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Why do the tosylation and mesylation of an alcohol proceed via different mechanisms?

More specifically,

  1. In tosylation, the lone pair of the alcohol attacks the sulfur in TsCl, but why does it not do so with MsCl? Surely, TsCl should be more sterically hindered due to the benzene ring.

  2. Why is the sulfene intermediate even formed in mesylation? Can that position be deprotonated by $\ce{Et3N}$? It's clear that this mechanism cannot happen with TsCl which has no alpha protons, but I fail to see why it should happen with MsCl.

Tosylation with pyridine:

Mechanism of tosylation with pyridine

Mesylation with triethylamine:

Mechanism of mesylation with triethylamine

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  • $\begingroup$ I've never seen the methyl proton of MsCl be deprotonated like that by TEA. I'll look it up, but I'm skeptical. $\endgroup$ – SendersReagent Mar 11 '16 at 11:48
  • $\begingroup$ My bad. Sulfene is formed using TEA, apparently, but I'm not sure that happens in in this reaction. The reason that reaction wouldn't happen with TsCl is because there are no alpha protons there. The methyl group protons are more acidic than they are in toluene, but less so than those on MsCl. $\endgroup$ – SendersReagent Mar 11 '16 at 11:51
  • $\begingroup$ Nevermind, my whole world has flipped upside-down. Sulfene is indeed an intermediate. Never seen that before. $\endgroup$ – SendersReagent Mar 11 '16 at 11:58
  • $\begingroup$ If you check out the text book by March, it will verify sulfenes and give evidence that sulfonyl chlorides do not react like acyl chlorides, as you correctly depict. $\endgroup$ – Beerhunter Mar 11 '16 at 12:57
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    $\begingroup$ Note that the mechanism for substitution is still probably not concerted. The addition and fragmentation is likely two steps. $\endgroup$ – Zhe Mar 3 '17 at 16:09
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The only real difference between an alkanesulfonyl chlorides and arylsulfonyl chlorides is the $\alpha$-hydrogen. In a mechanistic study of the hydrolysis of methanesulfonyl chloride, the reaction was found to have a very small secondary kinetic isotope effect for $\mathrm{pH}<6.7$, indicating no bond breakage to the isotopically labelled hydrogen and thereby an $\mathrm{S_N2}$ reaction mechanism.

KIE study

For $\mathrm{pH}>6.7$ there is a large primary kinetic isotope effect, indicating bond breakage to the isotopically labelled hydrogen, corresponding to the formation of the sulfene intermediate.$^{[1]}$ This shows that though methanesulfonyl chloride isn't incapable of direct attack by alcohols, in the presence of basic amines, which serve the additional purpose of driving the reaction to completion by accepting the alcohol proton, it is more quickly deprotonated to form the sulfene.

While pyridine isn't that great of a base ($\mathrm{p}K_\mathrm{b}=5.21$) and won't form the sulfene to any great extent, triethylamine ($\mathrm{p}K_\mathrm{b}=11.01$) and trimethylamine ($\mathrm{p}K_\mathrm{b}=9.81$) are much stronger bases and will deprotonate methanesulfonyl chloride to give the sulfene to a greater extent. The mechanism is just as dependent on the base as it is the sulfonating agent, so all these considerations must be taken into account.


$^{[1]}$ King, J. F.; Lam, J. Y. L.; Skonieczny, S. Journal of the American Chemical Society 1992, 114 (5), 1743–1749.

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    $\begingroup$ I finally got around to reading this paper that has already been cited multiple times. Thank you for not saying that "the pKa of MsCl is 6.7" - that is inaccurate and quite illogical, too (a typical sulfone has pKa ~25-30). I guess the bottom line is that a similar mechanism with TsCl would operate if there was an $\alpha$-hydrogen, but since there isn't, it is restricted to the direct displacement mechanism. I'll bounty later today. $\endgroup$ – orthocresol Mar 10 '17 at 16:43
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The pKa of Mesyl Chloride can be looked at from the following work by J. F. King, J. Y. L. Lam, and S. Skonieczny in their paper - J. Am. Chem. Soc. 1992, 114, 1743 - 1749.

They have shown that in pH range 6.7-11.8, rate-determining attack by hydroxide anion forms sulfene which is quickly trapped by water. So the Pka of Mesyl Chloride can be said to be 6.7; this is less than the Pka of Et3N at 10.75. So Mesyl chloride will be forming the sulfene intermediate if treated with Et3N. And the SN2 attack by Oxygen happens in both cases, I don't know what you wanted to ask in your first question. Your mechanisms themselves show the attack in both cases by oxygen on the sulfur atom. I hope I am correct in my analogy. Apologies if I am wrong somewhere.

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1 & 2. An acid-base reaction can only occur on MsCl, since as you point out it is the only one with acidic alphaprotons. The protons are indeed quite acidic since the negative charge is stabilized by the two oxygens. (pKa ~6.7, thanks @Mrityunjay Gupta)

Et3N is quite basic (pKa ~11), and acid-base reactions will always occur first since they are much faster than other reactions. I'm quite sure the alcohol also attacks the sulfur on MsCl, but the a/b-reaction is just faster. The elimination of Cl- on MsCl follows an E1Cb-mechanism.

Source: Clayden Organic chem. 2nd ed pp. 403-404, J. Am. Chem. Soc., 1992, 114 (5), pp 1743–1749 (pKa of MsCl)

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  • $\begingroup$ This answer is actually pretty reasonable, but it should be expanded on slightly. $\endgroup$ – gannex Mar 6 '17 at 4:18

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