Preparation of 1-amidoalkyl-2-naphthol derivatives using barium phosphate nano-powders

Article abstract of DOI:10.1016/j.cclet.2015.08.011

Barium phosphate (Ba₃(PO₄)₂) nano-powder was successfully synthesized via a simple precipitation route without any surfactant. The prepared nano-powder was applied for the facile synthesis of 1-amidoalkyl-2-naphthol derivatives using multi-component reaction of aldehydes, 2-naphthol and an amide (or urea) in high yields.

Full text of DOI:10.1016/j.cclet.2015.08.011

Accepted Manuscript
Title: Preparation of 1-amidoalkyl-2-naphthol derivatives
using barium phosphate nano-powders
Author: Hadi Taghrir Majid Ghashang Mohammad Najafi
Bireghan
PII:
S1001-8417(15)00334-4
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2015.08.011
CCLET 3414
To appear in:
Chinese Chemical Letters
Please cite this article as: H. Taghrir, M. Ghashang, M.N. Bireghan, Preparation of
1-amidoalkyl-2-naphthol derivatives using barium phosphate nano-powders, Chinese
Chemical Letters (2015), http://dx.doi.org/10.1016/j.cclet.2015.08.011
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Graphical Abstract
Preparation of 1-amidoalkyl-2-naphthol derivatives using barium phosphate nano-powders
Hadi Taghrira, Majid Ghashangb, *, Mohammad Najafi Bireghanb
aDepartment of Chemistry, Science and Research Branch, Islamic Azad University, Arak, Iran
bDepartment of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University, Najafabad, Iran
O
Y
Ba3(PO4)2 nanopowders
O
OH
Ar
NH
OH
+ Ar-CHO +
Y
NH2
Solvent-f ree
100 oC
Ar: H; 4-Cl; 2-Cl; 2,4-diCl; 4-NO2;
3-NO2; 4-CH3; 4-tert-Butyl; 4-F
Y: CH3; Ph; 3-MePh; CH3NH
Barium phosphate (Ba3(PO4)2) nano-powder was successfully synthesized via a simple precipitation route without any
surfactant. The prepared nano-powder was applied for the facile synthesis of 1-amidoalkyl-2-naphthol derivatives using multi-
component reaction of aldehydes, 2-naphthol and an amide (or urea) in high yields.
Page 1 of 10

Original article
Preparation of 1-amidoalkyl-2-naphthol derivatives using barium phosphate nano-
powders
Hadi Taghrira, Majid Ghashangb, ∗,Mohammad Najafi Bireghanb
a Department of Chemistry, Science and Research Branch, Islamic Azad University, Arak, Iran
b Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University, Najafabad, Iran
ARTICLE INFO
ABSTRACT
Article history:
Barium phosphate (Ba3(PO4)2) nano-powder was successfully synthesized via a simple
precipitation route without any surfactant. The prepared nano-powder was applied for the
facile synthesis of 1-amidoalkyl-2-naphthol derivatives using multi-component reaction of
aldehydes, 2-naphthol and an amide (or urea) in high yields.
Received 9 April 2015
Received in revised form 21 July 2015
Accepted 3 August 2015
Available online
Keywords:
Multi-component reaction
1-Amidoalkyl-2-naphthol
Barium phosphate (Ba3(PO4)2)
2-Hydroxydibenzofuran
1. Introduction
Establishing methods to synthesize 1,3-amino oxygenated functional groups is an immensely important pursuit in organic synthesis
due to the role of this functional group as an antibiotic, HIV protease inhibitor and building block in a many biomolecules as well as
pharmaceutically interesting compounds [1-3]. 1-Amidoalkyl-2-naphthols are a class of these molecules that are prepared via multi-
component reaction of aldehydes, 2-naphthol, and an amide (or urea). Several Lewis and Brønsted acidic catalysts have been used for
this transformation, including montmorillonite K10 [4], Ce(SO4)2 [5], I2 [6], K5CoW12O40.3H2O [7], p-TSA [8], ultrasound-promoted
sulfamic acid [9], zirconyl(IV) chloride [10], silica sulfuric acid [11], cation-exchanged resins [12], sulphamic acid [13], SiO2-HClO4
[14], polymer-supported sulphonic acid [15], 4-(1-imidazolium) butane sulfonate (IBS) [16], ionic liquids [17,18], heteropoly acid
[19], strontium(II) triflate [20], PPA-SiO2 [21], NBS [22], NaHSO4 [23], Cu-exchanged heteropoly acids [24], NaHSO4.SiO2 [25],
ferric hydrogensulfate [26], trityl chloride [27], nickel-doped SnO2 nanoparticles [28] and NiO-SnO2 composite nano-powder [29].
Metal phosphates glasses, such as barium phosphates, have been of large interest for a variety of technologies due to several
exclusive properties such as high thermal expansion coefficient, low viscosity, UV transmission, or electrical conduction. Important
biological applications for calcium phosphate glasses exist, also, as it was demonstrated that they are biocompatible as bones and
dental implants [30-33].
Despite this wide range of applications, the use of alkaline phosphates such as barium and calcium phosphates has not been
receiving any attention in organic synthesis. This work is justified as a first work for the evaluation of the catalytic activity of barium
phosphates.
Barium phosphate is known for its luminescence and was found to be a good host for rare earth-doped luminescent materials.
