Zwitterionic-type molten salt: An efficient mild organocatalyst for synthesis of 2-amidoalkyl and 2-carbamatoalkyl naphthols

Article abstract of DOI:10.1016/j.catcom.2010.06.001

A green, general, and efficient method has been developed for the synthesis of 2-amidoalkyl and 2-carbamatoalkyl naphthol derivatives through a one-pot three-component condensation of 2-naphthol, aldehydes and amide or carbamates in the presence of zwitte

Full text of DOI:10.1016/j.catcom.2010.06.001

Catalysis Communications 11 (2010) 1157–1159
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Zwitterionic-type molten salt: An efficient mild organocatalyst for synthesis of
2-amidoalkyl and 2-carbamatoalkyl naphthols
⁎
Dhiman Kundu, Adinath Majee, Alakananda Hajra
Department of Chemistry, Visva-Bharati University, Santiniketan 731235, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A green, general, and efficient method has been developed for the synthesis of 2-amidoalkyl and 2-
carbamatoalkyl naphthol derivatives through a one-pot three-component condensation of 2-naphthol,
aldehydes and amide or carbamates in the presence of zwitterionic-type molten salt as mild organocatalyst
under solvent-free conditions.
Received 18 December 2009
Received in revised form 29 May 2010
Accepted 1 June 2010
Available online 9 June 2010
© 2010 Elsevier B.V. All rights reserved.
Keywords:
Zwitterionic salt
Organocatalyst
Multicomponent reaction
2-Amidoalkyl naphthol
2-Carbamatoalkyl naphthol
1. Introduction
amidoalkyl naphthols, a few reports was found describing the
synthesis of 2-carbamatoalkyl naphthols [16,21]. In addition, most
One-pot catalytic conversion of organic reactions with readily
available, non-toxic, and inexpensive reagents has attracted signifi-
cant research interest in recent years [1]. Multicomponent reactions
with atom-economy under catalytic solvent-free conditions are ideal
protocols for the development of environment-friendly and cost-
advantageous chemical processes [2,3]. Compounds bearing 1,3-
amino-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 and lipinavir [4,5]. 2-Amidoalkyl and 2-carbamatoalkyl
naphthol derivatives are of significant importance because of their
promising biological and pharmaceutical activities [6,7]. With the aim
to improve the reaction's efficiency, several methods have been
developed using different catalysts such as montmorillonite K10 clay
[8], Ce(SO4)2 [9,10], iodine [11], K5CoW12O40·3H2O [12], p-TSA [13],
sulfamic acid [14], cation-exchanged resins [15], silica-sodium
hydrogen sulphate [16], silica-perchloric acid [17,18], acidic ionic
liquid [19], and phosphorus pentaoxide [20] for synthesis of 2-
amidoalkyl naphthol derivatives by condensation of aryl aldehydes, 2-
naphthol, and amide. Although these methods are quite useful, many
of these methods suffer from limitations such as the requirement for a
large excess of reagents, long reaction times, harsh reaction condi-
tions and also involvement of toxic solvents. The recovery and
reusability of the catalyst are also a problem. By contrast with 2-
of these reactions were limited to only aromatic aldehydes. Thus,
there is a need for a simple, environment-friendly efficient and more
general method for the synthesis of these useful derivatives. Recently,
we reported the reaction of 2-naphthol and aldehyde (2:1) to form
dibenzoxanthenes [22] and the condensation of 2-naphthol, alde-
hydes and urea (1:1:1.5) to form naphthoxazinones [23]. Our goal is
to develop a tandem process that would allow in situ trapping of
ortho-quinone methides [24–26] with nitrogen nucleophiles to
provide a rapid access to amidoalkyl naphthol derivatives.
As a part of our continuing programme to explore molten salt
promoted novel reactions [27,28], we have observed that an imidazole-
based zwitterionic-type molten salt, 4-(1-imidazolium) butane sulfo-
nate (IBS) promotes the condensation of 2-naphthol, aldehyde and
carbamate or amide to produce 2-amidoalkyl and 2-carbamatoalkyl
naphthol derivatives under solvent-free conditions (Scheme 1).
