High-yield 2C-H synthesis by Sonson
Procedure
Into a three-necked 1L round bottomed flask fitted with an argon inlet, a condenser, an addition funnel and a stirring magnet, there was added 20g LAH to 350ml dry THF. The contents were allowed to cool in a ice/water bath for about 30min with stirring set on max. Then 25g of 2,5-dimethoxy-B-nitrostyrene was added slowly (addition time about 1h) as a THF solution (350ml). More ice was added during the addition to keep things reasonalbly cool. When all of the nitrostyrene had been added the the flask was allowed to stand in the ice/water bath for an additional 20mins with stirring left on. The cooling bath was removed and a heating was applied and the contents was kept at refluxing conditions for 20h. The flask was again cooled in ice/water and 20ml THF:H20 (50:50) was added drop by drop through the condenser. The argon flow was increased a little at this point to purge the hydrogen faster.
Then 20ml 4N NaOH was added slowly. Each portion was allowed to react before the next was added. 60ml water was added and the reaction mixture stirred for an hour or so until it was almost white and granular. The mixture was filtered through a porcelain filter and the filter cake was extracted twice with 50 ml portions of THF in a separate beaker. The organic solvents was combined and evaporated under vacuum. The residue was dissolved in water/HCl (pH=1). The aqueous phase was washed with 3×50 ml CH2Cl2. The organic phase was re-extracted with 50ml HCl/water. Then the combined aqueous phase was made basic with NaOH (pH=14) and extracted with 4x50ml CH2Cl2. The organic phase was dried with K2CO3 and evaporated. The residue (2C-H) was only slightly colored and weighed 16.98g (75%).
A bit more cost effective then earlier methods using LAH I dare say!
According to the original JMC article it is also possible to directly dry the THF solution after filtering off the inorganic lithium/aluminum salts, evaporate the solvent and distill directly to get the freebase. About the same amount of work, and you’ll get an even cleaner product.
I have also found the following variation:
5.5g of the nitrostyrene was put in a continous soxhlet extractor. To the flask was added 3.8g LAH in 200ml dry ether. After the extraction was complete the mixture was allowed to reflux 6 more hours. Work-up with conc. Na-K-tartrate. Gave 3.5g (87%). Distilled (140C/2mm) to give 3g pure freebase.
Eliminates the use of THF but you’ll need a soxhlet extractor.
