Nano Fe3O4@ZrO2/SO42?: A highly efficient catalyst for the protection and deprotection of hydroxyl groups using HMDS under solvent-free condition

Article abstract of DOI:10.1080/10426507.2016.1236104

In this work, we introduce a new procedure for the protection and deprotection process of various types of alcohols and phenols by HMDS in the presence of nano magnetic sulfated zirconia (Fe₃O₄@ZrO₂/SO₄^2?) as a solid acid catalyst under very mild and solvent-free condition. This method has interesting advantages like short reaction times and a simple workup process. With regard to some outstanding benefits of this new heterogeneous catalyst such as excellent yield, reusability of the catalyst and easy thermal stability, high acidity, strong and excellent magnetic properties, this method can be very interesting in aspect of green chemistry Principles.

Full text of DOI:10.1080/10426507.2016.1236104

ACCEPTED MANUSCRIPT
Nano Fe3O4@ZrO2/SO42: A highly efficient catalyst for the protection and deprotection of
hydroxyl groups using HMDS under solvent-free condition
Hossein Ghafuri*a, Fatemeh Paravand a and Afsaneh Rashidizadeh a
a Catalyst and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University
of Science and Technology (IUST), Narmak, Tehran 16846-13114, Iran E-mail: ghafuri@iust.ac.ir
Nano Fe3O4@ZrO2/SO42: A highly efficient catalyst for the protection and deprotection of
hydroxyl groups using HMDS under solvent-free condition
ABSTRACT
In this work, we introduce a new procedure for the protection and deprotection process of
various types of alcohols and phenols by HMDS in the presence of nano magnetic sulfated
2
zirconia (Fe3O4@ZrO2/SO4 ) as a solid acid catalyst under very mild and solvent-free
condition. This method has interesting advantages like short reaction times and a simple
workup process. With regard to some outstanding benefits of this new heterogeneous
catalyst such as excellent yield, reusability of the catalyst and easy thermal stability, high
acidity, strong and excellent magnetic properties, this method can be very interesting in
aspect of green chemistry Principles.
ACCEPTED MANUSCRIPT
1

ACCEPTED MANUSCRIPT
KEYWORDS
2
Magnetic nanocatalyst; Fe3O4@ZrO2/SO4 ; trimethylsilyl ethers; HMDS; solvent-free
condition
Introduction
Protection and deprotection of functional groups are indispensable processes in multi-step
syntheses of complex organic molecules.1 Protections of hydroxyl groups have received attention
in recent years because of their role in synthetic organic and analytical chemistry.2-4 Conversion
of alcohols to their corresponding silylethers is one of the most popular and widely used
strategies for protecting the hydroxyl groups.5 1,1,1,3,3,3-hexamethyldisilazane (HMDS) has
emerged as the most versatile reagent in recent years, for the trimethylsilyl (TMS) protection of
alcohols and phenols. HMDS is a stable, commercially available and inexpensive compound. Its
handling does not require special precautions and the workup is convenient because the only by
product of the reaction is ammonia which is easily removed from the reaction medium.6
However, the low silylation power of HMDS is the main drawback to its application,7 therefore
several catalytic system have been developed to activate this reagent, such as (CH3)3SiCl, I2, K-
10 montmorillionite, ZnCl2, Lithium perchlorate supported on silica gel, Silica sulfuric acid.7-17
Some of these protocols suffer from several aspects such as the use of expensive reagents, longer
reaction times, harsh reaction conditions, tedious experimental procedures. Therefore, the
development of simple, efficient, clean, high yielding and environmentally friendly approaches,
using new catalysts for the protection of hydroxyl groups is an important task for organic
chemists.
ACCEPTED MANUSCRIPT
2

