Ecofriendly and efficient multicomponent method for preparation of 1-amidoalkyl-2-naphthols using maltose under solvent-free conditions

Article abstract of DOI:10.1007/s11164-014-1564-2

An efficient and entirely green protocol for preparation of 1-amidoalkyl-2-naphthols employing a multicomponent one-pot condensation reaction of 2-naphthol, amides or urea, and aromatic aldehydes in the presence of maltose under solvent-free conditions is

Full text of DOI:10.1007/s11164-014-1564-2

Res Chem Intermed
DOI 10.1007/s11164-014-1564-2
Ecofriendly and efficient multicomponent method
for preparation of 1-amidoalkyl-2-naphthols using
maltose under solvent-free conditions
•
Belgheis Adrom Nourallah Hazeri
•
•
Malek Taher Maghsoodlou
Mansooreh Mollamohammadi
Received: 12 December 2013 / Accepted: 12 February 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract An efficient and entirely green protocol for preparation of 1-amidoalkyl-2-
naphthols employing a multicomponent one-pot condensation reaction of 2-naphthol,
amides or urea, and aromatic aldehydes in the presence of maltose under solvent-free
conditions is described. The present approach of this methodology offers several
advantages such as mild conditions, high yields, clean reaction profiles, operational
simplicity, and environmentally benign and simple work-up procedures.
Keywords Green protocol Á Amidoalkyl naphthols Á Multicomponent
reaction Á Maltose Á Solvent-free conditions
Introduction
Multicomponent reactions (MCRs) play an important role in combinatorial
chemistry because of their ability to synthesize small drug-like molecules with
several degrees of structural diversity. These reactions allow compounds to be
synthesized in few steps and usually in a one-pot manner [1]. As well as offering
time and energy savings and having simple procedures, the advantages of these
reactions include high bond-forming efficiency and low expenditure [2]. Therefore,
finding and designing new MCRs has been the subject of extensive research.
Amidoalkyl naphthols and their derivatives have attracted considerable interest
in recent years in terms of biologically important antibacterial properties, natural
products, and potent drugs, including a number of nucleoside antibiotics and human
immunodeficiency virus (HIV) protease inhibitors, such as ritonavir and lopinavir
[3, 4]. 1-Amidomethyl-2-naphthols can be converted into important ‘‘drug-like’’
B. Adrom Á N. Hazeri (&) Á M. T. Maghsoodlou Á M. Mollamohammadi
Department of Chemistry, Faculty of Science, University of Sistan & Baluchestan,
P. O. Box 98135-674, Zahedan, Iran
e-mail: nhazeri@chem.usb.ac.ir
123

B. Adrom et al.
1-aminomethyl-2-naphthols by amide hydrolysis [5]. The hypertensive and brady-
cardiac effects of these compounds have been evaluated [6]. Intramolecular
cyclization of amidoalkyl naphthols by Vilsmeier reagent produces 1,3-oxazines
[7]. Synthesis of 1,3-oxazines has attracted attention because of their potential as
antibiotics [8] and as antitumor [9], anticonvulsant [10], antipsychotic [11],
antimalarial [12], antianginal [13], and antihypertensive [14] agents, and as potent
antirheumatic agents [15]. Preparation of 1-amidoalkyl-2-naphthols can be carried
out by condensation of aryl aldehydes, 2-naphthol, and acetonitrile or acetamide in
the presence of Lewis or Brønsted acid catalysts such as montmorillonite K10 clay
[16], Ce(SO4)2 [17], iodine [18], succinic acid [19], Fe(HSO4)3 [20], ethylammonium
nitrate (EAN) [21], TrCl [22], and zeolite H-BETA [23]. However, the major
problems associated with these reactions in most of the published procedures are high
catalyst loading, long reaction times, unsatisfactory yields, harsh reaction conditions,
expensive catalysts, and tedious work-up procedures. Therefore, development of a
suitable method using additional reagents and catalysts for efficient synthesis of
1-amidoalkyl-2-naphthols remains an attractive field for researchers.
In view of the above and as a part of our ongoing program on MCRs [24, 25], we
present herein an ecofriendly, simple, and efficient method for synthesis of
1-amidoalkyl-2-naphthol compounds via a one-pot three-component reaction using
2-naphthol, amides/urea, and aromatic aldehydes in the presence of maltose under
solvent-free conditions (Scheme 1).
The principles of green chemistry have been introduced to eliminate or reduce the
use of hazardous materials such as H2SO4 or H3PO4 in chemical processes. Cleaner
technologies are possible using environmentally friendly materials such as carbohy-
drates, because these materials are cheap, safe, and environmentally benign [26]. For
this reason, we focused our investigation on the development of new green synthetic
methods for preparation of 1-amidoalkyl-2-naphthols. This is a one-pot reaction under
solvent-free conditions, which is not only operationally simple, clean, and efficient but
also consistently gives the corresponding products in good to excellent yields.
Results and discussion
We performed a set of preliminary experiments on 2-naphthol, acetamide, and
benzaldehyde in the presence of catalyst as a model reaction. In the initial work,
R
NHCOR
OH
O
O
OH
+
Maltose (20 mol%)
solvent-free, 100 °C
+
R
NH2
Ar
H
1
4a-ac
2
3
R = CH3, Ph, NH2
Scheme 1 Maltose-catalyzed synthesis of 1-amidoalkyl-2-naphthols 4
123

