Aminolysis of epoxides using iridium trichloride as an efficient catalyst

Article abstract of DOI:10.1055/s-0029-1216899

Iridium trichloride catalyzes the ring opening of epoxides by aryl, heterocyclic, or aliphatic amines under mild conditions. The reactions proceed at room temperature to afford the corresponding b-amino alcohols in excellent yields. In general, the aminolysis of cyclopentene oxide is faster than that of cyclohexene oxide in the presence of iridium trichloride as a catalyst. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216899

2790
PAPER
Aminolysis of Epoxides Using Iridium Trichloride as an Efficient Catalyst
Catalytic
y
minolysis
o
o
f
Epoxides ti Agarwal, Anju Duley, Rashmi Rani, Rama Krishna Peddinti*
Department of Chemistry, Indian Institute of Technology, Roorkee 247 667, Uttarakhand, India
Fax +91(1332)273560; E-mail: rkpedfcy@iitr.ernet.in
Received 6 April 2009; revised 27 April 2009
oxide and its derivatives into the corresponding alde-
Abstract: Iridium trichloride catalyzes the ring opening of ep-
oxides by aryl, heterocyclic, or aliphatic amines under mild condi-
tions. The reactions proceed at room temperature to afford the
corresponding b-amino alcohols in excellent yields. In general, the
hydes.18 We therefore wondered whether iridium(III)
chloride would catalyze the reaction of epoxides with
aryl, heterocyclic, or aliphatic amines to give the corre-
aminolysis of cyclopentene oxide is faster than that of cyclohexene sponding amino alcohols.
oxide in the presence of iridium trichloride as a catalyst.
Initially, we studied the reaction between cyclohexene ox-
Key words: epoxides, iridium trichloride, amines, amino alcohols,
aminolysis
ide (1a) and aniline (2a) (Scheme 1). When cyclohexene
oxide was treated with aniline in the presence of 5 mol%
of iridium trichloride in dichloromethane at room temper-
ature for 17 h, the amino alcohol 3a was isolated in 98%
yield (Table 1, entry 1). Encouraged by this result, we
treated cyclohexene oxide with various aniline derivatives
in the presence of iridium trichloride at room temperature
to afford the corresponding b-amino alcohols in excellent
yields in most of the cases that we studied. The results are
summarized in Table 1. Even anilines bearing 2,6-dimeth-
yl or 4-nitro functionalities produced the corresponding
arylaminocyclohexan-1-ols 3g and 3h in acceptable
yields of 49 and 60%, respectively (entries 7 and 8, re-
spectively).
b-Amino alcohols are an important class of organic com-
pounds that are widely used in natural products and me-
dicinal chemistry and as chiral auxiliaries and ligands.1,2
The most practical and commonly used method for syn-
thesizing these compounds is the direct aminolysis of an
epoxide with an excess of an amine at an elevated temper-
ature. However, the need for high temperatures is disad-
vantageous for sensitive functional groups and can causes
problems of regioselectivity. To eliminate such problems
in the ring opening of epoxides by amine nucleophiles,
several activators or promoters, such as Lewis acids or
metal salts, have been introduced.3–13 Nevertheless, in
some cases yields are unsatisfactory, and several of these
catalysts fail to bring about the cleavage of epoxides by
deactivated or sterically hindered aromatic amines. Here,
we report our results on a mild and efficient method for
the synthesis of b-amino alcohols by nucleophilic ring
opening of epoxides by aryl, heterocyclic, or aliphatic
amines with iridium trichloride as a catalyst.
OH
IrCl3•xH2O
O
+
H2N
CH2Cl2
n
R
n
N
H
R
n = 2, 1a
n = 1, 1b
2a–h
n = 2, 3a–h
n = 1, 4a–h
Scheme 1
We then tested the catalytic activity of iridium trichloride
for the ring opening of cyclopentene oxide (1b) with
aniline (2a). The reaction proceeded smoothly and gave
the amino alcohol 4a in 91% yield (Table 1, entry 9). To
establish the generality of the methodology, cyclopentene
oxide was treated with various aniline derivatives in the
presence of iridium trichloride in dichloromethane at
room temperature (Scheme 1). The desired amino alco-
hols 4b–h were obtained in yields comparable to those of
products derived from cyclohexene oxide (Table 1, en-
tries 10–16). Note that, in general, the iridium trichloride-
catalyzed ring opening of cyclopentene oxide with
anilines was faster than that of cyclohexene oxide.
It is generally believed that carbon–metal bonds in third-
row transition-metal complexes are more stable than those
of first- or second-row transition-metal complexes. Con-
sequently, the third-row transition-metal complexes are
expected to be very stable, limiting their use as catalysts
in organic transformations.14 Despite this, considerable
progress has recently been made in the use of iridium
complexes as catalysts in hydrogenation reactions and
carbon–carbon and carbon–heteroatom bond-forming re-
actions.14–17 The most commonly used catalysts for these
transformations are dichloro(cyclooctadiene)iridium or
dichloro(h5-pentamethylcyclopentadiene)iridium in the
presence of a phosphine ligand, or iridium complexes that
themselves contain phosphine ligands. Recently, iridi-
um(III) chloride hydrate (IrCl3·xH2O) was used to effect a
Meinwald rearrangement for the conversion of styrene
The nucleophilic cleavage by aniline of the nonsymmetri-
cal epoxides 1c and 1d (Scheme 2) gave the b-amino
alcohols 5a and 6a, respectively (Table 1, entries 17 and
18).