Different methods have been reported for the preparation of barium phosphate including conventional solid-state reaction, sol–gel,
simple precipitation, and hydrothermal method [34-37]. However the solid state method has disadvantages of poor particle distribution,
high sintering temperature and long reaction time. Recently these problems has been improved by chemical synthetic methods which
can be done at lower temperatures and have chemical homogeneity [38-39]. In this paper a modified simple precipitation method is
applied for the preparation of barium phosphate nanopowder.
Based on the above information and due to our interest in developing the synthetic methodologies for the construction of
heterocyclic compounds [40-45], herein, a detailed account of our focused attention toward construction of the 1-amidoalkyl-2-
naphthol derivatives is reported, via the reaction of aldehydes, 2-naphthol and an amide (or urea) in high yields in the presence of
Ba3(PO4)2 nanopowder as catalyst (Scheme 1).
———
∗ Corresponding author.
E-mail address: ghashangmajid@gmail.com (Majid Ghashang)
Page 2 of 10

O
Y
Ba3(PO4)2 nanopowders
O
OH
Ar
NH
OH
+ Ar-CHO +
Y
NH2
Solvent-f ree
100 oC
Ar: H; 4-Cl; 2-Cl; 2,4-diCl; 4-NO2;
3-NO2; 4-CH3; 4-tert-Butyl; 4-F
Y: CH3; Ph; 3-MePh; CH3NH
Scheme 1. Preparation of 1-amidoalkyl-2-naphthol derivatives.
2. Experimental
2.1. Reagents and Instrumentation
All reagents were purchased from Merck and Aldrich and used without further purification. All yields refer to isolated products after
purification. The NMR spectra were recorded on a Bruker Avance DPX 400 MHz instrument. The spectra were measured in DMSO-d6
relative to TMS (0.00 ppm). Elemental analysis was performed on a Heraeus CHN-O-Rapid analyzer. TLC was performed on silica gel
Polygram SIL G/UV 254 plates. The powder X-Ray diffraction patterns were measured with a Bruker D8 Advance diffractometer
using CuKα irradiation. FE-SEM was taken by a Hitachi S-4160 photograph to examine the shape and size of BaPO4 nano-particles.
Dynamic light scattering (DLS) measurement was done using a Malvern Zetasizer Nano ZS (ZEN 3600) instrument.
2.2. Preparation of Ba3(PO4)2 nano-powder
To an aqueous solution of BaCl2 (10 mmol BaCl2 in 50 mL of water), NH4H2PO4 (10 mmol dissolved in 50 mL of EtOH/H2O
(50/50)+ triethyl ammonium chloride (15 mmol) + 5 mL NH4OH (aqueous solution 37%)) was added drop-wise with vigorous stirring
at room temperature. After the dropping process was completed, the resultant mixture was aged for 30 min. The afforded precipitates
were separated from the mother liquor by filtration and were washed with distilled water several times, then were dried at 100 °C. The
BaPO4 nano-particles were pulverized for analysis.
2.3. General procedure
To a mixture of aromatic aldehyde (1 mmol), 2-naphthol / dibenzofuran-2-ol (1 mmol) and acetamide/bezamide/urea (1.3 mmol)
o
was added Ba3(PO4)2 nano-particles (0.1 mmol), and the mixture was heated at 100 C in an oil bath for the appropriate time. The
o
progress of the reaction was monitored by TLC. After completion of the reaction, mass was cooled to 25 C and the mixture was
dissolved in pure acetone. The catalyst was removed by simple filtration. The solvent was evaporated and the solid product was
purified by recrystallization from ethanol.
N-((2-Hydroxynaphthalen-1-yl)(phenyl)methyl)-3-methylbenzamide: 1H NMR (400 MHz, DMSO-d6): δ 2.43 (s, 3H), 6.98 (d, 1H, J
= 8.7 Hz), 7.06-7.58 (m, 11H), 7.89-7.95 (m, 3H), 8.02 (d, 1H, J = 8.3 Hz), 9.47 (d, 1H, J = 8.7 Hz, NH), 10.37 (s, 1H, OH); 13C NMR
(100 MHz, DMSO-d6): δ 21.2, 56.9, 118.9, 126.6, 126.8, 126.9, 127.6, 127.9, 128.3, 128.6, 128.7, 128.9, 129.2, 130.6, 130.9, 131.1,
133.0, 134.5, 136.1, 137.8, 142.9, 158.8, 167.1; Calcd. for C25H21NO2: C, 81.72; H, 5.76; N, 3.81, Found: C, 81.85; H, 5.89; N, 3.93.
N-((4-Bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-3-methylbenzamide: 1H NMR (400 MHz, DMSO-d6): δ 2.44 (s, 3H), 7.01-
7.58 (m, 11H), 7.90-7.95 (m, 3H), 8.02 (d, 1H, J = 8.4 Hz), 9.14 (d, 1H, J = 8.6 Hz, NH), 10.31 (s, 1H, OH); 13C NMR (100 MHz,
DMSO-d6): δ 21.3, 57.0, 118.8, 124.2, 126.6, 126.7, 126.8, 127.8, 128.3, 128.6, 128.7, 129.2, 130.5, 130.9, 131.2, 131.7, 132.9, 134.4,
135.9, 137.7, 142.9, 158.8, 167.0; Calcd. for C25H20BrNO2: C, 67.27; H, 4.52; N, 3.14, Found: C, 67.41; H, 4.69; N, 3.31.
