Additional file
Butadiene sulfone as ‘volatile’, recyclable dipolar, aprotic solvent
for conducting substitution and cycloaddition reactions
Yong Huang,a,c,† Esteban E. Ureña-Benavides,a,c,† Afrah J. Boigny, a Zachary S. Campbell, a Fiaz S.
Mohammed,a Pamela Pollet, b,c Jason S. Fisk, d Bruce Holden, d Charles A. Eckert a,b,c and Charles L.
Liotta a,b,c
a
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta,
30332, GA, USA
b.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332,
GA, USA
c.
Specialty Separations Center, Georgia Institute of Technology, Atlanta, 30332, GA, USA
d.
†
The Dow Chemical Company, Midland, Michigan, 48674, USA
Yong Huang and Esteban E. Ureña-Benavides are co-first authors contributing to this article.
*
E-mail address of the corresponding author: charles.liotta@chemistry.gatech.edu;
pamela.pollet@chemistry.gatech.edu.
Preparation of Benzyl Azide (1)
The benzyl azide used for the cycloaddition reactions was synthesized and isolated first in
acetonitrile water. Benzyl chloride (6.2 g) and sodium azide (4.4 g) were added to a three neck
round bottom flask, followed by addition of 20 mL of water and 80 mL of acetonitrile. The
reaction mixture was heated to 60 C and allowed to react overnight. Benzyl azide (1) was
extracted with dichloromethane, dried over MgSO4 and filtered. Acetonitrile and
dichloromethane were evaporated under reduced pressure to yield a clear yellow liquid.
Characterizations
Nuclear magnetic resonance (NMR): 1H-NMR and 13C-NMR spectra were measured on a Bruker
Avance III 400 spectrometer, and NMR yield was quantified by internal standard.
Gas chromatography/flame ionization detector (GC-FID): GC-FID was using a Shimadzu
GC2010 gas chromatograph fitted with a Supelco PTA-5 (30m x 0.32 mm x 1.00 µm, length x
inside diameter x film thickness) capillary column. The injector temperature was held constantly
at 300 C, and column oven was increased from 90 C to 300 C at a ramp rate of 15 C/min.
GC-FID detector temperature was held at 320 C. The used calibration curves are listed as below
in Fig.S6.
Triple quadrupole tandem mass spectrometer with ionization via ESI (ESI-MS): experiments
were run on a Quattro LC, made by Micromass, which is now part of Waters. The capillary
voltage was 3.5kV, and the cone voltage was 20V. The instrument was scanned from 1501500Da in 3 seconds. Nitrogen was used as both the nebulizing gas, at a flow of 100L/hr, and
the desolvation gas, at 600L/hr.
Ion trap/orbitrap tandem mass spectrometer (LTQ Orbitrap XL): made by Thermo Instruments.
The source voltage was 5kV, the capillary voltage was 35V, and the tube lens voltage was 110V.
The sheath gas was nitrogen, at a flow of 10 arbitrary units, and the auxiliary gas was nitrogen, at
a flow of 5 arbitrary units. The mass resolution was 30,000, and the instrument was scanned
from 75-2000Da.
Differential scanning calorimeter (DSC): DSC was carried out on a TA DSC Q20, under
nitrogen flow, at a scanning rate of 10 ºC min-1.
2
1
3
3
1
2
Fig.S1.a 1H-NMR of p-Toluenesulfonyl Cyanide (3) in DMSO-d6 for 2 days at 50 C.
p-Toluenesulfonyl Cyanide 1H NMR (DMSO-d6, ppm): δ = 2.46 (s, 3H), 7.64 (d, J= 8.6 Hz, 2H),
8.05 (d, J= 8.4 Hz, 2H). The same reaction solution (TsCN and DMSO-d6) was then spiked with
toluenesulfonic acid, and the 1H-NMR result was shown in Fig.S1.b.
2
1
y
y
z
3
x
z
x
3
1
2
Fig.S1.b 1H-NMR of p-Toluenesulfonyl Cyanide in DMSO-d6 for 2 days at 50 C, spiked with
toluenesulfonic acid.
The increased peaks x, y, z correspond to the increased amount of p-toluenesulfonate. pToluenesulfonate 1H NMR (DMSO-d6, ppm): δ = 2.30 (s, 3H), 7.19 (d, J=7.7 Hz, 2H), 7.69 (d,
J=7.8 Hz, 2H).
2
1
z
y
3
x
z
x
y
Fig.S1.c 1H-NMR of p-Toluenesulfonyl Cyanide in DMSO-d6 for 4 days at 50 C.
