One-pot synthesis of 1-amidoalkyl-2-naphthols from 2-naphthol, aldehydes, and amides under solvent-free conditions

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One-pot Synthesis of 1-Amidoalkyl-2-
naphthols from 2-Naphthol, Aldehydes,
and Amides under Solvent-free
Conditions
Min Wang a , Zhi-Guo Song b & Yan Liang a
a College of Chemistry and Chemical Engineering , Bohai University ,
Jinzhou, 121000, P. R. China
b Center for Science and Technology Experiment , Bohai University ,
Jinzhou, 121000, P. R. China
Published online: 06 Oct 2011.
To cite this article: Min Wang , Zhi-Guo Song & Yan Liang (2011) One-pot Synthesis of 1-Amidoalkyl-2-
naphthols from 2-Naphthol, Aldehydes, and Amides under Solvent-free Conditions, Organic
Preparations and Procedures International: The New Journal for Organic Synthesis, 43:5, 484-488,
DOI: 10.1080/00304948.2011.613700
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Organic Preparations and Procedures International, 43:484–488, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.613700
One-pot Synthesis of 1-Amidoalkyl-2-naphthols
from 2-Naphthol, Aldehydes, and Amides
under Solvent-free Conditions
Min Wang,1 Zhi-Guo Song,2 and Yan Liang1
1College of Chemistry and Chemical Engineering, Bohai University,
Jinzhou 121000, P. R. China
2Center for Science and Technology Experiment, Bohai University,
Jinzhou 121000, P. R. China
Amidoalkylnaphthols are important precursors for the synthesis of 1,3-amino oxygenated
compounds frequently found in biologically important natural products and potent drugs
including a number of nucleoside antibiotics and HIV protease inhibitors.1–3 Furthermore,
1-amidoalkyl-2-naphthols have been reported to show cardiovascular activity.4 To the best
of our knowledge, there have been reports on the synthesis of amidoalkylnaphthols cat-
alyzed by p-toluenesulfonic acid,5 H2NSO3H,6 Fe(HSO4)3,7 Sr(OTf)2,8 I2,9 Al(H2PO4)3,10
heteropoly acid K5CoW12O40·3H2O,11 Brønsted acidic ionic liquid,12 and heterogeneous
catalysts like Indion-130,13 montmorillonite K10,14 Al2O3-SO3H,15 and Al2O3-HClO4
16
via a one-pot MCR.17,18 However, some of the reported methods suffer from disadvan-
tages such as long reaction times, toxic and corrosive solvent, high reaction temperature
(>100◦C), and the need to use microwave or ultrasonic irradiation in some cases. Therefore,
it seemed desirable to develop greener and milder methods for the synthesis of amidoalkyl-
naphthols. During the course of our study on Lewis acid–catalyzed organic reactions, we
found stannous chloride to be an inexpensive and commercially available catalyst to ef-
ficiently catalyze the one-pot three-component Mannich-type reaction19 and now report a
one-pot MCR of 2-naphthol (1), aldehydes (2) and primary amides (3) in the presence of 2
mol% SnCl2·2H2O at 80◦C without solvent (Scheme 1).
Most products were formed within short reaction times and in excellent yields. The
results showed that SnCl2·2H2O is an excellent catalyst for this conversion. Compared
with the reported procedure employing Sr(OTf)2 as a catalyst,8 the new protocol has many
advantages such as use of small amounts of catalyst, and of no toxic solvent. Although Table
1 shows that the scope of the reaction is wide, no product was obtained with urea and thiourea
as a reaction partner. A possible mechanism for this transformation involves the initial
condensation of 2-naphthol with the aldehyde catalyzed by SnCl2·2H2O to generate an
Submitted March 11, 2011.
Address correspondence to Min Wang, College of Chemistry and Chemical Engineering, Bohai
University, Jinzhou 121000, P. R. China. E-mail: minwangszg@yahoo.com.cn
484

One-Pot Synthesis of Amidoalkylnaphthols
485
NHCOR2
OH
R1
OH
SnCl2 2H2O
R1CHO
R2CONH2
+
+
80 oC, solvent- free
4a-4v
1
2
3
Scheme 1
ortho-methylidenequinone (o-MQ) intermediate,5,20 this would then followed by Michael
addition of the amide to o-MQ generated in situ to give the desired amidoalkylnaphthols 4.
