Preparation of methyl/benzyl(2-hydroxynaphthalen-1-yl)(aryl)methylcarbamate derivatives using magnesium hydrogen sulfate

Article abstract of DOI:10.1007/s11164-013-1044-0

A new approach to the synthesis of methyl/benzyl(2-hydroxynaphthalen-1-yl) (aryl)methylcarbamate derivatives based on the reaction of aldehydes, 2-naphthol and methyl/benzyl carbamate, using a catalytic amount of magnesium hydrogen sulfate [Mg(HSO₄

Full text of DOI:10.1007/s11164-013-1044-0

Res Chem Intermed
DOI 10.1007/s11164-013-1044-0
Preparation of methyl/benzyl(2-hydroxynaphthalen-1-
yl)(aryl)methylcarbamate derivatives using magnesium
hydrogen sulfate
Majid Ghashang
Received: 30 December 2012 / Accepted: 11 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A new approach to the synthesis of methyl/benzyl(2-hydroxynaphtha-
len-1-yl)(aryl)methylcarbamate derivatives based on the reaction of aldehydes,
2-naphthol and methyl/benzyl carbamate, using a catalytic amount of magnesium
hydrogen sulfate [Mg(HSO4)2] as an efficient heterogeneous catalyst under solvent-
free conditions has been developed.
Keywords Magnesium hydrogen sulfate [Mg(HSO4)2] ꢀ Metal hydrogen sulfate ꢀ
Carbamate ꢀ 1-Carbamatoalkyl-2-naphthol ꢀ Methyl/benzyl(2-hydroxynaphthalen
-1-yl)(aryl)methylcarbamate
Introduction
Finding methods for the synthesis of carbamate derivatives is an immensely
important part of organic synthesis due to the role of these functional groups as a
privileged building block in a myriad of pharmacologically active compounds as
well as natural products [1–5]. These functional groups are ubiquitous due to their
wide-ranging potential for synthetic applications [6–9]. They are present in a variety
of natural products and are versatile precursors for the synthesis of pharmaceuticals
such as mitomycin [10, 11], saxitoxin [12], and bleomycin [13]. In addition,
carbamates are intermediates of the Curtius degradation route to amines [14]. They
abound as nitrogen- or oxygen-protecting groups [14]. Therefore, as a consequence
of their valuable biological activities, great interest has been shown in the
preparation of carbamate derivatives [15–17].
M. Ghashang (&)
Department of Chemistry, Faculty of Sciences, Islamic Azad University, Najafabad Branch,
P.O. Box 517, Najafabad, Esfahan, Iran
e-mail: ghashangmajid@gmail.com
123

M. Ghashang
Three-component condensation of aldehydes, 2-naphthol, and methyl/benzyl
carbamate is a useful strategy for the preparation of carbamates leading to the
synthesis of methyl/benzyl(2-hydroxynaphthalen-1-yl)(aryl)methylcarbamate deriv-
atives, and has been carried out using various precursors, such as PPA–SiO2 [18],
p-Toluenesulfonic acid (P-TSA) [19], Brønsted acidic ionic liquids [20],
SiO2–NaHSO4 [21], zwitterionic-type molten salt [22], HClO4–SiO2 [23], silica-
supported preyssler nano-particles [24], magnesium (II) 2,2,2-trifluoroacetate [25],
[NMP?HSO4-] [26], triethyl amine-bonded sulfonic acid [27], aluminum meth-
anesulfonate [28], and 1,3-disulfonic acid imidazolium hydrogen sulfate [29] .
Although these procedures have some advantages such as good to excellent yields,
in the field of modern organic chemistry the discovery of new synthetic
methodologies to facilitate the preparation of organic compounds is a demand
point of research activity.
The present work concentrates on the three-component condensation of
2-naphthol, aromatic aldehydes and methyl/benzyl carbamate in the presence of
magnesium hydrogen sulfate, Mg(HSO4)2 [30, 31] as a catalyst under thermal,
solvent-free conditions (Scheme 1).
Results and discussions
Initially, the condensation reaction of benzaldehyde, 2-naphthol and methyl
carbamate was chosen as a model and the influence of Mg(HSO4)2 as a catalyst
was examined to find the optimal reaction conditions (Scheme 2).
To optimize the reaction conditions, the reaction was carried out by using
different solvents (Table 1, entries 1–6) or solvent-free condition (Table 1, entry 7).
It was observed that the solvent-free condition was the best reaction media in terms
of reaction times and yields (Table 1, entry 7).
To find an optimized amount of Mg(HSO4)2 and the reaction temperature, the
reaction was carried out by varying the amount of the catalyst and at different
reaction temperatures (Table 1, entries 8–14). Maximum yield was obtained when
0.2 mmol of the catalyst was used at 100 °C (Table 1, entry 14). The results are
summarized in Table 1.
Next, the scope and efficiency of this procedure was explored for the synthesis of
a wide variety of substituted 1-carbamatoalkyl-2-naphthol (Scheme 1; Table 2).
As expected, this reaction proceeded smoothly and the desired products were
obtained in good yields. In general, aromatic aldehydes were well tolerated in this
O
Y
O
OH
Mg(HSO4)2
Ar
NH
OH
+ Ar-CHO +
Y
NH2
Solvent-free
100 oC
Y: CH3O; PhCH2O
Scheme 1 Preparation of methyl/benzyl(2-hydroxynaphthalen-1-yl)(aryl)methylcarbamate derivatives
123

