Nanocrystalline titania-based sulfonic acid (TiO2-Pr-SO 3H) as a new, highly efficient and recyclable solid acid catalyst for the N-Boc protection of amines at room temperature

Article abstract of DOI:10.1016/j.jorganchem.2013.07.033

Sulfonic acid-functionalized nanoporous titania (TiO₂-Pr-SO ₃H) was prepared from the reaction of (3-mercaptopropyl) trimethoxysilane and TiO₂, then by oxidation of thiols group with hydrogen peroxide. The morphology and acidity of synthesized catalyst was characterized by FT-IR, SEM, TEM, TGA and XRD techniques and Hammett acidity test. The catalytic performance of TiO₂-Pr-SO₃H was investigated in the N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature. Our novel method is mild, chemoselective and has the advantages such as heterogeneous catalysis, low cost and the recyclability of the catalyst.

Full text of DOI:10.1016/j.jorganchem.2013.07.033

Accepted Manuscript
Nanocrystalline titania-based sulfonic acid (TiO -Pr-SO H) as a new, highly efficient
2
3
and recyclable solid acid catalyst for the N-Boc protection of amines at room
temperature
S.V. Atghia, S. Sarvi Beigbaghlou
PII:
S0022-328X(13)00536-6
10.1016/j.jorganchem.2013.07.033
JOM 18150
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 24 April 2013
Revised Date: 6 July 2013
Accepted Date: 10 July 2013
Please cite this article as: S.V. Atghia , S.S. Beigbaghlou, Nanocrystalline titania-based sulfonic
acid (TiO -Pr-SO H) as a new, highly efficient and recyclable solid acid catalyst for the N-Boc
2
3
protection of amines at room temperature, Journal of Organometallic Chemistry (2013), doi: 10.1016/
j.jorganchem.2013.07.033.
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ACCEPTED MANUSCRIPT
Synopsis
Nanocrystalline titania based sulfonic acid (TiO2-Pr-SO3H) as a new, highly
efficient and recyclable solid acid catalyst for the N-Boc protection of amines
at room temperature
S. V. Atghia*, S. Sarvi Beigbaghlou
Sulfonic acid-functionalized nanoporous titania (TiO2-Pr-SO3H) was prepared from the
reaction of (3-mercaptopropyl) trimethoxysilane and TiO2. The morphology and acidity of
synthesized catalyst was characterized by various techniques and the catalytic performance of
TiO2-Pr-SO3H was investigated in the N-tert-butoxycarbonylation of amines under solvent-free
conditions.

ACCEPTED MANUSCRIPT
OH
OH
OH
O
O Si
O
2
(MeO)3Si
SH
O
i
SH
T
Toluene, reflux, 24 h
O
O
O
1. 10 wt% H2O2, r.t.
2. 1N H2SO4, r.t.
Si
SO3H
Boc
H
N
Boc O,
TiO2-Pr-SO3H
2
N
R1
R2
solvent-free, r.t.
R1
R2
R1 and R2= Alkyl or Aryl

ACCEPTED MANUSCRIPT
Nanocrystalline titania-based sulfonic acid (TiO2-Pr-SO3H) as a new, highly efficient
and recyclable solid acid catalyst for the N-Boc protection of amines at room
temperature
S. V. Atghia*, S. Sarvi Beigbaghlou
Young Researchers Club, Rasht Branch, Islamic Azad University, Rasht, Iran
*Corresponding author: E-mail address: atghia@yahoo.com, Tel: +98 181 4245530
Abstract
Sulfonic acid-functionalized nanoporous titania (TiO2-Pr-SO3H) was prepared from the reaction of (3-
mercaptopropyl) trimethoxysilane and TiO2, then by oxidation of thiols group with hydrogen peroxide. The
morphology and acidity of synthesized catalyst was characterized by FT-IR, SEM, TEM, TGA and XRD
techniques and Hammett acidity test. The catalytic performance of TiO2-Pr-SO3H was investigated in the N-
tert-butoxycarbonylation of amines under solvent-free conditions at room temperature. Our novel method is
mild, chemoselective and has the advantages such as heterogeneous catalysis, low cost and the recyclability
of the catalyst.
