Synthesis of β-amino alcohols using MgO as a new catalyst under solvent-free conditions

Article abstract of DOI:10.1139/V07-135

MgO catalyzed efficiently the ring opening of epoxides with a range of aromatic and aliphatic amines to produce β-substituted alcohols in high yields under solvent-free conditions. Exclusive trans stereoselectivity is observed for cyclic epoxide.

Full text of DOI:10.1139/V07-135

65
Synthesis of ␤-amino alcohols using MgO as a
new catalyst under solvent-free conditions
Mona Hosseini-Sarvari
Abstract: MgO catalyzed efficiently the ring opening of epoxides with a range of aromatic and aliphatic amines to
produce β-substituted alcohols in high yields under solvent-free conditions. Exclusive trans stereoselectivity is observed
for cyclic epoxide.
Key words: MgO, β-amino alcohols, solvent-free, epoxide, amine.
Résumé : Dans des conditions n’impliquant aucun solvant, l’oxyde de magnésium, MgO, catalyse d’une façon efficace
l’ouverture du cycle des époxydes avec une grande variété d’amines aliphatiques et aromatiques pour conduire avec des
rendements élevés aux alcools β-substitués correspondants. On observe exclusivement l’ouverture stéréosélective trans
avec les époxydes cycliques.
Mots-clés : MgO, β-aminoalcools, sans solvant, époxyde, amine.
[Traduit par la Rédaction] Hosseini-Sarvari 71
Introduction
Scheme 1. Synthesis of β-amino alcohols catalyzed by MgO.
OH
MgO (10 mol%)
The formation of β-amino alcohols from epoxides and
amines is an important reaction in medicinal and organic
chemistry, as they are useful synthetic intermediates for the
preparation of β-amino acids, natural products, and chiral
auxiliaries (1). Opening of epoxides with amines developed
in the past few years, and many catalysts (reagents) were
used, such as metal triflates (2), metal halides (3), polymer
supported (4), montmorillonite K10 (5), and metal salt (6).
Different reaction media, such as ionic liquids (7), ultra-
sound (8), microwave irradiation (9), solvent-free conditions
(SFC), and water (10) were also employed. These processes
are useful; however, they suffer from disadvantages, such as
the use of expensive or air-sensitive reagents, extended reac-
tion times, and the requirement for protracted work-up pro-
cedures, or are limited in the range of amines specially
aliphatic amines.
MgO is an environmentally safe, non-volatile, non hygro-
scopic, odourless, and white powder with outstanding physi-
cal properties and stability. It is commercially available and
is a very cheap chemical. Recently, it was shown that MgO
has the prospect to be used as a substitute for conventional
basic catalytic materials. It has been used as an efficient het-
erogeneous catalyst in many important organic reactions
(11).
O
R–NH2
R
solvent-free, 80 °C
N
H
2
1a
3
R = alkyl and aryl
Results and discussion
The condensation between an amine and an epoxide lead-
ing to the formation of a β-amino alcohol should be a facile
reaction due to the good electrophilic and nucleophilic prop-
erties of the epoxide and amine groups, respectively. This re-
action may not require any catalytic assistance in the
absence of electronic/steric factors that might decrease the
electrophilicity/nucleophilicity of the epoxide/amine groups.
Thus, the condensation of cyclohexene oxide with 4-
methylaniline, 4-methoxyaniline, and 4-bromoaniline af-
forded 70%–90% yields, in 6–8 h, under neat conditions at
80 °C without the requirement of any additional reagent/cat-
alyst. The treatment of cyclohexene oxide with aniline af-
forded the corresponding β–aminol alcohols in 60% yields
in 12 h. However, no significant β-amino alcohol formation
was observed (1H NMR) when cyclohexene oxide was
treated with 4-nitroaniline at 100 °C under neat conditions.
The presence of the strong electron-withdrawing property
of the nitro group in 4-nitroaniline decreases the nucleo-
philicity of the amine group. Thus, the combination of this
substrate with cyclohexene oxide constitutes a model reac-
tion for evaluating the efficiency of a catalyst. Hence,
cyclohexene oxide was treated with 4-nitroaniline under var-
ious conditions (Table 1). Clearly, the best results were
reached with MgO under solvent-free conditions (Table 1,
entry 1).
