[MeC(OH)2]+ClO4-: A new efficient organocatalyst for the preparation of 1-amido- and 1-carbamato-alkyl naphthols

Article abstract of DOI:10.1055/s-0031-1289906

[MeC(OH)₂]⁺ClO₄^- as a super acidic ionic liquid is found to be a new and highly efficient catalyst in the synthesis of amidoalkyl naphthols via three-component condensation of β-naphthol and aldehydes with nitri

Full text of DOI:10.1055/s-0031-1289906

LETTER
2947
–
[MeC(OH)2]+ClO4 : A New Efficient Organocatalyst for the Preparation of
1-Amido- and 1-Carbamato-alkyl Naphthols
O
rganocatalys
a
t
for the
P
re
t
paratio
e
n
of 1-Ami
m
do- and 1-Carbama
e
to-alkyl Na
h
phthols Tamaddon,* Javad Moazeni Bistgani
Department of Chemistry, Yazd University, P. O. Box 89195-741, Yazd, Iran
Fax +98(351)8210644; E-mail: ftamaddon@yazduni.ac.ir
Received 28 June 2011
ported zinc chloride, ZnCl2/SiO2) as catalyst.27 In contin-
Abstract: [MeC(OH)2]+ClO4– as a super acidic ionic liquid is found
to be a new and highly efficient catalyst in the synthesis of ami-
doalkyl naphthols via three-component condensation of b-naphthol
and aldehydes with nitriles, amides, or carbamates.
uation of our work, we have studied the catalytic behavior
of [MeC(OH)2]+ClO4– as a super acid in the synthesis of
amidoalkyl naphthols. Herein we report an improved
method for the synthesis of various types of amidoalkyl
phenols via three-component condensation of phenols and
aldehydes with nitriles, amides, or carbamates
(Scheme 2).
Key words: multicomponent reactions, amidoalkyl naphthols, ion-
ic liquids, super acids
Multicomponent reactions (MCR) are of great interest to
generate products by forming multiple new bonds in a sin-
gle pot. Efficiency, atom economy, and simplicity are fea-
tures that make MCR useful for the one-pot synthesis of
complex molecules.1 Amidoalkyl naphthols are used as
precursors in the synthesis of aminoalkyl phenols2 and ox-
azines.3 These compounds exhibit a broad spectrum of
medicinal activities such as antibiotic, antitumor, antima-
larial, antianginal, antihypertensive, antipsychotic, and
antirheumatic properties.4–8
OH
stirring
–
+
MeCOOH + HClO4
Scheme 1
OH
Me
ClO4
OH2
30 min
R1
NHCOR2
OH
[MeC(OH)2]+ ClO4– (1 mol%)
EtOAc, r.t.
+
R2CN or R2CONH2
+
Amidoalkyl naphthols are mainly prepared via the one-
pot, three-component condensation of phenol derivatives
and aldehydes with nitriles, amides, or carbamates.9–11 Al-
though this reaction has been promoted by a variety of ho-
mogeneous and heterogeneous Lewis or Brønsted acid
catalysts,12–16 some of these procedures suffer from limit-
ed scope, low yields, use of expensive catalysts, and long
reaction times. In addition, few catalyzed syntheses of
amidoalkyl phenols take place at room temperature, and
some investigations have pointed to the generation of
dibenzoxanthene as a side product at high temperature.
R1CHO
R
1 = aryl, alkyl R2 = aryl, alkyl, NH2, OR3
Scheme 2
Initially, to find the optimal conditions, reaction of ben-
zaldehyde, 2-naphthol, and benzamide as a model system
was performed under various conditions and loading of
catalyst. As Table 1 shows, the best results were obtained
in the presence of 1 mol% of [MeC(OH)2]+ClO4 either at
–
80 °C under solvent-free conditions or in ethyl acetate at
room temperature (Table 1, entries 5 and 6). In both cases,
as the reaction progressed, the reaction product precipitat-
ed. Comparative studies of the model reaction using the
same amounts of AcOH or HClO4 on their own under sol-
vent-free conditions showed that the desired amidoalkyl
naphthol was formed in 50% yield together with the cor-
responding dibenzoxanthene as side product in 50% yield.