1
N-((2-Hydroxynaphthalen-1-yl)(3-nitrophenyl)methyl)-3-methylbenzamide: H NMR (400 MHz, DMSO-d6): δ 2.44 (s, 3H), 7.01-
7.59 (m, 7H), 7.90-7.97 (m, 4H), 8.02 (d, 1H, J = 8.4 Hz), 8.05 (s, 1H), 8.22 (d, 1H, J = 8.0 Hz), 9.17 (d, 1H, J = 8.5 Hz, NH), 10.39 (s,
1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 21.2, 57.0, 118.9, 124.7, 125.3, 126.7, 126.8 (2C), 127.1, 127.8, 128.2, 128.5 (2C), 128.9,
130.5, 130.9, 131.2, 132.9, 134.5, 135.8, 137.7, 139.6, 145.3, 158.8, 166.9; Calcd. for C25H20N2O4: C, 72.80; H, 4.89; N, 6.79, Found:
C, 72.97; H, 5.06; N, 6.94.
1
N-[(2-Hydroxydibenzofuran-1-yl)(phenyl)methyl)-3-methylbenzamide: H NMR (400 MHz, DMSO-d6): δ 2.43 (s, 3H, CH3), 7.05-
7.70 (m, 13H), 7.75 (d, 1H, J = 8.1 Hz), 7.90-7.94 (m, 2H), 8.76 (d, 1H, J = 8.5 Hz, NH), 9.94 (s, 1H, OH); 13C NMR (100 MHz,
DMSO-d6): δ 21.2, 57.0, 111.9, 112.4, 119.8, 119.9, 122.7, 122.9, 124.6, 125.4, 127.5 (2C), 127.8, 128.3, 128.4, 128.7, 128.9, 130.6,
135.9, 137.7, 142.7, 153.9, 155.5, 156.8, 167.6; Calcd. for C27H21NO3: C, 79.59; H, 5.19; N, 3.44, Found: C, 79.72; H, 5.36; N, 3.57.
1
N-[(2-Hydroxydibenzofuran-1-yl)(4-methylphenyl)methyl)-3-methylbenzamide: H NMR (400 MHz, DMSO-d6): δ 2.27 (s, 3H,
CH3), 2.43 (s, 3H, CH3), 7.05 (d, 1H, J = 8.6 Hz, CH), 7.09 (d, 2H, J = 7.9 Hz), 7.11-7.35 (m, 6H), 7.45 (t, 1H, J = 7.9 Hz), 7.62 (d,
1H, J = 8.0 Hz), 7.70 (d, 1H, J = 8.0 Hz), 7.75 (d, 1H, J = 8.3 Hz), 7.91-7.96 (m, 2H), 8.79 (d, 1H, J = 8.6 Hz, NH), 10.02 (s, 1H, OH);
13C NMR (100 MHz, DMSO-d6): δ 21.2, 21.7, 57.2, 111.8, 112.5, 119.7, 119.9, 122.7, 123.0, 124.7, 125.5, 127.6, 127.8, 128.0, 128.5,
128.7, 129.8, 130.6, 135.8, 137.6, 139.8, 142.8, 153.8, 155.6, 157.1, 167.0; Calcd. for C28H23NO3: C, 79.79; H, 5.50; N, 3.32. Found:
C, 79.98; H, 5.67; N, 3.47.
Page 3 of 10

1
N-[(2-Hydroxydibenzofuran-1-yl)(4-methoxyphenyl)methyl)-3-methylbenzamide: H NMR (400 MHz, DMSO-d6): δ 2.42 (s, 3H,
CH3), 3.77 (s, 3H, OCH3), 6.97 (d, 2H, J = 7.9 Hz), 7.03 (d, 1H, J = 8.5 Hz, CH), 7.11-7.36 (m, 6H), 7.44 (t, 1H, J = 8.0 Hz), 7.63 (d,
1H, J = 8.0 Hz), 7.70 (d, 1H, J = 8.0 Hz), 7.75 (d, 1H, J = 8.3 Hz), 7.91-7.96 (m, 2H), 8.74 (d, 1H, J = 8.5 Hz, NH), 10.05 (s, 1H, OH);
13C NMR (100 MHz, DMSO-d6): δ 21.0, 55.9, 57.0, 111.8, 112.4, 114.1, 119.6, 119.9, 122.5, 122.9, 124.6, 125.3, 127.4, 127.7, 128.5,
128.7, 130.6, 130.9, 135.8, 137.7, 142.7, 154.1, 155.6, 156.9, 160.6, 167.1; Calcd. for C28H23NO4: C, 76.87; H, 5.30; N, 3.20, Found:
C, 77.06; H, 5.42; N, 3.35.
N-[(2-Hydroxydibenzofuran-1-yl)(3-nitrophenyl)methyl)-3-methylbenzamide: 1H NMR (400 MHz, DMSO-d6): δ 2.43 (s, 3H, CH3),
7.08 (d, 1H, J = 8.5 Hz, CH), 7.14 (d, 1H, J = 8.2 Hz), 7.20 (t, 1H, J = 8.0 Hz), 7.27 (t, 1H, J = 7.9 Hz), 7.35 (d, 1H, J = 7.8 Hz), 7.43-
7.46 (m, 2H), 7.63 (d, 1H, J = 8.0 Hz), 7.70 (d, 1H, J = 7.9 Hz), 7.75 (d, 1H, J = 8.4 Hz), 7.89-7.95 (m, 3H), 8.06 (s, 1H), 8.21 (d, 1H,
J = 7.9 Hz), 8.81 (d, 1H, J = 8.5 Hz, NH), 10.15 (s, 1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 21.2, 57.6, 111.9, 112.6, 119.7,
119.9, 122.6, 122.9, 124.7, 124.9, 125.5, 125.8, 127.0, 127.5, 127.9, 128.4, 128.7, 129.0, 130.8, 135.8, 137.7, 139.8, 145.3, 153.8,
155.3, 156.9, 167.2; Calcd. for C27H20N2O5: C, 71.67; H, 4.46; N, 6.19, Found: C, 71.78; H, 4.59; N, 6.34.