Keywords: Heterogeneous catalysis; solid acid, di-tert-butyl dicarbonate (Boc2O); N-Boc protection; TiO2.
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1. Introduction
The development of mild and selective methods for the protection and deprotection of functional groups
continues to be an important tool in the synthetic chemistry of polyfunctional molecules [1]. The presence of
an amino group in various biologically active compounds makes its protection as a necessity during their
synthesis. Among the various amine protecting groups, the tert-butoxycarbonyl (Boc) is one of the most
used, owing to its stability towards nucleophiles and strong basic conditions and because of its easy removal
[1]. Various reagents and procedures have been employed over the years to introduce this group using di-
tert-butyl dicarbonate (Boc2O). The conventional procedure employs (Boc)2O and base catalysts such as
DMAP [2, 3], NaHMDS [4], K2CO3 [5], and Et3N [6], the last one being most commonly used. However the
unpleasant smell, high toxicity, requirement in large excess, and non-recyclability of these catalysts makes
the method objectionable, especially from the standpoint of green chemistry.
Lately acid-catalyzed N-Boc protection of amines has been widely studied with many homogeneous as
well as heterogeneous catalysts. Many of these procedures involve I2 [7], yttria-zirconia [8], ZrCl4 [9],
Zn(ClO4)2.6H2O [10], LiClO4 [11], Cu(BF4)2 [12], La(NO3)3 [13], montmorillonite clays [14, 15], sulfonic
acid functionalized silica [16], H3PW12O40 [17], thioglycoluril [18], thiourea [19], sulfamic acid [20],
HClO4-SiO2 [21], saccharin sulfonic acid [22], ionic liquids [23, 24] and catalyst free conditions [25].
These procedures, although effective, have various drawbacks such as requirement of long reaction times,
use of solvent, potential hazards (e.g., perchlorates are strong oxidizers and explosive in nature [26, 27] and
ZrCl4 is highly moisture sensitive, decomposes on storing and liberates corrosive HCl fumes), difficulty in
preparation of catalyst (e.g., preparation of yttria-zirconia involves use of sulfuric acid at 500 °C) and
formation of side-products such as isocyanates [28, 29], poly-acylated products [30], urea [31] and N,N-di-
Boc derivatives [31, 32].
In recent years, there has been considerable growth of interest in the catalysis of organic reactions by
solid acid catalysts. Solid acid catalysts provide numerous opportunities for recovering and recycling
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catalysts from reaction environments [33]. These features can lead to improved processing steps, better
process economics, and environmentally friendly industrial manufacturing. In general, metal oxides have
been used extensively either as such or as supports in conjunction with other active components for many
industrial oxidation, reduction and acid–base catalyzed reaction. Among the semiconductor oxides TiO2 due
to its low cost and long term stability has been widely used as solid acid catalyst in organic transformations;
such as chemoselective trimethylsilylation of alcohols and phenols [34], Friedel–Crafts alkylation of indoles
[35], synthesis of bis(indolyl) methanes [36], Mannich synthesis of β-aminocarbonyls [37] and esterification
of free fatty acids [38].
However traditional heterogeneous catalysts have many limitations in the nature of their active sites. For
example nanoparticles of TiO2 only can catalyze the reactions with their low Lewis acidic properties
therefore modification of these nanoparticles very attended by chemists [39-42].
With this in mind, in the present study, the synthesis of chemically adsorbed sulfonic acid on TiO2
(TiO2-Pr-SO3H) by the reaction of (3-mercaptopropyl) trimethoxysilane and TiO2, and oxidation of thiols
group with H2O2 is reported. The characterization of TiO2-Pr-SO3H was performed by means of various
techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning
electron microscopy (SEM), transmition electron microscopy (TEM) and thermogravimetric analysis (TGA).
The acidic property of the synthesized catalyst was evaluated by the calculation of Hammett acidity function
[43]. The assessment of the catalyst was carried out in the N-tert-butoxycarbonylation of amines under
solvent-free conditions at room temperature (Scheme 1).