One-pot catalytic organic transformations using organo-
catalysts have attracted significant interest in recent
years.17–19 The readily prepared nonaqueous mixture of
acetic acid and percholoric acid which is able to protonate
very weak organic bases was proposed as a super acid
(pH = –4.4) by Conant and Hall in 1927.20–22 This mix-
–
ture, with the composition [MeC(OH)2]+ClO4 , can be
With these results in hand, we carried out further reactions
in EtOAc at room temperature. A control experiment
without catalyst did not afford the product even after heat-
ing. Various 1-amidoalkyl phenols were isolated in excel-
lent yields by the reaction of 2-naphthol, aromatic or
aliphatic aldehydes and amides using 1 mol% of
considered as an acidic room-temperature ionic liquid and
should be a good catalyst in organic transformations
(Scheme 1). To our knowledge, this super acid has not
been previously evaluated.
In a continuation of our investigations into catalytic
organic transformations,23–26 we have recently reported
Ritter and Ritter-type reactions using silzic (silica-sup-
–
[MeC(OH)2]+ClO4 at room temperature. As illustrated in
Table 2, various substrates were well tolerated. Aromatic
aldehydes bearing electron-withdrawing groups reacted
faster than those with electron-donating groups while the
SYNLETT 2011, No. 20, pp 2947–2950
x
x
.x
x
.2
0
1
1
Advanced online publication: 23.11.2011
DOI: 10.1055/s-0031-1289906; Art ID: D20411ST
© Georg Thieme Verlag Stuttgart · New York

2948
F. Tamaddon, J. M. Bistgani
LETTER
position of substitution did not have a significant effect on Furthermore, this protocol was not limited to amides.
the reaction.
Thus three-component reaction of 2-naphthol and alde-
hydes with methyl carbamat or urea led to the formation
of the corresponding adducts in high yield (Table 2, en-
tries 12 and 13).
Table 1 Optimization of the Reaction of Benzaldehyde, 2-Naph-
thol, and Benzamide
Ph
NHCOPh
OH
OH
catalyst
Table 3 Synthesis of Amidoalkyl Naphthols via Ritter-Type Reac-
PhCONH2
+
PhCHO
+
tion Using [MeC(OH)2]+ClO4
–
R1
NHCOR2
OH
Entry Catalyst (mol%), solvent
Temp Time
Yield
(°C)
80
80
r.t.
80
r.t.
80
r.t
(min) (%)a
[MeC(OH)2]+ClO4
–
R CHO R2CN +
1
β-naphthol
+
1
2
AcOH (50), –
HClO4 (20), –
80
80
23
19
12
9
50b
50b
85
85
94
95
91
92
90
90
80 °C, solvent-free
Entry R1
R2
Time Yield Obs. mp Lit. mp
(h)
(%)a (°C)
(°C)
237–239 239–2408
246–248 247–2498
222–224 223–2258
239–242 240–24210
239–242
–
3
[MeC(OH)2]+ClO4 (0.5), EtOAc
[MeC(OH)2]+ClO4– (0.5), –
[MeC(OH)2]+ClO4– (1), EtOAc
[MeC(OH)2]+ClO4– (1), –
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
5.5 88
4
4-O2NC6H4
4-MeC6H4
n-Pr
5
7
91
84
5
6
6.5 85
87
4-BrC6H4 4-O2NC6H4 5.5 90
7
[MeC(OH)2]+ClO4– (2), EtOAc
[MeC(OH)2]+ClO4– (2), –
8
4-BrC6H4 Ph
6
8
80
r.t.
80
8
237–240
9
[MeC(OH)2]+ClO4– (5), EtOAc
[MeC(OH)2]+ClO4– (5), –
6
4-BrC6H4 2-furyl
4-ClC6H4 Ph
5
90
241–244
10
5
5.5 85
236–239
a Isolated yield.
b Dibenzoxanthene was formed as a side product.
a Isolated yield.
Table 2 Synthesis33,34 of 1-Amidoalkyl and 1-Carbamato-alkyl Naphthols Using [MeC(OH)2]+ClO4
–
R1
NHCOR2
OH
[MeC(OH)2]+ClO4
–
R1CHO + R2CONH2 β-naphthol
+
80 °C, solvent-free
or EtOAc, r.t.
Entry
R1
R2
Time (min)
Yield (%)a
Obs. mp (°C)
Lit. mp (°C)
239–2409
247–2499
223–2259
234–23611
–
1
Ph
Ph
9
8
95
94
88
90
91
90
91
89
88
91
91
85
87
237–239
246–248
222–224
235–238
228–231
239–242
232–234
222–225
232–235
239–242
237–240
216–218
174–176
2
4-O2NC6H4
4-MeC6H4
2-furyl
2-pyrrole
n-Pr
Ph
3
Ph
23
11
13
16
12
17
20
13
12
27
33
4
Ph
5
Ph
6
Ph
240–24211
232–23312
–
7
Ph
Me
8
2-pyrrole
n-Pr
Me
9
Me
–
10
Ph
4-BrC6H4
4-BrC6H4
MeO
NH2
–
11
4-O2NC6H4
Ph
–
12
217–21831
176–17832
13
Ph
a Isolated yield.