SYNTHESIS 2009, No. 16, pp 2790–2796
x
x.
x
x
.
2
0
0
9
Advanced online publication: 14.07.2009
DOI: 10.1055/s-0029-1216899; Art ID: Z06309SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Catalytic Aminolysis of Epoxides
2791
Table 1 Iridium Trichloride Catalyzed Ring Opening of Epoxides with Anilines at Room Temperature
Entry
1
Epoxide
Aniline
Producta
Time (h) Yieldb (%)
OH
PhNH2
(2a)
O
(3a)
(3b)
(3c)
(3d)
(3e)
17
32
29
32
30
98
96
89
86
89
N
H
(1a)
OH
4-MeOC6H4NH2
(2b)
2
3
4
5
N
H
OMe
OH
4-ClC6H4NH2
(2c)
N
H
Cl
OH
4-BrC6H4NH2
(2d)
N
H
Br
OH
4-F3CC6H4NH2
(2e)
N
H
CF3
OH
3,5-Me2C6H3NH2
(2f)
6
7
(3f)
42
23
90
49
N
H
OH
2,6-Me2C6H3NH2
(2g)
(3g)
N
H
OH
4-O2NC6H4NH2
(2h)
8
9
(3h)
(4a)
(4b)
(4c)
(4d)
(4e)
48
23
24
5
60
91
89
96
96
94
N
H
NO2
OH
PhNH2
(2a)
O
N
H
(1b)
OH
4-MeOC6H4NH2
(2b)
10
11
12
13
N
H
OMe
OH
4-ClC6H4NH2
(2c)
N
H
Cl
OH
4-BrC6H4NH2
(2d)
5
N
H
Br
OH
4-F3CC6H4NH2
(2e)
6
N
H
CF3
Synthesis 2009, No. 16, 2790–2796 © Thieme Stuttgart · New York

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J. Agarwal et al.
PAPER
Table 1 Iridium Trichloride Catalyzed Ring Opening of Epoxides with Anilines at Room Temperature (continued)
Entry
14
Epoxide
Aniline
Producta
Time (h) Yieldb (%)
OH
3,5-Me2C6H3NH2
(2f)
(4f)
24
98
N
H
OH
2,6-Me2C6H3NH2
(2g)
15
16
(4g)
(4h)
24
30
48
53
N
H
OH
4-O2NC6H4NH2
(2h)
N
H
NO2
O
PhNH2
(2a)
HN
17
18
(5a)
(6a)
12
89
78
OH
OH
(1c)
(1d)
O
H
N
O
PhNH2
(2a)
O
4
a Reactions were carried out with epoxide (1 equiv), aryl amine (1 equiv), and IrCl3·xH2O (0.05 equiv, 5 mol%) in CH2Cl2 at r.t. (see general
procedure).
b Yields are for the pure and isolated products.
(Scheme 3); the results are shown in Table 2. The corre-
sponding amino alcohols 3i–l and 4i–l were obtained in
HN
very high yields (Table 2).
PhNH2
O
OH
The structures of the b-amino alcohols 3–6 were assigned
1
IrCl3•xH2O
CH2Cl2
on the basis of IR spectra, H (500 MHz) and 13C (125
1c
5a
MHz) NMR spectra, and mass spectra. The trans-stereo-
chemistry of b-amino alcohols 3 and 4 was deduced from
the coupling constants of the protons on C-1 and C-2. For
OH
O
H
O
N
O
PhNH2
1
instance, in the H NMR (500 MHz) spectrum of 2-[(4-
IrCl3•xH2O
CH2Cl2
chlorophenyl)amino]cyclohexan-1-ol (3c), two 1H signals
appeared at d = 3.09 (ddd, J = 4.0, 9.0, 11.5 Hz, 1 H) and
d = 3.37 (ddd, J = 4.5, 9.5, 10.5 Hz, 1 H) for the CHNH
and CHOH protons, respectively, which are indicative of
a trans-stereochemistry. Additionally, the 1H NMR spec-
tra for the 2-(arylamino)cycloalkanols were in agreement
with the spectra of these compounds reported in the liter-
ature.3a,4c,9,10
6a
1d
Scheme 2
OH
R1
IrCl3•xH2O
R1
O
+
HN
R2
n
N
CH2Cl2
n
R2
We believe that the IrCl3·xH2O-mediated epoxide ring
opening involves the coordination of the metal salt to the
oxygen atom of the epoxide, thereby increasing the elec-
trophilicity at the two carbon atoms. Nucleophilic attack
by the nitrogen atom of the amine at a carbon atom fol-
lowed by oxirane ring opening and proton transfer leads to
the formation of an amino alcohol and concurrent release
of the metal salt to complete the catalytic cycle.
