Nano-TiO2: An efficient and reusable heterogeneous catalyst for ring opening of epoxides under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2011.559608

Nano-TiO₂ is an effective heterogeneous catalyst for the ring opening of epoxides with aromatic amines to afford-amino alcohols in good to excellent yields at room temperature under solvent-free conditions. It was found that the catalyst is recyclable, and the activity of the catalyst was not weakened markedly even after several reaction cycles. In addition, the catalytic activity of TiO₂ strongly depends on particle size or surface area.

Full text of DOI:10.1080/00397911.2011.559608

This article was downloaded by: [Brown University]
On: 03 June 2012, At: 04:55
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Nano-TiO2: An Efficient and Reusable
Heterogeneous Catalyst for Ring
Opening of Epoxides Under Solvent-Free
Conditions
Xi'an Chen a , Huayue Wu a , Shun Wang a & Shaoming Huang a
a Nanomaterials and Chemistry Key Laboratory, Wenzhou University,
Wenzhou, China
Available online: 27 Dec 2011
To cite this article: Xi'an Chen, Huayue Wu, Shun Wang & Shaoming Huang (2012): Nano-TiO2: An
Efficient and Reusable Heterogeneous Catalyst for Ring Opening of Epoxides Under Solvent-Free
Conditions, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 42:16, 2440-2452
To link to this article: http://dx.doi.org/10.1080/00397911.2011.559608
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 2440–2452, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.559608
NANO-TiO2: AN EFFICIENT AND REUSABLE
HETEROGENEOUS CATALYST FOR RING OPENING OF
EPOXIDES UNDER SOLVENT-FREE CONDITIONS
Xi’an Chen, Huayue Wu, Shun Wang, and Shaoming Huang
Nanomaterials and Chemistry Key Laboratory, Wenzhou University,
Wenzhou, China
GRAPHICAL ABSTRACT
Abstract Nano-TiO2 is an effective heterogeneous catalyst for the ring opening of epoxides
with aromatic amines to afford b-amino alcohols in good to excellent yields at room tem-
perature under solvent-free conditions. It was found that the catalyst is recyclable, and the
activity of the catalyst was not weakened markedly even after several reaction cycles. In
addition, the catalytic activity of TiO2 strongly depends on particle size or surface area.
Keywords b-Amino alcohol; epoxide; heterogeneous catalyst; nano-TiO2; solvent-free
INTRODUCTION
b-Amino alcohols are versatile building blocks in the synthesis of a vast range
of biologically active natural and synthetic products, amino acids, and chiral auxili-
aries for asymmetric synthesis.[1] One of the most practical and widely used methods
for the synthesis of these compounds is the direct aminolysis of epoxides at elevated
temperature with an excess of amine. Recently, several useful modifications of the
classical procedures have been reported: Activators=promoters such as metal
amides,[2] metal alkoxides,[3] metal triflates,[4] metal halides,[5] silica and alumina=
modified alumina,[6] clay,[7] and different reaction media including ionic liquids,[8]
water,[9] fluoro alcohols,[10] supercritical carbon dioxide,[11] and others,[12] have been
developed to perform ring-opening reaction of epoxides under mild conditions.
Received January 4, 2011.
Address correspondence to Xi’an Chen or Shaoming Huang, Nanomaterials and Chemistry Key
Laboratory, Wenzhou University, Wenzhou 325027, China. E-mail: xianchen@wzu.edu.cn; smhuang@
wzu.edu.cn
2440