Preparation of 1-amidoalkyl-2-naphthols using maltose
different carbohydrates as catalyst were screened in the model reaction. The
reaction did not progress even after 24 h in the absence of catalyst. Also, the
reaction was performed in the presence of sucrose, xylose, and lactose, with the
product being obtained in moderate yield. However, 20 mol.% maltose proved to be
an efficient catalyst, giving high yield (Table 1). As shown in Table 1, the shortest
time and best yield were achieved at 100 °C.
To evaluate the generality of the process, several examples illustrating the present
method for synthesis of 1-amidoalkyl-2-naphthols 4 were studied (Table 2). The
reactions of 2-naphthol with various aromatic aldehydes and amides or urea were
carried out in the presence of 20 mol.% maltose at 100 °C. In all the reactions, good
to excellent yields were obtained in short reaction times (0.2–2 h). Clean and
complete conversions leading to the corresponding amidoalkyl naphthols were
observed, and no side products such as dibenzoxanthenes were formed. Aromatic
aldehydes carrying either electron-withdrawing (nitro) or electron-donating (halide,
alkyl, alkoxy) groups were all suitable for the reaction. On the other hand, the scope
of different amide components was studied. Both amides (benzamide and acetamide)
and urea participated well in the reactions. As compared with the amides, urea
afforded the corresponding amidoalkyl naphthol in longer reaction time (Table 2).
A suggested mechanism for this transformation is proposed in Scheme 2. As
reported in the literature [27], reaction of 2-naphthol with aldehydes in the presence
of catalyst is known to give ortho-quinone methides (o-QMs). The same o-QMs,
generated in situ, have been reacted with amides via conjugate addition to form
1-amidoalkyl-2-naphthol derivatives 4a–ac.
Conclusions
We have developed a new method for preparation of 1-amidoalkyl-2-naphthol
derivatives via one-pot three-component reaction of 2-naphthol with aromatic
Table 1 Optimization of catalyst for synthesis of 1-amidoalkyl-2-naphthols
Entry
Catalyst
Mol.%
Temperature (°C)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
Lactose
Sucrose
Xylose
10
10
10
10
15
20
30
20
20
100
100
100
100
100
100
100
80
8
5
7
5
4
2
1
5
2
48
65
25
80
85
93
87
72
75
Maltose
Maltose
Maltose
Maltose
Maltose
Maltose
120
Reaction conditions: 2-naphthol, acetamide, and benzaldehyde in the presence of catalyst
The best result were obtained with 20 mol.% maltose in 100 °C are highlighted in bold
a
Isolated yield
123

