Nitrostyrenes to oximes with sodium dithionite

[Barium]

This is the easiest way so far to reduce nitrostyrenes to oximes. I haven't been able to get all the way to amines yet, but that's just a matter of time. I know I'll be able to get amines with this lovely and cheap as shit reducing agent. The best route to amines is probably reduction to nitroalkanes with aqueous sodium borohydride/PTC followed by dithionite-reduction to the amine.


General procedure for reducing nitrostyrenes to oximes

100 mmol 1-(2,4-dimethoxyphenyl)-2-nitropropene (22,3g)
250 mmol Sodium dithionite (43,5g)
MeOH, EtOH, or IPA
Water
Sodium carbonate

To a 500 ml roundbottom flask equipped with a magnetic stirbar is added the nitrostyrene and 25 ml MeOH and stirring is started. Sodium dithionite is added in one portion followed by 100 ml water. Immediately when the water is added the yellow color of the alcoholic solution dissapears. The temperature remains steady for about five minutes when suddenly almost all of the nitrostyrene dissolves and gets reduced within one minute and the temperature increases to about 60°C. The mixture is now completely colorless. Stirring is continued for five minutes while cooling is applied by surrounding the reaction vessel with cold water.

When the temperature has dropped to 20°C solid sodium carbonate is added in portions to neutralize the acidic solution. When the pH 8 has been reached 200 ml cold water is added to the flask. When more sodium carbonate is added and the pH increases to above 10 the colorless solution turns cloudy and a crystalline mass falls out. The addition of sodium carbonate is continued until no more crystals forms. The mixture which is now very thick with white crystals is filtered and the crystals are washed once with 5% acetic acid and twice with cold water.

Yield 18,1 g 2,4-dimethoxyphenylacetone oxime (87%)

[moo]

Why don't you go drink a few pints with Varma and Kabalka and brag a little about your research!  Good work!

[Chimimanie]

Yes, I knew we could use good ol' dithionite for our purpose....

That is great to have researchers like you, Barium, to test new routes.

[Antibody2]

love oximes, awesome work barium. wondering how this might fare on nitropropenes?

[SpicyBrown]

Does anybody know if the aldoxime resulting from this type of a procedure on a phenyl-2-nitroethene would stand up to reduction by sodium metal in ethanol?

-SpicyBrown

[Megatherium]

The best route to amines is probably reduction to nitroalkanes with aqueous sodium borohydride/PTC followed by dithionite-reduction to the amine.

I guess the reaction conditions for the nitroalkane --> amine reduction would be similar than the ones above.  Am I right?  It would be great to see how the / / reduction compares to the Zn reduction / ammonium formate of an arylnitropropane. 

It is misterous to see how all those reductions of nitropropenes get stuck in oximes: Pd/C, Pb - DMF, Fe + HCl (where the oxime is converted in a ketone).

[zorohydride]

Well done, Chappy. This has to be one of the most facile reductions of a nitrostyrene that I have ever seen. Kudos to you. So now what? How about a facile borohydride reduction under alkaline conditions to yield the n-hydroxyamine which may have activity. Note of caution, are you sure about the acetic acid wash of an oxime; could this lower yield and form a ketone?

[Rhodium]

Strangely enough,

https://www.thevespiary.org/rhodium/Rhodium/chemistry/redamin.dithionite.html

says that imines are reduced to the corresponding amine with sodium dithionite, while oximes are hydrolyzed to the corresponding carbonyl compound.

Oh well, at least we can look forward to dithionite being another reducing agent with which we can go from phenyl-2-nitropropenes to pheny-2-propanones.

Dithionite preparations:

Post 429965

(lugh: "Inorganic Syntheses", Chemistry Discourse)

https://www.thevespiary.org/rhodium/Rhodium/chemistry/dithionites.html

[GC_MS]

I applied the dithionite procedure twice on p-methoxyphenyl-2-nitropropene (10 mmol), one time using MeOH and a second time utilizing EtOH. In both cases, the end result is an amorph crusty yellow solid; the yellow is very similar to the nitropropene colour. When I screen a solution of the solid in MeOH via GC/MS, I retrieve a major compound with M+ = 193. This, for sure, is not the ketoxime but most probably the unreacted nitropropene. Other compounds in the chromatogram are solvent impurities, and a trace of anisaldehyde (area 0.4% of the chromatogram).
When adding the dithionite to the nitropropene/alcohol suspension, there was no raise in temperature. In case of using EtOH as co-solvent, the reaction mixture has also been slightly heated (ca 35-40°C), but as demonstrated, this did not give the hoped results.

EDIT - Before everybody starts yelling, screaming and panicking: I'm not claiming the method is bogus, only that I have been unable to reproduce the method by applying it on a different substance.