2. Results and discussions
In a typical experimental procedure, a mixture of 2-naphthol,
aldehyde and amide in presence of 10 mol% molten salt was heated at
80 °C for a certain period of time as required to complete the reaction. A
wide range of structurally diverse aldehydes underwent condensation
by this reaction to provide 2-amidoalkyl naphthol derivatives in
excellent yields. The results are summarized in Table 1. As evident
from the results, this procedure is uniformly effective for both aliphatic
and aromatic aldehydes. The aliphatic aldehydes such as n-butyralde-
hyde, iso-butyraldehyde, and valeraldehyde were subjected under the
reaction conditions and corresponding desired products were isolated
⁎
Corresponding author. Tel.: +91 3463 261526; fax: +91 3463 262728.
E-mail address: alakananda.hajra@visva-bharati.ac.in (A. Hajra).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.06.001

1158
D. Kundu et al. / Catalysis Communications 11 (2010) 1157–1159
Scheme 1. Three-component synthesis of 2-amidoalkyl and 2-carbamatoalkyl naphthols.
in excellent yields. Aromatic aldehydes with both activating and de-
activating groups such as such as Me, OMe, Cl, Br, F and NO2 reacted to
afford the corresponding products almost equally in high yields. Both
acetamide and benzamide underwent smoothtransformation under the
reaction conditions.
Inaddition, thescope and efficiencyof the reactionwere explored for
the synthesis of 2-carbamatoalkyl naphthols using carbamate, 2-
naphthol and aldehydes. The desired products were obtained in good
yields without formation of any side products (Table 2). The con-
densation reaction proceeded very well with aliphatic aldehydes such as
propionaldehyde, n-butyraldehyde, iso-butyraldehyde, and cyclohe-
haxecarboxaldehyde under the reaction conditions. The efficiency and
generality of present protocol can be realized by direct comparing the
entry 1 presented here with a recently reported method [16] where
same reaction did not proceed. However, heteroaromatic aldehydes do
not produce the corresponding 2-carbamatoalkyl naphthols, instead
leads to multiple products.
formation o-quinone methide (o-QM) intermediate [24–26]. Further,
nucleophilic conjugate addition of amide or carbamate on o-QM
intermediate leads to the formation of amidoalkyl naphthol as a product
in excellent yields. In this reaction, the zwitterionic-type molten salt
may act a bifunctional organocatalyst [28–30]. It could activate both
aldehydic carbonyl oxygen and acidic hydrogen of 2-naphthol [31].
Our attention was then turned to the possibility of recycling the
catalyst from the reaction media since the recovery and reuse of the
catalyst are highly preferable for a greener process. At the completion
of the reaction, the reaction mixture was poured into crushed ice and
stirred for 5–10 min. The solid separated was filtered under suction.
The catalyst was recovered from the aqueous layer after evaporation
under reduced pressure, and reused for subsequent reactions. The
reusability of the catalyst was investigated by using 2-naphthol,
benzaldehyde and benzamide as model substrates. After five recycles,
the catalyst still had a high activity and gave the corresponding
product in good yield (77% for entry 11, Table 1).
A mechanistic rationale portraying the probable sequence of events
is given in Scheme 2. The reaction is believed to proceed through the
3. Experimental
Typical procedure for the synthesis of Methyl [1-(2-Hydroxynaphtha-
len-1-yl)-butyl] carbamate (entry 2, Table 2): A mixture of 2-naphthol
(288 mg, 2 mmol), n-butyraldehyde (179 μl, 144 mg, 2 mmol), and
methylcarbamate (165 mg, 2.4 mmol) was taken in a round-bottom
flask with glass stopper in presence of molten 4-(1-imidazolium)
butane sulfonate (41 mg, 10 mol%) and the whole mixture was stirred
at 80 °C (oil bath) for 20 min as indicated by TLC for a complete
reaction. The reaction mixture, being cooled to room temperature was
poured into crushed ice (20 g) and stirred for 5–10 min. The solid
separated was filtered under suction. The aqueous layer consisting of
zwitterionic salt was extracted with ethyl acetate (5 mL) to remove
the organic impurities. The catalyst was recovered from aqueous layer
after evaporation under reduced pressure and used for subsequent
reaction. The analytical pure sample was prepared by recrystallization
Table 1
Preparation of amidoalkyl naphthols.