1
N-[(2-Hydroxydibenzofuran-1-yl)(4-bromophenyl)methyl)-3-methylbenzamide: H NMR (400 MHz, DMSO-d6): δ 2.42 (s, 3H,
CH3), 7.04 (d, 1H, J = 8.6 Hz, CH), 7.14 (d, 1H, J = 8.3 Hz), 7.18-7.37 (m, 7H), 7.44 (t, 1H, J = 8.0 Hz), 7.63 (d, 1H, J = 7.9 Hz), 7.69-
7.75 (m, 2H), 7.89-7.93 (m, 2H), 8.79 (d, 1H, J = 8.6 Hz, NH), 9.96 (s, 1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 21.3, 57.3, 111.8,
112.3, 119.6, 119.9, 122.5, 122.9, 124.5, 124.9, 125.4, 127.6, 127.7, 128.6, 128.9, 129.2, 130.4, 131.6, 135.8, 137.7, 142.7, 153.9,
155.4, 156.9, 167.3; Calcd. for C27H20BrNO3: C, 66.68; H, 4.14; N, 2.88, Found: C, 76.85; H, 4.29; N, 3.01.
1
N-[(2-Hydroxydibenzofuran-1-yl)(3-nitrophenyl)methyl)benzamide: H NMR (400 MHz, DMSO-d6): δ 7.07 (d, 1H, J = 8.6 Hz,
CH), 7.14 (d, 2H, J = 8.4 Hz), 7.19-7.28 (m, 2H), 7.46 (d, 1H, J = 7.9 Hz), 7.51-7.64 (m, 4H), 7.69-7.76 (m, 2H), 7.87-7.92 (m, 3H),
8.04 (s, 1H), 8.21 (d, 1H, J = 7.9 Hz), 8.86 (d, 1H, J = 8.5 Hz, NH), 10.21 (s, 1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 57.5, 111.8,
112.5, 119.5, 119.8, 122.5, 122.8, 124.7, 124.8, 125.6, 125.9, 127.0, 127.6, 127.9, 128.6, 128.7, 129.1, 135.2, 139.5, 145.4, 153.8,
155.2, 156.8, 167.0; Calcd. for C26H18N2O5: C, 71.23; H, 4.14; N, 6.39, Found: C, 71.41; H, 4.39; N, 6.47 .
1
N-[(2-Hydroxydibenzofuran-1-yl)(4-bromophenyl)methyl)benzamide: H NMR (400 MHz, DMSO-d6): δ 7.05 (d, 1H, J = 8.5 Hz,
CH), 7.13 (d, 1H, J = 8.2 Hz), 7.18-7.41 (m, 6H), 7.52-7.75 (m, 6H), 7.88 (d, 2H, J = 7.8 Hz), 8.65 (d, 1H, J = 8.5 Hz, NH), 9.84 (s,
1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 57.6, 111.9, 112.5, 119.6, 119.9, 122.5, 122.9, 124.3, 124.7, 125.4, 127.4, 127.8, 128.8,
128.9 (2C), 131.6, 134.9, 143.0, 153.8, 155.7, 156.9, 167.2; Calcd. for C26H18BrNO3: C, 66.11; H, 3.84; N, 2.97, Found: C, 66.26; H,
3.95; N, 3.11.
N-[(2-Hydroxydibenzofuran-1-yl)(4-bromophenyl)methyl)acetamide: 1H NMR (400 MHz, DMSO-d6): δ 2.01 (s, 3H, CH3), 6.91 (d,
1H, J = 8.4 Hz, CH), 7.13 (d, 1H, J = 8.3 Hz), 7.19 (t, 1H, J = 7.9 Hz), 7.28 (t, 1H, J = 7.9 Hz), 7.35-7.41 (m, 4H), 7.63 (d, 1H, J = 7.9
Hz), 7.70-7.75 (m, 2H), 8.24 (d, 1H, J = 8.4 Hz, NH), 9.14 (s, 1H, OH); 13C NMR (100 MHz, DMSO-d6): δ 23.3, 57.0, 111.9, 112.6,
119.5, 119.8, 122.5, 122.7, 124.3, 124.8, 125.6, 127.7, 128.9, 131.7, 142.8, 153.9, 155.7, 156.9, 169.4; Calcd. for C21H16BrNO3: C,
61.48; H, 3.93; N, 3.41, Found: C, 61.66; H, 4.11; N, 3.59.
3. Results and discussion
In order to determine the crystalline structure and phase composition of the Ba3(PO4)2 nano-powder, X-ray diffraction (XRD)
analysis using Cu-Kα radiation was applied (Fig. 1). The XRD pattern of Ba3(PO4)2 nano-powder exhibited diffraction pattern
characteristics of the tetragonal structure with pronounced 18.32, 26.47, 28.82, 32.77, 38.17, 38.52, 42.22, 43.42, 48.27, 48.72, 52.77
and 54.57 peaks (Fig. 1). The average crystallite diameter of the as prepared powder was determined by XRD, using the highest peak
of the Ba3(PO4)2 phase, according to the Scherrer equation. The average crystalline size estimated at 80 nm.
