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SiliaBond® Sulfonic Acids – Versatile and Useful Products for Purification Needs
Geneviève Gingras, Annie Michaud, Delphine Desplantier-Giscard, Michel Morin and François Béland*
SiliCycle® Inc., www.silicycle.com
1200 Ave Saint-Jean-Baptiste
1200,
Saint-Jean-Baptiste, suite 114,
114 Quebec City,
City Quebec,
Quebec Canada,
Canada G2E 5E8
*[email protected]
“Catch and Release” Purification of Amines using SiliaBond® SCX & SCX-2
Amine Free Basing using SiliaBond® SCX & SCX-2
Supported sulfonic acids are a class of strong acids (pKa <<1) widely
used in different fields of synthetic organic chemistry.
Amine purification and elimination of basic impurities are easily and efficiently accomplished
by a “Catch and Release” purification with the SiliaBond® SCX and SCX-2.
Using the “Catch and Release” method, SiliaBond® Sulfonic Acids quickly
deprotonate amine with very high yields.
Their applications are widely known and their various forms are used
in a large number of settings: from the drug discovery laboratories to
the manufacturing processes.
“Catch and Release” Purification of Amines using SiliaBond® Products in MeOH
SiliCycle® SiliaBond® Sulfonic Acids
SiliCycle® has developed the two following SiliaBond® Sulfonic Acids:
Amine
pKa
O
O
S
S
OH
O
SiliaBond® SCX-2
[PN: R51230B]
We are presenting different applications using SiliaBond® Sulfonic
Acids to demonstrate the effectiveness and versatility of these silicabased products in bulk and SPE cartridge medias such as:
9 “Catch and Release” purification of amine (or removal of basic
impurities)
9 Amine free basing
9 Boc groups deprotection
Silica
× 300
Polymer
Silica, in toluene, 110°C,4 h
15kV
500μm
× 30
Polystyrene, in toluene, 110°C, 1h
Principle of “Catch and Release” Purification in SPE
1) Column
conditioning
2) Apply
sample
3) Interference
elution
Catch
(%)
Release
(%)b
Release
(%)b
4) Amine released with
ammonia /methanol
98
100
100
100
Aniline
4.62
100
95
100
90
4-Methoxyaniline
5.29
100
100
100
92
2-Aminothiazole
5.39
100
100
100
Morpholine
8.36
100
100
100
87
Benzylmethylamine
9.58
100
100
100
92
Cyclohexylamine
10.64
100
95
100
79
Tributylamine
10.75
100
100
100
91
Quinuclidine
11.00
100
94
100
65
Amine
collected
a
.
OH
N
TFA
Amine salts
Ephedrine •
SiliaBond® SCX
SiliaBond® SCX-2
Yieldb (%)
Yieldb (%)
92.8
93.4
98.7
95.3
97.9
95.4
HCl
TFA
AcOH
a:
“Catch and Release” procedure using SiliaBond® SCX and SCX-2 SPE Cartridges (4eq. in
MeOH), b: Yields were determined by GC-FID
Boc- Groups Deprotection using SiliaBond® SCX
The tert-butoxycarbonyl
(Boc-) is widely used as an
amino protecting group in
organic synthesis and can
be easily removed by our
SiliaBond® SCX with high
yield and purity (Exp #3).
Exp #1: Room temperature
Reaction time: 1h
Note: Deprotection not completed
4-Nitroanilinec
0.98
97
100
100
100
Aniline
4.62
100
96
100
88
4-Methoxyaniline
5.29
100
100
100
92
2-Aminothiazole
5.39
100
100
100
88
Morpholine
8.36
100
89
100
83
Benzylmethylamine
9.58
100
97
100
84
Cyclohexylamine
10.64
96
96
100
74
Tributylamine
10.75
100
98
100
92
Conclusion
Quinuclidine
11.00
100
98
100
77
SiliaBond® Sulfonic Acids (SCX & SCX-2) are two versatile, easy to use,
and very efficient products for purification needs. Both can be used in
many applications such as:
Solvent Effect on the “Catch and Release” Purification of 2-Aminothiazolea
Eluted
non-basic impurities
SiliaBond® SCX
or
SiliaBond® SCX-2
HCl
AcOH
87
a: 10 min stirring for both Catch and Release steps, b: Release % is calculated in function of the
Catch % proportion, c: in CH2Cl2
Amine
“Caught”
OH
Amine Free Basing using SiliaBond® productsa
0.98
SiliaBond® SCX-2 (or SiliaBond® Propylsulfonic Acid)
No static charge
Solvent independent
High thermal and mechanical stability
10kV 50μm
Catch
(%)
4-Nitroanilinec
Characteristics of SiliaBond® products
No swelling
Suitable for µ-wave use
Bulk media (4 eq.)a
SiliaBond® SCX (or SiliaBond® Tosic Acid)
OH
O
SiliaBond® SCX
[PN: R60530B]
SPE Cartridge (2 eq.)
N
Acetone
CH2Cl2
MeOH
THF
Catch (%)
≥ 98
≥ 98
100
100
Release (%)
100
100
100
100
Using SiliaBond® SCX SPE Cartridge (2.0 eq.)
(N.B.: SiliaBond® SCX-2
can also be used for the
Boc- group deprotection).
Exp #2: Room temperature
Reaction time: 17h
Note: Deprotection not completed
Exp #3: using µ-wave irradiation
Reaction time: 5 x 1min
Yield: 99% (isolated product)
7.6
7.2
6.8
6.4
6.0
5.6
5.2
4.8
4.4
4.0 3.6
PPM
3.2
2.8
2.4
2.0
1.6
1.2
0.8
0.4
Using SiliaBond® SCX (3.0 eq.)
“Catch and Release” purification of amine
Removal of basic impurities from an unpurified sample
Amine free basing
Boc- group deprotection
Acknowledgements
The authors
Th
th
th k Annie
thank
A i Cummings,
C
i
Sté h
Stéphane
P ll ti and
Pelletier
d Catherine
C th i
Tessier for their analytical support.