2. Experimental
2.1. Materials
Chemicals were purchased from Fluka, Merck, and Aldrich chemical companies. All yields refer to the
isolated products. Products were characterized by their physical constants and comparison with authentic
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samples. The purity determination of the substrate and reaction monitoring were accompanied by thin-layer
chromatography (TLC) on silica-gel polygram SILG-UV 254 plates.
2.2. Instrumention
Thermogravimetric analyses were conducted using a TGA PYRIS 1 thermoanalyzer instrument
(PerkinElmer Instruments, Waltham, MA, USA). Samples were heated from 25 °C to 600 °C at ramp
10°C/min under N2 atmosphere. Wide-angle XRD measurements were performed at room temperature on a
Siemens D-500 X-ray diffractometer (Munich, Germany), using Ni-filtered Cu-Kα radiation (λ=0.15418
nm). IR and FT-IR spectra were obtained in KBr wafers on Shimadzu IR-470 (Kyoto, Japan) and Perkin
Elmer RX1 (Waltham, MA, USA) spectrophotometers respectively. TEM analysis was performed on a
Philips model CM 10 (FEI Co., Hillsboro, OR, USA) instrument. Sample was prepared by sonicating a small
amount of powder in methanol, and then placing a drop of the mixture on a 3-mm TEM Cu grid having a
lacey carbon support film. Scanning election microphotographs were obtained on a LEO 1430VP
instrument. The absorption spectra in the UV-visible regions were recorded by a Perkin Elmer LAMBDA 25
1
recording spectrophotometer. H and 13C NMR spectra were measured in CDCl3 with a Brucker DRX-
400AVANCE (Karlsruhe, Germany) spectrometer at 400 and 100 MHz, respectively.
2.3. Catalyst preparation
2.3.1. Synthesis of 3-mercaptopropyltitania
To 20 g of TiO2 (anatase, from Sigma-Aldrich) in dry toluene, 25 mL of (3-mercaptopropyl)
trimethoxysilane was added, and the reaction mixture was refluxed for 24 h. After this period, the mixture
was filtered to obtain 3-mercaptopropyltitania (MPT), which was washed with acetone and dried.
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2.3.2. Oxidation of 3-mercaptopropyltitania (MPT)
MPT was oxidized with 10 wt. % H2O2 in methanol (20 mL) for 24 h at room temperature. The prepared
sample was then treated with 1 N H2SO4 at ambient temperature for complete protonation, and then the
mixture was filtered and washed with H2O, and acetone to obtain TiO2-Pr-SO3H catalyst (Scheme 2).
2.4. Catalyst characterizations
2.4.1. FT-IR analysis
FT-IR spectra for the pure TiO2 and TiO2-Pr-SO3H samples are shown in Fig. 1. In the case of TiO2,
the peaks at 3446 and 1773 cm−1 correspond to the ─OH stretching and bending vibrations of the adsorbed
water respectively. The spectrum of functionalized TiO2 by sulfonic acid displays almost the same pattern as
that of pristine TiO2, but the band at 3000 to 3600 cm-1 that centered in 3444 cm-1 is flattened in sulfonated
TiO2 which can be attributed to the modification of TiO2. CH stretching vibrations of silylating agent was
observed at 2963 and 2908 cm-1, and the bands at 1040 and 914 cm−1 can be collectively attributed to Si–O
stretching vibrations. Furthermore the peak corresponding to 1375 cm−1 is the stretching frequency of S=O
in SO3H. Also, the band around 2357 cm−1 in TiO2 is attributed to ambient CO2, which probably aggregation
of TiO2 nanoparticles in TiO2-Pr-SO3H is leaded to eliminate of this peak (see SEM images).
2.4.2. Wide-angle X-ray diffraction
XRD patterns of TiO2 and TiO2–Pr–SO3H are given in Fig. 2. XRD patterns clearly show anatase lines. It
seems the peak intensities of TiO2 and TiO2–Pr–SO3H are almost same as those of TiO2, and the sulfate
modification does not change the phase of TiO2. The average crystallite sizes of TiO2 and TiO2–Pr–SO3H,
determined using Debye–Scherrer equation, are 15.3 and 20 nm, respectively, which demonstrated that
sulfate modification increases the size of TiO2.
