the pinacol-pinacolone rearrangement

The Pinacol Rearrangement

THE PINACOL-PINACOLONE REARRANGEMENT

REFERENCES:1] J.Clayden, N.Greeves, s.Warren, P.Wothers, ‘Organic Chemistry’, Oxford University Press, pg.no; 984-9882] Jerry March, ‘Advanced Organic Chemistry’, Fourth Edition, Wiley Interscience Publication, pg.no; 3] Sachin.K.Ghosh, ‘Advanced General Organic Chemistry’, Second Edition, New Central Book Agency pvt. ltd., pg.no:603-6094] R.O.C.Norman, J.M.Coxon, ‘Principles of Organic Synthesis’, Third Edition, Chapman & Hall Publications, pg.no; 433-4395] R.K.Bansal, ‘A Text Book of Organic Chemistry’, Fifth Edition, New Age International Publishers, pg.no: 437

The Pinacol Rearrangement:

R= Alkyl / Aryl / Hydrogen

Vicinal diols / Glycols / 1, 2-Diols when treated with acids rearrange to give aldehydes ok Ketones. This rearrangement is called as pinacol rearrangement; the reaction gets its name from the typical compound pinacol which is rearranged to pinacolone.

PINACOL PINACOLONE

Parag Mehta, S.Y.BPharm

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Mechanism: It is an intramolecular reaction. The reaction involves a 1, 2- shift.

There is migration even though the positive charge is already on the tertiary carbon i.e. the carbocation formed is a tertiary carbocation. Here we have another source of electrons to stabilize the carbocation i.e. the lone pairs of electrons on oxygen. Oxygen is very good at a stabilizing a positive charge on the adjacent carbon. By rearranging, the first formed carbocation gets a positive charge into a position where the oxygen can stabilize it.Carbocations stabilized by an oxygen atom are even more stable than tertiary alkyl cations. The new carbocation can immediately stabilize itself by losing a proton.The driving force for the reaction is the formation of a stable OXONIUM ion, the conjugate acid of the ketone. The overall reaction is the dehydration of the glycol.The rearrangement can be viewed as push and pull mechanism: the carbocation left after departure of water ‘pulls’ the migrating group across at the same time as the oxygen’s lone pair pushes it.Ring contraction and ring expansion can also take placeRing Contraction:

Ring Expansion:


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When drawing the mechanism for symmetrical compounds it doesn’t matter which hydroxyl group is protonated or which C-C bond migrates.However when two different groups are present on carbons bearing the hydroxyl group, two questions arise:

(1) Which of the two OH’s will be protonated?(2) Which of the groups will migrate?

The answer to the first question lies in the stability order of the carbocation formed. Usually that OH receives the proton which produces the more stable carbocation by the elimination of water molecule. Thus in

the OH group on the carbon holding the phenyl groups will receive the proton since the stability of diphenyl carbocation is greater than that of dimethyl carbocation.The stability of carbocation depends on the delocalization of the positive charge on the carbon either through resonance or through hyper conjugation. For this order the decreasing stability order of carbocation is

There is no clear cut answer in so far as migratory preference is concernedThe general order of migration isTERTIARY ALKYL >CYCLOHEXYL >SEC-ALKYL >BENZYL >PHENYL > PRIMARY ALKYL > METHYL > HYDROGENIn terms of electron-donating ability the usual migratory preference is

An aryl group migrates more readily than an alkyl group because the former forms a more stable bridged intermediate (the aryl cation) than the latter.The migratory aptitude of an o-aryl group is less than that of a m-aryl or a p-aryl group because of stearic hindrance.However there are reactions in which mere electron-donating ability does not decide which one will migrate.


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It has been found that a group in anti or trans position with respect to the leaving group, H2O, in the more stable conformation of the protonated substance migrates preferentially. The factor takes precedence over the migratory aptitude factor. The requirement that the migrating group be anti to the leaving group has important consequences in alicyclic systems.

For e.g.: cis-1, 2- dimethylcyclohexane-1, 2-diol undergoes a methyl shift to give 2, 2-dimethlcyclohexanone whereas the trans-isomer undergoes ring contraction to give cyclopentanone derivative:

Which group preferentially migrates may depend on the reaction conditions as well as nature of the substrate. Thus the action of cold, concentrated sulphuric acid on 1, 1- dimethyl-2, 2- diphenyl glycol (1)Produces mainly the ketone (2) {due to methyl migration}, While treatment of (1) with acetic acid containing a trace of sulphuric acid gives mostly (3) {due to phenyl migration}.


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If at least one R is hydrogen, aldehydes can be produced as well as ketones. Generally aldehydes formation is favored by the use of mild conditions i.e. lower temperatures, weaker acids.

The intramolecular nature of the reaction is supported by the cross-over experiment in which a mixture of and

has been treated with acid. In this reaction only intramolecular product:

are obtained. The cross products:are not obtained. Thus cross migration does not take place in this reaction i.e. the reaction is essentially an intramolecular one.Rearrangement reactions of 1, 2- halohydrines and 1, 2- amino alcohols to pinacolones are analogous reactions and are called as pinacolic rearrangements; these are carried out by treating the former compounds with Ag+ and the latter with HNO2.(NaNO2+ HCl).

Since highly branched oxo compounds are very difficult to prepare by other reactions, this rearrangement has interesting applications in synthesis.E.g.: Methyl isopropyl ketone is easily prepared from 2, 3- dichloro-2-methylbutane by this rearrangement.

A valuable application is the synthesis of spirocyclic sing systems or spiranes and there derivatives. Spirocycles are pairs of rings joined at a single carbon atom.

1, 2- diols containing substituents with strong negative inductive effect do not undergo the pinacol rearrangement.


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Epoxides when treated with acidic reagent such as BF3- etherate or MgBr2- etherate or sometimes heat alone follow the same rearrangement.

R=Alkyl, Aryl or Hydrogen

EXAMPLES


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the pinacol-pinacolone rearrangement

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