Synlett 2011, No. 20, 2947–2950 © Thieme Stuttgart · New York

LETTER
Organocatalyst for the Preparation of 1-Amido- and 1-Carbamato-alkyl Naphthols
2949
(23) Tamaddon, F.; Amrollahi, M. A.; Sharafat, L. Tetrahedron
Lett. 2005, 46, 7841.
(24) Tamaddon, F.; Khoobi, M.; Keshavarz, E. Tetrahedron Lett.
2007, 48, 3643.
(25) Tamaddon, F.; Nasiri, A.; Farokhi, S. Catal. Commun. 2011,
12, 1477.
(26) Tamaddon, F.; Tavakoli, F. manuscript submitted for
publication.
(27) Tamaddon, F.; Tavakoli, F. J. Mol. Catal. A: Chem. 2011,
337, 52.
(28) Bamoharram, F. F.; Heravi, M. M.; Roshani, M.;
Sane Charkhi, M. J. E.-J. Chem. 2011, 8, 523.
(29) An, L. T.; Lu, X. H.; Ding, F. Q.; Jiang, W. Q.; Zou, J. P.
Chin. J. Chem. 2008, 26, 2117.
(30) Wang, M.; Liang, Y. Monatsh. Chem. 2010, 142, 153.
(31) Shaterian, H. R.; Hosseinian, A.; Ghashang, M. Tetrahedron
Lett. 2008, 49, 5804.
Ritter-type reaction of acetonitrile, b-naphthol, and alde-
hydes has been also reported as an alternative for the prep-
aration of amidoalkyl naphthols.31 Therefore, we studied
reaction of b-naphthol and aldehydes with nitriles in the
–
presence of [MeC(OH)2]+ClO4 under solvent-free condi-
tions. A series of amidoalkyl naphthols was prepared in
good to excellent yields (Table 3).
In conclusion, we have developed an efficient catalytic
process for the synthesis of amidoalkyl naphthols from
both amides or nitriles in the presence of 1 mol% of
–
[MeC(OH)2]+ClO4 as a super acidic ionic liquid. Short
reaction times, high yield, purity of the products, and sim-
ple workup and isolation are the features of this proce-
dure.
(32) Hajipour, A. R.; Ghayeb, Y.; Sheikhan, N.; Ruoho, A. E.
Tetrahedron Lett. 2009, 50, 5649.
Acknowledgment
(33) General Procedure for the [MeC(OH)2]+ClO4 -
–
We are grateful to the Research Council of Yazd University.
Catalyzed Synthesis of Amidoalkyl Naphthols
A mixture of an aldehyde (1 mmol), b-naphthol (1 mmol)
with amide, nitrile, urea, or carbamate (1 mmol) in the
presence of [MeC(OH)2]+ClO4– (1 mol%) was stirred in
EtOAc (1 mL) at r.t. (or at 80 °C under solvent-free
conditions) for the given times. After completion of the
reaction (TLC monitoring), H2O was added, and the
precipitate was filtered off to give the corresponding
amidoalkyl naphthols. Most of the products were known and
characterized by comparison of their melting points and
spectral data with those reported in the literature without
further purification. In some cases the products were
recrystallized from EtOH–H2O (60:40).
References and Notes
(1) Hobbs, H. R.; Thomas, N. R. Chem. Rev. 2007, 107, 2786.
(2) Shen, A. Y.; Tsai, C. T.; Chen, C. L. Eur. J. Med. Chem.
1999, 877.
(3) Damodiran, M.; Selvam, N. P.; Perumal, P. T. Tetrahedron
Lett. 2009, 50, 5474.
(4) Johnson, P. Y.; Silver, R. B. J. Heterocycl. Chem. 1973, 10,
1029.
(5) Haneishi, T.; Okazaki, T.; Hata, T.; Tamura, C.; Nomura,
M.; Naito, A.; Seki, I.; Arai, M. J. Antibiotics 1971, 24, 797.
(6) Lesher, G. Y.; Surrey, A. R. J. Am. Chem. Soc. 1955, 77,
636.
