sodium hydride reactions

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Sodium hydride

Sodium hydride is the chemical compound with the empirical formula NaH. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na⁺ and H⁻ ions, in contrast to molecular hydrides such as borane, methane, ammonia, and water. It is an ionic material that is insoluble in organic solvents (although soluble in molten Na), consistent with the fact that H⁻ ions do not exist in solution. Because of the insolubility of NaH, all reactions involving NaH occur at the surface of the solid.

How to Make It

Sodium hydride can be prepared by a direct reaction between hydrogen gas and sodium metal.

2 Na + H₂ = 2NaH

Prominent Reactions

NaH reacts violently with water to produce sodium hydroxide and hydrogen gas that gets ignited by the heat of the reaction ^[5].

NaH + H₂O = NaOH + H₂

Alcohols react with sodium hydride to produce alkoxide ions. In the below reaction, ethanol reacts with NaH forming sodium ethoxide and hydrogen ^[10].

CH₃CH₂OH + NaH = CH₃CH₂O^–Na⁺ + H₂

Similarly, methanol reacts with sodium hydride producing the sodium salt of methanol and hydrogen gas.

CH₃OH + NaH = CH₃ONa + H₂

Sodium Hydride Uses

As a powerful reducing and deprotonating agent for many organic reactions ^[2].
As a desiccant or drying agent for lab chemicals ^[2].
Its application as a hydrogen storage agent in fuel cell vehicles is being explored due to its ability to release hydrogen ^[2].
As a strong base, it finds application in organic and inorganic fine chemical preparation ^[6].

Is It Dangerous

NaH is a severe irritant to eyes, skin and respiratory system causing burns and is harmful if ingested. It is a highly inflammable and corrosive compound. Precaution must be taken against an explosion hazard if it comes in contact with water ^{[2, 7]}. When it is heated to the point of decomposition, it emits highly poisonous fumes of oxides of sodium ^[1]. After a reaction, unwanted sodium hydride should be destroyed by careful quenching or disposal ^[9].

Interesting Facts

In spite of its high basicity, NaH is not nucleophilic ^[12].

Sodium Hydride (NaH) Price

It costs around $30-50 per kilogram. The price may vary with suppliers.

Abstract

The hazards associated with the thermal decomposition of chemically incompatible sodium hydride solvent matrices are known, with reports from the 1960s detailing the inherent instability of NaH/dimethyl sulfoxide, NaH/N,N-dimethylformamide, and NaH/N,N-dimethylacetamide mixtures. However, these hazards remain underappreciated and undercommunicated, likely as a consequence of the widespread use of these NaH/solvent matrices in synthetic chemistry.

We report herein detailed investigations into the thermal stability of these mixtures and studies of the formation of gaseous products from their thermal decomposition. We expect this contribution to promote awareness of these hazards within the wider scientific community, encourage scientists to identify and pursue safer alternatives, and most importantly, help to prevent incidents associated with these reactive mixtures.

Diphenylacetonitrile

During the course of our experiments on the α-methylation of diphenylacetonitrile (1) to prepare tertiary carbonitrile 2 a, we investigated its reaction with NaH (3 equiv) and MeI (1.2 equiv) in THF (85 °C in a sealed tube; Scheme 1). Although the desired tertiary nitrile 2 a was isolated in 74 % yield, we were surprised to observe the formation of 1,1-diphenylethane (3 a) in 25 % yield as a side product. Assuming that 3 a was formed by the decyanation of nitrile 2 a, we expected that this decyanation reaction could be generalized to a more versatile synthetic strategy. Therefore, we optimized the reaction conditions for the decyanation of nitrile 2 a by NaH (Table 1). We found that NaH alone was not sufficient to drive the decyanation (Table 1, entry 1).

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Upon the methylation of 1 with NaH and MeI (Scheme 1), a stoichiometric amount of sodium iodide (NaI) is necessarily generated, and thus we speculated that the cooperation of NaH and NaI could be the key to the decyanation. Indeed, the treatment of 2 a with NaH (3 equiv) and NaI (2 equiv) in THF delivered 3 a in 96 % yield (Table 1, entry 2). Although KI was not optimally effective as an additive (Table 1, entry 3), LiI rendered the process very rapid to afford 3 a in 98 % yield within 3.5 h (entry 4).

Decyanation

Similarly, a reaction with MgI₂ produced 3 a in 96 % yield, albeit at a slower reaction rate (Table 1, entry 5). Interestingly, LiBr or LiCl did not promote the decyanation effectively (Table 1, entries 6 and 7), thus indicating the important role of dissolved iodide ions in enabling this unprecedented decyanation by NaH. When the amount of LiI was decreased (Table 1, entries 8 and 9), we found that the use of even a catalytic amount of LiI (20 mol %) enabled full conversion of 2 a with a longer reaction time (48 h; entry 9).

