Lithium Aluminium Hydride Tetrahydrofuran Explosion

A researcher at X was seriously injured when reducing a substrate using lithium aluminum hydride (LAH) in tetrahydrofuran (THF). Shortly thereafter, at least two other accidents involving procedures using LAH and THF have been documented. Due to the inherent hazards of LAH and THF, researchers must thoroughly plan out experimental protocols and incorporate safety measure to mitigate the hazards of this procedure. We have consulted with an outside expert in these issues, and he has made a number of important safety recommendations for this procedure.

Experimental Review

Following a typical protocol, an experimenter would:

  • Heat and flush a 3-neck, glass flask with nitrogen to drive off all moisture.

  • Remove heat source and cool the flask, but continue to flush with nitrogen.

  • Add a stir bar, THF (freshly distilled), and LAH

  • Flush with nitrogen for the rest of the procedure surround the flask with an ice bath.

  • Turn on the stirrer.

  • Start water running through the closed loop of the condenser.

  • Start drop-wise addition of the substrate (which is dissolved in freshly distilled THF)

However, this 'typical' setup is not necessarily the best setup.

Experimental Recommendations

Listed below are several recommendations pertaining to this procedure:

  • Use enough solvent to dissolve all LAH. Adding substrate to a slurry of undissolved LAH and solvent is almost as dangerous as adding it to dry LAH. The solubility of LAH in THF is 13g LAH/100g THF at 25oC, and in diethyl ether, 35g LAH/100g diethyl ether. Aldrich does not make solutions more concentrated than 1M (38g/liter). It is recommended to make solutions no more concentrated than 1M.

  • Add LAH to THF rather than adding THF to LAH when preparing solutions. Dissolving LAH in THF is very exothermic! If THF is added to dry LAH, the LAH can easily overheat and decompose exothermically, especially on larger-scale reactions.

  • Keep the ratio of LAH to substrate low. If the reaction goes awry, it's safer to have only a 2-fold excess LAH rather than a 10-fold excess to deal with.

  • Ensure that the stopcock on the substrate dropping funnel works smoothly. If the stopcock sticks, too much substrate may be delivered, creating excess heat in the reaction flask.

  • Ensure that the reaction flask is under a nitrogen blanket. Double check that the nitrogen inlet tube is securely fastened and all air is excluded from the reaction vessel.

  • Prepare the substrate carefully to exclude any residual solvents that might react with LAH. This way, you won't have to use as much excess LAH.

  • Ensure that the substrate/THF solution is free of peroxides. Any added THF should be freshly distilled.

  • Use chilled silicone oil instead of ice and water as a cooling medium. This is now current industrial practice for large-scale reactions. If the flask breaks for any reason, LAH will not react with silicone like it does with water.

  • Use an explosion shield when working with large-scale reactions. Lowering the fume hood sash and wearing protective eyewear is adequate with smaller scale reactions.

  • Quench the reaction mixture, by addition of water or other quenching agents, using extreme caution. Add the quenching agents slowly!

If you have any questions, call your safety office.