P-toluenesulfonyl chloride (p-TsCl)-catalyzed trimethylsilylation of hydroxyl groups using hexamethyldisilazane and their regeneration under mild conditions: The first example for catalytic application of p-toluenesulfonyl chloride

Article abstract of DOI:10.1080/10426500802453872

The first catalytic application of p-toluenesulfonyl chloride (p-TsCl) for the efficient and selective trimethylsilylation of various types of hydroxyl groups with hexamethyldisilazane (HMDS) in dichloromethane and desilylation of these compounds in water is reported. The reactions were carried out at room temperature and were found to proceed in good to excellent yields.

Full text of DOI:10.1080/10426500802453872

This article was downloaded by: [University of Nebraska, Lincoln]
On: 05 January 2015, At: 10:17
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
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
p-Toluenesulfonyl Chloride
(p-TsCl)-Catalyzed
Trimethylsilylation of
Hydroxyl Groups Using
Hexamethyldisilazane and
Their Regeneration Under Mild
Conditions: The First Example
for Catalytic Application of p-
Toluenesulfonyl Chloride
Ardeshir Khazaei a , Amin Rostami b & Fatemeh
Mantashlo a
a Faculty of Chemistry , Bu-Ali Sina University ,
Hamadan, Iran
b Department of Chemistry, Faculty of Science ,
University of Kurdistan , Sanandaj, Iran
Published online: 04 Sep 2009.
To cite this article: Ardeshir Khazaei , Amin Rostami & Fatemeh Mantashlo (2009) p-
Toluenesulfonyl Chloride (p-TsCl)-Catalyzed Trimethylsilylation of Hydroxyl Groups
Using Hexamethyldisilazane and Their Regeneration Under Mild Conditions: The First
Example for Catalytic Application of p-Toluenesulfonyl Chloride, Phosphorus, Sulfur,
and Silicon and the Related Elements, 184:9, 2288-2296
To link to this article: http://dx.doi.org/10.1080/10426500802453872
PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
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. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 184:2288–2296, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802453872
p-Toluenesulfonyl Chloride (p-TsCl)-Catalyzed
Trimethylsilylation of Hydroxyl Groups Using
Hexamethyldisilazane and Their Regeneration Under
Mild Conditions: The First Example for Catalytic
Application of p-Toluenesulfonyl Chloride
Ardeshir Khazaei,1 Amin Rostami,2
and Fatemeh Mantashlo1
1Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Iran
2Department of Chemistry, Faculty of Science, University of Kurdistan,
Sanandaj, Iran
The first catalytic application of p-toluenesulfonyl chloride (p-TsCl) for the efficient
and selective trimethylsilylation of various types of hydroxyl groups with hexam-
ethyldisilazane (HMDS) in dichloromethane and desilylation of these compounds
in water is reported. The reactions were carried out at room temperature and were
found to proceed in good to excellent yields.
Keywords Hexamethyldisilazane; hydroxyl group; p-toluenesulfonyl chloride;
trimethylsilylation
INTRODUCTION
The protection–deprotection sequence is one of the most frequently en-
countered functional-group transformations in organic synthesis.1 In
particular, the sequence for hydroxyl groups is extremely important be-
cause of enormous demands for natural product synthesis and for phar-
maceutical agents. The use of a silyl ether function as a protecting group
of the hydroxy functionality is well documented in organic synthesis.2
Several methods have become available for silylation of hydroxy func-
tional groups using a variety of silylating agents, such as trimethylsilyl
chloride in the presence of a base,3 Li2S,4 or Mg,5 ketene methyl-
trialkylsilyl acetals,6 allyl silanes,7 ethyl trimethylsilyl acetate,8N,
Received 15 August 2008; accepted 5 September 2008.
The authors acknowledge the Bu-Ali Sina University and Kurdistan University Re-
search Councils for partial support of this work.
Address correspondence to Ardeshir Khazaei, Faculty of Chemistry, Bu-Ali Sina Uni-
versity, Hamadan, 65178-38683, Iran. E-mail: khazaei 1326@yahoo.com
2288

