Highly effective opening of epoxides with aromatic amines in presence of β-Cyclodextrin in water

Article abstract of DOI:10.14233/ajchem.2018.21260

This paper reports a simple, mild, and convenient method to synthesize β-amino alcohols. These β-amino alcohols were achieved in excellent yields (80-96 %) by ring-opening reaction of oxiranes with aromatic amines catalyzed by β-cyclodextrin at 30 oC in w

Full text of DOI:10.14233/ajchem.2018.21260

Asian Journal of Chemistry; Vol. 30, No. 5 (2018), 1165-1170
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21260
Highly Effective Opening of Epoxides with Aromatic
Amines in Presence of β-Cyclodextrin in Water
1,2
1,2
1,2
SIPING TANG1,2,*, ZHIFENG XU , JUNHUA LI , PEIHONG DENG1,2 and LANYONG FENG
1Department of Chemistry and Material Science, Hengyang Normal University, Hengyang 421008, Hunan Province, P.R. China
2Key Laboratory of Functional Organometallic Materials of Hunan Province, Hengyang 421008, Hunan Province, P.R. China
*Corresponding author: Fax: +86 734 3456099; Tel: +86 734 8450056; E-mail: tsp00@163.com
Received: 30 January 2018;
Accepted: 9 March 2018;
Published online: 29 March 2018;
AJC-18859
This paper reports a simple, mild, and convenient method to synthesize β-amino alcohols. These β-amino alcohols were achieved in
excellent yields (80-96 %) by ring-opening reaction of oxiranes with aromatic amines catalyzed by β-cyclodextrin at 30 ºC in water.
β-cyclodextrin as the catalyst greatly accelerated the reactions and can be recovered and reused.
Keywords: Oxiranes, β-Cyclodextrin, β-Amino alcohols, Ring-opening
to attempt ring opening of aromatic epoxides with aromatic
amines in the presence of β-cyclodextrin in water.
INTRODUCTION
β-Amino alcohols are versatile intermediates in the synthesis
of a wide range of biologically active natural and synthetic
products such as unnatural amino acids [1,2] and chiral auxiliaries
[3]. The classical approach for the preparation of β-amino
alcohols involves the ring opening of epoxides at elevated temper-
atures in an excess amount of amines [4]. These reactions are
accompanied by poor regioselectivity and long reaction time.
To avoid these drawbacks, other methods were reported recently,
which involved the use of metal amides [5-7], metal triflates
[8-10], metal halides [11-14], organobismuth triflate complex
[15], copper(II) tetrafluoroborate [16], ionic liquid [17], phospho-
molybdic acid-Al2O3 [18], thiourea [19] and Hβ zeolite [20].
However, most of these methods involve the use of expensive
reagents, air- and/or moisture-sensitive catalysts, hazardous
organic solvents and suffering from poor regioselectivity. In
view of these limitations, inexpensive, environmentally benign
and highly efficient catalysts are expected to be developed for
the ring-opening of epoxides directly with anilines.
Having hydrophobic cavities, cyclodextrins form host-
guest complexes with substrates via non-covalent bonding. The
complexation depends on the size, shape and hydrophobicity
of the guest molecule. β-Cyclodextrin catalyzes chemical
reactions by supramolecular catalysis with high efficiency. No
investi-gations of ring opening of epoxides with aromatic
amines in the presence of β-cyclodextrin in water have been
reported. Our earlier study on ester hydrolysis successfully
catalyzed by β-cyclodextrin derivatives [21-23] promoted us
EXPERIMENTAL
All the reactions were carried out without any special pre-
cautions in an atmosphere of air. Oxiranes and amines were
purchased from Sigma-Aldrich. β-Cyclodextrin (β-CD, reagent
grade) was recrystallized twice from H2O and dried in vacuo
for 12 h at 100 ºC. Water used as the solvent in all reactions was
double distilled. 1 H NMR, 13C NMR and HMBC spectra were
recorded on BRUKER 500- or 400-MHz spectrometers. High-
resolution mass spectra (HRMS) were observed on Bruker
LC-Q-TOF spectrometer.
