Bi3+ catalyzed regioselective ring opening of epoxides with aromatic amines

Article abstract of DOI:10.1081/SCC-120006000

Epoxides undergo the facile ring opening with anilines to afford the corresponding β-amino alcohols in excellent yields by bismuth trichloride in acetonitrile at ambient temperature.

Full text of DOI:10.1081/SCC-120006000

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3+
Bi CATALYZED REGIOSELECTIVE RING OPENING OF
EPOXIDES WITH AROMATIC AMINES
a
a
b
N. Raghavendra Swamy , G. Kondaji & K. Nagaiah
a
Organic Chemistry Division-III , Fine Chemical Laboratory , Indian Institute of Chemical
Technology , Hyderabad, 500 007, India
b
Organic Chemistry Division-III , Fine Chemical Laboratory , Indian Institute of Chemical
Technology , Hyderabad, 500 007, India
Published online: 16 Aug 2006.
3+
To cite this article: N. Raghavendra Swamy , G. Kondaji & K. Nagaiah (2002) Bi CATALYZED REGIOSELECTIVE RING OPENING
OF EPOXIDES WITH AROMATIC AMINES, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:15, 2307-2312, DOI: 10.1081/SCC-120006000
To link to this article: http://dx.doi.org/10.1081/SCC-120006000
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 15, pp. 2307–2312, 2002
3Q
Bi CATALYZED REGIOSELECTIVE
RING OPENING OF EPOXIDES WITH
AROMATIC AMINES
N. Raghavendra Swamy, G. Kondaji, and K. Nagaiah*
Organic Chemistry Division-III,
Fine Chemical Laboratory, Indian Institute of
Chemical Technology, Hyderabad, India 500 007
ABSTRACT
Epoxides undergo the facile ring opening with anilines to
afford the corresponding b-amino alcohols in excellent
yields by bismuth trichloride in acetonitrile at ambient
temperature.
b-Amino alcohols are an important class of compounds, which are
known to have a wide range of biological activities in the field of drugs
[
1–3]
and pharmaceuticals.
They have also been used as chiral auxiliaries in
[
4]
asymmetric synthesis. One of the best routes for the synthesis of b-amino
alcohols involves the ring opening of epoxides by amines in the presence of
either Lewis acids or Bronsted acids.
*Corresponding author. Fax: þ91-40-7160387/7160757; E-mail: nagaiah@iict.ap.
nic.in
2
307
DOI: 10.1081/SCC-120006000
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2
308
RAGHAVENDRA SWAMY, KONDAJI, AND NAGAIAH
Recently, a variety of activators have been introduced in literature to
[
5]
carry out epoxide opening at room temperature. In the past few years,
[6]
[7]
several metal triflates and metal halides have also been used to catalyze
the opening of epoxides with amines. These procedures required longer
[
8]
reaction time to achieve desired product. However, there are still some
limitations with the literature methods. For example deactivated aromatic
amines such as p-nitroaniline failed to react with epoxides and required
[8]
higher temperature. Further metal triflates are highly expensive.
In view of the current thrust on catalytic processes there is a merit in
developing a truly catalytic opening of epoxide with amine using inexpensive
and non-polluting reagents. Herein, we wish to report bismuth trichloride
catalyzed ring opening of epoxides with anilines. The reaction proceeds
efficiently at ambient temperature and the products are obtained in excellent
yields. Furthermore other functionalities such as chloro –OH, –NO , –CH3
2
and –OCH were compatible under the reaction conditions. As the reaction
3
conditions are very mild no by-products are observed. We first examined the
reaction of cyclohexane oxide with aniline in the presence of bismuth
trichloride in acetonitrile at ambient temperature affording the correspond-
ing amino alcohol [a] in 97% yield (Entry 1). This success has encouraged us
to extend the generality of the reaction to other epoxides with various
amines (Table). For example 2-Me aniline (Entry 1) and 2-hydroxy aniline
(Entry 1) reacted well to give corresponding amino alcohol in excellent
1
yields. All the products are fully characterized by H NMR, IR and mass
spectral data. The trans stereochemistry of amino alcohol (entry) was deter-
mined from the coupling constants of ring protons at ꢀ 3.34 (ddd, J ¼ 9.9,
1
.9 and 4.5) of the peak at 3.34 ppm (CH–OH). In H NMR spectrum like-
9
wise the peak at 3.14 ppm for CH–NHPh showed the similar kind of split-
ting pattern (ddd, J ¼ 10.8, 9.3, 3.9 Hz) spectra.