ACCEPTED MANUSCRIPT
Deprotection of trimethylsilyl ethers to their corresponding hydroxyl compounds under
mild condition is interesting for reactions in organic synthesis, and a wide variety of catalysts
have been already reported for these conversions. Recently, to improve these reactions, many
21
catalysts such as BF3·Et2O-CHCl3,18 aqueous acid,19 TiO2-HClO4,20 silica sulfuric acid,
9
22
montmorillonite K-10 and silica chloride
have been developed. Despite of all reported
studies, some of these methods suffer from one or more disadvantages like formation of large
amounts of by-products, low yield of the products, hard workup, high cost or toxicity of the
reagent and non-recyclability of the catalysts. Therefore, to overcome these drawbacks,
enhancement of heterogeneous catalysts for the deprotection of trimethylsilyl ethers represents
an attractive research task in organic chemistry.
In continuation of our research on one-pot multicomponent reactions,23, 24 we have
2
recently reported the synthesis of nano magnetic sulfated zirconia Fe3O4@ZrO2/SO4 and its
application in the Strecker reaction as the first multicomponent reaction.25, 26 Herein, we wish to
report the application of Fe3O4@ZrO2/SO42 as an efficient catalyst for the silylation of hydroxyl
groups under solvent-free condition at room temperature (see Scheme 1).
2-
Fe3O4@ZrO2/SO4
H
N
R OH +
R OSiMe3
Me3Si
SiMe3
r.t, Solvent-free
2
Scheme 1: O-Silylation of alcohols catalysed by Fe3O4@ZrO2/SO4 .
Results and discussion
ACCEPTED MANUSCRIPT
3

ACCEPTED MANUSCRIPT
Nano magnetic sulfated zirconia was prepared through the method that we have reported recently
(for more details please see supporting information) 25, 26. The catalytic applicability of nano
2
magnetic sulfated zirconia Fe3O4@ZrO2/SO4 in activation of HMDS for the protection of
benzyl alcohol under solvent-free condition at room temperature was examined as a model
2
reaction. To demonstrate the effect of the solid acid catalyst Fe3O4@ZrO2/SO4 , the reaction of
HMDS and benzyl alcohol was examined in the absence of catalyst. However, this reaction
remained incomplete and only 10% of the desired product was obtained after 120 min. Also, we
evaluated the different amount of catalyst in this model reaction. When 80.0 mg of
2
Fe3O4@ZrO2/SO4 was used the reaction went to completion in 15 min, and 90% of product
2
was isolated (Table 1). In order to ensure the efficiency of Fe3O4@ZrO2/SO4 in the protection
reaction, we also investigated the treatment of other types of alcohols in the absence of catalyst,
such as phenol, diphenylmethanol, naphthalen-2-ol and 2-methylbutan-2-ol. It seems that these
2
reactions were not completed in the absence of the Fe3O4@ZrO2/SO4 . Therefore, these
conditions were applied to the trimethylsilylation of other types of hydroxyl groups. The data in
Table 2 clearly show that other types of alcohols, such as acid sensitive alcohols, as well as
phenols and substituted phenols can be successfully converted to the corresponding
trimethylsilyl ethers under these conditions (entries 9-17, Table 2).
[Insert Table 1]
[Insert Table 2]
O-Silylation of various primary alcohols including derivatives of benzyl alcohols with
electron-donating or electron-withdrawing groups proceeds efficiently with notable isolated yield
ACCEPTED MANUSCRIPT
4

ACCEPTED MANUSCRIPT
(entries 1-8, Table 2). We extended our methodology to hindered secondary and tertiary
alcohols. In the case of tertiary alcohols, the yield of TMS ethers was rather lower and longer
reaction times were required than for less sterically hindered substrates. It should be noted that in
the case of hindered tertiary alcohols, no elimination by-products were observed at all. Also, in
the presence of an amino group, only the hydroxyl group reacts with HMDS to form the
corresponding silylated product (entries 15, 16, Table 2). In the case of diols and
dihydroxyarenes, only bis-silylated diols were formed (entries 5, 17, Table 2).
We also investigated the deprotection of corresponding silylethers in the presence of
2
Fe3O4@ZrO2/SO4 under solvent-free condition at room temperature (Table 3). The removal of
the protective group can be carried out under mild reaction conditions as easily as the related
protection process. The results have indicated the convenient efficiency of synthesized nano
magnetic as catalyst in this reaction. Regarding to the structure of this catalyst, it exhibits both
Brønsted and Lewis acid sites which can cause to improve the reaction. In general, benzylic
trimethylsilyl ethers have shorter reaction times in comparison to phenolic trimethylsilyl ethers,
and also for trimethylsilyl ethers substituted with electron-withdrawing groups decreased
2
reaction rates are observed (Table 3). Table 4 shows the efficiency of Fe3O4@ZrO2/SO4 in
comparison with results reported in the literature. Short reaction time, solvent-free condition and
simple recovery make our system better choice.
[Insert Table 3]
[Insert Table 4]
The recovery and reusability of the catalyst was investigated in the silylation of benzyl
ACCEPTED MANUSCRIPT
5