Entry
Aldehyde R1
Amide R2
Time h/(min)
Yielda(%)
1
2
3
4
5
6
7
8
n-C3H7
n-C4H9
Me2CH
Ph
Me
Me
Ph
(20)
(25)
(20)
2
3
2
2
2
1.5
1.5
2
75
74
75
80
75
85
84
85
88
90
80
78
84
90
Me
Me
Me
Me
Me
Me
Me
Ph
4-OMe-C6H4
4-F-C6H4
4-Br-C6H4
4-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
Ph
4-Me-C6H4
4-Cl-C6H4
3-NO2-C6H4
9
10
11
12
13
14
Ph
Ph
Ph
2
2
2
a
Isolated yield.
Table 2
Preparation of carbamatoalkyl naphthols.
Entry
Aldehyde R1
Carbamate R2
Time h/(min)
Yielda(%)
1
2
3
C2H5
n-C3H7
Me2CH
OMe
OMe
OMe
(15)
(20)
(20)
72b
77
76
4
OMe
(25)
74
5
6
7
8
9
10
Ph
OMe
OMe
OMe
OMe
OBn
OBn
2
2
1.5
1.5
2
78
82
85
88
75
72
4-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
Ph
2-Cl-C6H4
3.5
aIsolated yield. bPropionaldehyde was taken 1.5 equiv. w.r.t. 2-naphthol.
Scheme 2. A plausible reaction mechanism.

D. Kundu et al. / Catalysis Communications 11 (2010) 1157–1159
1159
from ethanol (420 mg, 77% as white powder). mp 160–161 °C; IR
References
(KBr) 3305, 2954, 1685, 1525, 1340 cm−1; 1H NMR (300 MHz, DMSO-
d6): δ=9.97 (s, 1H), 8.10 (d, J=8.1 Hz, 1H), 7.76 (d, J=8.1 Hz, 1H),
7.67 (d, J=8.7 Hz, 1H), 7.44 (t, J=7.5 Hz, 1H), 7.26 (t, J=7.5 Hz, 1H),
7.17 (d, J=9.0 Hz, 2H), 5.53 (q, J=7.2 Hz, 1H), 3.48 (s, 3H), 2.02–1.96
(m, 1H), 1.81–1.74 (m, 1H), 1.37–1.33 (m, 1H), 1.25–1.14 (m, 1H), 0.87
(t, J=7.2 Hz, 3H); 13C NMR (75 MHz, DMSO-d6): δ=156.2, 152.8, 132.1,
128.6, 128.5, 128.3, 126.3, 122.4 (2 °C), 119.9, 118.5, 51.3, 48.0, 36.4, 19.6,
13.8; Anal. Cald. for C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.18;
H, 6.92; N 4.94.
[1] N. Mizuno, M. Misono, Chem. Rev. 98 (1998) 199.
[2] K. Tanaka, F. Toda, Chem. Rev. 100 (2000) 1025.
[3] H.R. Hobbs, N.R. Thomas, Chem. Rev. 107 (2007) 2786.
[4] D. Seebach, J.L. Matthews, J. Chem. Soc. Chem. Commun. (1997) 2015.
[5] E. Juaristi, In Enantioselective Synthesis of β-Amino Acids, John Wiley & Sons, New
York, 1997.
[6] T. Dingermann, D. Steinhilber, G. Folkers, In Molecular Biology in Medicinal
Chemistry, Wiley-VCH, 2004.
[7] A.Y. Shen, C.T. Tsai, C.L. Chen, Eur. J. Med. Chem. 34 (1999) 877.
[8] S. Kantevari, S.V.N. Vuppalapati, L. Nagarapu, Catal. Commun. 8 (2007) 1857.
[9] N.P. Selvam, P.T. Perumal, Tetrahedron Lett. 47 (2006) 7481.
[10] N.P. Selvam, P.T. Perumal, Tetrahedron 64 (2008) 2972.
[11] B. Das, K. Laxminarayana, B. Ravikanth, B.R. Rao, J. Mol. Catal. A Chem. 261 (2007)
180.
