Where will a H+ attack on 6-hydroxyhexan-2-one? Protonation can take place either on the ketone or the alcohol. So where will it attack? In short, on which of the two oxygen atoms is electron density higher?


  • $\begingroup$ Well,what do you think? $\endgroup$ – Yusuf Hasan Dec 26 '18 at 4:16
  • $\begingroup$ As a hint, consider which lone pair is more "free" i.e. less tightly bound to the oxygen nucleus $\endgroup$ – Yusuf Hasan Dec 26 '18 at 4:29
  • $\begingroup$ You mean on alcohol? $\endgroup$ – Franshu Dec 26 '18 at 8:15
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    $\begingroup$ Please note that the site of preferred protonation may not be the one that leads to reactivity. Since proton transfer between heteroatoms is very fast, you are operating under Curtin-Hammett kinetics, so the more reactive intermediate (regardless of its concentration) will be the one that reacts. $\endgroup$ – Zhe Dec 26 '18 at 19:57
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    $\begingroup$ Well put @Zhe! This is not an either/or situation. I hope Franshu isn't under the misapprehension that protonation occurs at only one of the two oxygens. In CH3OH/H+ this hydroxyketone will lead to the cyclic, pyran mixed ketal (and/or 2-methyl dihydropyran) whose mechanism of formation requires protonation of the ketone oxygen. $\endgroup$ – user55119 Dec 26 '18 at 21:13