n = 2, 1a
n = 1, 1b
2i–l
n = 2, 3i–l
n = 1, 4i–l
Scheme 3
To establish the applicability of this catalytic method to
heterocyclic and aliphatic amines, amines such as pyrroli-
dine (2i), piperidine (2j), morpholine (2k), or butan-1-
amine (2l), were treated with cyclohexene oxide (1a) or
cyclopentene oxide (1b) in the presence of IrCl3·xH2O
In summary, we have demonstrated a novel and mild
method for ring opening of epoxides with aromatic
Synthesis 2009, No. 16, 2790–2796 © Thieme Stuttgart · New York

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Catalytic Aminolysis of Epoxides
2793
Chem Ltd.) with EtOAc–hexanes as an eluent system. Melting
points are uncorrected. IR spectra of the compounds were recorded
on a Thermo Nicolet FT-IR NexusTM and are expressed as wave-
numbers (cm–1). 1H and 13C NMR spectra were recorded at 500 and
125 MHz, respectively, on a Bruker FT-NMR. The 1H NMR spectra
were recorded in CDCl3 using TMS as the internal standard. Chem-
ical shifts of 1H NMR spectra were given in parts per million with
respect to TMS, and the coupling constant J was measured in Hz.
Mass spectra were recorded by GC-MS (Perkin-Elmer Clarus 500
GC).
Table 2 Iridium Trichloride-Catalyzed Ring Opening of Epoxides
with Heterocyclic and Aliphatic Amines at Room Temperature
Entry Epoxide Amine
Producta
Time Yield
(h) (%)b
OH
N
pyrrolidine
(2i)
O
1
2
(3i) 14 87
(1a)
OH
N
Catalytic Ring Cleavage of Epoxides by Amines; General Pro-
cedure
piperidine
(2j)
(3j) 18 85
IrCl3·xH2O (21 mg, 0.05 mM, 5 mol%) was added to a stirred mix-
ture of the epoxide (1 mM) and amine (1 mM) in CH2Cl2 (2 mL) at
r.t. The reaction was monitored by TLC at regular intervals. When
the reaction was complete, the solvent was evaporated in a rotary
evaporator, and the residue was purified by column chromatogra-
phy [silica gel (EtOAc–hexanes, 10:90 for aromatic amine prod-
ucts; 60:40 for heterocyclic and aliphatic amine products)].
OH
N
morpholine
(2k)
3
(3k) 24 79
O
OH
trans-2-(Phenylamino)cyclohexanol (3a)
Purple solid; yield: 187 mg (98%); mp 60–61 °C (Lit.3a 58–59 °C).
BuNH2
(2l)
4
5
(3l) 20 84
N
H
IR (KBr): nmax = 3388 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.18 (t, J = 8.0 Hz, 2 H), 6.73 (dd,
J = 8.0, 19.0 Hz, 3 H), 3.36 (ddd, J = 4.0, 9.5, 13.0 Hz, 1 H), 3.15
(ddd, J = 4.0, 9.5, 13.0 Hz, 1 H), 2.70 (br s, 1 H), 2.11 (d, J = 12.5
Hz, 2 H), 1.81–1.68 (m, 2 H), 1.45–1.34 (m, 2 H), 1.31 (t, J = 10.5
Hz, 2 H), 1.05 (dq, J = 3.5, 12.5 Hz, 1 H).
OH
pyrrolidine
(2i)
O
(4i) 10 84
N
(1b)
OH
N
13C NMR (CDCl3, 125 MHz): d = 146.7, 128.3, 117.3, 113.4, 73.4,
59.1, 32.2, 30.5, 24.0, 23.3.
piperidine
(2j)
6
(4j) 15 82
MS (EI, 70 eV): m/z =191 [M+].
trans-2-[(4-Methoxyphenyl)amino]cyclohexanol (3b)
Brown liquid; yield: 212 mg (96%).
OH
N
morpholine
(2k)
7
8
(4k) 22 82
IR (KBr) : nmax = 3485 cm–1.
1H NMR (CDCl3, 500 MHz): d = 6.78 (d, J = 9.0 Hz, 2 H), 6.69 (d,
J = 9.0 Hz, 2 H), 3.75 (s, 3 H), 3.33 (ddd, J = 4.5, 10.0, 13.5 Hz, 1
H), 3.01 (ddd, J = 4.0, 9.5, 13.0 Hz, 1 H), 2.15–2.06 (m, 2 H), 1.80–
1.68 (m, 2 H), 1.43–1.24 (m, 3 H), 1.01 (dq, J = 3.5, 11.5 Hz, 1 H).
O
OH
BuNH2
(2l)
(4l) 23 86
N
H
13C NMR (CDCl3, 125 MHz): d = 153.2, 141.0, 116.8, 114.9, 74.2,
62.0, 55.8, 33.1, 31.3, 25.1, 24.3.
a Reactions were carried out with epoxide (1 equiv), amine (1 equiv),
and IrCl3·xH2O (0.05 equiv, 5 mol%) in CH2Cl2 at r.t. (see general
procedure).