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2441
However, these methodologies suffer from one or more disadvantages such as long
reaction times, moderate yields, use of stoichiometric or moisture-sensitive catalyst,
costly reagents=catalysts, hazardous organic solvents, and potential hazards in hand-
ling pyrophoric=moisture-sensitive reagents in the preparation of the catalyst. There-
fore, the development of a chemically stable and nontoxic catalyst for promoting this
transformation under environmentally friendly conditions is still needed.
In recent years, there has been increasing consideration on the use and design
of environmentally friendly solid catalysts to reduce the amount of toxic waste.
Nanoscale metal oxides[13] have been efficiently used in the destruction of hazardous
chemicals and catalysts for organic transformations such as epoxidation,[14] benzyla-
tion,[15] Friedel–Crafts acylation,[16] and click chemistry.[17] These high reactivities
depend on large surface areas or unusually reactive morphologies to a certain extent.
Recently, TiO2 and nanosize-TiO2 are being used as catalysts to promote organic
reactions such as carboxymethylation of bisphenol A,[18] oxidative desulfuriza-
tion,[19] selective oxidation of aldehydes,[20] as well as methylation of phenol.[21] It
is well known that there are many Lewis acidic sites (Tiþ) on the surface of TiO2,
which may activate the epoxide through the weak interaction with the oxygen atom
of the epoxide. Aiming at the development of green and efficient organic methodol-
ogies, recently we reported highly regioselective ring opening of epoxides in aqueous
media, water, or solvent-free conditions.[22] Herein, we report, for the first time, that
nano-TiO2 particles can be an efficient heterogeneous catalyst for promoting
ring-opening reactions of epoxides with aromatic amines under mild conditions.
The possible mechanism for this promotion is also discussed.
RESULTS AND DISCUSSION
In an effort to develop a better catalytic system, various reaction parameters
were studied for the preparation of b-amino alcohols by the reaction of styrene oxide
with aniline, and the results are summarized in Table 1. It is clear from Table 1 that
the catalytic activity of the TiO2 particles is strongly influenced by their size.
Ring-opening reaction employing with TiO2 (10 mol%), 5–10 nm gives to 3a and
4a in excellent total yield (95%) after 3 h at room temperature under solvent-free con-
ditions. As the TiO2 size increases, the yields decrease (Table 1, entries 1–4). The rea-
son is that the smaller TiO2 particles have a larger surface area for the contact of the
reactants, which is supported by the data of surface area. However, the regioselectiv-
ity is not affected by the size or reaction media, and as expected 3a was obtained as
the major product (the ratio 3a=4a is close to 94=6) because of the formation of the
stabilized benzylic cation during ring opening of the styrene oxide under different
conditions. Interestingly, when the same size TiO2 modified by hexadecyltrimethox-
ysilane was used as catalyst for the same reaction, the total yield was reduced to only
62% from 86% (Table 1, entry 2). The reduction of the yield was believed to be the
result of the enhancement of steric hindrance of TiO2 and blocking the contact
between the reactants and Ti, which verified that Ti on the surface of TiO2 plays
an important role in promoting the ring opening of epoxides. We also found that
the yield was affected by adding different amounts of nano-TiO2, and better conver-
sions were achieved by using 10 mol% TiO2 (Table 1, entry 1). Prolonging the reac-
tion time did not improve the yields of corresponding products (Table 1, entries 1, 6,

2442
X. CHEN ET AL.
Table 1. Reaction of styrene oxide with aniline under various reaction conditions
Entry
Catalyst size (nm)
Surface aera (m2gꢀ1
)
Time (h)
Solvent
Total yield (%)a,b
1
2
5–10
25
110
78
3
3
3
4
4
1
5
3
3
3
3
3
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
CH3CH2OH
CH3CN
95, 80,c 95d
86, 62e
73
45
3
60
70
15
4
400–600
Catalyst-free
5–10
5
—
5
70
6
110
110
110
110
110
110
110
7
5–10
5–10
95
50
8
9
5–10
5–10
60
44
10
11
12
CH2Cl2
Toluene
H2O
5–10
5–10
40
62
aIsolated yield.
bThe ratio of isomer 3a=4a is close to 94=6, which was determined by 1H NMR.
cLoading catalyst 5 mol%.
dLoading catalyst 15 mol%.
eTiO2 was modified by hexadecyltrimethoxysilane.
and 7). The yields were unsatisfactory when various solvents were used such as
CH3CH2OH, CH3CN, CH2Cl2, toluene, or H2O (Table 1, entries 8–12).
Furthermore, we chose a variety of structurally divergent aromatic amines or
epoxides possessing a wide range of functional groups to understand the scope
and the generality of the nano-TiO2 promotion effect for the epoxide ring opening
reaction, and the results are summarized in Table 2. In the case of aryl-substituted
epoxides, the reaction proceeds with a remarkable regioselectivity to give 3 of the
two possible regioisomers (3 and 4, Table 2) in good to excellent yields as a result
of the more hindered carbon of the epoxides attacked by diversified aromatic amines
(entries a–g). It is worth mentioning that anilines bearing electron-withdrawing
groups do not fail to react in the evaluated reaction conditions, and complete regios-
electivity to forming the isomer 3 was observed (entries b and g). Furthermore, the
attack occurs the less hindered carbon of the epoxide to give regioisomer 4 as main
products when alkyl-substituted unsymmetrical epoxides were used as substrates
(entries m–p). We can also find the regioselectivity was affected by substituted
groups of epoxides to some extent. When steric hindrance of substituted group
increases, the regioselectivity for the isomer 4 is improved (entries m and p). As
for cyclohexene oxide, a very clean reaction with a variety of aromatic amines was
observed (entries h–l), and the amino alcohols had trans-stereochemistry. The
1
trans-configuration of amino alcohols was identified with characteristic H NMR
signals appearing at d 3.13 (ddd, 1H, J ¼ 11.0, 9.5, and 3.8 Hz) for the CHNH

