Preparation of methyl (2-hydroxynaphthalen-1-yl)(aryl)methyl/ benzylcarbamate derivatives using magnesium (II) 2,2,2-trifluoroacetate as an efficient catalyst

Article abstract of DOI:10.3184/174751911X13182405888457

Multi-component condensation reactions of aldehydes, 2-naphthol and methyl/benzyl carbamate have been done by using magnesium 2,2,2-trifluoroacetate [Mg(OOCCF3)₂] as an efficient catalyst. This methodology results in the synthesis of a variety

Full text of DOI:10.3184/174751911X13182405888457

622 RESEARCH PAPER
NOVEMBER, 622–625
JOURNAL OF CHEMICAL RESEARCH 2011
Preparation of methyl (2-hydroxynaphthalen-1-yl)(aryl)methyl/
benzylcarbamate derivatives using magnesium (II) 2,2,2-trifluoroacetate
as an efficient catalyst
Mohammad Reza Mohammad Shafiee*, Raheleh Moloudi and Majid Ghashang
Department of Chemistry, Faculty of Sciences, Islamic Azad University – Najafabad Branch, Najafabad, Esfahan, PO Box 517, Iran
Multi-component condensation reactions of aldehydes, 2-naphthol and methyl/benzyl carbamate have been done
by using magnesium 2,2,2-trifluoroacetate [Mg(OOCCF3)2] as an efficient catalyst. This methodology results in the
synthesis of a variety of methyl (2-hydroxynaphthalen-1-yl)(aryl)methyl/benzylcarbamate derivatives in high yields.
Despite their importance from pharmacological and synthetic points of view, comparatively few methods for
the preparation of 1-carbamatoalkyl 2-naphthol derivatives have been reported via multi-component reactions of
aldehydes, 2-naphthol and carbamate using acidic catalysts. Magnesium 2,2,2-trifluoroacetate [Mg(OOCCF3)2] has
been prepared from the reaction of trifluoroacetic acid and magnesium chloride. The prepared catalyst has been
characterised through a powder X-ray diffraction pattern.
Keywords: magnesium 2,2,2-trifluoroacetate, carbamate, X-ray diffraction, 1-carbamatoalkyl 2-naphthol, multi-component
reaction
Carbamate skeletons are important components of natural
products and versatile precursors for synthesis of pharmaceu-
ticals such as mitomycin,1,2 saxitoxin3 and bleomycin.4 In
addition, carbamates are intermediates of the Curtius degrada-
tion route to amines.5 They abound as nitrogen or oxygen
protecting groups.5 Therefore, the preparation of carbamate
derivatives has attracted considerable attention.
Compounds containing both carbamate and a hydroxyl
group such as 1-carbamatoalkyl 2-naphthols are of consider-
able interest because hydrolysis of carbamates can produce
a variety of amino alcohols. These compounds are the main
sub-structure of 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.6-11 1-Carbamatoalkyl 2-naphthol derivatives are of
significant importance because of their promising biological
and pharmaceutical activities. Despite their importance from
pharmacological and synthetic points of view, comparatively
few methods for the preparation of 1-carbamatoalkyl 2-
naphthol derivatives have been reported in the literature via
multi-component reactions of aldehydes, 2-naphthol and
carbamate using acidic catalysts.12–21
was examined by XRD studies. The XRD pattern of
Mg(OOCCF3)2 is shown in Fig. 1 and reveals that the actual
phase was F6MgC4O4 (rhombohedral).
However, in a control reaction where no catalyst was used,
no product was formed and conversion of 2-naphthol was
found to be 0% after 2 h. This shows that the catalyst is essen-
tial for the product formation. Our investigation began with
an evaluation employing different catalysts and the reaction of
4-chlorobenzaldehyde, 2-naphthol and methyl carbamate was
chosen as a model of the reaction to form methyl (4-chlorophenyl)
(2-hydroxynaphthalen-1-yl)methylcarbamate (Scheme 2). Note
that under the same reaction conditions, Mg(OOCCF3)2 exhib-
ited much better activity than others and gave quite higher
yields for this transformation. Therefore, Mg(OOCCF3)2 was
selected as the active component for the preparation of 1-
carbamatoalkyl 2-naphthols. The results are summarised in
Table 1.
To choose the optimum conditions, initially, the reaction
of 4-chlorobenzaldehyde, 2-naphthol and methyl carbamate
was chosen as a model and the influence of Mg(OOCCF3)2 as
A general tendency in catalysis is to transform a successful
homogeneous catalytic reaction into a heterogeneous process
in which the catalyst can be easily separated from the reaction
mixture, allowing its reuse and the design of continuous
flow operations. The present work concentrates on the prepa-
ration and application of magnesium 2,2,2-trifluoroacetate
[Mg(OOCCF3)2] as a new Lewis acid in the synthesis of a
variety of 1-carbamatoalkyl 2-naphthol derivatives (Scheme 1).
Results and discussion
Mg(OOCCF3)2 has been prepared from the reaction of dry
MgCl2 withCF3COOH.ThecrystallinityofpureMg(OOCCF3)2
Fig. 1 X-ray diffraction patterns of Mg(OOCCF3)2.
Scheme 1 Preparation of 1-carbamatoalkyl-2-naphthol derivatives.
* Correspondent. E-mail: mohammadreza.mohammadshafiee@gmail.
com