MS (EI, 70 eV): m/z = 221 [M+].
trans-2-[(4-Chlorophenyl)amino]cyclohexanol (3c)
Brown solid; yield: 200 mg (89%); mp 74–75 °C.
b Yields are for pure and isolated products.
IR (KBr): nmax = 3419 cm–1.
amines and heterocyclic and aliphatic amines by using iri-
dium trichloride as the catalyst. Our study showed that iri-
dium trichloride participates in a catalytic cycle for ring
opening of epoxides by aryl, heterocyclic, or aliphatic
amines. A noteworthy feature of the present methodology
is that highly deactivated and sterically demanding
anilines also cleave epoxides in reasonable yields at room
temperature.
1H NMR (CDCl3, 500 MHz): d = 7.12 (td, J = 2.0, 8.5 Hz, 2 H),
6.65 (td, J = 2.5, 9.0 Hz, 2 H), 3.37 (ddd, J = 4.0, 9.5, 10.5 Hz, 1
H), 3.09 (ddd, J = 4.0, 9.0, 11.5 Hz, 1 H), 2.14–2.06 (m, 2 H), 1.82–
1.69 (m, 2 H), 1.43–1.28 (m, 2 H), 1.14–1.02 (m, 2 H).
13C NMR (CDCl3, 125 MHz): d = 147.7, 129.3, 118.3, 114.4, 74.4,
60.1, 33.2, 31.5, 24.9, 24.3.
MS (EI, 70 eV): m/z = 225 [M+].
trans-2-[(4-Bromophenyl)amino]cyclohexanol (3d)
Wheat-colored solid; yield: 232 mg (86%); mp 110–111 °C.
Organic solvents were dried by standard methods when necessary.
Commercially available reagents were used without further purifi-
cation unless mentioned. Aniline was freshly distilled under re-
duced pressure before use. All reactions were monitored by TLC on
aluminum plates coated with silica gel. The TLC plates were visu-
alized with a UV lamp or in an iodine chamber. Column chromatog-
raphy was performed by using silica gel (100–200 mesh; SD Fine-
IR (KBr): nmax = 3485 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.12 (d, J = 8.5 Hz, 2 H), 6.64 (d,
J = 8.5 Hz, 2 H), 3.36 (ddd, J = 4.5, 10.0, 14.0 Hz, 1 H), 3.09 (ddd,
J = 4.0, 9.5, 11.5 Hz, 1 H), 2.60 (br s, 2 H), 2.15–2.06 (m, 2 H),
Synthesis 2009, No. 16, 2790–2796 © Thieme Stuttgart · New York

2794
J. Agarwal et al.
PAPER
1.81–1.70 (m, 2 H), 1.44–1.26 (m, 3 H), 1.05 (dq, J = 3.5, 13.0 Hz,
1 H).
13C NMR (CDCl3, 125 MHz): d = 70.7, 65.0, 47.2, 33.3, 25.3, 24.2,
23.6, 21.2.
13C NMR (CDCl3, 125 MHz): d = 147.0, 132.1, 116.3, 110.0, 74.5,
60.1, 33.3, 31.5, 24.9, 24.3.
MS (EI, 70 eV): m/z = 169 [M+].
trans-2-(Piperidin-1-yl)cyclohexanol (3j)
Colorless liquid; yield: 156 mg (85%).
MS (EI, 70 eV): m/z = 269 [M+].
trans-2-{[4-(Trifluoromethyl)phenyl]amino}cyclohexanol (3e)
Brown viscous liquid; yield: 230 mg (89%).
IR (KBr): nmax = 3446 cm–1.
1H NMR (CDCl3, 500 MHz): d = 3.38 (dt, J = 5.0, 10.0 Hz, 1 H),
2.72–2.66 (m, 2 H), 2.40–2.31 (m, 2 H), 2.19–2.12 (m, 2 H), 1.84–
1.68 (m, 2 H), 1.67–1.51 (m, 4 H), 1.51–1.43 (m, 2 H), 1.32–1.12
(m, 5 H).
IR (KBr): nmax = 3385 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.39 (d, J = 8.5 Hz, 2 H), 6.71 (d,
J = 8.5 Hz, 2 H), 3.73 (br s, 1 H), 3.40 (ddd, J = 4.5, 9.5, 13.5 Hz,
1 H), 3.21 (ddd, J = 4.0, 9.0, 11.0 Hz, 1 H), 2.36 (br s, 1 H), 2.15–
2.08 (m, 2 H), 1.83–1.71 (m, 2 H), 1.45–1.20 (m, 3 H), 1.18–1.02
(m, 1 H).
13C NMR (CDCl3, 125 MHz): d = 71.0, 68.5, 50.0, 33.3, 26.7. 25.6,
24.8, 24.1, 22.2.
MS (EI, 70 eV): m/z = 183 [M+].