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2443
Table 2. Reaction of various epoxides with aromatic amines in the presence of TiO2 (5–10 nm)a
Entry
R1
R2
Yieldb (%)
Ratio 3:4c
a
b
c
d
e
f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
95
86
91
91
94
85
65
94:6
>99:1
94:6
4-F(C6H4)
4-Cl(C6H4)
4-Br(C6H4)
2-Me(C6H4)
4-Me(C6H4)
4-NO2(C6H4)
94:6
93:7
90:10
>99:1
—
g
h
i
Ph
93
88
88
90
92
—
2-Me(C6H4)
4-F(C6H4)
4-Cl(C6H4)
4-Br(C6H4)
j
—
—
—
k
l
m
n
ClCH2-
ClCH2-
ClCH2-
Ph
4-Cl(C6H4)
4-F(C6H4)
95
90
87
25:75
25:75
20:80
o
p
Ph
91
13:87
aEpoxides (2 mmol) were treated with aromatic amines (2 mmol) in the presence of 5–10 nm TiO2
(10 mol %) at room temperature under solvent-free condition for 3 h.
bIsolated yield.
cThe ratio of isomer 3=4 was determined by 1H NMR or calculated after isolation.
and at 3.33 (ddd, 1H, J ¼ 10.0, 9.5, and 4.2 Hz) for the CHOH protons and a 13C
NMR signal at d 60.0 for the CHNH carbon.[4c,5b]
When the substrate was extended to alky amine (phenethylamine), the corre-
sponding b-amino alcohol was not obtained. This demonstrated the chemoselectivity
of this reaction catalyzed by nano-TiO2. Possibly TiO2 are strong Lewis acids, form-
ing complex metal salts on the surface with aliphatic amines that cause the catalyst
destruction and make the metal oxide ineffective for use as a catalyst for the opening
of epoxide rings by aliphatic amines. To confirm this, cyclohexene oxide was treated
with aniline and phenethylamine in one pot. As Scheme 1 shows, the corresponding
b-amino alcohols were not obtained when 1 equiv. of aniline and phenethylamine
were used as reactants and the yield of 2-(phenylamino)cyclohexanol increased with
the amount of phenethylamine decrease, which revealed that the catalytic activity of
TiO2 will be destroyed by alky amine. Therefore, the role of TiO2 in promoting the

2444
X. CHEN ET AL.
Scheme 1. Cyclohexene oxide was treated with aniline and=or phenethylamine in the presence of 5–10 nm
TiO2 (10 mol%) at room temperature in the absence of solvent for 3 h.
opening of epoxide rings with aromatic amines is believed to be that of a kind of
Lewis acid. A plausible mechanism of the reaction involved the activation of epoxide
through the weak interaction between the oxygen atom of epoxide and Lewis acidic
sites (Tiþ) on the surface of TiO2 to make it susceptible to nucleophilic attack by the
nitrogen atom of aniline either on terminal carbon to produce product A or on the
more hindered carbon to give the product B (Scheme 2).
The reusability of catalyst (nano-TiO2) was further investigated in subsequent
aminolysis reactions, taking the aminolysis of cyclohexene oxide as an example
(Scheme 3). The catalyst was easily recycled by simple centrifugation after diluting
the reaction mixture with ethyl acetate and was reused after drying in the oven.
The catalyst (TiO2) was reused for five runs without any appreciable loss of activity
(Fig. 1).
To explore the kinds of catalysts suitable for the aminolysis of epoxides, differ-
ent metal oxides with similar sizes were used as catalysts for this reaction, taking the
Scheme 2. Possible catalytic cycle for the ring opening of epoxide.

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2445
Scheme 3. Aminolysis of cyclohexene oxide in the presence of 5–10 nm TiO2 (10 mol%) at room tempera-
ture in the absence of solvent for 3 h.
Figure 1. Reusing of the catalyst in subsequent aminolysis reactions.
aminolysis of cyclohexene oxide as an example. Among the catalysts used, TiO2 is
the most effective one with a yield of 85%. It is a pity that lower yields of b-amino
alcohols were observed with other metal oxides such as ZrO2, Al2O3, SiO2, ZnO, and
CuO (entries 3–7, Table 3).
Table 3. Aminolysis of cyclohexene oxide in the presence of different metal oxides (10 mol%)
Entrya
Catalyst
Size (nm)
Yield (%)b
1
2
3
4
5
6
7
TiO2
TiO2
ZrO2
Al2O3
SiO2
25
60
50
30
30
30
40
85
73
48
35
55
30
10
ZnO
CuO
aCyclohexene oxide (2 mmol) were treated with aniline (2 mmol) in the presence of metal oxides
(10 mol%) at room temperature under solvent-free condition for 3 h.
bIsolated yield.

