Tris(trimethylsilyl)methane as an internal 13C NMR chemical shift thermometer

Article abstract of DOI:10.1002/(sici)1097-458x(199806)36:133.0.co;2-4

Tris(trimethylsilyl)methane has excellent properties for an internal chemical shift thermometer to measure temperatures in ¹³C DNMR spectroscopy [Δδ between the ¹³C signals of Si(CH₃)₃ and CH carbons]. It is chemically inert, soluble in most organic solvents and has an almost linear dependence of Δδ on temperature. The sensitivity (approximately 1 °C Hz^-1 at 90 MHz) allows the measurement of temperature to within 1 °C. The chemical shift is solvent dependent, so each solvent mixture must be calibrated. Calibrations are presented for seven solvents.

Full text of DOI:10.1002/(sici)1097-458x(199806)36:133.0.co;2-4

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 36, S118ÈS124 (1998)
Tris(trimethylsilyl)methane as an internal 13C NMR
chemical shift thermometer¤
William H. Sikorski, Aaron W. Sanders and Hans J. Reich*
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
Received 12 January 1998; accepted 10 February 1998
ABSTRACT: Tris(trimethylsilyl)methane has excellent properties for an internal chemical shift thermometer to
measure temperatures in 13C DNMR spectroscopy [*d between the 13C signals of Si(CH ) and CH carbons]. It is
3 3
chemically inert, soluble in most organic solvents and has an almost linear dependence of *d on temperature. The
sensitivity (approximately 1 ¡C Hz~1 at 90 MHz) allows the measurement of temperature to within 1 ¡C. The
chemical shift is solvent dependent, so each solvent mixture must be calibrated. Calibrations are presented for seven
solvents. ( 1998 John Wiley & Sons, Ltd.
KEYWORDS: NMR; 13C NMR; tris(trimethylsilyl)methane; chemical shift thermometer; temperature measurement; silanes
INTRODUCTION
which restricts their temperature ranges and makes
them susceptible to all the errors and inconvenience
associated with sample substitution or capillary inser-
tion. Many of these also measure intermolecular chemi-
cal shifts, which creates potential problems with sample
preparation and purity. An ideal shift thermometer
would (1) be a non-interactive robust molecule useable
as an internal standard, (2) utilize an intramolecular shift
so that only a single material needs to be added, (3) be
e†ective over a wide range of temperatures, (4) give a
linear response of chemical shift to temperature, (5)
have a sufficiently strong *d vs. T dependence that
accurate temperatures can be measured and (6) give
solvent-independent shifts. To help address this funda-
mental need, we have identiÐed a 13C chemical shift
thermometer, tris(trimethylsilyl)methane (1), which
fulÐls all of these requirements except item (6). It can be
added directly to nearly any organic solution under
study, as it has no signiÐcant Lewis acidity or basicity
and is demonstrably stable to media which are acidic,
basic, oxidative or reductive. Bis(trimethylsilyl)methane
(2) is also a candidate, but we selected 1 because of its
greater temperature sensitivity and lower volatility,
which makes the preparation of 13C-enriched material
more convenient.
There are three principal techniques for the measure-
ment of rates by NMR spectroscopy: (1) the use of peak
integrations to monitor reactant and/or product con-
centrations for classical kinetic studies on the labor-
atory time-scale, (2) dynamic NMR spectroscopy
(DNMR) and (3) saturation transfer (Ho†man-Forsen)
experiments allowing measurements of the rates of
reversible reactions at equilibrium on the millisecond to
second time-scale (conformational processes, ligand
reorganizations, pyramidal inversions and chemical
reactions).1 Accurate temperature measurement is an
important requisite for obtaining reliable data in all
three experiments, but the DNMR experiment has par-
ticularly demanding requirements. Since the actual set
temperatures of NMR temperature control devices are
often inaccurate, the primary standards for precision
NMR temperature measurement are usually thermistor
or thermocouple devices. Since NMR experiments are
not compatible with the insertion of an electronic device
into the sample during the measurement of spectra, it is
common to use chemical shift thermometers as second-
ary standards.
For 1H NMR spectroscopy, the most commonly
used chemical shift thermometer is methanol,2a,b
which works over the temperature range from [100 to
60 ¡C. Both the methanol 1H thermometer and others
that have been proposed for 1H [ethylene
glycol,2b Yb(fod) ÈMe CO3a], 13C [MeIÈMe Si,3c
RESULTS AND DISCUSSION
Figure 1 shows a variable-temperature study of 13C-
enriched 1 in an ethereal solvent mixture that we rou-
tinely use for our low-temperature NMR studies of
organolithium reagents.4 The chemical shift of the
3
2
4
CCl ÈMe CO,3d HOAcÈDy(NO ) ,3e Cl CHCOOH,3g
4
2
3 3
2
Yb(fod) ÈMe CO3a],
19F
(C F ÈCHFCl ,3b
3
2
6 6
2
CFCl ÈCF Cl 3b) or 59Co [Co(acac) 3f] NMR are
3
2
2
3
inherently external temperature calibration devices,
* Correspondence to: H. J. Reich, Department of Chemistry, Uni-
versity of Wisconsin, Madison, Wisconsin 53706, USA.