ACCEPTED MANUSCRIPT
alcohol with HMDS. After completing the reaction, the catalyst was easily separated by an
external magnet, washed with ethanol and dried at room temperature and used directly for the
next reaction. The isolated catalyst was reused for 5 runs without observable loss of its catalytic
activity (Figure 1). This catalyst exhibits excellent selectivity in this reaction and can be used for
the protection of OH groups in competition with NH2 and COOH (Scheme 2). The suggested
mechanism for the reaction is shown in Scheme 3.
[Insert Scheme 2]
[Insert Scheme 3]
[Insert Figure 1]
Conclusion
2
In conclusion, Fe3O4@ZrO2/SO4 is found to be an efficient novel, heterogeneous catalyst for
the selective silylation of various hydroxyl groups with HMDS under solvent-free condition.
This method offers several advantages including high yields, short reaction times, easy workup
procedure, reusability of catalyst and environmentally benign reaction conditions.
Experimental
Chemicals and Instruments
All chemicals used, such as iron(III) chloride, iron(II) chloride, zirconium(IV) chloride,
ammonium sulfate, alcohols, HMDS and solvents were supplied by Merck and Aldrich chemical
companies. FT-IR spectra were obtained over the region 400-4000 cm1 with a Nicolet IR 100
1
FT-IR instrument by use of spectroscopic grade KBr. H NMR spectra were recorded using a
ACCEPTED MANUSCRIPT
6

ACCEPTED MANUSCRIPT
Avance Bruker DRX-500 spectrometer at 500 MHz in CDCl3 as solvent. The powder X-ray
diffraction pattern was recorded using a X-PERT-PRO diffractometer with CuKα, (λ = 1.54 Å)
irradiation, in the range of 5 to 80 (2θ) with a scan step of 0.026. The morphology of the catalyst
was studied with scanning electron microscopy using SEM (KYKY, EM 3200) on gold coated
2
samples. The magnetic properties of Fe3O4@ZrO2/SO4 nanoparticles were measured with a
Vibrating Magnetometer/ Alternating Gradient Force Magnetometer (VSM/, MDKFD). The
2
BET surface area and pore volume of Fe3O4@ZrO2/SO4 was determined with a Micromeritics
ASAP 2020 apparatus using nitrogen as the analysis gas. The Supplemental Materials presented
additional characterization information for the catalyst (Figures S 1 – S 7).
General procedure for the protection of hydroxyl groups using HMDS
2
To a mixture of alcohols (1.0 mmol) and HMDS (1.5 mmol) was added Fe3O4@ZrO2/SO4
(80.0 mg) and the mixture was stirred at room temperature for an appropriate time (Table 2).
After completion of the reaction, as indicated by thin-layer chromatography (TLC), the catalyst
was separated by an external magnet and the products were obtained by evaporation of the
volatile portion under reduced pressure. All compounds are known and were characterized on the
1
basis of their spectroscopic data (IR, H NMR) and by comparison with those reported in the
literature.
General procedure for the deprotection of trimethylsilyl ethers (removal of TMS groups)
2
using Fe3O4@ZrO2/SO4
To a mixture of trimethylsilyl ether (1.0 mmol), 80.0 mg Fe3O4@ZrO2/SO42 was added and the
ACCEPTED MANUSCRIPT
7

