Comparative study of the regioselective synthesis of β-aminoalcohols under solventless conditions catalyzed by sulfated zirconia and SZ/MCM-41

Article abstract of DOI:10.3390/12112515

Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of β-aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel and SZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by XRD, SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both acid materials were useful as catalysts, even when they were recycled several times. The β-aminoalcohols were characterized by FT-IR, ¹H- and ¹³C-NMR and GC-MS.

Full text of DOI:10.3390/12112515

Molecules 2007, 12, 2515-2532
molecules
ISSN 1420-3049
2007 by MDPI
www.mdpi.org/molecules
©
Full Paper
Comparative Study of the Regioselective Synthesis of
β-Aminoalcohols under Solventless Conditions Catalyzed by
Sulfated Zirconia and SZ/MCM-41
1
,
1
1
Guillermo Negrón-Silva *, C. Xochitl Hernández-Reyes , Deyanira Angeles-Beltrán , Leticia
2
2
2
Lomas-Romero , Eduardo González-Zamora and Juan Méndez-Vivar
1
2
Departamento de Ciencias Básicas and Departamento de Química, UAM, Av. San Pablo No 180. C.
P. 02200, México D. F., México; E-mail addresses: C. X. Hernández: floronix@yahoo.com.mx; D.
Angeles-Beltrán: dab@correo.azc.uam.mx; L. Lomas-Romero: llr@xanum.uam.mx; E. González-
Zamora: egz@xanum.uam.mx; J. Méndez-Vivar: jmv@xanum.uam.mx
*
Author to whom correspondence should be addressed. e-mail: gns@correo.azc.uam.mx
Received: 29 September 2007; in revised form: 13 November 2007 / Accepted: 13 November 2007 /
Published: 15 November 2007
Abstract: Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of β-
aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel and
SZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by XRD,
SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both acid
materials were useful as catalysts, even when they were recycled several times. The β-
1
13
aminoalcohols were characterized by FT-IR, H- and C-NMR and GC-MS.
Keywords: Sulfated zirconia, SZ/MCM-41, β-aminoalcohols, oxirane, solventless
reactions.
Introduction
Since the discovery that sulfated zirconia (SZ) has a high catalytic activity in organic reactions
under mild conditions, it has been the subject of numerous studies on its synthesis, characterization
and applications [1]. The strength, nature and structure of sulfated zirconia have been studied for a
long time, starting with Arata and Hino [2], who reported that zirconia, upon proper treatment with

Molecules 2007, 12
2516
4
sulfuric acid or ammonium sulfate, exhibits 10 times stronger acidity than that of 100% sulfuric acid.
It is known that sulfated zirconia belongs to the solid superacids family and that the stability, structure
and acidity type are directly related to the preparation and sulfation processes. [3] Some authors
mention that the strong acidity of sulfated zirconia is due to a combination of Lewis and Brønsted acid
sites. Sulfated species with covalent bonds as S=O on the surface of SZ are needed for acidity. Other
authors have suggested that water absorption in SZ generates both types of acid sites. In this context,
some acid models have been proposed to explain the acid features of SZ [4]. Sulfated zirconia acidity
has proven to be useful in organic transformations such as n-butane isomerization, [5] Friedel-Craft
acylations, [6,7] fine chemical organic transformations, [8] alcohol dehydrations, [9] and
polymerizations [10].
Typically, the surface area of solid catalysts is an important factor that directly influences their
2
-1
catalytic performance. Sulfated zirconia exhibits an area of close to 100 m g . New reports have
shown that sulfated zirconia supported on MCM-41 shows an increased surface area, generating a
good catalyst for cumene cracking, [11] isomerization of n-butane [12] or n-pentane, [13] and
veratrole acylation [14].
β-Aminoalcohols are present in several biologically active natural and synthetic products;
unnatural amino acids, chiral auxiliaries, as chiral catalysts in asymmetric synthesis [15], and their
existence is fundamental because of their biological and chemical reactivity. One of the most common
synthesis methods for β-aminoalcohols is the opening of oxiranes with heteronucleophiles with
nitrogen or oxygen. The classical approach for the synthesis of β-aminoalcohols, involving
nucleophilic opening of epoxides by amines requires heat treatment and requires an excess of amine.
Several catalysts have been utilized in these reactions: montmorillonite [16], Ti(o-i-Pr)
18] basic metal amides, [19] SmCl [20], metal triflates such as Sn(OTf) , Cu(OTf)
Yb(OTf) [21], ammonium decatungstocerate (IV) [22], RuCl [23], zirconium (IV) chloride [24],
cyclodextrins [25] and also CeCl [26], silica-gel [27], alumina [28], ionic liquids [29], water [30],
LiClO ·3H O [31], and heteropolyacids, for example H 40 [32, 33] and K O [34].
4
[17], SmI
2
,
[
3
2
2
, LiOTf and
3
3
3
4
2
3
PW12
O
5 2
CoW12O40·3H
We have successfully used sulfated zirconia for Biginelli condensation reactions, [35] for the Paal
Knorr reaction in the synthesis of tetrahydroindolone derivatives [36] and for the acylal protection and
deprotection reactions [37]. In this paper we have synthesized, characterized and evaluated sulfated
zirconia and SZ/MCM-41 in the oxirane opening with amines to obtain β-aminoalcohols under mild,
solventless conditions.
Results and Discussion
Figure 1 corresponds to the sulfated zirconia (SZ) tetragonal phase, in correspondence with ICSD
collection code: 066787, given by reflections in 2θ = 30.18° (relative intensity is 100) as well as peaks
at 34.616°, 35.283°, 50.214°, 50.770°, 59.291°, 60.187° and 63.724° [38].

Molecules 2007, 12
2517
1
1
1
4 0 0
2 0 0
0 0 0
8
6
4
2
0 0
0 0
0 0
0 0
0
2
0
3 0
4 0
5 0
6 0
7 0
8 0
2
th e ta
Figure 1. XRD of sulfated zirconia.
8
0
0
0
0
0
0
0
0
0
7
6
5
4
3
2
1
Adsorption
Desorption
0
0.1
0.2
0.3
0.4
0.5
0.6
P/Po)
0.7
0.8
0.9
1
(
Figure 2. Nitrogen adsorption-desorption plot of SZ.
Figure 2 shows the adsorption-desorption plot that gave an isotherm plot type IV in the BET
Brunauer, Emett and Teller) classification; the isotherm hysteresis loop indicated a uniform pore size
(
-1
distribution [39]. The surface area calculated by BET was 86.15 m²g , the pore size measured 41.623
-1
Å and the pore volume value was 0.089 cm³g . The UV-vis spectrum of sulfated zirconia displays a
broad signal centered in 210 nm that is assigned to the tetragonal phase of sulfated zirconia [40]; a
similar spectrum is observed for SZ/MCM-41 (Figure 3).

Molecules 2007, 12
2518
1
1
0
0
0
0
0
.2
.0
.8
.6
.4
.2
.0
SZ/MCM-41
SZ
-
0.2
2
00
300
400
500
600
700
800
Wavenumber
Figure 3. UV-vis spectra of SZ and SZ/MCM-41.
1
200
000
1200
1
000
8
6
4
2
00
00
00
00
0
1
SZ/MCM-41, 4 days
SZ//MCM-41, 6 days
2
3
4
5
6
7
8
9
10
8
6
4
2
00
00
00
00
0
2 theta
2
0
40
theta
60
80
2
Figure 4. XRD of SZ/MCM-41 dried 4 and 6 days.
The powder XRD pattern of SZ/MCM-41 shows an intense diffraction peak due to the (100)
reflection of MCM-41 at low 2θ ranges, in addition to (110) and (200) in 2θ = 4.5° and 2θ = 5°
respectively, which are characteristic of mesoporous materials (Figure 4). When sulfated zirconia is
supported in siliceous MCM-41, we observed that the structure of the mesoporous molecular sieve is
maintained after loading the SZ, the (100) reflection intensity can be observed, as well as the (110)
reflection. We also noted that sulfated zirconia was formed on the support in two phases; monoclinic
(
2θ =28°) and tetragonal (2θ = 30°, 35°, 50°, 60°). This is ascribed to the transformation from the
metaestable tetragonal phase to the monoclinic phase that is retarded in the presence of promoters.
However, an increase of the monoclinic phase was observed when the drying time decreased from 6 to
-1
4
days. The BET surface calculated for SZ/MCM-41 dried for 6 days was 314.92 m²g .