¤ Dedicated to Professor John D. Roberts on the occasion of his 80th
birthday.
( 1998 John Wiley & Sons, Ltd.
CCC 0749-1581/98/SI0118È07 $17.50

TRIS(TRIMETHYLSILYL)METHANE AS A CHEMICAL SHIFT THERMOMETER
S119
ranges of the respective solvents (except for toluene,
which was only measured from [89 to 68 ¡C). SigniÐ-
cantly, even at the temperature extremes, the compound
is well behaved.
Various methods have been proposed for calibrating
chemical shift thermometers, including direct measure-
ment with a static thermistor probe,2a detection of the
melting of various solids either through the sharpening
of the signals in the NMR spectrum,5a,c or visual
inspection of the sample,5b and detection of the clearing
points of liquid crystals (marked by the appearance of
sharp signals in the NMR spectrum).5c The MeOH
thermometer has been calibrated repeatedly by Van
Geet,2 and his work highlights the careful attention to
detail that is necessary to calibrate a chemical shift ther-
mometer properly. Van GeetÏs studies included the
important observation that there was a temperature
gradient along the length of the tube (ca. 0.5 ¡C cm~1 in
his instrument), which was slightly larger when the
sample was not spinning.2a Hence it is important that a
thermocouple or thermistor device be inserted accu-
rately to the center of the receiver coil to obtain an
accurate reading. Further, since the temperature probe
is a heat conductor, its very presence alters the tem-
perature of the solution.2b
We have used two variations of a thermocouple-
based procedure for calibrating our thermometer. The
Ðrst was a sample substitution protocol, where the tem-
perature was measured in one sample containing an
inserted thermocouple and the spectrum was measured
in a second one, otherwise identical. Each sample was
equilibrated for an appropriate length of time (15 min
for a 10 mm sample tube). Since the sample could not
be spun during the temperature measurement, we mea-
sured spectra on non-spinning samples. A second pro-
cedure involved a single sample in an open tube. After
sample equilibration the thermocouple was inserted
into the sample such that the sensing element was at the
center of the receiving coil, and the temperature was
measured. The spectrum was then taken with the ther-
mocouple raised, and the thermocouple was again
lowered into the sample for a second temperature mea-
surement. These measurements were performed on a
spinning sample. The sample substitution and direct
insertion methods gave slightly di†erent results (1È2 ¡C)
at the low and high temperature extremes.
Figure 1. 13C NMR spectra (90.56 MHz, 360 MHz proton
frequency) from a variable-temperature study of 0.20 M
tris(trimethylsilyl)methane (13C–H) (1) in 3 : 2 THF–
diethylether.
methine carbon (large signal) is highly temperature
dependent, the CH signal (doublet, 2J \ 3.2 Hz)
3
CC
much less so. Over the course of a 200 ¡C temperature
range from [140 to ]60 ¡C, the chemical shift di†er-
ence between the two carbon signals, l(CH) [ l(CH ),
3
spans 230 Hz, giving a sensitivity of better than 1 Hz
¡C~1 on a 360 MHz proton frequency instrument.
Calibration
We calibrated this shift thermometer in a variety of sol-
vents. Figure 2 highlights the remarkable result that the
chemical shift di†erence between the two carbons is an
almost linear function of temperature in a variety of sol-
vents, displaying nearly identical slopes in all cases.
These calibrations were performed over the entire liquid
The results reported in Fig. 1 lead to the equations in
Table 1 for calculating the temperature, where *d \
d(CH) [ d(CH ). We use *d rather than *l values here
3
to make the equations independent of the spectrometer.
The digital resolution under the conditions that we
measured our spectra was 0.64 Hz. Hence temperatures
determined using this method are probably accurate to
within 1 ¡C. Although higher digital resolution could
easily be achieved (with temperature measurements to
within 0.2 ¡C), it is very difficult to calibrate the ther-
mometer that accurately and other sources of error such
as heating by the decoupler, signal broadening and the
e†ects of spinning the sample prevent achieving higher
accuracy.
Figure 2. Graph relating the 13C chemical shift diþer-
ence in Hz between the methine and methyl carbons of
tris(trimethylsilyl)methane (1) to temperature in
pentane, benzene-d , toluene, 3 : 2 THF–diethylether,
6
chloroform-d, dichloromethane and methanol.
