Sciencemadness Discussion Board

borohydride/alcohol reactions and role in reductions

Templar - 18-5-2016 at 05:08

Hey guys, I have been thinking about something.

I have been looking into the reduction of alpha methyl and beta nitrostyrenes, specifically reducing the double bond to convert them to nitroalkanes.
I cannot find much conventional literature about use in this application, except research papers which dont seem to provide much in the way of reaction mechanics.

I have gathered from a few sources, not formal, that when a alcohol system is used, the borohydride reacts with the alcohol to form a trimethoxyborohydride if methanol is used, or triacetoxyborohydride if ethanol is used, and so forth. It was also suggested that this was the reducing agent responsible for reducing the double bond.
Some sources discourage use of methanol saying it will react and consume the borohydride, instead using isopropanol or ethanol which react slower.

This brings me to my next thought, nitrostyrenes are known to dimerize via michael adduct (alkene + alkane reaction, in this case alkene + nitroalkane), and that using a large excess (2.5 - 4 molar) of sodium borohydride to which the nitrostyrene is added incrementally will reduce this significantly.
It is remarked here that alpha methyl nitrostyrenes dimerize to a much lesser extent, but no concrete explanation exists as to why.

Other sources remark that adding the borohydride to the nitrostyrene in alcoholic solution is better, limiting the amount of trialkoxyborohydride produced.
I dont think it is the intermediate formed during the reduction of the nitroalkene that causes dimerization, nor that the reaction between methanol and borohydride is a bad thing, could it then be said that having the borohydride in methanol and adding the nitrostyrene dissolved in THF or propyl propanoate would reduce dimerization by immediately reducing nitroalkene to nitroalkane as it is added?

I am still looking for (formal) literature sources, I will post them if I find them.

SILICA GEL-ASSISTED REDUCTION OF NITROSTYRENES
TO 2-ARYL-l-NITROALKANES WITH SODIUM BOROHYDRIDE is one but I cant upload the pdf for some reason. It says that dimerization is most severe with vinyl unsubstituted nitrostyrenes, eg beta nitrostyrenes.



Cheers

[Edited on 18-5-2016 by Templar]

Crowfjord - 18-5-2016 at 15:22

Quote:

or triacetoxyborohydride if ethanol is used


Surely you mean triethoxy. Triacetoxyborohydride results from use of acetic acid.

I can attest to methanol decomposing sodium borohydride more quickly than ethanol. The evolution of hydrogen gas is noticeably more rapid.

This has been covered on the forum before, but nitrostyrenes are Michael acceptors just like alpha, beta-unsaturated carbonyl compounds. The dimerization that takes place does so via the Michael reaction: in basic (or even neutral) conditions, the nitroalkane can become deprotonated and add across the double bond of the nitroalkene. Alpha methyl nitroalkenes react in this way much more slowly due to stearic hindrance, assumably. Silica gel is added to act as a weak acid, to prevent the base-catalyzed addition. However, adding small portions of nitroalkene to a large excess of sodium borohydride in ethanol and a cosolvent. This effectively reduces all nitroalkene to nitroalkane before the two have a chance to run into each other and form the dimeric product.



[Edited on 18-5-2016 by Crowfjord]

Templar - 18-5-2016 at 18:11

Thanks for the input. Yes that was a typo, I got confused thinking that acetoxy and ethoxy are the same.

Is the reaction between borohydride and alcohol required to produce the reducing agent responsible for reducing the double bond? This is the question..

Will this reaction still occur in say, DMF or other solvent capable of dissolving the borohydride without reaction? THF could be another example but solubility of sodium borohydride is very low; 100mg/100ml I believe.

If this alcohol borohydride reaction isnt necessary, then maybe isopropanol would work better, and reduce the amount of borohydride required.

There is always a large excess of borohydride remaining at the end of these reactions too; this sounds like a serious inefficiency. Acetic acid must be added in significant quantities to destroy this at the end when using a 4x molar excess of borohydride.

Crowfjord - 18-5-2016 at 18:42
Quote:

Is the reaction between borohydride and alcohol required to produce the reducing agent responsible for reducing the double bond? This is the question..


