant levels, not only for the possibility to
perform environmentally benign synthesis, but also for the good yields [2].
It is noteworthy that 1-amidomethyl-2-naphthols can be converted to important biologically
active 1-aminomethyl-2-naphthol derivatives by amide hydrolysis reaction. The hypotensive and
bradycardiac effects of these compounds have been evaluated [3-4]. The preparation of 1-
amidoalkyl-2-naphthols can be carried out by multi-component condensation of aryl aldehydes,
2
-naphthol and acetonitrile or amide in the presence of Lewis or Brønsted acid catalysts [5-16].
However, some of these catalysts suffer from the drawback of green chemistry such as
prolonged reaction times, low yields and toxicity of the catalyst. Therefore, introducing clean
processes and utilizing eco-friendly and green catalysts which can be simply recycled at the end
of reactions have been under permanent attention. The demand for environmentally benign
procedure with heterogeneous and reusable catalyst promoted us to develop a safe alternate
method for the synthesis of amidoalkyl naphthols.
As a consequence of our interest in the application of solid acid catalysts in organic
synthesis [17-20], herein, we describe an efficient method for the synthesis of 1-amidoalkyl-2-
naphthols by one-pot condensation reaction of 2-naphthol, aldehydes and amides using catalytic
amounts of boric acid under solvent-free conditions (Scheme 1).
O
O
OH
R'
H BO
3
3
H
+
+
R'
NH2
neat, 120 o
C
NH
OH
R
O
R
Scheme 1
_
*
_________
Corresponding author. E-mail: zahed.karimi@yahoo.com

474
Zahed Karimi-Jaberi and Hadi Fakhraei
Boric acid (H BO ) is a useful and environmentally benign catalyst which has been
3
3
successfully utilized in numerous reactions [21-29], for example, the aza Michael addition [26],
the Biginelli reaction [27], transesterification of ethyl acetoacetate [28], the Mannich reaction
[
29] and by our group in the synthesis of dibenzoxanthenes [17], α-aminophosphonates [18],
dihydroquinazolinones [19] and benzimidazoles [20]. It offers milder conditions relative to
common mineral acids. Boric acid is a readily available and inexpensive reagent and can
conveniently be handled and removed from the reaction mixture. Thus, the remarkable catalytic
activities together with its operational simplicity make it the most suitable catalyst for the
synthesis of 1-amidoalkyl 2-naphthols.
RESULTS AND DISCUSSION
To optimize the reaction conditions, the reaction of 2-naphthol, benzaldehyde and acetamide
was used as a model reaction. Reactions at different conditions and various molar ratios of
substrates in the presence of boric acid revealed that the best conditions were solvent-free at 120
o
C. After completion of the reaction, the catalyst (boric acid) can be separated from the reaction
mixture by washing the product with water.
Table 1. Synthesis of 1-amidoalkyl-2-naphthols.
o
Entry
1
R
H
R′
Product
Yield (%)
73
m.p. ( C)
OH
CH
3
244-245
NHCOCH3
OH
2
4-CH
3
CH
3
71
221-222
NHCOCH3
H C
3
OH
NHCOCH3
OMe
3
4
2,5-(OMe)
2
CH
3
71
76
251-256
241-243
MeO
OH
3-NO
2
CH
3
O N
2
NHCOCH3
OH
5
4-NO
2
CH
3
75
248-249
NHCOCH3
O N
2
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Short Communication
475
o
Entry
6
R
R′
Product
Yield (%)
72
m.p. ( C)
OH
3-F
CH
3
248-249
F
NHCOCH3
OH
7
4-Cl
CH
3
72
223-225
NHCOCH3
Cl
OH
8
9
2-Cl
CH
CH
CH
3
71
73
68
214-215
199-201
124-126
NHCOCH3
Cl
OH
2,4-Cl
2
3
NHCOCH3
Cl
Cl
OH
1
1
0
1
4-NMe
2
3
NHCOCH3
Me N
2
OH
H
Ph
75
234-236
NHCOPh
OH
1
1
2
3
4-NO
2
Ph
Ph
76
72
238-240
285-286
NHCOPh
O N
2
OH
2-Cl
NHCOPh
Cl
To show the generality of this method the optimized system was used for the synthesis of
other amidoalkyl naphthol derivatives. The results are summarized in Table 1. Various
Bull. Chem. Soc. Ethiop. 2012, 26(3)

476
Zahed Karimi-Jaberi and Hadi Fakhraei
functionalities present in the aryl aldehydes, such as chloro, flouro, methyl and methoxy groups
o
were tolerated under these conditions at 120 C (Table 1).
However, the reactions of aliphatic aldehydes would fail to give the desired products as well
as the known catalysts, such as montmorillonite K10 [5], K CoW O .3H O [8], and Fe(HSO )
4 3
5
12 40
2
[
9].
The reaction can also proceed with benzamide instead of acetamide (Table 1, entries 11-13).