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)

S120
W. H. SIKORSKI, A. W. SANDERS AND H. J. REICH
Table 1. Calibrations for the tris(trimethylsilyl)methane chemical
shift thermometer
Pentane
C D
Toluene
Temp. (¡C) \ 83.231(*d) [ 86.6
Temp. (¡C) \ 82.249(*d) [ 19.9
Temp. (¡C) \ 77.931(*d) [ 24.9
Temp. (¡C) \ 84.711(*d) [ 36.5
Temp. (¡C) \ 81.729(*d) [ 44.5
Temp. (¡C) \ 78.675(*d) [ 58.1
Temp. (¡C) \ 83.925(*d) [ 83.9
([124 to 26 ¡C)
(9 to 69 ¡C)
6
6
([89 to 68 ¡C)
([56 to 49 ¡C)
([89 to 33 ¡C)
([139 to 60 ¡C)
([80 to 42 ¡C)
CDCl
3
CH Cl
2
2
3 : 2 THFÈEt O
2
MeOH
quence. If there are signiÐcant temperature gradients
across a sample, or if the temperature changed during a
lengthy acquisition, there will be di†erential broadening
of the two signals, thus providing an internal check on
the physical and temporal temperature homogeneity
while the spectrum is acquired. This is illustrated in a
high-resolution experiment of a sample containing a
2 : 1 ratio of 13C labeled and unlabeled 1 designed to
measure the 13CÈ13C isotope shift of the Me groups for
(Me Si) 13CH (Fig. 3). Here the linewidth of the CH
signals is 0.15 Hz whereas that of the CH signal 0.75
Hz. Hence there was an approximately 0.7 ¡C tem-
perature shift during the experiment, or temperature
gradient across the sample. Since a spectrum taken sub-
sequently had much sharper lines for the CH signal, this
was probably a shift in temperature with time.
Stability of tris(trimethylsilyl)methane
To be used as an internal standard, the compound
needs to be inert. To test this, we subjected 1 to a
variety of conditions. It had already been demonstrated
to be resistant to strong bases (metalation with MeLi in
THFÈEt O has been reported to require 20 h at room
2
temperature,6 although through NMR observations we
have determined that 3 days are actually required for
complete metalation). In our own NMR studies of
lithium reagents, we have been making routine use of
this chemical shift thermometer, and its presence has
never been a problem. We have speciÐcally tested the
stability of 1 to basic conditions (NaOHÈMeOH), acidic
conditions (CF COOHÈCDCl ), oxidative conditions
3
3
3
3
3
(m-chloroperbenzoic acidÈCH Cl ) and reducing condi-
An inherent problem with an internal chemical shift
thermometer is that the sample becomes contaminated.
If a compound is to be recovered, it needs to be separat-
2
2
tions (NaBH ÈMeOH) and found it to be una†ected
after 1 week at room temperature.
4
ed
from
the
chemical
shift
thermometer.
Tris(trimethylsilyl)methane has a boiling point of 80 ¡C
at 2 mmHg and, although it contains no chromophore,
it is extremely non-polar and can generally be removed
by chromatography.
The spectra in Fig. 1 illustrate some other limitations
of this method. The signals move across the 2È5 ppm
region of the 13C NMR (in all solvents tested), which
could lead to some interference if a compound under
study has signals in this location. Fortunately, this
region is usually fairly bare, although studies of other
Using the chemical shift thermometer
The advantages of an internal chemical shift thermom-
eter are substantial, and include the following: the tem-
perature being recorded is always the true temperature
at the position of the receiver coil at the time of the
acquisition (or, if acquiring in a nucleus other than 13C,
immediately before or after, with almost no disturbance
of the sample); reliable operation is limited only by the
practical limits of the freezing and boiling points of the
solvent; and the DNMR experiment itself becomes
decoupled
from
the
temperature
calibration
(calibrations of a solvent can even be performed long
after an experiment has been done, even on a di†erent
spectrometer if the DNMR experiment was performed
with the internal standard present). Because the ther-
mometer is part of the solution, one does not need to
use a capillary (temperature gradients across the capil-
lary wall are a potential problem, and the presence of
the capillary can a†ect signal quality), nor does one
need to exchange NMR tubes to measure the tem-
perature, which is inherently imprecise, and very time
consuming since numerous samples need to be equili-
brated. Furthermore, exchanging tubes can be a real
problem for low-temperature studies of sensitive
samples or classical kinetic studies followed by NMR
where sample warming must be avoided.
Figure 3. 13C NMR spectrum of a 2 : 1 ratio of 13C labeled
and unlabeled 1 in acetone-d . The isotope shift of the
6
The fact that only the CH signal of 1 shows a sub-
stantial temperature dependence has a valuable conse-
SiMe carbon is 0.15 Hz upüeld (1.65 ppb). 2J
3.31 Hz.
\
3
C, Si, C
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)

TRIS(TRIMETHYLSILYL)METHANE AS A CHEMICAL SHIFT THERMOMETER
S121
alkylsilanes, for instance, could be compromised. Since
the chemical shifts of the SiMe and CH carbons cross,
3
there is a “blindÏ spot of 1È2 ¡C when the two signals are
too close to be distinguished (e.g. [58 ¡C in 3 : 2
THFÈEt O).
