Reduction of Nitrostyrenes with Red-Al (Vitride)

by Strontium

After a couple of reductions the last days I can truly say -Fuck the LAH, all the way down to the sulfur pit it once came from. Red-Al IS really the easy way to go reducing nitro-compounds with a metal hydride.

Red-Al comes as a ready to use liquid, as 70:30 Red-Al:Toluene

Red-Al is non-pyrophoric

Reductions can in most cases take place without any dilution at all. Just add the dry nitro-compound as it is, in small portions. Example: 10g over 5 minutes, or less.

The litterature says that reflux should be maintained for about 2hrs after addition is complete. If you are in a hurry and 50-60% yield is sufficient, then skip the reflux. You have at least 50% yield direct after the addition is complete.

No need for cooling during addition since 80-110 deg C is a perfect reaction temp. Just add to compound to be reduced at a rate that keeps the toluene boiling.

Workup is a beauty.

After the reaction is complete, hydrolyze with 5%(aq)NaOH, very carefully in the beginning since unreacted Red-Al reacts violently with water. 175ml 5% NaOH/mol Red-Al used. Add portionwise and stir well after every addition. When this ration is used the aluminum salts will stay in solution as sodium aluminate. No precipitation whatsoever. Just one organic phase and a water phase. Separate them and wash the organic phase twice with water to dissolve the 2-methoxyethanol formed during the hydrolysis. Now acidify the organic phase with 5-10%HCl and separate. Eventual honey is now in the water layer. Make this water solution alkaline and the honey separates out as usual. Extract with DCM or toluene and evaporate solvent under reduced pressure. Water aspirator works just fine for boiling off toluene at 40-50°C.

Red-Al, Vitride, Sodium dihydrobis(2-methoxyethoxy)aluminate, Sodium aluminum bis(2-methoxyethoxy)hydride. CAS [22722-98-1]

For reducing nitro-compounds one need to use 3 moles red-al to one mole nitro-compound. Even if not needed it´s a good thing to use a small amount of toluene to dilute the reaction if it should get too hot.

After a few trials and errors using Red-Al and obtaining crappy yields, some adjustments have been done. To perform reductions of nitroethenes or propenes, this is how to do:

  1. Dissolve the nitroalkene to be reduced in toluene. The solubility is not that exeptional but OK.
  2. Pour the amount Red-Al to be used in a reaction vessel. Dilute this with equal amount(by volume)toluene. For a reduction using 100ml diluted Red-Al use a 500ml reaction vessel.
  3. Start adding the nitroalkene solution in 10-15 1-2ml portions/min. Keep adding in this manner until temp reached 50 deg C. Stop adding and let stir until temp dropped back to about 30 deg C. Due to good heat transfering properties of toluene, temp drops back in a matter of minutes.
  4. When all nitroalkene has been added perform hydrolysis with 175ml 5%(aq) NaOH/mol Red-Al (1 mol Red-Al = 280ml). Do this dropwise until the first violent reaction has subsided. This is unreacted Red-Al being chewed away by the water. You´ll notice when this reaction is over. Then add NaOH soln in 50ml portions. Separate the bottom water layer from the top toluene layer. Wash the toluene with two portions water to get rid of the produced 2-methoxyethanol. 2-methoxyethanol is rather toxic so be careful with it.

You do now have a toluene solution of your freebase together with impurities. Work this up in the usual way.

In my original posting on this topic I stated that the nitroalkene could be added dry to the undiluted Red-Al. The violent reaction conditions will create a mess of side ractions. When work up is done a huge amount of black tar will be the major product. Dry adding can work for some more sturdy compounds but not for most nitroalkenes. Therefore dilution is a nessicity.

THF can vey well be used as solvent for the nitroalkene instead of toluene. This will not interfear with the reduction in any way.

If the reduction is done according to the above descriptions one can expect 50% yield. If on the other hand reflux is being maintained for two hours after all nitroalkene have been added, 70-80% yield can be expected.

