Chemoselective trimethylsilylation of alcohols catalyzed by saccharin sulfonic acid

Article abstract of DOI:10.1007/s00706-008-0004-7

Saccharin sulfonic acid was easily prepared by the reaction of saccharin with neat chlorosulfonic acid at room temperature. This reagent is efficiently able to catalyze the chemoselective trimethylsilylation of alcohols with hexamethyldisilazane in the pr

Full text of DOI:10.1007/s00706-008-0004-7

Monatsh Chem (2009) 140:61–64
DOI 10.1007/s00706-008-0004-7
ORIGINAL PAPER
Chemoselective trimethylsilylation of alcohols catalyzed
by saccharin sulfonic acid
Farhad Shirini Æ Mohammad Ali Zolfigol Æ
Masoumeh Abedini
Received: 19 May 2008 / Accepted: 2 June 2008 / Published online: 9 October 2008
Ó Springer-Verlag 2008
Abstract Saccharin sulfonic acid was easily prepared by
the reaction of saccharin with neat chlorosulfonic acid at
room temperature. This reagent is efficiently able to cata-
lyze the chemoselective trimethylsilylation of alcohols
with hexamethyldisilazane in the presence of amines and
thiols.
alcohols. Its handling does not need special precaution,
and workup of the reaction mixture is not time consuming
because the by-product of the reaction is ammonia, which
is easily removed from the reaction mixture. However, the
low silylating power is considered the main drawback for
the application of HMDS. To overcome this restriction, a
variety of catalysts has been reported; of them, sulfonic
acids [6], N, N0, N0, N000-tetramethyltetra-2,3-pyridinopor-
phyrazinato copper (II) [7], poly(N-bromobenzene-1,3-
disulfonamide) (PBBS) [8], trichloroisocyanuric acid [9],
sulfonic acid-functionalized silica [10], Al(HSO4)3 [11],
ZrCl4 [12], silica triflate [13], and Fe(HSO4)3 [14] are
examples. Although these procedures are an improve-
ment, most of them suffer from disadvantages such as
long reaction times, forceful reaction conditions, low
selectivity, tedious workup, and use of toxic or expensive
reagents.
Keywords Saccharin ꢀ Saccharin sulfonic acid ꢀ
Alcohols ꢀ Trimethylsilylation ꢀ Hexamethyldisilazane
Introduction
Trimethylsilylation is one of the most important and pop-
ular methods for protecting the alcoholic hydroxyl group
during a multistep synthesis [1, 2]. Generally, the forma-
tion of silyl ethers carried out by treatment of alcohols with
silyl chlorides or silyl triflates in the presence of stoichi-
ometric amounts of a base such as 4-(N,N-dimethylamino)
pyridine [3], Li2S [4], and sometimes a nonionic super base
catalyst [5]. However, some of these methods suffered
from drawbacks such as lack of reactivity or the difficulty
in removing amine salts drived from the reaction of by-
produced acids and cobases during the course of the
reaction.
Results and discussion
In continuation of our ongoing research program on the
development of new methods for protecting the alcoholic
hydroxyl group [11–17], we found that saccharin reacts
with neat chlorosulfonic acid to give saccharin sulfonic
acid (SaSA) (I) during an easy and clean reaction. The
method needs no special workup procedure, because
hydrochloric acid (HCl) gas is evolved from the reaction
vessel immediately (Scheme 1).
Hexamethyldisilazane (HMDS) is an expensive and
commercially available reagent used for the silylation of
F. Shirini (&) ꢀ M. Abedini
On the basis of the structure of SaSA, we anticipated
that this reagent would act as an efficient catalyst in
reactions that need the use of acidic reagents to speed up.
Therefore, we were interested in using SaSA for pro-
moting trimethylsilylation (TMS) of alcohols with HMDS
(Table 1, Scheme 2).
Department of Chemistry, College of Science,
University of Guilan, 41335 Rasht, Iran
e-mail: shirini@guilan.ac.ir
M. A. Zolfigol
College of Chemistry, Bu-Ali Sina University,
Hamadan, Iran
123