(p-TsCl)-Catalyzed Trimethylsilylation
2289
N-bis(trimethylsilylurea),9 methyl 3-(trimethylsilyloxy)crotonate,10
trimethylsilyl
azide,11 N-trimethylsilyl-2-oxazolidinone,12 N, O-
bis(trimethylsilyl)acetamide,13 and hexamethyldisilane.14 However,
some of these silylating agents suffer from drawbacks such as lack
of reactivity or difficulty in removal of byproducts of the silylation
reaction.
1,1,1,3,3,3-Hexamethyldisilazane (HMDS), one of the most common
silylating agents, readily silylates alcohols, acids, amines, thiols, phe-
nols, amides, thioamides, sulfonamides, enolizable ketones, etc. The
byproduct of this reaction is ammonia, which is readily removed from
the reaction medium. However, the low silylation power of HMDS is the
main drawback to its use,15 and thus various catalysts for the activation
of this reagent have been reported.16–21 Although these methods pro-
duce good results in many instances, few of these catalysts can perform
both protection and deprotection of hydroxyl groups as trimethylsi-
lyl ethers do. Therefore, there is still a demand to develop new mild
methods for the trimethylsilylation of hydroxyl compounds and their
regeneration in the presence of inexpensive, selective, and bench-top
catalysts.
Similar to protection, deprotection of the trimethylsilyl ethers consti-
tutes an important process in the synthetic chemistry of polyfunctional
molecules including the total synthesis of natural products. Although
several methods have been reported for the deprotection of trimethylsi-
lyl ethers,22–26 the development of a mild, efficient, and ecofriendly
method for the deprotection of trimethylsilyl ethers continues to be
desirable.
RESULTS AND DISCUSSION
p-Toluenesulfonyl chloride is a cheap, commercially available reagent
that has been widely used as a sulfonyl transfer reagent27 and as an
initiator in a wide range of polymerization reactions,28 but there is
only one report of its use as a chlorinating agent for α-chlorination of
ketones.29 However, to the best of our knowledge, there is no report
on the catalytic application of p-toluenesulfonyl chloride in organic
transformations.
In a result of our investigations on preparation and catalytic ap-
plications of N-halogen compounds (as source of positive halogen) in
organic synthesis,30–34 herein for the first time we disclose the use of
a catalytic amount of p-toluenesulfonyl chloride as a source of “Cl+”
for efficient O-trimethylsilylation of a wide variety of hydroxyl groups

2290
A. Khazaei et al.
(alcohols and phenols) using readily available HMDS and the desilyla-
tion of the corresponding TMS ethers in water (Scheme 1).
SCHEME 1
We first examined the effect of different ratios of ROH:HMDS:
catalyst. The 1.0:0.7:0.06 ratio hydroxyl groups gave the best results
and produced trimethylsilyl ethers in quantitative yields. The results
of the reactions of a diverse range of hydroxyl compounds are collected
in Table I.
The reported data show that p-TsCl can affect the O-
trimethylsilylation of primary, secondary, and tertiary alcohols in good
to excellent yields. Primary benzylic alcohols with electron-donating
and electron-withdrawing groups were terimethylsilylated in the pres-
ence of 0.03–0.06 mmol of catalyst, and the corresponding trimethylsi-
lyl ethers were obtained in good to excellent yields (Table I, Entries
1–6). Benzhydrol and 1-phenylethanol as two model compounds for
secondary benzylic alcohols were satisfactorily subjected to trimethylsi-
lylation as well (Table I, Entries 9,7). Trimethylsilylation of linear
and cyclic saturated primary and secondary alcohols was achieved in
the presence of a catalyst (0.1–0.2 mmol) at room temperature (Table
I, Entries 7–8 and 11–15). Interestingly, 1-adamantanol as a model
for the hindered tertiary alcohols was converted to the corresponding
trimethylsilyl ethers (Table I, Entry 16). These results indicate that
primary and secondary hydroxyl groups react faster than the tertiary
ones. The reaction conditions are mild and are not sufficiently acidic to
cause side reactions.
To explore the generality and scope of the reaction, 2-naphthol
and resorcinol as two model compounds for phenols were subjected to
trimethylsilylation catalyzed by p-TsCl in good yields (Table I, Entries
17–18).
As shown in Table I, the amounts of HMDS and catalyst depend
on the nature of the alcohol used as substrate. Therefore, we explored
the ability of this method to discriminate between different kinds of
hydroxyl groups (primary, secondary, and tertiary). In a binary mixture
of 2,4-dichlorobenzyl alcohol (as a model for primary alcohol) and 1-
phenylethanol (as a model for secondary alcohol), the primary alcohol
was completely converted to the corresponding trimethylsilyl ether,

