A convenient three-component synthesis of carbamatoalkyl naphthols catalyzed by cerium ammonium nitrate

Article abstract of DOI:10.4314/bcse.v27i3.11

A highly efficient synthesis of carbamatoalkyl naphthols has been performed by a one-pot threecomponent condensation of 2-naphthol, aldehydes, and methyl/ethyl/benzyl carbamates in the presence of cerium ammonium nitrate under solvent-free conditions at 70 °C. The solvent, optimal amounts of raw materials and catalyst, and reaction temperature are investigated. Experimental results show that only 0.1 mmol catalyst is enough to induce the conversion. Most reactions are performed within a short reaction time. The structures of all products were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. A mechanism to rationalize the reaction has been proposed.

Full text of DOI:10.4314/bcse.v27i3.11

Bull. Chem. Soc. Ethiop. 2013, 27(3), 421-426.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v27i3.11
ISSN 1011-3924
 2013 Chemical Society of Ethiopia
A CONVENIENT THREE-COMPONENT SYNTHESIS OF CARBAMATOALKYL
NAPHTHOLS CATALYZED BY CERIUM AMMONIUM NITRATE
Min Wang1*, Yang Liu1, Zhiguo Song2 and Shuang Zhao1
1College of Chemistry, Chemical Engineering and Food Safety, Bohai University, Jinzhou
121013, China
2Management Center for Experiment, Bohai University, Jinzhou 121013, China
(Received October 2, 2012; revised February 25, 2013)
ABSTRACT. A highly efficient synthesis of carbamatoalkyl naphthols has been performed by a one-pot three-
component condensation of 2-naphthol, aldehydes, and methyl/ethyl/benzyl carbamates in the presence of cerium
ammonium nitrate under solvent-free conditions at 70 oC. The solvent, optimal amounts of raw materials and
catalyst, and reaction temperature are investigated. Experimental results show that only 0.1 mmol catalyst is
enough to induce the conversion. Most reactions are performed within a short reaction time. The structures of all
products were characterized by IR, 1H NMR, 13C NMR, MS, and elemental analysis. A mechanism to rationalize
the reaction has been proposed.
KEY WORDS: Carbamatoalkyl naphthols, Cerium ammonium nitrate, One-pot synthesis, Solvent-free
conditions
INTRODUCTION
Compounds bearing 1,3-amido 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, lipinavir, and the hypotensive [1]. In
addition, 1-carbamatoalkyl-2-naphthols can convert to 1-aminomethyl-2-naphthols by a
carbamate hydrolysis reaction. 1-Aminomethyl-2-naphthols have been reported to show
cardiovascular activity [2].
Though carbamatoalkyl naphthols are very important, only a few literatures focused on their
synthesis have been published. The reported catalysts include triethylbenzylammonium chloride
[3], SiO2-NaHSO4 [4], Brønsted-acidic ionic liquids [5], silica-supported polyphosphoric acid
[6], silica-supported Preyssler nano particles [7], SiO2-HClO4 [8], Zwitterionic-type molten salt
-
-
[9], [MeC(OH)2]+ClO4 [10], ionic liquid [NMP]+HSO4 [11], sulfamic acid functionalized
magnetic nanoparticles [12], Mg(OOCCF3)2 [13], [Dsim]HSO4 [14], and [Et3N-SO3H]Cl [15],
etc. However, most of these methods suffer from drawbacks including low yields, expensive
reagents and catalysts. Therefore, the development of high yielding and less expensive catalytic
method is desired.
Cerium ammonium nitrate (CAN) has been widely used in organic transformations due to its
many advantages such as high reactivity, commercial availability, ease of handling, and stability
in different solvents. We herein describe the catalytic activity of CAN for the efficient three-
component synthesis of carbamatoalkyl naphthols (4a-r) under solvent-free conditions (Scheme
1).
NHCO R
2
2
R
1
OH
CAN
70 C, solvent- free
OH
R CHO
1
NH CO R
2 2
+
+
2
o
3
1
2
4a-4r
Scheme 1. Three-component synthesis of carbamatoalkyl naphthols catalyzed by CAN.
__________
*Corresponding author. E-mail: minwangszg@yahoo.com.cn

