In the reaction of Grignard reagent with a primary and secondary amide, nucleophilic acyl substiution doesn't happen. The reason given is that R- is a strong base as well as strong nucleophile, an acidic H is present in amide and finally, acid-base reactions are much faster than nucleophilic reactions. However, in basic amide hydrolysis, nucleophilic acyl substitution is able to occur despite OH- also being a strong base and nucleophile. Why doesn't the acid-base reaction occur here?

  • 3
    $\begingroup$ OH- is nowhere near as strong a base as a Grignard. Look up the pKa of a typical amide proton. $\endgroup$
    – Waylander
    Jun 10, 2022 at 6:03
  • $\begingroup$ @Waylander AFAIK, amides are weak acids as well as weak bases. OH- is a(relatively) strong base and so the amide should react like an acid. Even, if the reaction is slower than that with Grignard, shouldn't it still be much faster than SN2th? $\endgroup$
    – user121185
    Jun 10, 2022 at 6:11
  • 1
    $\begingroup$ The pKa of a typical amide is around 20, OH- is not stronger enough to deprotonate it $\endgroup$
    – Waylander
    Jun 10, 2022 at 7:42


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.