A novel regioselective desulfation method specific to silyl ester of primary sulfate using silylating agents. Selective preparation of secondary alkyl sulfates having a primary hydroxy group

Article abstract of DOI:10.1246/bcsj.74.181

The treatment of bis(trimethylsilyl)ester of 1-O-Decylglycerol-2,3-Disulfate with trimethylsilyl-N-trimethylsilylacetimidate (BSA) or (dimethylamino)trimethylsilane caused regioselective desulfation to afford 1-O-decyl glycerol-2-sulfate selectively in good yield. Silylating agents, having nitrogen, seems to be responsible for facilitating trimethylsiloxysulfonyl cation transfer.

Full text of DOI:10.1246/bcsj.74.181

Short Articles
181
Bull. Chem. Soc. Jpn., 74, 181–182 (2001)
A Novel Regioselective Desulfation
Method Specific to Silyl Ester of
Primary Sulfate Using Silylating
Agents. Selective Preparation of
Secondary Alkyl Sulfates Having a
Primary Hydroxy Group
Scheme 1.
Table 1. Reaction of Glyceryl Ether Disulfates with Var-
ious Silylating Agents
Mineko Horibe* and Hiroyuki Oshita
Entry Substrate
Silylating Agent
Yield/%a)
Material Science Research Center, Lion Corporation,
7-13-12 Hirai, Edogawa-ku, Tokyo 132-0035
3
4
4
5
0
1
2
3
4
1a
1b
1a
1a
BSA
BSA
Me2NSiMe3
2a 81
(Received July 13, 2000)
2a 63 < 1 25
2b 81 < 1
0
0
(Me3SiNH)2CO 2c 29 < 1
The treatment of bis(trimethylsilyl)ester of 1-O-de-
cylglycerol-2,3-disulfate with trimethylsilyl-N-trimethyl-
silylacetimidate (BSA) or (dimethylamino)trimethylsilane
caused regioselective desulfation to afford 1-O-decyl glyc-
erol-2-sulfate selectively in good yield. Silylating agents,
having nitrogen, seems to be responsible for facilitating trim-
ethylsiloxysulfonyl cation transfer.
5
6
7
8
9
1a
1a
1a
1c
1a
1c
2d 32
2e 31
3
6
26
0
0
0
0
0
0
0
(Me3Si)2NHb)
Me3SiCl
Me3SiOTf
2f
2g
6
0
0
(Me3SiO)2SO2 2h
7
10
BSA
2a 41 < 1
a) Determined by measuring the relative integration (1H NMR) of
the quenched mixtures. b) The reaction was carried out in the pres-
ence of catalytic amount of Me3SiCl.
During the past decade, considerable attention has been giv-
en to O-alkyl glycerol sulfate esters as surfactants, because of
their unique properties, such as high dispersibility and biodeg-
radation.1,2 In general, O-alkyl glycerol sulfate esters are pre-
pared from alkyl glycerol by the sulfation of hydroxy groups
with sulfation reagents, such as sulfur trioxide and chlorosulfu-
ric acid.3,4,5 Because these sulfation reagents are considerably
reactive, it is difficult to obtain regioselective sulfation prod-
ucts from glycerol derivatives having plural hydroxy groups.