JOURNAL OF CHEMICAL RESEARCH 2011 623
Scheme 2 Preparation of methyl (4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methylcarbamate using Mg(OOCCF3)2 as catalyst.
catalyst was examined to find the optimal conditions for the
reaction. As shown in Table 1, in the absence of catalyst no
product was obtained (entry 1). Our investigations show that
the use of catalyst is unavoidable for this transformation.
Among the tested solvents such as methanol, ethanol, water,
dichloromethane, n-hexane, ethyl acetate and a solvent-free
system, condensation of 4-chlorobenzaldehyde, 2-naphthol
and methyl carbamate is more facile and proceeded to give
highest yield, under solvent-free conditions (Table 2, entries
1–7). Next, the effect of temperature and amount of catalyst on
the rate of the reaction was investigated (Table 2, entries 8–14).
It was found that the reaction using Mg(OOCCF3)2 (0.1 mmol)
at 100 °C provided the best yield (Table 2, entry 12). The
results are summarised in Table 2.
(such as nitro) were reactants, the reaction time was shorter
than that with electron-donating groups (such as methyl).
Though meta- and para- substituted aromatic aldehydes gave
good results, ortho-substituted aromatic aldehydes (such as
2-chloro and 2-nitro) gave lower yields and a longer reaction
time because of the steric effects. As a result, the reaction of
butyraldehyde with 2-naphthol and methyl carbamate failed to
give any product (Table 3; Entry 16). Encouraged by the results
obtained with methyl carbamate, we turned our attention to
benzyl carbamate (Table 3). As shown in Table 3, 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 3,
entries 11–15).
We then explored the scope and efficiency of these
procedures for the synthesis of a wide variety of substituted
1-carbamatoalkyl2-naphthols(Scheme 1,Table 3).Asexpected,
this reaction proceeded smoothly and the desired products
were obtained in good to excellent yields. A series of aromatic
aldehydes were investigated (Table 3, entries 1–10). However,
when aromatic aldehydes with electron-withdrawing groups
The work-up procedure is very straightforward; that is, the
products were isolated and purified by simple filtration and
crystallization from ethanol. Our protocol avoids the use of dry
media during the reaction process, making it superior to the
previous methods.
To exhibit the merit of the present work in comparison
with previously reported results, we compared results of
PPA-SiO2,12 p-TSA/[bmim]Br,13 Brønsted acidic ionic liquid,14
SiO2–NaHSO4,15 4-(1-imidazolium) butane sulfonate16 and
