(263d) Lithium Borohydride Quench Characterization and Off-Gassing Management

Gas generation is a common occurrence in organic synthesis as gaseous side-products are often generated. To ensure such reactions can be carried out at any scale, proper characterization is needed. Accurate balanced equations are necessary to determine the theoretical amount of gas generated, however analytical methods must be used to quantify the rate and total amount of gas released. In this work, excess LiBH₄ from a reduction reaction was quenched using acetic acid, resulting in hydrogen off-gassing. Full quenching of the borohydride species was required to ensure safe scale-up and avoid pressurization during downstream processing. An initial large amount of gas and heat release were observed and controlled during lab development. However, a slow residual release was also observed over 48 hours. This residual off-gassing level was so low that it was below the detection threshold of typical lab-scale gas flowmeters.

A process analytical technique was developed that could effectively and reliably quantify the rate and amount of hydrogen gas generated. Raman was used to monitor the degradation of the borohydride species, and thus could be used as a proxy for hydrogen off-gassing. Once we had a reliable method for tracking quench completion, numerous strategies were investigated to mitigate safety issues prior to scale-up. We demonstrated that heating the quench for an extended time resulted in the complete consumption of excess LiBH4 and the subsequent borohydride species. This approach was implemented in two successful batches with no safety incidents related to the quench or hydrogen off-gassing. Further investigation was done to identify alternative quench methods for use in future campaigns, including sacrificial carbonyls and stronger acids.