In conclusion the present procedure for the preparation of b-amino
compounds has the advantage of mild reaction conditions, reduced reaction
time inexpensive catalyst, high yields of products and simple experimental
work-up procedure which makes it an useful and important addition to the
present existing methodologies.

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RING OPENING OF EPOXIDES BY AMINES
2309
Table. BiCl3 Catalyzed Epoxide Opening with Aromatic Amines
a
b
Yield (%)
Entry
Amino Alcohol
Time (h)
a.
b.
c.
d.
e.
f.
R¼H, Ar¼C H
97
96
95
96
97
97
96
94
1.0
1.0
1.5
1.5
1.5
1.0
1.5
1.5
6
5
4
4
R¼H, Ar¼C
R¼H, Ar¼C
6
H
H
–O–OH
–p-Cl
6
R¼H, Ar¼C H –O–Me
6
4
R¼C
2
H
5
, Ar¼C
6 5
H
R¼H, Ar¼C
6
H
4
–p-Ome
6 5
–C H
g.
h.
R¼Ph, Ar¼ÀCH
2
R¼H, Ar¼C H –p-NO
6
4
2
i.
j.
k.
l.
R¼H, R¼C
6
H
5
97
96
96
95
1.0
1.5
1.0
1.5
6 4
R¼H, Ar¼C H –O–Me
R¼C H , Ar¼C H
2
5
6
5
R¼H, Ar¼C
6
H
–p-NO
4 2
m.
R¼H, Ar¼C
6
H
5
97
1.5
a
1
All products were characterized by H NMR, IR and Mass spectrum and also
comparison with authentic compounds.
b
Isolated and unoptimized yields.
General Procedure for the Generation of b-Amino Alcohols from
Epoxides: A solution of an epoxide (1 mmol) and an aromatic amine
(
(
1.1 mmol) in acetonitrile (10mL) was treated with bismuth trichloride
5 mol%) stirred under N atmosphere for 1.5 h at room temperature. The
2
reaction was monitored by TLC. The reaction upon completion the solvent
was removed on a rotary evaporator and the crude product was purified
over silica gel by column chromatography to provide pure trans amino
alcohol in high yield.

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2
310
RAGHAVENDRA SWAMY, KONDAJI, AND NAGAIAH
ꢀ
trans-2-(Phenylamino)cyclohexanol (a): M.p. 58–59 C (lit. m.p.
ꢀ
1
0–62 C), R 0.25 (1 : 10 EtOAc in petroleumether); H NMR (CDCl3,
6
5
2
9
7
6
f
00 MHz): ꢀ 1.04–1.22 (m, 1H), 1.34–1.52 (m, 3H), 1.75–1.82 (m, 2H),
.12–2.31 (m, 2H), 3.04 (bs, 2H, NH and OH), 3.14 (ddd, 1H, J ¼ 10.8,
.3, 3.9 Hz), 3.34 (ddd, 1H, J ¼ 9.9, 9.9 and 4.5 Hz), 6.75–6.81 (m, 3H),
1
3
.1–7.25 (m, 2H); C NMR (CDCl , 500 MHz): ꢀ 24.2, 24.9, 31.5, 33.1,
3
0.0, 74.3, 114.2, 118.2, 129.2, 147.7.