Molecules 2007, 12
2519
−
1
The IR spectra of the sulfated zirconia indicated that pyridine adsorbed in the 1350–1600 cm
−
1
region, as shown in Figure 5, where two strong bands near 1490 and 1450 cm and a weak band at
−
1
1
540 cm can be observed when desorption temperature was 50°C. When the temperature was
increased, the bands became weaker. The IR pyridine desorption spectra of SZ/MCM-41 showed
−
1
−1
broad bands at 1490 and 1450 cm and a slight and broad band at 1540 cm . In general, the band at
−
1
−1
1
445 cm is assigned to the adsorption of pyridine on Lewis acidic sites, and the band at 1545 cm is
associated to the adsorption on Brønsted acidic sites [11].
4.0
3.8
3.6
3.4
3.2
3.0
2.8
2.6
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
1700
1650
1600
1550
1500
1450
Wav enumbers (cm-1)
Figure 5. IR spectra of desorption of pyridine from SZ.
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-
0.5
1700
1650
1600
1550
1500
1450
Wavenumbers (cm-1)
Figure 6. IR spectra of desorption of pyridine from SZ/MCM-41.
These results indicate that the acidic sites over sulfated zirconia and SZ/MCM-41correspond
mainly to Lewis species. The calculated amounts of pyridine adsorbed on both types of acid sites at
different desorption temperatures are reported in Table 1.

Molecules 2007, 12
2520
Table 1. Acidity measurement results for SZ and SZ/MCM-41.
-1
-1
Temperatur Sulfated Zirconia (µmol py g )
SZ/MCM-41 (µmol py g )
e (°C)
Brønsted
Lewis
179
74
Total
280
143
85
Brønsted
Lewis
224
71
Total
242
101
35
5
0
101
69
18
30
18
5
1
2
3
00
00
00
33
52
17
14
27
41
5
10
The SEM-EDS technique was used to observe and quantify SZ dispersion on MCM-41. Figure 7
shows thin layers of SZ crystallized and dispersed on the support. The semi-quantitative analysis of the
sample performed by EDS and the corresponding emission spectra of SZ/MCM-41 are shown in
Figure 8.
Figure 7. SEM image of SZ/MCM-41.
Element
Wt %
40.94
31.38
2.32
O
Si
S
Zr
25.36
100
Total
Figure 8. Composition of SZ/MCM-41.

Molecules 2007, 12
2521
The results of the experiments related to Scheme 1 are presented and compared in the Table 2.
Scheme 1. Aminolysis of oxiranes.
H
N
OH
H
N
OH
O
+
R NH2
1
SZ or SZ/MCM-41
60°C
+
2
a, R =Ph
1
R1
R
R1
R
solventless
2
b, R =PhCH2
1
1
2
3
R
4
Recycling tests were performed for SZ and SZ/MCM-41. Once the catalysts were used, recovered,
and reactivated at 550°C for 1 h, they were utilized in the reaction again. Entry 15 (2, 3-Epoxy-3-
phenoxy propane) and benzylamine were employed as reagents. When the recycled catalysts were
tested no significant changes in yield were observed, neither with SZ nor with SZ/MCM-41. XRD
analysis was performed in order to notice that an increase of the monoclinic phase (2θ = 28°), after the
SZ sample was reactivated three times (Figure 9). SZ/MCM-41 is predominantly monoclinic after
three recycling periods as shown in figure 10.
Figure 9. XRD patterns of reactivated SZ.
cycle 3
cycle 2
cycle 1
Position [°2 theta]
Figure 10. XRD patterns of reactivated SZ/MCM-41.

Molecules 2007, 12
2522
Table 2. SZ and SZ/MCM-41 as catalysts.
Entry
1
1
2
Time
h)
3/4 Yield (%)
Cat. = SZ
3/4 Yield (%)
(
Cat. = SZ/MCM-41
2a
2a
0.5
5
74/0
23/0
63/0
O
Cl
[
41,42]*
2
61/20
O
[
43]
*
3
2b
2a
6
5
82/0
35/0
55/0
O
O
4
63/13
5
2b
2a
5
5
81/0
97/0
54/0
84/0
O
[
44,45(b,c)]
6
O
7
2b
2a
5
5
71/0
93/0
14/0
99/0
O
[
45]
8
O
9
2b
2a
5
83/0
0/96
45/0
5/91
O
[
46](d),
1
4
0
O
5(c), 42]*
1
6
[
41,47]
1
1
2b
2a
53/31
81/0
55/25
83/0
O
[
41]
1
2
5
5
O
O
1
3
2b
87/0
81/0
[
41, 46]
1
4
O
2a
2b
2a
2b
0.5
0.5
1
86/0
87/0
76/0
77/0
81/0
52/0
57/0
51/0
O
[
41]
1
5
O
O
O
O
1
6
7
1
O
1
O
O
O
O
O
1
9
8
2a
2b
1
1
76/0
85/0
59/0
82/0
O
[48]
1
O
Yields of the isolated possible products 3 or 4 shown in Scheme 1; the regioselectivity was evaluated by
GC-MS; * the structures of the minor products in entries 2, 4 and 10 were determined by CI mode GC-MS.

Molecules 2007, 12
2523
Sulfated zirconia and SZ/MCM-41 were used as catalysts in the β-aminoalcohols synthesis in
agreement with scheme 1. The specific area increase of the SZ/MCM-41 compared to that of the SZ
does not reflect in a better yield in the epoxide aminolysis reactions, which may be attributed to an
overall greater acid strength of the former; at the same time a better regioselectivity was noticed in
entries 2 and 4. Thus, the surface properties seem to play a secondary role in catalytic activity in
comparison to other factors, such as acidity [49].
Conclusions
In summary, we have described a simple procedure for the synthesis of β-aminoalcohols using SZ
and SZ/MCM-41. The catalysts were recovered and reused without any appreciable loss of their
activity.
Experimental
General
Powder X-ray diffraction (XRD) patterns were obtained with an X´Pert instrument using Cu Kα
radiation. Nitrogen adsorption/desorption isotherms were plotted at -196 °C on a Micromeritics ASAP
2
020 equipment. IR spectra were recorded on a Perkin-Elmer FT-IR system/GX spectrometer. SEM-
EDS analysis was performed using a SEM XL30 ESEM microscopy. The reaction products were
analyzed by means of a Hewlett Packard 6890/5973 GC/MS system equipped with an HP-5 column,
with the oven program 70-200°C (10°C/min) for 4 min then, 200-280°C (10°C/min) for 3 min, inj. 250
ºC, det. 280 °C; the detector was set in the Chemical Ionization mode using methane as reactive gas.
1
13
H-NMR and C-NMR spectra were measured at 500 and 125 MHz, respectively, on a Bruker Avance
DMX-500 spectrometer using CDCl as solvent and tetramethylsilane as internal standard. Pyridine
3
adsorption infrared spectra test was carried out in a Nicolet 750 spectrometer.
Sulfated zirconia synthesis
Zirconium n-propoxide (20 mL, 70 % n-propanol) were mixed with 2-propanol (30 mL) and stirred
with a magnetic bar. Then, distilled water (3.2 mL) was mixed with sulfuric acid (1 mL, 98%) and this
solution was added dropwise in order to carry out the hydrolysis and gelation of the zirconium n-
propoxide. The solid was dried at 80°C until complete alcohol evaporation and then calcined in air at
600°C for 6 h.
MCM-41 synthesis
Pure siliceous MCM-41 was prepared from a gel described elsewhere [50]. Mixing
cetyltrimetylammonium bromide (7.289 g) with deionized water (200 mL) at 30°C gave a clear
solution, and then triethylamine (3.34 mL) was added. After stirring for a few minutes, TMAOH (18
mL, 10 wt %) and finally TEOS (22.35 mL) were added. The resulting gel, with molar composition 1
TEOS : 0.2 CTMABr : 0.6 EA : 0.2 TMAOH : 150 H O, was placed in glass bottles and sonicated for
2

