User friendly synthesis of VogelS silyl sulfinate and its application in quantitative Gc-Ms analysis

Article abstract of DOI:10.1080/10426507.2014.996644

The synthesis of trimethylsilyl 2-methylprop-2-ene-1-sulfinate (Vogel's silyl sulfinate) from methallyltrimethylsilane and SO2 in the presence of Tf2NTMS was developed. The title compound silylates carbohydrates and other polyhydroxylated compounds by producing SO2 and isobutene as gaseous side products. This silylation procedure is perfectly suitable for derivatization and subsequent GC-MS quantitative analysis of ribose and malic acid as representatives of organic polyhydroxylated compounds.

Full text of DOI:10.1080/10426507.2014.996644

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User Friendly Synthesis of Vogel's Silyl Sulfinate and its
Application in Quantitative GC-MS Analysis
a
a
Irina Novosjolova & Māris Turks
a
Faculty of Material Science and Applied Chemistry, Riga Technical University, Paula Valdena
Str. 3, Riga, LV-1007, Latvia
Accepted author version posted online: 16 Mar 2015.
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USER FRIENDLY SYNTHESIS OF VOGEL’S SILYL SULFINATE AND ITS
APPLICATION IN QUANTITATIVE GC-MS ANALYSIS
Irina Novosjolova, Māris Turks*
Faculty of Material Science and Applied Chemistry, Riga Technical University,
Paula Valdena Str. 3, Riga, LV-1007, Latvia; e-mail: maris_turks@ktf.rtu.lv
Abstract
The synthesis of trimethylsilyl 2-methylprop-2-ene-1-sulfinate (Vogel’s silyl sulfinate) from
methallyltrimethylsilane and SO
2
in the presence of Tf
2
NTMS was developed. The title compound
and isobutene
silylates carbohydrates and other polyhydroxylated compounds by producing SO
2
as gaseous side products. This silylation procedure is perfectly suitable for derivatization and
subsequent GC-MS quantitative analysis of ribose and malic acid as representatives of organic
polyhydroxylated compounds.
1
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Keywords
Trimethylsilyl 2-methylprop-2-ene-1-sulfinate, silylation, GC-MS derivatization, ribose, malic
acid
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INTRODUCTION
The use of gas chromatography (GC) with capillary columns in the quantitative and qualitative
analysis of carbohydrates and other polyhydroxylated organic substances is often superior to
other analytical techniques due to its sensitivity especially if it is coupled with mass
1
spectrometric (MS) detection. On the other hand, organic molecules possessing several polar
functional groups such as -OH, -COOH, -NH , and -SH are characterized by low volatility. They
2
also tend to interact with GC column material thus producing asymmetric chromatographic
2
signals with extensive tailing. The extensively used derivatization procedure to enhance the
2
,3
volatility of organic substances for their gas chromatographic analysis is silylation.
Trimethylsilyl derivatives of polyhydroxylated compounds are characterized by excellent
thermal stability and ionization when MS detection is used. Various silylation procedures and
derivatization technologies have been developed up to now, including the injection port
2
derivatization. Regardless the fact that the first silylation was introduced in 1944, the search for
4
improved silylation conditions and novel reagents is still ongoing. Very often one commercially
available silyl group donor should be combined with others and only the resulting silylating
5
cocktail is efficient as derivatization reagent for quantitative GC-analysis. In 2005, Vogel and
coworkers reported efficient and traceless silylation of simple alcohols, phenols and carboxylic
6
acids with trimethylsilyl 2-methylprop-2-ene-1-sulfinate (Vogel’s silyl sulfinate). The aim of
the present research is to develop an user-friendly gram-scale synthesis of the title reagent and to
demonstrate its applications in quantitative GC-MS analysis of polyhydroxylated organic
compounds.