In this pursuit, and during the course of the studies aimed
at developing solvent-free procedures (12), for the first time,
MgO-catalyzed ring opening of epoxides by amines in sol-
vent-free conditions is reported in this paper (Scheme 1).
Received 27 September 2007. Accepted 2 November 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 13 December 2008.
M. Hosseini-Sarvari.1 Department of Chemistry, Shiraz
University, Shiraz 71454, Islamic Republic of Iran.
To evaluate the generality, reaction of various epoxides
were carried out with various aromatic, aliphatic, primary,
1(e-mail: hossaini@susc.ac.ir).
Can. J. Chem. 86: 65–71 (2008)
doi:10.1139/V07-135
© 2007 NRC Canada

66
Can. J. Chem. Vol. 86, 2008
Table 1. Reaction between cyclohexene oxide (2d) and 4-nitroaniline (1l) in the presence of vari-
ous catalysts and conditions
Entry
Catalyst/conditions
Time (h)
Yielda (%)
1
2
3
4
5
6
7
MgO (10 mol%)/neat
MgO (10 mol%)/CH2Cl2
MgO (10 mol%)/PhMe
MgO (10 mol%)/THF
No catalyst/neat
12
24
24
24
65
Trace
Trace
Trace
No reaction
No reaction
24
Mesoporous aluminizilicate (13)
H3PW12O40 (14)
35
8
9
10
11
Sulfamic acid (15)
No reaction
CaO (10 mol%)/neat
K2CO3 (10 mol%)/neat
CuO (10 mol%)/neat
24
24
24
Trace
43
Trace
aYields are for the isolated compounds.
and secondary amines under the catalytic influence of MgO,
and excellent results were obtained (Table 2). The reaction
protocol is simple and does not require dry glassware and re-
agents. This is very important for scaling-up the process.
The final amino alcohol was isolated in >99% purity in
50%–98% yield.
ing from nucleophilic displacement of the chlorine could be
detected through MS analysis of the reaction mixture.
The reuse ability and catalytic activity of MgO was stud-
ied in this system. The catalyst was recovered by centrifu-
gation after diluting the reaction mixture with Et2O and
dried in an oven at 100 °C for 3 h and was reused repeatedly
without any significant loss of catalytic activities. As shown
in Table 3, the yields of 2-(2-picolylamine)cyclohexanol
(3d) only decreases a little after the reuse of MgO for three
times.
In conclusion, the results demonstrated that MgO effi-
ciently catalyze the formation of β-amino alcohols from
amines and epoxides in high yields under mild and solvent-
free reaction conditions. The facile synthesis of these materi-
als, their benign nature, the ease of handling, and the simpli-
fied reaction and isolation procedures make them a highly
attractive alternative to current methodologies.
The results summarized in Table 2 reveal that excellent
yields were obtained with aromatic and aliphatic amines. In
the case of cyclohexene oxide, in each occasion, the resul-
tant racemic 2-aryl/alkylaminocyclohexanol was obtained
1
with exclusive trans diastereoselectivity as detected by H
NMR spectroscopic analysis (Table2, entries 5–26). The re-
actions are remarkably clean, and no chromatographic sepa-
ration is necessary to get the spectra-pure compounds except
in a few cases (Table 2, entries 16–20) where some starting
materials remained; the conversion being less than 100%.
Primary and secondary amines react very rapidly. Aniline
and its derivatives with electron-donating substitutes also re-
act quite fast. However, anilines with electron-accepting sub-
stitutes, as well as satirically hindered anilines, react very
slowly, and aminolysis required prolonged reaction times.
The reaction of diamines showed good results without any
significant influence of their structures on the product
yields; these products can be used for preparation of
macrocyclic compounds. The conversion of aniline into 2-
aryl/alkylaminocyclohexanol on a 100 mmol scale pro-
ceeded just as well as the 1 mmol reaction.