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2.4.3. SEM analysis
The representative SEM images of TiO2 and TiO2–Pr–SO3H are shown in Fig. 3a,b,c,d with ×30000 and
50000 magnifications. All of the SEM images exhibit a cloud-like structure and small spherical-shaped
particles. In TiO2–Pr–SO3H, aggregation of TiO2 nanoparticles was clearly seen. However, the SEM
micrographs of the catalyst show some modifications with respect to TiO2 such that the primary surface
structure of TiO2 has changed.
2.4.4. TEM analysis
TEM images of TiO2–Pr–SO3H are shown in Fig. 4. TiO2–Pr–SO3H particles are seen in different sizes
ranging from 20 to 100 nm, and the average crystallite sizes of TiO2–Pr–SO3H, determined using XRD, was
20 nm. As can be seen in Fig. 4, the particles are slightly corroded in the modification path. This is indicated
in the figure by the arrow.
2.4.5. Thermal analysis
TGA was performed for the characterization of TiO2-Pr-SO3H in comparable with TiO2 (Fig. 5). The
TGA curve of TiO2 display a weight loss (4 wt.%) below 100 °C which corresponds to the loss of the
physically adsorbed water. Also, there is a slight weight loss (3 wt.%) in the range of 100 °C to 600 °C,
which possibly corresponds the to dehydroxylation of TiO2.
TGA of catalyst shows an initial weight loss (4 wt.%) due to the desorption of water below 100 ºC. This
is followed by a second weight loss that started at 245 ºC, corresponding to the loss of the covalently bound
organic group. From this weight loss, it is calculated that the loading of the organic group bound to the
titania surface was 2.52 mmol g-1. Also from the TGA, we understood that TiO2-Pr-SO3H has a greater
thermal stability (until 245 °C) relative to TiO2 [44].
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2.4.6 Surface Acidity studies
The Hammett acidity function (H0) can effectively express the acidity strength of an acid in organic
solvents, [45-47]. It can be calculated using the following equation:
H0 = pK(I)aq + log([I]s /[IH+]s)
Here, ‘I’ represents the indicator base (mainly substituted dinitroanilines), and [IH+]s and [I]s are
respectively the molar concentrations of the protonated and unprotonated forms of the indicator. The pK(I)aq
values are already known (for example the pK(I)aq value of 4-nitroaniline is 0.99) and can be obtained from
many references. According to the Lambert–Beer’s Law, the value of [I]s/[IH+]s can be determined and
calculated using the UV–visible spectrum.
In our experiment, 4-nitroaniline was chosen as the basic indicator and CCl4 was chosen as the solvent
because it is aprotic. The maximal absorbance of the unprotonated form of 4-nitroaniline was observed at
329 nm in CCl4. As Fig. 6 shows, the absorbance of the unprotonated form of the indicator in TiO2-Pr-SO3H
was weak as compared to the sample of the indicator in CCl4, which indicated that the indicator was partially
in the form as [IH+]. The results obtained are listed in Table 1, which shows the acidity strength of TiO2-Pr-
SO3H.
2.5. General procedure for synthesis of N-tert-butylcarbamates
An amine (1 mmol) was added to a magnetically stirred mixture of TiO2-Pr-SO3H (10 mg) and di-tert-
butyl dicarbonate (240 mg, 1.1 mmol) at room temperature. The mixture was stirred until completion of the
reaction (TLC), then diluted with EtOAc (10 mL) and filtered. The residue contains only the catalyst and
kept for recovery. The filtrate was washed with water (3×20 mL) and brine (2×20 mL) and dried over
anhydrous MgSO4, then solvent was distillated off under vacuum to yield the highly pure N-Boc derivative.
