Environmentally friendly preparation of amidoalkyl naphthols

Article abstract of DOI:10.1080/00397910802006396

A new, facile, and cost-effective process involving the solvent-free synthesis of amidoalkyl naphthols using a three-component, one-pot condensation reaction of β-naphthol, aromatic aldehyde, and amides in the presence of Al(H2PO4)3 as heterogeneous catal

Full text of DOI:10.1080/00397910802006396

This article was downloaded by: [University of Illinois Chicago]
On: 25 July 2012, At: 17:23
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Environmentally Friendly
Preparation of Amidoalkyl
Naphthols
Hamid Reza Shaterian a , Azita Amirzadeh a
Fahimeh Khorami a & Majid Ghashang a
,
a Department of Chemistry, Faculty of Sciences,
University of Sistan and Baluchestan, Zahedan, Iran
Version of record first published: 28 Aug 2008
To cite this article: Hamid Reza Shaterian, Azita Amirzadeh, Fahimeh Khorami
& Majid Ghashang (2008): Environmentally Friendly Preparation of Amidoalkyl
Naphthols, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 38:17, 2983-2994
To link to this article: http://dx.doi.org/10.1080/00397910802006396
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.

The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 38: 2983–2994, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802006396
Environmentally Friendly Preparation of
Amidoalkyl Naphthols
Hamid Reza Shaterian, Azita Amirzadeh, Fahimeh Khorami, and
Majid Ghashang
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
Abstract: A new, facile, and cost-effective process involving the solvent-free
synthesis of amidoalkyl naphthols using a three-component, one-pot conden-
sation reaction of b-naphthol, aromatic aldehyde, and amides in the presence
of Al(H2PO4)3 as heterogeneous catalyst under thermal conditions and micro-
wave irradiation has been described. This new approach has the advantage of
consistently excellent yields and short reaction times. The catalyst has shown a
very stable catalytic activity in the reaction conditions and also can be recovered
and recycled.
Keywords: Aluminum tris(dihydrogen phosphate), amidoalkyl naphthol, hetero-
geneous catalyst, multicomponent reaction, solvent-free
INTRODUCTION
Solid-phase organic synthesis (SPOS) has become increasingly important
in synthesizing large numbers of combinatorial and parallel compound
collections.[1] Acidic catalysts have been used, mainly in industry, for pro-
ducing more than 1 ꢀ 108 Mt=year of products.[2] Among acidic catalysts,
the most commonly used are HF, H2SO4, HClO4, and H3PO4. Solid acids
have many advantages such as ease of handling and environmentally
safe disposal.[3,4] Also, wastes and by-products can be minimized or
avoided by developing cleaner synthetic routes.[5] Heterogeneous organic
Received December 31, 2007.
Address correspondence to Hamid Reza Shaterian, Department of Chemistry,
Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674,
Zahedan, Iran. E-mail: hrshaterian@hamoon.usb.ac.ir
2983

2984
H. R. Shaterian et al.
reactions have proven useful to chemists in the laboratory as well as in
the industrial context. These reactions are affected by the reagents
immobilized on the porous solid supports and have advantages over
the conventional solution-phase reactions because of the good dispersion
of active reagent sites, associated selectivity, and easier workup.[6] On the
other hand, thermal and microwave-assisted solvent-free organic
synthesis has attracted increasing attention by providing a much faster,
simpler, and more energy-efficient technique for rapid synthesis then
the conventional methods.
Compounds bearing 1,3-amino oxygenated functional groups are
ubiquitous to a variety of biologically important natural products and
potent drugs including a number of nucleoside antibiotics and HIV
protease inhibitors, such as ritonavir and lipinavir.[7,8] In this research,
we represent an advance in the context of synthetic methodology for
a class of biologically important molecules; it is noteworthy that
1-amidomethyl-2-naphthols can convert to important biologically active
1-aminomethyl-2-naphthol derivatives by an amide hydrolysis reaction.
The hypotensive and bradycardiac effects of these compounds have been
evaluated.[7,8] Amidoalkyl naphthols have been prepared by multicompo-
nent condensation of aryl aldehydes, 2-naphthol, and acetonitrile or
amide in the presence of Lewis or Brønsted acid catalysts such as mont-
morillonite K-10 clay,[9] Ce(SO4)2,[10] iodine,[11] K5CoW12O40ꢁ3H2O,[12]
p-TSA,[13] sulfamic acid,[14] zirconyl(IV) chloride,[15] silica sulfuric
acid,[16] and cation-exchanged resins.[17]
However, some of these catalysts suffer from drawbacks such as pro-
longed reaction times, low yields, toxicity, and low recovery and reusabil-
ity of the catalyst. Therefore, introducing clean processes and utilizing
ecofriendly and green catalysts that can be simply recycled at the end of
reactions have received attention. Herein, we report a simple and efficient
method for one-pot preparation of 1-amidoalkyl-2-naphthols using
Al(H2PO4)3 as catalyst by the three-component condensation (Scheme 1).
Scheme 1. One-pot preparation of 1-amidoalkyl-2-naphthols using Al(H2PO4)3
as catalyst.