13C NMR (CDCl3, 125 MHz): d = 150.6 126.7 (q, J = 3.8 Hz), 124.9
(q, J = 268.8 Hz), 119.4 (q, J = 43.8 Hz), 113.0, 74.6, 59.4, 33.5,
31.6, 24.8, 24.2.
trans-2-(Morpholin-4-yl)cyclohexanol (3k)
Brown liquid; yield: 146 mg (79%).
MS (EI, 70 eV): m/z = 259 [M+].
IR (KBr): nmax = 3461 cm–1.
1H NMR (CDCl3, 500 MHz): d = 4.00 (br s, 1 H), 3.80–3.48 (m, 4
H), 3.40 (dt, J = 4.5, 10.0 Hz, 1 H), 2.75 (ddd, J = 3.0, 5.5, 9.5 Hz,
2 H), 2.45 (ddd, J = 3.0, 6.0, 9.5 Hz, 2 H), 2.24–2.13 (m, 2 H), 1.87–
1.80 (m, 2 H), 1.76–1.60 (m, 1 H), 1.32–1.15 (m, 4 H).
trans-2-[(3,5-Dimethylphenyl)amino]cyclohexanol (3f)
Brown solid; yield: 197 mg (90%); mp 34–36 °C.
IR (KBr): nmax = 3384 cm–1.
1H NMR (CDCl3, 500 MHz): d = 6.42 (s, 1 H), 6.37 (s, 2 H), 3.33
(ddd, J = 4.0, 9.5, 13.5 Hz, 1 H), 3.12 (dt, J = 4.0, 9.5 Hz, 1 H), 2.83
(br s, 2 H), 2.23 (s, 6 H), 2.15–2.07 (m, 2 H), 1.80–1.70 (m, 2 H),
1.45–1.27 (m, 3 H), 1.04 (dq, J = 4.0, 12.5 Hz, 1 H).
13C NMR (CDCl3, 125 MHz): d = 70.4, 68.3, 67.4, 48.4, 33.1, 25.4,
23.9, 22.1.
MS (EI, 70 eV): m/z = 185 [M+].
13C NMR (CDCl3, 125 MHz): d = 147.8, 139.0, 120.3, 112.3, 74.5,
60.1, 33.0, 31.7, 25.0, 24.2, 21.4.
trans-2-(Butylamino)cyclohexanol (3l)
Colourless liquid; yield: 144 mg (84%).
MS (EI, 70 eV): m/z = 219 [M+].
IR (KBr): nmax = 3411 cm–1.
1H NMR (CDCl3, 500 MHz): d = 3.16 (dt, J = 4.5, 9.5 Hz, 1 H),
2.83–2.76 (m, 1 H), 2.51–2.44 (m, 1 H), 2.20 (ddd, J = 4.0, 9.5, 11.5
Hz, 1 H), 2.13–2.01 (m, 2 H), 1.19–1.15 (m, 2 H), 1.51–1.42 (m, 2
H), 1.37 (sextet, J = 7.5 Hz, 2 H), 1.32–1.21 (m, 3 H), 1.18–0.94 (m,
1 H), 0.93 (t, J = 7.5 Hz, 3 H).
trans-2-[(2,6-Dimethylphenyl)amino]cyclohexanol (3g)
Brown viscous liquid; yield: 107 mg (49%).
IR (KBr): nmax = 3432 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.0 (d, J = 7.5 Hz, 2 H), 6.84 (t,
J = 7.5 Hz, 1 H), 3.41 (dt, J = 4.0, 10.0 Hz, 1 H), 2.87 (ddd, J = 4.0,
9.5, 11.0 Hz, 1 H), 2.29 (s, 6 H), 1.85–1.79 (m, 1 H), 1.76–1.71 (m,
1 H), 1.68–1.62 (m, 1 H), 1.42–1.23 (m, 3 H), 1.19–1.06 (m, 2 H).
13C NMR (CDCl3, 125 MHz): d = 73.3, 68.5, 46.4, 33.8, 32.6, 30.3,
25.0, 24.5, 20.4, 13.9.
MS (EI, 70 eV): m/z = 171 [M+].
13C NMR (CDCl3, 125 MHz): d = 144.0, 129.8, 129.1, 122.3, 75.1,
63.4, 33.1, 32.5, 25.3, 24.3, 19.2.
trans-2-(Phenylamino)cyclopentanol (4a)
Purple solid; yield: 161 mg (91%); mp 55–57 °C (Lit.3a 54–55 °C).
MS (EI, 70 eV): m/z = 219 [M+].
IR (KBr): nmax = 3452 cm–1.
trans-2-(4-Nitrophenylamino)cyclohexanol (3h)
Yellow solid; yield: 141 mg (60%); mp 120–121 °C (Lit.3a 119–
121 °C).
1H NMR (CDCl3, 500 MHz): d = 7.16 (t, J = 7.5 Hz, 2 H), 6.70 (t,
J = 7.5 Hz, 1 H), 6.63 (d, J = 8.0 Hz, 2 H), 3.99 (q, J = 4.5 Hz, 1
H), 3.55 (q, J = 6.5 Hz, 1 H), 3.10 (br s, 2 H), 2.26–2.18 (m, 1 H),
1.97–1.89 (m, 1 H), 1.82–1.55 (m, 3 H), 1.35 (sextet, J = 6.5 Hz, 1
H).
