Efficient one-pot synthesis of 1-carbamatoalkyl-2-naphthols using aluminum methanesulfonate as a reusable catalyst

Article abstract of DOI:10.1007/s11164-012-0744-1

A wide range of 1-carbamatoalkyl-2-naphthols were synthesized via a one-pot three-component condensation of 2-naphthol, aldehydes, and carbamates in the presence of aluminum methanesulfonate at 70 C under solvent-free conditions. The catalyst is reusable

Full text of DOI:10.1007/s11164-012-0744-1

Res Chem Intermed (2013) 39:2123–2131
DOI 10.1007/s11164-012-0744-1
Efficient one-pot synthesis of 1-carbamatoalkyl-
2-naphthols using aluminum methanesulfonate
as a reusable catalyst
•
Zhiguo Song Xiaohu Sun Lianli Liu Yan Cui
•
•
Received: 27 June 2012 / Accepted: 24 July 2012 / Published online: 5 August 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A wide range of 1-carbamatoalkyl-2-naphthols were synthesized via a
one-pot three-component condensation of 2-naphthol, aldehydes, and carbamates in
the presence of aluminum methanesulfonate at 70 °C under solvent-free conditions.
The catalyst is reusable and could be recycled for several runs without any distinct
decrease in its efficiency. A plausible mechanism for this three-component reaction
was proposed.
Keywords Carbamatoalkyl naphthol Á Aluminum methanesulfonate Á
Multicomponent reaction Á Solvent-free
Introduction
Compounds containing 1,3-amino-oxygenated functional groups are frequently
found in biologically active natural products and potent drugs such as nucleoside
antibiotics and HIV protease inhibitors [1–3]. Recently, we have reported the
reactions of 2-naphthol, aldehydes, and amides or urea to form amidoalkyl naphthol
derivatives [4], which proceed through the in situ formation of ortho-quinone
methides (o-QMs), intermediates with amide acting as a nucleophile. Carbamates
instead of amides in the mentioned reaction produce carbamatoalkyl naphthols,
which can be deprotected more easily than the amide group [5]. Amidoalkyl
naphthols and carbamatoalkyl naphthols are all important intermediates for
preparing 1-aminomethyl-2-naphthols, which exhibit important cardiovascular
activity [6]. Therefore, the discovery of simple and green methods for synthesis
of carmatoalkyl naphthols is of prime importance.
Z. Song (&) Á X. Sun Á L. Liu Á Y. Cui
Management Center for Experiment, Bohai University, Jinzhou 121000, People’s Republic of China
e-mail: lnszgsky@yahoo.com.cn
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NHCO2R2
OH
R1
OH
.
Al(MS)3 4H2O (2 mol%)
R1CHO
NH2CO2R2
+
+
70 oC, solvent- free
3
1
2
4a-4x
Scheme 1 Al(MS)3Á4H2O-catalyzed synthesis of 1-carmatoalkyl-2-naphthols under solvent-free
conditions
To the best of our knowledge, the synthesis of carbamatoalkyl naphthols have
been largely overlooked, and only a few references about their synthesis have been
reported [7–17]. In these references, 1-carmatoalkyl-2-naphthols can be synthesized
by a one-pot three-component reaction from 2-naphthol, aldehydes, and methyl or
benzyl carbamates. Though these methods achieved good results, many of them
suffer from at least one of the following disadvantages: low yields, expensive
catalyst, higher reaction temperature ([100 °C), and a large excess of reagents and
catalysts (10 mol%). Now, during our continuous study on green and efficient
multicomponent reactions, we report here a one-pot three-component synthesis of
1-carmatoalkyl-2-naphthols from equivalent 2-naphthol, aldehydes, and methyl/
ethyl/benzyl carbamates in the presence of 2 mol% aluminum methanesulfonate
(Al(MS)3Á4H2O) under solvent-free conditions at 70 °C (Scheme 1). Metal
methanesulfonates (M(MS)xÁaH2O) as water-tolerant Lewis acids catalysts have
been well documented in recent years [18–24]. For this, the new synthetic protocol
enlarges the application scope of M(MS)xÁaH2O in organic synthesis.
Experimental
General
Melting points were determined by using an RY-1 micromelting point apparatus.