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RESULTS AND DISCUSSION
The previously reported syntheses of Vogel’s silyl sulfinate 2 were using either sufficiently
strong Lewis acids to execute the sila-ene reaction between allylsilanes and SO
2
at low
temperatures in liquid SO
2
or weak Lewis acids that required to carry out this reaction in a
7
pressure reactor. By careful choice of Lewis acid and solvent we have found that the synthesis
of 2 can be accomplished at ambient temperature by a simple bubbling of gaseous SO through a
2
toluene solution of 1 in the presence trimethylsilyl bis(trifluoromethanesulfonyl)imide
8
(
Tf
bis(trifluoromethanesulfonyl)imide (Tf
sila-ene reaction. After applying the flow of SO
2
NSiMe
3
; Gosez Lewis acid) (Scheme 1). Methallylsilane (1) was mixed with
2
NH) to produce the required catalyst in situ before the
for 2 h the reaction mixture was directly
2
fractionally distilled under reduced pressure to provide product 2 in 71% yield. The developed
synthetic procedure is suitable for preparation of 2 in at least 30-40 g scale.
With the compound 2 in hand we proceeded to its applications as GC-MS derivatization reagent.
The presence of high number of functional groups and several tautomeric forms in solution
9
makes carbohydrates as excellent examples for the GC-derivatization method evaluation.
Additionally, per-O-silylated monoscaharides have found useful applications in synthetic organic
1
0
chemistry. When a suspension of
Vogel’s silylsulfinate 2 clean GC-MS traces and H-NMR spectrum were obtained after 2 h at
ambient temperature. The only co-products were isobutene and SO . Both analyses
independently showed a mixture of isomers in a ratio 35:65. Their structures were attributed as
D
-ribose in CH
3
CN (or CD CN) was treated with an excess of
3
1
2
per-O-silylated α-
Scheme 2).
D
-ribopyranose (α-3) and per-O-silylated β-D-ribopyranose (β-3), respectively
(
4
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This prompted us to evaluate the potential application of 2 as the derivatization reagent for
quantitative GC-MS analysis. Indeed, GC-MS analysis of
with 2 in CH CN provided good linear correlation (Figure 1a). The error of quantification of
ribose was below 0.5%. Further we have chosen -malic acid as an example of hydroxy
D-ribose samples that were treated
3
D-
L
dicarboxylic acid for quantification experiment after derivatization with 2 (Scheme 3). Also in
this case, the series of derivatized samples provided excellent linear correlation and the
experimental error of quantification of L-malic acid was below 1.5% (Figure 1b).
In conclusion we have developed an user-friendly synthetic procedure towards Vogel’s silyl
sulfinate 2. We have demonstrated for the first time its application as the derivatization reagent
in the quantitative GC-MS analysis of polyhydroxylated organic compounds with
malic acid as the representative examples.
D-ribose and L-
EXPERIMENTAL
Trimethylsilyl 2-methylprop-2-ene-1-sulfinate (2).
A three neck round-bottom flask was charged with a gas inlet tube and Vigreux column the top
of which contains the Liebig’s condenser. The system was evacuated in vacuo, flame-dried, and
cooled under N
4.2 mmol, 6 mol-%) in anh. toluene (30 mL) was slowly added to a solution of
methallyltrimethylsilane (44 mL, 0.25 mol, 1.06 equiv. (~2.5 mL, 14.2 mmol is consumed by
Tf NH)) in anh. toluene (50 mL) at ambient temperature. An exotermic reaction with evolution
of isobutene was observed and the resulting reaction mixture was stirred at ambient temperature
2
atmosphere. A solution of bis(trifluoromethanesulfonyl)imide (Tf
2
NH) (4.0 g,
1
2
for 20 min to ensure the formation of Tf
2
NSiMe
3
. Then gaseous SO was bubbled through the
2
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resulting mixture at ambient temperature over 1,5-2 h. Initially (the first 30-45 min.) a slightly
exothermic reaction was observed. The gas inlet tube was removed, the system was attached to
vacuum and toluene was distilled at 35 °C (55-60 mbar; bath temp. 80 °C). Then the pressure
was adjusted to 1.2 Torr and Vogel’s silyl sulfinate 2 was collected in the following fractions: I
fraction (2.6 g, b.p. 35-41 °C, GC purity 93.0%), II fraction (17.0 g, b.p. 41-49 °C, GC purity
98.6%), III fraction (13.1 g, b.p. 49-50 °C, GC purity 99.6%). The total yield calculated on pure
1
substance: 32.2 g (71%). H NMR (CDCl
3
, 400 MHz): 5.06 (m, 1H, Ha-C(3)), 4.96 (m, 1H, Hb-
C-
C(3)), 3.38, 3.33 (2dd, AB syst., J=12.0, 1.0 Hz, 2H, H-C(1)), 1.84 (dd, J=1.5, 1.0 Hz, 3H, H
3
1
3
C(2)), 0.30 (s, 9H, H
Silylation of -ribose.
