[johno91]

I did a lab in which I reduced vanillin to vanillyl alcohol. We used NaBH4 as the reducing agent. I want to find a better way to do the lab, or increase the yield. My TA told me to try to find a reducing agent that works in the presence of phenols (acid) and does not require base. He said to search for 'neutral reducing agents.' I've tried to find a reducing agent capable of this but have not been able to so far.

So if someone could point me in the right direction or show me a practical way to synthesize vanillyl alcohol with a catalyst other than NaBH4 or LiAlH4 it would be much appreciated.

[Babcock_Hall]

I can think of at least one reducing agent that works in acid.  However, phenol itself is a weak acid, with a pKa value of about 10.  I would not expect the pKa of the phenolic group in vanillin to be identical, but I would expect it to be in the same vicinity.  So I am not sure what your concern actually is.

[Dan]

I guess this is a theoretical question since vallinyl alcohol is so cheap most would just buy it.

Did you try googling "neutral reducing agents"? Also try "neutral reducing agents aldehyde".

I actually did this and got answers in the first couple of hits.

Hint: there are several borohydride reagents that tolerate pH<7, some of which can easily be made in situ from sodium borohydride

Note: It is against the forum rules to provide a direct answer to your question, you must show you have attempted it.

I must say though, I agree with Babcock_Hall, sodium borohydride does work perfectly well. I suspect the yield issues you have are more to do with purification methods than the efficiency of the reaction itself.

Here is an example of a literature procedure for the reduction of vanillin with sodium borohydride. The yield is 98%, see page 6.

http://pubs.acs.org/doi/suppl/10.1021/ol902672a/suppl_file/ol902672a_si_001.pdf

[johno91]

I should have been more clear. In lab we added NaBH4 and made the solution basic with NaOH. I'm trying to find a reducing agent that will work in the presence of vanillin which is slightly acidic, so I do not have to add NaOH. I did search for neutral reducing agents and found this article but my university's access to the website is acting up and I can't get on to read the full article. From what I gather it is a neutral, selective reducing agent which is what I want but I'm wary to use it since I can't see any examples from the article. Is there any chance it will interfere with the hydroxy or ether on vanillin, or is that what 'selective and neutral' means?

Thanks for the quick responses.

[Dan]

I'm trying to find a reducing agent that will work in the presence of vanillin

Sodium borohydride reduces vanillin in 98% yield - you don't get much better than that. Again:

Here is an example of a literature procedure for the reduction of vanillin with sodium borohydride. The yield is 98%, see page 6.

http://pubs.acs.org/doi/suppl/10.1021/ol902672a/suppl_file/ol902672a_si_001.pdf

[orgopete]

I agree with Dan here. No evidence has been presented that the yield of the reaction is actually low. No report of recovered starting material or by products has been given. For all we know, the yield was high and the recovery was low.

[fledarmus]

I agree with orgopete. Borohydride and aluminum hydride reactions can be difficult to get complete recovery because the boron and aluminum adducts can be difficult to break down and remove. Especially the aluminates which can form precipitate sludges so fine that they pass through (or worse yet, plug) filters. The reduction should go cleanly to completion, but isolating all of your product may be a challenge. I would focus on that aspect rather than trying to find another reducing agent. When you work up your reactions, you may need to let it stir for a while after you quench (a good time to grab lunch or coffee) before doing your extraction or filtration.

[discodermolide]

I agree with orgopete. Borohydride and aluminum hydride reactions can be difficult to get complete recovery because the boron and aluminum adducts can be difficult to break down and remove. Especially the aluminates which can form precipitate sludges so fine that they pass through (or worse yet, plug) filters. The reduction should go cleanly to completion, but isolating all of your product may be a challenge. I would focus on that aspect rather than trying to find another reducing agent. When you work up your reactions, you may need to let it stir for a while after you quench (a good time to grab lunch or coffee) before doing your extraction or filtration.

My contribution. i've found that LiBH4 reductions are very efficient, work up with acetic acid/and an appropriate solvent, avoids the problems with non-filterable salts.
This I have done on large scale.
Red-Al is also a good one.