2446
X. CHEN ET AL.
EXPERIMENTAL
All catalysts (metal oxides) and other chemicals were purchased from Aladdin
or Energy chemical companies and were used without further purification. Titanium
1
dioxide is anatase. H NMR and 13C NMR spectra were recorded on a FT-Bruker
AT-500 instrument using tetramethylsilane (TMS) as an internal standard and
CDCl3 as the solvent. J values are given in hertz. Infrared (IR) spectra were mea-
sured on a Perkin-Spectrum GX instrument. Thermogravimetric and differential
thermal analysis (TG-DTA) curves were obtained on a Perkin-instrument. TG-DTA
for the air-dried sample was performed from 50 to 800 ꢁC at a heating rate of
10 ꢁC ꢂ minꢀ1 under nitrogen gas flow. Silica gel 60 GF254 was used for analytical
and preparative thin-layer chromatography (TLC). All yields refer to isolated pro-
ducts. Surface areas of TiO2 particles were determined by the Brunauer–Emmett–
Teller (BET) method on a Micromeritics ASAP 2020 instrument.
Typical Procedure for Ring Opening of Epoxides with Amines
To a magnetically stirred mixture of cyclohexene oxide (2 mmol) and aniline
(2 mmol), TiO2 (5–10 nm, 0.016 g, 0.2 mmol) was added, and the reaction mixture
was stirred at room temperature for the appropriate time. After completion of the
reaction, the reaction mixture was diluted with ethyl acetate. The catalyst was sepa-
rated by simple centrifugation and washed with ethyl acetate. Then the filtrate was
concentrated under reduced pressure to provide the crude product, which was pur-
ified by column chromatography on silica gel (200–300 mesh) with ethyl acetate–pet-
roleum (1:6) to afford the pure 2-(phenylamino)cyclohexanol (Table 2, entry h).
Yield: 93%. Solid, mp 60–61 ꢁC. Spectral data: 1H NMR: (500 MHz, CDCl3) d
7.24–7.19 (m, 2H), 6.75–6.70 (m, 3H), 3.33 (ddd, 1H, J ¼ 10.0, 9.5, and 4.2 Hz),
3.13 (ddd, 1H, J ¼ 11.0, 9.5, and 3.8 Hz), 2.81 (br s, 1H), 2.12–2.09 (m, 2H),
1.78–1.69 (m, 2H), 1.40–1.32 (m, 1H), 1.32–1.27 (m, 2H), 1.05–1.02 (m, 1H). 13C
NMR (125 MHz, CDCl3) d 147.8, 129.3, 118.3, 114.3, 74.5, 60.0, 33.1, 31.6, 24.9,
24.2. The catalyst was then dried and preserved for the next run. Characterization
data of all other products are shown, and products were characterized by compari-
son of their physical and spectral data with those of known samples.[4d,7,12c]
Characterization Data
2-Phenyl-2-(phenylamino)ethanol (3a). 1H NMR (500 MHz, CDCl3) d
7.40–7.28 (m, 5H), 7.08–7.11 (m, 2H), 6.69–6.66 (m, 1H), 6.57–6.55 (m, 2H), 4.50
(dd, 1H, J ¼ 7.0, 4.0 Hz), 3.93 (dd, 1H, J ¼ 11.0, 3.5 Hz), 3.74 (dd, 1H, J ¼ 11.0,
7.0 Hz). 13C NMR (125 MHz, CDCl3) d 147.2, 140.1, 129.2, 128.8, 127.6, 126.7,
117.9, 113.8, 67.4, 59.9.
2-(4-Fluorophenylamino)-2-phenylethanol (3b). 1H NMR (500 MHz,
CDCl3) d 7.34–7.24(m, 5H), 6.81–6.77 (m, 2H), 6.50–6.47 (m, 2H), 4.42 (dd, 1H,
J ¼ 7.0, 4.0 Hz), 3.91 (dd, 1H, J ¼ 11.5, 4.0 Hz), 3.71 (dd, 1H, J ¼ 11.5, 7.0 Hz).
13C NMR (125 MHz, CDCl3) d 156.9, 155.1, 143.6, 139.9, 128.9, 127.7, 126.7,
115.7, 115.5, 114.8, 114.7, 67.3, 60.5.