IR (KBr): nmax = 3413 cm–1.
1H NMR (CDCl3, 500 MHz): d = 8.10 (td, J = 3.5, 9.0 Hz, 2 H),
6.66 (td, J = 3.5, 9.5 Hz, 2 H), 4.37 (br s, 1 H), 3.49 (dt, J = 4.0, 9.5
Hz, 1 H), 3.32 (br s, 1 H), 2.18–2.12 (m, 2 H), 1.87–1.77 (m, 2 H),
1.51–1.12 (m, 5 H).
13C NMR (CDCl3, 125 MHz): d = 147.7, 129.3, 117.6, 113.3, 78.3,
62.2, 32.9, 31.2, 21.1.
MS (EI, 70 eV): m/z = 177 [M+].
13C NMR (CDCl3, 125 MHz): d = 153.5, 138.0, 126.4, 111.9, 74.6,
59.1, 33.8, 31.5, 24.6, 24.2.
trans-2-[(4-Methoxyphenyl)amino]cyclopentanol (4b)
Brown viscous liquid; yield: 184 mg (89%).
MS (EI, 70 eV): m/z = 236 [M+].
IR (KBr): nmax = 3381 cm–1.
trans-2-(Pyrrolidin-1-yl)cyclohexanol (3i)
Brown liquid; yield: 147 mg (87%).
1H NMR (CDCl3, 500 MHz): d = 6.78 (dd, J = 3.5, 8.5 Hz, 2 H),
6.67 (dd, J = 3.5, 7.0 Hz, 2 H), 4.07 (q, J = 5.0 Hz, 1 H), 3.75 (s, 3
H), 3.56–3.51 (m, 1 H), 2.68 (br s, 2 H), 2.28–2.18 (m, 1 H), 2.03–
1.94 (m, 1 H), 1.86–1.58 (m, 3 H), 1.41 (sextet, J = 6.5 Hz, 1 H).
IR (KBr): nmax = 3455 cm–1.
1H NMR (CDCl3, 500 MHz): d = 4.00 (br s, 1 H), 3.34 (dt, J = 4.5,
9.5 Hz, 1 H), 2.71–2.66 (m, 2 H), 2.58–2.53 (m, 2 H), 2.45 (dt,
J = 3.5, 12.0 Hz, 1 H), 2.14–2.06 (m, 1 H), 1.81–1.68 (m, 7 H),
1.32–1.18 (m, 4 H).
13C NMR (CDCl3, 125 MHz): d = 152.7, 141.1, 115.5, 114.9, 77.9,
63.7, 55.8, 32.7, 30.9, 20.9.
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Catalytic Aminolysis of Epoxides
IR (KBr): nmax = 3366 cm–1.
2795
MS (EI, 70 eV): m/z = 207 [M+].
1H NMR (CDCl3, 500 MHz): d = 8.51–7.95 (m, 2 H), 6.59 (d,
J = 9.5 Hz, 1 H), 4.60 (br s, 1 H), 4.18–4.08 (m, 1 H), 3.69 (quintet,
J = 6.5 Hz, 1 H), 2.38–2.22 (m, 1 H), 1.99 (quintet, J = 7.0 Hz, 1 H),
1.92–1.69 (m, 3 H), 1.46 (sextet, J = 7.0 Hz, 1 H).
trans-2-[(4-Chlorophenyl)amino]cyclopentanol (4c)
Brown viscous liquid; yield: 202 mg (96%).
IR (KBr): nmax = 3403 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.10 (td, J = 3.5, 5.5 Hz, 2 H),
6.57 (td, J = 3.0, 5.0 Hz, 2 H), 4.02 (q, J = 4.5 Hz, 1 H), 3.51–3.46
(m, 1 H), 2.30–2.21 (m, 1 H), 2.02–1.96 (m, 1 H), 1.86–1.68 (m, 3
H), 1.37 (sextet, J = 7.0 Hz, 1 H).
13C NMR (CDCl3, 125 MHz): d = 153.7, 137.2, 126.5, 111.6, 78.0,
61.6, 33.0, 32.7, 21.0.
MS (EI, 70 eV): m/z = 222 [M+].
13C NMR (CDCl3, 125 MHz): d = 146.6, 129.1, 121.8, 114.5, 77.9,
62.1, 32.8, 31.0, 21.1.
trans-2-(Pyrrolidin-1-yl)cyclopentanol (4i)
Brown liquid; yield: 130 mg (84%).
MS (EI, 70 eV): m/z = 211 [M+].
IR (KBr): nmax = 3371 cm–1.
1H NMR (CDCl3, 500 MHz): d = 4.21 (dt, J = 4.5, 6.5 Hz, 1 H), 3.30
(br s, 2 H), 2.81–2.71 (m, 4 H), 2.63 (dt, J = 5.5, 8.0 Hz, 1 H), 2.06–
1.94 (m, 2 H), 1.89–1.82 (m, 4 H), 1.78–1.58 (m, 4 H).
trans-2-[(4-Bromophenyl)amino]cyclopentanol (4d)
Brown liquid; yield: 246 mg (96%).