The average crystalline size of the Ba3(PO4)2 nano-powder was characterized by field emission scanning electron microscopy (FE-
SEM). Fig. 2 shows the FE-SEM micrographs of the Ba3(PO4)2 nano-particles. Based on the FE-SEM observation, the Ba3(PO4)2 nano-
particles contain spherical or ellipsoidal shapes. The particle sizes were mainly distributed in the range of 60-200 nm. The size of about
50 particles of Ba3(PO4)2 was measured and the average particle size was obtained as 85 nm.
The dynamic light scattering (DLS) analysis was used to determine the particle size distribution of Ba3(PO4)2 nano-powder. Fig. 3
shows grain size distributions of Ba3(PO4)2 nano-powders. The powder milled for 2 h and sonicated in ethanol for 1 h had monomodal
distributions with median particle size of 88 nm.
In order to introduce the application of Ba3(PO4)2 nanopowders in organic synthesis, the preparation of 1-amidoalkyl-2-naphthol
derivatives was investigated, and as a preliminary test reaction, catalytic three-component reaction of bezaldehyde, 2-naphthol and an
acetamide in the presence of Ba3(PO4)2 nanopowder as a catalyst was examined (Scheme 1). Ba3(PO4)2 nanopowder exhibited high
activity and the corresponding product was produced in high yield (Table 1). The use of bulk commercial Ba3(PO4)2 instead of
Ba3(PO4)2 nanopowder in the test reaction gives the product in lower yield (72%) under the same reaction condition as solvent-free,
catalyst (0.083 mmol), T = 100 °C, time: 45 min. The higher surface area of Ba3(PO4)2 nanopowder is the reason for better catalytic
activities than those of bulk material.
To optimize the reaction conditions, the reaction was carried out using different solvents (Table 1, entries 2-7) or solvent-free
condition (Table 1, entry 1). It was found that solvent-free is the best conditions of the reaction in terms of reaction times and yields
(Table 1, entry 1). Polar solvents gave a low yield of product, but non-polar solvents did not affect the reaction, and no yield of product
was obtained in non-polar media.
Page 4 of 10

Secondly, the effect of temperature and catalyst amount on the reaction was investigated, and it was found that 0.1 mmol of
Ba3(PO4)2 at 100 °C catalyze the reaction smoothly with a high yield of product (Table 1, entry 13).
Finally, to understand the scope and limitation of this reaction, different aldehydes and ureas/amides were investigated (Table 2).
The reaction of 2-naphthol, with various benzaldehydes containing electron donation and electron withdrawing groups and acetamide /
benzamide /urea was carried out in the presence of 0.1 mmol Ba3(PO4)2 nanopowders at 100 °C and a series of 1-amidoalkyl-2-
naphthols were obtained in good to high yields (Table 2, entries 1-22). In all cases, benzaldehydes carrying either electron-donating or
electron-withdrawing groups reacted successfully and gave the products in high yields. However, in the case of alkylaldehydes,
complicated products were formed under the similar conditions, which probably resulted from the aldol formation (Table 2, entry 22).
The use of cyclohexanecarbaldehyde did not correspond to the expected product (Table 2, entry 23). Based on the obtained results, the
electronic effects and the steric effects of the substituents played significant roles in the yields of products. Aromatic aldehyde systems
that possessed substitutions at the ortho, meta, or para positions afforded products, however, aromatic aldehydes containing electron-
withdraing groups gave higher yields than those with electron-donating groups.
Encouraged by the results obtained with 2-naphthol, we extended this protocol to the one-pot, three-component reaction of aromatic
aldehyde, amides, and 2-hydroxydibenzofuran using the above reaction condition optimized for 2-naphthol. The reactions with various
aromatic aldehydes bearing electron-donating and electron-withdrawing groups and amides gave product in excellent yields (Table 3).
The use of 1-naphthol instead of 2-naphthol resulted in a complex mixture of products that cannot be separated easily from the
reaction mixture. Thus 1-naphthol is not found to be a suitable starting material.
On the basis of obtained results as well as literature surveys [4-29], a plausible mechanism was portrayed for the synthesis of 1-
amidoalkyl-2-naphthol derivatives (Scheme 2). At first the electrophilic center of aldehyde is more activated by the interaction of
oxygen nucleophile with barium phosphate which facilitates nucleophilic attachment of 2-naphthol to form intermediate A, which
continues via water elimination to ortho-quinone methides (B). Activation of this intermediate by barium phosphate catalyst following
by the Michael addition of the amide group leads to the formation of targeted molecules (Scheme 2).
Ba3(PO4)2
Ar
OH
O
Ba3(PO4)2
O
O
Ba3(PO4)2
-H2O
Ar
H
Ar
H
OH
A
O
Ar(H)
NH
Ar
H
O
O
Ar
H
O
Ba3(PO4)2
Ar
Ba3(PO4)2
NH2
(R)Ar
OH
B
Scheme 2. A plausible mechanism for the synthesis of 1-amidoalkyl-2-naphthol derivatives.
Finally, the crude product was dissolved in pure acetone and centrifuged to recover the catalyst by filtration (10 nm filter papers),
which was followed by washing several times with acetone, drying at 100 °C for 1 h, and reuse without significant loss of catalyst
activity (five runs were examined). The results of catalyst recovery are summarized in Fig. 4.
