[Sunitha]

Hello Everyone,

I wanted to try LAH for ester reduction. We have 2.4M LAH in THF in our lab. My substrate(ester) is not soluble in THF, Diethyl ether, acetone, dioxane, DME, and acetonitrile but soluble in DMF. In the protocol, the solid LAH was dissolved in THF and added dropwise to the ester. When I followed the same protocol but used liquid LAH dissolved in THF and ester dissolved in DMF and proceeded to reaction, but the reaction was not successful with undesired products. Could anyone please provide suggestions on how to take care of the reaction and any other solvents suggestions? I need to reduce 2 sites on my substrate and tried using 2-5equivalents. 

[rolnor]

LAH reacts fast with DMF, you could try t-BuOH/Lithium borohydride,

[Sunitha]

Thanks for your response. We don't have LiBH4 in our lab. I dissolved my ester in DMF, added LAH to THF, and added LAH in THF drop-wise to the ester. I continued the reaction as per protocol. In the NMR, noticed the aromatic region is missing. I tried increasing the equivalents of LAH to 6eq, but still, the products are the same which is undesired. I tried NaBH4, but it did not work at all. Should I proceed with THF to dissolve my ester even though the ester is not soluble in THF? Please provide suggestions. Thank you.

[Babcock_Hall]

If LAH is reacting with the solvent, then increasing its number of equivalents will not help.  Without knowing more, it seems to me that either you need to find a reducing agent that is compatible with DMF, or you need a different substrate that leads to the same product.

[rolnor]

you can try dimethoxyethane as solvent, then you can heat this to reflux to dissolve your ester. diglyme, dioxane can also work

[kriggy]

I would try to run it in suspension. SOME ester will dissolve in THF and by this part being reduced by LAH, you get more ester dissolved and reduced.

You can possibly saponify the ester and reduce the acid with borane / LAH / NaBH4+I2

[rolnor]

I would try to run it in suspension. SOME ester will dissolve in THF and by this part being reduced by LAH, you get more ester dissolved and reduced.

You can possibly saponify the ester and reduce the acid with borane / LAH / NaBH4+I2

Aggre kriggy, especially if reflux is used, thats why I suggest higher boiling solvent

[Sunitha]

I have tried running it as it is in THF as per the protocol and extended it to 24 hours too, but there is no reaction progress, it's just the starting material. As per the protocol, with the water workup, there is a dehydrative ring closure. I'm not sure what other solvent I can use in this reaction. I cannot change my substrate now, as this step is almost the final one. Do impurities affect this reaction? If the compound is a mixture will it affect the reaction? Please provide suggestions.

Thank you.

[rolnor]

I have suggested diglyme, dioxane or dimethoxyethane. They have higher boilingpoint