Amidoalkyl Naphthols
2985
RESULTS AND DISCUSSION
To find optimum conditions, first the reaction of benzaldehyde,
2-naphthol, and acetamide in the presence of Al(H2PO4)3 (0.05 g) as a
model was performed under thermal solvent-free conditions at different
temperatures in an oil bath and also in a microwave oven under different
irradiation power. As can be seen from Table 1, shorter time and excel-
lent yield were achieved at 125 ꢂC and 450 W respectively (Table 1).
Next, to optimize the quantity of the catalyst, the reaction of benzal-
dehyde with 2-naphthol and acetamide was carried out using different
quantities of Al(H2PO4)3 under solvent-free thermal conditions at
125 ꢂC (Table 2). As can be seen from Table 2, the best results were
obtained using 0.075 g of the catalyst.
Thus, we prepared a range of 1-amidoalkyl-2-naphthols under
optimized reaction conditions: (un)substituted benzaldehyde (1 equiv),
2-naphthol (2 equiv), and acetamide or benzamide in the presence of
Al(H2PO4)3 (0.075 g) as a catalyst under solvent-free thermal (method A)
and microwave irradiation (method B) conditions (Table 3).
As summarized in Table 3, 1-amidoalkyl-2-naphthol derivatives were
obtained in good to excellent yields in short reaction times without
formation of any side products such as dibenzoxanthenes (Scheme 1
and Table 3). The reaction time upon microwave irradiation can be
shortened considerably as compared to solvent-free thermal conditions.
Aromatic aldehydes with substituents carrying either electron-donating
or electron-withdrawing groups reacted successfully and gave the
Table 1. Effect of temperature and MW irradiation power in
the synthesis of N-[phenyl-(2-hydroxynapthalen-1-yl)-methyl]
acetamide in the presence of Al(H2PO4)3 (0.05 g) under ther-
mal solvent-free and microwave (MW) irradiation conditionsa
Entry
Temperature (ꢂC)
Time
48 h
Yield (%)b
1
2
3
4
5
6
7
8
50
80
100
125
67
80
89
92
55
58
63
67
15 h
80 min
31 min
1.5 min
2.5 min
3 min
MW (1000 W)
MW (850 W)
MW (600 W)
MW (450 W)
4 min
aThe molar ratio of benzaldehyde=2-naphthol=acetamide is
1=1=1.2.
bYields refer to pure isolated product.