ACCEPTED MANUSCRIPT
mixture was stirred at room temperature for an appropriate time (Table 3). After completion of
the reaction, as indicated by thin-layer chromatography (TLC), 10.0 mL CCl4 was added to the
reaction mixture, the catalyst was separated by an external magnet, and the product was obtained
by evaporation of the volatile portion under reduced pressure. All compounds are known and
1
were characterized on the basis of their spectroscopic data (IR, H NMR) and by comparison
with those reported in the literature.
Spectroscopic data of representative compounds
2a. Table 2. Entry 1. IR: ν = 1253, 1068, 643 cm1. 1H NMR: δ = 0.16 (s, 9H), 4.70 (s, 2H), 7.23-
7.34 (m, 5H).
1
2b. Table 2. Entry 6. IR: ν = 1253, 1095, 844 cm1. H NMR: δ = 0.10 (s, 9H), 4.72 (s, 2H),
7.19-7.31 (m, 4H).
2i. Table 2. Entry 9. IR: ν = 3057, 2960, 1468, 1255, 969, 928, 854 cm1.
2s. Table 2. Entry 19, IR: ν = 1631, 1599, 1255, 854 cm1. 1H NMR: δ = 0.39 (s, 9H), 7.11-7.84
(m, 7H).
Acknowledgements
The authors gratefully acknowledge the partial support from the research council of the Iran
University of Science and Technology (IUST).
ACCEPTED MANUSCRIPT
8

ACCEPTED MANUSCRIPT
References
(1)
(2)
(3)
(4)
Wuts, P. G.; Greene, T. W. Greene's protective groups in organic synthesis; John Wiley
& Sons, 2006.
Kusmierz, J.; DeGeorge, J.; Sweeney, D.; May, C.; Rapoport, S. J. Chromatogr. B
Biomed. Sci. Appl. 1989, 497, 39-48.
Wan, P. J.; Dowd, M. K.; Thomas, A. E.; Butler, B. H. J. Am. Oil Chem. Soc. 2007, 84,
701-708.
Sartori, G.; Ballini, R.; Bigi, F.; Bosica, G.; Maggi, R.; Righi, P. Chem. Rev. 2004, 104,
199-250.
(5)
(6)
(7)
(8)
(9)
Still, W. C.; Schneider, M. J. J. Am. Chem. Soc. 1977, 99, 948-950.
Lalonde, M.; Chan, T. Synthesis 1985, 1985, 817-845.
Karimi, B.; Golshani, B. J. Org. Chem. 2000, 65, 7228-7230.
Cossy, J.; Pale, P. Tetrahedron Lett. 1987, 28, 6039-6040.
Zhang, Z.-H.; Li, T.-S.; Yang, F.; Fu, C.-G. Synth. Commun. 1998, 28, 3105-3114.
(10) Firouzabadi, H.; Karimi, B. Synth. Commun. 1993, 23, 1633-1641.
(11) Azizi, N.; Yousefi, R.; Saidi, M. R. J. Organomet. Chem. 2006, 691, 817-820.
(12) Ghafuri, H.; Eftekhari-Sis, B.; Hashemi, M. M. Phosphorus Sulfur Silicon Relat. Elem.,
2007, 182, 1645-1651.
(13) Shaterian, H. R.; Shahrekipoor, F.; Ghashang, M. J. Mol. Catal. A: Chem. 2007, 272,
142-151.
(14) Mojtahedi, M. M.; Abaee, M. S.; Eghtedari, M. Appl. Organomet. Chem. 2008, 22, 529-
532.
ACCEPTED MANUSCRIPT
9

ACCEPTED MANUSCRIPT
(15) Firouzabadi, H.; Iranpoor, N.; Sobhani, S.; Ghassamipour, S.; Amoozgar, Z. Tetrahedron
Lett. 2003, 44, 891-893.
(16) Khazaei, A.; Zolfigol, M. A.; Rostami, A.; Choghamarani, A. G. Catal. Commun. 2007,
8, 543-547.
(17) Kadam, S. T.; Kim, S. S. J. Organomet. Chem. 2009, 694, 2562-2566.
(18) Kelly, D. R.; Roberts, S. M.; Newton, R. F. Synth. Commun. 1979, 9, 295-299.
(19) Newton, R. F.; Reynolds, D. P.; Finch, M. A.; Kelly D. R.; Roberts, S. M. Tetrahedron
Lett. 1979, 20, 3981-3982.
(20) Shirini, F.; Atghia, S. V.; Jirdehi, M. G. Catal. Commun. 2012, 18, 5-10.
(21) Bamoniri, A.; Zolfigol, M.; Mohammadpoor-Baltork, I.; Mirjalili, B. J. Iran. Chem. Soc.
2006, 3, 85-88.
(22) Bamoniri, A.; Mirjalili, B.; Zolfigol, M.; Mohammadpoor-Baltork, I. J. Iran. Chem. Soc.
2007, 4, 332-335.
(23) Ghafuri, H.; Roshani, M. RSC Adv. 2014, 4, 58280-58286.
(24) Ghafuri, H.; Khodashenas, S.; Naimi-Jamal, M. R. J. Iran. Chem. Soc. 2015, 12, 599-
604.
(25) Ghafuri, H.; Rashidizadeh, A.; Ghorbani, B.; Talebi, M. New J. Chem. 2015, 39, 4821-
4829.
(26) Ghafuri, H.; Rashidizadeh, A.; Zand, H. R. E. RSC Adv. 2016, 6, 16046-16054.
(27) Zareyee, D.; Karimi, B. Tetrahedron Lett. 2007, 48, 1277-1280.
(28) Narsaiah, A. V. J. Organomet. Chem. 2007, 692, 3614-3618.
(29) Azizi, N.; Saidi, M. R. Organometallics 2004, 23, 1457-1458.
ACCEPTED MANUSCRIPT
10