(p-TsCl)-Catalyzed Trimethylsilylation
2291
TABLE I Trimethylsilylation of the Alcohols or Phenols Using HMDS
Catalyzed with p-TsCl in CH2Cl2 at Room Temperature
HMDS: Time
Cat (mmol) (min)
Yieldsa
(%)
Entry
Substrate
Product
1
2
3
4
5
4-OMe-C6H4CH2OH
4-Cl-C6H4CH2OH
2,4-(Cl)2C6H3CH2OH
4-F-C6H4CH2OH
0.7:0.03
0.7:0.06
0.7:0.06
0.7:0.06
0.7:0.06
7
9
12
20
20
4-OMe-C6H4CH2OSiMe3
4-Cl-C6H4CH2OSiMe3
2,4-(Cl)C6H3CH2OSiMe3
4-F-C6H4CH2OSiMe3
4-NO2-C6H4CH2OSiMe3
81
97
95
96
92
4-NO2-C6H4CH2OH
6
0.1: 0.7
11
75
7
8
9
10
PhCH2CH2OH
CH3(CH2)14CH2OH
PhCH(OH)CH3
PhCH(OH)Ph
0.7:0.1
0.7:0.1
0.7:0.1
0.7:0.1
8
9
17
17
PhCH2CH2OSiMe3
CH3(CH2)14CH2OSiMe3
PhCH(OSiMe3)CH3
PhCH(OSiMe3)Ph
83
78
95
80
11
12
0.7:0.1
14
91
0.7:0.1
30
86
13
0.7:0.2
150
82
14
15
16
CH3(CH2)4CH(OH)CH3
0.7:0.1
1.4:0.2
0.7:0.2
10 CH3(CH2)4CH(OSiMe3)CH3
73
85
78
30
h17
17
18
0.06: 0.7
1.4:0.12
16
19
90
83
aAll products were characterized by comparison of their spectral data (1H-NMR, IR)
with those of authentic samples.
while 0% conversion was observed for the secondary alcohol (Scheme
2).
Excellent selectivity was also observed for 1-phenylethanol in the
presence of 1-adamantanol (as a model for tertiary alcohol). The only
observed product was 1-phenylethyl trimethylsilyl ether in 100% con-
version (Scheme 3).

2292
A. Khazaei et al.
SCHEME 2
SCHEME 3
Organic reactions in water have received much attention because
water is a cheap, safe, and environmentally benign solvent.35 However,
we investigated the possibility of deprotection of trimethylsilyl ethers
using p-TsCl as catalyst in water. It was found that the TMS group
could be removed efficiently in the presence catalytic amount of p-
TsCl in water at room temperature in good to excellent yields. Various
types of structurally diverse TMS ethers were deprotected using this
procedure, and the results are summarized in Table II.
The actual role of p-toluenesulfonyl chloride is not clear. On the
basis of the previously reported mechanisms for applying of p-TsCl for
α -chlorination of ketones,29 one explanation for these processes is that
p-TsCl might act as a source for the formation of Cl+ , which polarizes
the Si–N bond in HMDS to produce the reactive silylating agent (as a
Lewis acid). Therefore the mechanism shown in Scheme 4 is proposed.
SCHEME 4
However, at this time we have obtained no experimental evidence for
these two features of p-TsCl, and the actual role of this reagent should