2
The spectra in Fig. 1 were measured on a 99% 13C-
enriched sample (see below for the preparation); here
the areas of the CH and Si(CH ) signals are in an
3 3
approximately 10 : 1 ratio. The intensity ratio is further
Figure 5. Calibration of 1 in mixed solvents. Plot of
exacerbated by the doublet splitting of the minor SiMe
peak. Unlabeled material can also be used (see Fig. 4);
chemical shift between CH and CH carbons at [ 20 ¡C
3
3
vs. volume fraction for methanol–chloroform (left) and
here the signals are in a 1 : 9 ratio (both signals can be
detected in 80 scans of a 2% solution in a 10 mm tube;
below this concentration the minor CH signal becomes
hard to detect). A very e†ective alternative is to use a
1 : 10 ratio of 13C-labeled and unlabeled material (Fig.
4). This uses very little of the expensive labeled material
and balances the intensities of the two carbon signals
(both singlets) while maintaining a slight di†erence for
identiÐcation purposes (the methyl and methine carbons
are present in an approximately 5 : 4 ratio). With this
mixture, only 5 mol% relative to the compound under
investigation (0.2 vol.% of the sample) is necessary for
an adequate signal-to-noise ratio.
The dispersion of lines in Fig. 2 illustrates a potential
problem with the method. The fact that di†erent sol-
vents give curves with substantially di†erent o†sets
raises the question of whether calibration curves are
a†ected by solutes. At the extremes, the o†set between
the calibrations for pentane (or methanol) and benzene
(or toluene) is the equivalent of 60 ¡C. The addition of
5% of an aromatic substrate (benzene) to a pentane
solution might cause a 3 ¡C error if the calibration curve
for pure pentane were used. We have found that cali-
brations for mixed solvents can be extrapolated owing
to the nearly linear dependence on the volume ratio
pentane–toluene (right).
value, but the user should be careful to perform cali-
brations of the thermometer using samples that are rep-
resentative of the actual experiment, especially if
substrates and solvents are likely to have large *d
o†sets and high concentrations are to be used.
On the positive side, the curves show only minimal,
barely detectable, deviations from linearity. The small
systematic deviations occur only at the highest and
lowest temperatures near the boiling points and freezing
points of the solvent, where systematic errors are likely
to be largest (e.g. solvent reÑux). This means that only
two or three temperatures need to be calibrated, prefer-
ably no more than 50 or 60 ¡C apart, near the upper
and lower limits of the DNMR experiment. In fact, the
slopes for all solvents are so similar that a single cali-
bration point will lead to acceptable results over a
narrow temperature range. Hence calibration of a rea-
listic solventÈsubstrate mixture is still much less work
(and more reliable) than a normal sample-substitution
protocol which needs to be performed at multiple tem-
peratures, and every time an experiment is re-run.
Bis(trimethylsilyl)methane (2) as a shift
thermometer
(Fig. 5). Thus for 2 : 1 and 1 : 2 (v/v) MeOHÈCDCl the
3
actual temperatures di†ered by 0.4 and [ 1.1 ¡C,
respectively from the calculated values assuming a
linear dependence. For 2 : 1 and 1 : 2 (v/v) pentaneÈ
toluene the deviations were [ 1.4 and 1.3 ¡C, respec-
tively. We carried out some spot checks and found that,
for example, the addition of 1 M styrene oxide to 3 : 2
THFÈdiethylether gave no detectable change in the *d
We have documented the utility of 1 as a NMR chemi-
cal shift thermometer. Bis(trimethylsilyl)methane (2) is
also a candidate and shares many of the desirable
properties of 1, and even has some advantages over it.
For example, the peak ratio at natural abundance is
6 : 1 vs. 9 : 1 for 1 (reducing the need for labeled
material), and the two signals do not cross, so there is
no “blind spotÏ. Compound 2 is also substantially more
volatile than 1 (b.p. 133 ¡C), which is an advantage for
sample puriÐcation, but could restrict its use in high-
temperature situations. A disadvantage is that the
chemical shift sensitivity, which is already marginal for
1 (1.15 Hz ¡C~1), is smaller (0.8 Hz ¡C~1) for 2. It has
not been established what the chemical shift dependence
on solvent is, or whether the temperature dependence is
as linear as found for 1.