[Antibody2]

when the proceedure was attempted on 2,5-dimethoxynitrostyrene. Three atempts in all, all in MeOH, using a tech grade of dithionite. These were the observations

1 - In all cases the colour was reduced
2 - In all cases the colour reduction took from 0.5 hours to two hours
3 - temp rose only slightly with a 100mmol rxn but not w/ 25mmol rxns
4-1st attempt (100mmol) using sodium dithionite containing some alkali, rxn remained a mixture throughout, at the end of which( 2hours) a HOAc and H2O insoluble crystal was obtained which yeilded nothing but foul sulfur smell during Al/Hg/HOAc redxn

5- 2nd attempt (25mmol)using dithionite that had been H2O washed to neutrality, temp to 65C was breifly applied everything went into solution, nothing crystalized  - complete failure

6 - 3rd attempt (25mmol)using dithionite that had been H2O washed to neutrality,  resulted in less than 5mmol of what is assumed to be the oxime (i have no physical properties here bees, anyone else?)

this was reduced ok but have yet to take a MP.

[Barium]

 Running in circles pulling my hair and screaming like mad

I have no idea why you got those results GC_MS. I´ve used this method on plain 1-phenyl-2-nitropropene and 1-(2,4,5-trimethoxyphenyl)-2-nitropropene too and got excellent results. I have not verified the identity of the oximes by any other method than HPLC and mp. When I have reduced 1-phenyl-2-nitropropene to the ketoxime in the past using hydrogenation, SnCl₂ and CTH (sodium hypophosphite-Pd/C) the result has always been a product contaminated with about 20% P2P. The dithionite reduction gave less than 1% P2P contamination.

Was there a color change?
How alkaline did you make the post-reaction solution?

I'll get some p-MeO-benzaldehyde to see if I get the same results. Don't be surprised if there is no noticible exotherm on a 10 mmol scale. Water is a very effective heat-sink. Did you add water to the reaction by the way?

AB2: 2,5-DMNS does indeed get reduced but I fear that the oxime is, to a large extent, hydrolysed in the aqueous acidic enviroment to the aldehyde. I have no idea how the aldehyde behaves under those conditions.

[Antibody2]

Barium - damn! that's really too bad. a two step circle.

I am curious an another note altogather. What is the water soluble intermediate in this reaction prior to the sodium carbonate addition?

[GC_MS]

My dithionite turned out to be utter crap. It might be wise to store it in a freezer if you only use it occasionally.

[Ganesha]

Good post GC_MS!

One more paper from same author on same subject:

Reduction of aldehydes and ketones by sodium dithionite

Johannes G. De Vries, Richard M. Kellogg;
J. Org. Chem.; 1980; 45(21); 4126-4129.

[armageddon]

Hi bees!

I just want to know: has anyone tried the reduction described by Barium (besides GC_MS who unsuccessfully used partially decomposed dithionite?)? It seems to work so easy and nice, I wondered why nobody verified it yet!?
(I mean reduction of nitropropenes to oximes, not ketones to alcohols)

THX, A

[Vitus_Verdegast]

But I never managed to get a high yield from it. Also, I had the same unpleasant sulfurous smell (most probably H₂S ) that AB2 describes above evolving from the final acidic Al/Hg reduction of the oxime.

[armageddon]

Hi!

A friend of mine (called SWIA for simplicity) told me yesterday that he verified the usability of sodium dithionity for reducing P2NP to the oxime - and was very confused about the yield he got!

The poor boy ( ) placed a 500ml erlenmayer in a 50°C water bath, in which he suspended 100mmol P2NP in 30ml EtOH, added 50g sodium dithionite (86% purity) and finally 200ml water and started stirring while monitoring the rxn. temp.

First the temperature slowly rose to ~45°C and the dithionite dissolved (yellow flakes appeared). After a couple of minutes, the temp. suddenly shot up to over 70°C while the rxn homogenized to a milky off-white suspension.
Stirring was continued for five minutes, then the water bath was exchanged with a cooling water bath (10°C) and rxn allowed to cool down to ~20°C.

Then, solid Na2CO3 was added until gas evolution ceased, followed by addition of 300ml water and trituration to pH10 with NaOH. The whole lot was then placed in the fridge overnight and suction filtered to give a lot of white, transparent, crunchy needles.

So far, so good.

After the crystals had been air dried for one day, SWIA weighed them - 29 grams!! Even with his poor chemistry knowledge he was able to judge that this was far too much - compared to the amount of P2NP he had put in!

Well 100mmol (16.3g) P2NP should give 14.9g oxime - in the best case possible.

So: what went wrong? are the crystals some carbonate? Hydroxide (probably not)? Is the dithionite involved? Or (my favourite exp.) are they just hydrated, meaning SWIA shoud've dried them with a drying agent/dessicator?

Help is greatly appreciated!

THX A

[Barium]

I'll run a couple of dithionite reductions again in a couple of days, just to verify my previous results. The substrates will be a couple of different nitropropenes.

[armageddon]

Hi!

My buddy "SWIA" tried to take a mp of his unknown crystalline substance gotten from dithionite reduction of P2NP - it is >100°C...

("burning" it on a piece of aluminum foil caused it to somewhat dehydrate, first becoming wet and then solidifying to a white something!?)

Seems like SWIA got a lot of huge sodiumcarbonate decahydrate crystals!

- But where did his oxime go?  

Greetz A

[arseholio]

Any verification for this reaction at all?