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. Author manuscript; available in PMC: 2021 Mar 25.
Published in final edited form as: J Am Chem Soc. 2020 Apr 1;142(15):6852–6855. doi: 10.1021/jacs.0c00331

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

Ryan A Woltornist 1, David B Collum 1,*
PMCID: PMC7993549  NIHMSID: NIHMS1677373  PMID: 32233406

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-labelled NaHMDS has been improved.

A select few groups have been hailing the organic chemistry community to pay more attention to organosodium chemistry. We joined in only recently and possibly may not be the last to do so. To this end, we submit that 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 to begin to study how aggregation and solvation influence reactivity and selectivity.5 An unexpectedly important protocol revolves around the interrogation of structure using 15N–29Si coupling observed in 15N-labelled NaHMDS. Lukevics and coworkers used natural abundance to examine 1JN–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.

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-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 calculations.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 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).

Figure 1.

Figure 1.

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DFT-computed toluene-complexed dimer 1a.

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 shows two homodimers 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 form 1b as shown by titrations.13 Dimer 1b has been characterized crystallographically.2c

Figure 2.

Figure 2.

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29Si NMR spectra of (a) [15N]NaHMDS (0.20 M) in toluene at −80 °C showing homodimer 1a, (b) NaTMDS (0.20 M) in toluene at −80 °C showing homodimer 2a, (c) a 1:1 mixture of [15N]NaHMDS and NaTMDS (0.20 M total titer) in toluene recorded at −80 °C showing homo- and heterodimers 1a and 3a, and (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.

Figure 3.

Figure 3.

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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.

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).

Figure 4.

Figure 4.

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DFT-computed, THF-complexed dimer 1a and monomer 4.

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.

Figure 5.

Figure 5.

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The 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 6.

Figure 6.

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The 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).

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 crystallographically,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 50% of the titer derives from monomer 6. 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-labelled substrate in >100 solvents, we did not record a single 29Si NMR spectrum: we didn’t 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.

Supplementary Material

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Figure 7.

Figure 7.

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The 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 to fit to a model based on an A2S2–AS4 equilibrium (Supporting Information).

Funding Sources

We thank the National Institutes of Health (GM131713) for support.

Footnotes

Supporting Information: Spectroscopic, computational, and MCV data. This material is available free of charge via the Internet at http://pubs.acs.org.

The authors declare no competing financial interests.

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Supplementary Materials

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