Infrared spectra were recorded on a Varian Scimitar 2000 series Fourier transform
instrument. 1H and 13C NMR spectra were recorded on an Agilent 400-MR
instrument in DMSO-d6 using TMS as an internal standard. Mass spectra were
obtained with an Agilent 1100 series LC/MSD VL ESI instrument. Elemental
analyses (C, H, N) were conducted using the Elemental Analyzer EA 2400II (Perkin
Elmer). Metal methanesulfonates were synthesized according to Ref. [25], and the
characterized results of Al(MS)3Á4H2O were consistent with those in Ref. [24].
General procedure for preparation of 1-carmatoalkyl-2-naphthols catalyzed
by Al(MS)3Á4H2O
A mixture of 2-naphthol 1 (0.721 g, 5 mmol), aldehydes 2 (5 mmol), carbamates 3
(5 mmol), and Al(MS)3Á4H2O (0.038 g, 0.1 mmol) was magnetically stirred at
70 °C in a water bath and the reaction was followed by TLC. After completion, the
mixture was cooled to room temperature, washed with cold water, and recrystallized
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Efficient one-pot synthesis of 1-carbamatoalkyl-2-naphthols
2125
from aqueous EtOH (60 %, v). The filtrate containing the catalyst was evaporated
under reduced pressure to give the recovered catalyst, which could be reused
1
without further treatment. The products were characterized by IR, H NMR, 13C
NMR, LC/MS, and elemental analysis. Spectral data for some new compounds are
given below:
Methyl ((2-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4e):
white solid, IR (KBr): 3,431, 3,220, 1,690, 1,527, 1,341, 1,051, 819, 753,
1
706 cm-1; H NMR (400 MHz, DMSO-d6): d 9.96 (s, 1H, OH), 8.04 (d, 1H,
J = 8.2 Hz, NH), 7.86 (d, 1H, J = 7.1 Hz, ArH), 7.77 (q, 2H, J = 8.6 Hz, ArH),
7.52 (d, 1H, J = 4.6 Hz, ArH), 7.40 (dd, 2H, J = 12.3, 6.8 Hz, ArH), 7.26 (d, 3H,
J = 13.9 Hz, ArH), 7.16 (d, 1H, J = 8.6 Hz, ArH), 6.91 (d, 1H, J = 7.8 Hz, CH),
3.54 (s, 3H, OCH3); 13C NMR (125 MHz, DMSO-d6): d 156.5, 153.9, 139.8, 133.0,
132.9, 130.3, 129.9, 129.7, 129.0, 128.8, 128.7, 126.9, 126.7, 123.3, 122.7, 119.0,
117.4, 51.9, 50.1; MS (ESI): m/z (%) 340 (M–H)-; Anal. calcd. for C19H16NO3Cl:
C, 66.77; H, 4.72; N, 4.10. Found: C, 66.58; H, 4.83; N, 4.02.
Methyl ((2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4g):
1
white solid, IR (KBr): 3,403, 3,260, 1,678, 1,519, 1,061, 874, 753, 718 cm-1; H
NMR (400 MHz, DMSO-d6): d 9.97 (s, 1H, OH), 8.02 (d, 1H, J = 8.5 Hz, NH),
7.96 (d, 1H, J = 7.8 Hz, ArH), 7.78 (q, 2H, J = 8.7 Hz, ArH), 7.57-7.38 (m, 4H,
ArH), 7.28 (t, 1H, J = 7.3 Hz, ArH), 7.14 (d, 1H, J = 8.7 Hz, ArH), 6.85 (d, 1H,
J = 8.0 Hz, CH), 3.55 (s, 3H, OCH3); 13C NMR (125 MHz, DMSO-d6): d 156.6,
154.0, 139.3, 133.5, 133.0, 132.3, 131.6, 130.1, 129.0, 128.9, 128.6, 127.0, 126.9,
123.0, 122.8, 119.0, 116.7, 52.0, 49.8; MS (ESI): m/z (%) 375 (M–H)-; Anal. calcd.
for C19H15NO3Cl2: C, 60.66; H, 4.02; N, 3.72. Found: C, 60.82; H, 3.94; N, 3.75.