Get better results with Red-Al

by Barium

Red-Al [sodium bis(2-methoxyethoxy)aluminum hydride] is a very good reducing agent and a good substitute for lithium aluminum hydride (LAH). Compared to LAH, red-al is not sensitive to oxygen (but to moisture) and is very soluble in ether, THF, 1,4-dioxane, toluene and benzene.

There is a write-up on Rhodium´s page which describes the reduction of 1-(2,4,5-trimethoxyphenyl)-2-nitropropene to TMA-2 using red-al and toluene. What this write-up lacks is some necessary advice in order to get as good, or better, yields as with LAH.

In theory each mol of a phenyl-2-nitroalkene needs 4 mols red-al to produce the amine. Which can lead one to think that a slight excess (0.2-0.5 mol, due to the contact with moisture in the air and some in the substrate) red-al is enough to get some smashing +95% yields. Sorry!! To get the good yields, in my experience between 85-97%, one must use quite an excess red-al due to some wierd side reactions which both can and will take place otherwise.

As a rule of thumb 8mol red-al/mol nitrostyrene gives good results, BUT the thing to look for is the color of the reaction mixture. It should remain colorless or just slightly colored. If it becomes strongly colored I can almost guarantee the yield will not be higher than 30-40%.

Example of the procedure.

100 mmol (25.3g) 1-(2,4,5-trimethoxyphenyl)-2-nitropropene dissolved in 500ml toluene (toluene dissolves 50g/L) is added dropwise to 800 mmol red-al (225 ml of a 65% solution in toluene) diluted with 200ml toluene. Adjust the addition so the temperature doesn´t exceed 70 deg C. When about 2/3 of the nitroalkene has been added it´s time to keep an eye on the color. Up until now the yellow color from each drop of the nitroalkene solution has dissapered at one it hits the hydride solution. This is the way it should behave until all is added. If not, immediately one sees a remaining color, stop the addition and add 50-100 mmol red-al then continue the dripping. When all nitroalkene has been added allow the reaction mixture to stir and come back to room temperature during 1-2 hours. When the gas evolution has ceased the reaction is over. The work-up is done according to the procedure at Rhodium´s page.

Further examples of Red-Al reductions, the procedures below refers to saturated nitroalkanes:


I added 5g 1-(2,5-dimethoxyphenyl)-2-nitroethane dissolved in 20ml toluene dropwise to 4eq. (26ml) sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) during 10 min, and allowed this to stir overnight at room temp. After the usual workup this gave 4,65g (90,4%) 2C-H*HCl.


20g (78mmol) 1-(2,4,5-trimethoxyphenyl)-2-nitropropane was dissolved in 100ml toluene and added dropwise to 98ml (350mmol, 4,5 eq.) Red-Al diluted with 100ml toluene during cooling in a icebath. The addition took some 25 minutes and the temp was not allowed to rise above 80 deg C. When addition was complete the reaction mixture was stirred for 1 hour @ 70 deg C. Then a test was done to see if there was still excess hydride left. A glass rod was dipped into the toluene solution and then immersed in water to see if any gas evolution or fizzing occurred. Yes it did, so there was still hydride not consumed. The excess hydride was destroyed with AcOEt added dropwise until the exotherm ended (This is preferred over water because it causes no violent gas evolution). Then 66,5ml 5%NaOH was added and everything was stirred until all solids went into solution. The contents of the flask was transferred to a sep funnel and the bottom aqueous layer removed. The organic phase washed with 2x100ml water and finally with 100ml brine. The solvent was then dried with MgSO4 and diluted with more toluene to a final volume of 500ml. HCl dissolved in IPA was then added dropwise untill pH 5 was reached and the huge crop of crystals was filtred off. The crystals were rinsed with acetone and dried.Yield: 17,51g (67mmol, 86%) TMA-2*HCl as white crystals.

Lilienthal's Voice:

By using ethyl acetate to destroy excess alanate you are probably ethylating at least a part of your amine (actually this is a known route to produce methyl-ethyl-tryptamines). There are at least two independent papers out describing this effect.