Lithium Aluminum Deuteride: Application in Synthetic Works

lithium aluminum deuteride (lithium aluminum deuteride, lithium aluminum deuteride LiAlD4, α) commonly abbreviated to LAH, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. The solid is dangerously reactive toward water, releasing gaseous hydrogen (H2). This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters, carboxylic acids, and amides. 

Example 1[1]

The preparation of 2-(7-methoxy-1-naphthyl) ethylamine. 56g 7-methoxy-1-naphthaleneacetonitrile, 120ml ammonia water, 332ml 95percent ethanol, 20g Raney-Ni was added into autoclave. H2 was introduced after vacuuming it. The operation was repeated for 3 times. The reaction was stirred for 12 hours while H2 was introduced and the condition of 300 atm and 60°C was maintained. After completion of the reaction, the reaction was kept overnight at room temperature. On the next day, it was vacuumed and N2 gas was introduced. The autoclave was opened up, and the reaction solution was filtered to remove the catalyst. The filtrate was vacuum evaporated until dry to obtain 56g light green oil. The content is measured as 96.95 percent by HPLC, and the yield is 95 percent.

Example 2[2]

In a typical reaction, 0.015 g of catalyst and 2 mmol of the reactant were taken in 10 mL of ethanol under hydrogen atmosphere. The reaction was monitored by thin-layer chromatography (TLC). After complete disappearance of the starting material, the catalyst was separated by simple filtration and the solvent was removed under reduced pressure to obtain the pure product.

Example 3[3]

In a glove box, an autoclave was charged with the desired ketone (0.5 mmol), toluene (2 mL), Mn complex 1 (14 mg, 5 mol%) followed by t-BuOK (5.6 mg, 10 mol%), in this order. The autoclave is then closed and charged with H2 (50 bar).

Example 4 [4]

An oven dried 12 L flask was flushed with argon and charged with lithium aluminum hydride (78 g, 2.1 mol) and ether (3 L). Methyl-3-methoxypropionate (424 g, 3.59 mol) was added dropwise over a 4 hours period. After the addition was complete the mixture was stirred for an additional 30 minutes, then cooled to 0° C. The reaction was quenched by cautious dropwise addition of water (78 mL), followed by 15percent sodium hydroxide (78 mL), and finally water (234 mL). Celite (200 g) was added as a filtering aid. The resulting mixture was stirred at room temperature for 30 minutes. The brown suspension was filtered, and the filter cake was thoroughly washed with ether (500 mL). The combined filtrates were transferred to an extraction funnel. The aqueous phase was discarded, and the organic phase was drained into a 4 L Erlenmeyer flask. Anhydrous magnesium sulfate (100 g) was added to the flask and stirred for 30 minutes. The inorganic salt was filtered from the solvent solution, and the filtrate was concentrated on the rotary evaporator at atmospheric pressure to give 285 g clear colorless oil. The oil was stirred at room temperature under house vacuum overnight to give 196 g (60 percent) clear colorless oil. This intermediate was used in the next step without further purification.

References

1.    Tianjin Taipu Pharmaceutical Science & Technology Development Co., Ltd. Agomelatine And Pharmaceutical Compositions Thereof, EP2474522[P], 2012, A1, Page column 8-9. 
2.    Lakshmi Kantam M, Parsharamulu, Manorama. Layered double hydroxides supported nano palladium: An efficient catalyst for the chemoselective hydrogenation of olefinic bonds[J]. Journal of Molecular Catalysis A: Chemical, 2012, 365:115 – 119.
3.    Bruneau-Voisine A, Wang A, Roisnel T, Darcel C, Sortais JB, Hydrogenation of ketones with a manganese PN3P pincer pre-catalyst[J]. Catalysis Communications, 2017,92:1 - 4
4.    Nihon Med-Physics Co., Ltd. Intermediate Compound of Technetium Nitride Complex for Radiodiagnostic Imaging. US2010/160615[P], 2010, A1, Page column 6

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