Molecules 2007, 12
2524
4
h. The precipitated solid was recovered by filtration and washed with deionized water, dried at 60 °C
overnight and calcinated at 540 °C for 6 h under air flow.
Synthesis of sulfated zirconia supported on MCM-41
Preparation of the sulfated zirconia supported in MCM-41 (SZ/MCM-41) has been already
described [13]. In a first procedure, siliceous MCM-41 (300 g) were mixed with zirconium sulfate (15
mL) in methanol (1 wt %), the heterogeneous mixture was stirred 14 h. Then, the impregnated solid
was dried for 6 days at 50 °C and finally calcinaed at 660 °C for 3 h in air flow.
β-Aminoalcohol synthesis
In a general procedure oxirane 1 (1 mmol) and nucleophile (aniline or benzylamine, 2, 1.1 mmol)
were placed in a vial equipped with a magnetic stirrer and plastic cap. The mixture was heated at 60 °C
in the presence of sulfated zirconia or sulfated zirconia on MCM-41 (50 mg) without solvent (Scheme
1
). After the reaction, the mixture was left at room temperature, the catalyst was recovered by filtration
and the organic product was dried in a rotavapor under reduced pressure and the products were
1
purified by silica gel or alumina column chromatography. All products were identified by FR-IR, H-
1
3
NMR, C-NMR and by comparison with the previously described physical and spectroscopic data of
the β-aminoalcohols.
1
-Chloro-3-(phenylamino)propan-2-ol (Entry 1). GC-MSD for C
9
H
12NOCl (mw: 185.66 g/mol):
+
+
+
+
-1
[M+1] = 186, [M+29] = 214, [M+41] = 226, [M-17] = 168; IR (cm ): 3396, 1602, 1499, 1419,
1
1
314, 1261, 1161, 1156, 1088, 1075, 958, 851, 823, 748, 692; H-NMR: δ (ppm) 7.16-7.21 (m, 2H,
Ar-H), 6.75 (tt, 1H, J
H, -CH-OH), 3.63 (dd, 1H, J
Cl), 3.46 (bs, 2H, -OH, -NH), 3.33 (dd, 1H, J = 4.3, J = 13.3 Hz, -NH-CH-CH-OH), 3.17 (dd, 1H, J =
1
= 1.0, J
2
= 7.3 Hz, Ar-H), 6.65 (dd, 2H, J
1
= 1.0, J
2
= 8.6 Hz, Ar-H), 4.01-4.06 (m,
1
1
= 4.5, J = 11.3 Hz, -CH-Cl), 3.58 (dd, 1H, J
2
1
= 6.0, J = 11.3 Hz , -CH-
2
1
2
1
1
3
7
.4, J
2
= 13.3 Hz, -NH-CH-CH-OH); C-NMR: δ (ppm) 147.42, 129.32, 118.36, 113.39, 69.65, 47.52,
4
7.15.
1
-(Phenylamino)hexan-2-ol (Entry 2). m.p.: 51-52 °C; GC-MSD for C12H12NO (mw: 193.29 g/mol):
+
+
+
+
-1
[M+1] = 194, [M+29] = 222, [M+41] = 234, [M-17] = 176, IR (cm ): 3273, 2969, 2929, 2831,
1
1
7
1
2
2
602, 1499, 1460, 1436, 1380, 1309, 1251, 1222, 1139, 1084, 1009, 984, 886, 844; H-NMR: δ (ppm)
.16-7.20 (m, 2H, Ar-H), 6.72 (tt, 1H, J
H, -OH or NH), 3.80-3.85 (m, 1H, -CH-OH), 3.26 (dd, 1H, J
.99 (dd, 1H, J = 8.6, J = 12.8 Hz -NH-CH-CH-OH), 1.98 (bs, 1H, -OH or NH), 1.49-1.56 (m,
H, -CH -CH-OH), 1.31-1.48 (m, 4H, - CH -CH -CH ), 0.92 (t, 3H, J= 7.3 Hz, -CH -CH );
C-NMR: δ (ppm) 148.30, 129.29, 117.87, 113.26, 70.41, 50.33, 34.82, 27.80, 22.74, 14.04.
1
= 1.0, J
2
= 7.3 Hz, Ar-H), 6.63-6.66 (m, 2H, Ar-H), 3.94 (bs,
1
= 3.2, J = 12.8 Hz -NH-CH-CH-OH),
2
1
2
2
2
2
3
2
3
1
3
+
1
-(Benzylamino)hexan-2-ol (Entry 3). GC-MSD for C13
H
21NO (mw: 207.32 g/mol): [M+1] = 208,
+
+
+
-1
1
[
M+29] = 236 [M+41] = 248, [M-17] = 190; IR (cm ): 2927, 1635, 1453, 1026, 735, 696; H-NMR:
δ (ppm) 7.24-7.27 (m, 2H, Ar-H), 7.30-7.35 (m, 3H, Ar-H), 3.83 (d, 1H, J= 13.2 Hz, -NH-CH-Ar),
.78 (d, 1H, J= 13.2 Hz -NH-CH-Ar), 3.60-3.67 (m, 1H, -CH-OH), 2.75 (dd, 1H, J = 3.0, J = 12.0 Hz
3
1
2