Synthesis of β-amino alcohols: β-Cyclodextrin (0.50
mmol) was dissolved in water (15 mL) by warming to 50 ºC
until a clear solution was formed; then oxirane (0.50 mmol)
dissolved in acetone (2 mL) was added and the mixture was
allowed to reach reaction temperature. Amine (0.50 mmol)
was added and the mixture was stirred at reaction temperature
until the reaction was complete (TLC). The organic material
was extracted with ethyl acetate. The organic layer was dried
over anhydrous Na2SO4 and the solvent was removed under
vacuum. The resulting crude product was further purified by
silica-gel (60-120 mesh) column chromatography with petroleum
ether:ethyl acetate (4:1) as eluent. The filtrate was evaporated
to dryness under reduced pressure. The resulting residue was
dissolved in a small amount of hot water and the aqueous solution
was poured into ethyl acetate (25 mL) to give precipitate and

1166 Tang et al.
Asian J. Chem.
filtrated to recover β-cyclodextrin (> 95 %), and recovered
β-cyclodextrin was dried for 12 h at 95 ºC before reuse. NMR
spectra of all compound β-amino alcohols were recorded in
CDCl3 solvent. The new compounds 16B, 17B, 18B, 19B, 20B
and 21B were characterized by 1H NMR, 13C NMR, HMBC
and HRMS spectra.
129.32, 127.87, 121.43, 119.73, 117.85, 114.55, 111.49, 69.93,
68.68, 46.35 ppm.
1-(2-Nitrophenylamino)-3-phenoxypropan-2-ol (7A)
[Ref. 24]: 1H NMR (400 MHz, CDCl3): δ 8.34 (brs, 1H), 8.19
(dd, J = 8.6, 1.6 Hz, 1H), 7.50-7.40 (m, 1H), 7.37-7.27 (m,
2H), 7.03-6.90 (m, 4H), 6.68 (ddd, J = 8.4, 7.0, 1.1 Hz, 1H),
4.32 (d, J = 16.6 Hz, 1H), 4.10 (qd, J = 9.4, 5.0 Hz, 2H), 3.71-
3.59 (m, 1H), 3.59-3.48 (m, 1H). 13C NMR (100 MHz, CDCl3):
δ 158.16, 145.52, 136.26, 129.66, 127.02, 121.59, 115.79,
114.55, 113.75, 69.68, 68.61, 45.58 ppm.
Spectral data
1-Phenoxy-3-(phenylamino)propan-2-ol (1A) [Ref. 13]:
1H NMR (500 MHz, CDCl3): δ 7.29 (dd, J = 8.5, 7.5 Hz, 2H),
7.18 (dd, J = 8.4, 7.5 Hz, 2H), 6.98 (t, J = 7.4 Hz, 1H), 6.91 (d,
J = 7.9 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H), 6.67 (d, J = 7.7 Hz,
2H), 4.24 (ddt, J = 8.4, 7.1, 4.2 Hz, 1H), 4.04 (qd, J = 9.4, 5.1
Hz, 2H), 3.42 (dd, J = 13.0, 4.3 Hz, 1H), 3.28 (dd, J = 13.0,
7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 158.69, 148.34,
129.85, 129.60, 121.61, 118.33, 114.84, 113.57, 70.32, 69.10,
46.91 ppm.
1
2-Phenyl-2-(phenylamino)ethanol (8B) [Ref. 26]: H
NMR (500 MHz, CDCl3): δ 7.34 (dt, J = 15.1, 7.4 Hz, 4H),
7.30-7.20 (m, 1H), 7.09 (t, J = 7.8 Hz, 2H), 6.67 (t, J = 7.3 Hz,
1H), 6.56 (d, J = 7.9 Hz, 2H), 4.48 (dd, J = 6.8, 4.3 Hz, 1H),
3.91 (dd, J = 11.1, 4.2 Hz, 1H), 3.73 (dd, J = 11.1, 7.0 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 147.86, 140.45, 129.14, 128.26,
126.79, 117.92, 113.90, 67,38, 59.87 ppm.