HClO4–SiO2,17 in the synthesis of methyl (2-hydroxynaph-
thalen-1-yl)(phenyl)methylcarbamate. As shown in Table 4,
Mg(OOCCF3)2 can act as an effective catalyst with respect to
the reaction yield of the product.
Table 1 Catalyst screening
Entry Catalyst
Time/min Yield/%a
1
2
3
4
5
6
7
8
9
–
120
50
–
Trifluoroacetic acid (0.2 mmol)
MgCl2 (0.2 mmol)
MgO (0.2 mmol)
ZnO (0.2 mmol)
CaCl2 (0.2 mmol)
BaCl2 (0.2 mmol)
ZnCl2 (0.2 mmol)
Mg(OOCCF3)2 (0.2 mmol)
50
55
35
40
45
60
67
89
100
210
150
140
100
120
15
Conclusion
In conclusion, we have presented an efficient and powerful
method for the preparation of 1-carbamatoalkyl 2-naphthols
catalysed by Mg(OOCCF3)2. The reactions were carried out
under solvent-free conditions with short reaction times and
produce the corresponding products in good yields. The
present methodology offers several advantages such as good
yields, simple procedure, shorter reaction times and milder
conditions and the products were purified without resorting
to chromatography.
a Isolated yield; reaction condition: 4-chlorobenzaldehyde
(1 mmol), 2-naphthol (1 mmol) and methyl carbamate
(1.3 mmol); solvent-free, 100 °C.
Table 2 Optimisation of the reaction conditions in the pre-
paration of methyl (4-chlorophenyl)(2-hydroxynaphthalen-1-
yl)methylcarbamate
Experimental
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 Perkin
Elmer 781 spectrophotometer. Elemental analysis was performed on
a Heraeus CHN-O-Rapid analyser. Melting points were determined
in open capillaries with a Buchi 510 melting point apparatus. TLC
was performed on silica gel polygram SIL G/UV 254 plates. The
powder X-ray diffraction patterns were measured with D8, Avance,
Bruker, axis, diffractometer using CuKα irradiation.
Entry
Catalyst
(mmol)
T/°C
Solvent
Time/min Yield/%a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.04
0.1
0.32
0.4
Reflux H2O
Reflux CH2Cl2
500
500
500
500
500
500
18
300
100
15
–
35
60
67
40
55
85
–
70
81
73
87
75
70
Reflux Methanol
Reflux Ethanol
Reflux n–hexane
Reflux Ethyl acetate
100
–
–
–
–
–
–
–
–
–
80
Magnesium 2,2,2-trifluoroacetate [Mg(OOCCF3)2]; typical procedure
A 50 mL suction flask was equipped with a dropping funnel. The gas
outlet was connected to a vacuum system through an alkaline solution
trap. Anhydrous MgCl2 (10 mmol) was charged into the flask and
trifluoroacetic acid (20 mmol) was added dropwise over a period
of 30 min at room temperature. HCl evolved immediately. After
completion of the addition, the mixture was shaken for 30 min at
120
100
100
100
100
40
20
19
20
a Isolated yield.