Molecules 2007, 12
2525
-
NH-CH-CH-OH), 2.47 (dd, 1H, J = 9.4, J = 12.0 Hz -NH-CH-CH-OH), 2.36 (bs, 2H, -OH, NH),
1
2
1
3
1
2 3 2 3
.25-1.46 (m, 6H, -CH -CH ), 0.89 (t, 3H, J= 7.2 Hz, -CH -CH ); C-NMR: δ (ppm) 139.79, 128.49,
1
28.13, 69.53, 54.72, 53.59, 34.73, 27.80, 22.77, 14.01.
1
-(Phenylamino)hex-5-en-2-ol (Entry 4). m.p.: 32-33 °C; GC-MSD for C H NO (mw: 191.27 g/mol):
12 17
+
+
+
-1
[M+1] = 192, [M+29] = 220, [M+41] = 232. IR (cm ): 3282, 2936, 2933, 2912, 2833, 1640, 1603,
1
1
7
1
496, 1463, 1434, 1414, 1300, 1250, 1221, 1182, 1108, 1072, 1022, 997, 912; H-NMR: δ (ppm) 7.15-
1 2
.20 (m, 2H, Ar-H), 6.73 (tt, 1H, , J = 1.0, J = 7.3 Hz, Ar-H), 6.63-6.66 (m, 2H, Ar-H), 5.81-5.89 (m,
H, -CH=CH ), 5.07 (ddd, 1H, J = 1.6, J = 3.5, J = 17.1 Hz, -CH -CH=CH), 4.98-5.01 (m, 1H, -CH -
2
1
2
3
2
2
CH=CH), 3.98 (bs, 1H, -OH or NH), 3.83-3.88 (m, 1H, -CH-OH), 3.26 (dd, 1H, J
1
= 3.3, J
2
= 12.9 Hz, -
NH-CH-CH-OH), 3.01 (dd, 1H, J = 8.5, J = 12.9 Hz, -NH-CH-CH-OH), 2.14-2.30 (m, 2H, -CH -
1
2
2
CH=CH
2
), 2.10 (bs, 1H, -OH or -NH), 1.63 (ddd, 2H, J
1
= 6.4, J
2
= 7.7, J
3
= 7.7 Hz, -CH
2
-CH
2
-CH-
1
3
OH); C-NMR: δ (ppm) 148.20, 138.12, 129.27, 117.92, 115.14, 113.28, 69.82, 50.22, 34.05, 29.92.
+
1
-(Benzylamino)hex-5-en-2-ol (Entry 5). GC-MSD for C13
H
19NO (mw: 205.3 g/mol): [M+1] = 206,
+
+
+
-1
[
M+29] = 234, [M+41] = 246, [M-17] = 188. IR (cm ): 2918, 2836, 1700, 1638, 1444, 1134, 1043,
1
9
5
1
88, 906, 852, 727, 693; H-NMR: δ (ppm) 7.29-7.35 (m, 4H, Ar-H), 7.25-7.28 (m, 1H, Ar-H), 5.78-
.86 (m, 1H, -CH=CH
H, J= 13.2 Hz -NH-CH-Ar), 3.63-3.68 (m, 1H, -CH-OH), 2.75 (dd, 1H, J
= 9.4, J = 12.0 Hz, -NH-CH-CH-OH), 2.38 (bs, 2H, -OH, -NH), 2.06-
2 2
), 1.43-1.57 (m, 2H, -CH -CH -CH-OH); C-NMR: δ (ppm) 139.73,
2
), 4.94-5.05 (m, 2H, -CH=CH
2
), 3.83 (d, 1H, J= 13.2 Hz, -NH-CH-Ar), 3.77 (d,
1
= 3.0, J = 12.0 Hz, -NH-
2
CH-CH-OH), 2.48 (dd, 1H, J
1
2
1
3
2
1
.26 (m, 2H, -CH
2
-CH=CH
2
38.39, 128.47, 128.11, 127.16, 114.74, 68.89, 54.55, 53.54, 34.07, 29.92.
2
-(Phenylamino)cyclopentanol (Entry 6). m.p.: 56-57 °C; GC-MSD for C11H15NO (mw: 177.25
+
+
+
+
-1
g/mol): [M+1] = 178, [M+29] = 206, [M+41] = 218, [M-17] = 160; IR (cm ): 3397, 2957, 1599,
1
1
506, 1482, 1436, 1316, 1259, 1182, 1154, 1112, 1033, 973, 752, 694; H-NMR: δ (ppm) 7.20-7.24
(
m, 2H, Ar-H), 6.69-6.77 (m, 3H, Ar-H), 4.06-4.09 (m, 1H, -CH-OH), 3.62-3.65 (m, 1H, NH-CH),
.23 (bs, 2H, -OH, -NH), 2.27-2.33 (m, 1H, CH -CH-OH), 2.01 (ddd, 1H, J = 1.9, J = 6.5, J = 13.1
Hz, CH -CH-OH), 1.73-1.90 (m, 2H, CH -CH-NH), 1.63-1.70 (m, 1H, CH -CH), 1.39-1.46 (m, 1H,
CH -CH); C-NMR: δ (ppm) 147.71, 129.24, 117.49, 113.31, 78.18, 62.06, 32.82, 31.15, 20.98.
3
2
1
2
3
2
2
2
1
3
2
2
-(Benzylamino)cyclopentanol (Entry 7). m.p.: 42-42 °C; GC-MSD for C12H17NO (mw: 191.28
+
+
+
+
-1
g/mol): [M+1] = 192, [M+29] = 220, [M+41] = 232, [M-17] = 174. IR (cm ): 2941, 1452, 1062,
1
7
J
2
2
34, 696; H-NMR: δ (ppm) 7.30-7.32 (m, 4H, Ar-H), 7.22-7.27 (m, 1H, Ar-H), 3.89 (dd, 1H, J
1
= 6.4,
2
= 12.6 Hz, -CH-OH), 3.83 (d, 1H, J= 13.0 Hz, -NH-CH-Ar), 3.74 (d, 1H, J= 13.0 Hz, -NH-CH-Ar),
.88 (ddd, 1H, J = 5.8, J = 7.4, J = 7.5 Hz, HO-CH-CH-NH-), 2.34 (bs, 2H, -OH, -NH), 1.92-2.05 (m,
H, CH -CH-OH), 1.61-1.74 (m, 2H, CH -CH-NH), 1.48-1.55 (m, 1H, CH -CH), 1.30-1.38 (m, 1H,
-CH); C-NMR: δ (ppm) 139.94, 128.25, 128.25, 128.46, 127.09, 66.29, 52.53, 32.63, 30.12,
1
2
3
2
2
2
1
3
CH
2
2
0.39.
2
-(Phenylamino)cyclohexanol (Entry 8). m.p.: 52-53 °C; GC-MSD for C HN O (mw: 191.28 g/mol):
1
-1
2
17
+
+
+
+
[M+1] = 192, [M+29] = 220, [M+41] = 232, [M-17] = 174; IR (cm ): 3395, 2939, 2923, 2856,
1
599, 1513, 1497, 1450, 1436, 1321, 1306, 1259, 1241, 1182, 1152, 1101, 1055, 1048, 1037, 992, 932,

Molecules 2007, 12
2526
1
8
6
64, 849, 740, 688; H-NMR: δ (ppm) 7.17 (t, 2H, J= 7.4 Hz, Ar-H), 6.73 (t, 1H, J= 7.3 Hz, Ar-H),
.69 (dd, 2H, J = 0.9, J = 8.5 Hz, Ar-H), 3.32 (ddd, 1H, J = 4.3, J = 9.4, J = 10.2 Hz, -CH-OH), 3.11
1
2
1
2
3
(
ddd, 1H, J = 4.0, J = 9.3, J = 11.3 Hz, -CH-NH), 3.07 (bs, 2H, -OH, -NH), 2.08-2.11 (m, 2H, CH -
1
2
3
2
1
3
CH-OH), 1.65-1.69 (m, 1H, CH
2
-CH-NH), 1.23-1.41 (m, 3H), 0.97-1.05 (m, 1H); C-NMR:
δ (ppm) 147.75, 129.23, 118.18, 114.24, 74.35, 33.08, 31.50, 24.90, 24.20.
2
-(Benzylamino)cyclohexanol (Entry 9). m.p.: 64-65 °C; GC-MSD for C H NO (mw: 205.31 g/mol):
1
3
-1
19
+
+
+
+
[M+1] = 206, [M+29] = 234, [M+41] = 246, [M-17] = 188. IR (cm ): 3294, 3060, 2925, 2852,
1
8
1
2
1
603, 1499, 1449, 1429, 1351, 1339, 1224, 1198, 1153, 1099, 1076, 1060, 1029, 972, 920, 893, 880,
1
45, 830, 747; H-NMR: δ (ppm) 7.28-7.33 (m, 4H, Ar-H), 7.21-7.25 (m, 1H, Ar-H), 3.93 (d, 1H, J=
2.9 Hz, -NH-CH-Ar), 3.67 (d, 1H, J= 12.9 Hz, -NH-CH-Ar), 3.18-3.23 (m, 1H, -CH-OH), 2.83 (bs,
1 2 3 2
H, -OH, -NH), 2.30 (ddd, 1H, J = 2.3, J = 7.4, J = 9.3 Hz, HO-CH-CH-NH-CH -Ar), 2.10-2.15 (m,
H), 1.93-2.02 (m, 1H), 1.64-1.74 (m, 2H), 1.14-1.29 (m, 3H), 0.96-1.04 (m, 1H);
1
3
C-NMR: δ (ppm) 140.05, 128.36, 128.08, 126.95, 73.45, 62.95, 50.62, 33.37, 30.20, 24.92, 24.25.
+
2
2
1
4
-Phenyl-2-(phenylamino)ethanol (Entry 10). GC-MSD for C H NO (mw: 213.28 g/mol): [M+1] =
1
2
15
+
+
+
+
+
-1
14, [M+29] = 242, [M+41] = 254, [M-17] = [M-17] = 196, [M-31] = 182; IR (cm ): 3388, 1600,
1
503, 1452, 1429, 1352, 1314, 1266, 1180, 1154, 1065, 1025, 993; H-NMR: δ (ppm) 7.31-7.37 (m,
H, Ar-H), 7.26 (tt, 1H, J
1
= 1.6, J
2
= 7.1 Hz, Ar-H), 7.07-7.11 (m, 2H, Ar-H), 6.68 (tt, 1H, , J
= 4.2, J = 7.0 Hz, -CH-NH), 4.47 (bs, 1H,
= 11.1 Hz, CH-CH-OH), 3.75 (dd, 1H, J = 7.0, J = 11.1 Hz,
1
= 1.0,
J
2
= 7.3 Hz, Ar-H), 6.55-6.58 (m, 2H, Ar-H), 4.50 (dd, 1H, J
1
2
-OH or -NH), 3.93 (dd, 1H, J
1
= 4.2, J
2
1
2
1
3
CH-CH-OH), 1.74 (bs, 1H, -OH or -NH); C-NMR: δ (ppm) 147.20, 140.09, 129.17, 128.83, 127.61,
1
26.72, 117.87, 113.84, 67.36, 59.85.
2
-(Benzylamino)-2-phenylethanol (Entry 11). m.p.: 97-99 °C; GC-MSD for C15
H
17NO (mw: 227.31
+
+
+
+
+
-1
g/mol): [M+1] = 228, [M+29] = 256 [M+41] = 268, [M-17] = 210, [M-31] = 196; IR (cm ): 3058,
1
3
025, 1599, 1494, 1452, 1351, 1196, 1116, 1067, 1047, 1027, 911, 850; H-NMR: δ (ppm) 7.35-7.38
(
m, 2H, Ar-H), 7.27-7.33 (m, 7H, Ar-H), 7.23-7.26 (m, 1H, Ar-H), 3.81 (dd, 1H, J
1
= 4.4, J
2
= 8.7 Hz,
Ar-CH-NH), 3.76 (d, 1H, J= 13.0 Hz, Ar-CH-NH), 3.70 (dd, 1H, J
1
= 4.5, J
2
= 10.8 Hz, CH-CH-OH),
3
.60 (d, 1H, J= 13.0 Hz, Ar-CH-NH), 3.55 (dd, 1H, J = 8.7, J = 10.8 Hz, CH-CH-OH), 2.15 (bs, 2H, -
1 2
1
3
OH and -NH); C-NMR: δ (ppm) 140.42, 139.99, 128.70, 128.43, 128.21, 127.69, 127.27, 127.08,
6
6.74, 63.75, 51.18.
+
2
2
1
7
1
-(Benzylamino)-1-phenylethanol (Entry 11). GC-MSD for C15H17NO (mw: 227.31 g/mol): [M+1] =
+
+
+
-1
28, [M+29] = 256 [M+41] = 268, [M-17] = 210; IR (cm ): 3062, 2924, 2835, 1600, 1490, 1453,
1
433, 1346, 1334, 1207, 1182, 1099, 1064, 1037, 1024, 978, 917, 875, 853; H-NMR: δ (ppm) 7.29-
.37 (m, 8H, Ar-H), 7.24-7.28 (m, 2H, Ar-H), 4.73 (dd, 1H, J
H, J= 13.3 Hz, Ar-CH-NH), 3.81 (d, 1H, J= 13.3 Hz, Ar-CH-NH), 2.94 (dd, 1H, J
= 8.9, J = 12.2 Hz, CH-CH-Ar), 2.24 (bs, 2H, -OH and -NH); C-NMR:
δ (ppm) 142.38, 128.49, 128.37, 128.10, 127.52, 127.18, 125.81, 71.76, 56.49, 53.50.
1
= 3.6, J
2
= 8.9 Hz, -CH-OH), 3.86 (d,
1
= 3.6, J = 12.2 Hz,
2
1
3
CH-CH-Ar), 2.75 (dd, 1H, J
1
2
1
-Phenyl-3-(phenylamino)propan-2-ol (Entry 12). m.p.: 63-64 °C; GC-MSD for C15H17NO (mw:
+
+
+
+
-1
2
27.31 g/mol): [M+1] = 228, [M+29] = 256, [M+41] = 268, [M-17] = 210; IR (cm ): 3342, 2927,