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2447
2-(4-Chlorophenylamino)-2-phenylethanol (3c). 1H NMR (500 MHz,
CDCl3) d 7.34–7.25 (m, 5H), 7.04–7.02 (m, 2H), 6.48–6.46 (m, 2H), 4.57 (br s,
1H), 4.44 (dd, 1H, J ¼ 6.5, 4.5 Hz), 3.93 (dd, 1H, J ¼ 11.0, 4.0 Hz), 3.74 (dd, 1H,
J ¼ 11.0, 6.5 Hz). 13C NMR (125 MHz, CDCl3) d 145.7, 139.6, 129.0, 128.9, 127.8,
126.7, 122.5, 114.9, 67.3, 59.9.
2-(4-Bromophenylamino)-2-phenylethanol (3d). 1H NMR (500 MHz,
CDCl3) d 7.40–7.22 (m, 5H), 7.14 (d, 2H, J ¼ 9.0 Hz), 6.40 (d, 2H, J ¼ 9.0 Hz),
4.60 (br s, 1H), 4.50 (dd, 1H, J ¼ 7.0, 4.0 Hz), 3.91 (dd, 1H, J ¼ 11.0, 3.0 Hz), 3.74
(dd, 1H, J ¼ 11.0, 6.5 Hz). 13C NMR (125 MHz, CDCl3) d 146.2, 139.6, 131.8,
128.9, 127.8, 126.7, 115.4, 109.5, 67.3, 59.8.
2-(o-Toluidino)-2-phenylethanol (3e). 1H NMR (500 MHz, CDCl3) d
7.33–7.25 (m, 5H), 7.05–7.07 (m, 1H), 6.95–6.92 (m, 1H), 6.41–6.37 (m, 1H),
6.38–6.36 (m, 1H), 7.14 (d, 2H, J ¼ 9.0 Hz), 6.40 (d, 2H, J ¼ 9.0 Hz), 4.53 (dd, 1H,
J ¼ 7.0, 4.0 Hz), 4.39 (br s, 1H), 3.95 (dd, 1H, J ¼ 11.0, 4.0 Hz), 3.78 (dd, 1H,
J ¼ 11.0, 7.0 Hz), 2.27 (s, 3H). 13C NMR (125 MHz, CDCl3) d 145.2, 140.2, 130.1,
128.8, 127.6, 127.0, 126.7, 122.6, 117.5, 111.5, 67.5, 59.8, 17.7.
2-(p-Toluidino)-2-phenylethanol (3f). 1H NMR (500 MHz, CDCl3) d
7.36–7.24 (m, 5H), 6.92–6.89 (m, 2H), 6.50–6.48 (m, 2H), 4.47 (dd, 1H, J ¼ 7.0,
3.6 Hz), 3.93–3.90 (m, 1H), 3.74–3.70 (m, 1H), 2.19 (s, 3H). 13C NMR (125 MHz,
CDCl3) d 144.9, 140.3, 129.7, 128.8, 127.5, 126.7, 117.0, 114.0, 67.4, 60.2, 20.4.
2-(4-Nitrophenylamino)-2-phenylethanol (3g). 1H NMR (500 MHz,
CDCl3) d 7.99–7.97(m, 2H), 7.38–7.29 (m, 5H), 6.48–6.47 (m, 2H), 5.51 (br s, 1H),
4.58 (dd, 1H, J ¼ 10.0, 5.5 Hz), 4.02 (dd, 1H, J ¼ 11.0, 3.0 Hz), 3.84 (dd, 1H,
J ¼ 11.0, 6.0 Hz). 13C NMR (125 MHz, CDCl3) d 152.6, 138.5, 138.4, 129.1, 128.2,
126.6, 126.2, 112.2, 66.9, 59.2.
2-(o-Toluidino)cyclohexanol (3i). 1H NMR (500 MHz, CDCl3) d 7.11 (t,
1H, J ¼ 8.0 Hz), 7.06 (d, 1H, J ¼ 7.5 Hz), 6.77 (d, 1H, J ¼ 8.5 Hz), 6.90 (t, 1H,
J ¼ 7.5 Hz), 3.42 (ddd, 1H, J ¼ 10.0, 9.5, 4.2 Hz), 3.20 (ddd, 1H, J ¼ 11.5, 9.0,
3.8 Hz), 2.74 (br s, 1H), 2.13 (s, 1H), 2.12 (m, 2H), 1.79–1.71 (m, 2H), 1.43–1.37
(m, 1H), 1.35–1.31 (m, 2H), 1.07–1.04 (m, 1H). 13C NMR (125 MHz, CDCl3) d
145.8, 130.4, 127.2, 123.1, 117.9, 74.7, 60.0, 33.2, 31.9, 25.0, 24.3, 17.7.
2-(4-Fluorophenylamino)cyclohexanol (3j). 1H NMR (500 MHz, CDCl3) d
6.90–6.86 (m, 2H), 6.66–6.63 (m, 2H), 3.33 (ddd, 1H, J ¼ 10.0, 9.5, 4.2 Hz), 3.19 (br s,
1H), 3.02 (ddd, 1H, J ¼ 9.5, 9.0, 3.8 Hz), 2.77 (br s, 1H), 2.12–2.07 (m, 2H), 1.79–1.70
(m, 2H), 1.39–1.34 (m, 1H), 1.32–1.27 (m, 2H), 1.04–1.01 (m, 1H). 13C NMR
(125 MHz, CDCl3) d 157.3, 155.4, 144.1, 144.0, 115.8, 115.7, 115.6, 115.6, 74.5,
61.2, 33.2, 31.5, 25.0, 24.2.
2-(4-Chlorophenylamino)cyclohexanol (3k). 1H NMR (500 MHz, CDCl3)
d 7.12–7.09 (m, 2H), 6.63–6.61 (m, 2H), 3.36 (br s, 1H), 3.34 (ddd, 1H, J ¼ 10.0,
9.5, 4.2 Hz), 3.07 (ddd, 1H, J ¼ 10.5, 9.5, 3.8 Hz), 2.62 (br s, 1H), 2.12–2.07 (m,
2H), 1.78–1.70 (m, 2H), 1.40–1.37 (m, 1H), 1.36–1.34 (m, 2H), 1.05–1.02 (m, 1H).
13C NMR (125 MHz, CDCl3) d 146.5, 129.1, 122.8, 115.4, 74.5, 60.4, 33.2, 31.5,
24.9, 24.2.