Experimental
Chemicals were purchased from Fluka, Merck, B. D. H.,
and Aldrich Chemical Companies. Progress of the reactions
was followed by TLC using silica-gel polygrams SIL G/UV
254 plates. NMR spectra were recorded on a Bruker DPX
250 MHz instrument. Mass spectra were recorded on a
Shimadzu GC MS-QP 1000 EX apparatus. Microanalyses
were performed on a PerkinElmer 240-B microanalyzer.
The ratio of the two regioisomeric products was deter-
1
mined by GC–MS and H NMR (based on the methane and
methylene proton signals). In the MS the regioisomer of α-
product exhibited a daughter ion at m/z (M+ – 31) due to the
CH2OH, and the diagnostic feature in the mass spectra of the
β-product (3a) was the ion peak at m/z (M+ – 106) arising
from the loss of PhCHO. The GC–MS revealed the product
to be a mixture of β-product (3a) and α-product in a ratio of
95:5 on the basis of the daughter ions at m/z 228–106 and
228–31, corresponding to β-product (3a) and α-product, re-
spectively. Also, a 95:5 ratio could be determined for β-prod-
uct (3a): α-product, taking into consideration the integral
values of the corresponding benzyl protons.
General procedure
A mixture of MgO (10 mol%, 0.004 g), amine (1 mmol),
and 1,2-epoxide (1 mmol) was heated in an oil bath at 80 °C
and stirred with a magnetic stirrer. The progress of the reac-
tion was monitored by TLC. After the reaction was com-
plete, the obtained product was poured into water, stirred
well to dissolve the MgO, and then extracted with ethyl ace-
tate. The organic solvent was then evaporated, and the pure
product was obtained. This was further purified by
recrystallization with
a suitable solvent (ether). The
regioisomers were separated after silica-gel column chroma-
tography (20% Hexane/EtOAc). The structures of the prod-
Excellent chemo selectivity was achieved with
epichlorohydrin (Table 2, entry 4) resulting in 93% yield of
the amino alcohol corresponding to nucleophilic attack at
the terminal carbon of the epoxide moiety. No product aris-
ucts were confirmed by GC–MS, H NMR, 13C NMR, and
1
comparison with authentic samples obtained commercially
or prepared by reported methods.
© 2007 NRC Canada

Hosseini-Sarvari
67
Table 2. Synthesis of β-amino alcohols.
Time(h) Yieldsa
%
1,2-Epoxide (2)
Product (3)
Entry
Amine (1)
N
N
Ph
OH
O
1
1a
2a
3a
3b
2
90b
H2N
N
H
β
Ph
Ph
α
2
3
1a
1a
2a
3a
12
3
33c
95b
O
2b
N
Ph
N
O
O
β
α
H
OH
93b
98
N
4
5
1a
1a
2c
3c
1
1
O
N
Cl
H
Cl
OH
β
α
OH
2d
3d
O
N
N
H
NH2
NH2
NH2
OH
6
7
1b
1c
1d
1e
1f
2d
3e
3f
3
2
1
1
3
95
98
98
97
90
N
H
OH
2d
2d
2d
2d
N
H
OH
8
3g
3h
3i
N
H
OH
OMe
NH2
9
MeO
N
H
10
NH2
OH
N
H
Br
Br
OH
11
12
1g
1h
2d
2d
3j
3
95
90
Br
NH2
N
H
Br
Br
NH2
3k
0.5
OH
Br
HO
N
H
NH2
OH
13
14
1i
1j
2d
2d
3l
1
2
95
98
N
H
OH
3m
NH2
OH
COMe
N
H
MeOC
HO2C
O2N
15
16
1k
1l
2d
2d
3n
3o
3
94
65
NH2
OH
CO2H
N
H
OH
NO2
12
NH2
N
H
O2N
NH2
OH
17
1m
2d
3p
18
63
N
H
NO2
© 2007 NRC Canada

68
Can. J. Chem. Vol. 86, 2008
Table 2 (concluded).