Molecules 2007, 12
2527
1
600, 1559, 1557, 1494, 1454, 1433, 1411, 1314, 1272, 1249, 1179, 1079, 1063, 1027, 830, 741, 687;
1
H-NMR: δ (ppm) 7.30-7.35 (m, 2H, Ar-H), 7.23-7.28 (m, 4H, -NH, Ar-H), 7.15-7.19 (m, 2H, Ar-H),
.71-6.75 (m, 1H, Ar-H), 6.61-6.64 (m, 2H, Ar-H), 4.00-4.10 (m, 1H, -CH-OH), 3.30 (dd, 1H, J = 3.4,
6
1
J
J
2
1
= 12.9 Hz, -NH-CH-CH-OH), 3.08 (dd, 1H, J
1
= 8.1, J
2
= 12.9 Hz, -NH-CH-CH-OH), 2.88 (dd, 1H,
= 13.6 Hz, Ar-CH-CH-OH), 2.24 (bs,
= 5.2, J = 13.6 Hz, Ar-CH-CH-OH), 2.82 (dd, 1H, J
2
1
= 7.8, J
2
1
3
1
H, -OH or -NH), 1.72 (bs, 1H, -OH or-NH); C-NMR: δ (ppm) 148.15, 137.74, 129.35, 129.23,
28.65, 126.66, 117.84, 113.30, 71.14, 49.44, 41.63.
1
1
-(Benzylamino)-3-phenylpropan-2-ol (Entry 13). m.p.: 58-61°C; GC-MSD for C H NO (mw:
1
-1
6
19
+
+
+
+
2
41.34 g/mol): [M+1] = 242, [M+29] = 270, [M+41] = 282, [M-17] = 224; IR (cm ): 3149, 3061,
027, 2842, 1602, 1493, 1452, 1425, 1359, 1342, 1178, 1113, 1103, 1080, 1029, 1014, 896, 861, 792,
3
1
7
48, 697; H-NMR: δ (ppm) 7.17-7.33 (m, 10H, Ar-H), 3.83-3.87 (m, 1H, -CH-OH), 3.75 (d, 1H, J=
1
3.2 Hz, -NH-CH-Ar), 3.68 (d, 1H, J= 13.2 Hz, -NH-CH -Ar), 2.62-2.76 (m, 5H, -NH-CH -CH-OH, -
2
2
1
3
NH, -OH, HO-CH-CH-Ar), 2.52 (dd, 1H, J
1
2
= 9.0, J = 12.0 Hz, HO-CH-CH-Ar); C-NMR:
δ (ppm) 139.65, 138.31, 129.27, 128.36, 128.11, 127.05, 126.25, 70.55, 54.01, 53.49, 41.58.
1
2
1
2
-Phenoxy-3-(phenylamino)propan-2-ol (Entry 14). m.p.: 52-53 °C; GC-MSD for C15H17NO (mw:
+
+
+
+
-1
43.31 g/mol): [M+1] = 244, [M+29] = 272, [M+41] = 284, [M-17] = 226. IR (cm ): 3333, 1600,
1
588, 1508, 1496, 1467, 1437, 1303, 1242, 1160, 1080, 1046, 995, 942, 884, 815, 750; H-NMR: δ
(
ppm) 7.28 (dd, 2H, J
J= 7.4 Hz, Ar-H), 6.90 (dd, 2H, J
H, J = 1.0, J = 8.6 Hz, Ar-H), 4.20-4.24 (m, 1H, -CH-OH), 4.04 (dd, 1H, J
CH-CH-O-Ar), 4.00 (dd, 1H, J = 6.1, J = 9.5 Hz, HO-CH-CH-O-Ar), 3.94 (bs, 1H, -OH or -NH), 3.40
dd, 1H, J = 4.3, J = 13.0 Hz, –NH-CH-CH-OH), 3.26 (dd, 1H, J = 7.2, J = 13.0 Hz, –NH-CH-CH-
OH), 2.76 (bs, 1H, -OH, or -NH); C-NMR: δ (ppm) 158.38, 148.03, 129.56, 129.29, 121.26, 118.03,
1
= 7.4, J
2
= 8.7 Hz, Ar-H), 7.17 (dd, 2H, J
= 1.0, J = 8.8 Hz, Ar-H), 6.77 (t, 1H, J= 7.3 Hz, Ar-H), 6.65 (dd,
= 4.1, J = 9.5 Hz, HO-
1 2
= 7.3, J = 8.6 Hz, Ar-H), 6.97 (t, 1H,
1
2
2
1
2
1
2
1
2
(
1
2
1
2
1
3
1
14.52, 113.26, 70.02, 68.76, 46.61.
1
2
2
1
2
-(Benzylamino)-3-phenoxypropan-2-ol (Entry 15). m.p.: 71-72 °C; GC-MSD for C16H19NO (mw:
+
+
+
+
-1
57.34 g/mol): [M+1] = 258, [M+29] = 286, [M+41] = 298, [M-17] = 240; IR (cm ): 3266, 3003,
938, 2853, 2716, 1600, 1586, 1497, 1464, 1454, 1363, 1339, 1304, 1294, 1247, 1211, 1158, 1115,
1
068, 1043, 1022, 897, 882, 791, 749; H-NMR: δ (ppm) 7.22-7.32 (m, 7H, Ar-H), 6.93 (t, 1H, J= 7.3
Hz, Ar-H), 6.88 (d, 2H, J= 7.9 Hz, Ar-H), 4.04-4.08 (m, 1H, -CH-OH), 3.95 (d, 1H, J= 9.9 Hz, HO-
CH-CH-O-Ar), 3.92 (d, 1H, J= 9.9 Hz, HO-CH-CH-O-Ar), 3.82 (d, 1H, J= 13.2Hz, Ar-CH-NH), 3.78
(
d, 1H, J= 13.2 Hz, Ar-CH-NH), 2.84 (dd, 1H, J
1
= 3.9, J
2
= 12.1 Hz, -NH-CH-CH-OH), 2.75 (dd, 1H,
1
3
J
1 2
= 7.9, J = 12.1 Hz, -NH-CH-CH-OH), 2.68 (bs, 2H, -NH, -OH); C-NMR: δ (ppm) 158.56, 139.82,
1
29.43, 128.41, 128.07, 127.06, 120.96, 114.49, 70.38, 68.37, 53.78, 51.27.
1
2
1
2
-(Phenylamino)-3-(o-tolyloxy)propan-2-ol (Entry 16). m.p.: 51-52 °C; GC-MSD for C12H19NO (mw:
+
+
+
+
-1
57.33 g/mol): [M+1] = 258, [M+29] = 286, [M+41] = 298, [M-17] = 240. IR (cm ): 3328, 2932,
1
604, 1496, 1464, 1436, 1368, 1306, 1288, 1245, 1196, 1123, 1070, 1051, 1043, 842, 745; H-NMR: δ
(
ppm) 7.12-7.20 (m, 4H, Ar-H), 6.88 (t, 1H, J= 6.9 Hz, Ar-H), 6.80 (d, 1H, J= 8.3 Hz, Ar-H), 6.73 (t,
1H, J= 7.3 Hz, Ar-H), 6.66 (d, 2H, J= 7.6 Hz, Ar-H), 4.22-4.28 (m, 1H, -CH-OH), 4.04 (dd, 2H, J
1
=
4
.5, J = 5.7 Hz, CH -O-Ar), 4.00 (bs, 1H, , -OH or -NH), 3.45 (dd, 1H, J = 4.3, J = 13.0 Hz, NH-CH-
2
2
1
2