(7) Matsuoka, H.; Ohi, N.; Mihara, M.; Suzuki, H.; Miyamoto,
K.; Maruyama, N.; Tsuji, K.; Kato, N.; Akimoto, T.; Takeda,
Y.; Yano, K.; Kuroki, T. J. Med. Chem. 1997, 40, 105.
(8) Ren, H.; Grady, S.; Gamenara, D.; Heinzen, H.; Moyna, P.;
Croft, S.; Kendrick, H.; Yardley, V.; Moyna, G. Bioorg.
Med. Chem. Lett. 2001, 11, 1851.
(34) Selected Characterization Data
N-[(2-Hydroxynaphthalen-1-yl)(phenyl)methyl]-
benzamide (Table 2, Entry 1)9,18
White solid; mp 235–237 °C. IR (KBr): nmax = 1625, 3065,
3418 cm–1. 1H NMR (300 MHz, DMSO-d6): d = 7.20–7.90
(m, 16 H), 8.10–8.13 (d, 1 H, J = 8.4 Hz), 9.02 (d, 1 H,
J = 8.4 Hz), 10.33 (s, 1 H, NH) ppm. 13C NMR (75 MHz,
DMSO-d6): d = 50.0, 119.1, 119.4, 123.4, 127.1, 127.2,
127.5, 127.8, 128.9, 129.1, 129.2, 129.3, 130.1, 132.1,
133.0, 135.0, 142.7, 147.0, 153.9, 166.4 ppm.
(9) Khodaei, M. M.; Khosropour, A. R.; Moghanian, H. Synlett
2006, 916.
N-[(2-Hydroxynaphthalen-1-yl)(4-nitrophenyl)methyl]-
(10) Das, B.; Laxminarayana, K.; Ravikanth, B.; Rao, B. R.
J. Mol. Catal. A: Chem. 2007, 261, 180.
benzamide (Table 2, Entry 2)29,8
Yellow solid; mp 247–249 °C. IR (KBr): nmax = 1641, 3234,
3410 cm–1. 1H NMR (300 MHz, DMSO-d6): d = 7.22–7.56
(m, 9 H), 7.82–7.91 (m, 4 H), 8.06 (d, 1 H, J = 8.4 Hz), 8.14
(d, 2 H, J = 8.4 Hz), 9.04 (d, 1 H, J = 8.1 Hz), 10.35 (s, 1 H,
NH) ppm. 13C NMR (75 MHz, DMSO-d6): d = 49.1, 117.4,
118.6, 122.6, 122.8, 123.4, 127.0, 127.4, 127.5, 128.4,
128.7, 130.0, 131.6, 132.2, 134.0, 146.2, 150.2, 153.4, 166.3
ppm.
(11) Szatmari, I.; Fulop, F. Synthesis 2009, 775.
(12) Patil, S. B.; Singh, P. R.; Surpur, M. P.; Samant, S. D.
Ultrason. Sonochem. 2007, 14, 515.
(13) Shaterian, H. R.; Yarahmadi, H. Tetrahedron Lett. 2008, 49,
1297.
(14) Das, B.; Laxminarayana, K.; Thirupathi, P.; Ramarao, B.
Synlett 2007, 3103.
(15) Rashinkar, G.; Salunkhe, R. J. Mol. Catal. A: Chem. 2010,
316, 146.
(16) (a) Kunda, D.; Majee, A.; Hajra, A. Catal. Commun. 2010,
11, 1157. (b) Zhang, Q.; Luo, J.; Wei, Y. Green Chem. 2010,
12, 2246.
(17) Foroughifar, N.; Mobinikhaledi, A.; Moghanian, H.;
Ebrahimi, S.; Bodaghi Fard, M. A. Synlett 2008, 821.
(18) Nandi, G. C.; Samai, S.; Kumar, R.; Singh, M. S.
Tetrahedron Lett. 2009, 50, 7220.
(19) Niralwad, K. S.; Shingate, B. B.; Shingare, M. S. Chin.
Chem. Lett. 2011, 22, 551.
(20) Hall, N. F.; Conant, J. B. J. Am. Chem. Soc. 1927, 49, 3047.
(21) Conant, J. B.; Hall, N. F. J. Am. Chem. Soc. 1927, 49, 3062.
(22) Matsumoto, K. Tetrahedron 1968, 24, 6851.