2986
H. R. Shaterian et al.
Table 2. Effect of amount of Al(H2PO4)3 in the synthesis of
N-[phenyl-(2-hydroxynapthalen-1-yl)-methyl]acetamide under
thermal solvent-free conditionsa
Entry
Catalyst (g)
Time (min)
Yield (%)b
1
2
3
4
5
0.05
0.075
0.1
0.15
0.2
31
21
17
15
14
92
93
90
87
85
aThe molar ratio of benzaldehyde=2-naphthol=acetamide is
1=1=1.2.
bYields refer to the pure isolated products.
products in high yields. The aromatic aldehydes with electron-
withdrawing groups reacted faster than the aromatic aldehydes with
electron-donating groups, as would be expected. Electron-withdrawing
groups on the benzaldehyde in the o-QMs intermediates increase the rate
of the 1,4-nucleophilic addition reaction because the alkene lowest
unoccupied molecular orbital (LUMO) is at lower energy in the presence
of electron-withdrawing groups compared with electron-donating
groups.[18] Aliphatic aldehydes such as propionaldehyde were also exam-
ined, but the yields were trace amounts compared to aromatic aldehydes
(Table 3, entry 21).
Al(H2PO4)3 can act as a Brønsted acid and also a Lewis acid because
of the empty aluminum p orbital. Although an operation process chart
(OPC) of catalyst in this work is unknown, a possible mechanism is pro-
posed in Scheme 2. The reaction of 2-naphthol with aromatic aldehydes
in the presence of an acid catalyst is known to give ortho-quinone
methides (o-QMs).[13] The same o-QMs, generated in situ, have been
reacted with acetamide or benzamide via conjugate addition to form
1-amidoalkyl-2-naphthol derivatives.
To show the merit of the present work in comparison with reported
results in the literature, we compared results of Al(H2PO4)3 with mont-
morillonite K-10 clay,[9] Ce(SO4)2,[10] iodine,[11] and K5CoW12-
O40ꢁ3H2O[12] in the synthesis of 1-amidomethyl-2-naphthol derivatives.
As shown in Table 4, Al(H2PO4)3 can act as an effective catalyst with
respect to reaction times and yields of the obtained products. Thus, the
present protocol with Al(H2PO4)3 as catalyst is convincingly superior
to the recently reported catalytic methods.
The reusability of the catalysts is an important benefit and makes them
useful for commercial applications. Thus, the recovery and reusability of

2987

2988
H. R. Shaterian et al.
Scheme 2. Suggested mechanism for preparation of 1-amidoalkyl-2-naphthols.
Al(H2PO4)3 was investigated. The recyclability of the catalyst in the reac-
tion of benzaldehyde and 2-naphthol in the presence of Al(H2PO4)3 was
checked (Table 3, method A, entry 2). The separated catalyst can be reused
after washing with acetone and drying at 100 ꢂC. The catalyst was recov-
ered in excellent yields and was used in the reaction five times; it showed
the same activity as fresh catalyst without any loss of its activity.
In conclusion, an efficient method for synthesis of 1-amidoalkyl-2-
naphthols via a three-component reaction of aryl aldehydes, 2-naphthol,
and acetamide or benzamide in the presence of Al(H2PO4)3 as effective
catalyst under thermal solvent-free and microwave irradiation was
described. The operational simplicity of the procedure, shorter reaction
times, simple workup, environmental friendliness, excellent yield, cost-
effective recovery, and reusability of the catalyst for a number of times
without appreciable loss of activity are also attractive. The catalyst can
Table 4. Comparison results of Al(H2PO4)3 with montmorillonite K-10 clay,[9]
Ce(SO4)2,[10] iodine,[11] and K5CoW12O40ꢁ3H2O[12] in the synthesis amidoalkyl
naphthola
Molar ratio
aldehyde=
2-naphthol
(catalyst)
Yield
Time (%)
Entry
Catalyst
Ce(SO4)2
Conditions
1
2
3
1=1=(1 mol%) Reflux
1=1=(5 mol%) Solvent-free, 125 ꢂC 5.5 h
1=1=0.1 g
36 h
72
85
89
I2
Montmorillonite
K10 clay
Solvent-free, 125 ꢂC 1.5 h
4
5
K5CoW12O40 ꢁ 3H2O 1=1=0.01 g
Solvent-free, 125 ꢂC 2 h
90
Al(H2PO4)3 1=1=0.075 g
Solvent-free, 125 ꢂC 21 min 93
aBased on 2-naphthol, benzaldehyde, and acetamide.