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2.6. Selected spectral data
2.6.1. tert-Butyl 3-phenylpropylcarbamate: Colorless oil; IR (KBr): ν = 3390, 2988, 2930, 1686, 1610, 1508,
1
1358, 1317, 1289, 1258, 1170, 998, 855 cm-1; H NMR (CDCl3, 400 MHz): δ = 1.50 (s, 9H), 1.83 (qin, J
=7.2, 7.6 Hz, 2H), 2.67 (dd, J= 7.6 and 8.0, 2H), 3.18 (d, J= 6.0 Hz, 2H), 4.74 (s, 1H, N-H), 7.22 (dd, J= 5.6
13
and 7.6 Hz, 3H), 7.32 (d, J= 8.0 Hz, 2H) ppm; C NMR (CDCl3, 100 MHz): δ = 28.5, 31.8, 33.2, 40.3,
125.9, 128.40, 128.44, 141.6, 156.1 ppm.
2.6.2. tert-butyl 4-methylbenzylcarbamate: Off-White solid; m.p. 72-73 oC; IR (KBr): ν = 3395, 2980, 2920,
1680, 1600, 1508, 1360, 1320, 1295, 1260, 1172, 1000, 858, 761, 694 cm-1; 1H NMR (CDCl3, 400 MHz): δ
= 1.50 (s, 9H), 2.36 (s, 3H), 4.30 (d, J= 5.2, 2H), 4.88 (br s, 1H), 7.16 (d, J= 7.6 Hz, 2H), 7.20 (d, J= 8.0 Hz,
2H) ppm; 13C NMR (CDCl3, 100 MHz): δ = 21.1, 28.4, 44.5, 79.4, 127.5, 129.3, 135.9, 137.0, 155.9 ppm.
2.6.3. tert-butyl cyclohexylcarbamate: Colorless solid; m.p. 65-67°C; IR (CCl4) ν = 3364, 2973, 2934, 2854,
1
1681, 1520 1448, 1366, 1315, 1251, 1233, 1168 cm-1; H NMR (CDCl3, 400 MHz) δ 1.04-1.15 (m, 3H),
1.26-1.34 (m, 2H), 1.44 (s, 9H), 1.57- 1.71 (m, 3H), 1.90-1.93 (m, 2H), 3.43 (bs, 1H), 4.43 (bs, 1H) ppm.
2.6.4. tert-butyl 3-methoxyphenylcarbamate: Brown solid, m.p. 52-54 °C; IR (KBr): ν = 3320, 2990, 2920,
1
1690, 1600, 1530, 1450, 1420, 1362, 1285, 1240, 1160, 1045, 1032, 960, 870, 842 cm-1; H NMR (CDCl3,
400 MHz): δ 1.55 (s, 9H), 3.82 (s, 3H), 6.61 (dd, J=8.0 and 8.4 Hz, 1H), 6.64 (br s, 1H), 6.87 (d, J= 8.0 Hz,
13
1H), 7.14 (s, 1H), 9.19 (dd, J= 8.0 and 8.4 Hz, 1H) ppm; C NMR (CDCl3, 100 MHz): δ 28.4, 55.3, 80.5,
104.1, 108.9, 110.7, 129.7, 139.7, 152.7, 160.3 ppm.
o
2.6.5. tert-butyl- 2-(phenylamino)ethylcarbamate: White solid; m.p. 80-82 C; IR (KBr): ν = 3414, 3395,
1
2980, 2920, 1680, 1600, 1508, 1360, 1320, 1295, 1260, 1172, 1000, 858, 761, 694 cm-1; H NMR (CDCl3,
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400 MHz): δ = 1.50 (s, 9H), 3.28 (t, J= 5.6 Hz, 2H), 3.39 (m, 2H), 4.02 (br s, 1H), 4.90 (br s, 1H), 6.64 (d,
J= 8.0 Hz, 2H), 6.74 (dd, J= 7.2 and 7.6 Hz, 1H), 7.21 (dd, J= 7.6 and 8.0 Hz, 2H) ppm; 13C NMR (CDCl3,
100 MHz): δ = 28.4, 40.11, 44.37, 79.58, 112.76, 117.54, 129.34, 148.06, 156.47 ppm.
3. Results and discussion
In order to optimize the reaction conditions, we conducted the N-Boc protection of benzyl amine with
Boc2O in the presence of various amount of TiO2-Pr-SO3H with stirring at ambient temperature without
solvent, and the results are summarized in Table 2. It is clear that, the reaction can be carried out in the
presence of catalytic amount of TiO2-Pr-SO3H and the yields are excellent, it was found that the reaction is
not accomplish without the catalyst. It is notable that, this reaction carried out in the presence of bare TiO2
too, and tert-butyl benzylcarbamate obtained after 60 min with 45% yield. This demonstrated that the
modification of TiO2 for promotion of this reaction is necessary.