Ethyl ((2-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4l): white
1
solid, IR (KBr): 3,402, 3,277, 1,686, 1,531, 1,334, 1,038, 813, 744, 697 cm-1; H
NMR (400 MHz, DMSO-d6): d 9.79 (s, 1H, OH), 7.92 (d, 1H, J = 8.6 Hz, NH),
7.81–7.72 (m, 4H, ArH), 7.61 (q, 2H, J = 7.5 Hz, ArH), 7.44 (dt, 2H, J = 7.5,
6.5 Hz, ArH), 7.29–7.26 (m, 2H, ArH), 7.05 (d, 1H, J = 8.7 Hz, CH), 4.04 (q, 2H,
J = 7.0 Hz, CH2), 1.15 (t, 3H, J = 7.0 Hz, CH3); 13C NMR (125 MHz, DMSO-d6):
d 156.4, 154.0, 149.0, 136.9, 133.3, 132.5, 130.3, 129.3, 128.8, 128.5, 128.1, 127.0,
124.4, 123.0, 122.8, 118.8, 116.5, 60.5, 48.1, 15.0; MS (ESI): m/z (%) 365 (M–H)-;
Anal. calcd. for C20H18N2O5: C, 65.57; H, 4.95; N, 7.65. Found: C, 65.43; H, 5.02;
N, 7.58.
Ethyl ((3-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4m): white
1
solid, IR (KBr): 3,395, 3,277, 1,678, 1,527, 1,348, 1,045, 808, 752, 701 cm-1; H
NMR (400 MHz, DMSO-d6): d 10.24 (s, 1H, OH), 8.13 (d, 1H, J = 8.2 Hz, NH),
8.07 (d, 1H, J = 8.1 Hz, ArH), 7.98 (d, 1H, J = 7.8 Hz, ArH), 7.82 (t, 3H,
J = 8.4 Hz, ArH), 7.64 (d, 1H, J = 7.8 Hz, ArH), 7.56 (t, 1H, J = 8.0 Hz, ArH),
7.44 (t, 1H, J = 7.5 Hz, ArH), 7.31 (t, 1H, J = 7.5 Hz, ArH), 7.23 (d, 1H,
J = 8.8 Hz, ArH), 6.97 (d, 1H, J = 7.8 Hz, CH), 4.08 (q, 2H, J = 6.8 Hz, CH2),
1.18 (t, 3H, J = 6.8 Hz, CH3); 13C NMR (125 MHz, DMSO-d6): d 156.7, 153.5,
148.1, 145.5, 133.2, 132.3, 130.3, 130.1, 129.1, 128.7, 127.3, 123.5, 123.1, 121.9,
120.9, 118.8, 118.3, 60.7, 50.3, 15.0; MS (ESI): m/z (%) 365 (M–H)-; Anal. calcd.
for C20H18N2O5: C, 65.57; H, 4.95; N, 7.65. Found: C, 65.70; H, 5.04; N, 7.59.
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Z. Song et al.
Ethyl ((4-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4n): white
1
solid, IR (KBr): 3,430, 3,185, 1,685, 1,518, 1,351, 1,049, 821, 739, 708 cm-1; H
NMR (400 MHz, DMSO-d6): d 10.21 (s, 1H, OH), 8.15 (d, 2H, J = 8.8 Hz, NH and
ArH), 7.94–7.73 (m, 4H, ArH), 7.49 (d, 2H, J = 8.6 Hz, ArH), 7.43 (t, 1H,
J = 7.5 Hz, ArH), 7.30 (t, 1H, J = 7.5 Hz, ArH), 7.23 (d, 1H, J = 8.8 Hz, ArH),
6.97 (d, 1H, J = 7.7 Hz, CH), 4.07 (q, 2H, J = 6.7 Hz, CH2), 1.17 (t, 3H,
J = 6.7 Hz, CH3); 13C NMR (125 MHz, DMSO-d6): d 156.7, 153.5, 151.1, 146.4,
132.3, 130.3, 129.0, 128.7, 127.5, 127.2, 123.7, 123.2, 123.0, 118.8, 118.4, 60.7,
50.5, 15.0; MS (ESI): m/z (%) 365 (M–H)-; Anal. calcd. for C20H18N2O5: C, 65.57;
H, 4.95; N, 7.65. Found: C, 65.72; H, 5.04; N, 7.53.