Molecules 2007, 12
2528
CH-OH), 3.29 (dd, 1H, J = 7.2, J = 13.0 Hz, NH-CH-CH-OH), 2.59 (bs, 1H, -OH or -NH), 2.25 (s,
1
2
1
3
3
3
H, Ar-CH ); C-NMR: δ (ppm) 156.41, 148.04, 130.83, 129.30, 126.92, 126.62, 121.00, 118.01,
1
13.25, 111.11, 70.06, 68.87, 46.77, 16.28.
1
2
2
1
-(Benzylamino)-3-(o-tolyloxy)propan-2-ol (Entry 17). m.p.: 76-77 °C; GC-MSD for C H NO (mw:
1
-1
7
21
2
+
+
+
+
71.36 g/mol): [M+1] = 272, [M+29] = 300, [M+41] = 312, [M-17] = 255. IR (cm ): 3277, 3026,
858, 2822, 1603, 1592, 1495, 1377, 1341, 1306, 1289, 1245, 1191, 1154, 1121, 1098, 1073, 1050,
1
037, 1029, 995, 982, 935, 915, 888, 838, 767, 745, 737, 693; H-NMR: δ (ppm) 7.29-7.33 (m, 4H,
Ar-H), 7.22-7.27 (m, 1H, Ar-H), 7.10-7.14 (m, 2H, Ar-H), 6.85 (t, 1H, J= 7.3 Hz, Ar-H), 6.78 (d, 1H,
J= 7.8 Hz, Ar-H), 4.06-4.10 (m, 1H, -CH-OH), 3.97 (dd, 1H, , J = 5.5, J = 9.5 Hz, CH-O-Ar), 3.93
dd, 1H, J = 5.0, J = 9.5 Hz, CH-O-Ar), 3.84 (d, 1H, J= 13.2 Hz, Ar-CH-NH), 3.79 (d, 1H, J= 13.2
1
2
(
1
2
Hz, Ar-CH-NH, 2.89 (dd, 1H, J
1 2 1 2
= 4.0, J = 12.2 Hz, NH-CH-CH-OH), 2.80 (dd, 1H, J = 7.6, J = 12.2
1
3
Hz, NH-CH-CH-OH), 2.56 (bs, 2H, -OH, -NH)), 2.19 (s, 3H, Ar-CH3); C-NMR: δ (ppm) 156.62,
1
39.86, 130.65, 128.42, 128.08, 127.08, 126.77, 120.67, 111.08, 70.43, 68.47, 53.82, 51.38, 16.22.
1
-(4-Methoxyphenoxy)-3-(phenylamino)propan-2-ol (Entry 18). m.p.: 69-71 °C; GC-MSD for
+
+
+
+
C
16 3
H19NO (mw: 273.33 g/mol): [M+1] = 274, [M+29] = 302, [M+41] = 314, [M-17] = 256; IR
-1
(
cm ): 3377, 2998, 2926, 2830, 1607, 1526, 1503, 1459, 1438, 1292, 1264, 1228, 1218, 1180, 1153,
1
1
125, 1113, 1036, 918, 878, 823, 749, 741; H-NMR: δ (ppm) 7.17 (dd, 2H, J
1
= 7.3, J
2
= 8.6 Hz, Ar-
H), 6.80-6.85 (m, 4H, Ar-H), 6.72 (t, 1H, J= 8.3 Hz, Ar-H), 6.64 (d, 2H, J= 8.6 Hz, Ar-H), 4.17-4.21
m, 1H, -CH-OH), 3.99 (dd, 2H, J = 4.1, J = 9.5 Hz, HO-CH-CH-O-Ar and -OH or -NH), 3.95 (dd,
H, J = 8.1, J = 9.5 Hz, HO-CH-CH-O-Ar), 3.73 (s, 3H, -OCH ), 3.38 (dd, 1H, J = 4.3, J = 12.9 Hz, –
NH-CH-CH-OH), 3.24 (dd, 1H, J = 7.2, J = 12.9 Hz, –NH-CH-CH-OH), 2.80 (bs, 1H, -OH or -NH);
(
1
2
1
1
2
3
1
2
1
2
1
3
C-NMR: δ (ppm) 154.16, 152.54, 148.05, 129.28, 117.96, 115.52, 114.69, 113.23, 70.83, 68.82,
5
5.69, 46.57.
1
-(Benzylamino)-3-(4-methoxyphenoxy)propan-2-ol (Entry 19). m.p.: 94-95 °C; GC-MSD for
+
+
+
+
C
12 3
H21NO (mw: 287.36 g/mol): [M+1] = 288, [M+29] = 316, [M+41] = 328, [M-17] = 270; IR
-1
(
cm ): 3288, 2905, 2828, 1509, 1506, 1466, 1455, 1444, 1345, 1291, 1232, 1107, 1077, 1068, 1049,
1
1
013, 949, 906, 874, 836, 815, 753, 743, 699; H-NMR: δ (ppm) 7.27-7.33 (m, 4H, Ar-H), 7.22-7.26
(
m, 1H, Ar-H), 6.78-6.84 (m, 4H, Ar-H), 4.02-4.06 (m, 1H, -CH-OH), 3.90 (d, 2H, J= 5.2 Hz, CH
Ar), 3.83 (d, 1H, J= 13.2 Hz, Ar-CH-NH), 3.79 (d, 1H, J= 13.2 Hz, Ar-CH-NH), 3.74 (s, 3H, -OCH
.84 (dd, 1H, J = 3.9, J = 12.2 Hz, NH-CH-CH-OH), 2.75 (dd, 1H, J = 7.8, J = 12.2 Hz, NH-CH-CH-
OH), 2.59 (bs, 2H, -OH, -NH); C-NMR: δ (ppm) 153.97, 152.75, 139.84, 128.43, 128.06, 127.05,
2
-O-
3
),
2
1
2
1
2
1
3
1
15.48, 114.60, 71.20, 68.48, 55.66, 53.77, 51.24.
In view of the difficulties associated with the purification process, the minority products from
entries 2, 4 and 10 were identified through gas chromatography coupled to a mass detector in the
chemical ionization mode, which displayed different retention times, with the same molecular ions,
and fragmentation patterns that were different respect to those of the majority products.
+
+
+
+
1
-(Phenylamino)hexan-2-ol (Entry 2). [M+1] = 194, [M+29] = 222, [M+41] = 234 m/z [M- OH] =
+
176, [M- CH
2
OH ] = 162.