Preparation of methyl/benzyl(2-hydroxynaphthalen-1-yl)
CHO
OH
+
O
Mg(HSO4)2
OH
+
O
NH2
HNCOOCH3
Scheme 2 Preparation of methyl(2-hydroxynaphthalen-1-yl)(phenyl)methylcarbamate using Mg(HSO4)2
as catalyst
Table 1 Optimization of the reaction conditions in the preparation of methyl(2-hydroxynaphthalen-1-
yl)(phenyl)methylcarbamate
Entry
Catalyst (mmol)
T (°C)
Solvent
Time (min)
Yield (%)a
1
2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.05
0.1
0.15
0.2
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
100
H2O
400
400
400
400
400
400
20
–
CH2Cl2
14
45
61
20
35
80
–
3
Methanol
4
Ethanol
5
n-Hexane
6
Ethyl acetate
7
–
–
–
–
–
–
–
–
8
25
300
45
9
80
71
77
68
70
73
88
10
11
12
13
14
a
120
15
100
60
100
40
100
35
100
27
Isolated yield
reaction system (Table 2, entries 1–13). Based on the obtained results, the electronic
effects and the steric effects of the substituents played significant roles in the yields
of products. When ortho-substituted aldehydes (Table 2, entries 6, 7, 11) were used
in this process, the corresponding product was obtained in good yields but in longer
reaction times. Electron-withdrawing groups on the aldehyde were able to facilitate
the transformation by giving evidently higher yield of products and shorter reaction
times than the entries using electron-donating atom-functionalized aldehydes
(Table 2). In contrast to the findings of aromatic aldehydes, aliphatic aldehydes did
not provide corresponding products under present conditions (Table 2, entries
22–23).
Encouraged by the results obtained with methyl carbamate, we turned our
attention to benzyl carbamate (Table 2). As shown in Table 2, the reactions of
2-naphthol and aryl aldehydes with benzyl carbamate under the mentioned reaction
conditions progressed smoothly and the desired products were obtained in good
yields (Table 2, entries 14–21).
123

M. Ghashang
Table 2 Preparation of 1-carbamatoalkyl-2-naphthol derivatives using Mg(HSO4)2 as catalyst
(0.2 mmol, 100 °C)
Entry Aldehyde
Carbamate
Time Yield m.p. [lit. m.p.
Ref.
(min) (%)a °C]
1
27
21
20
23
88
91
95
90
211–213
[213]19
O
O
O
O
CHO
H3C
O
NH2
NH2
NH2
NH2
2
203–205
[206]19
Cl
CHO
H3C
H3C
H3C
O
O
O
3
4
197–199
[195–197]19
Br
CHO
190–192
[191–193]20
CHO
Br
5
6
7
25
27
25
89
84
95
200–202
[201–203]20
O
O
O
CHO
CHO
H3C
H3C
H3C
O
O
O
NH2
NH2
NH2
Cl
181–183
[182–184]19
Cl
189–191
[192]21
Cl
Cl
CHO
8
9
15
17
96
95
205–207
[205–207]21
O
O
O2N
CHO
H3C
H3C
O
O
NH2
NH2
249–251
[252]21
CHO
O2N
H3C
10
45
75
187–189
[188]25
O
CHO
H3C
O
NH2
123