ACCEPTED MANUSCRIPT
(30) Firouzabadi, H.; Iranpoor, N.; Amani, K.; Nowrouzi, F. J. Chem. Soc., Perkin Trans. 1
2002, 2601-2604.
(31) Ghorbani-Vaghei, R.; Zolfigol, M. A.; Chegeny, M.; Veisi, H. Tetrahedron Lett. 2006,
47, 4505-4508.
2
Table 1: Optimization of O-silylation of benzyl alcohol using Fe3O4@ZrO2/SO4
Entry a
Catalyst (mg)
Time (min)
Yield (%)b
2-
Fe3O4@ZrO2/SO4
1
2
3
4
5
-
120
43
35
15
30
10
75
80
92
90
10
40
80
90
a Reaction conditions: benzyl alcohol (1.0 mmol), HMDS (1.5 mmol), catalyst, solvent-free. b
Isolated yields.
Table 2: Silylation of various alcohols with HMDS in the presence of Fe3O4@ZrO2/SO42 as the
catalyst
Time
(min)
Yield
(%)b
Entry
1
Substrate
Product
OSiMe3
OH
15
90
2a
ACCEPTED MANUSCRIPT
11

ACCEPTED MANUSCRIPT
OSiMe3
OH
2
12
80
H3C
H3C
2b
OSiMe3
OH
3
4
5
6
7
8
10
12
90
90
85
90
85
88
H3CO
H3CO
2c
OSiMe3
CH3
OH
CH3
2d
OSiMe3
OSiMe3
OH
OH
100
25
2e
OSiMe3
OH
O2N
O2N
2f
OSiMe3
NO2
OH
NO2
35
2g
2h
OSiMe3
OH
25
Cl
Cl
OH
OSiMe3
9
40
50
75
95
95
90
2i
OSiMe3
OH
Cl
10
11
Cl
2j
OSiMe3
Cl
OH
Cl
2k
OSiMe3
OH
Cl
Cl
Cl
12
13
100
120
94
87
Cl
OSiMe3
2l
OH
I
I
2m
ACCEPTED MANUSCRIPT
12

ACCEPTED MANUSCRIPT
OSiMe3
OH
Cl
Cl
Cl
Cl
Cl
Cl
Cl
14
15
55
20
80
87
Cl
Cl
Cl
2n
OH
OSiMe3
NH2
NH2
2o
OSiMe3
OH
NH2
NH2
16
17
250
34
90
90
2p
OSiMe3
OH
OSiMe3
OH
OH
2q
2r
OSiMe3
18
19
20
30
20
25
90
75
70
OSiMe3
OH
2s
OSiMe3
OH
2t
21
15
83
OSiMe3
2u
OH
OH
OSiMe3
22
23
50
30
70
82
OSiMe3
OH
2v
OSiMe3
CH3
OH
CH3
H3C
H3C
CH3
CH3
2w
ACCEPTED MANUSCRIPT
13