Amidoalkyl Naphthols
2989
be prepared easily with readily available inexpensive reagents, which are
heterogeneous and nonhazardous.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used without
further purification. Al(H2PO4)3 was prepared according to the reported
procedure.[19,20] All yields refer to isolated products after purification.
Products were characterized by comparison with authentic samples and
by spectroscopy data (IR, NMR spectra). The NMR spectra were
recorded on a Bruker Avance DPX 300- and 500-MHz instrument. The
spectra were measured in DMSO-d6 relative to TMS (0.00 ppm). IR spec-
tra were recorded on a Jasco FT-IR 460-plus spectrophotometer. Mass
spectra were recorded on an Agilent technologies 5973 network mass
selective detector (MSD) operating at an ionization potential of 70 eV.
Melting points were determined in open capillaries with a Buchi 510
melting-point apparatus. Thin-layer chromatography (TLC) was per-
formed on silica-gel polygram SIL G=UV 254 plates.
[19,20]
Preparation of Al(H2PO4)3
The catalyst was prepared by taking a mixture of alumina (neutral) and
concentrated phosphoric acid (88%) in a silica boat maintaining the
molar ratio of alumina–H3PO4 as 1:3 and heating at 200–220 ꢂC on a
hot sand bath [Eq. (1)]. The mixture was stirred at the stipulated tempera-
ture until the swampy mass solidified, and then the temperature was
reduced to around 100 ꢂC. The whole was then placed in a vacuum des-
iccator and cooled to ambient temperature. The catalyst thus prepared
was finally transferred and stored in an air-tight sample vial. The catalyst
has been reported previously in the literature and was characterized by
comparison of IR spectroscopy and the powder XRD with known
samples.[19,20] [Al(H2PO4)3: 317.84 g molꢃ1].
Al2O3 þ H3PO4
AlðH2PO4Þ3 þ H2O"
ð1Þ
ꢃ!Heat20
General Procedure: Preparation of Amidoalkyl Naphthols Using
Al(H2PO4)3 as Catalyst
To a mixture of 2-naphthol (4 mmol), aldehydes (4 mmol), and acetamide
(4.8 mmol), Al(H2PO4)3 (0.3 g) was added. The mixture was stirred at
125 ꢂC in an oil bath (method A) or inserted in a microwave oven

2990
H. R. Shaterian et al.
(Samsung model KE300R) at 450 W (method B) for the appropriate time
(Table 3). The reaction was followed by thin-layer chromatography
(TLC). After completion, the mixture was cooled to 25 ꢂC; then the solid
material was dissolved in acetone. The catalyst was recovered by simple
filtration. Then filtrate solution was evaporated under vacuum and the
solid obtained was recrystallized from aqueous EtOH (20%).The spectral
data of some representative amidoalkyl naphthols are given next.
N-[Phenyl-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide[10]
(Table 3, Entry 2)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.95 (s, 3H), 7.10–7.19 (m, 4H),
7.21–7.25 (m, 4H), 7.33 (t, J ¼ 7.4 Hz, 1H), 7.74 (d, J ¼ 9.0 Hz, 1H,),
7.77 (d, J ¼ 8.1 Hz, 1H), 7.84 (s, 1H), 8.44 (d, J ¼ 8.4 Hz, 1H), 10.02
(s, 1H) ppm; 13C NMR (125 MHz, DMSO-d6): 23.2, 40.3, 119.2, 119.4,
122.9, 123.8, 126.6, 126.8, 128.5, 126.8, 128.9, 129.1, 129.8, 132.8,
143.1, 153.7, 169.0 ppm; IR (KBr, cmꢃ1): 3399, 3246, 3062, 1640, 1582,
1514, 1372, 1337, 1060, 808, 742, 696, 623.
N-[(4-Chloro-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide[10]
(Table 3, Entry 4)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.95 (s, 3H), 7.04 (d, J ¼ 8.0 Hz,
1H), 7.10 (d, J ¼ 8.5 Hz, 2H), 7.17 (d, J ¼ 8.5 Hz, 1H), 7.18 (m, 3H),
7.32 (t, J ¼ 7.6 Hz, 1H), 7.74 (m, 3H), 8.43 (d, J ¼ 8.5 Hz, 1H), 10.10
(s, 1H) ppm; 13C NMR (125 MHz, DMSO-d6): 20.5, 23.2, 48.0, 118.8,
119.1, 123.1, 126.8, 128.9, 128.5, 129.1, 129.4, 130.1, 131.2, 132.8,
142.4, 153.7, 169.7 ppm; IR (KBr, cmꢃ1): 3392, 2962, 2700, 2613, 1637,
1577, 2523, 1490, 1436, 1374, 1331, 1278, 1243, 1171, 1091, 819, 747,
588, 499.
N-[(3-Nitro-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide[10]
(Table 3, Entry 6)
1H NMR (500 MHz, DMSO-d6): d ¼ 2.01 (s, 3H), 7.17 (t, J ¼ 8.0 Hz,
1H), 7.19 (d, J ¼ 8.6 Hz, 1H), 7.24 (t, J ¼ 7.5 Hz, 1H), 7.38 (t, J ¼ 7.4 Hz,
Hz, 1H), 7.51 (m, 2H), 7.78 (t, J ¼ 8.6 Hz, 2H), 7.83 (br, 1H), 7.98
(m, 2H), 8.58 (d, J ¼ 8.0 Hz, 1H), 10.16 (s, 1H) ppm; 13C NMR
(125 MHz, DMSO-d6): 23.1, 48.2, 118.3, 118.9, 120.9, 121.8, 123.2,
127.3, 123.2, 128.9, 129.2, 130.1, 130.5, 132.6, 133.4, 145.9, 148.2,