624 JOURNAL OF CHEMICAL RESEARCH 2011
Table 3 Preparation of 1-carbamatoalkyl-2-naphthol derivatives using Mg(OOCCF3)2 as catalyst (0.1 mmol, 100 °C)
Entry
1
Aldehyde
Carbamate
Time/min
21
Yield/%a
85
M.p. [lit. m.p./°C]ref
210–212 [213]7
2
20
25
30
10
15
35
40
20
20
20
10
5
87
83
90
92
89
88
83
90
82
81
87
88
84
79
–
201–203 [206]7
[181–183 [182–184]7
189–191 [192]9
206–208 [205–207]9
249–251 [252]9
188
3
4
5
6
7
8
228–230 [230–232]8
203–205 [202–204]7
237–239 [241–242]9
180–182 [179–180]9
202
9
10
11
12
13
200–202 [205–207]8
188–190 [185–186]9
165–167 [163–165]9
–
14
20
30
250
15
16
a Isolated yield.

JOURNAL OF CHEMICAL RESEARCH 2011 625
Table 4 Comparison results of Mg(OOCCF3)2 with other catalysts reported in the literature
Entry
Catalyst
Condition
Time/min
Yield/%a
1
2
3
4
5
6
7
PPA-SiO2
SiO2–NaHSO4
HClO4-SiO2
4-(1-imidazolium) butane sulfonate
p-TSA/[bmim]Br
Brønsted acidic ionic liquid
Mg(OOCCF3)2
Solvent-free; 100 °C
Solvent-free; 100 °C
Solvent-free; 85 °C
Solvent-free; 80 °C
Solvent-free; 60 °C
Solvent-free; 90 °C
Solvent-free; 100 °C
6
3.5
5
120
55
2
90
81
90
78
76
87
85
21
a Isolated yield; based on the preparation of methyl (2-hydroxynaphthalen-1-yl)(phenyl)methylcarbamate.
100 °C, while the residual HCl was eliminated by suction. Finally, a
white solid Mg(OOCCF3)2 was obtained in 95% yield.
Received 10 August 2011; accepted 10 October 2011
Paper 1100841 doi: 10.3184/174751911X13182405888457
To a mixture of benzaldehyde (1 mmol), 2-naphthol (1 mmol) and
methyl carbamate (1.3 mmol) was added Mg(OOCCF3)2 (0.025 g;
0.1 mmol) and the mixture was heated at 100 °C in an oil bath for
the appropriate time (Table 3). The progress of the reaction was mon-
itored 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. The solvent was evaporated and
the solid product was purified by recrystallisation from ethanol.
Methyl (2-hydroxynaphthalen-1-yl)(p-tolyl)methylcarbamate (Table 2,
entry 7): 1H NMR (400 MHz, DMSO-d6): δ = 2.21 (s, 3H, CH3), 3.56
(s, 3H, OCH3), 6.83 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 7.6 Hz, 2H),
7.11–7.27 (m, 4H), 7.37 (t, J = 6.8 Hz, 1H), 7.63 (brs, 1H), 7.74 (d,
J = 8.8 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 6.0 Hz, 1H,
NH), 10.12 (s, 1H, OH) ppm; 13C NMR (125 MHz, DMSO-d6): 22.2,
51.8, 53.2, 120.1, 120.6, 124.1, 127.6, 127.8, 128.0, 130.0, 130.1,
130.2, 130.8, 133.6, 137.0, 140.9, 154.5, 158.1, ppm; IR (KBr, cm-1):
3422, 3306, 3025, 2950, 1687, 1628, 1579, 1555, 1518, 1436, 1377,
1272, 1243, 1182, 1141, 1067, 1040, 940, 852, 816, 781, 748, 708.
C20H19NO3: Found: C, 74.81; H, 5.99; N, 4.39. requires: C, 74.75; H,
5.96; N, 4.36%.
Benzyl (2,4-dichlorophenyl)(2-hydroxynaphthalen-1-yl)methylcar-
bamate (Table 2, entry 12): 1H NMR (400 MHz, DMSO-d6): δ = 5.02
(d, J = 12.8 Hz, 1H), 5.08 (d, J = 12.7 Hz, 1H), 6.87 (s, 1H), 7.14 (d,
J = 8.4 Hz, 1H), 7.28–7.60 (m, 10H), 7.74–7.80 (m, 2H), 8.02–8.11
(m, 2H), 9.98 (s, 1H, OH) ppm; 13C NMR (125 MHz, DMSO-d6):
51.1, 67.1, 117.8, 120.2, 124.0, 124.3, 128.1, 128.2, 129.1, 129.3,
129.9 (2C), 130.2, 130.3, 131.3, 132.9, 133.6, 134.2, 134.8, 138.7,
140.4, 155.2, 157.2 ppm; IR (KBr, cm-1): 3415, 3342, 3065, 2935,
1686, 1628, 1586, 1513, 1432, 1372, 1340, 1305, 1270, 1243, 1212,
1139, 1069, 1054, 936, 879, 844, 819, 744; C25H19Cl2NO3: Found:
C, 66.41; H, 4.25; N, 3.14; requires: C, 66.38; H, 4.23; N, 3.10%.
Published online: 22 November 2011
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