# Comparing rates of hydrolysis in cyclohexane ring (involving neighbouring group participation)

I need to compare the rates of hydrolysis of these three compounds.

MY ATTEMPT:

• By definition hydrolysis is either $\ce{S_N1}$ or elimination.But water being a weak base (and weak nucleophile) $\ce{S_N1}$ is preferable.

• $\ce{PhS^-}$ is a better leaving group than $\ce{Cl-}$ due to mesomeric effects.

• Comparing with the middle compound the leftmost and rightmost compound will certainly have higher rate of hydrolysis due to presence of good leaving group $\ce{PhS^-}$

• But how to compare between the leftmost and rightmost compound's rates?

• You asked this before. chemistry.stackexchange.com/questions/58888/… – orthocresol Sep 22 '16 at 2:59
• In fact, no, this is slightly more complicated. I would expect there to be some degree of neighbouring group participation by the SPh (forming a sulfonium ion, followed by water attacking) This can only happen in the trans configuration, however it requires ring flip into the higher-energy trans-diaxial conformation. Complicated. – orthocresol Sep 22 '16 at 3:01
• @orthocresol We don't need to worry about the ring flip I guess as it will take place automatically. – user14857 Sep 22 '16 at 4:55
• Ring flip definitely happens. The only issue is that the trans-diaxial conformation will be less populated, which will affect the rate negatively. I can't determine just from this alone which isomer is going to react faster. In the absence of NGP the cis isomer is faster, but NGP speeds up the trans isomer reaction. Is it enough to make it faster than the cis? I would guess yes, but I don't know. – orthocresol Sep 22 '16 at 5:20
• @orthocresol I know it might be less populated.However internal attack mechanism rate supersedes all the external attack mechanisms.So $rate_3$ must be highest by any logic... – user14857 Sep 22 '16 at 5:23

The third reaction infact occurs via neighbouring group participation.

• In the third compound $\ce{S}$ atom attacks carbon containing $\ce{Cl}$ by $\ce{SN_{NGP}}$ forming sulphonium ion. An attack by $\ce{H2O}$ on the least hindered carbon of the three member ring occurs. In this case both the carbopns in three member ring will be similar though. So the third compound has highest rate of reaction.

(I'd like to add "This can only happen in the trans configuration, however it requires ring flip into the higher-energy trans-diaxial conformation." as pointed out by - @orthocresol in the comments to the orginal question.)

Adding as a proof that trans reacts faster than cis form during NGP in cyclohexane ring. http://meskvmcollege.org/upload/study_material/30275.pdf (See page 10 of the pdf)

• The first compound has second highest rate. Anchimeric assistance cannot occur in cis form. Negative inductive effect by $\ce{Cl}$ enhances the rate. Reaction mechanism is $\ce{S_N1}$ and water itself acts as nucleophile.

• The central compound has the lowest rate among the three. $\ce{S_N1}$ mechanism occurs and $\ce{Cl}$ is replaced by $\ce{OH}$ where water itself acts as nucleophile.

So summing up: $$\ce{rate_3>rate_1>rate_2}$$