Amidoalkyl Naphthols
2991
153.9, 170.3 ppm; IR (KBr, cmꢃ1): 3373, 3088, 2598, 1645, 1524, 1350,
1232, 1158, 1063, 808, 705.
N-[(4-Fluoro-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide[10]
(Table 3, Entry 7)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.94 (s, 3H), 7.01 (t, J ¼ 9.0 Hz,
2H), 7.06 (d, J ¼ 8.1 Hz, 1H), 7.11 (m, 2H), 7.17 (t, J ¼ 8.0 Hz, 1H),
7.22 (t, J ¼ 7.4 Hz, 1H), 7.31 (t, J ¼ 8.1 Hz, 1H), 7.74 (m, 3H), 8.45
(d, J ¼ 8.5 Hz, 1H), 10.04 (s, 1H) ppm; 13C NMR (125 MHz, DMSO-
d6): 23.1, 47.7, 115.0, 115.2, 118.9, 119.0, 122.8, 126.8, 128.2, 128.4,
128.8, 129.1, 129.8, 132.8, 139.2, 153.5, 160.2, 162.3, 169.8 ppm; IR
(KBr, cmꢃ1): 3392, 2974, 1627, 1576, 1508, 1438, 1334, 1225, 1062,
823, 748, 601, 489.
N-[(2,5-Dimethoxy-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-
acetamide (Table 3, Entry 17)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.88 (s, 3H), 3.48 (s, 3H), 3.64
(s, 3H), 6.72–6.77 (m, 2H), 7.10–7.23 (m, 4H), 7.39 (s, 1H), 7.66–7.73
(m, 2H), 8.15–8.27 (m, 2H), 9.75 (s, 1H) ppm; 13C NMR (125 MHz,
DMSO-d6): 22.5, 44.4, 55.2, 55.9, 111.1, 111.9, 115.7, 118.5, 118.9,
122.0, 123.2, 125.7, 128.1, 128.6, 131.7, 132.4, 150.7, 152.7, 153.1,
168.1 ppm.; IR (KBr, cmꢃ1): 3365, 3174, 1644, 1497, 1436, 1277, 1218,
1052, 819, 727, 624.; MS: m=z ¼ 351 (Mþ, 17.83%), 308 (5.82%), 276
(5.87%), 262 (36.04%), 261 (100.00%), 218 (16.71%), 144 (6.60%), 115
(7.99%). Anal. calcd. for C21H21NO4: C, 71.78; H, 6.02; N, 3.99%.
Found: C, 71.73; H, 5.93; N, 4.08%.
N-[(4-Methyl-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide
(Table 3, Entry 18)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.96 (s, 3H), 2.21 (s, 3H), 7.03–7.08
(m, 5H), 7.19 (d, J ¼ 8.8 Hz, 1H), 7.24 (t, J ¼ 7.1 Hz, 1H), 7.34 (m, 1H),
7.74 (d, J ¼ 8.8, 1H), 7.78 (d, J ¼ 7.9 Hz, 1H), 7.82 (br, 1H), 8.36
(d, J ¼ 8.1, 1H), 9.91 (s, 1H) ppm; 13C NMR (125 MHz, DMSO-d6):
20.4, 22.6, 47.6, 118.4, 118.9, 122.2, 123.1, 125.9, 126.1, 128.3, 128.4,
128.9, 132.2, 134.9, 139.4, 143.2, 152.9, 168.9 ppm; IR (KBr, cmꢃ1):
3396, 3055, 2923, 1625, 1515, 1437, 1276, 1181, 813, 744, 482.; MS:
m=z ¼ 305 (Mþ , 21%), 246 (29.158%), 245 (50.55%), 231 (100%), 232