(p-TsCl)-Catalyzed Trimethylsilylation
2293
TABLE II Deprotection of Trimethylsilyl Ethers in the Presence of a
Catalytic Amount of p-TsCl (0.07 mmol) in Water (3 mL) at Room
Temperature
Entry
Substrate
Time(min)
Product
Yieldsa(%)
1
2
4-MeO-C6H4CH2OSiMe3
4-Cl-C6H4CH2OSiMe3
Immediate
Immediate
4-MeO-C6H4CH2OH
4-Cl-C6H4CH2OH
85
90
3
20
86
4
5
CH3(CH2)14CH2OSiMe3
PhCH2CH2OSiMe3
12
CH3(CH2)14CH2OH
PhCH2CH2OH
83
87
Immediate
6
6
95
7
8
9
10
5
80
91
95
CH3(CH2)4CH(OSiMe3)CH3
CH3(CH2)4CH(OH)CH3
5
10
11
12
25
22
60
72
78
Immediate
13
9
73
aAll products were characterized by comparison of their spectral data (1H-NMR, IR)
with those of authentic samples.
be further studied in detail. We also suggest the mechanisms shown in
Scheme 5 for desilylation of trimethylsilyl ethers using p-TsCl in water.
CONCLUSION
In summary, in this article the first catalytic application of p-TsCl for
protection of a variety of hydroxyl groups as TMS ethers using HMDS
and deportation of them under very mild conditions has been shown.
The main advantages of our protocol are fast reaction, selectivity, inex-
pensive reagent, easy work-up conditions, mild conditions, and good to
high yields. Therefore this procedure could be utilized in transforma-
tions that need mild reaction conditions. Further research on catalytic

2294
A. Khazaei et al.
SCHEME 5
applications of P-TsCl for other functional group transformations is
currently ongoing.
EXPERIMENTAL
General Procedure for Trimethylsilylation of Alcohols and
Phenols Using HMDS Catalyzed with p-TsCl in CH2Cl2
Alcohols or phenols (1 mmol) were added to a mixture of HMDS (0.7
mmol) and p-TsCl (0.06 mmol) in CH2Cl2 (5 mL), and then the mixture
was stirred at room temperature for the specified time (Table I). The
progress was monitored by TLC. After completion of the reaction, 2.5%
aqueous NaOH (10 mL) was added, then the trimethylsilyl ethers were
extracted with CH2Cl2 (3 × 10 mL), and the organic layer was dried over
anhydrous Na2SO4. CH2Cl2 was removed under reduced pressure, and
the product was purified through a short column of silica gel to obtain
pure trimethylsilyl ethers.
General Procedure for Deprotection of Trimethylsilyl Ethers
Catalyzed with p-TsCl
p-TsCl (0.08 mmol) was added to a mixture of TMS ethers (1 mmol) in
H2O (3 mL), then the mixture was stirred at room temperature for the
specified time (Table II). The progress of the reaction was monitored
by TLC. After completion of the reaction, the alcohols or phenols were
extracted with CH2Cl2 (3 × 10 mL), and the organic layer was dried

