Reactions of Amides

[@Ak-ch1je]

Hope u know that ur still saving people's life man. Thank you for the great video🫡

[@mariaph9700]

Hi Joe. Thanks for the video. Does amide (the reactant at 0:56) react with Amine (like NH3) instead of the water in your example?

[@jOeCHEM]

Hi Mariah! Thank you for watching! I'm not sure I understand your question. The reaction shown at kzbin.info/www/bejne/aYfTYpepfa2lmpo is meant to be an example of amide hydrolysis in acid. As a result, given our conditions, we are in an acidic environment (I could have used H2SO4 as my acid instead of generically specifying "H+"). In that case, we would have no ammonia around (NH3) in our environment to react with. Does that clear anything up? Or if not, can you explain a bit more so I can understand your question?

[@mariaph9700]

@@jOeCHEM Hey Joe. Thank you for replying! What I meant was whether or not amide would react with an amine, as in class I encountered an example similar but not same what you showed in the video. I have attached my in class question below: ibb.co/C2phN4x.

[@jOeCHEM]

@@mariaph9700 Thank you for clarifying (I understand your question now). Please checkout this video kzbin.info/www/bejne/qqLHqYR7d6epea8 I've made on acid halides. Acid halides are MUCH more reactive than amides, and if you have a "hard" nucleophile, an acid halide will be attacked twice. "Hard" nucleophiles are really reactive nucleophiles, such as Grignards, organolithiums, and hydride ions. However, "soft" nucleophiles (less reactive nucleophiles than the "hard" ones) only add once, which is the case of your problem with the amine attacking the acid chloride. If your amine was deprotonated and had a negative charge, maybe it would be a "hard" nucleophile, but a neutral amine would certainly be a "soft" nucleophile and do addition only one time to a reactive carbonyl. And because amides are a MUCH less reactive carbonyl than acid halides (check out this video that discusses different carbonyl derivative reactivity kzbin.info/www/bejne/rqbahndmmr5kbZI), no further attack happens. To attack the amide with a subpar (or "soft") nucleophile, you have to activate the carbonyl via protonation, which means you need acid to catalyze the reaction. However, if you have a amine nucleophile, your amine will just react with the acid present, doing acid base reactions and leaving your amide alone. Does that make sense?

[@mariaph9700]

@@jOeCHEM Very thorough explanation, thank you so much. I had no idea we needed to consider hard nu vs soft nu in this questions too. For Orgo 2, is it safe to know that Hard nu are Grignard (RMgX), organolithium (RLi) and hydrides (H-) and everything else is considered soft? My teacher briefly went over this hard-soft nucleophile in conjugated addition but I am not sure if this is all we need to know.

[@jOeCHEM]

@@mariaph9700 so I say this cautiously (because I'm not your teacher nor am I in your class), but yeah, in my experience those three (RMgX, organolithium, and H-) are the standard "hard" nucleophiles and everything else is "soft".