Efficient synthesis of β-amino alcohols catalyzed by niobium pentachloride: Regioselective ring opening of epoxides with aromatic amines

Article abstract of DOI:10.1080/00397910600908884

Epoxides undergo a rapid ring-opening reaction with aromatic amines catalyzed by niobium pentachloride under mild reaction conditions. All the reactions were carried out at room temperature to afford the corresponding β-amino alcohols in excellent yields

Full text of DOI:10.1080/00397910600908884

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Efficient Synthesis of β‐Amino Alcohols
Catalyzed by Niobium Pentachloride:
Regioselective Ring Opening of Epoxides with
Aromatic Amines
A. Venkat Narsaiah a , D. Sreenu a & K. Nagaiah a
a Division of Organic Chemistry, Fine Chemicals Laboratory , Indian Institute
of Chemical Technology , Hyderabad, India
Published online: 24 Nov 2006.
To cite this article: A. Venkat Narsaiah , D. Sreenu & K. Nagaiah (2006) Efficient Synthesis of β‐Amino
Alcohols Catalyzed by Niobium Pentachloride: Regioselective Ring Opening of Epoxides with Aromatic Amines,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:21, 3183-3189, DOI: 10.1080/00397910600908884
To link to this article: http://dx.doi.org/10.1080/00397910600908884
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Synthetic Communicationsw, 36: 3183–3189, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600908884
Efficient Synthesis of b-Amino Alcohols
Catalyzed by Niobium Pentachloride:
Regioselective Ring Opening of Epoxides
with Aromatic Amines
A. Venkat Narsaiah, D. Sreenu, and K. Nagaiah
Division of Organic Chemistry, Fine Chemicals Laboratory, Indian
Institute of Chemical Technology, Hyderabad, India
Abstract: Epoxides undergo a rapid ring-opening reaction with aromatic amines
catalyzed by niobium pentachloride under mild reaction conditions. All the reactions
were carried out at room temperature to afford the corresponding b-amino alcohols
in excellent yields and with high regioselectivity.
Keywords: Aromatic amines, b-amino alcohols, epoxides, niobium pentachloride
INTRODUCTION
The b-amino alcohols are versatile intermediates and major functional groups
for the synthesis of various biologically active natural and synthetic products,
synthetic amino acids, b-blockers, insecticidal agents, chiral auxiliaries, and
oxazolines, which have been widely explored as protecting groups.[1]
Because of remarkable synthetic demand, the development of an efficient
and environmentally friendly method for the regioselective ring opening of
epoxides constitutes an active area of investigation in organic synthesis.
One of the most straightforward synthetic approaches for the preparation of
b-amino alcohols involves heating an epoxide with an excess of amines at
Received in India April 12, 2006
IICT Communication No. 050916.
Address correspondence to K. Nagaiah, Division of Organic Chemistry, Fine
Chemicals Laboratory, Indian Institute of Chemical Technology, Hyderabad
500 007, India. E-mail: nagaiah@iict.res.in
3183

3184
A. V. Narsaiah, D. Sreenu, and K. Nagaiah
elevated temperatures. Because some functional groups may be susceptible to
high temperature, and also to control the regioselectivity, A variety of activa-
tors or promoters such as metal amides, metal triflates, transition-metal
halides,[2] microwaves, and ionic liquids[3] have been developed to perform
the epoxide ring-opening reactions with amines under mild reaction con-
ditions.[4] The introduction of a new and efficient method for this transform-
ation under more convenient and general conditions is still in demand.
Niobium pentachloride is well known in the literature as a mild and
efficient catalyst for various organic transformations.[5]
RESULTS AND CONDITIONS
As part of our ongoing program into develop various new synthetic method-
ologies,[6] herein we report our results on regioselective ring opening of
various oxiranes with aromatic amines using a catalytic amount (10 mol%)
of niobium pentachloride under mild reaction conditions.
In a typical experiment, styrene oxide 1 (2 mmol) and aniline 2 (2 mmol)
were stirred in the presence of niobium pentachloride (0.2 mmol) at room
temperature in dichloromethane to obtain the corresponding b-amino
alcohol 3a in 95% yield (Scheme 1). The reaction was completed within
1 h, and the epoxide opening takes place in a regioselective manner preferen-
tially at the benzylic position. Only a single product was obtained in all the
styrene oxide reactions, and the structure of the product was confirmed by
its 1H NMR spectrum. In a similar manner, glycidyl aryl ethers and
aliphatic alkyl oxiranes reacted smoothly with aryl amines to afford the corre-
sponding b-amino alcohols (4i–4p) in very good yields with high regioselec-
tivity. The epoxide opening takes place in a regioselective manner
preferentially at the terminal opening. In these reactions also, only a single
product was obtained, and the structure of the product was confirmed by its
1H NMR spectrum. Furthermore, a cycloalkyl epoxide such as cyclohexene
oxide reacted smoothly with different substituted aromatic amines to afford
the corresponding b-amino alcohols (5e–5h) in excellent yields with high
regioselectivity (Scheme 2).
The stereochemistry of the ring-opening products (Scheme 2) was found
to be trans from the coupling constants. In the case of epichlorohydrin
Scheme 1.

