I've been trying to reduce a schiff base that contains 2 benzene rings for the past 3 months now. I've used methanol, a methanol/chlororform mixture and dissolve the schiff base in methanol while dissolving the reducing agent in methanol. The reducing agent that I used most frequently was sodium borohydrate. I have used lithium alluminium hydrate also. According to the literature the sodium borohydrate should work but it doesn't.
Hi there,
It turns out that sodium borohydride reacts slowly with methanol (try putting some NaBH4 in methanol, it starts bubbling right away!), as well as ethanol. It could be that with the concentrations/method you are using, the NaBH4 reacts before it has time to attack your imine carbons. First thing I would try is increasing your concentration of NaBH4 and your imine. They don't have to completely dissolve as long as they are present in the flask.
Maybe try isopropanol (NaBH4 isn't very soluble in PrOH, but it is soluble enough and it doesn't react with it!)?Let it stir overnight and maybe sample via TLC or NMR to see if it is done before quenching the reaction.
I would stay with NaBH4. If you use LiAlH4, use THF under N2, stir overnight and be careful when you quench.
Use an excess of your reducing agent. All of the hydrides might not go to the reduction (for example. the first 1 on NaBH4 could go towards the reduction, but the other 3 react with solvent to make H2!).
I hope that helps.
-Kyle
Alcohols react with NaBH4 quite quickly, I would not use any alcohols for reductions with NaBH4.
I would recommend to use anhydrous THF or Chloroform.
In addition: With time NaBH4 undergoes hydrolysis when stored in air. You might want to take a small amount of your NaBH4 and put it on a watch glass. Pour some water or methanol on it: If it doesn't bubble, your NaBH4 had already been hydrolyzed and needs to be replaced.
Best,
Markus
Markus
Thanks for your advice. I've also tried adding the sodium borohydrate pinchwise but still doesn't work and I've just tested it with methanol and water and seems to work fine. In my case, its 2 carbon-Nitrogen double bonds that I'm trying to reduce. What do you think is the most suitable method to use?
I am working on the same reaction..means trying to form schiff's base of ketone and aniline and then reduce with NaBH4..I need guidance.
also,I want to know how to do work up after the reaction??
Last week I reduced a double bond in my schiff base compund with sodium borohydrate. First I solved my product in methanol and added dry NaBH4 spoonwise. This reaction was under room temerature or cooled down with ice when it was starting to warm up too much. While the adding period the reaction was stirred (of course). After 2 h I stopped the reaction by adding some drops acid. Then I removed the methanol and started to clean-up with ether.
I am also working on the same type of reaction, have synthesized imine and then opted to reduce it with sodium borohydride in methanol : DCM (1:4). Solid precipitated out from the reaction mixture but the problem is precipitated solid is not completely soluble in most of the solvents. Only some portion is soluble. What can be the Insoluble portion (might be some complex) which is forming in large quantity and desired soluble reduced compound is in small quantity.
Check out J. Org. Chem. 22, 1068 (1957). Uses an excess of NaBH4 in MeOH. I have repeated the prep with good results.
Last time I used methanol for the reaction and it worked quite effective.
If the schiff base only soluble in Non-polar or Polar aprotic solvents then what is the solution? I tried MeoH as a solvent to reduce my schiff base but the schiff would not soluble even i add excess amount of NaBH4.
Hi All,
In response to Theetharappan, another solvent to try is THF and let the reaction stir longer.
Kyle
Methanol has long been known to work for this reaction with good results. It should be dehydrated first before doing the reaction. THF could be tried instead if the Schiff base does not dissolve in methanol.
use a mixture of methanol and DCM. 1:1 to dissoilve your Schiff base and then add solid sodium borohydride little by little under ice and then stiir at room tenperature for at least 12hrs
I've had luck with isopropanol for slow NaBH4 reductions (see my C-S bond reduction here: http://pubs.rsc.org/-/content/articlehtml/2018/nj/c7nj03724d. The solvent doesn't react as quick as methanol or ethanol, so the NaBH4 is around longer to react with your substrate. Try heating it at 60 degrees (with a way to vent the H2 gas that is formed, don't seal it!). Doing this with an excess of NaBH4 should be a good way to get those recalcitrant reductions to go. As for workup, rotovap down, then wash with water to remove the salts and excess isopropanol, unless your product is water-soluble. Your product can then be recyrstallized if need be.
Kyle
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