N-[(2-Hydroxynaphthalen-1-yl)(p-tolyl)methyl]-
benzamide (Table 2, Entry 3)8,9
White solid; mp 223–225 °C. IR (KBr): nmax = 1627, 3043,
3413 cm–1. 1H NMR (300 MHz, DMSO-d6): d = 1.97 (s, 3 H,
CH3), 2.23 (s, 3 H, CH3), 7.05–7.38 (m, 8 H), 7.74–7.81 (m,
2 H), 7.85 (d, 1 H, J = 8.4 Hz), 8.38 (d, 1 H, J = 8.4 Hz), 9.94
(s, 1 H, NH) ppm. 13C NMR (75 MHz, DMSO-d6): d = 20.5,
22.6, 47.6, 118.4, 119.0, 122.3, 126.0, 126.2, 128.5, 129.0,
132.3, 135.0, 139.5, 153.0, 169.0 ppm.
N-[1-(2-Hydroxynaphthalen-1-yl)butyl]benzamide
(Table 2, Entry 6)30
White solid; mp 240–242 °C. IR (KBr): nmax = 3415, 3222,
3204, 1633, 1575, 1528, 1342, 1074, 815, 747, 716 cm–1. 1H
NMR (300 MHz, DMSO-d6): d = 10.09 (s, 1 H), 8.60 (d, 1
Synlett 2011, No. 20, 2947–2950 © Thieme Stuttgart · New York

2950
F. Tamaddon, J. M. Bistgani
LETTER
J = 7.5 Hz), 7.70 (d, 1 H, J = 9.1 Hz) ppm. 13C NMR (75
MHz, DMSO-d6): d = 23.2, 40.3, 119.2, 122.9, 123.8, 126.6,
126.8, 128.5, 128.8, 128.9, 129.1, 129.8, 132.8, 143.1,
153.7, 169.0 ppm.
H, J = 6.3 Hz), 8.23 (d, 1 H, J = 7.6 Hz), 7.81 (t, 3 H, J = 7.2
Hz), 7.71 (d, 1 H, J = 8.8 Hz), 7.53–7.44 (m, 4 H), 7.31 (t, 1
H, J = 7.3 Hz), 7.20 (d, 1 H, J = 8.8 Hz), 6.04 (q, 1 H, J = 7.1
Hz), 2.15–2.10 (m, 1 H), 1.90–1.80 (m, 1 H), 1.51–1.42 (m,
1 H), 1.30–1.20 (m, 1 H), 0.95 (t, 3 H, J = 7.3 Hz) ppm. 13
C
4-Bromo-N-[(2-hydroxynaphthalen-1-yl)(phenyl)-
methyl]benzamide (Table 2, Entry 10)
NMR (75 MHz, DMSO-d6): d = 165.2, 152.8, 134.7, 132.1,
131.1, 128.5, 128.4, 128.3, 128.2, 126.9, 126.3, 122.3,
119.8, 118.6, 118.5, 46.6, 36.0, 19.6, 13.8 ppm.
Yellow solid; mp 239–242 °C. IR (KBr): nmax = 3408, 3246,
3146, 1626 cm–1. 1H NMR (400 MHz, DMSO-d6): d = 7.22
(m, 7 H), 7.41 (t, 2 H, J = 8.0 Hz), 7.66 (t, 2 H, J = 4.4 Hz),
7.78 (m, 4 H), 8.02 (d, 1 H, J = 8.0 Hz), 7.20 (m, 2 H), 9.08
(d, J = 4.0 Hz, 1 H), 10.26 (s, 1 H) ppm. 13C NMR (100
MHz, DMSO-d6): d = 49.7, 115.5, 118.2, 122.6, 126.8,
128.3, 128.8, 128.9, 133.1, 142.8, 153.6, 167.8 ppm. Anal.
Calcd for C24H18BrNO2: C, 66.68; H, 4.20; Br, 18.48; N,
3.24; O, 7.40. Found: C, 66.75; H, 4.11; N, 3.15.
N-[Phenyl-(2-hydroxy-naphthalen-1-yl)-methyl]-
acetamide (Table 2, Entry 7)11,28
White solid; mp 232–233 °C. IR (KBr): nmax = 3390, 3246,
3062, 1640, 1582, 1514, 1372, 1337, 1060, 808, 742, 696,
623 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.95 (s, 3 H),
7.10 (m, 1 H), 7.12 (m, 1 H), 7.15 (m, 1 H), 7.17 (m, 1 H),
7.20 (m, 2 H), 7.21 (m, 1 H), 7.25 (m, 1 H), 7.35 (t, 1 H,
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