4. Conclusion
[12] L. Nagarapu, M. Baseeruddin, S. Apuri, S. Kantevari, Catal. Commun. 8 (2007)
1729.
[13] M.M. Khodaei, A.R. Khosropour, H. Moghanian, Synlett (2006) 916.
[14] S.B. Patil, P.R. Singh, M.P. Surpur, S.D. Samant, S. D. Ultrason. Sonochem. 14 (2007)
515.
[15] S.B. Patil, P.R. Singh, M.P. Surpur, S.D. Samant, Synth. Commun. 37 (2007) 1659.
[16] H.R. Shaterian, A. Hosseinian, M. Ghashang, Tetrahedron Lett. 49 (2008) 5804.
[17] G.H. Mahdavinia, M.A. Bigdeli, M.M. Heravi, Chin. Chem. Lett. 19 (2008) 1171.
[18] H.R. Shaterian, H. Yarahmadi, M. Ghashang, Tetrahedron 64 (2008) 1263.
[19] A.R. Hajipour, Y. Ghayeb, N. Sheikhan, A.E. Ruoho, Tetrahedron Lett. 50 (2009)
5649.
[20] G.C. Nandi, S. Samai, R. Kumar, M.S. Singh, Tetrahedron Lett. 50 (2009) 7220.
[21] H.R. Shaterian, A. Hosseinian, M. Ghashang, Chin. J. Chem. 27 (2009) 821.
[22] S. Urinda, D. Kundu, A. Majee, A. Hajra, Heteroatom Chem. 20 (2009) 232.
[23] A. Hajra, D. Kundu, A. Majee, J. Heterocyclic Chem. 46 (2009) 1019.
[24] A. Wolff, V. Boechmer, W. Vogt, F. Ugozzoli, G.D. Andreetti, J. Org. Chem. 55 (1990)
5665.
In summary, we have demonstrated herein that imidazole-based
zwitterionic-type molten salt is a new class of bifunctional organoca-
talyst for the synthesis of 2-amidoalkyl and 2-carbamatoakyl naphthol
derivatives through a three-component condensation reaction under
solvent-free conditions. The present procedure is equally effective to
aliphatic and aryl aldehydes. The non-hazardous experimental condi-
tions, reusable catalyst, ease of reaction, short reaction times, high
yields, and metal-free catalyst are the notable advantages of this
procedure. Thus, it provides a better and more practical alternative to
the existing methodologies.
[25] B. Das, K. Laxminarayana, M. Krishnaiah, Y. Srinivas, Synlett (2007) 3107.
[26] R.W. Vander de Water, T.R.R. Pettus, Tetrahedron 58 (2002) 5367.
[27] B.C. Ranu, S.S. Dey, S.S.A. Hajra, Tetrahedron 59 (2003) 2417.
[28] D. Kundu, R.K. Debnath, A. Majee, A. Hajra, Tetrahedron Lett. 50 (2009) 6998.
[29] A.K. Chakraborti, S.R. Roy, D. Kumar, P. Chopra, Green Chem. 10 (2008) 1111.
[30] A. Chakraborti, S.R. Roy, J. Am. Chem. Soc. 131 (2009) 6902.
[31] The electrophilic activation of the aldehyde carbonyl is expected to take place
through hydrogen bond formation with the C-2 hydrogen atom of the
imidazolium moiety. In addition, molten-salt plays the electrophilic/electrophil-
ic-nucleophilic dual activation role for aza-Michael addition in the final step to
form the product. Recently Chakraborti et al. have described an “eletrophilic
nucleophilic dual activation” role of the ionic liquid. See ref. [29,30].
Acknowledgments
A. H. is pleased to acknowledge the financial support from DST
(Grant No. SR/FTP/CS-107/2006). We are thankful to DST-FIST and
UGC-SAP. D. K. thanks CSIR for a fellowship. A. M. acknowledges
financial support from CSIR (Grant No. 01(2251)/08/EMR-II). We also
express our sincere thanks to Prof. B. C. Ranu, Department of
Chemistry, Indian Association for the Cultivation of Science, for his
advice and constant encouragement.