Preparation of methyl/benzyl(2-hydroxynaphthalen-1-yl)
Table 2 continued
Entry Aldehyde
Carbamate
Time Yield m.p. [lit. m.p.
Ref.
(min) (%)a °C]
11
60
70
229–231
[230–232]20
O
CHO
CH3
H3C
O
NH2
12
20
23
91
83
203–205
[202–204]19
O
O
CHO
F
H3C
H3C
O
O
NH2
NH2
13
237–239
[241–242]20
CHO
NO2
CHO
14
15
28
30
89
94
180–182
[179–180]21
O
Ph
O
NH2
NH2
201–203
[202]25
Cl
O
O
Ph
Ph
O
O
Cl
CHO
16
21
91
200–202
[205–207]20
CHO
CHO
NH2
O2N
17
18
25
40
96
87
187–189
[185–186]21
O
O
F
Ph
Ph
O
O
NH2
NH2
165–167
[163–165]19
CHO
Cl
19
20
30
30
94
93
188–190 [–]
O
O
Br
CHO
Ph
Ph
O
O
NH2
NH2
183–185
[183–185]20
CHO
Br
123

M. Ghashang
Table 2 continued
Entry Aldehyde
Carbamate
Time Yield m.p. [lit. m.p.
Ref.
(min) (%)a °C]
21
32
88
200–202
[203]21
O
CHO
Ph
O
NH2
Cl
22
23
a
250
250
–
–
–
–
CHO
O
H3CO
NH2
CHO
O
H3CO
NH2
Isolated yield
The work-up procedure is very clear-cut; that is, the products were isolated and
purified by simple filtration and crystallization from aqueous ethanol. Our protocol
avoids the use of dry media during the reaction process, making it superior to the
reactions that use solvent.
Conclusion
In conclusion, a rapid and environmentally benign protocol for the preparation of
methyl/benzyl(2-hydroxynaphthalen-1-yl)(aryl)methylcarbamate in a one-pot pro-
cedure has been developed. The present protocol features simple operations, short
reaction time, environmental friendliness, and good yields.
Experimental
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). IR spectra were recorded on a
Perkine Elmer 781 spectrophotometer. Elemental analysis was performed on a
Heraeus CHN-O-Rapid analyzer. Melting points were determined in open capillar-
ies with a BUCHI 510 melting point apparatus. TLC was performed on silica gel
polygram SIL G/UV 254 plates.
123

Preparation of methyl/benzyl(2-hydroxynaphthalen-1-yl)
Typical procedure
To a mixture of benzaldehyde (1 mmol), 2-naphthol (1 mmol) and methyl
carbamate (1.3 mmol), Mg(HSO4)2 (0.2 mmol) was added and the mixture was
heated at 100 °C in an oil bath for the appropriate time (Table 2). The progress of
the reaction was monitored by TLC. After completion of the reaction, the mass was
cooled to 25 °C and the mixture was dissolved in pure acetone. The catalyst
was removed by simple filtration. Solvent was evaporated and the solid product was
purified by recrystallization from ethanol.
Benzyl (4-bromophenyl)(2-hydroxynaphthalen-1-yl)methylcarbamate (Table 2,
entry 19)
1H NMR (400 MHz, DMSO-d6):d = 5.03(d, J = 12.6 Hz, 1H), 5.09(d, J = 12.6 Hz,
1H), 6.88 (d, J = 7.9 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 7.22–7.42 (m, 10H), 7.48 (d,
J = 7.3 Hz, 2H), 7.78–7.84 (m, 2H), 7.93 (d, J = 7.3 Hz, 1H), 10.15 (s, 1H, OH) ppm;
13C NMR (100 MHz, DMSO-d6): 51.4, 66.5, 119.5, 121.3, 123.7, 124.6, 125.4, 127.5,
128.6, 129.0, 129.4, 129.9, 130.2, 131.6, 132.5, 133.5, 135.7, 138.5, 143.0, 154.6,
157.7 ppm; IR (KBr, cm-1): 3421, 3,171, 3,021, 2,962, 1,687, 1,630, 1,572, 1,488,
1,436, 1,347, 1,267, 940, 821, 710; [Found: C, 65.07; H, 4.47; N, 3.11 C25H20BrNO3;
Requires C, 64.95; H, 4.36; N, 3.03].
Acknowledgment We are grateful to the Najafabad Branch, Islamic Azad University Research Council
for partial support of this research.
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