2992
H. R. Shaterian et al.
(31.20%), 202 (16.12%), 115 (10.04%). Anal. calcd. for C20H19NO2: C,
78.66; H, 6.27; N, 4.59%. Found: C, 78.72; H, 6.21; N, 4.63%.
N-[(4-Nitro-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide
(Table 3, Entry 19)
1H NMR (500 MHz, DMSO-d6): d ¼ 2.02 (s, 3H), 7.19 (d, J ¼ 8.0 Hz,
1H), 7.22 (d, J ¼ 8.8 Hz, 1H), 7.28 (t, J ¼ 7.5 Hz, 1H), 7.41 (t, J ¼ 7.3
Hz, 1H), 7.52–7.58 (m, 2H), 7.81 (t, J ¼ 9.4 Hz, 2H), 7.87 (d, J ¼ 7.0 Hz,
Hz, 1H), 8.03 (m, 2H), 8.60 (d, J ¼ 8.0 Hz, 1H), 10.11 (s, 1H) ppm; 13C
NMR (125 MHz, DMSO-d6): 22.5, 47.6, 117.7, 118.4, 120.3, 121.1,
122.5, 126.6, 128.3, 129.4, 129.8, 132.1, 132.7, 145.3, 147.7, 153.2,
169.5 ppm; IR (KBr, cmꢃ1): 3391, 3267, 2593, 1648, 1603, 1522, 1438,
1063, 825, 739, 447.; MS: m=z ¼ 336 (Mþ , 26.66%), 319 (75.99%), 276
(52.02%), 260 (54.15%), 231 (63.80%), 202 (45.11%), 230 (100%), 115
(18.05%). Anal. calcd. for C19H16N2O4: C, 67.85; H, 4.79; N, 8.33%.
Found: C, 67.91; H, 4.81; N, 8.24%.
N-[(3-Fluoro-phenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide
(Table 3, Entry 20)
1H NMR (500 MHz, DMSO-d6): d ¼ 1.98 (s, 3H), 6.92–6.98 (m, 3H),
7.12 (d, J ¼ 8.3 Hz, 1H), 7.19–7.27 (m, 3H), 7.37 (t, J ¼ 7.3 Hz, 1H),
7.76 (d, J ¼ 8.6 Hz, 1H), 7.80 (d, J ¼ 8.0 Hz, 1H), 7.84 (br, 1H), 8.44
(d, J ¼ 8.2 Hz, 1H), 10.01 (s, 1H) ppm; 13C NMR (125 MHz, DMSO-
2
2
d6): 22.5, 47.5, 112.5 (d, JC-F ¼ 22.1 Hz), 112.7 (d, JC-F ¼ 20.9 Hz),
118.3, 118.4, 122.1, 122.4, 122.9, 126.4, 128.3, 128.5, 129.4, 129.8 (d,
3
1
3JC-F ¼ 8.1 Hz), 132.1, 145.9 (d, JC-F ¼ 6.6 Hz), 153.1, 162.0 (d, JC-
¼ 241.2 Hz), 169.3 ppm; IR (KBr, cmꢃ1): 3410, 3160, 1640, 1589,
F
1545, 1484, 1439, 1335, 1280, 1064, 989, 814, 497.; MS: m=z ¼ 310
(4.79%), 309 (Mþ, 21.45%), 251 (9.00%), 250 (51.75%), 249
(100.00%), 231 (14.44%), 220 (16.11%), 122 (7.31%), 115 (9.01%). Anal.
calcd. for C19H16FNO2: C, 73.77; H, 5.21; N, 4.53%. Found: C, 73.74; H,
5.25; N, 4.48%.
ACKNOWLEDGMENTS
We are thankful to the Sistan and Baluchestan University Research
Council for the partial support of this research.

