Sodium Hexamethyldisilazide: Using 15N-29Si Scalar Coupling to Determine Aggregation and Solvation States

Article abstract of DOI:10.1021/jacs.0c00331

²⁹Si NMR spectroscopy, the method of continuous variations, and density functional theory computations show that sodium hexamethyldisilazide (NaHMDS) is a disolvated dimer in toluene, a mixture of disolvated dimer and tetrasolvated monomer in THF/toluene, and exclusively monomer in neat THF. The dioxane-solvated NaHMDS only partially deaggregates to monomer even in neat dioxane. ¹⁵N-²⁹Si coupling constants and ²⁹Si chemical shifts show a high and dependable correlation with the aggregation state. Monitoring either chemical shift or coupling constant versus THF concentration even in the high-temperature, rapid-exchange limit affords the solvation numbers consistent with DFT computations. The preparation of ¹⁵N-labeled NaHMDS has been improved.

Full text of DOI:10.1021/jacs.0c00331

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Sodium Hexamethyldisilazide: Using N−29Si Scalar Coupling to
Determine Aggregation and Solvation States
Ryan A. Woltornist and David B. Collum*
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ABSTRACT: 29Si NMR spectroscopy, the method of continuous variations, and density functional theory computations show that
sodium hexamethyldisilazide (NaHMDS) is a disolvated dimer in toluene, a mixture of disolvated dimer and tetrasolvated monomer
in THF/toluene, and exclusively monomer in neat THF. The dioxane-solvated NaHMDS only partially deaggregates to monomer
even in neat dioxane. 15N−29Si coupling constants and 29Si chemical shifts show a high and dependable correlation with the
aggregation state. Monitoring either chemical shift or coupling constant versus THF concentration even in the high-temperature,
rapid-exchange limit affords the solvation numbers consistent with DFT computations. The preparation of 15N-labeled NaHMDS
has been improved.
select few groups have been hailing the organic chemistry
Acommunity to pay more attention to organosodium
Figure 1. DFT-computed, toluene-complexed dimer 1a.
chemistry. We joined in only recently and possibly may not be
the last to do so. To this end, sodium hexamethyldisilazide
(NaHMDS) is arguably the preeminent organosodium reagent
in both academic and industrial laboratories.1 Despite its
prominence, studies of its properties in solution are restricted
to a couple of NMR spectra2,3 and a handful of computations.4
We have embarked on an extensive study using a
combination of methods to determine the structure of
NaHMDS in over 30 commonly employed organic solvents
Figure 2. 29Si NMR spectra of (a) [15N]NaHMDS (0.20 M) in
to begin to study how aggregation and solvation influence
toluene at −80 °C showing homodimer 1a, (b) NaTMDS (0.20 M)
reactivity and selectivity.5 An unexpectedly important protocol
in toluene at −80 °C showing homodimer 2a, and (c) a 1:1 mixture
revolves around the interrogation of structure using 15N−29Si
of [15N]NaHMDS and NaTMDS (0.20 M total titer) in toluene
recorded at −80 °C showing homo- and heterodimers 1a and 3a. (d)
29Si NMR spectrum of 0.15 M [15N]NaHMDS in 0.75 M THF with
Me2NEt (DMEA) as cosolvent recorded at −120 °C shows dimer 1b
and monomer 4.
coupling observed in 15N-labeled NaHMDS. Lukevics and co-
1
workers used natural abundance to examine JN−Si coupling in
a series of disilazanes including NaHMDS in benzene.3
Unaided by additional data, their suggestion that NaHMDS
is tetrameric in benzene was suspect,2a,b but the tactic had
merit.
Received: January 10, 2020
We find a highly predictable correlation of 15N−29Si
coupling with aggregation state. The high sensitivity,
resolution, and quantitation offered by 29Si NMR spectroscopy
and the low cost of the 15N label (7% the cost of an NMR
tube) render this of potential interest to those studying M−
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A