2448
X. CHEN ET AL.
2-(4-Bromophenylamino)cyclohexanol (3l). 1H NMR (500 MHz, CDCl3)
d 7.24 (d, 2H), 6.58 (d, 2H), 3.38 (br s, 1H), 3.35 (ddd, 1H, J ¼ 9.5, 9.5, 4.2 Hz),
3.08 (ddd, 1H, J ¼ 11.0, 9.5, 4.0 Hz), 2.59 (br s, 1H), 2.11–2.07 (m, 2H), 1.78–1.71
(m, 2H), 1.40–1.37 (m, 1H), 1.34–1.27 (m, 2H), 1.06–1.02 (m, 1H). 13C NMR
(125 MHz, CDCl3) d 146.9, 132.0, 115.9, 109.8, 74.5, 60.2, 33.3, 31.5, 24.9, 24.2.
1-Chloro-3-(phenylamino)propan-2-ol (4m). 1H NMR (500 MHz, CDCl3)
d 7.21–7.18 (m, 2H), 6.75–6.78 (m, 1H), 6.67–6.69 (m, 2H), 4.09–4.06 (m, 1H),
3.68–3.60 (m, 2H), 3.37 (dd, 1H, J ¼ 13.5, 4.2 Hz), 3.22 (dd, 1H, J ¼ 13.0, 7.0 Hz),
3.05 (br s, 1H). 13C NMR (125 MHz, CDCl3) d 147.4, 129.4, 118.6, 113.6, 69.8,
47.7, 47.4.
1-Chloro-3-(4-chlorophenylamino)propan-2-ol (4n). 1H NMR (500 MHz,
CDCl3) d 7.14–7.12 (m, 2H), 6.60–6.58 (m, 2H), 4.09–4.05 (m, 1H), 3.70–3.60 (m,
2H), 3.34 (dd, 1H, J ¼ 13.0, 4.0 Hz), 3.20 (dd, 1H, J ¼ 13.5, 7.0 Hz), 2.87 (br s,
1H). 13C NMR (125 MHz, CDCl3) d 146.2, 129.2, 123.0, 114.5, 69.8, 47.6, 47.2.
1-Chloro-3-(4-fluorophenylamino)propan-2-ol (4o). 1H NMR (500 MHz,
CDCl3) d 6.92–6.88 (m, 2H), 6.65–6.62 (m, 2H), 4.09–4.05 (m, 1H), 3.67–3.59 (m,
2H), 3.55 (br s, 1H), 3.32 (dd, 1H, J ¼ 13.0, 4.0 Hz), 3.17 (dd, 1H, J ¼ 13.0,
7.5 Hz). 13C NMR (125 MHz, CDCl3) d 157.6, 155.7, 143.5, 115.9, 115.8, 114.93,
114.90, 114.87, 114.84, 69.7, 48.3, 47.5.
1-Phenoxy-3-(phenylamino)propan-2-ol (4p). 1H NMR (500 MHz,
CDCl3) d 7.31–7.28 (m, 2H), 7.20–7.17 (m, 2H), 6.99–6.96 (m, 1H), 6.93–6.91 (m,
2H), 6.75–6.72 (m, 1H), 6.69–6.67 (m, 2H), 4.27–4.24 (m, 1H), 4.09–4.02 (m, 2H),
3.43 (dd, 1H, J ¼ 13.0, 4.5 Hz), 3.30 (dd, 1H, J ¼ 13.0, 7.0 Hz). 13C NMR
(125 MHz, CDCl3) d 158.4, 148.1, 129.6, 129.3, 121.4, 118.1, 114.6, 113.3.
Modification and Characterization of the Catalyst
The surface of TiO2 nanoparticles was functionalized by treatment with
hexadecyltrimethoxysilane agent. TiO2 (5 g, 25 nm) was suspended in 15 ml dimethyl
benzene, and 2.0 ml hexadecyltrimethoxysilane was added. After stirring as slurry for
12 h at room temperature, the precipitate was collected by centrifugation at 7000 rpm
and washed with dichloromethane more than five times to remove the extra hexade-
cyltrimethoxysilane.
The organic groups on the surface of the modified nanoparticles were examined
by Fourier transform–infrared (FT-IR) spectroscopy and TG-DTA, and results are
shown in Figs. 2 and 3 respectively. Figure 2 shows the IR spectrum of nano-TiO2
before (a) and after (b) modification with hexadecyltrimethoxysilane agent. The
main characteristic band of Ti-O is in the range of 500–780 cmꢀ1. The absorption
peaks near 2900 cmꢀ1, 1467 cmꢀ1, and 1400 cmꢀ1 are ascribed to CH3- and -CH2-
groups, and the -(CH2)n- vibration peak being near 720 cmꢀ1 may be covered by
Ti-O. The absorption peak at 1060 cmꢀ1 reflects Si-O-Si structure that is produced
by condensation of hexadecyltrimethoxysilane agent. The absorption at 3428 cmꢀ1
results from -OH vibration becoming weaker, which implies some hydroxyl groups
of the nano-TiO2 surface have been reacted.