In conclusion, the mild and solvent-free conditions, short reaction times (0.2–7 h),
excellent yields (except for p-anisaldehyde), inexpensive, non-toxic, and commercially
available catalyst, and simple work-up make this procedure a useful process for the synthesis
of a variety of amidoalkylnaphthols.
Table 1
Preparation of Amidoalkylnaphthols Catalyzed by SnCl2·2H2O
Product
R1
R2
Time (h)
Yield (%)
mp (◦C)
lit. (◦C)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
0.3
1
1
1
0.2
1
0.5
2
2
0.3
0.2
3
96
94
93
86
94
93
91
92
66
85
90
83
82
89
85
83
88
84
77
30
80
77
236–238
262–264
234–236
238–240
266–268
185–186
237–239
208–210
205–208
244–246
239–241
243–245
218–220
256–258
244–246
204–206
235–237
227–229
219–220
185–187
176–179
224–226
233–23516
266–26720
233–23512
239–24121
—
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
4-ClC6H4
187–1888
—
2,4-Cl2C6H3
4-CH3C6H4
4-CH3OC6H4
CH3CH2
CH3CH2CH2
C6H5
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
209–21112
206–20820
244–2458
—
241–24311
218–21920
255–2568
245–24610
206–20720
237–23820
225–22822
222–2237
183–1857
173–17523
—
1
1.5
1
1
4-ClC6H4
1.5
1.5
2
7
1.5
1
2,4-Cl2C6H3
4-CH3C6H4
4-CH3OC6H4
CH3CH2
4t
4u
4v
CH3
CH3
CH3CH2CH2

486
Wang, Song, and Liang
Experimental Section
Melting points were determined using an RY-1 micromelting point apparatus. Infrared spec-
tra were recorded on a Scimitar 2000 series Fourier Transform instrument from VARIAN.
1H NMR spectra were obtained on a Bruker AV-500 spectrometer in DMSO-d6 using TMS
as an internal standard. 13C NMR spectra were performed on a Bruker AV-500 spectrome-
ter at 125 MHz in DMSO-d6 using TMS as an internal standard. Elemental analyses were
carried out on an EA 2400II elemental analyzer (Perkin Elmer).
General Procedure
To a mixture of 2-naphthol (1.44 g, 10 mmol), the aldehyde (10 mmol) and the amide (11
mol) with a stir bar was added SnCl2·2H2O (0.2 mmol), the reaction mixture was stirred
on a pre-heated water bath at 80◦C. After completion of the reaction (monitored by TLC,
v(ethyl acetate)/v(petroleum ether) = 1/3), the reaction mixture was cooled to R.T., where
upon it solidified. The solid mixture was tritwashed with 15 mL H2O/EtOH (v/v = 1/1),
and the collected solid was recrystallized from EtOH. The products were characterized by
comparison of their mp, IR, 1H NMR, 13C NMR and elemental analysis with those reported
for the authentic samples. Combustion analysis and spectral data for new compounds are
given below:
N-[(2-Chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl]benzamide (4e), white
1
solid, IR (KBr): 3426, 3067, 1633 cm−1; H NMR (500 MHz, DMSO-d6): δ 9.92 (s,
1H, OH), 9.01 (d, J = 6.2 Hz, 1H, NH), 8.08 (d, J = 8.6 Hz, 1H, ArH), 7.89 (d, J = 7.3
Hz, 2H, ArH), 7.82 (d, J = 7.5 Hz, 1H, ArH), 7.78 (d, J = 8.8 Hz, 1H, ArH), 7.52 (t, J =
7.3 Hz, 1H, ArH), 7.44-7.40 (m, 5H, ArH), 7.36 (d, J = 5.0 Hz, 1H, CH), 7.30-7.22 (m,
3H, ArH), 7.19 (d, J = 8.8 Hz, 1H, CH); 13C NMR (125 MHz, DMSO-d6): δ 165.3, 153.6,
138.7, 134.2, 132.9, 132.7, 131.1, 130.1, 129.4, 128.6, 128.5, 128.3, 128.1, 127.4, 126.6,
126.3, 122.8, 122.3, 118.6, 116.8, 48.6.
Anal. Calcd. for C24H18ClNO2: C, 74.32; H, 4.68; N, 3.61. Found: C, 74.25; H, 4.61;
N, 3.67.