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Figure 5. 29Si chemical shift (green) and 15N−29Si coupling constants
(black) plotted versus [THF] in 2:1 pentane/toluene as cosolvent
measured at −20 °C. The curves are fits to a model based on an
A2S2−AS4 equilibrium (Supporting Information).
Figure 3. Job plot showing relative integrations of the 29Si resonances
of NaHMDS homodimer 1a (red), NaTMDS-derived homodimer 2a
(blue), and heterodimer 3a (green; eq 1) versus the measured16 mole
fraction of NaHMDS (XNaHMDS) at 0.20 total molarity17 in neat
toluene-d8 at −80 °C.
Figure 6. 15N−29Si coupling constants plotted versus [THF] in 2:1
pentane/toluene as cosolvent measured at −20 °C (black), 20 °C
(green), and 50 °C (blue). The functions are fits to a model based on
an A2S2−AS4 equilibrium (Supporting Information).
Figure 4. DFT-computed, THF-complexed dimer 1a and monomer
4.
crystallographically for many metals, including sodium.13 The
29Si NMR spectrum shows a doublet with 1JN−Si = 7.9 Hz akin
to that for the benzene solvate noted by Lukevics, which
proves to be characteristic of dimeric NaHMDS (Figure 1).
The dimer assignment was secured using the method of
continuous variations (MCV).14 Mixtures of NaHMDS and
the structurally similar sodium tetramethyldisilazide
[NaTMDS; (HMe2Si)2NNa]15 in toluene show two homo-
dimers along with a heterodimer manifesting a 29Si singlet
corresponding to the TMDS fragment and a doublet with
coupling characteristic of dimers (1JN−Si = 8.9 Hz; Figure 2c).
Plotting the proportions of homo- and heteroaggregates versus
measured16 mole fraction of NaHMDS (XNaHMDS) affords the
Job plot in Figure 3. Quantitative heterodimerization is
supported computationally (eq 1) and presumably derives
from steric relief in the NaHMDS homodimer 1. An analogous
Job plot is obtained in toluene with 5.0 equiv of THF,
conditions in which THF quantitatively displaces toluene to
N(SiR3)2 and M−N(SiR3)(R) derivatives. We present herein
preliminary studies that focus on three prominent solvents:
toluene, THF, and dioxane.
A
29Si{1H} INEPT experiment circumvented the problems
posed by background signal from glass NMR tubes and NOE
effects,6 allowing the relative integrations to be ascertained.
[15N]NaHMDS was prepared in 45% overall yield from
15NH4Cl by an optimized protocol.7 1H and 13C NMR spectra
are archived Supporting Information. Density functional theory
(DFT) computations were carried out at the M06-2X level of
theory8,9 for geometry optimizations and single-point calcu-
lations.10 The standard Def2-SVP basis set was used for
geometry optimizations, and the expanded basis set Def2-
TZVP for single point calculations.11,12
The high solubility of NaHMDS in toluene and insolubility
in hexane implicated an explicit π complexation, as observed
B
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50% of the titer derives from monomer 6 (Figure 7). DFT
computations indicate monomer 6 is only trisolvated.
We have shown that chemical shift and 15N−29Si coupling
for the dimers (7.5−8.5 Hz) and monomers (13.0−13.5 Hz),
in conjunction with results from a much more broadly based
study,5 are highly diagnostic of aggregation state. From a single
spectrum, even at ambient temperatures, one can assess the
relative proportions of monomers and dimers. Ironically, in
over a dozen papers describing the structure of lithium
hexamethyldisilazide using 15N-labeled substrate in >100
solvents, we did not record a single 29Si NMR spectrum: we
did not need them. Belatedly, we find the analogous
[15N]LiHMDS/THF dimer and monomer 15N−29Si couplings
are 7.0 and 11.7 Hz, respectively. We suspect that other
organometallic complexes with silazide-based ligands are likely
to show diagnostic trends as well.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c00331.
■
sı
Spectroscopic, computational, and MCV data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Figure 7. 15N−29Si coupling constants plotted versus [THF] (black)
and [1,4-dioxane] (green) in 2:1 pentane/toluene as cosolvent
measured at 20 °C. The functions are fit to a model based on an
A2S2−AS4 equilibrium (Supporting Information).
David B. Collum − Baker Laboratory, Cornell University,
Ithaca, New York 14853-1301, United States; orcid.org/
0000-0001-6065-1655; Email: dbc6@cornell.edu
Author
Ryan A. Woltornist − Baker Laboratory, Cornell University,
Ithaca, New York 14853-1301, United States
form 1b as shown by titrations.13 Dimer 1b has been
characterized crystallographically.2c
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c00331
