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Why are thioesters relatively reactive with regard to nucleophilic attack? Prof says to wait until pchem 3 when we learn about orbital symmetry. He also said that sulfur’s d-orbitals (?!) don't have the correct symmetry to participate in resonance with the carbonyl carbon.

Wait. I thought that sulfur didn’t utilize its d-orbitals. Was it previously taught that sulfur’s lone pairs were in d-orbitals? Why would sulfur even need d-orbitals when in a thioester? Can't we just explain this based on the poor overlap between carbon's 2p and sulfur's hypothetical 3p orbitals?

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  • $\begingroup$ Apply the concepts discussed here to thioesters $\endgroup$ – ron Mar 10 '15 at 14:36
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    $\begingroup$ @ron So would you chalk a thioester's reactivity to the 2p-3p bond between the C and S? $\endgroup$ – Dissenter Mar 10 '15 at 14:58
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    $\begingroup$ Yes, similar to an acid chloride. $\endgroup$ – ron Mar 10 '15 at 15:15
  • $\begingroup$ @Ron so d orbitals are irrelevant? $\endgroup$ – Dissenter Mar 10 '15 at 18:32
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    $\begingroup$ Some do, some don't ($\ce{d_{z^2}}$), it also depends on the relative orientation of the orbitals. For example an s orbital has the proper symmetry to interact with a p orbital if the interaction is along the long axis of the p-orbital and at the "end" of the p orbital. On the other hand, due to symmetry, interaction along the long axis but at the center of the p-orbital cannot result in constructive overlap. $\endgroup$ – ron Mar 10 '15 at 18:46
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According to these lecture notes from Gonzaga University:

The question arises over why thioesters occupy a prominent place in metabolism while oxygen esters play a relatively minor role. One answer is thermodynamic. The sulfur in the thioester linkage is less able to participate in electron delocalization through the acyl group (the usual explanation given for this is poor overlap between the 2p orbital of carbon and the 3p orbital of sulfur), and this makes the thioester bond less stable than the ester bond. Hence, the thioester bond has a more negative standard free energy of hydrolysis (−7.5 kcal/mole vs. about −5 kcal/mole for most oxygen esters). In many cases, it appears that thioesters are more reactive than oxygen esters, undergoing more facile nucleophilic displacement reactions at the acyl group. The reactivity of a thioester at the alpha carbon compares favorably with that of ketones.

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Because resonance structure 2c [see web page - CF] makes a more significant contribution for a thioester than an analogous structure for an ester, the acyl carbon is more positive, hence more susceptible to nucleophilic attack. An attacking nucleophile would be more readily acylated by a thioester than it would be by an ester. Furthermore, the C-S bond is weaker than the C-O bond, and the thiolate (or thiol, if protonated) is a better leaving group than alkoxide (or alcohol). These factors all make a thioester in general a better acylating agent than an ester.

So the answer doesn't seem to involve d orbitals explicitly, but instead the difference between 2p and 3p orbitals (as well as other factors).

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    $\begingroup$ Just to put it in some context, a thioester is about the same reactivity as a ketone. $\endgroup$ – jerepierre Mar 10 '15 at 14:30

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