1
2-[N-(2-Hydroxycyclohexyl)amino]phenol (b): H NMR (CDCl ): ꢀ
3
1
3
.0–1.2 (m, 1H), 1.22–1.48 (m, 3H), 1.6–1.8 (m, 2H), 1.95–2.2 (m, 2H),
.0–3.12 (m, 1H), 3.4–3.55 (m, 1H), 4.17 (br s, 2H, exchangeable), 6.45
(
M.S. m/z (%): 207 (65, M), 148 (100). Anal. calcd. for C H NO : C,
td, 1H, J ¼ 7.3, 2.6 Hz), 6.7–6.81 (m, 3H), 8.8 (br s, 1H, exchangeable);
1
2
17
2
6
9.6; H, 8.2; N, 6.8%. Found: C, 69.8; H, 8.4; N, 6.6.
1
-(4-Chlorophenyl)amino-1-cyclohexanol (c): H NMR (CDCl /TMS):
2
1.0–1.18 (m, 1H), 1.25–1.36 (m, 3H), 1.7–1.82 (m, 2H), 2.05–2.15 (m, 2H),
3
ꢀ
2
.7–3.1 (m, 3H), 3.25–3.41 (m, 1H), 6.55 (d, 2H, J ¼ 5.20Hz), 7.05 (d, 2H,
þ
37
J ¼ 5.29 Hz); EIMS (relative intensity): 227 (M , 48.24
Cl), 226
þ
þ
35
(
1
(M þ 1) , 61.65), 225 (M , 10 0 Cl), 208 (7.26), 194 (1.74),
82 (9.26), 166 (61.77), 153 (13.77), 140(26.49), 130(23.37), 117
(
1
8.24), 91 (8.31); IR (KBr): 3416, 3388, 3322, 2934, 2861, 1871, 1597,
À1
509, 1451, 1324, 1260 cm . Anal. calcd. for C H ClNO: C, 63.85;
1
2
16
ꢀ
H, 7.14; N, 6.21. Found: C, 63.56; H, 7.11; N, 6.0; m.p. 102–104 C,
yield 95%.
trans-2-(o-Methylphenylamino)cyclohexanol (d): Viscous liquid, R 0.37
(
(
f
1
1 : 10EtOAc in petroleum ether); H NMR (CDCl , 500 MHz): ꢀ 1.08–1.26
3
m, 1H), 1.38–1.51 (m, 3H), 1.78–1.85 (m, 2H), 2.16 (m, 2H), 2.18 (s, 3H),
3
.0(bs, 2H, NH and OH), 3.23 (ddd, 1H, J ¼ 10.9, 9.3 and 3.9 Hz), 3.44
(
ddd, 1H, J ¼ 10.5, 10.5 and 4.8 Hz), 6.72–6.85 (m, 1H), 6.81 (d, 1H,
1
3
J ¼ 7.8 Hz), 7.12–7.3 (m, 2H); C NMR (CDCl , 500 MHz): ꢀ 17.62,
3
2
1
4.21, 24.92, 31.75, 33.17, 59.72, 74.44, 111.46, 117.73, 123.0, 127.06,
30.32, 145.62; LCMS (APCI; m/z) 20 6 (M þ 1).
þ
trans-2-(N-Ethyl-N-phenylamino)cyclohexanol (e): Viscous liquid;
H NMR (CDCl ): ꢀ 0.9–1.15 (m, 1H), 1.2–1.29 (t, 3H, J ¼ 4.65 Hz),
1
3
1
.25–1.5 (m, 3H), 1.7–1.8 (m, 2H), 2.15–2.25 (m, 2H), 2.9 (s, 1H), 3.2–3.4
(
7
m, 3H), 3.55–3.7 (m, 1H), 6.8 (t, 1H, J ¼ 4.5 Hz), 6.95 (d, 2H, J ¼ 9.0Hz),
þ
.25 (t, 2H, J ¼ 4.5 Hz); MS : m/z 219 (M ); Anal. calcd. for C H NO:
1
4
21
C, 76.67; H, 9.65; N, 6.39. Found: C, 76.72; H, 9.72; N, 6.42.