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2449
Figure 2. FT-IR spectra of (a) bare TiO2 nanoparticles (red curve) and (b) TiO2 nanoparticles modified
with hexadecyltrimethoxysilane (blue curve). (Figure is provided in color online.)
The characterized results indicated that the hexadecyltrimethoxysilane has
been grafted on the surface of nano-TiO2 particles. The TG-DTA profiles of
nano-TiO2 before (a) and after (b) modification with hexadecyltrimethoxysilane
agent are shown in Fig. 3. Little weight loss was both found for bare TiO2 nanopar-
ticles and modified TiO2 below 200 ꢁC, which may be associated with eliminating the
weakly adsorbed water. Two steps of weight loss and corresponding exothermic
peaks were found, which indicates that the surface modifier has been connected
Figure 3. TG-DTA profile of (a) bare TiO2 nanoparticles and (b) TiO2 nanoparticles modified with
hexadecyltrimethoxysilane.

2450
X. CHEN ET AL.
Figure 4. Possible structure of modified TiO2 with hexadecyltrimethoxysilane.
through covalent bonds. Two exothermic peaks of 353 ꢁC and 480 ꢁC seem to imply
that the surface structure of TiO2 may not be a single one, and the probable structure
is shown in Fig. 4.[23]
CONCLUSION
We have demonstrated that nano-sized TiO2 particles can be mild, efficient,
regio- and chemoselective heterogeneous catalysts for the promotion of the reactions
of various epoxides and aromatic amines. This is believed to be due to their surface
property and high surface area. The advantages such as nontoxicity and low cost of
the catalyst, simplicity of operation, mild conditions, recycling of the catalyst, and
no solvent make this method industrially attractive. This finding could open a way
to develop more nano-sized oxides for more organic reactions. Further studies are
currently in progress in our laboratory.
ACKNOWLEDGMENTS
The work was supported in part by grants from NSFZJ (Y4080177, Y4090248,
R4090137), NSFC for Distinguished Young Scholars (51025207), and ZJED
Innovative Team for S. Huang.
REFERENCES
1. (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835–875; (b) Johannes, C.
W.; Visser, M. S.; Weatherhead, G. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120,
8340–8347; (c) Corey, E. J.; Zhang, F. Y. Angew Chem. Int. Ed. 1999, 38, 1931–1934.
2. (a) Kissel, C. L.; Rickborn, B. J. Org. Chem. 1972, 37, 2060–2063; (b) Yamada, J.;
Yumoto, M.; Yamamoto, Y. Tetrahedron Lett. 1989, 30, 4255–4258.
3. (a) Rampalli, S.; Chaudhari, S. S.; Akamanchhi, K. G. Synthesis 2000, 22, 78–80;
(b) Sagawa, S.; Abe, H.; Hase, Y.; Inaba, T. J. Org. Chem. 1999, 64, 4962–4965.