N-[(2,4-Dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl]benzamide
(4g),
white solid, IR (KBr): 3423, 3069, 1634 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 9.97 (s,
1H, OH), 9.18 (d, J = 6.3 Hz, 1H, NH), 8.05 (d, J = 8.6 Hz, 1H, ArH), 7.89 (d, J = 7.2
Hz, 2H, ArH), 7.82 (d, J = 7.4 Hz, 1H, ArH), 7.78 (d, J = 8.8 Hz, 1H, ArH), 7.57 (d, J =
2.1 Hz, 1H, ArH), 7.52-7.42 (m, 5H, ArH), 7.37 (dd, J = 2.1, 6.3 Hz, 1H, CH), 7.30-7.27
(m, 2H, ArH), 7.18 (d, J = 8.8 Hz, 1H, ArH); 13C NMR (125 MHz, DMSO-d6): δ 165.5,
153.7, 138.2, 134.1, 133.6, 132.7, 132.1, 131.4, 131.2, 129.6, 128.6, 128.3, 128.1, 127.5,
126.7, 126.5, 122.6, 122.3, 118.6, 116.1, 48.3.
Anal. Calcd. for C24H17Cl2NO2: C, 68.26; H, 4.06; N, 3.32. Found: C, 68.35; H, 4.02;
N, 3.28.
N-[1-(2-Hydroxynaphthalen-1-yl)butyl]benzamide (4k), white solid. IR (KBr):
1
3416, 3222, 3204, 1632 cm−1; H NMR (500 MHz, DMSO-d6): δ 10.08 (s, 1H, OH),
8.60 (d, J = 6.3 Hz, 1H, NH), 8.22 (d, J = 7.6 Hz, 1H, ArH), 7.81 (t, J = 7.2 Hz, 3H, ArH),
7.71 (d, J = 8.8 Hz, 1H, ArH), 7.53-7.44 (m, 4H, ArH), 7.31 (t, J = 7.3 Hz, 1H, ArH), 7.20
(d, J = 8.8 Hz, 1H, ArH), 6.04 (q, J = 7.1 Hz, 1H, CH), 2.19-2.11 (m, 1H, CH2), 1.92-1.85
(m, 1H, CH2), 1.51-1.41 (m, 1H, CH2), 1.33-1.23 (m, 1H, CH2), 0.93 (t, J = 7.3 Hz, 3H,

One-Pot Synthesis of Amidoalkylnaphthols
487
CH3); 13C NMR (125 MHz, DMSO-d6): δ 165.2, 152.8, 134.7, 132.0, 131.0, 128.5, 128.4,
128.3, 128.2, 126.9, 126.2, 122.3, 119.8, 118.6, 118.5, 46.6, 36.0, 19.6, 13.8.
Anal. Calcd. for C21H21NO2: C, 78.97; H, 6.63; N, 4.39. Found: C, 78.87; H, 6.58; N,
4.43.
N-[1-(2-Hydroxynaphthalen-1-yl)butyl]acetamide (4v), white solid. IR (KBr):
1
3409, 3220, 2956, 1642 cm−1; H NMR (500 MHz, DMSO-d6): δ 9.86 (s, 1H, OH),
8.13 (d, J = 8.6 Hz, 1H, NH), 8.02 (s, 1H, ArH), 7.77 (d, J = 7.7 Hz, 1H, ArH), 7.68 (d,
J = 8.8 Hz, 1H, ArH), 7.46 (t, J = 7.2 Hz, 1H, ArH), 7.28 (t, J = 7.3 Hz, 1H, ArH), 7.18
(d, J = 8.8 Hz, 1H, ArH), 5.82 (q, J = 7.6 Hz, 1H, CH), 2.05-1.97 (m, 1H, CH2), 1.88-1.80
(m, 4H, CH2 and CH3), 1.40-1.30 (m, 1H, CH2), 1.22-1.13 (m, 1H, CH2), 0.88 (t, J =
7.4 Hz, 3H, CH3); 13C NMR (125 MHz, DMSO-d6): δ 168.4, 152.9, 132.2, 128.4, 128.2,
128.1, 126.0, 122.1, 119.8, 118.5, 45.5, 35.9, 22.7, 19.5, 13.7.
Anal. Calcd. for C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.77; H, 7.38; N,
5.36.
Acknowledgment
This research work was financially supported by the Education Committee of Liaoning
Province of China (No. 2009A033) and Committee of Science and Technology of Liaoning
Province of China (No. 20091001).
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