Thermal Sulfenate-Sulfoxide Rearrangement
J. Am. Chem. Soc., Vol. 122, No. 14, 2000 3373
7.31 (d, J ) 9.1 Hz, 2 H), 6.69 (d, J ) 15.8 Hz, 1H), 6.33 (d, J ) 15.9
Hz, 1 H). 13C NMR (CDCl3) δ 78.5, 120.1, 123.1, 124.3, 126.8, 128.5,
128.7, 135.7, 136.2, 151.6. IR (neat): 1577, 1509, 1335, 1085, 1052,
966 (C-D bend), 910, 836, 740. MS (CI, [M + H]+) calcd: 290.8020,
obsd: 290.8020.
conditions, retention times were ∼11 min for the sulfoxide, ∼15 min
for naphthalene, and ∼17 min for the sulfenate.
The separation and quantification of the sulfenate and its products
of thermolysis in toluene was performed by HPLC with a normal phase
column (LiChrosphere, 100 Å silica 5 µm, 4.6 × 250 mm). The
injection volume was 20 µL; the eluent is a gradient of hexanes and
ethyl acetate. First 5 min: isocratic mixture of 8% ethyl acetate/92%
hexanes, then a linear gradient for 3 min to reach 90% ethyl acetate/
10% hexanes, and finally an isocratic mixture of 90% ethyl acetate/
10% hexanes for 2 min. Under these conditions, retention times were
∼11.5 min for the sulfoxide, ∼2.2 min for anthracene and ∼3.6 min
for the sulfenate. The amounts of sulfenates and sulfoxide were
calculated as the ratio between the area of their respective absorption
peaks at 340 nm and the area of the anthracene peak.
Kinetic Studies, Monitoring of the Reaction, Determination of
the Activation Parameters. Preparation of the Stock Solutions. Four
stock solutions of sulfenate were prepared with about the same
concentration: c ) 10-3 mol/L. In acetonitrile without base, 24.8 mg
of cinnamyl-4-nitrobenzenesulfenate and 6 mg of naphthalene were
dissolved in 89 mL of acetonitrile. Another stock solution was prepared
with 71 mg of cinnamyl-4-nitrobenzenesulfenate, 21 mg of naphthalene
and 250 mL of acetonitrile. In acetonitrile with base, 100 mg of
cinnamyl-4-nitrobenzenesulfenate, 63 mg of naphthalene and 20 µL
of 2,6-Di-tert-butylpyridine were dissolved in 250 mL of acetonitrile.
In toluene, 78 mg of cinnamyl-4-nitrobenzene sulfenate and 50 mg of
anthracene were dissolved in 250 mL of toluene. All solutions were
degassed upon preparation by sonication/vacuum to remove any
potential oxygen from the solution and avoid an oxidation of the
sulfenate into sulfinate during storage.
Kinetic Studies with/without Base. Thermolysis of Cinnamyl-4-
nitrobenzene Sulfenate in Acetonitrile-d3, with ∼0.17% of Base
Added. Cinnamyl-4-nitrobenzene sulfenate (74 mg) and 2-naphthyl
acetonitrile (28 mg) were dissolved in 4.0 mL of acetonitrile-d3, and
three tubes each containing 0.6 mL of this solution were prepared.
(Concentration of sulfenate: ∼6.44 10-2 mol‚L-1). A solution of 2,6-
di-tert-butylpyridine (20 µL, ∼0.12 M) in acetonitrile-d3 was added to
the remaining solution and mixed, and three other NMR tubes were
Experimental Procedure for Thermolysis. The solution is placed
in a 13 × 100 mm test tube containing a small magnetic stirrer. The
tube is closed with a septum (fits in the inner ring of the septum). The
solution is degassed with ultrasounds/vacuum for 10 min then the test
tube is placed under nitrogen. A 500 mL three necks round-bottom
flask is filled almost to the top with solvent (depending on the desired
temperature, the nature of the solvent varies) and a thermometer is
placed on one neck with an adapter. A condenser is placed on the second
neck of the flask. The third neck of the flask is closed with a glass
stopper hat can be easily removed and replaced by the 13 × 100 mL
test tube with the septum. The 19/32 glass neck fits tightly with the
outer ring of the septum. The liquid is refluxed in the round-bottom
flask and is stirred with a large magnetic stirrer at a fast speed to ensure
homogeneity of the temperature in the liquid. When the temperature is
stable, the glass stopper is removed and the solution of sulfenate in
the test tube is placed in the refluxing liquid. The stirring plate is moved
in a way that the small magnetic stirrer in the test tube can rotate and
maintain homogeneity of the temperature inside the test tube. Some
solution of sulfenate is taken out of the test tube via a syringe (∼0.05
mL) regularly and is immediately cooled to dry ice temperature in a
small vial. The vial is then placed and stored in dry ice until the solution
can be used for injection in HPLC. Typically, the first collection via a
syringe was performed at least one minute after the test tube was placed
in the refluxing solvent to allow the contents to reach a constant and
homogeneous temperature. The liquids used in the round-bottom flask
were chosen for their boiling points and were: methylene chloride (bp
40 °C), acetone (bp 56 °C), tetrahydrofuran (bp 66 °C) and ethyl acetate
(bp 77.1 °C).
