Large scale nitroalkene --> amide

[silenziox]

I'm referring on the

Large-scale MDA from piperonal

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/mda.txt)

Could the "200 g of LiAlH4 dissolved in 10 L of ice cold anhydrous THF" ratio be suppressed to f.ex. 5L of THF?
Never done LAH reductions, but I think this is the way to go..

[hest]

Yes, no problem. Bu the 200g LiAlH4 might bee hard to get ;-)

[silenziox]

No it isn't. It's just damn expensive (~160usd/200g).

But back to the question, what's the minimum amount of the solvent "best" to use on LAH-reductions?

[Rhodium]

The maximum solubility of LiAlH₄ in THF at 25°C is 130g/kg, and with the density of THF being 0.89 this is equivalent to ~115g/L. However, many sources reccommend that for safety reasons, the maximum concentration used in practice should be limited to around 1 mole/liter, which is 38g LiAlH₄ per liter of solution. Therefore I don't reccommend that you go any lower than 5 liters of THF to dissolve 200g LiAlH₄.

Also, as both the dissolution of LiAlH₄ in THF as well as the addition of the nitrostyrene to the LiAlH₄ solution are very exothermic processes, I wholeheartedly reccommend that you use an ice-bath to cool the reaction flask and the THF to 0-5°C before adding the LiAlH₄, and that you do it slowly in portions of at most 10-20g. Use a two-necked reaction flask, or if you must use a single-neck setup, don't allow the powder funnel to cover the entire neck when adding each LiAlH₄ portion, as there will always be a positive pressure in the flask during addition. Allow the temperature to return to 0-5°C before adding the next portion. The concentrated nitrostyrene solution in THF is to be added dropwise so that the evolved heat gets a chance to dissipate, otherwise a runaway reaction may result.

See the following documents:

Post 376864

(Rhodium: "Lab-size Mushroom Cloud", Methods Discourse)

Post 465429

(Rhodium: "LAH will fizz even with dry THF...", Newbee Forum)

http://www.dehs.umn.edu/whatshot/LithiumAH.html