Comparing Fig.S1.C (reaction at 4 days) with Fig.S1.a (reaction at 2 days), p-Toluenesulfonyl
Cyanide was further consumed and its peaks became much smaller.
NL:
1.59E7
ce140723-01n#95-109 RT:
2.29-2.63 AV: 15 SB: 15
0.54-0.88 T: FTMS - p ESI
Full ms [150.00-2000.00]
171.0119
R=50718
z=1
100
90
Relative Abundance
80
70
60
50
40
30
20
10
0
NL:
8.73E5
171.0110
100
C 7 H 7 O 3 S:
C 7 H7 O 3 S 1
pa Chrg 1
90
80
70
60
50
40
30
20
10
0
160
180
200
220
240
260
m/z
280
300
320
340
360
Fig.S2 Negative Ion trap/orbitrap tandem MS of major product obtained upon reaction of DMSO
with p-toluenesulfonyl cyanide.
Exact mass analysis was consistent with the p-toluenesulfonate (ESI-FTMS (m/z): calcd. for
C7H7O3S 171.0110, found 171.0119 [M]-).
Fig.S3.a 13C NMR of 1-benzyl-5-p-toluenesulfonyl tetrazole (2) using cheletropic switch and
followed by solvent extraction prior to column chromatographic procedure.
No appreciable differences were observed between Fig.S2.a and Fig.S2.b, which suggests that
comparable purities can be obtained without the need for subsequent column chromatography.
Fig.S3.b 13C NMR of 1-benzyl-5-p-toluenesulfonyl tetrazole (2) using cheletropic switch and
followed by solvent extraction after the column chromatographic procedure.
GT Mass Spectrometry Laboratory
01-Jul-2014 11:06:46
Urena TetrazoleProduct (methanol)
ce140701qb 6 (0.391) Sm (SG, 2x0.20); Cm (4:10-30:39)
Scan ES+
4.04e7
315.1
100
%
332.2
316.1
333.2
317.2
347.2
356.2
378.2
0
m/z
280
285
290
295
300
305
310
315
320
325
330
335
340
345
350
355
360
365
370
375
380
385
390
395
400
405
Fig.S4 ESI-MS spectra of 1-Benzyl-5-(p-toluenesulfonyl)tetrazole (2) from cycloaddition
chemistry using BS as solvent: 315 [M+H]+, 332 [M+H2O]+
410
415
Fig.S5 DSC scan of 1-Benzyl-5-(4-methylphenylsulfonyl)tetrazole (2) product from
cycloaddition chemistry reaction using BS as solvent.
DSC scan started at 25 °C, and then temperature was increased to 160 °C at a ramp rate of
10 °C/min. The initial heating process helped to eliminate thermal history of sample. Next, DSC
was cooled down to -20 °C for sample to crystallize, and then was heated to 160 °C to determine
its melting point and enthalpy of fusion.
6000000
y = 28,294,277.39x - 24,087.43
R² = 1.00
5000000
Peak area
4000000
3000000
2000000
1000000
0
0
0.05
-1000000
0.1
0.15
0.2
0.25
Concentration (mol/L)
Fig.S6.a GC-FID calibration curve for internal standard biphenyl.
This curve was used to calculate the concentration of biphenyl in reaction solution, which was
then used to determine the concentration of BnCl before reaction.
3000000
y = 14,431,708.94x - 15,059.71
R² = 1.00
2500000
Peak area
2000000
1500000
1000000
500000
0
0
-500000
0.05
0.1
0.15
0.2
0.25
Concentration (mol/L)
Fig.S6.b GC-FID calibration curve for BnAz (1).
This curve kept track of concentration of BnAz in reaction solution. GC yield of BnAz was able
to be calculated.
3500000
y = 15,800,237.11x - 12,130.60
R² = 1.00
3000000
Peak area
2500000
2000000
1500000
1000000
500000
0
-500000
0
0.05
0.1
0.15
0.2
0.25
Concentration (mol/L)
Fig.S6.c GC-FID calibration curve for BnCl.
This curve was used to calculate the concentration of BnCl in reaction solution. Conversion of
BnCl at different reaction time was able to be determined.
Fig.S7.a Piperylene sulfone 1H NMR (DMSO-d6, ppm): δ = 2.27 (s, J=7.2 Hz, 3H), 3.78 (m, 3H),
6.07 (m, 2H).
Fig.S7.b Piperylene sulfone 13C NMR (DMSO-d6, ppm): δ = 12.86, 54.42, 58.93, 123.35,
131.39.