Titration of solutions of [15N]NaHMDS (0.15 M) in DMEA
to record 29Si NMR spectra with added THF at −120 °C
reveals a markedly upfield-shifted resonance displaying a large
coupling (1JN−Si = 13.4 Hz, Figure 2d) characteristic of
NaHMDS monomers (Figure 4). The monomer becomes the
sole observable form by 10 equiv (1.50 M).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Institutes of Health (GM131713) for
support.
■
Exchange of free and sodium-bound THF is rapid even at
−120 °C. Although computations are supportive of both di-
and tetrasolvated dimer, a host of other monodentate solvents
show disolvation to be the norm.5 Couplings and chemical
shifts are proxies for aggregation even in the high-temperature,
rapid-exchange limit as illustrated in Figure 5. Figure 6 shows
the temperature dependence of the deaggregation, revealing
the anticipated preference for monomer at lower temperatures.
Moreover, the curves in Figures 5 and 6 result from fits
according to the equilibrium in Figure 4 with tetrasolvated
monomer 4. Analogous fits assuming a trisolvated monomer
are decidedly inferior.
The correlation of coupling constant to aggregation state can
also be used to assign dimer−monomer ratios in solvents that
eluded assignment at lower temperatures. The prominent
ethereal solvent 1,4-dioxane produced a highly insoluble white
crystalline material at low temperature probably owing to a
polymeric network of monomers characterized crystallo-
graphically,18 precluding solution structural studies. 29Si
spectra in the rapid exchange limit at 20 °C show dioxane-
concentration-dependent coupling consistent with partial
deaggregation of dimer 5 to monomer 6 at 20 °C. In neat
dioxane, the 10.7 Hz coupling indicates that approximately
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(7) (a) [15N]Hexamethyldisilazane was prepared from [15N]NH3
by mixing [15N]ammonium chloride (3.0 g, 55.0 mmol, >99% 15N
isotopic purity) with 6.00 g (0.15 mol) of granular NaOH in a 25 mL
in a one-neck, round-bottom flask cooled to −78 °C. The mixture was
warmed with a heat gun for approximately 20 min. After the transfer
of ammonia was complete, 1-(trimethylsilyl)imidazole (14.7 g, 15.3
mL, 105 mmol, 98% purity) was added to ammonia at −78 °C and
stirred. HCl begins to off-gas, and imidazole precipitates immediately.
Anhydrous diethyl ether (20 mL) is then added to the flask, and the
mixture is held at 0 °C for 40 min. Cholesterol (3.0 g) was added to
the [15N]hexamethyldisilazane with stirring for 45 min to remove
excess 1-(trimethylsilyl)imidazole. Short-path distillation at atmos-
pheric pressure removed the diethyl ether. Vacuum distillation (40
mm Hg, 20 °C) afforded 4.75 mL (47% yield) of (Me3Si)215NH. (b)
[15N]-Sodium hexamethyldisilazide (1) was prepared by a known
procedure as follows.20 Sliced sodium metal (1.20 g, 52.4 mmol) was
added to a flame-dried, fine-mesh swivel frit setup (Supporting
Information) in the glovebox. The apparatus was moved to a Schlenk
line for the remainder of the procedure. Under an argon atmosphere,
[15N]HMDS (7.31 g, 9.45 mL, 45.0 mmol) and 40 mL of DMEA
were added to the reaction flask at room temperature. Isoprene (2.62
mL, 26.2 mmol) dissolved in 8 mL of dry DMEA was then added over
1 h via syringe pump to the mixture. After addition of isoprene, the
reaction was stirred at rt for an additional 2 h. The solution was then
filtered through the frit and canula transferred to a second coarse
swivel frit setup, and the solution was evaporated to dryness under
vacuum for at least 10 h to yield a white powder. The powder was
then suspended in dry pentane (∼20 mL), stirred for 1 h, and filtered.
Washing with an additional 20 mL of pentane yielded 6.70 g (91%
yield) of [15N]NaHMDS, which was transferred to a glovebox and
stored at room temperature. It should be noted that NaHMDS can be
recrystallized as described previously20 but with no detectable
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molarity, refers to the concentration of the monomer subunit
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1
improvement. H NMR spectrum (500 MHz, toluene-d8) δ 0.160
ppm; 13C NMR spectrum (125.72 MHz, toluene-d8) δ 7.28 ppm; 29Si
NMR spectrum (99.36 MHz, toluene-d8) −14.6 ppm. (c) NaTMDS
(2) was prepared using the same method described for NaHMDS.
13C NMR spectrum (125.72 MHz, toluene-d8) δ 5.93 ppm; 29Si NMR
spectrum (99.36 MHz, toluene-d8) −25.57 ppm.
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D
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