422
Min Wang et al.
EXPERIMENTAL
General
Melting points were determined using a RD-II micromelting point apparatus. Infrared spectra
1
were recorded on a Scimitar 2000 series Fourier transform instrument of Varian. H NMR 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. All the reagents were analytical grade and were purchased from the Shanghai
Chemical Reagent Company. TLC was performed on silica gel polygram SIL G/UV 254 plates.
Typical procedure for the synthesis of carbamatoalkyl naphthols (4)
To a mixture of β-naphthol (5 mmol), an aldehyde (5 mmol), and a carbamate (5.5 mmol), CAN
(0.1 mmol) was added. The reaction mixture was magnetically stirred on a preheated water bath
at 70 oC. After completion of the reaction (monitored by TLC), the reaction mixture was cooled
to r.t., washed with H2O/EtOH (v/v = 1/1), and the residue was recrystallized from H2O/EtOH
1
(v/v = 2/3). The products were characterized by m.p., IR, H NMR, 13C NMR and elemental
analysis. Spectral data for new compounds are given below.
Methyl ((2-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4e)
White solid. IR (KBr): 3431, 3220, 1690, 1527, 1341, 1051, 819, 753, 706 cm-1; 1H NMR (400
MHz, DMSO-d6): δ = 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 (dd, 2H, J = 17.4, 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 (100 MHz, DMSO-d6): δ = 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 (EI, 70 eV): m/z (%) 340 [(M-H)-, 100]. Anal. calcd. for C19H16NO3Cl: C, 66.77;
H, 4.72; N, 4.10. Found: C, 66.89; H, 4.64; N, 4.17.
Methyl ((2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4g)
White solid. IR (KBr): 3403, 3260, 1678, 1519, 1062, 874, 753, 718 cm-1; 1H NMR (400 MHz,
DMSO-d6): δ = 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 (dd, 2H, J = 17.8, 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 (100
MHz, DMSO-d6): δ = 156.6, 153.9, 139.2, 133.5, 133.0, 132.4, 131.6, 130.1, 129.0, 128.9,
128.6, 127.0, 126.9, 123.1, 122.8, 118.9, 116.7, 52.0, 49.8; MS (EI, 70 eV): m/z (%) 375 [(M-
H)-, 100]. Anal. calcd. for C19H15NO3Cl2: C, 60.66; H, 4.02; N, 3.72. Found: C, 60.51; H, 4.07;
N, 3.61.
Ethyl ((2-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4l)
White solid. IR (KBr): 3402, 3277, 1686, 1531, 1334, 1039, 813, 744, 697 cm-1; 1H NMR (400
MHz, DMSO-d6): δ 9.79 (s, 1H, OH), 7.92 (d, 1H, J = 8.6 Hz, NH), 7.81-7.72 (m, 4H, ArH),
7.61-7.58 (m, 2H, 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
(100 MHz, DMSO-d6): δ 156.4, 154.0, 149.0, 136.9, 133.3, 132.5, 130.3, 129.4, 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 (EI, 70 eV): m/z (%) 365
[(M-H)-, 100]. Anal. calcd. for C20H18N2O5: C, 65.57; H, 4.95; N, 7.65. Found: C, 65.71; H,
4.87; N, 7.72.
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Synthesis of carbamatoalkyl naphthols catalyzed by cerium ammonium nitrate
423
Ethyl ((4-nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4m)
White solid. IR (KBr): 3430, 3185, 1685, 1518, 1351, 1049, 821, 739, 708 cm-1; 1H NMR (400
MHz, DMSO-d6): δ = 10.21 (s, 1H, OH), 8.15 (d, 2H, J = 8.8 Hz, ArH), 7.94-7.73 (m, 4H, NH
and 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 (100 MHz, DMSO-d6): δ = 156.7, 153.5, 151.1,
146.4, 132.3, 130.3, 129.1, 128.8, 127.5, 127.2, 123.7, 123.2, 123.0, 118.8, 118.4, 60.7, 50.5,
15.0; MS (EI, 70 eV): m/z (%) 365 [(M-H)-, 100]. Anal. calcd. for C20H18N2O5: C, 65.57; H,
4.95; N, 7.65. Found: C, 65.43; H, 5.02; N, 7.72.
Ethyl ((2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4n)
White solid. IR (KBr): 3412, 3071, 1683, 1514, 1336, 1052, 815, 743, 721 cm-1; 1H NMR (400
MHz, DMSO-d6): δ = 9.93 (s, 1H, OH), 8.04 (d, 1H, J = 8.6 Hz, NH), 7.81-7.75 (m, 3H, 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); 13
C
NMR (100 MHz, DMSO-d6): δ = 156.1, 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 (EI, 70 eV): m/z
(%) 389 [(M-H)-, 100]. Anal. calcd. for C20H17NO3Cl2: C, 61.55; H, 4.39; N, 3.59. Found: C,
61.41; H, 4.44; N, 3.63.
Benzyl ((2-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4q)
White solid. IR (KBr): 3421, 3170, 1700, 1518, 1335, 1050, 819, 754, 694 cm-1; 1H NMR (400
MHz, DMSO-d6): δ = 9.96 (s, 1H, OH), 8.04 (d, 2H, J = 7.8 Hz, ArH), 7.81-7.75 (m, 2H, NH
and 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 (100 MHz,
DMSO-d6): δ = 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, 118.9, 117.3, 65.8, 50.1; MS (EI, 70 eV): m/z
(%) 416 [(M-H)-, 100]. Anal. calcd. for C25H20NO3Cl: C, 71.86; H, 4.82; N, 3.35. Found: C,
71.98; H, 4.89; N, 3.27.
Benzyl ((4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl) carbamate (4r)
White solid. IR (KBr): 3402, 3200, 1681, 1515, 1321, 1042, 812, 746, 696 cm-1; 1H NMR (400
MHz, DMSO-d6): δ = 10.15 (s, 1H, OH), 7.93 (d, 1H, J = 8.2 Hz, NH), 7.82-7.77 (m, 3H, 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 (100 MHz, DMSO-d6): δ = 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, 123.0, 118.9,
118.7, 66.1, 50.3; MS (EI, 70 eV): m/z (%) 416 [(M-H)-, 100]. Anal. calcd. for C25H20NO3Cl: C,
71.86; H, 4.82; N, 3.35. Found: C, 71.73; H, 4.93; N, 3.39.
RESULTS AND DISCUSSION
First, in order to optimize the reaction conditions, the effects of solvent, molar ratio of raw
materials, amount of catalyst and reaction temperature on the products yields were evaluated by
carrying out the model reaction of β-naphthol 1, 2-nitrobenzaldehyde 2 and methyl carbamate 3
Bull. Chem. Soc. Ethiop. 2013, 27(3)