b-Amino Alcohols
3185
Scheme 2.
(Table 1, entries i–l) the ring-opening reaction proceeds very well, with one
product of b-amino alcohols but no side products. The four different
epoxides underwent ring opening with various substituted aromatic amines
to afford the corresponding b-amino alcohols in very good to excellent
yields. We noticed that the present reaction in the absence of NbCl5 could
1
not progress. All the products were characterized by H NMR, IR, and mass
spectroscopic data. This method does not require any anhydrous solvents or
stringent reaction conditions. No precautions need to be taken to exclude
moisture from the reaction medium. The reactions are clean and highly regio-
selective, affording high yields of products in a short reaction time of 1–4 h.
The scope and the generality of this process are illustrated with respect to
various epoxides and different substituted anilines. The advantages of
niobium pentachloride are its simplicity in handling and the easy workup
procedure for the isolation of products.
In conclusion, the present methodology describes a simple, convenient,
and efficient procedure for the regioselective ring opening of epoxides with
a variety of aromatic amines using a catalytic (10 mol) amount of niobium
pentachloride. The notable features of this procedure are mild reaction
conditions, excellent regioselectivity, cleaner reaction profiles, improved
yields, enhanced reaction rates, and simplicity of operation, which makes it
a useful and attractive process for the synthesis of b-amino alcohols of
biological and synthetic importance.
GENERAL PROCEDURE
Melting points were recorded on Buchi R-535 apparatus and are uncorrected.
IR spectra were recorded on a Perkin-Elmer FT-IR 240-c spectrophotometer.
1H NMR spectra were recorded on Gemini-200 spectrometer in CDCl3 using
TMS as internal standard. Mass spectra were recorded on a Finnigan MAT
1020 mass spectrometer operating at 70 eV. All the products’ physical and
spectroscopic data were compared with those reported in the literature.
Niobium pentachloride (0.2 mmol) was added to a mixture of epoxide
(2 mmol) and aniline (2 mmol) in dichloromethane (DCM, 10 mL). The
resulting mixture was stirred at room temperature for a specified period

3186
A. V. Narsaiah, D. Sreenu, and K. Nagaiah
Table 1. Niobium(V) chloride–catalyzed ring opening of epoxides
Reaction Yield
time (h) (%)b
Entry Substrate (1)
Aniline (2)
Producta
a
1.0
1.5
95
93
b
c
1.5
1.0
91
90
d
e
f
2.0
2.5
92
90
g
3.0
2.5
91
88
h
i
3.5
4.0
84
82
j
k
l
3.5
4.0
83
80
(continued)

b-Amino Alcohols
Table 1. Continued
3187
Reaction Yield
time (h) (%)b
Entry Substrate (1)
Aniline (2)
Producta
m
2.5
3.0
3.0
3.5
92
90
87
85
n
o
p
1
aAll the products characterized by H NMR, IR, and mass spectroscopy.
bYields were isolated and not optimized.
(Table 1). The progress of the reaction was monitored by thin-layer chromato-
graphy (TLC). After complete conversion of the starting material, the reaction
mixture was diluted by adding dichloromethane (20 mL). The mixture was
washed with water (2 ꢀ 20 mL) followed by brine solution. The organic layer
was dried over Na2SO4 and concentrated under reduced pressure to obtain the
crude products, which were purified by column chromatography (silica gel
60–120 mesh) while eluting with ethyl acetate–petroleum ether (3: 7).
Spectral Data of the Selected Products
2-(3-Chloro-2-methylphenylamino)-2-phenylethanol (3d): Brownish oil,
IR (neat) n 3412, 3326, 3068, 2942, 2851, 1605, 1554, 1436, 1372, 1251,
1
1128, 1049, 1018, 936, 847, 752 cm21; H NMR (CDCl3) d 2.35 (s, 3H),
3.70–3.80 (m, 1H), 4.40–4.50 (m, 1H), 4.95 (t, 1H, J ¼ 6.5 Hz), 6.18
(d, 1H, J ¼ 6.5 Hz), 6.65–6.80 (m, 1H) 7.25–7.40 (m, 6H); EIMS m/z (%)
261 (mþ 10), 230 (88), 156 (18), 125 (100), 103 (31), 91 (95), 77 (35), 61
(42), 57 (70), 43 (55). Calcd. for C15H16ClNO: C, 68.83; H, 6.16; N, 5.35.
Found: C, 68.81; H, 6.13; N, 5.32.
1-trans-2-(2-Chloro-3-methylphenylamino)-cyclohexanol (5h): Light-
colored solid, mp 49–508C; IR (KBr) n 3408, 3374, 3061, 2935, 2861,
1603, 1585, 1506, 1456, 1429, 1389, 1346, 1312, 1267, 1214, 1163, 1131,