Entry
Amine (1)
Product (3)
Time (h)
Yieldsa
%
1,2-Epoxide (2)
NH2
CF3
OH
18
19
1n
1o
2d
3q
4
3
78
N
H
CF3
NH
2d
3r
73
H2N
N
NH2
HN
N
HO
OH
OH
20
PhNHPh
1p
1q
1r
2d
2d
2d
3s
3t
24
2
50
86
94
Ph
N
Ph
OH
21
22
(CH3)2CHNHCH(CH3)2
N
OH
CH3CH2CH2NH2
3u
3
N
H
O
OH
23
24
1s
1t
2d
2d
3v
1
2
95
93
N
H
N
O
3w
H2N
NH2
HN
NH
OH
HO
O
O
25
26
1u
1v
2d
2d
3x
3y
2
3
90
82
H2N
NH2
HN
NH
OH
HO
O
O
O
O
HN
O
O
N
H
N
H
N
H
H
N
N
OH
O
O
a Yields of isolated pure product after silica-gel column chromatography (20% Hexane/EtOAc).
b
Products isolated in a 95:5 ratio of regioisomers. The major product was shown.
The reaction was carried out under catalyst-free conditions. Products isolated in 50:50 ratio of regioisomers.
c
[M+]. Anal. calcd. for C14H16N2O: C, 73.66; H, 7.06; found:
C, 73.34; H, 6.98.
Table 3. Reuse of MgO.
Number of use
Yield (%)
Recovery of MgO
1
2
3
98
94
92
96% (3.8 × 10–3 g)
95% (3.6 × 10–3 g)
95% (3.4 × 10–3 g)
1-Phenoxy-3-(pyridin-2-ylmethylamino)propan-2-ol (3b)
Oily liquid. Rf = 0.38 (EtOAc/MeOH/Et3N, 90/7/3). H
1
NMR (CDCl3, ppm) δ: 8.43 (1H, m), 7.50 (1H, m), 7.03–
7.16 (4H, m), 6.71–6.84 (3H, m), 5.60 (2H, br s, –NH,
–OH), 3.78–4.05 (5H, m). 13C NMR (CDCl3) δ: 53.2, 59.0,
114.5, 115.6, 121.0, 129.3, 137.0, 148.9, 158.4. MS m/z:
244 [M+]. Anal. calcd. for C14H16N2O2: C, 68.83; H, 6.60;
found: C, 68.65; H, 6.43.
1-Phenyl-2- ((pyridin-2-yl)methylamino)ethanol (3a)
1
Oily liquid. Rf = 0.13 (EtOAc/MeOH/Et3N, 90/7/3). H
NMR (CDCl3, ppm) δ: 8.34 (1H, d, J = 4.9), 7.49 (1H, m),
7.02–7.21 (7H, m), 4.72 (1H, d, J = 3.4), 4.62 (2H, dd, J =
2.8, 2.8), 3.90 (1H, –NH), 3.82 (1H, –OH), 2.64–2.76
(2H, m). 13C NMR (CDCl3) δ: 54.1, 56.8, 72.1, 122.5,
125.9, 127.3, 128.2, 136.6, 137.1, 149.0, 159.4. MS m/z: 228
1-Chloro-3-(pyridin-2-ylmethylamino)propan-2-ol (3c)
Oily liquid. Rf = 0.52 (EtOAc/MeOH/Et3N, 90/7/3). H
1
NMR (CDCl3, ppm) δ: 9.07 (1H, d, J = 5.1), 7.7 (1H, d, J =
5.9), 7.27 (2H, m), 5.61 (2H, br s, –NH, –OH), 3.97
© 2007 NRC Canada

Hosseini-Sarvari
69
(2H, m), 3.54 (2H, s), 2.76–3.01 (3H, m). 13C NMR (CDCl3)
δ: 46.5, 54.2, 54.3, 122.7, 135.0, 148.6, 169.1. MS m/z: 200
[M+]. Anal. calcd. for C9H13ClN2O: C, 53.87; H, 6.53;
found: C, 53.66; H, 6.22.
2-(3-Bromophenylamino)cyclohexanol (3j)
Oily liquid. 1H NMR (CDCl3, ppm) δ: 6.93–6.99 (1H, m),
6.75–6.79 (2H, m), 6.53–6.58 (1H, m), 4.15 (2H, br s, NH,
OH), 3.42 (1H, m), 3.10 (1H, m), 2.05 (2H, m), 1.64–1.73
(2H, m), 1.01–1.31 (4H, m). 13C NMR (CDCl3) δ: 24.4,
24.6, 31.6, 33.1, 56.9, 73.9, 115.7, 117.8, 120.4, 129.8,
148.4. MS m/z: 270 [M+]. Anal. calcd. for C12H16BrNO: C,
53.35; H, 5.97; found: C, 53.01; H, 5.67.