4. Conclusion
The nanopowder Ba3(PO4)2, prepared by a simple precipitation method, was used as an efficient catalyst for the preparation of 1-
amidoalkyl-2-naphthol derivatives. It was stated that the use of 0.083 mmol of Ba3(PO4)2 as catalyst for the catalytic condensation
reaction of aromatic aldehydes, 2-naphthol and amides / urea under ambient condition provides high yields of products. Certainly, the
simplicity of the accommodated catalytic system makes it suitable for further research and practical applications.
Acknowledgments
We are thankful to the Najafabad Branch, Islamic Azad University research council for partial support of this research
References
[1] T. Dingermann, D. Steinhilber, G. Folkers, In: Molecular Biology in Medicinal Chemistry, Wiley-VCH, 2004.
[2] A.Y. Shen, C.T. Tsai, C.L. Chen, Synthesis and cardiovascular evaluation of N-substituted 1-aminomethyl-2-naphthols, Eur. J. Med.
Chem. 34 (1999) 877-882.
[3] A.Y. Shen, C.L. Chen, C.I. Lin, Electrophysiological basis for the bradycardic effects of 1-(1-pyrrolidinylmethyl)-2-naphthol in rodents,
Chinese J. Physiol. 35 (1992) 45-54.
[4] S. Kantevari, S.V.N. Vuppalapati, L. Nagarapu, Montmorillonite K10 catalyzed efficient synthesis of amidoalkyl naphthols under solvent
free conditions, Catal. Commun. 8 (2007) 1857-1862.
Page 5 of 10

[5] N.P. Selvam, P.T. Perumal, A new synthesis of acetamido phenols promoted by Ce(SO4)2, Tetrahedron Lett. 47 (2006) 7481-7483.
[6] B. Das, K. Laxminarayana, B. Ravikanth, B.R. Rao, Iodine catalyzed preparation of amidoalkyl naphthols in solution and under solvent-
free conditions, J. Mol. Catal. A: Chem. 261 (2007) 180-183.
[7] L. Nagarapu, M. Baseeruddin, S. Apuri, S. Kantevari, Potassium dodecatungstocobaltate trihydrate (K5CoW12O40.3H2O): A mild and
efficient reusable catalyst for the synthesis of amidoalkyl naphthols in solution and under solvent-free conditions, Catal. Commun. 7
(2007) 1729-1734.
[8] M.M. Khodaei, A.R. Khosropour, H. Moghanian, A simple and efficient procedure for the synthesis of amidoalkyl naphthols by p-TSA in
solution or under solvent-free conditions, Synlett (2006) 916-920.
[9] S.B. Patil, P.R. Singh, M.P. Surpur, S.D. Samant, Ultrasound-promoted synthesis of 1-amidoalkyl-2-naphthols via a three-component
condensation of 2-naphthol, ureas/amides, and aldehydes, catalyzed by sulfamic acid under ambient conditions, Ultrason Sonochem. 14
(2007) 515-518.
[10] R.R. Nagawade, D.B. Shinde, Zirconyl(IV) chloride-catalyzed multicomponent reaction of β-naphthols: An expeditious synthesis of
amidoalkyl naphthols, Acta Chim. Slov. 54 (2007) 642-645.
[11] G. Srihari, M. Nagaraju, M.M. Murthy, Solvent-free one-pot synthesis of amidoalkyl naphthols catalyzed by silica sulfuric acid, Helv.
Chim. Acta 90 (2007) 1497-1504.
[12] S.B. Patil, P.R. Singh, M.P. Surpur, S.D. Samant, Cation exchanged resins: Efficient heterogeneous catalysts for facile synthesis of 1-
amidoalkyl-2-naphthols from one-pot, three-component condensations of amides/ureas, aldehydes, and 2-naphthol, Synth. Commun. 37
(2007) 1659-1664.
[13] R.R. Nagawade, D.B. Shinde, Sulphamic acid (H2NSO3H)-catalyzed multicomponent reaction of β-naphthol: An expeditious synthesis
of amidoalkyl naphthols, Chin. J. Chem. 25 (2007) 1710-1714.
[14] H.R. Shaterian, H. Yarahmadi, M. Ghashang, Silica supported perchloric acid (HClO4-SiO2): an efficient and recyclable heterogeneous
catalyst for the one-pot synthesis of amidoalkyl naphthols, Tetrahedron 64 (2008) 1263-1269.
[15] L.T. An, X.H. Lu, F.Q. Ding, W.Q. Jiang, J.P. Zou, Polymer-supported sulphonic acid catalyzed three-component one-pot synthesis of
α-amidoalkyl-β-naphthols, Chin. J. Chem. 26 (2008) 2117-2119.
[16] D. Kundu, A. Majee, A. Hajra, Zwitterionic-type molten salt: An efficient mild organocatalyst for synthesis of 2-amidoalkyl and 2-
carbamatoalkyl naphthols, Catal. Commun. 11 (2010) 1157-1159.
[17] A.R. Hajipour, Y. Ghayeb, N. Sheikhan, A.E. Ruoho, Bronsted acidic ionic liquid as an efficient and reusable catalyst for one-pot
synthesis of 1-amidoalkyl-2-naphthols under solvent-free conditions, Tetrahedron Lett. 50 (2009) 5649-5651.
[18] M.M. Heravi, N. Tavakoli-Hoseini, F.F. Bamoharram, Brønsted acidic ionic liquids as efficient catalysts for the synthesis of amidoalkyl
naphthols, Synth. Commun. 41 (2011) 298-306.
[19] A. Dorehgiraee, H. Khabazzadeh, K. Saidi, Heteropoly acid catalyzed synthesis of 1-amidoalkyl-2-naphthols in the presence of molten
tetraethyl ammonium chloride as an ionic liquid,Arkivoc (2009) 303-310.
