Name: pinacol coupling and solvent effects
Uploaded: 2023-04-30T11:22:57.000Z
Duration: 1 min 27 s
Channel: JoVE

Pinacol coupling is a radical dimerization reaction, and involves the reductive coupling of aldehydes or ketones in a hydrocarbon solvent to give vicinal diols.
A single electron transfer from a metal to a spin-paired molecule like ketone initiates the reaction and forms a ketyl &#8212;a radical anion. The ketyl can be represented with the radical on carbon or oxygen and the charge on the other.
Here, metals like sodium and magnesium act as a source of electrons.
The fate of the ketyl depends on the solvent used for the reaction.
In protic solvents, like ethanol, the ketyl gets protonated, followed by a second electron transfer to give an alkoxide anion, which upon acidification, forms alcohol.
However, in aprotic solvents, like benzene, the absence of protons allows the accumulation of ketyl, leading to its dimerization into a diol. This forms the basis of pinacol coupling.
Notably, the electrostatic repulsion between the negative charges does not impede the dimerization because metals like magnesium coordinate to ketyls by forming covalent metal&#8211;oxygen bonds, enabling them to react rapidly.

vicinale diolen via reductieve koppeling van aldehyden of ketonen: overzicht van pinacolkoppeling

Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview

Wilhelm Rudolph Fittig ontdekte de pinacolkoppelingsreactie in 1859. Het is een radicaaldimerisatiereactie en bestaat uit de reductieve koppeling van aldehyden of ketonen in aanwezigheid van koolwaterstofoplosmiddel om vicinale diolen op te leveren.


 <img alt="Figure1" src="/files/ftp_upload/12905/12905_PT_Figure_1.svg" style="text-align: center; height: 160px;" />


 De radicaalreactie wordt geïnitieerd door een enkele elektronenoverdracht van metalen zoals natrium en magnesium naar een spin-paarmolecuul zoals aldehyden of ketonen om een ketyl te genereren – een radicaalanion. De ketyl heeft een radicaalkarakter op het koolstofatoom en een lading op het zuurstofatoom. De resonantievorm ervan heeft een radicaal gepositioneerd op het zuurstofatoom en een lading op het koolstofatoom.


 Het gedrag van ketyl wordt sterk beïnvloed door het oplosmiddel waarin de reactie wordt uitgevoerd.


 Protische oplosmiddelen, zoals ethanol, protoneren de ketyl. Dit wordt gevolgd door een tweede elektronenoverdracht van metaal om een alkoxide-anion te geven. Verder vormt de verzuring van een alkoxide-anion alcohol. Hier lost het metaal op tijdens de reactie en fungeert het als een bron van vrije elektronen.


 In aanwezigheid van aprotische oplosmiddelen, zoals benzeen of ether, ondergaan ketylradicaalanionen geen protonering vanwege de afwezigheid van protonen. Dit bevordert de dimerisatie van ketyl en maakt deel uit van de beroemde pinacolkoppelingsreactie.


 Interessant is dat metalen zoals magnesium, aluminium of natrium de reactie bevorderen door covalente metaal-zuurstof bindingen te vormen, die coördineren met verschillende ketylradicalen en snel reageren om een diol te vormen. Opmerkelijk is dat de elektrostatische afstoting tussen de negatieve ladingen van de ketylen de dimerisatie niet belemmert. Kortom, protische oplosmiddelen bevorderen de vorming van alcohol, terwijl aprotische oplosmiddelen de voorkeur geven aan vicinale diolen.

Vicinale diolen via reductieve koppeling van aldehyden of ketonen: overzicht van pinacolkoppeling

Wilhelm Rudolph Fittig discovered the pinacol coupling reaction in 1859. It is a radical dimerization reaction and involves the reductive coupling of ...

vicinal-diols-via-reductive-coupling-aldehydes-or-ketones-pinacol

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Organic Chemistry

Organische chemie

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Onderdeel 1

Radical Chemistry

Radicale chemie

KEY TERMS AND CONCEPTS

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pinacol coupling and solvent effects

Pinacol coupling is a radical dimerization reaction that joins aldehydes or ketones to form vicinal diols. Wilhelm Rudolph Fittig first discovered this reaction in 1859. It is a reductive coupling, which means the molecules are joined after they gain electrons.