Especially, secondary alkyl sulfate, having a primary hydroxy
group, is difficulty to obtain.
Recently, Takano and co-workers have reported that pyridin-
ium salts of primary alkyl sulfates are easily desulfated in the
presence of trimethylsilyl-N-trimethylsilylacetimidate (BSA)
to give the corresponding trimethylsilylated alcohols, and in
the case of secondary alkyl sulfates, the sulfate group is not re-
moved under these conditions.6,7 The results imply that the des-
ulfation reaction would provide a useful method for the selec-
tive synthesis of secondary alkyl sulfates having primary hy-
droxy groups. In this context, we tried to investigate the des-
ulfation reactions of bistrimethylsilyl esters of 1-O-decyl glyc-
erol-2,3-disulfate by various silylating agents (Scheme 1, Table
1).
erol-2,3-disulfate 1b with 2 mol amt. of 2a afforded a mixture
consisting of 3 (63%), 1-O-decyl glycerol (5: 25%), and small
amount of 1-O-decyl glycerol-3-sulfate 4 (Entry 2).
Various silylating agents were also allowed to react with 1a,
as summarized in Table 1. The use of (dimethylamino)tri-
methylsilane 2b equally provided the desired sulfate 3 in good
yield with a high regioselectivity (Entry 3). In the case of 2c−e,
3 was barely obtained in 30−40% yield, but the formation of 3
was favored in these cases (Entries 4−6). On the other hand, 2f
gave 4 predominantly (Entry 7), and no 3 was obtained by the
use of 2g−h (Entries 8 and 9). The high regioselectivity in the
secondary sulfate formation by using 2a is not limited to the re-
action of the 1-O-alkyl glycerol-2,3-disulfate derivatives (1a
and 1b). Similar regioselectivity was observed in the 1-O-
phenylglycerol-2,3-disulfate 1c as well (Entry 10). It is note-
worthy that only silylating agents having nitrogen gave 3 pre-
dominantly (Entries 1−6 and 10).
In order to elucidate the reaction mechanism, the following
two reactions were carried out:
2a
C10H21OSO3SiEt3
−−−−−→
C10H21OSiMe3
CH3CN
100◦C,2 h
(1)
The treatment of bis(trimethylsilyl) ester of 1-O-decyl glyc-
erol-2,3-disulfate 1a8 with 2 mol amt. of trimethylsilyl-N-tri-
methylsilylacetimidate (BSA) 2a, and the subsequent hydroly-
sis with NaOH afforded the corresponding 1-O-decyl glycerol-
2-sulfate 3 in 81% yield with a high regioselectivity (Entry 1).
In contrast, the reaction of dipyridinium salt of 1-O-decyl glyc-
6
In the first of these, decyl triethylsilyl sulfate 6 was treated
with 2 mol amt. of 2a in acetonitrile. In this case, decyl tri-
methylsilyl ether was obtained as the main product (63%).
The result suggests that the trimethylsilyl group in 2a at-

