Nitro Reduction problems

[Xicori]

Dear fellow Bees!

Swim is asking for your advice, because every trial to reduce a nitro compound to the corresponding amine failed, using the Zn/HCOOH/Ammon formate procedure (

https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitro2amine.zn-formate.html

)

Sine some attempts witch plain formic acid/activated zinc failed swim decided to try it with ammonium formiate.

The ammonium formate was made by the neutralisation of formic acid witch excess of aqueous ammonia, followed by evaporation under reduced pressure to yield snow white hygroscopic crystals.

Swim tried to reduce 1-Phenyl-2-Nitropropanol (made via

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenyl-2-nitropropanol.html

today. Here is how it went:

The Nitropropanol (24,5g)(single spot on TLC/HPLC) was dissolved in 135ml of Methanole, and 18.9g of Zn dust (which was activated by stirring into 5% HCl for 2 min, followed by excessive water washes and a final acetone wash) was added to the light yellow solution.

To this was added under heavy stirring 27g of Ammonium formate in one portion, and a reflux condensor was placed on the flask. The reaction was very exothermic, and the methanole started to reflux within seconds.

The exothermic reaction was over after a few minutes, and the flask was stirred further 30min, until it had returned nearly to room temperatur. A lot of salts and the remaining zinc was filtered off, and the filter cake was washed with fresh methanole.

The methanole was removed on the rotary evaporator to leave some oily orange residue with a lot of inorganic (?) salts.
This was cooled, and 100ml of Et2O were added. The flask was swirled and the ether decanted from the insoluble stuff. The salts were washed once more with 100ml of ether, and the etheral extracts were combined (color: pale orange)-

The ether phase was washed twice with brine, and once with a little water. Then the ether was extracted two times with diluted HCl, and the combined aqueous phases were washed once with 25ml of toluene.

The aqueous extracts were evaporated to dryness under reduced pressure on the rotary evaporator to yield maybe one ml of an oily residue   


Does anybee have an idea what might have gone wrong?

How important is dryness of the reagents (solvent & amm. formate)?

What over nitro reduction systems come to mind for such a task?

gues swim´s synapses have to wait another time for the good 4-MAR...    ...but thats just a matter of time  

Hope that somebody can help me out!

bestw ishes,
xicori

[Nicodem]

I don't think you can reduce 1-Phenyl-2-Nitropropanol at the conditions described. The boiling methanol, the formed Zn salts, anhydrous conditions, formic acid or ammonium formate, are all bad news for the substrate. I’m afraid at those conditions the first thing that does happen is a dehydration of 1-Phenyl-2-Nitropropanol to 1-Phenyl-2-Nitropropene. What goes on later is a matter of debate over the side products (or unwanted products): P2P, its oxime, P2Pol or the retroaldol products of the substrate.

You might try the same reaction keeping it at 0°C with an ice bath while adding ammonium formate portion wise and really slowly making sure the temperature never goes above 5°C. Still I doubt even this would work, but I do think it is worth trying.
Good luck

[Xicori]

High Nicodem!

Thanks for your response...

I don´t think that the nitropropanol is that sensitive for dehydration, since it is even distillable at ~125°C @ 2-4mbar, and Bandil used the reduction successfully on 4-Fluoro-phenyl-2-nitropropanol.

I think the problem may be located somewhere else  

Swim also had a run on 2,4,5-Trimethoxyphenylnitropropane with plain formic acid and Zinc, and also this reaction failed

Best wishes,
xicori