62
F. Shirini et al.
O
O
of this new method, which make this procedure a useful
and attractive addition to the available methods. We are
exploring further applications of SaSA for other types of
functional group transformations.
r.t.
+
+
N SO3H HCl
ClSO3H (neat)
NH
S
S
O
O
O
O
I
Scheme 1
Experimental
A wide range of various alcohols, including benzylic,
primary, secondary, and tertiary ones, underwent TMS
with HMDS in the presence of catalytic amounts of SaSA
at room temperature in good to high yields.
Chemicals were purchased from Fluka, Merck, and
Aldrich Chemical companies. IR spectra were recorded
with a Shimadzu FT-IR 500 spectrophotometer using KBr
pellets. Elemental analysis of SaSA was done with a
GmbH VarioEL III analyzer and obtained results agreed
favorably with calculated values. All of the trimethylsilyl
ethers are known compounds and were characterized on
the basis of their spectroscopic data (infrared and nuclear
magnetic resonance), by comparison with those reported
in literature [12, 18–21], and also by regeneration of the
corresponding alcohols. All yields refer to the isolated
products. The purity determination of the substrate and
reaction monitoring were accompanied by thin-layer
chromatography (TLC) on silica-gel polygram SILG/UV
254 plates.
Primary benzylic alcohols (including electron releasing
or withdrawing groups) and aliphatic alcohols were trim-
ethylsilylated with excellent yields (Table 1, entries 1–15).
The protection of benzylic, cyclic, and linear secondary
alcohols were satisfactory subjected as well (Table 1,
entries 16–21). Interestingly, 1-adamantanol, as a model of
the hindered tertiary alcohols, was converted to the corre-
sponding trimethylsilyl ether under the same reaction
conditions (Table 1, entry 22). Because of the stability of
amines and thiols under the selected reaction conditions
(Table 1, entries 23, 24), the selective silylation of alcohols
in the presence of the above-mentioned substrates was
investigated (Table 1, entries 25, 26).
Saccharin sulfonic acid (SaSA, I, C7H5NO6S2)
A 500-cm3 suction flask charged with 17.1 g saccharin
(0.1 mol) was equipped with a constant pressure-dropping
funnel containing 11.65 g chlorosulfonic acid (0.1 mol)
and a gas inlet tube for conducting HCl gas over an
adsorbing solution, i.e. water. Chlorosulfonic acid was
added dropwise over a period of 10 min, and the reaction
mixture was stirred slowly in an ice bath for 10 min. The
mixture was then heated to room temperature and stirred
for an additional 30 min. The mixture was triturated with
10 cm3 n-hexane and filtered. The solid residue was
To illustrate the efficiency of the proposed method,
Table 2 compares some of our results with some of those
reported for the relevant reagents in the literature [9, 10,
14], which demonstrates its significant superiority.
In conclusion, SaSA, which can be easily prepared by
the reaction of saccharin and neat chlorosulfonic acid, is
efficiently able to catalyze the chemoselective trimethyl-
silylation of alcohols in the presence of amines and thiols.
The short reaction times, reagent availability, high product
yields, and easy workup are among the other advantages
Table 1 Chemoselective trimethylsilylation (TMS) of alcohols
Entry
Substrate
Product
Time/min
Yield/%a
1
2-Cl–Ph–CH2OH
2-Cl–Ph–CH2OTMS
4-Cl–Ph–CH2OTMS
4-Br–Ph–CH2OTMS
2-Br–Ph–CH2OTMS
2-Me–Ph–CH2OTMS
4-Me3C–Ph–CH2OTMS
3-NO2–Ph–CH2OTMS
2-NO2–Ph–CH2OTMS
3-MeO–Ph–CH2OTMS
3-PhCH2O–Ph–CH2OTMS
3,4-Cl2Ph–CH2OTMS
5
5
92
95
90
95
92
90
95
87
90
85
94
2
4-Cl–Ph–CH2OH
3
4-Br–Ph–CH2OH
2-Br–Ph–CH2OH
2-Me–Ph–CH2OH
4-Me3C–Ph–CH2OH
3-NO2–Ph–CH2OH
2-NO2–Ph–CH2OH
3-MeO–Ph–CH2OH
3-PhCH2O–Ph–CH2OH
3,4-Cl2Ph–CH2OH
10
10
5
4
5
6
5
7
15
15
10
20
5
8
9
10
11
123