IR (KBr): nmax = 3403 cm–1.
13C NMR (CDCl3, 125 MHz): d = 76.5, 73.3, 52.4, 34.2, 29.1, 23.3,
21.3.
1H NMR (CDCl3, 500 MHz): d = 7.25 (d, J = 8.5 Hz, 2 H), 6.53 (d,
J = 8.5 Hz, 2 H), 4.02 (q, J = 4.5 Hz, 1 H), 3.54 (q, J = 6.5 Hz, 1
H), 2.85 (br s, 2 H), 2.26 (sextet, J = 7.5 Hz, 1 H), 1.97 (sextet,
J = 7.0 Hz, 1 H), 1.85–1.57 (m, 3 H), 1.39 (sextet, J = 7.0 Hz, 1 H).
MS (EI, 70 eV): m/z = 155 [M+].
trans-2-(Piperidin-1-yl)cyclopentanol (4j)
Colourless liquid; yield: 139 mg (82%).
13C NMR (CDCl3, 125 MHz): d = 146.7, 131.9, 114.9, 109.2, 78.9,
62.2, 33.0, 31.1, 21.0.
IR (KBr): nmax = 3405 cm–1.
MS (EI, 70 eV): m/z = 255 [M+].
1H NMR (CDCl3, 500 MHz): d = 4.15 (dt, J = 5.5, 7.5 Hz, 1 H),
2.60–2.48 (m, 5 H), 2.12 (br s, 2 H), 2.00–1.80 (m, 2 H), 1.73–1.55
(m, 7 H), 1.52–1.43 (m, 3 H).
trans-2-{[4-(Trifluoromethyl)phenyl]amino}cyclopentanol (4e)
Brown viscous liquid; yield: 230 mg (94%).
13C NMR (CDCl3, 125 MHz): d = 75.5, 74.8, 52.3, 34.3, 26.9, 26.0,
24.5, 21.7.
IR (KBr): nmax = 3367 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.39 (d, J = 8.5 Hz, 2 H), 6.67 (d,
J = 8.5 Hz, 2 H), 4.07 (q, J = 4.5 Hz, 1 H), 3.64 (dt, J = 4.5, 6.5 Hz,
1 H), 2.34–2.25 (m, 1 H), 2.03–1.95 (m, 1 H), 1.91–1.62 (m, 3 H),
1.42 (sextet, J = 7.0 Hz, 1 H).
MS (EI, 70 eV): m/z = 169 [M+].
trans-2-(Morpholin-4-yl)cyclopentanol (4k)
Brown liquid; yield: 140 mg (82%).
13C NMR (CDCl3, 125 MHz): d = 150.2, 126.6 (q, J = 3.8 Hz),
125.1 (q, J = 393.8 Hz), 118.8 (q, J = 42.5 Hz), 78.1, 33.9, 31.1,
21.0.
IR (KBr): nmax = 3432 cm–1.
1H NMR (CDCl3, 500 MHz): d = 4.15 (dt, J = 5.5, 7.5 Hz, 1 H), 3.76
(t, J = 4.5 Hz, 3 H), 2.68–2.60 (m, 2 H), 2.60–2.48 (m, 3 H), 2.01
(dq, J = 7.5, 8.0 Hz, 1 H), 1.96–1.88 (m, 1 H), 1.80–1.73 (m, 2 H),
1.72–1.57 (m, 2 H), 1.54–1.46 (m, 1 H).
MS (EI, 70 eV): m/z = 245 [M+].
trans-2-[(3,5-Dimethylphenyl)amino]cyclopentanol (4f)
Brown viscous liquid; yield: 201 mg (98%).
13C NMR (CDCl3, 125 MHz): d = 75.3, 74.9, 67.0, 52.0, 34.4, 27.3,
21.4.
IR (KBr): nmax = 3391 cm–1.
MS (EI, 70 eV): m/z = 171 [M+].
1H NMR (CDCl3, 500 MHz): d = 6.38 (s, 1 H), 6.31 (s, 2 H), 4.06
(q, J = 5.0 Hz, 1 H), 3.63–3.58 (m, 1 H), 2.22–2.35 (m, 7 H), 2.02–
1.94 (m, 1 H), 1.87–1.61 (m, 3 H), 1.39 (sextet, J = 6.5 Hz, 1 H).
trans-2-(Butylamino)cyclopentanol (4l)
Colourless liquid; yield: 135 mg (86%).
13C NMR (CDCl3, 125 MHz): d = 147.3, 138.8, 119.9, 111.8, 77.7,
62.3, 32.4, 30.7, 21.4, 20.6.
IR (KBr): nmax = 3415 cm–1.