182 Bull. Chem. Soc. Jpn., 74, No. 1 (2001)
© 2001 The Chemical Society of Japan
tacks the nucleophilic oxygen of 6 in the reaction process. In
OTf anion. Therefore, the transfer of the trimethylsiloxysulfo-
nyl cation from the oxonium ion to OTf– did not occur in the re-
action (Eq. 4).
the second study, the desulfation reaction of decyl trimethyl-
1
silyl sulfate 7 with 2a in acetonitrile-d3 was monitored by H
and 29Si NMR spectroscopies.8 In the resulting reaction mix-
ture, bis(trimethylsilyl)sulfate and acetonitrile were detected
along with decyl trimethylsilyl ether as the main products:
C10H21OSO3SiMe3 +SiMe3OTf −→
7




2a
−OTf
C10H21O+ SO3SiMe3
(4)
C10H21OSO3SiMe3
−−−−−−−−−−→
CD3CN,100◦C,2h
SiMe3
2g
7
C10H21OSiMe3 +CH3CN+(Me3SiO)2SO2.
(2)
In summary, we developed an efficient method for the prepa-
ration of secondary alkyl sulfates having a primary hydroxy
group by the regioselective desulfation of bis(trimethylsilyl)
ester of 1-O-decyl glycerol-2,3-disulfate. The oxomium salts
might play an important role in proceeding the reaction.
From these results, we postulate a possible mechanism of
the desulfation reaction, illustrated in Scheme 2. As shown,
since the trimethylsilyl group seems to attack the alcoholic ox-
ygen of 7, oxonium salt 8 would be generated. The oxonium
salt should be liable to release the trimethylsiloxy sulfonyl cat-
ion, and the released cation would be trapped by the imidate
anion to give 9, which would subsequently decompose to ace-
tonitrile and bis(trimethylsilyl)sulfate. Because the oxonium
salt 8 would be the intermediate, a steric hindrance in the vicin-
ity of the oxygen atom of 8 would cause a difference in the ox-
onium formation between the primary alkyl sulfate and sec-
ondary alkyl sulfate, and the difference would affect the selec-
tivity of the reaction.
Experimental
Preparation of 1a. After a mixture of 1-O-decyl glycerol
(10.8 g, 50.0 mmol) with chloro sulfuric acid (14.0 g, 120.0 mmol)
in dichloromethane (40.0 ml) was stirred at r.t. for 0.5 h , chlorotri-
methylsilane (19.6 g, 180.0 mmol) was added. The solution was
stirred for 0.5 h at 50 °C and then concentrated under reduced
pressure to give the blown amorphous of 1a (26.0 g) quantitatively
without any impurities. 1a: 1H NMR(CDCl3) δ 0.42 (s, 18H), 0.85
(t, 3H), 1.24 (m, 14H), 1.53 (m, 2H), 3.45 (t, 2H), 3.69 (d, 2H),
4.38 (dd, 1H), 4.48 (dd, 1H), 4.83 (m, 1H).
General Procedure. A solution of 1a (2.6 g, 5.0 mmol) and
2a (2.03 g, 10.0 mmol) in acetonitrile (5.0 ml) was heated at 100
°C for 2 h. A NaOH solution was then added, and the solution was
evaporated. The yield was determined by 1H NMR of this residue.
The residue was easily purified by ODS gel chromatography or re-
1
crystallization. 3: H NMR (D2O) δ 0.90 (t, 3H), 1.31 (m, 14H),
1.61 (m, 2H), 3.52 (m, 2H), 3.71−3.89 (m, 3H), 3.85 (dd, 1H), 4.51
(m, 1H). 4: 1H NMR (D2O) δ 0.89 (t, 3H), 1.31 (m, 14H), 1.62 (m,
2H), 3.50−3.64 (m, 4H), 3.98−4.13 (m, 3H).
Scheme 2.
References
The postulated mechanism requires an electrophilic attack
of the trimethylsiloxysulfonyl cation on the imidate anion to
form bis(trimethylsilyl)sulfate. Evidence for this electrophilic
reaction process was gained in the reaction of 7 with 2b. In this
reaction, Me2NSO3SiM3 was obtained as a by-product along
with decyl trimethylsilyl ether (Eq. 3). This result shows that
an electrophilic attack of the trimethylsiloxysulfonyl cation to
Me2N– occurred in the reaction.9
1
M. Nakamura, T. Takeda, H.Yamada, M. Miyamato, and A.
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B. Gruber, B. Fabry, B. Giesen, and W. F. Muller, Tenside
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2
3
E. Gilbert, “Sulfation and Related Reactions,” Interscience
Publishers, NewYork (1965), Chap. 6.
4
5
E. Gilbert, Chem. Rev., 62, 549 (1962).
“Methoden der Organishen Chemie Band E11/Teil12,”ed
by Houben Weyl, Georg Thieme Verlag, Stuttgart (1985), p. 997.
R. Takano, M. Matsuno, K. Kamei-Hayashi, and S. Hirase,
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M. Matsuno, R. Takano, K. Kamei-Hayashi, and S. Hara,
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29Si NMR(CDCl3) δ 15.9 (C10H21OSiMe3), 33.9 ((Me3-
SiO)2SO2), 35.6 (C10H21OSO3SiMe3).
29Si NMR(CDCl3) δ 31.6 (Me2NOSO3SiMe3).
C10H21OSO3SiMe3 +Me2NSiMe3
6
7
2b
−−−−−−−−−−→
C10H21OSiMe3 +Me2NSO3SiMe3. (3)
7
CD3CN,100◦C,2h
In the case of 2g, which did not give a secondary sulfate in
the reaction with 1a, it seems reasonable to assume that the
formed oxonium salt is very stable because of the stability of
8
9