Ethyl ((2-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4o):
white solid, IR (KBr): 3,420, 3,229, 1,685, 1,525, 1,337, 1,051, 821, 752,
1
706 cm-1; H NMR (400 MHz, DMSO-d6): d 10.19 (s, 1H, OH), 8.28 (d, 1H,
J = 8.5 Hz, NH), 8.00 (q, 3H, J = 8.5 Hz, ArH), 7.77 (d, 1H, J = 5.9 Hz, ArH),
7.66–7.48 (m, 5H, ArH), 7.39 (d, 1H, J = 8.7 Hz, ArH), 7.15 (d, 1H, J = 8.3 Hz,
CH), 4.22 (q, 2H, J = 7.1 Hz, CH2), 1.36 (t, 3H, J = 7.1 Hz, CH3); 13C NMR
(125 MHz, DMSO-d6): d 156.1, 153.9, 139.8, 133.0, 132.8, 130.3, 129.9, 129.7,
129.0, 128.8, 128.6, 126.9, 126.7, 123.3, 122.7, 119.0, 117.5, 60.4, 50.0, 15.1; MS
(ESI): m/z (%) 354 (M–H)-; Anal. calcd. for C20H18NO3Cl: C, 67.51; H, 5.10; N,
3.94. Found: C, 67.72; H, 5.21; N, 3.87.
Ethyl ((4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4p): white
1
solid, IR (KBr): 3,424, 3,197, 1,676, 1,517, 1,330, 1,042, 820, 751, 711 cm-1; H
NMR (400 MHz, DMSO-d6): d 10.15 (s, 1H, OH), 7.93 (d, 1H, J = 8.3 Hz, NH), 7.80
(q, 2H, J = 8.2 Hz, ArH), 7.58 (d, 1H, J = 8.2 Hz, ArH), 7.41 (t, 1H, J = 7.3 Hz,
ArH), 7.33–7.22 (m, 6H, ArH), 6.87 (d, 1H, J = 8.1 Hz, CH), 4.05 (q, 2H,
J = 7.2 Hz, CH2), 1.17 (t, 3H, J = 6.9 Hz, CH3); 13C NMR (125 MHz, DMSO-d6): d
156.6, 153.3, 141.9, 132.3, 131.4, 129.9, 129.0, 128.7, 128.4, 128.2, 127.4, 127.1,
123.6, 123.0, 118.9, 60.7, 50.2, 15.0; MS (ESI): m/z (%) 354 (M–H)-; Anal. calcd. for
C20H18NO3Cl: C, 67.51; H, 5.10; N, 3.94. Found: C, 67.69; H, 5.01; N, 3.85.
Ethyl [(2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl] carbamate (4q):
white solid, IR (KBr): 3,412, 3,071, 1,683, 1,514, 1,336, 1,052, 815, 743, 721 cm-1
;
1H NMR (400 MHz, DMSO-d6): d 9.93 (s, 1H, OH), 8.04 (d, 1H, J = 8.6 Hz, NH),
7.78 (dd, 3H, J = 13.8, 8.3 Hz, ArH), 7.58 (d, 1H, J = 8.5 Hz, ArH), 7.49 (d, 1H,
J = 1.5 Hz, ArH), 7.44 (t, 1H, J = 7.5 Hz, ArH), 7.38 (dd, 1H, J = 6.8, 1.8 Hz,
ArH), 7.28 (t, 1H, J = 7.4 Hz, ArH), 7.14 (d, 1H, J = 8.8 Hz, ArH), 6.86 (d, 1H,
J = 8.1 Hz, CH), 3.98 (q, 2H, J = 6.7 Hz, CH2), 1.14 (t, 3H, J = 6.4 Hz, CH3);
13C NMR (125 MHz, DMSO-d6): d 156.2, 154.0, 139.3, 133.5, 132.9, 132.3, 131.6,
130.1, 129.0, 128.9, 128.6, 127.0, 126.9, 123.1, 122.8, 119.0, 116.8, 60.4, 49.7,
15.0; MS (ESI): m/z (%) 389 (M–H)-; Anal. calcd. for C20H17NO3Cl2: C, 61.55; H,
4.39; N, 3.59. Found: C, 61.71; H, 4.47; N, 3.50.
