[darkdevil]

Hi,
I am performing a reduction experiment on an aldehyde into an alcohol using sodium borohydride. In a typical work-up procedure, water and HCl was added to protonate the alkoxide and forming the neutralized alcohol.
I just wonder if I add an alkyl halide instead of water and HCl during the work-up part, will I get an ether rather than the alcohol? Is this possible so that I can do the etherification in a one-pot manner?

[AlphaScent]

This a good question I think.  The attached web page has the general mechanism about 3/4 of the way down.  The BH3 that is produced after the addition of a hydride atom will continue to react and form a tetrahedral intermediate that is cleaved during the acidic workup.  Is it crazy to think an alkyl halide would not react.  I am sure it would.  Conditions would have to be thought about though.  I know it would be nice to do the etherification in one step.  But why not isolate the alcohol and perform a well known and studied Williamson ether synthesis?

[AlphaScent]

http://shakti.trincoll.edu/~tmitzel/chem211fold/classnotes/1107_wed/1107_wed.htm

[orgopete]

I am performing a reduction experiment on an aldehyde into an alcohol using sodium borohydride. In a typical work-up procedure, water and HCl was added to protonate the alkoxide and forming the neutralized alcohol.

If you are performing a typical borohydride reduction, then you will be using an alcohol as solvent. This will compete with your desired ether formation. Secondly, as I understand the mechanism, HCl does more than protonate any alkoxide present. Boron will not be present as a simple trivalent cation. It will be present as a borate ester. The HCl protonates any remaining B-H bonds to give hydrogen, but it also hydrolyzes the borate esters to give boronic acid and your free alcohol. I suggest working up your nascent alcohol and if you wish, convert it to your ether without further ado.

[darkdevil]

I can obatain my alcohol as a pure product actually. But it does not go well with williamson ether synthesis. My alcohol is 1-Pyrenemethanol. When I do the etherification, the reaction did not seem to proceed well. I did 2 trials. the first one I used K2CO3 as base and DMF as solvent. while the second experiment I used NaOH(aq) and DMF. Both reactions did not give any changes in TLC. And I can even recover my alcohol (confirmed by NMR analysis) which means the reaction did not undergo properly as well. I do not have sodium hydride here, so I came up with this idea of doing the aldehyde reduction thing to get my ether directly in one-pot manner.

I think in another possible case I will try to make the alkoxide with sodium metal and then add my alkyl halide to get my ether.

Thanks

[kriggy]

What alkyl halide are you using?
And maybe more importantly, why are you using DMF as your solvent?

[darkdevil]

My alkyl halide is vinlybenzyl chloride.
the reason I use DMF is that I read about the effect of solvent may greatly affect the nucleophic attack. So I chose DMF as the solvent which it is polar aprotic and with a higher b.p.
I did a similar reaction before with DMF, K2CO3, Phenol amd a primary alkyl halide. The reaction worked fine with over 90% yield. I have no idea why the reaction I  trying now gave a quite different results as they are both primary alcohol and primary alkylhalide.

[AlphaScent]

Isnt it a benzylic alcohol?

[darkdevil]

This is the alcohol


And I think there is something to do with the solubility of the alcohol. This alcohol is not water soluble. Even if I add a crown ether, the reaction does not proceed. Still thinking how to do it :O

[orgopete]

When a phenol is used, potassium carbonate can convert it to its anion completely. With a benzylic alcohol, the equilibrium greatly favors the un-ionized form. As a result, the kinetics should result in a very very slow reaction.

You need a stronger base.

[darkdevil]

Hi,
It seems the reaction is proceeding using high concentration of KOH solution with THF and a equivalent amount of phase transfer catalyst with the alcohol.
Another TLC spot is on top of the starting material after 12 hours of reaction, but I can still see an adequate amount of starting material at the bottom. I am now trying to increase the temperature a little and wait.

[darkdevil]

And when I used a stronger base (eg. NaH). I can get 98% yield for the etherification with benzylic alcohol:alkyl halide in 1:1.1 ratio without large excess of alkyl halide

[AlphaScent]

Awesome.  Isnt it great when it works!!!

[Tcsbabie86]

Hi I am attempting a similar reaction except I am using a phenol with my alkyl halide being 2-chloroethanol.  I am having the same problem you were having where I am getting my starting material with no extra spots showing up on my tlc plates.  Do you have any advice on solvents and procedure for this to take place.

Thanks