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Building a better Birch reduction

Method ditches liquid ammonia for common organic solvent

by Leigh Krietsch Boerner
November 7, 2021 | A version of this story appeared in Volume 99, Issue 41


Benzoic acid reacts with lithium and ethylenediamine in tetrahydofuran to form a reduced cyclohexadiene.

The Birch reduction is an important organic transformation with a bit of a scary synthesis. Traditionally, chemists use highly toxic liquid ammonia at or below –33 °C for both reagent and solvent, which requires specialized equipment and a lot of caution. Kazunori Koide and coworkers at the University of Pittsburgh have redesigned the reaction, swapping in the less toxic tetrahydrofuran as the solvent, with ethylenediamine as the amine source (Science, 2021, DOI: 10.1126/science.abk3099). Used for making drugs and perfumes, the Birch reduction changes arenes into 1,4-cyclohexadienes using lithium, sodium, or potassium. Other groups have also reworked the reaction, Koide says, but they used expensive reagents, long reaction times, or both.

The new method takes 15 min to 1 h at 10 °C and can be scaled up to make over 50 g of product. The researchers used it to transform 37 carboxylic acids, aryl ethers, and heterocyclic amines in modest to high yields.

Koide notes that the simplicity of the method surprised the team. “I hope that people will start using the Birch reduction more actively without hesitation and with improved safety,” he says.


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