2-Phenyl-2-(o-tolylamino)ethan-1-ol (9B) [Ref. 27]:1H
NMR (400 MHz, CDCl3): δ 7.40-7.32 (m, 4H), 7.31-7.26 (m,
1H), 7.08 (d, J = 7.3 Hz, 1H), 6.99-6.90 (m, 1H), 6.65 (td, J =
7.4, 0.9 Hz, 1H), 6.39 (d, J = 7.9 Hz, 1H), 4.56 (dd, J = 7.0,
4.2 Hz,1H), 3.99 (dd, J = 11.1, 4.2 Hz, 1H), 3.80 (dd, J = 11.1,
7.0 Hz, 1H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3):δ145.13,
140.20, 130.13, 128.88, 127.65, 127.01, 126.70, 122.61, 117.54,
111.51, 67.55, 59.80, 17.72 ppm.
1-(o-Toluidino)-3-phenoxypropan-2-ol (2A) [Ref. 24]:
1H NMR (500 MHz, CDCl3): δ 7.32 (dd, J = 21.1, 12.8 Hz,
2H), 7.16 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 7.3 Hz, 1H), 7.02 (t,
J = 7.4 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 6.72 (dd, J = 17.4,
7.7 Hz, 2H), 4.46-4.22 (m, 1H), 4.13 (qd, J = 9.4, 5.0 Hz, 2H),
3.52 (dd, J = 12.8, 4.4 Hz, 1H), 3.38 (dd, J = 12.8, 7.0 Hz,
1H), 2.61 (brs, 1H), 2.21 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ 158.41, 146.00, 130.26, 129.61, 127.17, 122.71, 121.37,
117.65, 114.55, 110.11, 70.21, 68.76, 46.60, 17.52 ppm.
1-(p-Toluidino)-3-phenoxypropan-2-ol (3A) [Ref. 24]:
1H NMR (500 MHz, CDCl3): δ 7.38 - 7.30 (m, 2H), 7.02 (dd,
J = 15.0, 7.7 Hz, 3H), 6.98 - 6.92 (m, 2H), 6.64 (d, J = 8.4 Hz,
2H), 4.29 (ddt, J = 8.3, 7.2, 4.2 Hz, 1H), 4.09 (qd, J = 9.4, 5.1
Hz, 2H), 3.44 (dd, J = 12.9, 4.3 Hz, 1H), 3.31 (dd, J = 12.9,
7.2 Hz, 1H), 2.28 (s, 3H). 13C NMR (100 MHz, CDCl3): δ158.46,
145.79, 129.84, 129.59, 127.39, 121.33, 114.59, 113.55, 70.11,
68.87, 47.10, 20.40 ppm.
1-(2-Methoxyphenylamino)-3-phenoxypropan-2-ol (4A)
[Ref. 24]: 1H NMR (500 MHz, CDCl3): δ 7.33 (dd, J = 8.4, 7.6
Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.97 (d, J = 7.9 Hz, 2H), 6.91
(td, J = 7.7, 1.2 Hz, 1H), 6.85-6.78 (m, 1H), 6.77-6.69 (m, 2H),
4.32 (ddd, J = 10.9, 6.3, 4.6 Hz, 1H), 4.11 (qd, J = 9.4, 5.1 Hz,
2H), 3.88 (s, 3H), 3.49 (dd, J = 13.1, 4.6 Hz, 1H), 3.37 (dd, J =
13.1, 6.9 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 158.50,
147.18, 138.01, 129.57, 121.29, 121.28, 117.20, 114.60, 110.27,
109.63, 70.09, 68.89, 55.45, 46.56 ppm.
1-(4-Methoxyphenylamino)-3-phenoxypropan-2-ol (5A)
[Ref. 25]: 1H NMR (500 MHz, CDCl3): δ 7.33 (dd, J = 8.5, 7.5
Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 7.9 Hz, 2H),
6.86- 6.80 (m, 2H), 6.71-6.65 (m, 2H), 4.28 (tt, J = 8.1, 4.2
Hz, 1H), 4.09 (qd, J = 9.4, 5.1 Hz, 2H), 3.78 (d, J = 4.0 Hz,
3H), 3.41 (dd, J = 12.8, 4.2 Hz, 1H), 3.28 (dd, J = 12.8, 7.2
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 158.45, 152.68,
142.18, 129.59, 121.33, 114.97, 114.84, 114.58, 70.14, 68.86,
55.82, 47.81 ppm.