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filled with 0.6 mL of the basic solution. H NMR was taken before
and after thermolysis for each tube. The thermolysis itself was realized
by putting the NMR tube at 66 °C (the tip of the tube containing the
sample is placed in refluxing THF, in these conditions, it is assumed
that the sample is placed at constant temperature) for 20 min. Special
care was taken to ensure that tubes were stored at a dry ice temperature
and away from light during the course of the experiment.
Thermolysis of Cinnamyl-4-nitrobenzene Sulfenate in Acetoni-
trile-d3, with ∼0.44% of Acid Added. Cinnamyl-4-nitrobenzene
sulfenate (70 mg) and 2-naphthyl acetonitrile (25 mg) were dissolved
in 4.0 mL of acetonitrile-d3, and three tubes each containing 0.6 mL of
this solution were prepared. A solution of p-toluenesulfonic acid in
acetonitrile-d3 (50 µL, ∼0.12 M) was added to the remaining solution
and mixed, and three other NMR tubes were filled with 0.6 mL of the
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acidic solution. H NMR was taken before and after thermolysis for
each tube. The thermolysis itself was realized by putting the NMR
tube at 66 °C (the tip of the tube containing the sample is placed in
refluxing THF; in these conditions, it is assumed that the sample is
placed at constant temperature) for 15 min. Special care was taken to
ensure that tubes were stored at dry ice temperature and away from
light during the course of the experiment.
Thermolysis of Cinnamyl-4-nitrobenzene Sulfenate in Toluene-
d8, with ∼0.16 Equiv of Base Added. Cinnamyl-4-nitrobenzene
sulfenate (77 mg) and 2-naphthyl acetonitrile ( 23 mg) were dissolved
in 3.0 mL of toluene-d8 and three tubes each containing 0.5 mL of this
solution were prepared. (Concentration of sulfenate: ∼8.9 10-2
mol‚L-1). 2,6-Di-tert-butylpyridine (5 µL) was added to the remaining
solution and mixed, and three other NMR tubes were filled with 0.6
mL of the basic solution. 1H NMR was taken before and after
thermolysis for each tube. The thermolysis itself was realized by putting
the NMR tube at 66 °C (the tip of the tube containing the sample is
placed in refluxing THF, in these conditions, it is assumed that the
sample is placed at constant temperature) for 1 h. Special care was
taken to ensure that tubes were stored at dry ice temperature and away
from light during the course of the experiment.
Separation and Quantification with HPLC and Photodiode Array
Detector. The separation and quantification of the sulfenate and the
products of thermolysis in acetonitrile was performed by HPLC with
a reversed phase column (Nova Pak C18, 60 Å, 4 µm, 39 × 150 mm).
The injection volume was 20 µL; the eluent is a gradient of water and
acetonitrile. First minute: isocratic mixture of 30% acetonitrile/70%
water, then a linear gradient for 1 min to reach 60% acetonitrile/40%
water, then a linear gradient for 8 min to reach 100% acetonitrile, then
2 min of 100% acetonitrile. Under these conditions, retention times
were ∼6.7 min for the sulfoxide, ∼8.2 min for naphthalene, and ∼9.4
min for the sulfenate, determined by comparison with authentic samples.
The amounts of sulfenates and sulfoxide were calculated as the ratio
between the area of their respective absorption peaks at 254 nm and
the area of the naphthalene peak. This ratio is then considered as a
measure of the concentration of the different products.
Kinetic Isotope Effect Measurement. The measurement of kH/kD
was realized in deuterotoluene. NMR was used to determine the ratio
of cinnamyl-4-nitrobenzenesulfenate and cinnamyl-4-nitrobenzene-
sulfenate-d2 before the reaction and at 10-20% completion. Five
identical samples were prepared by dissolving 78 mg of cinnamyl-4-
nitrobenzenesulfenate-d2, 63 mg of cinnamyl-4-nitrobenzenesulfenate,
and 41 mg of 2-naphthylacetonitrile in 3.5 mL of toluene-d8. 2-Naph-
thylacetonitrile was used as reference. The solution was degassed using
vacuum/sonication for ∼10 min and was transferred in five different
For the study of the thermolysis in acetonitrile in the presence of
base a LiChrospher C18, 5 µm, 4.6 × 250 mm column was used with
a gradient of water and acetonitrile. First minute: isocratic mixture of
30% acetonitrile/70% water, then a linear gradient for 1 min to reach
50% acetonitrile/50% water, then a linear gradient for 16 min to reach
100% acetonitrile, and finally 5 min of 100% acetonitrile. Under these
1
NMR tubes (5 mm). The H NMR spectrum was obtained for each
tube. The solution in the NMR tube was then transferred to a small
test tube containing a small stirring bar and was placed for 4 min at
∼76 °C (in a refluxing ethyl acetate bath). The solution in the test
tube was then cooled by putting the test tube in an ice bath. The cold