Molecules 2007, 12
2529
+
+
+
1
-(Pphenylamino)hex-5-en-2-ol (Entry 4). [M+1] = 192, [M+29] = 220, [M+41] = 232. m/z [M-
+
+
OH] = 174, [M- CH
2
OH ] = 160.
+
+
+
2
-Phenyl-2-(phenylamino)ethanol (Entry 10). [M+1] = 214, [M+29] = 242, [M+41] = 254. m/z [M-
+
+
+
2
OH] = 196. The [M-31] = [M-CH OH] = 182 fragment was not observed.
Acknowledgements
The authors are grateful to Dr. Eduardo Terrés Rojas and Dr. Juan Navarrete Bolaños from
Instituto Mexicano del Petróleo for MEB-EDS and Pyridine FT-IR characterization of the catalytic
materials, respectively.
References and Notes
1
.
a) Mejri, I.; Younes, M. K.; Ghorbel, A. Comparative study of the textural and structural
properties of the aerogel and xerogel sulphated zirconia. J Sol-Gel Sci. Techn. 2006, 40, 3–8; b)
Pârvulescu, V.; Coman, S.; Grange, P.; Pârvulescu V. I. Preparation and characterization of
sulfated zirconia catalysts obtained via various procedures. Appl. Catal. A. 1999, 17, 27–43.
Arata, K.; Matsuhashi, H. Hino, M.; Nakamura, H. Synthesis of solid superacids and their
activities for reactions of alkanes. Catal. Today 2003, 81, 17–30.
2
3
.
.
Chen, W. H.; Ko, H. H.; Sakthivel, A.; Huang, S. J.; Liu, S. H.; Lo, A. Y.; Tsai, T. C.; Liu, S. B.
A solid-state NMR, FT-IR and TPD study on acid properties of sulfated and metal-promoted
zirconia: Influence of promoter and sulfation treatment. Catal. Today 2006, 116, 111–120.
Li, X.; Nagaoka, K.; Lercher, J. A. Labile sulfates as key components in active sulfated zirconia
for n-butane isomerization at low temperatures. J. Catal. 2004, 227, 130–137.
4
5
6
.
.
.
Marcus, R.; Diebold, U.; Gonzalez, R. D. The locus of sulfate sites on sulfated zirconia. Catal.
Letts. 2003, 86, 151–156.
Biró, K.; Figueras, F.; Békássy, S. Acylation of B15C5 crown ether by acetic anhydride in the
absence of solvent, on sulfated zirconias prepared in different conditions. Appl. Catal. A. 2002,
2
29, 235–243.
7
8
9
1
1
.
.
.
Deutsch, J.; Prescott, H. A.; Müller, D.; Kemnitz, E.; Lieskea, H. Acylation of naphthalenes and
anthracene on sulfated zirconia. J. Catal. 2005, 231, 269–278.
Reddy, B. M.; Sreekanth, P. M.; Lakshmanan, P. Sulfated zirconia as an efficient catalyst for
organic synthesis and transformation reactions. J. Mol. Catal. 2005, 237, 93–100.
Zhuang, Q.; Miller, J. M. One-pot sol-gel synthesis of sulfated ZrO -SiO catalysts for alcohol
2
2
dehydration. Can. J. Chem. 2001, 79 (8), 1220-1223.
0. Escalona-Platero, E.; Penarroya-Mentruit, M. Acetylene polymerization on sulfated zirconia:
detection of intermediates by infrared spectroscopy. Catal. Letts. 1997, 45 (1,2), 59-63.
1. a) Sun,Y.; Zhu, L.; Lu, H.; Wang, R.; Lin, S.; Jiang, D.; Xiao, F. S. Sulfated zirconia supported in
mesoporous materials. Appl. Catal. A. 2002, 237, 21–31; b) Yurdakoc, M.; Akcay, M.; Tonbul,
K.; Yurdakoc, K. Acidity of silica-alumina Catalysis by amine titration using Hammett indicators
and FT-IR Study. Turk J. Chem. 1999, 23, 319-327; c) Morterra, C.; Garronet, E.; Bolis, V.;

Molecules 2007, 12
2530
Fubini, B. An infrared spectroscopic characterization of the coordinative adsorption of carbon
monoxide on TiO . Spectrochim. Acta, Part A. 1987, 43, 1577-1581.
2
1
1
1
2. Chen, C. L.; Cheng, S.; Lin, H. P.; Wong, S. T.; Mou, C. Y. Sulfated zirconia catalyst supported
on MCM-41 mesoporous molecular sieve. Appl. Catal. A. 2001, 215, 21–30.
3. Wanga, W.; Wang, J. H.; Chena, C. L.; Xua, N. P.; Mou, C. Y. n-Pentane isomerization over
promoted SZ/MCM-41 catalysts. Catal. Today 2004, 97, 307–313.
4. Breda, A.; Signoretto, M.; Ghedini, E.; Pinna, F.; G. Cruciani. Acylation of veratrole over
promoted SZ/MCM-41 catalysts: Influence of metal promotion. Appl. Catal. A. 2006, 308, 216–
2
22.
1
5. Scarpi, D.; Lo Galbo, F.; Occhiato, E. G.; Guarna, A. Enantioselective addition of diethylzinc to
aldehydes using. 1,4-aminoalcohols as chiral ligands. Tetrahedron: Asymmetry 2004, 15, 1319–
1
324.
1
1
6. Mojtahedi, M. M.; Saidi, M. R.; Bolourtchian, M. Microwave-assisted Aminolysis of Epoxides
Under Solvent-free Conditions Catalyzed by Montmorillonite Clay. J. Chem. Res. 1999, 128–129.
7. Sagawa, S.; Abe, H.; Hase, Y.; Inaba, T. Catalytic Asymmetric Aminolysis of 3,5,8-
Trioxabicyclo[5.1.0]octane Providing an Optically Pure 2-Amino-1,3,4-butanetriol Equivalent. J.
Org. Chem. 1999, 64, 4962–4965.
1
1
8. Van de Weghe, P.; Collin, J. Ring opening reactions of epoxides catalyzed by samarium iodides.
Tetrahedron Lett. 1995, 36, 1649–1652.
9. Yamamoto, Y.; Asao, N.; Meguro, M.; Tsukada, N.; Nemoto, H.; Sadayori, N.; Wilson; J. G.;
Nakamura, H. Regio- and stereo-selective ring opening of epoxides with amide cuprate reagents.
J. Chem. Soc., Chem. Commun. 1993, 1201–1203.
20. Fu, X. L.; Wu, S. H. A regio-and stereoselective synthesis of β-amino alcohols. Synth. Commun.
1
997, 27, 1677–1683.
2
1. Mlynarski, J.; Jankowska, J.; Rakiel, B. Direct asymmetric aldol-Tishchenko reaction of aliphatic
ketones catalyzed by syn-aminoalcohol-YB (III) complexes. Chem. Commun. 2005, 38, 4854–
4
856.
2. Mirkhania, V.; Tangestaninejad, S.; Yadollahi, B.; Alipanah; L. Ammonium decatungstocerate
IV): an efficient catalyst for ring opening of epoxides with aromatic amines. Catal. Letts. 2005,
01, 93–97.
2
(
1
2
2
3. De, S. K. ; Gibbs, R. A. Ruthenium(III) Chloride–Catalyzed Ring Opening of Epoxides with
Aromatic Amines. Synth. Commun. 2005, 35, 2675–2680.
4. Raghavendra, S. N.; Goud, T. V.; Reddy, S. M.; Krishnaiah, P.; Venkateswarlu, Y. Zirconium
(
IV) Chloride Catalyzed Ring Opening of Epoxides with Aromatic Amines. Synth. Commun.
004, 34, 727–734.
5. Kamal, A.; Arifuddin
trimethylsilyl azide (TMSN
2
2
,
M.; Rao, M. V. Enantioselective ring opening of epoxides with
) in the presence of β-cyclodextrin: an efficient route to 1,2-azido
3
alcohols. Tetrahedron: Asymmetry 1999, 10, 4261–4264.
2
2
6. Reddy, L. R.; Reddy, M. A.; Bhanumathi, N.; Rao, K. R. Cerium Chloride-Catalysed Cleavage of
Epoxides with Aromatic Amines. Synthesis 2001, 831–832
7. Chakraborti, A. K.; Rudrawar, S.; Kondaskar, Atul. An efficient synthesis of 2-amino alcohols by
silica gel catalysed opening of epoxide rings by amines. Org. Biomol. Chem. 2004, 1277–1280