1-(2-Chlorophenylamino)-3-phenoxypropan-2-ol (6A)
[Ref. 24]: 1H NMR (500 MHz, CDCl3): δ 7.42-7.29 (m, 3H),
7.22-7.12 (m, 1H), 7.02 (t, J = 7.4 Hz, 1H), 6.96 (d, J = 7.9 Hz,
2H), 6.81-6.74 (m, 1H), 6.69 (td, J = 7.7, 1.3 Hz, 1H), 4.77 (brs,
1H), 4.32 (d, J = 3.6 Hz, 1H), 4.12 (qd, J = 9.4, 5.0 Hz, 2H),
3.47 (ddd, J = 19.9, 13.0, 5.5 Hz, 2H), 2.58 (d, J = 4.3 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 158.33, 143.93, 129.64,
1
2-Phenyl-2-(p-tolylamino)ethan-1-ol (10B): H NMR
(400 MHz, CDCl3): δ 7.49-7.18 (m, 5H), 6.94 (d, J = 8.1 Hz, 2H),
6.53 (d, J = 8.3 Hz, 2H), 4.51 (dd, J = 7.1, 4.2 Hz, 1H), 3.96
(dd, J = 11.1, 4.2 Hz, 1H), 3.77 (dd, J = 11.1, 7.2 Hz, 1H), 2.22
(s, 3H). 13C NMR (100 MHz, CDCl3): δ144.93, 140.33, 129.79,
129.68, 128.81, 127.56, 127.16, 126.76, 115.39, 114.08, 67.37,
60.20, 20.38 ppm.
2-[(2-Methoxyphenyl)amino]-2-phenylethan-1-ol (11B)
[Ref. 28]: 1H NMR (400 MHz, CDCl3): δ 7.42-7.30 (m, 4H),
7.26 (ddd, J = 9.4, 3.9, 1.7 Hz, 1H), 6.79 (dd, J = 7.7, 1.5 Hz,
1H), 6.75-6.60 (m, 2H), 6.42 (dd, J = 7.7, 1.7 Hz, 1H), 4.54
(dd, J = 7.3, 4.3 Hz, 1H), 3.95 (dd, J = 11.1, 4.3 Hz, 1H), 3.90
(s, 3H), 3.80 (dd, J = 11.1, 7.3 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 147.17, 140.25, 137.02, 128.81, 127.59, 126.75,
121.14, 117.17, 111.52, 109.46, 67.51, 59.81, 55.50 ppm.
2-[(4-Methoxyphenyl)amino]-2-phenylethan-1-ol (12B)
[Ref. 25]: 1H NMR (500 MHz, CDCl3): δ 7.45-7.23 (m, 7H),
6.68 (ddd, J = 8.4, 7.0, 1.1 Hz, 1H), 6.60 (d, J = 8.6 Hz, 1H),
4.71 (dd, J = 10.4, 6.0 Hz,1H), 4.18-4.00 (m, 1H), 3.93 (dd, J =
11.1, 6.2 Hz, 1H), 2.20 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
152.43, 141.32, 140.32, 128.81, 128.57, 128.04, 127.59,
126.75, 126.07, 115.31, 114.78, 67.37, 60.87, 55.71 ppm.
2-[(2-Chlorophenyl)amino]-2-phenylethan-1-ol (13B)
[Ref. 29]: 1H NMR (400 MHz, CDCl3): δ 7.56-7.20 (m, 6H),
6.96 (td, J = 8.2, 1.5 Hz, 1H), 6.61 (td, J = 7.7, 1.4 Hz, 1H), 6.44
(dd, J = 8.2, 1.3 Hz, 1H), 4.56 (dd, J = 6.5, 4.3 Hz, 1H), 3.99 (dd,
J = 11.1, 4.1 Hz, 1H), 3.83 (dd, J = 11.1, 6.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 143.06, 139.52, 129.14, 128.95, 127.82,
127.68, 126.68, 119.76, 117.86, 112.86, 67.38, 59.67 ppm.