3188
A. V. Narsaiah, D. Sreenu, and K. Nagaiah
1
1097, 1059, 946, 913, 854, 763, 748 cm21; H NMR (CDCl3) d 0.94–1.15
(m, 1H), 1.23–1.40 (m, 3H), 1.68–1.79 (m, 2H), 2.02–2.20 (m, 2H), 2.40
(s, 3H), 2.85 (brs, NH), 3.15 (ddd, 1H, J ¼ 4.0, 9.0 & 11.0 Hz), 3.38 (ddd,
1H, J ¼ 4.0, 10.0 & 10.0 Hz), 6.50 (d, 1H, J ¼ 6.5 Hz), 6.75 (d, 1H,
J ¼ 6.5 Hz), 7.05 (t, 1H, J ¼ 6.5 Hz); EIMS m/z (%) 241 (mþ 30), 204
(12), 189 (10), 127 (100), 114 (56), 90 (39), 75 (31), 65 (11), 51 (32).
Calcd. for C13H18ClNO: C, 65.13; H, 7.57; N, 5.84. Found: C, 65.10; H,
7.55; N, 5.81.
1-Chloro-3-(3-chloro-2-methylphenyl)-aminopropan-2-ol (4l): Brown-
colored syrup, IR (neat) n 3403, 3386, 3072, 2941, 2837, 1605, 1518, 1461,
1404, 1346, 1286, 1231, 1203, 1172, 1134, 1108, 1031, 917, 846,
1
748 cm21; H NMR (CDCl3) d 2.28 (s, 3H), 2.45 (brs, 1H), 3.25 (q, 1H,
J ¼ 6.5 Hz), 3.42 (dd, 1H, J ¼ 4.0 & 9.5 Hz), 3.65–3.75 (m, 2H), 4.00
(brs, 1H), 4.15 (brs, 1H), 6.53 (d, 1H, J ¼ 7.0 Hz), 6.80 (d, 1H,
J ¼ 7.0 Hz), 7.05 (t, 1H, J ¼ 7.0 Hz); EIMS m/z (%) 234 (mþ 10), 232
(15), 156 (41), 154 (100), 125 (15), 117 (10), 89 (20), 77 (12), 51 (10), 43
(12). Calcd. for C10H13Cl2NO: C, 51.30; H, 5.60; N, 5.98. Found C, 51.27;
H, 5.56; N, 5.95.
1-Phenoxy-3-(3-chloro-2-methylphenyl)-aminopropan-2-ol (4p): Light-
yellow oil, IR (neat) n 3403, 3371, 3065, 2943, 2849, 1636, 1606, 1541,
1
1508, 1431, 1362, 1308, 1256, 1137, 1046, 1012, 937, 851, 749 cm21; H
NMR (CDCl3) d 2.37 (s, 3H), 3.18 (dd, 1H, J ¼ 5.5 & 10.5 Hz), 3.32 (dd,
1H, J ¼ 5.5 & 10.5 Hz), 3.45–3.58 (m, 2H), 3.90–3.97 (m, 1H), 6.20
(d, 1H, J ¼ 7.0 Hz), 6.70–6.85 (m, 1H) 7.30–7.40 (m, 6H); EIMS m/z (%)
291 (mþ 21), 256 (18), 154 (21), 137 (100), 119 (56), 104 (11), 93 (15), 77
(25), 61 (412), 57 (37), 43 (51). Calcd. for C16H18ClNO2: C, 65.86; H,
6.22; N, 4.80. Found C, 65.84; H, 6.19; N, 4.78.
ACKNOWLEDGMENT
D. S. thanks Council of Scientific & Industrial Research (CSIR), New Delhi,
for providing a fellowship.
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