After these preliminary experiments, catalytic amount of TiO2-Pr-SO3H (10 mg) was used for N-tert-
butoxycarbonylation of various aliphatic, aromatic and heterocyclic amines and aminols. The results are
summarized in Table 3.
Aliphatic amines (Table 3; entries 1- 11) gave the corresponding N-Boc products in 89–98% yields. It is
notable that, 2-cyclohexenylethanamine (Table 3, entry 6), was protected rapidly without the isomerization
of double bond. Aromatic amines having various substituents such as Br, Me, Et and OMe groups were
converted to their N-tert-Boc derivatives efficiently (entries 12–21). Amino groups attached aromatic
heterocycle (entry 21) afforded the desired products in quantitative yields. The reaction conditions were mild
enough so that the acid sensitive moieties such methoxy group maintained intact under the reaction
conditions (entries 2, 3 and 16). Also amines with two adjacent amino groups successfully protected (entries
11, 18). No isocyanate or urea formation was observed at all (IR and NMR). Under the selected conditions
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N-Boc protection of alcohols, phenols and thiols was not successful and the starting material was recovered
unchanged after 2 h (Table 3, entries 22-27).
The selectivity of a method determines the importance of its application in organic reactions. Therefore,
the chemoselectivity of this method was also investigated and the results are reported in Table 4.
After performing one reaction under the conditions described in Table 3, the catalyst was recovered by
filtration, washed with acetone and dried at 100 °C for 1 h and then reused for more 14 consecutive run
under the same reaction conditions (Fig. 7). This reusability demonstrates the high stability and turnover of
titania-based sulfonic acid (TiO2-Pr-SO3H) under the conditions employed. It should be noted that, the
recyclability test was stopped after 15 runs.
The possible mechanism for the N-Boc protection of various amines in the presence of TiO2-Pr-SO3H as
a promoter is shown in Scheme 3. On the basis of this mechanism, TiO2-Pr-SO3H catalyzes the reaction by
the electrophilic activation of (Boc)2O to form a zwitterionic species, making the carbonyl group susceptible
to nucleophilic attack by the amine. Successive elimination of CO2 and tert-BuOH results in the formation of
N-Boc derivatives and regenerates TiO2-Pr-SO3H in the reaction mixture.
To illustrate the efficiency of the present method, Table 5 compares our result in N-Boc protection of
aniline with the same result reported by the relevant reagents in the literature.
4. Conclusion
In conclusion, we have developed a simple, efficient and chemoselective protocol for the N-tert-
butoxycarbonylation of various amines using TiO2-Pr-SO3H as a novel heterogeneous catalyst. The protocol
is a highly chemoselective offering potential in different applications. The methodology also has several
other advantages such as: (i) high reaction rates and excellent yields (ii) no side reactions (iii) ease of
preparation and handling of the catalyst (iv) cost efficiency and effective reusability of the catalyst (v)
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simple experimental procedure and solvent-free conditions. Further work to explore this novel catalyst in
other organic transformations is in progress.
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Scheme, figure and table captions
Scheme 1. N-Boc protection of amines.
Scheme 2. Preparation of nanoporous titania-based sulfonic acid (TiO2-Pr-SO3H).
Scheme 3. Proposed mechanism.
Fig. 1. FT-IR spectra of TiO2 and TiO2–Pr–SO3H.
Fig. 2. XRD patterns of TiO2 and TiO2–Pr–SO3H.
Fig. 3. SEM images of TiO2 and TiO2-Pr-SO3H. TiO2 (a) ×30000 and (b) ×50000 magnifications and TiO2-
Pr-SO3H(c) ×30000 and (d) ×50000 magnifications.