2-[(2-Nitrophenyl)amino]-2-phenylethan-1-ol (14B)
[Ref. 24]: 1H NMR (400 MHz, CDCl3): δ 8.75 (d, J = 5.0 Hz,
1H), 8.19 (dd, J = 8.8, 1.6 Hz, 1H), 7.41-7.28 (m, 5H), 6.78-
6.52 (m, 2H), 4.73 (dt, J= 10.5, 5.3 Hz, 1H), 4.04 (dd, J= 11.1, 4.0
Hz, 1H), 3.94 (dd, J = 11.1, 6.3 Hz, 1H). 13C NMR (100 MHz,

Vol. 30, No. 5 (2018)
Effective Opening of Epoxides with Aromatic Amines in Presence of β-Cyclodextrin in Water 1167
CDCl3): δ144.59, 138.68, 136.02, 129.13, 128.15, 126.82, 126.62,
115.97, 115.10, 67.12, 59.26 ppm.
2-(4-Chlorophenyl)-2-[(4-methoxyphenyl)amino]ethan-
1-ol (19B): m.f. C15H16NO2Cl. 1H NMR (400 MHz, CDCl3): δ
7.30 (s, 4H), 6.79-6.61 (m, 2H), 6.55-6.43 (m, 2H), 4.39 (dd,
J = 7.5, 4.1 Hz, 1H), 3.89 (dd, J = 11.1, 4.1 Hz, 2H), 3.70 (s, 3H),
3.69-3.64 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 152.53,
141.03, 138.97, 133.28, 129.00, 128.19, 115.32, 114.80, 67.22,
60.31, 55.73 ppm. HRMS (ESI) calculated for C15H16NO2Cl
(M+H)+ 278.0948, found (M+H)+ 278.0944.
2-(4-Chlorophenyl)-2-[(2-chlorophenyl)amino]ethan-
1-ol (20B): m.f. C14H13NOCl2. 1H NMR (500 MHz, CDCl3): δ
7.32 (dt, J = 11.3, 8.6 Hz, 5H), 6.99 (t, J = 7.6 Hz, 1H), 6.65 (t,
J = 7.5 Hz, 1H), 6.40 (d, J= 8.0 Hz, 1H), 5.19 (s, 1H), 4.54 (s, 1H),
4.20-3.92 (m, 1H), 3.82 (dd, J = 10.8, 7.0 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 142.79, 138.17, 133.53, 129.20, 129.10,
128.06, 127.66, 119.84, 118.11, 112.80, 67.14, 59.15 ppm.
HRMS (ESI) calculated for C14H13NOCl2 (M+H)+ 282.0452,
found (M+H)+ 282.0449.
2-(4-Chlorophenyl)-2-[(2-nitrophenyl)amino]ethan-1-
ol (21B): m.f. C14H13N2O3Cl. 1H NMR (400 MHz, CDCl3): δ
8.73 (d, J = 5.4 Hz, 1H), 8.21 (dd, J = 8.6, 1.5 Hz, 1H), 7.47- 7.26
(m, 4H), 6.69 (ddd, J = 8.4, 7.0, 1.1 Hz, 1H), 6.60 (d, J = 8.6 Hz,
1H), 4.71 (dd, J = 10.5, 6.0 Hz, 1H), 4.18-4.00 (m, 1H), 3.93
(dd, J= 11.1, 6.2 Hz, 1H). 13C NMR (400 MHz, CDCl3): δ144.29,
137.36, 136.07, 129.31, 128.02, 126.89, 116.23, 114.96, 99.99,
66.90, 58.68 ppm. HRMS (ESI) calculated for C14H13N2O3Cl
[M+Na]+ 315.0512, found [M+Na]+ 315.0510.