Benzyl ((2-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4s):
white solid, IR (KBr): 3,424, 3,250, 1,702, 1,528, 1,334, 1,046, 834, 752,
1
696 cm-1; H NMR (400 MHz, DMSO-d6): d 9.81 (s, 1H, OH), 8.08 (d, 1H,
J = 7.9 Hz, NH), 7.94 (d, 1H, J = 8.2 Hz, ArH), 7.79 (d, 1H, J = 8.0 Hz, ArH),
7.74 (t, 2H, J = 7.3 Hz, ArH), 7.62–7.26 (m, 11H, ArH), 7.08 (d, 1H, J = 8.5 Hz,
CH), 5.12 (d, 1H, J = 12.8 Hz, CH2), 5.06 (d, 1H, J = 12.8 Hz, CH2); 13C NMR
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Efficient one-pot synthesis of 1-carbamatoalkyl-2-naphthols
2127
Table 1 Screening of metal
Entry
Catalyst
Time (h)
Yield (%)
methanesulfonates and
aluminum salts for the
condensation of 2-naphthol,
2-nitrobenzaldehyde, and
methyl carbamate
1
2
3
4
5
6
7
8
9
Al(MS)3Á4H2O
Cu(MS)2Á4H2O
Zn(MS)2Á4H2O
Mg(MS)2Á6H2O
La(MS)3Á2H2O
Nd(MS)3Á2H2O
Ce(MS)3Á2H2O
AlCl3Á6H2O
0.5
0.8
2.0
4.0
6.0
3.0
5.0
1.0
2.0
93
77
58
55
51
46
21
83
61
Al(NO3)3Á9H2O
(125 MHz, DMSO-d6): d 156.3, 154.1, 149.0, 137.5, 136.8, 133.3, 132.5, 130.4,
129.7, 129.4, 128.9, 128.7, 128.5, 128.2, 128.1, 127.8, 127.2, 127.0, 124.5, 123.0,
122.9, 118.8, 116.4, 65.9, 48.3; MS (ESI): m/z (%) 427 (M–H)-; Anal. calcd. for
C25H20N2O5: C, 70.09; H, 4.71; N, 6.54. Found: C, 69.92; H, 4.82; N, 6.67.
Benzyl ((4-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4u): white
1
solid, IR (KBr): 3,414, 3,064, 1,686, 1,515, 1,347, 1,050, 824, 745, 695 cm-1; H
NMR (400 MHz, DMSO-d6): d 10.21 (s, 1H, OH), 8.15 (d, 2H, J = 8.7 Hz, NH and
ArH), 7.99 (d, 1H, J = 6.6 Hz, ArH), 7.93 (d, 1H, J = 6.4 Hz, ArH), 7.82 (t, 2H,
J = 8.7 Hz, ArH), 7.50 (d, 2H, J = 8.5 Hz, ArH), 7.41–7.28 (m, 7H, ArH), 7.24
(d, 1H, J = 8.8 Hz, ArH), 7.01 (d, 1H, J = 7.8 Hz, CH), 5.14 (d, 1H, J = 12.6 Hz,
CH2), 5.08 (d, 1H, J = 12.6 Hz, CH2); 13C NMR (125 MHz, DMSO-d6): d 156.6,
153.5, 151.0, 146.5, 137.2, 132.3, 130.3, 129.1, 128.8, 128.7, 128.2, 127.5, 127.2,
123.7, 123.3, 123.0, 118.7, 118.3, 66.3, 50.6; MS (ESI): m/z (%) 427 (M–H)-; Anal.
calcd. for C25H20N2O5: C, 70.09; H, 4.71; N, 6.54. Found: C, 70.25; H, 4.65; N, 6.42.
Benzyl ((2-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4v):
white solid, IR (KBr): 3,421, 3,170, 1,700, 1,518, 1,336, 1,050, 819, 753,
1
694 cm-1; H NMR (400 MHz, DMSO-d6): d 9.96 (s, 1H, OH), 8.04 (d, 2H,
J = 7.8 Hz, NH and ArH), 7.80 (d, 1H, J = 7.0 Hz, ArH), 7.75 (d, 1H, J = 8.0 Hz,
ArH), 7.52–7.25 (m, 10H, ArH), 7.16 (d, 2H, J = 7.3 Hz, ArH), 6.94 (d, 1H,
J = 5.8 Hz, CH), 5.09 (d, 1H, J = 12.0 Hz, CH2), 5.01 (d, 1H, J = 12.0 Hz, CH2);
13C NMR (125 MHz, DMSO-d6): d 156.0, 153.9, 139.7, 137.6, 133.0, 132.9, 130.3,
129.9, 129.7, 129.0, 128.9, 128.7, 128.1, 127.8, 126.9, 126.7, 123.3, 122.7, 119.0,
117.3, 65.8, 50.1; MS (ESI): m/z (%) 416 (M–H)-; Anal. calcd. for C25H20NO3Cl:
C, 71.86; H, 4.82; N, 3.35. Found: C, 71.69; H, 4.73; N, 3.41.