2-(Pyridin-2-ylmethylamino)cyclohexanol (3d)
1
Solid; mp 87 °C (lit. 87–88 °C) (2d). H NMR (CDCl3,
ppm) δ: 8.55 (1H, d, J = 4.8), 7.76 (1H, t, J = 5.8), 7.40
(1H, d, J = 2.9), 7.26 (1H, m), 5.20 (2H, br s, –NH, –OH),
4.34 (1H, d, J = 14.5), 4.10 (1H, d, J = 14.5), 3.62 (1H, m),
2.57 (1H, m), 2.01–2.08 (2H, m), 1.67–1.74 (2H, m), 1.18–
1.43 (4H, m). 13C NMR (CDCl3) δ: 24.0, 24.6, 28.8, 33.7,
50.0, 63.3, 72.0, 122.9, 137.1, 149.2, 156.0. MS m/z: 206
[M+]. Anal. calcd. for C12H18N2O: C, 69.87; H, 8.80; found:
C, 69.76; H, 8.66.
2-(4-Bromophenylamino)cyclohexanol (3k)
1
Solid; mp 67 °C. H NMR (CDCl3, ppm) δ: 7.11 (2H, m),
6.45 (2H, m), 3.45 (2H, br s, NH, OH), 3.18–3.25 (1H, m),
2.93–2.99 (1H, m), 1.94 (2H, m), 1.58–1.67 (2H, m), 1.09–
1.25 (4H, m). 13C NMR (CDCl3) δ: 24.4, 24.8, 31.4, 33.4,
59.9, 74.3, 115.7, 116.7, 131.8, 147.0. MS m/z: 269 [M+].
Anal. calcd. for C12H16BrNO: C, 53.35; H, 5.97; found: C,
53.04; H, 5.86.
2-(Phenylamino)cyclohexanol (3e)
1
Solid; mp 58 °C (lit. 58–59 °C) (3c). H NMR (CDCl3,
ppm) δ: 7.13 (2H, t, J = 7.5), 6.65–6.89 (3H, m), 3.45 (2H,
br s, NH, OH), 3.30–3.39 (1H, m), 3.10–3.14 (1H, m), 2.05–
2.10 (2H, m), 1.66–1.76 (2H, m), 1.05–1.35 (4H, m). 13C
NMR (CDCl3) δ: 23.9, 24.2, 31.3, 33.2, 60.3, 74.2, 115.2,
121.9, 129.3, 147.2. MS m/z: 191 [M+]. Anal. calcd. for
C12H17NO: C, 75.35; H, 8.96; Found: C, 75.00; H, 8.56.
2-(3-Hydroxphenylamino)cyclohexanol (3l)
Oily liquid. H NMR (CDCl3, ppm) δ: 7.06 (1H, s), 6.18–
6.27 (3H, m), 4.68 (2H, br s, NH, OH), 3.28 (1H, m), 3.03
(1H, m), 1.99–2.02 (2H, m), 1.61 (2H, m), 1.18–1.26
(4H, m). MS m/z: 206 [M+]. Anal. calcd. for C12H18NO2: C,
69.87; H, 8.79; found: C, 69.60; H, 8.70.
1
2-(p-Toluidino)cyclohexanol (3f)
1-(4-(2-Hydroxycyclohexylamino)phenyl-ethenone (3m)
Solid; mp 79 °C. H NMR (CDCl3, ppm) δ: 7.76 (2H, d,
1
Oily liquid. H NMR (CDCl3, ppm) δ: 6.78 (2H, d, J =
1
2.27), 6.48 (2H, d, J = 2.50), 3.09–3.14 (1H, m), 3.98 (2H,
br s, NH, OH), 2.87–2.93 (1H, m), 3.89 (3H, s), 1.89
(2H, m), 1.56 (2H, m), 1.06–1.18 (4H, m). 13C NMR
(CDCl3) δ: 20.4, 24.5, 25.0, 31.5, 33.1, 60.5, 74.3, 115.3,
127.5, 129.3, 145.5. MS m/z: 205 [M+]. Anal. calcd. for
C13H19NO: C, 76.06; H, 9.33; found: C, 75.98; H, 9.02.