2-(4-Chlorophenyl)-2-(phenylamino)ethanol (15B)
[Ref. 19]: 1H NMR (500 MHz, CDCl3): δ 7.28 (d, J = 27.6 Hz,
4H), 7.10 (dd, J = 8.4, 7.5 Hz, 2H), 6.69 (t, J = 7.3 Hz, 1H),
6.53 (d, J = 7.7 Hz, 2H), 4.46 (dd, J = 7.0, 4.1 Hz, 1H), 3.92 (dd,
J = 11.1, 4.1 Hz, 1H), 3.71 (dd, J = 11.1, 7.0 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 147.45, 138.58, 132. 8, 129.23, 128.16,
118.16, 113.88, 67.19, 59.34 ppm.
1
1-(Phenylamino)hexan-2-ol (22A) [Ref. 13]: H NMR
(400 MHz, CDCl3): δ 7.27-7.14 (m, 2H), 6.73 (t, J = 7.3 Hz,
1H), 6.65 (dd, J = 8.6, 0.9 Hz, 2H), 3.97-3.59 (m, 1H), 3.26
(dd, J = 12.9, 3.2 Hz, 1H), 3.00 (dd, J = 12.9, 8.6 Hz, 1H),
1.65-1.19 (m, 6H), 0.93 (t, J = 7.1 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ148.33, 129.33, 117.91, 113.31, 70.41, 50.34,
34.83, 27.83, 22.78, 14.08 ppm.
2-(4-Chlorophenyl)-2-(o-tolylamino)ethan-1-ol (16B):
1
m.f. C15H16NOCl. H NMR (400 MHz, CDCl3): δ 7.38-7.30
(m, 4H), 7.09 (d, J = 7.3 Hz, 1H), 7.01-6.94 (m, 1H), 6.67 (td,
J = 7.4, 0.9 Hz, 1H), 6.32 (d, J = 7.9 Hz, 1H), 4.50 (dd, J = 7.2,
4.1 Hz, 1H), 3.96 (dd, J = 11.1, 4.1 Hz, 1H), 3.75 (dd, J = 11.1,
7.2 Hz, 1H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3): δ144.89,
138.86, 133.30, 130.23, 129.05, 128.12, 127.03, 122.74, 117.81,
111.52, 67.34, 59.33, 17.70 ppm. HRMS (ESI) calculated for
C15H16NOCl (M+H)+ 262.0999, found (M+H)+ 262.0995.
2-(4-Chlorophenyl)-2-(p-tolylamino)ethan-1-ol (17B):
m.f. C15H16NOCl. 1H NMR (400 MHz, CDCl3): δ 7.30 (m, 4H),
6.93 (d, J = 8.0 Hz, 2H), 6.47 (d, J = 8.4 Hz, 2H), 4.44 (dd, J
= 7.3, 4.1 Hz, 1H), 3.90 (dd, J = 11.1, 4.1 Hz, 1H), 3.69 (dd, J
= 11.1, 7.3 Hz, 1H), 2.21 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ 144.63, 138.93, 133.26, 129.75, 129.00, 128.17, 127.45,
114.09, 67.22, 59.66, 20.42 ppm. HRMS (ESI) calculated for
C15H16NOCl (M+H)+ 262.0999, found (M+H)+ 262.0994.
2-(4-Chlorophenyl)-2-[(2-methoxyphenyl)amino]ethan-
1-ol (18B): m.f. C15H16NO2Cl. 1H NMR (400 MHz, CDCl3): δ
7.30 (s, 4H), 6.79 (dd, J = 7.5, 1.8 Hz, 1H), 6.75-6.63 (m, 2H),
6.34 (dd, J = 7.5, 1.9 Hz, 1H), 4.49 (dd, J = 7.3, 4.3 Hz, 1H), 3.93
(dd, J = 11.1, 4.2 Hz, 1H), 3.90 (s, 3H), 3.76 (dd, J = 11.1, 7.3 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 147.18, 138.89, 136.72,
133.25, 128.98, 128.15, 121.12, 117.43, 111.50, 109.51, 67.31,
59.31, 55.50 ppm. HRMS (ESI) calculated for C15H16NO2Cl
(M+H)+ 278.0948, found (M+H)+ 278.0945.