Benzyl ((4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4w):
white solid, IR (KBr): 3,402, 3,200, 1,681, 1,515, 1,321, 1,042, 812, 746,
1
696 cm-1; H NMR (400 MHz, DMSO-d6): d 10.15 (s, 1H, OH), 7.93 (d, 1H,
J = 8.2 Hz, NH), 7.80 (q, 3H, J = 7.9 Hz, ArH), 7.39–7.23 (m, 12H, ArH), 6.90
(d, 1H, J = 8.1 Hz, CH), 5.11 (d, 1H, J = 12.6 Hz, CH2), 5.01 (d, 1H, J = 12.6 Hz,
CH2); 13C NMR (125 MHz, DMSO-d6): d 156.5, 153.4, 141.8, 137.3, 132.3, 131.3,
129.9, 129.0, 128.8, 128.7, 128.4, 128.3, 128.2, 127.4, 127.0, 123.7, 123.4, 122.8,
118.9, 118.7, 66.2, 50.3; MS (ESI): m/z (%) 416 (M–H)-; Anal. calcd. for
C25H20NO3Cl: C, 71.86; H, 4.82; N, 3.35. Found: C, 72.01; H, 4.75; N, 3.41.
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Table 2 Optimization of various reaction conditions for the preparation of methyl [(2-nitrophenyl)
(2-hydroxynaphthalen-1-yl)methyl] carbamate
Entry
Solvent (mL)
Amount of
catalyst (mol%)
Temperature
(oC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
a
H2O (3)
2
2
2
2
1
3
2
2
2
0
70
3.0
3.0
3.0
0.5
0.5
0.5
1.5
0.5
0.5
4.0
0
EtOH (3)
Reflux
Reflux
70
14
CH3CN (3)
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
53
93, 92, 90, 87a
70
83
94
72
87
81
0
70
60
80
90
70
Catalyst was reused four times
Benzyl ((2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4x):
white solid, IR (KBr): 3,416, 3,066, 1,686, 1,522, 1,341, 1,054, 819, 744, 719 cm-1
;
1H NMR (400 MHz, DMSO-d6): d 9.92 (s, 1H, OH), 8.02 (d, 2H, J = 8.6 Hz, NH
and ArH), 7.80 (d, 1H, J = 8.0 Hz, ArH), 7.75 (d, 1H, J = 8.8 Hz, ArH), 7.56
(d, 1H, J = 8.4 Hz, ArH), 7.50–7.26 (m, 9H, ArH), 7.14 (d, 1H, J = 8.7 Hz, ArH),
6.87 (d, 1H, J = 6.7 Hz, CH), 5.09 (d, 1H, J = 12.8 Hz, CH2), 5.01 (d, 1H,
J = 12.8 Hz, CH2); 13C NMR (125 MHz, DMSO-d6): d 156.0, 154.0, 139.2, 137.5,
133.6, 133.0, 132.3, 131.6, 130.1, 129.1, 129.0, 128.7, 128.6, 128.1, 127.9, 127.0,
126.9, 123.1, 122.8, 118.9, 116.6, 65.9, 49.9; MS (ESI): m/z (%) 451 (M–H)-; Anal.
calcd. for C25H19NO3Cl2: C, 66.38; H, 4.23; N, 3.10. Found: C, 66.19; H, 4.15; N,
3.14.
Results and discussion
At the outset, we investigated the catalytic activity of different M(MS)xÁaH2O
(0.1 mmol) using the model reaction of 2-naphthol (5 mmol), 2-nitrobenzaldehyde
(5 mmol) and methyl carbamate (5 mmol) at 70 °C under solvent-free conditions.
The results are summarized in Table 1. After several trials, it was found that
Al(MS)3Á4H2O was the most efficient catalyst for this transformation, since it results
in the highest conversion to the desired product in the shortest reaction time
(Table 1, entry 1). Compared with conventional Lewis acids such as aluminum
chloride and aluminum nitrate, Al(MS)3Á4H2O showed excellent catalytic activity
(Table 1, entries 1, 8 and 9).
Next, we examined the above reaction under different conditions (Table 2).