trans-2-( p-Methoxyphenylamino)cyclohexanol (f): M.p. 58–59 C;
ꢀ
1
H NMR (CDCl , 500 MHz): ꢀ 1.0–1.13 (m, 1H), 1.3–1.41 (m, 3H),
3
1
3
3
.71–1.83 (m, 2H), 2.05–2.17 (m, 2H), 2.97 (ddd, 1H, J ¼ 10.9, 9.3,
.9 Hz), 3.28 (s, 2H, NH and OH), 3.31 (ddd, 1H, J ¼ 9.6, 9.6, 3.9 Hz),
1
3
.73 (s, 3H), 6.68 (d, 2H, J ¼ 8.0Hz), 6.78 (d, 2H, J ¼ 8.0Hz); C NMR

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RING OPENING OF EPOXIDES BY AMINES
2311
(
1
CDCl , 500 MHz): ꢀ 24.15, 24.86, 31.25, 33.07, 55.56, 61.48, 74.03, 114.67,
3
þ
16.28, 141.29, 152.73; LCMS (APCI, m/z) 222 (M þ 1).
trans-2-(N-Benzyl-N-phenylamino)cyclohexanol (g): Viscous liquid; IR
À1
1
(
Neat) 3000–3600 cm ; H NMR (CDCl , 500 MHz): ꢀ 1.38–1.49 (m, 4H),
3
1
3
2
ꢀ
1
8
.8–1.93 (m, 2H), 1.94 (m, 1H), 2.19–2.37 (m, 1H), 2.84 (br s, 1H, OH),
.65–3.81 (m, 2H), 4.48 (d, 2H, J ¼ 10.5 Hz), 6.82–6.93 (m, 1H), 7.0–7.19 (m,
1
H), 7.25–7.34 (m, 3H), 7.36–7.51 (m, 4H); C NMR (CDCl , 500 MHz):
3
3
24.19, 25.38, 26.99, 33.60, 48.91, 66.38, 70.62, 116.21, 118.62, 126.62,
26.76, 128.60, 128.96, 139.58, 149.7. Anal. calcd. for C H NO: C,
1
9
23
1.14; H, 8.19; N, 4.98. Found: C, 81.42; H, 8.32, N, 5.08.
trans-2-(4-Nitrophenylamino)cyclohexanol (h): M.p. 119–121 C; IR
ꢀ
À1
1
(
KBr): 3500 cm
; H NMR (CDCl , 500 MHz): ꢀ 1.3 (br s, 4H),
3
.75–1.86 (m, 2H), 2.0–2.12 (m, 2H), 3.29–3.38 (m, 1H), 3.43 (ddd, 1H,
1
J ¼ 10.2, 10.2, 4.5 Hz), 4.84 (s, 2H, NH and OH), 6.65 (d, 2H, J ¼ 9.3 Hz),
1
3
7
3
.98 (d, 2H, J ¼ 9.3 Hz): C NMR (CD OD, 500 Hz): ꢀ 25.34, 25.53, 32.24,
3
5.17, 59.22, 74.7, 112.12, 127.28, 137.0, 156.16. LCMS (APCI, m/z) 237
þ
(
M þ 1).
1
trans-2-(Phenylamino)cyclopentanol (i): H NMR (CDCl /TMS): ꢀ
3
1
2
7
.35–1.5 (m, 1H), 1.6–1.9 (m, 3H), 1.9–2.05 (m, 1H), 2.15–2.35 (m, 1H),
.4–3.1 (br s, 2H), 3.55–3.65 (m, 1H), 4.0–4.2 (m, 1H), 6.65–6.8 (m, 3H),
.1–7.25 (m, 2H), m.p. 57–58 C (lit. 57–58 C). Yield 97%.