Preparation of labeled tris(trimethylsilyl)methane
Figure 4. Typical 13C spectra obtained for the signals of
1 for a 2.7 vol.% solution of natural abundance 1 (left) in
toluene and a 0.29 vol.% sample of 9% enriched 1 (right)
Although DNMR studies can e†ectively be performed
in CDCl .
with an approximately 2% solution of 1, the sensitivity
3
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)

S122
W. H. SIKORSKI, A. W. SANDERS AND H. J. REICH
is greatly increased (by at least an order of magnitude)
by using material that is partially 13C labeled at the
methine carbon (see above). We developed a clean, effi-
cient synthesis of 13C-labeled tris(trimethylsilyl)methane
from commercially available 13C-paraformaldehyde
(Scheme 1). This synthesis involves several in situ elec-
trophilic traps which take advantage of the di†ering
reactivities of the starting materials, products and elec-
trophiles towards metalating agents. The Ðrst step is
precedented.7 The second step is based on the observ-
ation that at [ 78 ¡C, LDA does not react detectably
chemical shifts maintain strong linear correlations in all
solvents tested. An internal temperature thermometer
has numerous advantages over other methods, and 1
fulÐls most of the requirements of an ideal compound:
it is unobtrusive (its peaks are in a usually bare region
of the 13C NMR spectrum), it is unreactive and it has
no acidic or basic properties.
EXPERIMENTAL
with Me SiCl.8 However, bis(phenylseleno)methane (3)
Tetrahydrofuran (THF) was freshly distilled from
sodium benzophenone ketyl before use. Glassware was
placed overnight in a 110 ¡C oven or Ñame-dried before
3
metalates readily at [78 ¡C and is quenched by the
Me SiCl as it is formed. This reaction succeeds because
3
the product, bis(phenylseleno)trimethylsilylmethane (4),
purging with N to remove moisture. Common lithium
2
cannot be metalated by lithium diisopropylamide
(LDA) at [78 ¡C.
reagents were titrated using n-propanol in THF with
1,10-phenanthroline as an indicator.9 Lithium diisop-
ropylamide (LDA) was freshly prepared according to a
literature procedure.4b Temperatures of [78 ¡C were
achieved with a dry iceÈacetone bath and [20 ¡C with
a chemical freezer.
The third step takes advantage of an ideal balance of
reactivities of the starting material, product and
Me SiCl towards n-BuLi. Thus, the SeÈC bond of
3
bis(phenylseleno)trimethylsilylmethane is cleaved more
rapidly than n-BuLi is trapped by Me SiCl. This
Commercially available starting materials and
reagents (obtained from Aldrich Chemical unless stated
otherwise) included benzeneselenol (PhSeH), boron tri-
Ñuoride etherate (BF É OEt ), 13C-labeled para-
3
permits phenylseleno(trimethylsilyl)methyllithium to be
formed and trapped in situ. The product, bis(trimethyl-
silyl)phenylselenomethane (5), reacts sluggishly with
n-BuLi at [78 ¡C, so any excess n-BuLi is trapped by
3
2
formaldehyde (Cambridge Isotope Laboratories),
Me SiCl.
trimethylsilyl chloride (Me SiCl), and tris(trimethyl-
3
3
The Ðnal phenylseleno group is substituted in a
sily)methane ((Me Si) CH).
3
3
sequential reaction by adding n-BuLi, warming to
[20 ¡C for 30 min and trapping with Me SiCl, produc-
3
ing 1-13C in 71% overall yield from [13C]para-
NMR spectroscopy
formaldehyde. This synthetic sequence allows one to
arrive cleanly at any of the intermediates, and this syn-
thetic approach can be easy modiÐed to construct a
variety of derivatives.
For the characterization of synthesized compounds, 1H
and 13C NMR spectra were acquired on a Bruker
AC-300 spectrometer with CDCl as the solvent and
3
tetramethylsilane as the internal standard.
CONCLUSION
Temperature calibrations
The primary advantage of the use of 1 as an NMR ther-
mometer over other published NMR temperature mea-
surement techniques is that it can be added directly to
the solution being studied and measures the true inter-
nal temperature of the sample. It is soluble in all
common organic solvents, very little is needed and its
The temperature calibrations were performed in 10 mm
NMR tubes using a wide-bore AM-360 spectrometer at
360.148 MHz (1H) and 90.556 MHz (13C). Least
squares data is reported in Table 2. The digital
resolution was 0.15 Hz for 1H and 0.64 Hz for 13C. 13C
Scheme 1. Synthesis of 13C-labeled tris(trimethylsilyl)methane (1-13C).
