2
$\begingroup$

enter image description here

I know that sodium borohydride doesn't work particularly well on resonance-stabilized carbonyl groups (i.e. esters) but what about this carbonyl in the center of the above picture? This appears to be somewhat resonance-stabilized ... why would sodium borohydride still work here? Sodium borohydride is a nucleophilic reagent. On the other hand the second resonance contributor I've drawn is pretty crappy; yes - it's part of an aromatic system - but it's also a carbocation. And the R' group is inductively donating (although I suspect this is a fairly minor point).

Or does it just work in the above synthesis but not with a yield comparable to something such as sodium borohydride and formaldehyde?

enter image description here

$\endgroup$
  • $\begingroup$ Where did you find this synthesis? Could you give the source? Are they giving any more details? Maybe using the softer kind of reducing agent is due to selectivity reasons... $\endgroup$ – Martin - マーチン Nov 17 '14 at 3:16
  • $\begingroup$ @Martin This is the second to final step in the synthesis of Allegra (fexofenadine). $\endgroup$ – Dissenter Nov 17 '14 at 3:30
  • $\begingroup$ @Martin chemdrug.com/databases/SYNTHESIS/SYN/23/23156601a.gif $\endgroup$ – Dissenter Nov 17 '14 at 3:32
2
$\begingroup$

Sodium borohydride is definitely strong enough to reduce an acetophenone derivative. It is likely that the resonance stabilization does reduce the reactivity of the ketone. It's not often that a sodium borohydride reduction requires 35 hours. In the cases that I have run, usually less than one hour is sufficient.

I did some quick searching of whether an isolated ketone could be reduced in the presence of an acetophenone, and I did not find an adequate example of a case where only the isolated ketone was reduced. That says to me that the reactivity difference is not that great. Perhaps someone else has come across this though.

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.