J = 2.07), 6.56 (2H, d, J = 3.10), 4.30 (2H, br s, NH, OH),
3.43 (1H, m), 3.25 (1H, m), 2.48 (3H, s), 2.12 (2H, m),
1.69–1.79 (2H, m), 1.18–1.34 (4H, m). 13C NMR (CDCl3) δ:
23.9, 24.2, 24.6, 31.4, 33.5, 58.9, 74.2, 112.1, 113.6, 130.6,
130.8, 152.3, 196.6. MS m/z: 233 [M+]. Anal. calcd. for
C14H19NO2: C, 72.07; H, 8.21; found: C, 71.89; H, 7.98.
2-(m-Toluidino)cyclohexanol (3g)
1
4-(2-Hydroxycyclohexylamino)benzoic acid (3n)
Solid; mp 167 °C. H NMR (CDCl3, ppm) δ: 7.85 (2H, d,
Oily liquid. H NMR (CDCl3, ppm) δ: 7.02 (1H, s), 6.39–
1
6.60 (3H, m), 3.46 (2H, br s, NH, OH), 3.23 (1H, m), 3.03
(1H, m), 2.21 (3H, s), 2.00 (2H, m), 1.61–1.69 (2H, m),
1.17–1.35(4H, m). 13C NMR (CDCl3) δ: 21.5, 23.7, 25.0,
31.0, 33.4, 59.9, 75.6, 111.5, 115.6, 118.5, 128.7, 139.0,
148.0. MS m/z: 205 [M+]. Anal. calcd. for C13H19NO: C,
76.06; H, 9.33; found: C, 76.00; H, 9.30.
J = 2.32), 6.62 (2H, d, J = 2.12), 4.94 (2H, br s, NH, OH),
3.23–3.43 (2H, m), 2.10 (2H, m), 1.69 (2H, m), 1.02–1.47
(4H, m). 13C NMR (CDCl3) δ: 24.2, 24.4, 30.3, 32.9, 74.2,
113.7, 118.3, 132.2, 151.5, 171.1. MS m/z: 235 [M+]. Anal.
calcd. for C13H17NO3: C, 66.36; H, 7.28; found: C, 66.02; H,
6.98.
2-(4-Methoxyphenylamino)cyclohexanol (3h)
1
2-(4-Nitrophenylamino)cyclohexanol (3o)
Solid; m.p. 53 °C. H NMR (CDCl3, ppm) δ: 7.01 (2H, d,
Solid; mp 143 °C. 1H NMR (CDCl3, ppm) δ: 7.21
(2H, m), 6.64 (2H, m), 3.54 (2H, br s, NH, OH), 3.28–3.35
(1H, m), 3.00–3.12 (1H, m), 2.02 (2H, m), 1.68–1.77
(2H, m), 1.10–1.35 (4H, m). 13C NMR (CDCl3) δ: 24.8,
24.3, 32.4, 33.8, 60.15, 75.3, 115.9, 116.1, 131.6, 147.9. MS
m/z: 236 [M+]. Anal. calcd. for C12H16N2O3: C, 61.00; H,
6.83; found: C, 61.04; H, 6.86.
J = 2.27), 6.84 (2H, d, J = 2.50), 3.29–3.21 (1H, m), 4.01
(2H, br s, NH, OH), 2.87–2.93 (1H, m), 3.91 (3H, s), 2.18
(2H, m), 1.86 (2H, m), 1.36–1.48 (4H, m). 13C NMR
(CDCl3) δ: 21.4, 25.5, 25.8, 32.5, 34.1, 61.5, 75.7, 115.8,
127.1, 129.9, 145.1. MS m/z: 221 [M+]. Anal. calcd. for
C13H19NO2: C, 70.56; H,8.65; found: C, 70.32; H, 8.62.