Reagent 2 (52 μL, 304 μmol, 8 equiv.) was added to a suspension of
in CD CN (1 mL). The resulting mixture was kept for 2 h at ambient temperature and then
3
C-Si). C NMR (CDCl
3
,100.6 MHz): 134.4, 117.9, 69.3, 23.5, 0.6.
D
D
-ribose (5.77 mg, 38 μmol)
3
analyzed by GC-MS and NMR. GC-MS conditions: capillary column HP-5MS (5%
phenylmethylsiloxane) 30 m × 0,25 mm × 0,25 μm; injector temp. 250 °C; eluent He, flow rate
0
2
.8 ml/min; split injection 400:1; injection volume 0.2 μL; temp. regime: 70 °C 0 min, gradient
0 °C/min → 250 °C, gradient 120 °C/min → 310 °C, 310 °C for 1 min; MS-detector (ESI, 70
eV); MS Quad 150 °C; MS Source 230 °C. For the construction of the calibration curve the
o
corresponding solutions (CH
3
CN) were prepared in volumetric flasks (10 mL) and kept at 50 C
for 2 h prior analysis. The GC-MS correlation area for each data point was obtained in triplicate.
Silylation of -malic acid and construction of the calibration curve.
Reagent 2 (5 equiv) was added to a suspension of precisely weighted sample of malic acid in
CH CN and the volumetric flask (10 mL) was filled to the mark with CH CN. The resulting
L
3
3
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derivatization mixture was kept for 30 min at ambient temperature and analyzed by GC-MS (see
above): split injection 600:1; injection volume 1.0 μL; temp. regime: 50 °C 3 min, gradient 50
°C/min → 250 °C, 250 °C for 1 min, gradient 50 °C/min → 310 °C, 310 °C for 1 min.
ACKNOWLEDGMENTS
This work was financed by the Latvian Council of Science Grant No 12.0291. The authors thank
Professor E. Liepinsh for NMR analysis of per-O-silylated ribose. Generous donation of organic
solvents by JSC Grindeks is kindly acknowledged. I.N. thanks the European Social Fund within
the project «Support for the implementation of doctoral studies at Riga Technical University» for
a scholarship.
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REFERENCES
1. Zou, P.; Yang, X.; Huang, W.-W.; Zhao, H.-T.; Wang, J.; Xu, R.-B.; Hu, X.-L.; Shen, S.-
Y.; Qin, D. Molecules 2013, 18, 9933-9948.
2
3
. Wang, Q.; Ma, L.; Yin, C.-r.; Xu, L. J. Chromatogr. A 2013, 1296, 25-35.
. a) Poole, C. F. J. Chromatogr. A 2013, 1296, 2-14; b) Halket, J. M.; Zaikin, V. G. Eur. J.
Mass Spectrom. 2003, 9, 1-21.
4
5
. Van Look, G. Simchen, G. Heberle, J. Silylating Agents, Fluka, Buchs: Switzerland, 2nd
ed., 1995.