(p-TsCl)-Catalyzed Trimethylsilylation
2295
over anhydrous Na2SO4. Dichloromethane was removed under reduced
pressure, and the product was purified through a short column of silica
gel to obtain pure alcohol or phenol.
REFERENCES
[1] T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd ed.
(John Wiley, New York, 1999).
[2] K. Jarowicki and P. Kocienski, J. Chem. Soc. Perkin. Trans.1, 2109 (2001).
[3] R. G. Visser, H. J. T. Boos, and L. Brandsma, Recl. Trav. Chim. Pays-Bas, 99, 70
(1980).
[4] G. A. Olah, G. B. Gupta, S. Snaring, and R. Malhotra, J. Org. Chem., 44, 4272 (1979).
[5] I. Nishiguchi, Y. Kita, M. Watanabe, Y. Ishino, T. Ohno, and H. Maekawa, Synlett,
1025 (2000).
[6] Y. Kita, J. Haruta, J. Segawa, and Y. Tamura, Tetrahedron Lett., 20, 4311 (1979).
[7] G. A. Olah, A. Husain, B. G. B. Gupta, G. F. Salem, and S. C. Narang, J. Org. Chem.,
46, 5212 (1981).
[8] E. Nakamura, K. Hashimoto, and I. Kuwajima, Bull. Chem. Soc. Jpn., 54, 805
(1981).
[9] W. Verboom, G. W. Visser, and D. N. Reinhoudt, Synthesis, 807 (1981).
[10] T. Veysoglu and L. A. Mitscher, Tetrahedron Lett., 22, 1303 (1981).
[11] D. Amantini, F. Fringuelli, F. Pizzo, and L. Vaccaro, J. Org. Chem., 66, 6734 (2001).
[12] J. M. Aizpurua and C. Palomo, Bull. Soc. Chim. Fr Mem II, 265 (1982).
[13] Y. Tanabe, M. Murakami, K. Kitaichi, and Y. Yoshida, Tetrahedron Lett., 45, 8409
(1994).
[14] E. Hirakawa, K. Hironaka, H. Otsuka, and T. Hayashi, Chem. Commun., 3927
(2006).
[15] C. A. Bruynes and T. K. Jurriens, J. Org. Chem., 47, 3966 (1982).
[16] D. Zareyee and B. Karimi, Tetrahedron Lett., 48, 1277 (2007).
[17] F. Shirini, M. A. Zolfigol, and M. Abedini, Bull. Chem. Soc. Jpn., 78, 1982 (2005).
[18] J. S. Yadav, B. V. S. Reddy, A. K. Basak, G. Baishya, and A. V. Narsaiah, Synthesis,
3831 (2006).
[19] R. Ghorbani-Vaghei, M. A. Zolfigol, M. Chegeny, and H. Veisi, Tetrahedron Lett., 47,
4505 (2006).
[20] H. Firouzabadi, N. Iranpoor, S. Sobhani, and S. Ghassamipour, Synthesis, 295
(2005).
[21] B. Akhlaghinia and S. Tavakoli, Synthesis, 1775 (2005).
[22] A. Vakalopoulos and H. M. R. Hoffmann, Org. Lett., 2, 1447 (2000).
[23] Z. Yu and J. G. Vercade, J. Org. Chem., 65, 2065 (2000).
[24] M. H. Habibi, S. Tangestaninejad, I. Mohammadpoor-baltork, V. Mirkhani, and B.
Yadollahi, Tetrahedron Lett., 42, 6771 (2001).
[25] Y. G. Wang, X. X. Wu, and Z. Y. Jiang, Tetrahedron Lett., 45, 2973 (2004).
[26] R. D. Crouch and A. Williams, Synth. Commun., 36, 959 (2006).
[27] A. Khalafi-Nezhad, A. Parhami, M. V. Soltani-Rad, and A. Zarea, Tetrahedron Lett.,
46, 6879 (2005) and references therein.
[28] S. Mallakpour and E. Kowsari, J. Appl. Polym. Sci., 101, 455 (2006) and references
therein.
[29] K. M. Brummond and K. D. Gesenberg, Tetrahedron Lett., 40, 2231 (1999).

2296
A. Khazaei et al.
[30] A. Khazaei, A. Rostami, Z. Tanbakouchian, and Z. Zinati, J. Braz. Chem. Soc., 17,
206 (2006).
[31] A. Khazaei, M. A. Zolfigol, A. Rostami, and A. Ghorbani-Choghamarani, Catal.
Commun., 8, 543 (2007).
[32] A. Khazaei, A. Rostami, S. Rahmati, and M. Mahboubifar, Phosphorus, Sulfur, and
Silicon, 182, 537 ( 2007).
[33] A. Khazaei, A. Rostami, and M. Mahboubifar, Catal. Commun., 8, 383 (2007).
[34] A. Khazaei, A. Rostami, A. Raiatzadeh, and M. Mahboubifar, Can. J. Chem., 85,
336 (2007).
[35] P. A. Grieco, Organic Synthesis in Water (Blackie Academic Professional, London,
1998).