B. Adrom et al.
Table 2 Synthesis of 1-amidoalkyl-2-naphthol derivatives
Entry
Ar
R
Time (h)
Yield (%)a
Product
M.p. (lit. m.p.) (°C)
1
4-NO2–C6H4
4-Cl–C6H4
3-NO2–C6H4
2,4-Cl2C6H3
3-OMe–C6H4
2-Me–C6H4
4-Me–C6H4
Ph
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Ph
0.5
0.5
0.5
0.5
1
94
92
91
94
89
80
87
90
95
89
89
96
95
95
88
92
92
90
90
96
89
88
90
92
90
85
95
92
92
4a
4b
4c
4d
4e
4f
246–248 (248–250) [6]
228–229 (230–232) [20]
238–240 (236–237) [29]
199–201 (201–203) [6]
203–205 (203–205) [29]
197–199 (200–202) [34]
221–223 (223–225) [28]
243–245 (245–246) [18]
197–199 (194–196) [29]
230–232 (232–234) [18]
181–183 (184–186) [18]
242–244 (242–243) [6]
262–264 (264–266) [33]
238–240 (238–239) [30]
215–216 (207–209) [18]
238–240 (237–239) [32]
264–266 (265–267) [30]
234–236 (237–239) [18]
186–188 (187–189) [29]
176–178 (176–178) [35]
218–220 (220–221) [33]
208–210 (206–208) [33]
192–194 (192–193) [18]
192–194 (163–165) [17]
166–168 (168–169) [34]
174–176 (174–175) [31]
236–238
2
3
4
5
6
1.5
1.5
1
7
4g
4h
4i
8
9
2-Cl–C6H4
4-NCC6H4
4-OMe–C6H4
Ph
0.5
0.5
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
a
4j
4k
4l
0.5
0.3
0.3
1.5
0.5
0.5
0.3
1.5
0.2
0.5
1.5
1
2-NO2–C6H4
2,4-Cl2C6H3
4-Me–C6H4
4-NO2–C6H4
2-Cl–C6H4
3-NO2–C6H4
4-Cl–C6H4
4-NC–C6H4
4-NMe2–C6H4
4-OMe–C6H4
3-NO2–C6H4
4-NO2–C6H4
4-Cl–C6H5
Ph
Ph
4m
4n
4o
4p
4q
4r
4s
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4t
Ph
4u
4v
4w
4x
4y
4z
4aa
4ab
4ac
Ph
NH2
NH2
NH2
NH2
Ph
1
1.5
2
2,3-(MeO)2–C6H3
2-OH,5-Br–C6H3
C4H3S
0.5
0.8
1
Ph
220–222
Ph
221–223
Isolated yield
aldehydes and different amides/urea using maltose as a neutral organic catalyst at
100 °C under solvent-free conditions. The catalyst shows environmentally friendly
characters. Namely, it is inexpensive, clean, safe, nontoxic, and easily obtained.
Moreover, this method has several other advantages including mild reaction
conditions, high yields, operational simplicity, and clean and neutral reaction
conditions, which makes it a useful and attractive process for synthesis of a wide
variety of biologically active compounds.
123

Preparation of 1-amidoalkyl-2-naphthols using maltose
Maltose
Ar
H
H
O
OH
O
O
+
H
Ar
1
2
o-QMs
O
R
Ar
N
Maltose
Ar
H
H
H
O
O
O
OH
H2N
R
+
o-QMs
4
3
Scheme 2 Suggested mechanism for synthesis of amidoalkyl naphthols
Experimental
Melting points and infrared (IR) spectra of all compounds were measured on an
Electrothermal 9100 apparatus and a JASCO FT/IR 460 Plus spectrometer,
1
respectively. The H nuclear magnetic resonance (NMR) and 13C NMR spectra
were recorded on Bruker DRX-400 Avance instruments with dimethyl sulfoxide
(DMSO) as solvent. Mass spectra were recorded on an Agilent Technology (HP)
spectrometer operating at ionization potential of 70 eV. All reagents and solvents
obtained from Fluka and Merck were used without further purification.
Typical procedure for synthesis of 1-amidoalkyl-2-naphthols (4a–ac)
Maltose (20 mol.%, 0.068 g) was added into a mixture of benzaldehyde (1 mmol),
2-naphthol (1 mmol), and acetamide (1.1 mmol), then the reaction mixture was
heated to 100 °C and maintained for the appropriate time (Table 1). After
completion of the reaction as monitored by thin-layer chromatography (TLC), the
reaction mixture was washed with H2O (3 9 10 mL). The catalyst is solvable in
water and was removed from the reaction mixture. Then, the residue was
recrystallized from EtOH.
N-[(2,3-Dimethoxyphenyl)-(2-hydroxynaphthalen-1-yl)-methyl]-benzamide (4aa)
Yield: 95 %; m.p. 236–238 °C; IR (KBr, cm-1): 3,379 (N–H), 3,143 (O–H), 1,632
(C=O); 1H NMR (400 MHz, DMSO-d6): d = 3.56 and 3.76 (2s, 6H, 2OCH3), 6.92
(dd, 1H, J = 8 Hz, J = 1.6 Hz, Haromatic), 6.96 (t, 1H, J = 8.4 Hz, Haromatic), 7.12
(d, 1H, J = 6.8 Hz, Haromatic), 7.20 (d, 1H, J = 8.8 Hz, Haromatic), 7.28 (t, 1H,
123