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)

TRIS(TRIMETHYLSILYL)METHANE AS A CHEMICAL SHIFT THERMOMETER
S123
Table 2. Least-squares üt of *d vs. temperature for seven solvents (Fig. 2)
Solvent
Slope (Hz ¡C~1)
y-Intercept (Hz)
Correlation coefÐcient (r)
Pentane
1.088 ^ 0.016
1.101 ^ 0.010
1.162 ^ 0.016
1.151 ^ 0.009
1.069 ^ 0.014
1.108 ^ 0.009
1.079 ^ 0.011
94.20 ^ 1.16
21.92 ^ 0.44
28.92 ^ 0.81
66.90 ^ 0.66
39.00 ^ 0.52
49.34 ^ 0.45
90.55 ^ 0.49
0.9997
0.9999
0.9994
0.9997
0.9997
0.9998
0.9997
C D
Toluene
6
6
3 : 2 THFÈEt O
2
CDCl
3
CH Cl
2
2
MeOH
NMR spectra were Fourier transformed with a line
broadening parameter of 2 Hz. When non-deuterated
solvents were used, the spectrometer was run unlocked,
and shimming was performed on the 13C FID of an
isolated carbon.
To a 10 mm thin-walled NMR tube, truncated to 6
in, were added 3.0 ml of the appropriate solvent and 80
ll of tris(trimethylsilyl)methane (natural abundance) or
8 ll of 10% 13C-enriched tris(trimethylsilyl)methane.
integration standard. The 1H NMR spectrum was
recorded. The tube was then charged with 62 ll (0.8
mmol, 8 equiv.) of triÑuoroacetic acid. The tube was
sealed with a cap and ParaÐlm and placed in an 18 ¡C
constant-temperature bath. The tube was removed
periodically over 1 week and the 1H NMR spectrum
recorded. There was no degradation of the
tris(trimethylsilyl)methane signal vs. benzene within the
limits of the integrations (^5%) over 1 week. This pro-
cedure was repeated using 0.5 ml (8 equiv.) of 1.6 M
Sample substitution method. The temperatures were
measured using a thermocouple submerged in a second
10 mm NMR tube containing the same solvent mixture
and volume as the sample (a second NMR tube was
necessary because the presence of the thermocouple led
to extremely poor resolution). Both the compound
sample and the temperature probe sample were allowed
to equilibrate thermally for 15 min to a given spectro-
meter console setting. The spinner air was not turned
on at any point. The decoupler power was kept on at all
times (it detectably heats the sample) except for the few
seconds during which the temperature was actually
recorded, as irradiation of the thermocouple led to non-
sensical and sporadic readings in the temperature
display unit.
mCPBA in CDCl , 0.5 ml (8 equiv.) of 1.6 M NaOH in
3
CD OD and 0.5 ml (8 equiv.) of 1.6 M NaBH in
3
4
CD OD. No degradation was observed within the
3
limits of the integrations in any of the samples over 1
week.
Materials
13C-Labeled Bis(phenylseleno)methane (3). This synthesis was
performed according to a literature procedure.7 To a dried, argon-
purged, 5 ml round-bottomed Ñask with a septum and stirrer bar were
added 41.1 mg (1.32 mmol) of 13C-labeled paraformaldehyde, 3 ml of
CHCl and 315 ll (466 mg, 2.97 mmol) of PhSeH. The Ñask was
3
cooled to 0 ¡C and 210 ll (235 mg, 1.66 mmol) of BF É OEt were
3
2
added, turning the heterogeneous solution a pale yellow. The spec-
trum of the closed system was covered with a thin layer of grease to
limit formaldehyde evaporation, the Ñask was allowed to warm to
room temperature and the reaction mixture was stirred for 4 days.
Direct thermocouple insertion. The open tube was
placed in the spectrometer. The temperature was taken
before and after each 13C spectrum by inserting a ther-
mocouple directly into the NMR tube inside the
spectrometer. This was accomplished by threading the
thermocouple into a 3 ft long piece of glass tubing, with
the thermocouple protruding 1 in from the glass. The
glass rod was lined up with the tube by using a brass
sca†old inserted down the bore of the magnet to just
above the tube. A rubber stop was used to adjust the
height of the thermocouple and allow it to be placed at
the same position each time. The decoupler was turned
o† only brieÑy as the temperature was recorded. Any
point in which the temperature di†ered by more than
1 ¡C before and after the spectrum was obtained was
retaken.
The solution was taken up in 15 ml of 1 : 1 Et OÈhexane, washed with
2
15 ml of 10% NaOH, 15 ml of H O and 15 ml of brine, dried over
2
anhydrous MgSO and decanted. Volatile materials were removed by
rotary evaporation, and the last traces were removed with a vacuum
4
pump (0.01 mmHg), yielding 0.434 g (1.33 mmol, 100% crude yield) of
an orange liquid, which was used without further puriÐcation. 1H
NMR (300 MHz, CDCl ): d 4.20 (CH , d, 1J \ 156.45 Hz,
3
2
H, C
2J
H, Se
NMR (75.4 MHz, CDCl ): d 20.97 (CH , 1J
C, Se
\ 12.13 Hz), 7.22È7.29 (Ph, m, 6H), 7.48È7.55 (Ph, m, 4H). 13C
\ 87.10 Hz), 127.46
3
2
(CH), 129.06 (CH), 130.78 (C), 132.87 (CH).