Initially, H2O, EtOH, CH3CN and solvent-free condition were investigated to
optimize the reaction (Table 2, entries 1–4). It seems that solvent-free system is the
best choice in terms of reaction time and product yield (Table 2, entry 4). In this
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Efficient one-pot synthesis of 1-carbamatoalkyl-2-naphthols
2129
Table 3 Al(MS)3Á4H2O-catalyzed synthesis of 1-carbamatoalkyl-2-naphthols
Entry
R1
R2
Time (h)
Product
Yield (%)
Mp (oC)
Found
Reported
1
C6H5
Me
0.5
0.5
0.6
0.5
0.4
0.5
0.5
10.0
10.0
10.0
0.5
0.5
0.6
0.4
0.5
0.7
0.5
0.6
0.5
0.6
0.5
0.8
1.0
0.5
4a
4b
4c
4d
4e
4f
90
93
94
90
91
89
90
18
Trace
0
224–226
245–247
243–244
212–214
218–220
202–204
210–212
193–195
–
222–224 [9]
2
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
Me
241–242 [9]
3
Me
253–255 [9]
4
Me
206–208 [17]
5
Me
–
6
4-ClC6H4
Me
203–205 [9]
7
2,4-Cl2C6H3
4-CH3C6H4
4-OCH3C6H4
CH3CH2CH2
C6H5
Me
4g
4h
4i
–
8
Me
188 [17]
9
Me
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Me
4j
–
–
Et
4k
4l
83
87
93
89
91
90
88
85
90
95
92
91
90
91
197–199
215–216
245–246
229–231
216–217
219–221
196–197
185–187
208–210
200–202
202–204
211–213
178–180
208–210
195–196 [15]
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
Et
–
Et
4m
4n
4o
4p
4q
4r
4s
–
Et
–
Et
–
4-ClC6H4
Et
–
2,4-Cl2C6H3
C6H5
Et
–
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
180–182 [9]
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
–
4t
205–207 [9]
4u
4v
4w
4x
–
–
–
–
4-ClC6H4
2,4-Cl2C6H3
R O
O
2
Ar
H
R
NH
OH
1
NH CO R
2 2
R CHO
1
O
2
OH
Al(MS)
3
Al(MS)
3
o-QM
4
Scheme 2 Proposed mechanism
case, Al(MS)3Á4H2O could be reused four successive runs without distinct loss of
activity. Then, the amount of catalyst and suitable reaction temperature were studied
(Table 2, entries 4-9). The best result was obtained by carrying out the reaction
using 2 mol% Al(MS)3Á4H2O at 70 °C under solvent-free conditions (Table 2, entry
4). The product yield decreased when the reaction temperature was above 70 °C.
Perhaps the reason for this is that these reactions proceed too quickly to complete
123

2130
Z. Song et al.
the transformations. No product was obtained in the absence of a catalyst (Table 2,
entry 10).
Using the optimized reaction conditions, the scope and efficiency of the reaction
were explored for the synthesis of a wide variety of substituted 1-carbamatoalkyl-2-
naphthols using 2-naphthol, various aldehydes, and methyl/ethyl/benzyl carbamate.
The results are summarized in Table 3. As shown in Table 3, the direct three-
component reactions worked well with aromatic aldehydes carrying electron-
withdrawing groups such as NO2 and Cl. The position of the substituent on the
aromatic ring does not show any effect on the yield of the product. Under the same
conditions, the reactions proceed sluggishly with aromatic aldehydes carrying
electron-donating groups (Table 3, entries 8 and 9). No product was obtained when
aliphatic aldehyde such as propionaldehyde was used as the starting material
(Table 3, entry 10). Beside methyl carbamate, ethyl carbamate and benzyl
carbamate were also used as ammonia source, and they worked equally in the
amidoalkylation reaction.
A possible mechanism for this transformation is proposed in Scheme 2. As
reported in the literature [4, 26], reaction of 2-naphthol with aldehydes in the
presence of an acid catalyst is known to give o-QMs. The o-QMs generated in situ
reacted with carbamates to form the 1-carbamatoalkyl-2-naphthol derivatives 4.
Conclusions
In conclusion, we have described a new strategy for the synthesis of 1-carbamatoalkyl-
2-naphthols via a one-pot three-component condensation of 2-naphthol, aldehydes,
and methyl/ethyl/benzyl carbamates using the inexpensive, water-tolerant, and
recyclable Al(MS)3Á4H2O as a catalyst under solvent-free conditions. The method
offers several advantages including mild reaction conditions, simple work-up, easy
recovery, and reusable catalyst, and environmental friendly characteristics. Currently,
studies on the extension of multicomponent reactions are ongoing in our laboratory.
Acknowledgment This research work was financially supported by the Education Committee of
Liaoning Province of China (No. L2011198).
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