When 1 equivalent of LiI was used as the promoter, the amount of NaH could be decreased to 1.5–2 equivalents (Table 1, entries 10 and 11). However, the reduction of 2 a with LiH in the presence of LiI did not proceed at all, thus indicating the specific reactivity of NaH for the present decyanation.

Introduction

The use of NaH as a strong base is commonplace in synthetic organic chemistry. (1) Generally speaking, NaH is easy to handle and store and often offers predictable reactivity and high atom efficiency. As a result, it has been used to facilitate a wide range of chemical transformations. (2) The most commonly used solvents for reactions that use NaH are dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMAc) because of their complementary physical properties and their ability to solubilize both organic and inorganic compounds.

The hazards associated with the thermal instability of NaH/DMSO, NaH/DMF. And NaH/DMAc mixtures have been a growing concern within the chemistry community. (3) In addition to the desirable physical properties of DMSO to solubilize both organic and inorganic compounds, dimsyl ion (also known as sodium dimsylate or methyl sulfinyl carbanion), prepared via the reaction of NaH with DMSO under nitrogen at 70–75 °C, has found wide applications in a variety of chemical transformations since the seminal publication by Corey and Chaykovsky in the early 1960s. (4) The thermal instability of dimsyl ion was first highlighted by Corey and Chaykovsky in 1965 (4b) and further studied by many research groups. (5)

DMSO

The first reported explosion resulting from a NaH/DMSO mixture was in 1966, (6) when scientists at the Cancer Chemotherapy Research Department of Mount Zion Hospital and Medical Center (Palo Alto, CA) were scaling up a methylation reaction that employed NaH in DMSO, following a method reported by Russell and Weiner. (7) The scientists noted incomplete conversion when the reaction was carried out using a NaH/DMSO molar ratio of 0.19:1 and thus increased the ratio to 0.24:1. The reaction mixture was maintained at 70 °C for 1 h and then cooled. During which time they observed a sharp temperature spike followed. By an explosion that was accompanied by a noxious gas. Immediately after the disclosure of this incident, an analogous explosion from a NaH/DMSO mixture was reported, (8) albeit at a lower temperature (50 °C) and concentration (0.17:1 NaH/DMSO on a molar basis) compared with the conditions employed in the earlier incident. (6)

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The thermal decomposition of a NaH/DMF mixture was first observed in the early 1960s, first by Powers et al., who noted energetic decomposition during a NaH-mediated cleavage of a formyl group, (9) and Brimacombe et al. during the alkylation of a carbohydrate using NaH as the base. (10) Nasipuri et al. later reported the aromatization of various cyclohexenones using NaH in DMF, in which the authors acknowledged the decomposition of DMF in the presence of NaH but still carried out their reactions at 100 °C. (11) The researchers proposed that the active base in these reactions was sodium dimethylamine, resulting from the reaction of DMF with NaH.

EXPERIMENTAL SECTION

Compound 3

¹H NMR (500 MHz, CDCl₃), δ 3.08 (s, 6H, 2×CH₃), 5.13 (s, 4H, 2×CH₂Ph). And 7.24 – 7.39 (m, 6H, Ar-H), 7.59 – 7.67 (m, 4H, Ar-H); ¹³C NMR (126 MHz, CDCl₃), δ 47.8, 67.1, 127.3, 128.8, 130.3, 133.2; HRMS (FAB), calcd for C₁₆H₂₀N (M⁺), 226.1596, found 226.1599.

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Synthesis of Deuterated Compound 3

NaH (60% dispersion in oil, 20 mg, 0.5 mmol) added to a vigorously stirred solution of benzyl bromide. In DMF-d₆ (0.7 mL) in ice-water bath and stirred for 16 h. The solution mixed with hexanes and the top hexanes layer removed. The DMF layer analyzed by NMR. The sample purified by recrystallization from chloroform.

Compound 3-D

¹H NMR (500 MHz, DMF-d₆) δ 5.24 (s, 4H), 7.43 – 7.52 (m, 6H), 7.73 – 7.80 (m, 4H); ¹³C NMR; ¹³C NMR (126 M Hz, DMF- d₆) δ 46.5 (m), 65.8, 128.9, 130.3, 133.5, 139.5; HRMS (FAB), calcd for C₁₆H₁₄D₆N (M⁺), 232.1972, found 232.1980.

Syntheses of Compounds 7, 8 and 9

Two methods used.

Method A

NaH (60% dispersion on oil, 0.2 g, 5 mmol) added to a vigorously stirred solution of benzyl bromide. In anhydrous acetonitrile in three portions over a period of 5 h in ice-water bath under a nitrogen atmosphere. The mixture stirred overnight, then it filtered through layers of silica gel and Celite and washed with acetonitrile. The combined filtrate mixed with hexanes and top hexanes layer removed. The acetonitrile layer evaporated down to an oil. Which distilled (130 °C/20 mmHg) to yield compound 8 as a major product (55%). The ¹H NMR spectrum of this sample matched that of the authentic 3-phenylpropanenitrile purchased from Sigma-Aldrich.

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sodium hydride reactions

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