That's a good question. I'm not sure, but since that double bond is a good Michael acceptor, it is definitely in want of electrons and so should be pretty easy to reduce. As such, I don't think that the added reducing power of the trialcoxyborohydride would be absolutely necessary. I think alcohol is used to solvate the sodium borohydride since, as you know, it is not very soluble in THF. Then, because nitrostyrenes are not very soluble in cold alcohol, a cosolvent like THF or ethyl acetate is used for that.

I think I have read of isopropanol being used with success. And I think I have read of other reductions with sodium borohydride having been performed in DMSO. DMF would be interesting. I think it could work, but I would try isopropanol first just because it is cheaper and easier to aquire. Feel free to experiment and tell us about it.

As for the excess borohydride, I am pretty sure the purpose of using weak acids like silica gel is to circumvent just that. Very dilute reaction conditions and/or very slow addition of the nitroalkene may work too.

lullu - 19-5-2016 at 03:03

It is not required.
I can confirm that you can reduce them in good yield using aqueous NaBH4 solution with IPA as co-solvent.
I did not check the original reference but if I remember correctly they still use a 4 molar excess of NaBH4 for ß-nitrostyrenes in that silica gel paper, no?

Chemi Pharma - 19-5-2016 at 13:35

Forget about this old techniques guys.

Use Nickel Boride instead made in situ from sodium borohydride and nickel chloride.6H20 in methanol.

An OTC and greenish way to reduce everything thats LiALH4 does with no risk, low costs and high yields.

See the papers below:

http://www.sciencemadness.org/talk/files.php?pid=448180&...

http://www.sciencemadness.org/talk/files.php?pid=448180&...

http://www.sciencemadness.org/talk/files.php?pid=448180&...

http://www.sciencemadness.org/talk/files.php?pid=448180&...

http://www.sciencemadness.org/talk/files.php?pid=448180&...

http://www.sciencemadness.org/talk/files.php?pid=448180&...

lullu - 20-5-2016 at 07:02

Since when is NiCl2 considered "green chemistry" or is that just meant as a reference to the hexahydrate Chemi Pharma ;)?
The michael addition problem is still a problem here.
Anyone tried CuSO4/NaBH4 on beta-nitrostyrenes?

[Edited on 20-5-2016 by lullu]

Chemi Pharma - 20-5-2016 at 09:46

lol lullu:P

Although the green color of a methanolic solution of nickel chloride, the reaction between borohydrides and transition metal salts have been called as greenwish or enviromental friendly reactions. Don't ask me why!:) As far as i know nickel subproducts are also toxic to cells, like chromium and copper.

I don't see why michael addition is a problem here, cause the Nickel Boride reduces the nitro group and also the C=C bond of nitrostyrenes or nitroalkenes.

I have a paper about other NaBH4 combinations, even CUSO4 (topic 9 in the paper attached. See below



Attachment: sodium borohydride + combinations as a reducting agent.pdf (326kB)
This file has been downloaded 1505 times

morsagh - 22-5-2016 at 23:11

Very goog question. It is because green chemistry is not only about being ecological but too economic. You want to have the best yelds and you want as little as possible steps in synthesis...

Mush - 4-9-2017 at 14:59

Is there a way to recycle access NaBH4 after quenching the reaction mixture with GAA as Na triacetoxyborohydride? Has anyone tried to recover the unreacted NaBH4?

[Edited on 4-9-2017 by Mush]

Melgar - 4-9-2017 at 22:23

Quote: Originally posted by Mush  
Is there a way to recycle access NaBH4 after quenching the reaction mixture with GAA as Na triacetoxyborohydride? Has anyone tried to recover the unreacted NaBH4?

Quenching the reaction mixture with acid destroys the unreacted NaBH4, so to answer your question: no

Mush - 5-9-2017 at 08:39

Quote: Originally posted by Melgar  
Quote: Originally posted by Mush  
Is there a way to recycle access NaBH4 after quenching the reaction mixture with GAA ? Has anyone tried to recover the unreacted NaBH4 as Na triacetoxyborohydride?

Quenching the reaction mixture with acid destroys the unreacted NaBH4, so to answer your question: no



Indeed mineral acids and diluted acetic acid destroy the NaBH4. In anhyd. IPA adding GAA to the NaBH4 Na triacetoxyborohydride forms.

large excess of GAA was used to decompose the borohydride and yet the filtered very fine paste contacting with H2O started to release gas.
Nothing else could have been formed other than Na triacetoxyborohydride.



[Edited on 5-9-2017 by Mush]