Pinacol Rearrangement | Chemistry Optional Notes for UPSC PDF Download

Introduction

• The pinacol rearrangement is an acid-catalyzed rearrangement of 1,2-diols (vicinal diols)
• The acid serves to protonate one of the hydroxyl groups, which departs as water, giving a carbocation.
• Subsequently,  a C-O pi bond is formed as a C-C bond migrates to the adjacent carbon.
• It resembles the familiar hydride shifts and alkyl shifts in that a less stable carbocation is converted to a more stable carbocation (albeit with the twist is that this “more stable carbocation” is actually the resonance form of a protonated ketone).
• Pinacol rearrangements can result in ring expansions

The Pinacol Rearrangement

• Pinacol is a pleasant-smelling 1,2-diol (“vicinal” diol) with the following structure:
  
• When pinacol is treated with strong acid such as sulfuric acid (H₂SO₄),  a new ketone is formed and a molecule of water is lost from the diol.  Upon inspection, it can be seen that the carbon skeleton has undergone rearrangement:
  
• The most important thing to note here is that one of the highlighted CH₃ groups on C₂ has moved to C3.
• This reaction has become known as the pinacol rearrangement, and it is a fairly common rearrangement of 1,2-diols, having first been observed as far back as 1860. [See Ref 1]
• It is a special case of our old friends the 1,2-hydride shift and the 1,2-alkyl shift (See article: Rearrangement Reactions – Hydride Shifts)
• The reaction can be performed with a wide variety of other vicinal diols. Here is another example:
  
• In this case, a phenyl group migrates to the adjacent carbon to give a new ketone adjacent to a quaternary carbon.

Mechanism Of The Pinacol Rearrangement

• So how does this reaction work?
• If we think back to 1,2-hydride shifts and 1,2-alkyl shifts, we’ll recall that they involve formation of a carbocation followed by migration of H(-) or R(-) to generate a new carbocation. (See article: Rearrangement Reactions With Alkyl Shifts)
• So how might we generate a carbocation here from the vicinal diol and the acid?
• By protonating one of the alcohols, we generate its conjugate acid R-OH₂(+)
• Since H₂O is a much weaker base than HO(-), this molecule has a much better  leaving group. Breakage of the C-O bond then generates a carbocation.
  
• Now, the key rearrangement step can occur, whereby a methyl group (CH₃) can migrate from C-2 to C-3. The C₂-CH₃ bond breaks and the C₃-CH₃ bond forms, giving a new carbocation.
• Recall that rearrangements are generally favored when they result in a more stable carbocation. Is this true in this case?
• Actually, yes!
• If you look at the new carbocation that is formed, it can have its octet filled through donation of a lone pair by the adjacent oxygen, forming a new pi-bond in the process. (Note: this is often called, “pi-donation” and it’s extremely important).
• That is, this “carbocation” is actually just a resonance form of a protonated ketone!
• The final step is deprotonation of the protonated ketone with a weak base to give the neutral ketone.
• That’s it.
• Although I’ve shown the reaction as proceeding stepwise, it’s also perfectly acceptable to show it as occurring in a concerted fashion. Note 1.

Pinacol Rearrangements With Ring Expansion

• The pinacol rearrangement can also occur with ring expansion.
• That is, pinacol rearrangements of cyclic molecules can result in the formation of larger rings.
• This is fundamentally no different from the mechanism of a typical pinacol rearrangement.

Notes

• Note 1: Here is an example of showing the key rearrangement step as a concerted reaction. For more discussion on the plausibility of concerted versus stepwise pinacol rearrangements, see Ref 9.
  
• Note 2: Pinacol itself is often encountered in the Suzuki reaction, since boronic esters with pinacol are highly stable and can be purified by column chromatography.

Summary

• The pinacol rearrangement is a special case of carbocation rearrangement where migration of a carbon is accompanied by formation of a new C-O (pi) bond. The product is a ketone.
• The pinacol rearrangement is promoted by the addition of acid which assists in loss of water as a leaving group.
• Make sure you can draw the mechanism of pinacol rearrangements that result in ring expansion!