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Min Wang et al.
(Table 1). It was found that the best results were obtained with 0.1 mmol CAN under solvent-
o
free conditions at 70 C (Table 1, entry 4). The reaction was completed within 1.0 h and the
expected product was obtained in a 91% yield, while increase the amount of catalyst or evaluate
the reaction temperature further would decrease the product yield. A blank experiment of β-
naphthol, 2-nitrobenzaldehyde, and methyl carbamate in the absence of catalyst was
investigated. No product was obtained after 4.0 h (Table 1, entry 13).
Table 1. Condensation of β-naphthol, 2-nitrobenzaldehyde and methyl carbamate catalyzed by CAN under
various conditionsa.
Entry
1
Solvent (mL)
n (1) : n (2) : n (3)
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1
CAN (mmol)
Temp. (oC)
Time (h)
2.0
Yield (%)b
H2O (3)
0.1
0.1
70
70
70
70
70
70
70
70
70
50
60
80
70
0
2
EtOH (3)
1.0
6
3
CH3CN (3)
0.1
3.0
19
91
85
92
80
86
88
81
85
82
0
4
-
-
-
-
-
-
-
-
-
-
0.1
1.0
5
0.1
1.0
6
1 : 1 : 1.2
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
1 : 1 : 1.1
0.1
1.0
7
0.025
0.05
0.15
0.1
1.5
8
1.3
9
1.0
10
11
12
13
1.2
0.1
1.0
0.1
1.0
0
4.0
aβ-naphthol was 5 mmol. bYields refer to isolated pure products.
Table 2. Synthesis of carbamatoalkyl naphthols in the presence of CAN without solventa.
Entry
1
R1
R2
CH3
Time (h)
1.5
Product
4a
4b
4c
Yield (%)b
85
M.p. (oC)
Ph
224−225 [5]
241−243 [5]
244−246 [5]
210−211 [13]
218−220
202−204 [5]
210−211
-
2
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
4-CH3C6H4
4-CH3OC6H4
CH3CH2
CH3
1.0
91
3
CH3
0.6
92
4
CH3
0.7
4d
4e
92
5
CH3
1.0
89
6
CH3
1.0
4f
93
7
CH3
1.0
4g
4h
4i
88
8
CH3
10.0
10.0
10.0
1.5
trace
trace
0
9
CH3
-
10
11
12
13
14
15
16
17
18
CH3
4j
-
Ph
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2Ph
CH2Ph
CH2Ph
CH2Ph
4k
4l
80
203-204 [11]
215-216
229-230
196-198
185-187 [5]
206-208 [5]
211-213
179-181
2-NO2C6H4
4-NO2C6H4
2,4-Cl2C6H3
Ph
1.5
85
0.5
4m
4n
4o
4p
4q
4r
91
1.0
89
2.5
86
3-NO2C6H4
2-ClC6H4
4-ClC6H4
1.0
90
1.5
91
2.0
89
aβ-naphthol 5 mmol, aldehydes 5 mmol, carbamates 5.5 mmol, CAN 0.1 mmol, 70 oC. bYields refer to isolated
pure products.
Then, the scope and limitation of the reactions of β-naphthol 1, aldehydes 2, and
methyl/ethyl/benzyl carbamate 3 catalyzed by CAN were studied, the results were shown in
Bull. Chem. Soc. Ethiop. 2013, 27(3)