2-(2-Bromophenylamino)cyclohexanol (3i)
Oily liquid. 1H NMR (CDCl3, ppm) δ: 7.40–7.46 (1H, m),
7.16–7.18 (1H, m), 6.74–6.85 (1H, m), 6.56–6.60 (1H, m)
3.20 (2H, br s, NH, OH), 4.35 (1H, m), 3.38 (1H, m), 2.04–
2.10 (2H, m), 1.67–1.74 (2H, m), 1.13–1.43 (4H, m). 13C
NMR (CDCl3) δ: 24.0, 24.4, 31.5, 32.7, 59.7, 74.1, 112.9,
118.3, 128.3, 132.5, 144.9. MS m/z: 270 [M+]. Anal. calcd.
for C12H16BrNO: C, 53.35; H, 5.97; found: C, 53.01; H,
5.67.
2-(3-Nitrophenylamino)cyclohexanol (3p)
Solid; mp 157 °C. H NMR (CDCl3, ppm) δ: 7.48–7.54
1
(2H, m), 7.27 (1H, t, J = 8.04), 6.95 (1H, d, J = 5.04), 3.41
(2H, br s, NH, OH), 3.25 (1H, m), 3.20 (1H, m), 2.14
(2H, m), 1.73–1.82 (2H, m), 1.13–1.42 (4H, m). 13C NMR
(CDCl3) δ: 24.1, 24.7, 31.4, 33.5, 59.7, 74.5, 107.5, 112.5,
119.7, 129.8, 148.8. MS m/z: 236 [M+]. Anal. calcd. for
C12H16N2O3: C, 61.00; H, 6.83; found: C, 60.97; H, 6.561.
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Can. J. Chem. Vol. 86, 2008
2-(2-Trifluorophenylamino)cyclohexanol (3q)
2-(4-(4-(2-Hydroxycyclohexylamino)
Oily liquid. 1H NMR (CDCl3, ppm) δ: 7.16–7.35 (2H, m),
6.52–6.81 (2H, m) 4.27 (1H, m), 3.23–3.30 (1H, m), 3.19
(2H, br s, –NH, –OH), 1.92 (2H, m), 1.52 (2H, m), 1.07–
1.15 (4H, m). 13C NMR (CDCl3) δ: 24.2, 24.5, 33.4, 55.9,
59.5, 112.4, 113.0, 113.6, 114.6, 115.7, 116.5, 116.8, 117.0,
117.2, 126.2, 126.4, 126.5, 132.9, 144.9, 145.8. MS m/z: 259
[M+]. Anal. calcd. for C13H16F3NO: C, 60.22; H, 6.22;
found: C, 60.00; H, 6.02.
phenoxy)phenylamino)cyclohexanol (3x)
1
Oily liquid. H NMR (CDCl3, ppm) δ: 6.78 (4H, d, J =
8.77), 6.59 (4H, d, J = 8.85), 3.44 (4H, brs, NH, OH), 3.29
(2H, ddd, J= 9.20, 3.57, 9.77), 2.99 (2H, ddd, 8.95, 3.60,
8.97), 2.01–2.03 (4H, m), 1.68–1.80 (4H, m), 1.00–1.36
(8H, m). 13C NMR (CDCl3, ppm) δ: 24.3, 24.8, 32.4, 33.3,
60.8, 74.0, 115.0, 119.0, 143.4, 150.2. MS m/z: 396 [M+].
Anal. calcd. for C25H32N2O2: C, 72.70; H, 8.13; found: C,
72.63; H, 8.03.
2-(6-(2-Hydroxycyclohexylamino)pyridin-2-ylamino)
cyclohexanol (3r)
7-(2-Hydroxycyclohexyl)-5,6,7,8,9,10-hexahydro-2-H-
1,13,4,7,10-benzadioxatriazacyclopentadecine-3,11,
(4H,12H)-dione (3y)
Oily liquid. 1H NMR (DMSO, ppm) δ: 7.41 (2H, m), 6.97
(1H, t, J = 1.45), 5.50–5.70 (4H, m), 5.36 (4H, br s, NH,
OH), 2.30 (4H, m), 1.55 (4H, m), 104–1.27 (8H, m). 13C
NMR (DMSO) δ: 23.7, 24.2, 31.1, 34.1, 56.0, 73.3, 95.1,
138.4, 158.3. MS m/z: 305 [M+]. Anal. calcd. for
C17H27N3O2: C, 66.85; H, 8.91; found: C, 66.78; H, 8.56.