1H NMR (CDCl3, 500 MHz): d = 3.85 (q, J = 6.5 Hz, 1 H), 2.81 (q,
J = 7.5 Hz, 1 H), 2.66–2.53 (m, 2 H), 2.04–1.90 (m, 2 H), 1.76–1.59
(m, 2 H), 1.56–1.42 (m, 3 H), 1.32 (sextet, J = 7.0 Hz, 2 H), 1.28–
1.22 (m, 1 H), 0.90 (t, J = 7.0 Hz, 3 H).
MS (EI, 70 eV): m/z = 205 [M+].
trans-2-[(2,6-Dimethylphenyl)amino]cyclopentanol (4g)
Brown viscous liquid; yield: 98 mg (48%).
13C NMR (CDCl3, 125 MHz): d = 77.5, 66.7, 48.3, 32.6, 32.3, 30.0,
20.5, 20.3, 13.9
IR (KBr): nmax = 3376 cm–1.
1H NMR (CDCl3, 500 MHz): d = 6.99 (d, J = 7.5 Hz, 2 H), 6.81 (t,
J = 7.5 Hz, 1 H), 3.97 (q, J = 6.0 Hz, 1 H), 3.50–3.45 (m, 1 H), 2.30
(s, 6 H), 2.11–2.00 (m, 2 H), 1.77–1.69 (m, 2 H), 1.64–1.58 (m, 1
H), 1.46–1.40 (m, 1 H).
MS (EI, 70 eV): m/z = 157 [M+].
2-Phenyl-2-(phenylamino)ethanol (5a)
Brown liquid; yield: 190 mg (89%).
13C NMR (CDCl3, 125 MHz): d = 144.4, 128.8, 121.6, 78.5, 65.6,
31.5, 30.8, 29.5, 19.8, 18.8.
IR (KBr): nmax = 3397 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.31–7.24 (m, 4 H), 7.21–7.17 (m,
1 H), 7.06–7.01 (m, 2 H), 6.64–6.60 (m, 1 H), 6.50 (dd, J = 1.0, 8.5,
2 H), 4.41 (q, J = 4.0 Hz, 1 H), 3.83 (dd, J = 4.0, 11.0 Hz, 1 H), 3.64
(dd, J = 7.0, 11.0 Hz, 1 H).
MS (EI, 70 eV): m/z = 205 [M+].
trans-2-[(4-Nitrophenyl)amino]cyclopentanol (4h)
Brown viscous liquid; yield: 118 mg (53%).
Synthesis 2009, No. 16, 2790–2796 © Thieme Stuttgart · New York

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J. Agarwal et al.
PAPER
(3) (a) Sekar, G.; Singh, V. K. J. Org. Chem. 1999, 64, 287.
13C NMR (CDCl3, 125 MHz): d = 147.1, 140.1, 129.1, 128.7, 127.5,
126.6, 117.8, 113.8, 67.2, 59.8.
(b) Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2004,
45, 49. (c) Khosropour, A. R.; Khodaei, M. M.; Ghozati, K.
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M. Tetrahedron Lett. 2006, 47, 6557.
MS (EI, 70 eV): m/z = 213 [M+].
1-Phenoxy-3-(phenylamino)propan-2-ol (6a)
Brown liquid; yield: 189 mg (78%).
(4) (a) Chandrasekhar, S.; Ramachandar, T.; Prakash, J. S.
Synthesis 2000, 1817. (b) Reddy, L. R.; Reddy, M. A.;
Bhanumathi, N.; Rao, K. R. New J. Chem. 2001, 25, 221.
(c) Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2002,
43, 7891. (d) Sabitha, G.; Reddy, G. S. K. K.; Reddy, K. B.;
Yadav, J. S. Synthesis 2003, 2298. (e) Chakraborti, A. K.;
Kondaskar, A. Tetrahedron Lett. 2003, 44, 8315.
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7495. (g) Sundararajan, A.; Vijayakrishna, K.; Varghese, B.
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IR (KBr): nmax = 3558 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.32–7.27 (m, 2 H), 7.21–7.16 (m,
2 H), 7.00–6.96 (m, 1 H), 6.94–6.90 (m, 2 H), 6.76–6.71 (m, 1 H),
6.69–6.65 (m, 2 H), 4.28–4.20 (m, 1 H), 4.15–3.99 (m, 2 H), 3.43
(dd, J = 4.5, 13.0 Hz, 1 H), 3.29 (dd, J = 7.0, 13.0 Hz, 1 H).
13C NMR (CDCl3, 125 MHz): d = 158.3, 147.9, 129.5, 129.2, 121.2,
117.9, 114.4, 113.2, 69.9, 68.7, 46.5.
MS (EI, 70 eV): m/z = 243 [M+].
(5) Kamal, A.; Ramu, R. R.; Azhar, M. A.; Khanna, G. B. R.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
We thank the Council of Scientific and Industrial Research (CSIR)
and the Department of Science and Technology (DST), New Delhi
for providing financial assistance. J.A. thanks UGC and R.R. thanks
DST for the award of fellowships.
(11) Mojtahedi, M. M.; Abaee, M. S.; Hamidi, V. Catal.
Commun. 2007, 8, 1671.
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Synthesis 2009, No. 16, 2790–2796 © Thieme Stuttgart · New York