. a) Toledano, R. M.; Cortés, J. M.; Andini, J. C.; Vázquez, A.; Villén, J. J. Chromatogr. A
2
6
1
012, 1256, 191-196; b) Tzing, S.-H.; Ding, W.-H. J. Chromatogr. A 2010, 1217, 6267-
273; c) Wu, J.; Hu, R.; Yue, J.; Yang, Z.; Zhang, L. J. Chromatogr. A 2009, 1216, 1053-
058.
6
7
. Huang, X.; Craita, C.; Awad, L.; Vogel, P. Chem. Commun. 2005, 1297-1299.
. a) Bouchez, L.C.; Reddy Dubbaka, S.; Turks, M.; Vogel, P. J. Org. Chem. 2004, 69,
6413-6418; b) Marković, D.; Volla, C. M. R.; Vogel, P.; Varela-Álvarez, A.; Sordo, J. A.
Chem. Eur. J. 2010, 16, 5969; c) Bouchez, L.; Vogel, P. Synthesis 2002, 225-231.
. Mathieu, B.; Ghosez, L. Tetrahedron 2002, 58, 8219–8226.
8
9
. a) Ruiz-Matute, A. I.; Hernández-Hernández, O.; Rodríguez-Sánchez, S.; Sanz, M. L.;
Martínez-Castro, I. J. Chromatogr. B 2011, 879, 1226–1240; b) Medeiros, P. M.; Bernd
R.T. Simoneit, B. R. T. J. Chromatogr. A 2007, 1141, 271–278.
10. Kulkarni, S. S.; Gervay-Hague, J. Org. Lett. 2008, 10, 4739-4742.
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a)
b)
Figure 1. a) GC-MS traces of per-O-silylated ribopyranose, b) Calibration curves for
quantitative analysis of
D
-ribose and
L-malic acid.
9
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Scheme 1. Synthesis of Vogel’s silyl sulfinate
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3
3
3
JH1-H2 = 7.2 Hz
JH2-H3 = 2.5 Hz
JH3-H4 = 2.3 Hz
3.74H
3
.26
3
H
.42
H
67.3
O
0
.107
Me SiO
0
.108
3
19.0
3JH4-H5eq = 5.1 Hz
3JH4-H5ax = 10.2 Hz
2J
4JH1-H5eq = 0.4 Hz
4JH3-H5eq = 1.2 Hz
62.5
72.5
1
7.7
0
.111
OSiMe
.91H
3 0.390
3
7
4.0
93.6
H3.58
O
= 10.4 Hz
H5ax-H5eq
0
0
.099
.976
Me SiO
H4.72
3
SiMe3
7.4 0.115
-3
1
6.5
O
S
1
CH CN
3
0.670
D-ribose +
SiMe3
O
or CD CN
3.69H
3
2
3.51
3JH1-H2 = 3.5 Hz
3JH2-H3 = 2.8 Hz
3JH3-H4 = 3.7 Hz
3
H
.82
H
67.3
-3
O
0
.108
Me SiO
0
.276
3
57.5
69.5
1
6.8
91.8H4.83
3
JH4-H5eq = 4.4 Hz
3
.88H
7
2.6
H3.15
O
3
JH4-H5ax = 10.2 Hz
0
1
.091
.070
0.114
Me SiO
OSiMe
3
0.427
3
2
SiMe3
JH5ax-H5eq = 10.2 Hz
15.9
1
4.7
1
7.0 0.125
4J
= 1.0 Hz
H3-H5ax
0
.379
-3
-3 = 35 : 65
Scheme 2. Derivatization of D-ribose with TMS-groups and the NMR analysis (600 MHz,
1
13
29
CD
3
CN) of the products: δ H: x.xx; δ C: y.yy; δ Si: z.zz.
11
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Scheme 3. Derivatization of L-malic acid with 2
12
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