RESULTS AND DISCUSSION
Initially, for the model study, the ring opening reaction of
1,2-epoxy-3-phenoxy propane was carried out with aniline in
water using β-cyclodextrin as the catalyst (Table-1). The yield
was only 78 % after stirring for 8 h under 20 °C (Table-1,
entry 1). While the yield was up to 96 % when the temperature
was 30 °C and the yields were more than 95 % when the tempe-
rature was higher than 30 °C (Table-1, entries 2-6). However,
the ratio of the major isomer A decreased as the temperature
increased. The higher regioselectivity was achieved at 20 and
30 °C (Table-1, entries 2, 3). In order to understand the role of
catalyst, control reaction was proceeded at 30 °C (Table-1,
entry 7) and only 9 % of the product was obtained even with
prolonged reaction time in the absence of catalyst.
TABLE-1
RING-OPENING REACTION OF 1,2-EPOXY-3-PHENOXY PROPANE WITH ANILINE IN THE
PRESENCE OF CYCLODEXTRIN AT DIFFERENT REACTION CONDITIONS
NH2
O
O
O
OH
+
+
N
H
O
NH
OH
A
B
Entry
Temperature (°C)
Time (h)
Yield (%)b
Ratio (A:B)c
85:15
1
2
3
4
5
6
7
20
30
40
50
60
80
30a
8
8
8
8
6
78
96
95
96
95
96
9
85:15
82:18
73:27
72:28
65:35
84:16
5
16
aNo cyclodextrin; bIsolated yield; c The ratio of isomers was calculated by 1H NMR

1168 Tang et al.
Asian J. Chem.
With the optimized reaction conditions, the scope of the
low even after prolong the reaction time (Table-2, entries 7,
14, 21). Similar to 1,2-epoxy-3-phenoxy propane, the yields
of ring-opening of Styrene oxide, 4-chlorostyrene oxide and
1,2-epoxyhexane with aniline were also very low (< 10 %) in
the absence of cyclodextrin.
Unsymmetrical alkyl oxiranes such as 1,2-epoxy-3-phenoxy
propane and 1,2-epoxyhexane afforded β-amino alcohols with
preferential attack at the terminal position. For anilines with
ortho-substituents, only one isomer was obtained (Table-2,
reactions was investigated at 30 °C with the styrene oxide, 4-
chlorostyrene oxide, 1,2-epoxy-3-phenoxy propane and 1,2-
epoxyhexane as the substrates and series of aromatic amines
with electron-donating and electron-withdrawing groups as
the nucleophiles. As listed in Table-2, β-amino alcohols were
obtained in high yield (80-96 %). For amines with an electron-
withdrawing group, moderate yields were obtained (Table-2,
entries 6, 13, 20). However, for 2-nitroaniline, the yields were
TABLE-2
RING-OPENING REACTION OF EPOXIDES WITH AROMATIC AMINES IN THE PRESENCE OF β-CYCLODEXTRIN
HO
R1
HN R2
R1
cyclodextrin
30 oC, H2O
R2 NH2
+
+
R1
O
HO
NH R2
A
B
Entry
1
Epoxide
Amine
Time (h)
Yield (%)a,b
Ratio (A:B)c
85:15
O
O
O
O
O
O
O
NH2
O
8
96
NH2
CH3
O
O
O
O
O
O
2
3
4
5
6
7
7
84
87
86
90
70
100:0
83:17
100:0
82:18
100:0
NH2
H3C
NH2
6
OCH3
NH2
6
H3CO
NH2
24
Cl
NH2
7
8
24
7
20
90
83
88
93
100:0
7:93
NO2
NH2
O
O
O
O
NH2
CH3
9
7
3:97
NH2
10
11
11
8
0:100
10:90
H3C
NH2
OCH3

Vol. 30, No. 5 (2018)
12
Effective Opening of Epoxides with Aromatic Amines in Presence of β-Cyclodextrin in Water 1169
O
NH2
9
94
74
21
0:100
8:92
7:93
H3CO
O
O
NH2
13
14
24
24
Cl
NH2
NO2
NH2
O
O
O
O
O
O
O
15
16
17
18
19
20
6
8
84
84
86
91
93
76
12:88
9:91
Cl
Cl
Cl
Cl
Cl
Cl
Cl
NH2
CH3
NH2
8
0:100
15:85
0:100
5:95
H3C
NH2
10
10
24
OCH3
NH2
H3CO
NH2
Cl
NH2
21
22
26
16
15
71
6:94
NO2
NH2
O
100:0
aAll products were characterized by 1H NMR and 13C NMR; bIsolated yield; cThe ratio of isomers were calculated by 1HNMR
entries 2, 4, 6, 7, 22). In the case of aniline, 4-methylaniline
and 4-methoxyaniline, a mixture of two regioisomers was
isolated in ratios of 85:15, 83:17 and 82:18, respectively.