13C-Labeled bis(phenylseleno)trimethylsilylmethane (4). The
unlabeled compound has been reported.10 To a dried, N -purged, 25
2
ml round-bottomed Ñask with a septum and stirrer bar were added
0.17 g (0.52 mmol) of 3, 0.13 ml (0.11 g, 1.02 mmol) of Me SiCl and 10
3
ml of THF. A positive N pressure was maintained throughout the
2
reaction. The solution was cooled to [78 ¡C and 1.0 ml (1.06 mmol)
of 1.06 M LDA in THFÈhexane was added. The reaction mixture was
kept at this temperature for 2 h and quenched with 1 ml of MeOH, to
generate the easily removed Me SiOMe (b.p. 57 ¡C). Using quantitat-
3
ive transfers, the solution was taken up in 30 ml of 1 : 1 Et OÈhexane
2
and washed with 15 ml of 10% HCl and 2 ] 15 ml of H O. Volatile
2
Tests of chemical stability of 1
materials were removed by rotary evaporation. PuriÐcation by pre-
parative TLC (with hexane as eluent, R \ 0.50) yielded 0.167 g (0.418
f
mmol, 80.6%) of a pale yellow liquid. 1H NMR (300 MHz, CDCl ): d
To a dried 5 mm thin-walled NMR tube were added 0.5
3
0.16 (CH , d, 3J
\ 2.21 Hz, 9H), 3.82 (CH, d, 1J
\ 141.74 Hz),
3
H, C
H, C
ml of CDCl , 28 ll (0.1 mmol) of tris(trimethyl-
7.15È7.25 (Ph, m, 6H), 7.43È7.48 (Ph, m, 4H). 13C NMR (75.4 MHz,
3
silyl)methane and 0.1 mmol of benzene as an internal
CDCl ): d [1.41 (CH , d, 2J \ 3.82 Hz), 31.45 (CH, 1J
\ 94.10
3
3
CC C, Se
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)

S124
W. H. SIKORSKI, A. W. SANDERS AND H. J. REICH
Hz, 1J
\ 47.05 Hz), 127.50 (CH), 128.81 (CH), 131.54 (C), 133.93
Acknowledgements
C, Si
(CH).
13C-Labeled bis(trimethylsilyl)phenylselenomethane (5). To a
This work was supported by the National Science Foundation under
Grant No. CHE-9703589. The spectrometers are funded by the
National Science Foundation and the National Institute of Health
through Grant Nos NSF CHF-8306121, NIH 1 S10 RR02388-01
(Bruker AM-360) and NSF CHE-9208463, NIH 1 S10 RR08389-01
(Bruker AC-300).
dried, N -purged, 50 ml round-bottomed Ñask with a septum and
2
stirrer bar were added 0.167 g (0.418 mmol) of 4, 95 ll (0.75 mmol) of
Me SiCl and 10 ml of THF. A positive N pressure was maintained
3
2
throughout the reaction. The solution was cooled to [78 ¡C and
vigorously stirred while 0.1 mmol) of 1.06 M LDA in THFÈhexane was
added (to destroy any protic material) followed by 0.29 ml (0.62
mmol) of 2.13 M n-BuLi in pentane. The reaction mixture was stirred
at this temperature for 15 min before being quenched with 1 ml of
MeOH. The solution was warmed to room temperature, taken up in
30 ml of 1 : 1 Et OÈhexane and washed with 3 ] 20 mL of H O.
2
2
REFERENCES
Volatile materials were removed by rotary evaporation and the com-
pound was puriÐed by preparative TLC (with hexane as eluent, R \
f
0.53, preceding n-BuSePh, R \ 0.38) yielding 0.130 g (0.412 mmol,
f
1. J. SandstroŽ m, Dynamic NMR Spectroscopy. Academic Press,
London (1982).
2. (a) A. L. Van Geet, Anal. Chem. 40, 2227 (1968); (b) A. L. Van
Geet, Anal. Chem. 42, 679 (1970); see also D. S. Raiford, C. L. Fisk
and E. D. Becker, Anal. Chem. 51, 2050 (1979).
98.6%) of a pale yellow liquid. 1H NMR (300 MHz, CDCl ): d 0.13
3
(CH , d, 3J \ 1.84 Hz, 18 H), 1.29 (CH, d, 1J
\ 117.47 Hz),
3
H, C
H, C
7.12È7.24 (Ar, m, 3H), 7.43È7.48 (Ar, m, 2H). 13C NMR (75.4 MHz,
CDCl ): d 0.36 (CH , d, 2J \ 3.82 Hz), 15.80 (CH, 1J \ 70.57
3
3
CC
C, Se
Hz, 1J
\ 43.87 Hz), 126.17 (CH), 128.80 (CH), 131.45 (CH), 133.73
C, Si
3. (a) H. J. Schneider, W. Freitag and M. Schommer, J. Magn.