B. Adrom et al.
J = 7.6 Hz, Haromatic), 7.45 (t, 3H, J = 7.6 Hz, Haromatic), 7.50–7.53 (m, 2H,
H
aromatic), 7.74 (d, 1H, J = 8.6 Hz, Haromatic), 7.79 (d, 1H, J = 7.6 Hz, Haromatic),
7.86 (d, 2H, J = 6.8 Hz, Haromatic), 8.21 (d, 1H, J = 8.0 Hz, 1Hbenzylic), 8.98 (d, 1H,
J = 8.0 Hz, NH), 10.20 (brs, 1H, OH); 13C NMR (100 MHz, DMSO-d6):
d = 45.94, 56.09, 60.34, 112.14, 119.13, 119.25, 121.00, 122.98, 123.47, 123.83,
126.76, 127.59, 128.74, 128.88, 129.45, 131.72, 132.92, 134.95, 135.78, 146.68,
152.78, 153.70, 165.38; MS m/z (%): 413 (M?, 25), 382 (17), 308 (35), 261 (100),
246 (31), 218 (30), 167 (73), 149 (86), 127 (19), 105 (63), 77 (58), 57 (54).
N-[(4-Bromo-2-hydroxyphenyl)-(2-hydroxynaphthalen-1-yl)-methyl]-benzamide
(4ab)
Yield: (92 %); m.p. 220–222 °C; IR (KBr, cm-1): 3,379 (N–H), 3,225 (O–H), 1,599
1
(C=O); H NMR (400 MHz, DMSO-d6): d = 6.76 (d, 1H, J = 8.4 Hz, Haromatic),
7.20 (d, 1H, J = 9.2 Hz, Haromatic), 7.22 (d, 1H, J = 2.8 Hz, Haromatic), 7.28 (t, 1H,
J = 7.2 Hz, Haromatic), 7.39–7.53 (m, 6H, Haromatic), 7.74 (d, 1H, J = 8.8 Hz,
H
aromatic), 7.79 (d, 1H, J = 7.6 Hz, Haromatic), 7.86 (d, 2H, J = 7.8 Hz, Haromatic),
8.24 (d, 1H, J = 8.8 Hz, Hbenzylic), 8.94 (brs, 1H, NH), 10.12 (brs, 2H, OH); 13C
NMR (100 MHz, DMSO-d6): d = 45.90, 110.17, 117.73, 118.63, 119.29, 122.97,
123.53, 126.72, 127.74, 128.69, 128.79, 128.88, 129.53, 130.90, 130.96, 131.70,
132.02, 133.00, 134.83, 153.79, 154.67, 165.66; MS m/z (%): 447 (M?, 5), 311 (45),
261 (7), 247 (16), 202 (5), 144 (81), 121 (6), 105 (100), 77 (89), 51 (35).
N-[(2-Hydroxynaphthalen-1-yl)-thiophen-3-ylmethyl]-benzamide (4ac)
Yield: (92 %); m.p. 221–223 °C; IR (KBr, cm-1): 3,420 (N–H), 3,108 (O–H), 1,630
1
(C=O); H NMR (400 MHz, DMSO-d6): d = 7.23 (d, 1H, J = 8.8 Hz, Haromatic),
7.29–7.35 (m, 2H, Haromatic), 7.43–7.57 (m, 6H, Haromatic), 7.75 (d, 2H, J = 8.4 Hz,
H
aromatic), 7.81 (d, 1H, J = 9.2 Hz, Haromatic), 7.88 (d, 2H, J = 6.8 Hz, Haromatic),
8.04 (d, 1H, J = 8.8 Hz, Hbenzylic), 9.10 (d, 1H, J = 6.4 Hz, NH), 10.11 (brs, 1H,
OH); 13C NMR (100 MHz, DMSO-d6): d = 49.54, 109.64, 117.89, 119.01, 119.36,
123.08, 123.22, 126.56, 127.42, 127.80, 127.84, 127.98, 128.83, 128.90, 129.16,
130.34, 132.02,132.60, 133.65, 134.48, 153.88, 166.69; MS m/z (%): 378 (M?, 18),
273 (6), 256 (100), 227 (11), 144 (5), 122 (11), 105 (32), 77 (26), 57 (10).
Acknowledgments We gratefully acknowledge financial support from the Research Council of the
University of Sistan and Baluchestan.
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