The reaction begins with a single electron transfer from metals such as sodium or magnesium to an aldehyde or ketone. This forms a ketyl, a radical anion. In a ketyl, the carbon atom can carry radical character while the oxygen atom carries a negative charge. A resonance form also places the radical on oxygen and the charge on carbon.

The solvent has a major effect on the outcome. In protic solvents, such as ethanol, the ketyl is protonated first. A second electron transfer from the metal then gives an alkoxide anion. After acidification, this alkoxide forms an alcohol. In this way, the metal acts as a source of free electrons as it dissolves during the reaction.

In aprotic solvents, such as benzene or ether, protonation does not occur because there are no protons available. This favors ketyl dimerization and leads to pinacol coupling. Metals such as magnesium, aluminum, or sodium can help by forming covalent metal-oxygen bonds that coordinate several ketyl radicals. Even though the ketyls carry negative charge, electrostatic repulsion does not stop them from dimerizing. As a result, aprotic solvents favor vicinal diols, while protic solvents favor alcohol formation.

Pinacol Coupling and Solvent Effects

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Selective MnO2 Oxidation of Alcohols

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radical substitution: allylic chlorination

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Allylic Chlorination by Radical Chain Reaction

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radical substitution: allylic bromination

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Alkyl Halide Reduction with Tributyltin Hydride

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Peroxide Effect in HBr Addition to Alkenes

Hydrogen bromide can add to alkenes through a peroxide-driven radical pathway. In this reaction, hydroperoxides or peroxides change the usual addition pattern and lead to alkyl bromides with anti-Markovnikov regiochemistry, which means bromine ends up on the less substituted carbon. This regioselectivity can be explained by radical stability. When the bromine radical adds to the alkene at the less substituted carbon, the reaction forms a more stable tertiary radical intermediate. The same...

radical anti-markovnikov addition to alkenes: mechanism

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Hydrogen Bromide Addition to Alkenes by Radicals

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radical anti-markovnikov addition to alkenes: thermodynamics

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HBr Selectivity in Alkene Addition Thermodynamics

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vicinal diols via reductive coupling of aldehydes or ketones: pinacol coupling overview

Pinacol coupling is a radical dimerization reaction that joins aldehydes or ketones to form vicinal diols. Wilhelm Rudolph Fittig first discovered this reaction in 1859. It is a reductive coupling, which means the molecules are joined after they gain electrons. The reaction begins with a single electron transfer from metals such as sodium or magnesium to an aldehyde or ketone. This forms a ketyl, a radical anion. In a ketyl, the carbon atom can carry radical character while the oxygen atom...

alkenes via reductive coupling of aldehydes or ketones: mcmurry reaction

alkenes-via-reductive-coupling-aldehydes-or-ketones-mcmurry

Titanium-Coupled Alkenes from Carbonyls

The McMurry reaction turns aldehydes or ketones into alkenes with titanium metal. It first forms a diol-like intermediate through a coupling step, and then removes oxygen to make the double bond. In some cases, this process can be compared to pinacol coupling, which also joins carbonyl compounds. Titanium acts as a source of electrons in the first step. It transfers a single electron to the carbonyl group and forms a ketyl intermediate. That intermediate can lead to a vicinal diol, which is a...

&alpha;-hydroxy ketones via reductive coupling of esters: acyloin condensation overview

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Acyloin Condensation: Ester Coupling Pathway

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key terms and concepts

Learn how pinacol coupling joins aldehydes and ketones into vicinal diols, and how protic versus aprotic solvents change the product.

Pinacol Coupling and Solvent Effects | JoVE K12

organic chemistry

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Pinacol Coupling and Solvent Effects

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