(Table-2, entries 1, 3, 5).Alkenyl oxiranes such as styrene oxide
and (p-chlorophenyl) styrene oxide have been treated with
various amines in the presence of β-cyclodextrin. For most of
the amines, only one isomer was obtained (Table-2, entries
10, 12, 13, 14, 17, 19) and for anilines,anilines with ortho-
substituents, a mixture of two regioisomers was produced
(Table-2, entries 8, 9, 11, 15, 16, 18, 20, 21).
According to the literature [30], benzyl ring of the epoxides
insert into the cavity of β-cyclodextrin partially from the secon-
dary rim and the epoxides are fixed through supramolecular
interaction. Moreover, hydrogen bond is formed between the
hydroxyl group of β-cyclodextrin and the oxygen atom of
epoxides. Hydrogen bond favours nucleophiles to attack the
C-O bond of epoxide. For alkyl oxirane 1,2-epoxy-3-phenoxy
propane, terminal carbon atom is attacked more preferentially.
Steric effect may play important roles on the ring-opening
reaction.As the anilines with bukly ortho-substituents, only one
isomer was obtained. In the case of smaller steric-hindrance of
aniline and para-substituent anilines, mixed products were
obtained. For styrene oxide and (p-chlorophenyl) styrene oxide,
the C-O is activated by the hydrogen bond. Benzylic carbon atom
is attacked easily due to its high activity. So electronic effect
may affect this transformation deeply.Aromatic amines with the
substituent on the para-position attack the benzylic carbon
completely. The reaction intermediates of the ring-opening
catalyzed by β-cyclodextrin were proposed in Scheme-I.
In order to evaluate the recycling capability of β-cyclo-
dextrin, the ring opening of 1,2-epoxy-3-phenoxy propane with
aniline was carried out with recovered catalyst.As revealed in

1170 Tang et al.
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Scheme-I
Table-3, the recovered catalyst showed almost equal efficiency
in consecutive four cycles under identical reaction conditions
and all the ratios of two regioisomers A:B are 85:15, which
indicated that the catalyst was stable and suitable to be reused
for several times.
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TABLE-3
REUSE OF CYCLODEXTRIN FOR THE RING-
OPENING REACTION OF 1,2-EPOXY-3-PHENOXY
PROPANE WITH ANILINE
Cycle
1
2
3
4
Yield (%)a
aIsolated yield.
96
95
95
94
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Conclusion
In conclusion, β-cyclodextrin is a highly efficient and
reusable catalyst for the ring-opening of epoxides containing
benzene group with different aniline derivatives. Excellent
yields were achieved for this reaction along with high regio-
selectivity. This method is simple, economic, environmental
and efficient, which would be a useful way to modern synthetic
methodology in green chemistry.
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ACKNOWLEDGEMENTS
This work was supported by the National Natural Science
Foundation of China (Nos. 21102040, 21472038,21202041
and 21505035), the Key Project of science and technology
program of Hunan Provincial Education Department of China
(No.15A027), Key Laboratory of Functional Organometallic
Materials of Hunan Province.
https://doi.org/10.1002/asia.200900108.
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