In all these cases, the corresponding 1-amidoalkyl-2-naphthols were obtained in good yields at
20 °C without formation of any side products such as dibenzoxanthenes, which are normally
1
observed under the influence of strong acids. It is important to note that the synthesis of 1-
amidoalkyl-2-naphthols could not be achieved in the absence of catalyst (boric acid).
The proposed mechanism for the boric acid catalyzed preparation of 1-amidoalkyl-2-
naphthols from the reaction of 2-naphthol, aromatic aldehydes and amides is shown in Scheme
2
. As has been suggested earlier [7, 10], the reaction of 2-naphthol with aromatic aldehydes in
the presence of acid catalyst is known to give ortho-quinone methides (O-QMs). Further,
nucleophilic conjugate addition of amide on o-quinone methide intermediate leads to the
formation of amidoalkyl naphthol as a product.
ArCHO
3 3
H BO
OH
O
Ar
H
O-QMs
O
OH
NH
H N
R'
2
Ar
3 3
H BO
R'
O
Scheme 2
1
13
All the products were identified by H NMR, C NMR, IR, and mass spectroscopic methods
and the results were confirmed by comparison with those available in the literature.
In conclusion, we have developed a very simple and efficient method for the high-yielding
synthesis of 1-amidoalkyl-2-naphthols by one-pot three-component coupling of 2-naphthol,
various aromatic aldehydes and amides using boric acid as a heterogeneous acid catalyst. This
method offers some advantages in terms of simplicity of performance, low reaction times,
solvent-free condition, low cost, and it follows along the line of green chemistry. The catalyst is
readily available and inexpensive and can conveniently be handled and removed from the
reaction mixture.
EXPERIMENTAL
Typical procedure for the preparation of 1-amidoalkyl 2-naphthols. A mixture of 2-naphthol (1
o
mmol), aldehyde (1 mmol), amide (1.2 mmol) and H BO (0.05 g) at 120 C was stirred for 15
3
3
min. The progress of reactions was monitored by TLC (ethyl acetate/n-hexane = 1/3). After
completion of the reaction, the reaction mixture was diluted with water and extracted with
ethylacetate, dried over Na SO , concentrated under vacuum and the crude mixture was purified
2
4
by recrystalization from ethanol to afford pure products.
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Short Communication
477
Spectral data for selected products
1
2
.2.a N-[Phenyl-(2-hydroxy-naphthalen-1-yl)-methyl]-acetamide (Table 1, entry 1). H NMR
(
500 MHz, DMSO-d ): δ = 1.98 (s, 3H), 7.19-1.10 (m, 4H), 7.26-7.20 (m, 4H), 7.33 (t, J = 7.5
6
Hz, 1H), 7.74 (d, J = 9.2 Hz, 1H,), 7.80 (d, J = 8.0 Hz, 1H), 7.84 (s, 1H), 8.45 (d, J = 8.5 Hz,
1
3
1
1
3
H), 10.02 (s, 1H); C NMR (125 MHz, DMSO-d ): δ = 23.2, 40.4, 119.2, 119.4, 122.9, 123.8,
6
-1
26.6, 126.9, 128.5, 128.7, 128.9, 129.1, 129.8, 132.9, 143.1, 153.7, 169.1; IR (KBr, cm ):
399, 3246, 3062, 1640, 1582, 1514, 1372, 1337, 1060.
2
3
2
.2.b N-[(2,5-Dimethoxyphenyl)-(2-hydroxynapthalen-1-yl)-methyl]-acetamide (Table 1, entry
1
). H NMR (500 MHz, DMSO-d ): δ = 1.88 (s, 3H), 3.48 (s, 3H), 3.64 (s, 3H), 6.77-6.72 (m,
6
13
H), 7.23-7.10 (m, 4H), 7.39 (s, 1H), 7.73-7.66 (m, 2H), 8.27-8.15 (m, 2H), 9.75 (s, 1H);
C
NMR (125 MHz, DMSO-d ): δ = 22.5, 44.4, 55.2, 55.9, 111.1, 111.9, 115.7, 118.5, 118.9,
6
-
1
1
3
7
2
22.0, 123.2, 125.7, 128.1, 128.6,131.7, 132.4, 150.7, 152.7, 153.1, 168.1; IR (KBr, cm ):
365, 3174, 3002, 2939, 1614, 1577, 1497, 1436, 1370, 1317, 1277, 1218, 1084, 1052, 819,
97, 727; MS (EI, 70 eV) m/z = 351 (M+, 18%), 308 (6%), 276 (6%), 262 (36%), 261 (100%),
18 (17%), 205 (3%), 189 (5%), 164 (4%), 144 (7%), 115 (8%), 95 (2%), 77 (2%).
ACKNOWLEDGEMENTS
We gratefully acknowledge the financial support from the Research Council of Islamic Azad
University, Firoozabad Branch. We are also grateful to Mohammad Barekat for preparing some
of the starting materials.
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