[20] W. Su, W. Tang, J. Li, Strontium(II) triflate catalysed condensation of β-naphthol, aldehyde and urea or amides: a facile synthesis of
amidoalkyl naphthols, J. Chem. Res. (2008) 123-128.
[21] H.R. Shaterian, A. Hosseinian, M. Ghashang, PPA-SiO2 Catalyzed multicomponent synthesis of amidoalkyl naphthols, Synth. Commun.
38 (2008) 3375-3389.
[22] H.R. Shaterian, H. Yarahmadi, M. Ghashang, M. Safari Mehmandosti, N-Bromosuccinimide catalyzed one-pot and rapid synthesis of
acetamidobenzyl naphthols under mild and solvent-free conditions, Chin. J. Chem. 26 (2008) 2093-2097.
[23] H.R. Shaterian, H. Yarahmadi, Sodium hydrogen sulfate as effective and reusable heterogeneous catalyst for the one-pot preparation of
amidoalkyl naphthols, Arkivoc (2008) 105-114.
[24] H. Khabazzadeh, K. Saidi, N. Seyedi, Cu-exchanged heteropoly acids as efficient and reusable catalysts for preparation of 1-amidoalkyl-
2-naphthols, J. Chem. Sci. 121 (2009) 429-433.
[25]
H.R. Shaterian, H. Yarahmadi, M. Ghashang, One-pot synthesis of amidoalkyl naphthols using NaHSO4.SiO2 as an efficient and
recyclable heterogeneous catalyst, Turk. J. Chem. 33(2009) 1-9.
[26] H.R. Shaterian, H. Yarahmadi, M. Ghashang, An efficient, simple and expedition synthesis of 1-amidoalkyl-2-naphthols as 'drug like'
molecules for biological screening, Bioorg. Med. Chem. Lett. 18 (2008) 788-792.
[27] A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, et al., Trityl chloride as an efficient organic catalyst for the synthesis of 1-amidoalkyl-2-
naphtols in neutral media at room temperature, Appl. Catal. A: Gen. 386 (2010) 179-187.
[28] M. Dehbashi, M. Aliahmad, M.R. Mohammad Shafiee, M. Ghashang, Nickel doped SnO2 nanoparticles: Preparation and evaluation of
their catalytic activity in the synthesis of 1-amido alkyl-2-naphtholes, Synth. React. Inorg. Met. Org. Chem. 43 (2013) 1301-1306.
[29] M. Dehbashi, M. Aliahmad, M.R. Mohammad Shafiee, M. Ghashang, NiO-SnO2 nano-composite: Preparation and evaluation of their
catalytic activity in the synthesis of 1-amido alkyl-2-naphtholes, Lett. Org. Chem. 9 (2012) 711-719.
[30] J.E. Shelby, Introduction to Glass Science and Technology, 2nd ed. The Royal Society of Chemistry, 2005.
[31] A. Majjane, A. Chahine, M. Et-tabirou, et al., X-ray photoelectron spectroscopy (XPS) and FTIR studies of vanadium barium phosphate
glasses, Mater. Chem. Phys. 143 (2014) 779-787.
[32] L.L. Hench, R.J. Splinter, W.C. Allen, T.K. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials, J. Biomed.
Mater. Res. Symp. 2 (1972) 117-141.
[33] M. Ogino, L.L. Hench, Formation of calcium phosphate films on silicate glasses, J. Non-Cryst. Sol. 38-39 (1980) 673-678.
[34] F. Zhang, Z. Zhao, R. Tan, et al., Selective and effective adsorption of methyl blue by barium phosphate nano-flake, J. Colloid Interface
Sci. 386 (2012) 277-284.
[35] F. Zhang, W. Song, J. Lan, Effective removal of methyl blue by fine-structured strontium and barium phosphate nanorods, Appl. Surf.
Sci. 326 (2015) 195-203.
[36] L.K. Bharat, J.S. Yu, Ba3(PO4)2 hierarchical structures: synthesis, growth mechanism and luminescence properties, Cryst. Eng. Comm. 17
(2015) 4647-4653.
[37] M. Tong, J. Zhao, Y. Liang, et al., Synthesis and characterization of micro/nanostructured BaHPO4/Ba3(PO4)2/Ba5(PO4)3OH phases and
their luminescence, RSC Adv. 5 (2015) 27517-27525.
Page 6 of 10

[38] J.P. Liu, X.T. Huang, Y.Y. Li, et al., self-assembled cuo monocrystalline nanoarchitectures with controlled dimensionality and
morphology, Cryst. Growth Des. 6 ( 2006) 1690-1696.
[39] S.P. Garcia, S. Semancik, Controlling the morphology of zinc oxide nanorods crystallized from aqueous solutions:ꢀ the effect of crystal
growth modifiers on aspect ratio, Chem. Mater. 19 (2007) 4016-4022.
[40] M. Ghashang, Preparation and application of barium sulfate nano-particles in the synthesis of 2,4,5-triaryl and N-aryl(alkyl)-2,4,5-triaryl
imidazoles, Curr. Org. Synth. 9 (2012) 727-732.
[41] M. Ghashang, Zinc hydrogen sulfate promoted multi-component preparation of highly functionalized piperidines. Lett. Org. Chem. 9
(2012) 497-502.