Chemoselective trimethylsilylation of alcohols
63
Table 1 continued
Entry
12
Substrate
Product
Time/min
10
Yield/%a
89
CH2OH
CH2OTMS
13
14
15
16
17
18
Ph–CH2CH2OH
Ph–CH2CH2OTMS
10
10
10
10
5
95
92
90
92
90
80
Ph–CH2CH2CH2OH
Ph–CH(Me)CH2OH
Ph–CH(OH)–Ph
Ph–CH2CH2CH2OTMS
Ph–CH(Me)CH2OTMS
Ph–CH(OTMS)–Ph
4-Cl–Ph–CH(OH)–Ph
4-Cl–Ph–CH(OTMS)Ph
10
OTMS
OH
19
20
30
35
90
92
OH
OTMS
HO
TMSO
21
22
20
20
87
90
OH
OTMS
OTMS
OH
23
24
25
4-Me–Ph–NH2
4-Br–Ph–SH
4-Cl–Ph–CH2OH
?
4-Me–Ph–NHTMS
4-Br–Ph–STMS
4-Cl–Ph–CH2OTMS
?
10
10
10
0
0
95
?
0
4-Br–Ph–SH
2-Cl–Ph–CH2OH
?
4-Br–Ph–STMS
2-Cl–Ph–CH2OTMS
?
26
10
92
?
0
4-Me–Ph–NH2
4-Me–Ph–NHTMS
Products were identified spectroscopically and also by the conversion of the silyl ethers to the parent alcohols
a
Isolated yield
washed with 10 cm3 n-hexane and dried under vacuum.
Saccharin sulfonic acid was obtained as a white solid
(22.59 g, 90%), which was stored in a capped bottle. M.p.:
110–112 °C; FTIR: vꢀ ¼ 3; 100; 2,976, 1,726, 1,593, 1,462,
1,340, 1,292, 1,180, 1,130, 1,068, 1,007, 885, 853, 760,
General procedure
To a solution of 1 mmol substrate and 25 mg SaSA
(0.1 mmol) in 3 cm3 CH3CN, 120 mg HMDS (0.75 mmol)
were added dropwise within 5 min, with stirring at room
temperature. After completion of the reaction (TLC), the
706, 584, 519, 455 cm-1
.
123

64
F. Shirini et al.
O
References
SO3H
N
S
O
1. Greene TW, Wuts PG (1999) Protective groups in organic syn-
thesis. Wiley, New York
2. Kocienski PJ, Endres R, Noyori R, Trost BM (1994) Protective
groups. Thiemen, Stuttgart
O
ROH
ROTMS
HMDS, r.t., CH3CN
3. Chaudhari SK, Hernandez O (1979) Tetrahedron Lett 20:99
4. Olah GA, Gupta BGB, Narang SC, Malhorta R (1979) J Org
Chem 44:4272
Scheme 2
5. Azipurua JM, Palomo C (1985) Tetrahedron Lett 26:475
6. Goldschmidt AGT Ger Pat 2:758884
7. Akhlaghinia B, Asadi M, Safaee E, Heydarpoor M (2004)
Phosphorus Sulfur Silicon 179:2099
8. Ghorbani-Vaghei R, Zolfigol MA, Chegeny M, Veisi H (2006)
Tetrahedron Lett 47:4505
Table 2 Comparison of some of the results obtained by the silylation
of alcohols with hexamethyldisilazane (HMDS) in the presence of
saccharin sulfonic acid (SaSA) (I) with some of those reported by
trichloroisocyanuric acid (II) [9], sulfonic acid-functionalized silica
(III) [10], and Fe(HSO4)3 (IV) [14]
9. Khazaei A, Zolfigol MA, Rostami A, Ghorbani Choghamarani A
(2007) Catal Commun 8:543
10. Zareyee D, Karimi B (2007) Tetrahedron Lett 48:1277
11. Shirini F, Zolfigol MA, Abedini M (2005) Bull Chem Soc Jpn
78:1982
12. Shirini F, Mollarazi E (2007) Catal Commun 8:1393
13. Shirini F, Marjani K, Taherpour Nahzomi H, Zolfigol MA (2008)
Phosphorus Sulfur Silicon 183:168
14. Shirini F, Zolfigol MA, Abri AR (2008) Monatsh Chem 139:17
15. Shirini F, Zolfigol MA, Safari A (2006) J Chem Res(S) 154
16. Shirini F, Marjani K, Taherpour Nahzomi H (2007) Phosphorus
Sulfur Silicon 182:2235
Entry Product
Time/min/yield/%
II
I
III
IV
1
2
3
4
2-NO2–Ph–CH2OTMS 15/95
360/90 30/85
Ph–CH(OTMS)–Ph
Ph–CH2CH2OTMS
10/92 180/95 60/98
10/95 180/90 40/100
50/75
20/90 720/95 240/85 150/70
OTMS
17. Shirini F, Zolfigol MA, Mohammadi K (2004) Bull Korean Chem
Soc 25:235
18. Karimi B, Golshani B (2000) J Org Chem 65:7228
19. Tillu VH, Jadhav VH, Borate HB, Wakharkar RD (2004)
ARKIVOC 83
solvent was evaporated, and 5 cm3 n-hexane was added.
The mixture was filtered through a silica-gel pad and filter
cake was washed with 5 cm3 n-hexane. Evaporation of the
solvent gave almost pure product(s). Further purification
proceeded by bulb to bulb distillation under reduced
pressure or recrystallization to afford pure silyl ether.
20. Azizi N, Yousefi R, Saidi MR (2006) J Organomet Chem 691:817
21. Zareyee D, Karimi B (2007) Tetrahedron Lett 48:1277
Acknowledgment We are thankful to the University of Guilan
Research Council for the partial support of this work.
123