ACCEPTED MANUSCRIPT
COOH
OSiMe3
COOH
OH
24
20
90
2x
a Reaction conditions: alcohol (1.0 mmol), HMDS (1.5 mmol), catalyst (80 mg), solvent free. b
Isolated yield.
Table 3: Deprotection of silylethers in presence of Fe3O4@ZrO2/SO42 as the catalyst
Entry
1
Substrate
Product
Time (min)
10
Yield (%)b
85
OH
OSiMe3
3a
OH
OSiMe3
2
3
10
10
80
91
H3C
H3C
3b
OH
OSiMe3
H3CO
H3CO
3c
OH
CH3
OSiMe3
CH3
4
5
10
50
85
80
3d
OSiMe3
OSiMe3
OH
OH
3e
OH
OSiMe3
6
20
85
O2N
O2N
3f
OH
NO2
OSiMe3
NO2
7
8
30
20
77
80
3g
OH
OSiMe3
Cl
Cl
3h
ACCEPTED MANUSCRIPT
14

ACCEPTED MANUSCRIPT
OH
OSiMe3
9
30
90
3i
3j
OH
Cl
OSiMe3
10
11
12
45
70
80
91
85
82
Cl
OH
OSiMe3
Cl
Cl
3k
3l
OH
Cl
OSiMe3
Cl
Cl
Cl
OH
OSiMe3
13
14
80
50
75
80
I
I
3m
OSiMe3
OH
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
3n
Cl
OH
OSiMe3
15
15
83
NH2
NH2
3o
OH
OSiMe3
NH2
NH2
16
17
20
30
90
85
3p
OH
OSiMe3
OSiMe3
OSiMe3
OH
3q
OH
18
19
25
20
80
70
3r
OH
OSiMe3
3s
ACCEPTED MANUSCRIPT
15

ACCEPTED MANUSCRIPT
OH
OSiMe3
20
25
15
70
80
3t
21
OSiMe3
OSiMe3
OH
3u
3v
OH
22
45
72
OSiMe3
OH
OH
OSiMe3
CH3
CH3
23
24
25
20
80
75
H3C
H3C
CH3
CH3
3w
COOH
COOH
OSiMe3
OH
3x
a Reaction conditions: Silylethers (1.0 mmol), Fe3O4@ZrO2/SO42 (80.0 mg), solvent-free, room
temperature. b Isolated yields.
ACCEPTED MANUSCRIPT
16

ACCEPTED MANUSCRIPT
Table 4: Comparison of the efficiency of Fe3O4@ZrO2/SO42 with other catalysts for silylation
of benzyl alcohol using HMDS at room temperature
Entry
1
Catalyst
Solvent
CH2Cl2
Time
(min)
55
Yield
%a
Ref.
27
Sulfonic acid@nanoporous
99
silica
LaCl3
28
29
30
16
31
2
3
4
5
6
-
180
25
91
90
90
90
90
LiClO4
-
H3PW12O40
-
23
TCCA
CH2Cl2
CH2Cl2
240
90
Poly(N-bromobenzene-1,3-
disulfonamide)
2
7
-
15
90
This
Fe3O4@ZrO2/SO4
work
a Isolated yields.
ACCEPTED MANUSCRIPT
17

ACCEPTED MANUSCRIPT
100
50
0
1
2
3
4
5
No.of Runs
Figure 1: Recycling of Fe3O4@ZrO2/SO42 for the protection of benzyl alcohols.
2-
Fe3O4@ZrO2/SO4
H
N
R OH +
R OSiMe3
Me3Si
SiMe3
r.t, Solvent-free
2
Scheme 1 O-Silylation of alcohols catalyzed by Fe3O4@ZrO2/SO4
ACCEPTED MANUSCRIPT
18

ACCEPTED MANUSCRIPT
HMDS 1.2 eq
OSiMe3
H2N
OH
1mmol
PhCO2H
H2N
2-
Fe3O4 @ZrO2/SO4
Solvent free,rt
94%
HMDS 1.2 eq
PhOSiMe3
90%
PhCO2SiMe3
0%
PhOH
2-
Fe3O4 @ZrO2/SO4
Scheme 2: Selectivity of Fe3O4@ZrO2/SO42 in protection reactions
H
N
Me3Si
SiMe3
NH3
ROH
(Me3Si)2NH
ROSiMe3
NH3
Me3SiNH2
ROH
ROSiMe3
Scheme 3: Plausible mechanism for the O-silylation of alcohols with HMDS catalysed by
2
Fe3O4@ZrO2/SO4
ACCEPTED MANUSCRIPT
19

ACCEPTED MANUSCRIPT
Graphical Abstract
ACCEPTED MANUSCRIPT
20