Reson. 18, 393 (1975); (b) J. Bornais and S. Brownstein, J. Magn.
Reson. 29, 207 (1978); (c) D. W. Vidrine and P. E. Peterson, Anal.
Chem. 48, 1301 (1976); (d) J. J. Led and S. B. Petersen, J. Magn.
Reson. 32, 1 (1978); (e) P. J. Smolenaeres, M. T. Kelso and J. K.
Beattie, J. Magn. Reson. 52, 118 (1983); (f) G. C. Levy, J. T. Bailey
and D. A. Wright, J. Magn. Reson. 37, 353 (1980); (g) L. D. Field,
S. Sternhell and W. Veigel, Org. Magn. Reson. 22, 221 (1984).
4. (a) H. J. Reich and R. R. Dykstra, Angew. Chem., Int. Ed. Engl. 32,
1469 (1993); H. J. Reich and K. J. Kulicke, J. Am. Chem. Soc. 117,
6621 (1995); (b) H. J. Reich, J. M. Renga and I. L. Reich, J. Am.
Chem. Soc. 97, 5434 (1975).
5. (a) O. Yamamoto and M. Yanagisawa, Anal. Chem. 42, 1463
(1970); (b) C. Piccinni-Leopardi, O. Fabre and J. Reisse, Org.
Magn. Resonance 8, 233 (1976); (c) H. Friebolin, G. Schilling and
L. Pohl, Org. Magn. Reson. 12, 569 (1979).
6. M. A. Cook, C. Eaborn, A. E. Jukes and D. R. M. Walton, J.
Organomet. Chem. 24, 529 (1970).
(C).
13C-Labeled tris(trimethylsilyl)methane (1-13C).11 To a dried, N -
2
purged, 25 ml round-bottomed Ñask with a septum and stirrer bar
were added 0.130 g (0.412 mmol) of 5 and 10 ml of THF. A positive
N
pressure was maintained throughout the reaction. The solution
2
was cooled to [78 ¡C and 0.23 ml (0.49 mmol) of 2.13 M n-BuLi in
pentane was added dropwise. The solution was warmed to [20 ¡C
and held at this temperature for 30 min. To a separate dried and
purged 10 ml round-bottomed Ñask were added 68 ll (0.54 mmol) of
Me SiCl and 5 ml of THF. This Ñask was also cooled to [20 ¡C, the
3
Me SiCl solution was transferred via a cannula to the Ñask contain-
3
ing the anion and the resulting mixture was allowed to warm to room
temperature and stirred for 15 min before 1 ml of MeOH was added
to trap the remaining Me SiCl. The solution was taken up in 30 ml of
3
1 : 1 Et OÈhexane and washed with 2 ] 30 ml of H O. Volatile
2
2
materials were removed by rotary evaporation and the product was
isolated by preparative TLC using hexane as the eluent, cutting away
everything (no chromophore!) that ran ahead of the PhSeBu band
7. J. Gabriel and D. Seebach, Helv. Chim. Acta 67, 1070 (1984).
8. E. J. Corey and A. W. Gross, T etrahedron L ett. 25, 495 (1984).
9. S. C. Watson and J. F. Eastham, J. Organomet. Chem. 9, 165
(1967).
(R \ 0.38), and yielding 0.087 g (0.372 mmol, 90.4% or 71.3% overall
f
from 13C-labeled paraformaldehyde) of 1 (pale yellow liquid). 1H
NMR (300 MHz, CDCl ): d [0.73 (CH, d, 1J \ 100.19 Hz,
3
H, C
2J
\ 9.74 Hz, 1H), 0.15 (CH , d, 3J \ 1.47 Hz, 2J
\ 6.25
10. B.-T. Grobel and D. Seebach, Chem. Ber. 110, 852 (1977).
H, Si
3
H, C
H, Si
Hz, 27 H). 13C NMR (75.4 MHz, CDCl ): d 3.37 (CH , d, 2J \ 3.18
11. Compound 1-13C can also be efficiently prepared by reductive
3
3
CC
Hz), 4.05 (CH, 1J
\ 37.51 Hz). Mass spectrum: [M [ CH ]` \
silylation of 13CHCl (A. Guijarro, M. Yus, T etrahedron 52, 1797
C, Si
3
3
218.1254 (calc. for 13CC H Si [ CH , 218.1298).
(1996)).
9
28
3
3
( 1998 John Wiley & Sons, Ltd.
MAGNETIC RESONANCE IN CHEMISTRY, VOL. 36, S118ÈS124 (1998)