An efficient synthesis of [(tosylamino)alkyl]naphthalenols by nucleophilic addition of naphthalen-2-ol with N-tosyl imines using boron trifluoride etherate as catalyst

Article abstract of DOI:10.1002/hlca.201000224

[(Tosylamino)alkyl]naphthalenols have efficiently been synthesized by nucleophilic addition of naphthalen-2-ol with N-tosyl imines (derived from both aromatic and aliphatic aldehydes) in the presence of BF₃· OEt₂ as a catalyst at roo

Full text of DOI:10.1002/hlca.201000224

Helvetica Chimica Acta – Vol. 94 (2011)
289
An Efficient Synthesis of [(Tosylamino)alkyl]naphthalenols by Nucleophilic
Addition of Naphthalen-2-ol with N-Tosyl Imines Using Boron Trifluoride
Etherate as Catalyst1)
by Biswanath Das*, Cheruku Ravindra Reddy, Chava Sindhu, Duddukuri Nandan Kumar, and
Martha Krishnaiah
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
[(Tosylamino)alkyl]naphthalenols have efficiently been synthesized by nucleophilic addition of
naphthalen-2-ol with N-tosyl imines (derived from both aromatic and aliphatic aldehydes) in the
presence of BF3 · OEt2 as a catalyst at room temperature. The products are formed within 5 – 9 h in high
yields (72 – 91%).
Introduction. – Compounds possessing 1,3-amino oxygenated functional groups are
found in different bioactive natural products and important drugs such as HIV protease
inhibitors and nucleoside antibiotics [1]. They also exhibit biological properties
including bradycardiac and hypotensive activities [2]. In addition, they have been
applied as chelating agents and as catalysts [3]. Here, we report a simple method for the
synthesis of 1-[(tosylamino)alkyl]naphthalen-2-ols, which contains 1,3-amino oxy-
genated function.
Results and Discussion. – In continuation of our work [4] on the development of
useful synthetic methodologies, we have discovered that 1-[(tosylamino)alkyl]naph-
thalen-2-ols can be synthesized efficiently within 6 – 9 h by treatment of N-tosyl
aldimines with naphthalen-2-ol in the presence of BF3 · OEt2 as catalyst at room
temperature (Scheme 1). Recently, one method for the synthesis of these compounds
(in chiral form) has been reported, the synthesis involved a dinuclear zinc complex as a
catalyst, and the reaction time was 48 h [5].
Scheme 1
1
)
ꢂStudies on Novel Synthetic Methodologiesꢃ, Part 207.
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 94 (2011)
Initially, N-tosylbenzaldimine (1a; R ¼ Ph) was treated with naphthalen-2-ol for 8 h
using various catalysts at room temperature (Table 1). Considering the yield of the
products, BF3 · OEt2 was found to be most effective to catalyze the reaction. Even
within 6 h, a similar yield of the product was obtained in the presence of this catalyst.
Consequently, this catalyst was used to prepare a series of 1-[(tosylamino)alkyl]naph-
thalen-2-ols from various N-tosyl aldimines and naphthalen-2-ol (Table 2). The
conversion was complete within 6 – 9 h, and the products were formed in high yields
(72 – 91%). N-Tosyl aldimines were derived from both aromatic and aliphatic
aldehydes. The aromatic aldehydes containing electron-donating as well as electron-
withdrawing groups were used. A sterically hindered N-tosyl aldimine prepared from
naphthalene-2-carbaldehyde also underwent the conversion smoothly. Different
functional groups such as ether, halogen, nitrogen, and nitrile remained unchanged.
Table 1. Evaluation of the Activity of Different Catalysts for the Preparation of 1-[(Tosylamino)alkyl]-
naphthalen-2-olsa)
Entry
Catalyst
Yield [%]b)
1
2
3
BF3 · Et2O
Sc(OTf)3
Cu(OTf)2
InCl3
91
81
79
77
4
5
ZnCl2
69
6
ZrCl4
67
7
FeCl3
64
8
NaHSO4 · SiO2
62
9
10
I2
43
Trace
c
Ba(NO3)2
)
a) Reaction conditions: N-tosylbenzaldimine (1 mmol), naphthalen-2-ol (1 mmol), and catalyst (20 mol-
%) were stirred at r.t. for 8 h. b) Yield of the isolated product. c) The mixture was stirred for 24 h.
Table 2. Synthesis of [(N-Tosylamino)alkyl]naphthalen-2-olsa)
Entry
R
Time [h] Productb) M.p. [8] (solvent of crystallization) Yield [%]c)
1
2
3
4
5
6
7
8
9
4-ClꢀC6H4
7
9
8
5
7
6
6
8
9
9
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
168 – 170 (hexane/AcOEt 85 : 15)
195 – 197 (hexane/AcOEt 80 : 20)
181 – 183 (hexane/AcOEt 85 : 15)
156 – 158 (hexane/AcOEt 90 : 10)
155 – 157 (hexane/AcOEt 85 : 15)
174 – 176 (hexane/AcOEt 90 : 10)
171 – 173 (hexane/AcOEt 90 : 10)
207 – 209 (hexane/AcOEt 80 : 20)
182 – 185 (hexane/AcOEt 80 : 20)
184 – 186 (hexane/AcOEt 80 : 20)
177 – 179 (hexane/AcOEt 85 : 15)
91
87
84
89
90
86
91
89
88
88
72
3,4,5-(MeO)3ꢀC6H2
4-NCꢀC6H4
4-MeꢀC6H4
3-FꢀC6H4
Naphthalen-2-yl
Ph
2,3-(MeO)2ꢀC6H3
3-NO2ꢀC6H4
4-NO2ꢀC6H4
Pr
10
11
3j
3k
a) Reaction conditions: N-tosyl aldimine (1 mmol), naphthalen-2-ol (1 mmol) and BF3 · OEt2 (20 mol-
b
%) were used. ) The structures of the products were determined by their spectral analysis (IR, 1H- and
13C-NMR, and ESI- and HR-ESI-MS). c) Yield of isolated product.

Helvetica Chimica Acta – Vol. 94 (2011)
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1
The structures of the products were deduced from their spectral data (IR, H- and
13C-NMR, and ESI-, and HR-ESI-MS).
The catalyst, BF3 · OEt2 polarizes the ꢀCH¼Nꢀ bond of the N-tosyl aldimines to
facilitate the nucleophilic addition of naphthalen-2-ol (Scheme 2).
Scheme 2
The N-Ts group of the products can easily be removed [6] to afford the
corresponding (aminoalkyl)naphthalenols, which can be utilized to prepare their
various derivatives.
In conclusion, we have demonstrated a facile method for the synthesis of 1-
[(tosylamino)alkyl]naphthalen-2-ols from N-tosyl aldimines and naphthalen-2-ol using
BF3 · OEt2 as catalyst. The mild reaction conditions, shorter reaction times, operational
simplicity, and application of an inexpensive catalyst are the notable advantages of the
present method.
The authors thank UGC and CSIR, New Delhi, for financial assistance.
Experimental Part
General Procedure. To a soln. of N-tosyl aldimine (1.0 mmol) in CH2Cl2 (5 ml), naphthalen-2-ol
(1 mmol) was added under N2, followed by the addition of BF3 · OEt2 (0.2 mmol). The mixture was
stirred at r.t., and the reaction was monitored by TLC. After completion, the mixture was concentrated,
and H2O and AcOEt (10 ml each) were added. The org. layer was separated and concentrated. The
residue was subjected to column chromatography (SiO2; hexane/AcOEt) to obtain pure 1-[(tosylami-
no)alkyl]naphthalen-2-ol.
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Received June 5, 2010