Fig. 4. TEM images of TiO2–Pr–SO3H ( = corroded).
Fig. 5. TGA curves of TiO2 and TiO2-Pr-SO3H.
Fig. 6. Absorption spectra of 4-nitroaniline (indicator; curve A) and TiO2-Pr-SO3H (catalyst; curve B) in
CCl4.
Fig. 7. Reusability of the catalyst.
Table 1. Calculation of Hammett acidity function (H0) of TiO2-Pr-SO3H.
Table 2. Reaction of benzyl amine and Boc2O in the presence of different amount of TiO2-Pr-SO3H at room
temperature under solvent-free conditions.a
Table 3. N-Boc protection of amines in the presence of TiO2-Pr-SO3H under solvent-free conditions.
Table 4. Chemoselective N-Boc protection.
Table 5. Compared catalytic performance of TiO2-Pr-SO3H with some of the various catalysts in the N-Boc
protection of aniline.
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Boc
N
H
N
Boc O,
TiO2-Pr-SO3H
2
R1
R2
solvent-free, r.t.
R1
R2
R1 and R2= Alkyl or Aryl
Scheme 1.
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OH
OH
OH
O
O Si
O
2
(MeO)3Si
Toluene, reflux, 24 h
SH
O
O
i
i
SH
T
T
O
O Si
O
2
1. 10 wt% H2O2, r.t.
2. 1N H2SO4, r.t.
O
i
SO3H
T
Scheme 2.
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TiO2
RNH2
H
O
O
O
H N
TiO2
O
O
H
R
H
O
CO2
O
O
O
O
H
N
O
R
O
OH
O
Si O
O
2
Boc2O
O
HO3S
i
T
Scheme 3.
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Fig. 1.
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TiO2
TiO2-Pr-SO3H
10
20
30
40
50
60
70
80
2-Theta- Scale
Fig. 2.
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Fig. 3.
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Fig. 4.
21

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TiO2
TiO2-Pr-SO3H
100
95
90
85
80
75
70
65
60
55
50
25
100
175
250
325
400
475
550
Temprature (°C)
Fig. 5.
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2.8
2.3
1.8
1.3
0.8
0.3
-0.2
(A)
(B)
250
300
350
400
450
Wavelength (nm)
Fig. 6.
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Time (min) Yield (%)
98
97
98 95
96
93
94
96
95 93
94
96
97
92
95
100
80
60
40
20
0
28
27 28
25
26 27
25
25
25
25
25 25 25 25
25
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15
Run
Fig. 7.
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Table 1.
Entry
Catalyst
—
Amax
[I]s (%)
100
[IH+]s (%)
H0
—
1
2
2.4113
1.1862
0
TiO2-Pr-SO3H
49.19
50.80
0.98
Condition for UV–visible spectrum measurement: solvent, CCl4; indicator, 4-nitroaniline (pK(I)aq = 0.99),
1.44× 10-4 mol/L; catalyst, TiO2-HClO4, 20 mg, 25 °C.
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Table 2.
Entry
Amount of catalyst (mg)
Time (min)
Yield (%)b
1
2
3
4
5
—
5
1h
35
20
20
20
75
87
95
94
96
10
15
20
a Reaction conditions: benzyl alcohol, 1 mmol; Boc2O, 1.1 mmol.
b Isolated yield.
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Table 3.
Entry
Substrate
Product
Time (min)
Yielda,b (%)
NH2
NHBoc
1
2
18
91
NH2
NH2
NHBoc
15
98
H3CO
H3CO
OCH3
OCH3
NHBoc
3
4
5
6
16
20
22
10
96
95
90
93
H3CO
H3CO
NH2
NHBoc
NH2
NHBoc
H3C
H3C
NH2
NHBoc
NHBoc
NH2
NH2
7
8
9
8
94
89
91
NHBoc
HO
12
30
HO
N
N
H
Boc
NH2
NH2
NHBoc
NHBoc
11
18
91c
NH2
NHBoc
12
13
25
35
98
89
Br
NH2
Br
Et
NHBoc
NH2
Me
NHBoc
Me
14
15
45
30
91
94
Et
NH2
NHBoc
27