Amidoalkyl Naphthols
REFERENCES
2993
1. Bannwarth, W.; Hinzen, B. Combinatorial Chemistry: From Theory to
Application; Wiley=VCH: Weinheim, Germany, 2006.
2. Lowrie, J. F.; DeLilse, R. K.; Hobbs, D. W.; Diller, D. J. The different
strategies for designing gpcr and kinase targeted libraries. Comb. Chem. High
Throughput Screening 2004, 7, 495–510.
3. Corma, A. Solid acid catalysts. Curr. Opin. Solid State Mat. Sci. 1997, 2, 63–75.
4. Corma, A.; Garcia, H. Organic reactions catalyzed over solid acids. Catal.
Today 1997, 38, 257–308.
5. Sikdar, S. K.; Howell, S. G. On developing cleaner organic unit processes.
J. Cleaner Production 1998, 6, 253–259.
6. Varma, R. S. Solvent-free organic syntheses using supported reagents and
microwave irradiation. Green Chem. 1999, 1, 43–55.
7. Juaristi, E. Enantioselective Synthesis of b-Amino Acids; John Wiley & Sons:
New York, 1997.
8. Dingermann, T.; Steinhilber, D.; Folkers, G. In Molecular Biology in
Medicinal Chemistry; Wiley-VCH, Weinheim, 2004.
9. Kantevari, S.; Vuppalapati, S. V. N.; Nagarapu, L. Montmorillonite
K10 catalyzed efficient synthesis of amidoalkyl naphthols under solvent free
conditions. Catal. Commun. 2007, 8, 1857–1862.
10. Selvam, N. P.; Perumal, P. T. A new synthesis of acetamido phenols
promoted by Ce(SO4)2. Tetrahedron Lett. 2006, 47, 7481–7483.
11. Das, B.; Laxminarayana, K.; Ravikanth, B.; Rao, B. R. Iodine catalyzed
preparation of amidoalkyl naphthols in solution and under solvent-free
conditions. J. Mol. Catal. A: Chem. 2007, 261, 180–183.
12. Nagarapu, L.; Baseeruddin, M.; Apuri, S.; Kantevari, S. Potassium dode-
catungstocobaltate trihydrate (K5CoW12O40ꢁ3H2O): A mild and efficient
reusable catalyst for the synthesis of amidoalkyl naphthols in solution and
under solvent-free conditions. Catal. Commun. 2007, 7, 1729–1734.
13. Khodaei, M. M.; Khosropour, A. R.; Moghanian, H. A simple and efficient
procedure for the synthesis of amidoalkyl naphthols by p-TSA in solution or
under solvent-free conditions. Synlett 2006, 6, 916–920.
14. Patil, S. B.; Singh, P. R.; Surpur, M. P.; Samant, S. D. 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. 2007, 14, 515–518;
(b) Nagawade, R. R.; Shinde, D. B. Sulphamic acid (H2NSO3H)-catalyzed
multicomponent reaction of b-naphthol: An expeditious synthesis of
amidoalkyl naphthols. Chin. J. Chem. 2007, 25, 1710–1714.
15. Nagawade, R. R.; Shinde, D. B. Zirconyl(IV) chloride–catalyzed multicom-
ponent reaction of b-naphthols: An expeditious synthesis of amidoalkyl
naphthols. Acta Chim. Slov. 2007, 54, 642–646.
16. Srihari, G.; Nagaraju, M.; Murthy, M. M. Solvent-free one-pot synthesis of
amidoalkyl naphthols catalyzed by silica sulfuric acid. Helv. Chim. Acta 2007,
90, 1497–1504.

2994
H. R. Shaterian et al.
17. Patil, S. B.; Singh, P. R.; Surpur, M. P.; Samant, S. D. 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. 2007, 37, 1659.
18. Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry;
University Science Books: Sausalito, California, 2006.
19. Bharadwaj, S. K.; Hussain, S.; Kar, M.; Chaudhuri, M. K. Al(H2PO4)3: An
efficient catalyst for nitration of organic compounds with nitric acid. Catal.
Commun. 2008, 9, 919.
20. d’Yvoire, F. Bull. Soc. Chim. Fr. 1961, 2277, pdf file no.00-014-0546.