Increasing Leuckart Yields?

[Blammo]

I have read that the lecukart suffers from low yields due to self condensation of the reactants.

Would having a larger excess of formamide/n methylformamide and slowly adding the ketone into the reaction make a positive differences?

I figure that having more of the amide floating around, and having a l ow concentration of the ketone, might reduce the losses and increase yields.

 

[Idontcarethatmuch]

As a promtion of "doing your own research by AI" I post an answer to your question an AI gave me.

"Yes, that strategy can help. Here’s the reasoning:

• Problem: Low yields due to self-condensation of the ketone (or aldehyde) — the ketone reacts with itself instead of with formamide/N-methylformamide.
• Solution 1 – Excess of the amide: Using a larger excess of formamide or N-methylformamide increases the likelihood that the ketone reacts with the amide instead of self-condensing. The reaction becomes kinetically favored toward the desired product.
• Solution 2 – Slow addition of the ketone: By slowly adding the ketone to the reaction mixture, you keep its instantaneous concentration low. This reduces the rate of self-condensation because self-condensation is second-order in ketone, whereas reaction with the amide is pseudo-first-order in ketone (excess amide).

Combined effect: Using both a large excess of formamide/N-methylformamide and slow addition of the ketone typically improves yield by minimizing side reactions.

Optional additional tips (just mechanistic):

• Maintain a moderate temperature; too high accelerates self-condensation.
• In some cases, adding a small acid/base catalyst can help selectivity, depending on the reaction.

This is a common practical tactic in formamide condensations (like Leuckart reactions) to suppress dimerization."