[42] M.R. Mohammad Shafiee, M. Ghashang, A. Fazlinia, Preparation of 1,4-dihydropyridine derivatives using perchloric acid adsorbed on
magnetic Fe3O4 nanoparticles coated with silica, Curr. Nanosci. 9 (2013) 197-201.
[43] M. Ghashang, 1-Butyl-1-methylpyrrolidinium hydrogen sulfate promoted preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one
derivatives, Res. Chem. Intermed. 39 (2013) 2187-2195.
[44] M. Ghashang, S.S. Mansoor, K. Aswin, Thiourea dioxide: An efficient and reusable organocatalyst for the rapid one-pot synthesis of
pyrano[4,3-b]pyran derivatives in water, Chin. J. Catal. 35 (2014) 127-133.
[45] S Jabbarzarea, M. Ghashang, Preparation of 2-amino-5,7-dimethoxy-4-aryl/alkyl-4H-chromene-3-carbonitriles using Na2O-Al2O3-P2O5
glass–ceramic system, Chin. Chem. Lett. 26 (2015) doi:10.1016/j.cclet.2015.07.010.
Fig. 1. XRD pattern of Ba3(PO4)2 nano-particles.
Fig. 2. FE-SEM micrographs of Ba3(PO4)2 nano-particles.
Page 7 of 10

Fig. 3. Particle size distribution of Ba3(PO4)2 nano-particles.
Fig. 4. Catalyst recovery based on the reaction of 2-naphthol/benzaldehyde/acetamide.
Table 1
Optimization of the reaction conditions.
Entry
Solvent (20 mL)
t (°C)
100
Catalyst (mmol)
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.083
0.1
Time (min)
45
Yield (%)a
87
-
1
-
2
n-hexane
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25
50
80
100
130
100
100
100
100
100
100
150
150
150
150
150
150
300
200
120
45
30
30
25
20
60
90
250
3
CH2Cl2
-
4
CH3CN
10
15
5
-
-
10
40
87
83
81
77
78
61
43
20
5
EtOH
6
EtOAc
7
Et2O
8
9
-
-
-
-
-
-
-
-
-
-
-
10
11
12
13
14
15
16
17
18
0.3
0.5
0.05
0.025
0.01
a Isolated yield, based on 2-naphthol(1 mmol)/benzaldehyde (1 mmol)/acetamide (1.4 mmol).
Table 2
Preparation of 1-amidoalkyl-2-naphthol derivatives using Ba3(PO4)2 as catalyst (0.083 mmol, 100 °C).
Entry
1
Aldehyde
Amide source
O
Time (min)
45
Yield (%)*
87
M.P. [Lit. M.P.°C]Ref.
242-244 [245-246]26
CHO
NH2
O
220-220 [222-223]26
229-231 [230-232]26
227-229 [227-229]26
CHO
2
3
4
90
60
40
70
71
87
NH2
O
H3C
CHO
NH2
O
F
CHO
NH2
O
Br
207-209 [213-215]26
220-222 [223-225]26
CHO
Cl
5
6
85
50
74
87
NH2
O
CHO
NH2
Cl
Page 8 of 10

202-204 [201-203]26
243-245 [241-242]26
CHO
Cl
O
O
7
8
120
30
69
89
NH2
NH2
Cl
CHO
NO2
249-251 [248-250]26
241-243 [242-243]21
O
CHO
9
35
75
88
86
NH2
O2N
CHO
O
10
NH2
NH2
NH2
NH2
NH2
NH2
194-196 [193-194]10
184-186 [181–183]28
187-189 [187-188]21
263-265 [261-263]28
216-218 [216-217]9
CHO
O
O
O
O
O
11
12
13
14
15
120
80
85
90
84
79
88
F
CHO
Br
Cl
CHO
75
CHO
Cl
140
80
Cl
CHO
NO2
CHO
O
O
16
17
170
200
73
72
207-209 [204-206]28
NH2
NH2
175—177 [177—178]9
CHO
H3C
198-200 [200-202]22
171-173 [173-175]22
244-246 [241-243]28
211-213 [210-212]22
O
O
O
O
CHO
18
19
20
21
20
15
25
10
82
77
75
80
N
H
NH2
NH2
NH2
NH2
CHO
N
H
Cl
Cl
CHO
Cl
N
H
CHO
N
H
NO2
O
O
CHO
22
23
24
300
200
100
-
-
NH2
CHO
-
-
NH2
CHO
O
75
215-217 [-]
NH2
NH2
NH2
O
O
CHO
25
26
80
75
82
79
199-201 [-]
223-225 [-]
Br
CHO
NO2
* Isolated yield; 2-naphthol(1 mmol)/ aldehyde (1 mmol)/ amide (1.4 mmol)
Page 9 of 10

Table 3
Preparation of amidoalkyl dibenzofuranol derivatives using Ba3(PO4)2 as catalyst (0.083 mmol, 100 °C).
Entry
Aldehyde
Amide source
Time (h)
Yield (%)a
80
M.P. (°C)
208-210
O
CHO
1
24
NH2
CHO
O
2
3
4
5
6
30
30
20
20
20
70
65
89
94
89
189-191
194-196
227-229
230-232
221-223
NH2
H3C
CHO
O
NH2
H3CO
CHO
O
NH2
NO2
O
CHO
NH2
Br
CHO
O
NH2
NO2
O
CHO
CHO
7
8
20
24
80
70
229-231
217-219
NH2
Br
O
NH2
Br
a Isolated yield; 2-hydroxydibenzofuran (1 mmol)/ aldehyde (1 mmol)/ amide (1.4 mmol)
Page 10 of 10