1
Oily liquid. H NMR (CDCl3, ppm) δ: 8.03 (1H, s, NH),
6.96–7.01 (2H, m), 6.85–6.91 (2H, m), 4.51 (4H, s), 3.49
(4H, t, J = 5.37), 3.36 (1H, m), 3.20 (1H, m), 2.94 (4H, t,
J = 5.35), 2.0 (2H, m), 1.69 (2H, m), 1.26 (4H, m). 13C
NMR (CDCl3) δ: 24.0, 24.8, 32.1, 32.7, 38.0, 47.3, 66.8,
73.2, 120.0, 122.0, 165.0, 168.1, 168.6. MS m/z: 391 [M+].
Anal. calcd. for C20H29N3O5: C, 61.36; H, 7.47; found: C,
61.23; H, 7.43.
2-(Diphenylamino)cyclohexanol (3s)
Oily liquid. 1H NMR (CDCl3, ppm) δ: 6.67–7.32
(10H, m), 4.13–4.54 (1H, m), 3.02–3.23 (1H, m), 3.01 (2H,
br s, –NH, –OH), 2.34 (2H, m), 1.84 (2H, m), 1.12–1.34
(4H, m). 13C NMR (CDCl3) δ: 24.4, 25.9, 32.1, 33.4, 60.2,
74.1, 119.2, 120.6, 126.2, 146.4. MS m/z: 267 [M+]. Anal.
calcd. for C18H21NO: C, 80.86; H, 7.92; found: C, 80.45; H,
7.79.
Acknowledgement
The support of this work by the Shiraz University Re-
search Council is gratefully acknowledged.
2-(Diisopropylamino)cyclohexanol (3t)
1
Oily liquid. H NMR (CDCl3, ppm) δ: 3.73 (1H, m), 3.60
References
(2H, m), 3.39 (1H, m), 3.37 (2H, br s, –NH, –OH), 1.14–
2.25 (20H, m). 13C NMR (CDCl3) δ: 19.3, 23.7, 23.8, 29.9,
32.9, 46.5, 67.5, 72.8. MS m/z: 199 [M+]. Anal. calcd. for
C12H25NO:, 72.31; H, 12.64; found: C, 72.01; H, 12.54.
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1
Oily liquid. H NMR (CDCl3, ppm) δ: 4.56 (2H, br s,
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3.61 (1H, m), 2.27 (2H, m), 2.08 (3H, s), 1.22–1.33 (6H, m).
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72.7, 87.0. MS m/z: 157 [M+]. Anal. calcd. for C9H19NO: C,
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Oily liquid. H NMR (CDCl3, ppm) δ: 3.72 (4H, t, J =
4.9), 3.37 (1H, m), 2.72 (2H, t, J = 5.4), 2.41 (2H, t, J =
4.0), 2.15 (1H, m), 1.83 (2H, m), 1.71 (2H, m), 1.08–1.27
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67.4, 68.3, 70.5. MS m/z: 185 [M+]. Anal. calcd. for
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1
2-(4-(4-(2-Hydroxycyclohexylamino)benzyl)phenyl
amino)cyclohexanol (3w)
1
Oily liquid. H NMR (CDCl3, ppm) δ: 6.80 (4H, d, J =
5.85), 6.43 (4H, d, J = 4.36), 3.90–3.98 (2H, m), 3.59
(2H, s), 3.44 (4H, br s, NH, OH), 2.88–3.15 (2H, m), 0.84–
1.87 (16H, m). 13C NMR (CDCl3) δ: 20.8, 24.2, 30.8, 31.3,
40.0, 60.3, 73.8, 114.2, 129.4, 146.0. MS m/z: 392 [M+].
Anal. calcd. for C25H32N2O2: C, 76.49; H, 8.22; found: C,
76.33; H, 8.12.
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Hosseini-Sarvari
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© 2007 NRC Canada