NANO-TiO2: AN EFFICIENT AND REUSABLE CATALYST
2451
4. (a) Fujiwara, M.; Imada, M.; Baba, A.; Matsuda, H. Tetrahedron Lett. 1989, 30, 739–742;
(b) Beaton, M.; Gani, D. Tetrahedron Lett. 1998, 39, 8549–8552; (c) Sekar, G.; Singh, V.
K. J. Org. Chem. 1999, 64, 287–289; (d) Placzek, A. T.; Donelson, J. L.; Trivedi, R.;
Richard, A.; Gibbs, R. A.; De, S. K. Tetrahedron Lett. 2005, 46, 9029–9034; (e) Yadav,
J. S.; Reddy, A. R.; Narsaiah, A. V.; Reddy, B. V. S. J. Mol. Catal. A: Chem. 2007,
´
´
´
261, 207–212; (f) Mancilla, G.; Femenla-Rlos, M.; Maclas-Sanchez, A. J.; Collado, I.
´
G. Tetrahedron 2008, 64, 11732–11737; (g) Procopio, A.; Gaspari, M.; Nardi, M.;
Oliverio, M.; Rosati, O. Tetrahedron Lett. 2008, 49, 2289–2293.
5. (a) Chandrasekhar, S.; Ramachandar, T.; Prakash, J. S. Synthesis 2000, 1817–1818; (b)
Chakraborti, A. K.; Kondaskar, A. Tetrahedron Lett. 2003, 44, 8315–8319; (c) Swamy,
N. R.; Goud, T. V.; Reddy, S. M.; Krishnaiah, P.; Venkateswarlu, Y. Synth. Commun.
2004, 34, 727–734; (d) Pachon, L. D.; Gamez, P., VanBrussel, J. J.; Redijk, J. Tetrahedron
Lett. 2003, 44, 6025–6027; (e) Reddy, L. R.; Reddy, M. A.; Bhanumati, N.; Rao, K. R.
Synthesis 2001, 831–832; (f) McCluskey, A.; Leitch, S. K.; Garner, J.; Caden, C. E. Tetra-
hedron Lett. 2005, 46, 8229–8232.
6. (a) Kotsuki, H.; Hayashida, K.; Shimanouchi, T.; Nishizawa, H. J. Org. Chem. 1996, 61,
984–990; (b) Chakraborti, A. K.; Rudrawar, S.; Kondaskar, A. Org. Biomol. Chem. 2004,
2, 1277–1280; (c) Saikia, L.; Satyarthi, J. K.; Srinivas, D.; Ratnasamy, P. J. Catal. 2007,
252, 148–160; (d) Jitendra, K.; Satyarthi, L.; Srinivas, S. D.; Ratnasamy, P. Appl. Catal.
A: Gen. 2007, 330, 145–151; (e) Chakravarti, R.; Oveisi, H.; Kalita, P.; Pal, R. R.;
Halligudi, S. B.; Kantam, M. L.; Vinu, A. Micropor. and Mesopor. Mat. 2009, 123,
338–344; (f) Heravi, M. M.; Baghernejad, B.; Oskooie, H. A. Catal. Lett. 2009, 130,
547–550; (g) Kureshy, R. I.; Agrawal, S.; Kumar, M.; Khan, N. H.; Abdi, S. H. R.; Bajaj,
H. C. Catal. Lett. 2010, 134, 318–323.
7. Danafar, H.; Yadollahi, B. Catal. Commun. 2009, 10, 842–847.
8. Yadav, J. S.; Reddy, B. V.; Basak, A. K.; Narasaiah, A. V. Tetrahedron Lett. 2003, 44,
1047–1050.
9. Azizi, N.; Saidi, M. R. Org. Lett. 2005, 7, 3649–3651.
10. Das, U.; Crousse, B.; Kesavan, V.; Bonnet-Delpon, D.; Begue, J. P. J. Org. Chem. 2000,
65, 6749–6751.
11. Shi, M.; Chen, Y. J. Fluorine Chem. 2003, 122, 219–227.
12. (a) Saikia, L.; Satyarthi, J. K.; Gonnade, R.; Srinivas, D.; Ratnasamy, P. Catal. Lett.
2008, 123, 24–31; (b) Krishnan, G. R.; Sreekumar, K. Polymer 2008, 49, 5233–5240; (c)
Kamal, A.; Prasad, B. R.; Reddy, A. M.; Naseer, M.; Khan, A. Catal. Commun. 2007,
8, 1876–1880; (d) Mishra, A.; Ali, A.; Upreti, S.; Whittingham, M. S.; Gupta, R. Inorg.
Chem. 2009, 48, 5234–5243; (e) Chimni, S. S.; Bala, N.; Dixit, V. A.; Bharatam, P. V.
Tetrahedron 2010, 66, 3042–3049.
13. Klabunde, K. J.; Mulukutla, R. Nanoscale Materials in Chemistry; Wiley Interscience:
New York, 2001; Chap 7, p. 223.
14. Choudary, B. M.; Kantam, M. L.; Ranganath, K. V. S.; Mahender, K. J. Am. Chem. Soc.
2004, 126, 3396–3397.
15. Choudary, B. M.; Mulukutla, R. S.; Klabunde, K. J. J. Am. Chem. Soc. 2003, 125,
2020–2021.
16. Sarvari, M. H.; Sharghi, H. J. Org. Chem. 2004, 69, 6953–6956.
17. Kantam, M. L.; Kumar, K. B. S.; Sridhar, C. Adv. Synth. Catal. 2005, 347, 1212–214.
18. Su, K. M.; Li, Z. H.; Cheng, B. W.; Liao, K.; Shen, D. X.; Wang, Y. F. J. Mol. Catal. A:
Chem. 2010, 315, 60–68.
19. Yan, X. M.; Mei, P.; Lei, J. H.; Mi, Y. Z.; Xiong, L.; Guo, L. P. J. Mol. Catal. A: Chem.
2009, 304, 52–57.
20. Ohno, T.; Tsubota, T.; Kakiuchi, K.; Miyayama, S.; Sayama, K. J. Mol. Catal. A: Chem.
2006, 245, 47–54.

2452
X. CHEN ET AL.
21. (a) Gandhe, A. R.; Fernandes, J. B.; Varma, S.; Gupta, N. M. J. Mol. Catal. A: Chem.
2005, 238, 63–71; (b) Gandhe, A. R.; Naik, S. P.; Kakodkar, S. B.; Fernandes, J. B. Catal.
Commun. 2006, 7, 285–288.
22. (a) Chen, X. A.; Wu, H. Y.; Su, W. K.; Xu, R.; Liu, M. C.; Ding, J. C. J. Chem. Res.
Synop. 2007, 325–327; (b) Chen, X. A.; Wu, H. Y.; Xu, R.; Liu, M. C.; Ding, J. C.; Su,
W. K. Synth. Commun. 2008, 38(11), 1855–1865; (c) Zhang, C. F.; Chen, J.X.; Yu, X.
C.; Chen, X. A.; Wu, H. Y.; Yu, J. P. Synth. Commun. 2008, 38(11), 1875–1887.
23. Chen, Y. H.; Lin, A.; Gan, F. X. Appl. Surf. Sci. 2006, 252, 8635–8640.