Synthesis of carbamatoalkyl naphthols catalyzed by cerium ammonium nitrate
425
Table 2. Most reactions proceeded smoothly with good to excellent yields under the optimized
conditions. Aryl aldehydes with electron-withdrawing groups proved to be more active than
those with electron-donating groups. The position of the substituent on the aromatic ring shows
no effect on the product yield. The reaction of aliphatic aldehyde such as propionaldehyde
isolated no desired product (Table 2, entry 10). Beside methyl carbamate, ethyl carbamate and
benzyl carbamate were also utilized for the condensation, and they all participated well.
Reusability of the catalyst was also investigated. For this purpose, the same model reaction
was again studied under optimized conditions. After the completion of the reaction, the reaction
mixture was cooled to room temperature, and ethanol aqueous was added. Due to the fact that
the catalyst was soluble in ethanol and water, it could therefore be recovered by evaporating the
o
filtrate. The separated catalyst was washed with CH2Cl2, dried at 50 C for 1 h and reused in
another reaction. As shown in Table 3, the catalyst could be reused at least two times without
significant loss of activity. However, the reaction time had to prolong due to the loss of the
catalyst.
Table 3. The comparison of efficiency of CAN as catalyst in the synthesis of 4b after three timesa.
Run
First
Time (h)
1.0
Yield (%)b
Amount of catalyst (mg)
91
88
82
54.8
39.4
21.7
Second
1.3
Third
1.5
aβ-naphthol 5 mmol, 2-nitrobenzaldehyde 5 mmol, methyl carbamate 5.5 mmol, CAN 0.1 mmol (54.8 mg), 70 oC.
bYields refer to isolated pure products.
We propose a reaction mechanism of the CAN-catalyzed condensation. CAN act as a Lewis
acid catalyst that facilitates the formation of o-MQ, which further react with a nucleophile
(carbamate) to form the desired carbamatoalkyl naphthols 4 [16].
CONCLUSIONS
From the results above it can be concluded that CAN is an efficient catalyst for the one-pot
three-component condensation of β-naphthol, aromatic aldehydes (with electron-withdrawing
groups) and methyl/ethyl/benzyl carbamates. The new protocol offers several significant
advantages such as inexpensive and commercially available catalyst, mild reaction condition,
simple work-up and excellent yields (80−93%). This study enlarges the existing methods for the
synthesis of the title compounds.
ACKNOWLEDGEMENT
This research work was financially supported by the Education Committee of Liaoning Province
of China (No. L2011198).
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