trans-2-(o-Methylphenylamino)cyclopentanol ( j): Viscous liquid;
ꢀ
ꢀ
1
H NMR (CDCl ): ꢀ 1.35–1.5 (m, 1H), 1.55–1.85 (m, 3H), 2.2–2.45 (m,
3
2
H), 2.8 (s, 3H), 3.9–3.95 (m, 1H), 4.2–4.3 (m, 1H), 6.64 (dt, 1H, J ¼ 7.2,
0.6 Hz), 6.8 (d, 1H, J ¼ 8.7 Hz), 7.23 (m, 2H); MS: m/z 192 (M þ 1); Anal.
calcd. for C H NO: C, 78.35; H, 8.96; N, 7.32, Found: C, 78.59; H, 8.99;
2
1
17
N, 7.34.
trans-2-(N-Ethyl-N-phenylamino)cyclopentanol (k): Viscous liquid; Rf
À1
0
.37 (1 : 10 EtOAc in petroleum ether); IR (neat) 3100–3580 cm
;
1
H NMR (CDCl , 500 MHz): ꢀ 1.19 (t, 3H, J ¼ 6.9 Hz), 1.6–1.71 (m, 2H),
3
1
.8–1.93 (m, 2H), 2.0–2.12 (m, 2H), 3.28–3.41 (m, 2H), 3.91–4.12 (m, 1H),
4
.2–4.31 (m, 1H), 6.74–6.86(m, 1H), 6.88 (t, 1H, J ¼ 7.2, 0.9 Hz), 7.23–7.36
1
3
(
m, 2H); C NMR (CDCl , 500 MHz): ꢀ 14.63, 19.72, 25.69, 31.53, 40.55,
3
þ
6
7.60, 74.93, 114.76, 129.13, 149.37; LCMS (APCI, m/z) 20 6 (M þ 1).
Anal. calcd. for C N NO: C, 76.10; H, 9.27; N, 6.83. Found: C, 76.32;
1
3
19
H, 9.22; N, 6.90.
trans-2-(4-Nitrophenylamino)cyclopentanol (l): Semi solid, R 0.27 (1 : 4,
f
À1 1
EtOAc in petroleum ether); IR (KBr): 3100–3580 cm ; H NMR (CDCl ): ꢀ
3
1.4–2.02 (m, 5H), 2.22–2.31 (m, 1H), 3.65–3.71 (m, 1H), 3.75 (bs, OH), 3.85
(
2
1
bs, NH), 4.02–4.21 (m, 1H), 6.65 (d, J ¼ 9.3 Hz, 2H), 8.00 (d, J ¼ 9.3 Hz,
1
3
H). C NMR (CD OD, 500 MHz): ꢀ 22.29, 31.17, 33.69, 62.48, 78.37,
3
þ
12.24, 127.2, 137.92, 155.65; LCMS (APCI, m/z) 223 (M þ 1).

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2
312
RAGHAVENDRA SWAMY, KONDAJI, AND NAGAIAH
trans-2(Phenylamino)cyclooctanol (m): Viscous liquid; IR (neat)
À1
1
3
1
120–3620 cm
;
.86–1.97 (m, 4H), 3.22 (bs, 2H, NH and OH), 3.45–3.57 (m, 1H), 3.56
H NMR (CDCl , 500 MHz): ꢀ 1.6–1.73 (m, 8H),
3
(
ddd, 1H, J ¼ 9.5, 6.6, 2.7 Hz), 6.78–6.82 (m, 3H), 7.24–7.41 (m, 2H);
1
3
C NMR (CDCl , 500 MHz): ꢀ 23.27, 25.17, 25.67, 26.74, 29.63, 31.10,
3
6
0.02, 74.93, 115.11, 118.84, 129.35, 147.50; LCMS (APCI, m/z) 220
þ
(M þ 1). Anal. calcd. for C H NO: C, 76.71; H, 9.59; N, 6.39. Found:
C, 76.82; H, 9.62; N, 6.28.
1
4
21
ACKNOWLEDGMENT
NRVS and GK thanks CSIR, New Delhi for financial support.
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2
Received in the UK April 5, 2001