Molecules 2007, 12
2531
2
8. Xue, W. M.; Kung, M. C.; Kozlov, A. I.; Popp, K. E.; Kung, H. H. Catalytic aminolysis of
epoxide by alumina prepared from amine-protected Al precursor. Catal. Today 2003, 85, 219–
24.
2
2
3
3
3
9. Horváth, A.; Skoda-Földes, R.; Mahó, S.; Berente, Z.; Kollár, L. Facile ring opening of 2,3-
epoxy-steroids with aromatic amines in ionic liquids. Steroids 2006, 71, 706–711.
0. Azizi, N.; Saidi, M. R. Highly Chemoselective Addition of Amines to Epoxides in Water. Org.
Lett. 2005, 7, 3649–3651.
1. Azizi, N.; Saidi, M. R. LiClO .3H O promoted highly regioselective ring-opening of epoxides
4
2
with thiols under neutral conditions. Cat. Commun. 2006, 7, 224–227.
2. Babu, K. S.; Raju, B. C.; Kumar, S. P.; Mallur, Shanta G.; Reddy, S. V.; Rao, J. M.
Tungstophosphoric Acid (H PW O )-Catalyzed Regioselective Ring Opening of Epoxides with
3
12 40
Amines. Synth. Commun. 2005, 35, 879–885.
3
3
3. Azizi, N.; Saidi, M. R. Highly efficient ring opening reactions of epoxides with deactivated
aromatic amines catalyzed by heteropoly acids in water. Tetrahedron 2007, 63, 888–891.
4. Rafiee, E.; Tangestaninejad, S.; Habibi, M. H.; Mirkhani, V. Potassium Dodecatungstocobaltate
Trihydrate (K CoW O .3H O) as an Efficient Catalyst for Aminolysis of Epoxides. Synth.
5
12 40
2
Commun. 2004, 34, 3673–3681.
3
5. Angeles-Beltrán, D.; Lomas-Romero, L.; Lara-Corona, V. H.; González-Zamora, E.; Negrón-
Silva, G. Sulfated Zirconia-Catalyzed Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (DHPMs)
under Solventless Conditions: Competitive Multicomponent Biginelli vs. Hantzsch Reactions.
Molecules 2006, 11, 731–738.
3
3
3
6. Negrón, G.; Ángeles, D.; Lomas, L.; Martínez, Á.; Ramírez, M.; Martínez, Roberto. An Efficient
Synthesis Of 6,6-Dimethyl-2-(4-Nitrophenyl)-1-(R-Phenyl)-4,5,6,7-Tetrahydro-1h-4-Indolones
using a solid sulfated zirconia as catalyst. Heterocycles 2004, 63, 367–371.
7. Negrón, G. E.; Palacios, L. N.; Angeles, D.; Lomas, L.; Gaviño, R. A Mild and Efficient Method
for the Chemoselec tive Synthesis of Acylals from Aromatic Aldehydes and their Deprotections
Catalyzed by Sulfated Zirconia. J. Braz. Chem. Soc. 2005, 16, 490–494.
8. Klose, B. S.; Jentoft, R. E.; Hahn, A.; Ressler, T.; Kröhnert, J.; Wrabetz, S.; Yang, X.; Jentoft, F.
C. Mechanical stress induced activity and phase composition changes in sulfated zirconia
catalysts. J. Catal. 2003, 217, 487–490.
3
4
9. Webb, P. A.; Orr, C. Analytical methods in fine particle technology. Micromeritics Instrument
Corporation: Norcross, GA USA. 1997.
0. a) Du,Y.; Sun,Y.; Di, Y.; Zhao, L.; Liu, S.; Xiao, F. S. Ordered mesoporous sulfated silica-
zirconia materials with high zirconium contents in the structure. J. Porous Mater. 2006, 13, 163–
1
8
71; b) Li, M.; Feng, Z.; Xiong, G.; Ying, P.; Xin, Q.; Li, Can. J. Phys. Chem. B. 2001, 105,
107-8111.
4
4
4
1. Cepanec, I.; Litvić, M.; Mikuldaš, H.; Bartolinčića A.; Vinkovićb V. Calcium
trifluoromethanesulfonate-catalysed aminolysis of epoxides. Tetrahedron 2003, 59, 2435–2439.
2. De, S. K.; Gibbs, R. A. Ruthenium(III) Chloride–Catalyzed Ring Opening of Epoxides with
Aromatic Amines. Synth. Commun. 2005, 35, 2675–2680.
3. Westermann, J.; Schneider, M.; Platzek, J.; Petrov, O. Practical Synthesis of a Heterocyclic
Immunosuppressive Vitamin D Analogue. Org. Process Res. Dev. 2007, 11, 200–205.

Molecules 2007, 12
2532
4
4
4. Kondaskar, C.; Kondaskar, A. ZrCl as a new and efficient catalyst for the opening of epoxide
4
rings by amines. Tetrahedron Lett. 2003, 44, 8315–8319.
5. a) Fujiwara, M.; Imada, M.; Bab, A.; Matsuda, H. Tetraphenylstibonium triflate as a regio- and
chemoselective catalyst in the reaction of oxiranes with amines. Tetrahedron Lett. 1989, 30, 739–
7
42; b) Alam, M. M.; Varala, R.; Enugala, R.; Adapa, S. R. Synthesis of -Amino Alcohols by
Regioselective Ring Opening of Epoxides with Aromatic Amines Catalyzed by Tin (II) Chloride.
Lett. Org. Chem. 2006, 3, 187–190; c) Swamy, N. R.; Goud, T. V.; Reddy, S. M.; Krishnaiah, P.;
Venkateswarlu, Y. Zirconium (IV) Chloride Catalyzed Ring Opening of Epoxides with Aromatic
Amines. Synth. Commun. 2004, 34, 727–734.
4
6. a) Gupta, R.; Paul, S.; Gupta, A. K.; Kachroo, P. L.; Dandia, A. Opening of oxirane ring with N-
nucleophiles under microwave irradiation. Ind. J. Chem. Sect. B. 1997, 36B, 281–283; b) Yadav, J.
4
S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V. [Bmim]BF ionic liquid. A novel reaction
medium for the synthesis of β-amino alcohols. Tetrahedron Lett. 2003, 44, 1047–1050; c) Kumar,
S. R. and Leelavathi, P. Cadmium chloride-catalyzed regioselective opening of oxiranes with
aromatic amines–Animproved protocol for the synthesis of 2-amino alcohols. Can. J. Chem. 2007,
8
5, 37–41; d) Chakraborti, A. K.; Rudrawar, S; Kondaskar, A. Lithium bromide, an inexpensive
and efficient catalyst for opening of epoxide rings by amines at room temperature under solvent-
free condition. Eur. J. Org. Chem. 2004, 17, 3597–3600.
4
4
4
5
7. Chakraborti, A. K.; Kondaskar, A.; Rudrawar, S. Scope and limitations of montmorillonite K 10
catalysed opening of epoxide rings by amines. Tetrahedron 2004, 60, 9085–9091.
8. Greenwood, D. T.; Mallion, K. B.; Todd, A. H.; Turner, R. W. 2-Aryloxymethyl-2,3,5,6-
tetrahydro-1,4-oxazines, a new class of antidepressants. J. Med. Chem. 1975, 18 (6), 573–577.
9. Matsuhashi, H.; Tanaka, M.; Nakamura, H.; Arata, K. Formation of acid sites in ordered pores of
FSM-16 by modification with sulfated zirconia. Appl. Catal. A. 2001, 208, 1–5.
0. Luo, Y.; Lu, G. Z.; Guo, Y. L.; Wang, Y. S. Study on Ti-MCM-41 zeolites prepared with
inorganic Ti sources: synthesis, characterization and catalysis. Catal. Commun. 2002, 3, 129–134.
Sample Availability: Samples of the compounds are available from the authors.
2007 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
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