Chemistry of Enolates and Enols – Acidity of Alpha-Hydrogens

In the presence of carbonyl functional group, the alpha-hydrogens of a molecule exhibit acidity i.e. in the presence of a base they can be abstracted very easily to yield a carbanion.

In the presence of a base alpha-hydrogens to carbonyl functional group can be abstracted very easily to yield a carbanion

In the presence of a base alpha-hydrogens to carbonyl functional group can be abstracted very easily to yield a carbanion

The acidity of the α-hydrogen of carbonyl compounds depends on the stability of the carbanion formed (which is the conjugate base in this case). If the carbanion is more stable, the alpha-hydrogen is more acidic. The carbanion can be stabilized either with resonance – i.e. the carbanion lone pair to the oxygen of the carbonyl to form the stabilized enolate, or by inductive effect – if electron withdrawing groups are directly attached to the alpha-carbon.

Stabilization with resonance - i.e. the carbanion lone pair to the oxygen of the carbonyl

Stabilization with resonance form showing an enolate - i.e. the carbanion lone pair to the oxygen of the carbonyl

Stabilization by inductive effect - if electron withdrawing groups are directly attached to the alpha-carbon.

Stabilization by inductive effect - if electron withdrawing groups are directly attached to the alpha-carbon.

Note - Acidities of the alpha-hydrogen is measured in pKa. Lower pKa value of the hydrogen, more acidic it is.

Comparison of Acidities of Alpha – Hydrogens

Note - The pKa values are given assuming the R’ and R” groups are alkyl (mostly methyl group) and are an approximate value.

1] α-Hydrogens of Ketones vs Aldehydes

The alpha-hydrogens of ketones (pKa = 20) are less acidic as compared to aldehydes (pKa = 17). This is because the alkyl group R” of ketones pushes electrons via inductive effect on to the alpha-carbon. This would increase the electron density at the alpha-carbon to slightly destabilize the formation of the conjugate base – carbanion.

alpha-hydrogens of ketones (pKa = 20) are less acidic as compared to aldehydes (pKa = 17) due to inductive effect

alpha-hydrogens of ketones (pKa = 20) are less acidic as compared to aldehydes (pKa = 17) due to inductive effect

2] α-Hydrogens of Ketones vs Esters

The alpha-hydrogen of ketones (pKa = 20) is more acidic as compared to the alpha-hydrogens of esters (pKa = 25). The reason for this is that the ester functional group has free lone pairs on the oxygen which can participate in resonance with carbonyl group. This resonance competes with the resonance of the stabilization of the enolate resonance. Also the oxygen acts as an electron donating group via resonance and therefore makes the formation of carbanion more difficult.

alpha-hydrogen of ketones (pKa = 20) is more acidic as compared to the alpha-hydrogens of esters (pKa = 25) due to resonance with the oxygen lone pair

alpha-hydrogen of ketones (pKa = 20) is more acidic as compared to the alpha-hydrogens of esters (pKa = 25) due to resonance with the oxygen lone pair

3] α-Hydrogens of β-Diketones, β-Ketoesters and β-Diesters

Beta-diketones have extremely acidic alpha-hydrogens (pKa = 9), mainly because the formed negative charge on the conjugate base can be distributed on both the ketone groups on either side. For this reason abstraction of this proton can be achieved using even weak bases such as sodium hydroxide.

Beta-diketones have extremely acidic alpha-hydrogens (pKa = 9), mainly because the formed negative charge on the conjugate base can be distributed on both the ketone groups on either side

Beta-diketones have extremely acidic alpha-hydrogens (pKa = 9), mainly because the formed negative charge on the conjugate base can be distributed on both the ketone groups on either side

Similarly, beta-ketoesters (pKa = 11) and beta-diesters (pKa = 13) also have lower pKa values compared to the simple ketones or esters due to the additional resonance stabilization by the alternate carbonyl group.

 beta-ketoesters (pKa = 11) and beta-diesters (pKa = 13) also have lower pKa values compared to the simple ketones or esters due to the additional resonance stabilization by the alternate carbonyl group.

beta-ketoesters (pKa = 11) also have lower pKa values compared to the simple ketones or esters due to the additional resonance stabilization by the alternate carbonyl group.

 beta-ketoesters (pKa = 11) and beta-diesters (pKa = 13) also have lower pKa values compared to the simple ketones or esters due to the additional resonance stabilization by the alternate carbonyl group.

beta-ketoesters (pKa = 11)also have lower pKa values compared to the simple ketones or esters due to the additional resonance stabilization by the alternate carbonyl group.

pKa List for α-Hydrogens

The following images displays the pKa for alpha-hydrogens of different functional groups.

Note - These image is taken from http://www.chem.ucalgary.ca/courses/350/Carey/Ch21/ch21-2.html and can also be found in reference 1.In case of carboxylic acids and amides, the alpha-hydrogen is not the most acidic one and therefore the most acidic hydrogen is shown.

pKa list for alpha-hydrogens of carboxylic acids, nitro compounds, amides, aldehydes, ketones, esters, nitriles, amides and alkanes. Note - the pKa value is for the hydrogen highlighted in red and it may not be the alpha-hydrogen.

pKa list for alpha-hydrogens of carboxylic acids, nitro compounds, amides, aldehydes, ketones, esters, nitriles, amides and alkanes. Note - the pKa value is for the hydrogen highlighted in red and it may not be the alpha-hydrogen.

pKa list for alpha-hydrogens of beta-diketone, beta-ketoester, beta-diesters. Note - the pKa value is for the hydrogen highlighted in red and it may not be the alpha-hydrogen.

pKa list for alpha-hydrogens of beta-diketone, beta-ketoester, beta-diesters. Note - the pKa value is for the hydrogen highlighted in red and it may not be the alpha-hydrogen.

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References

  1. Advanced Organic Chemistry: Reactions and synthesis. By Francis A. Carey, Richard J. Sundberg
  2. Organic-Chemistry.org (accessed on February 13, 2011)
  3. http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/crbacid3.htm (accessed on February 13, 2011)
  4. http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/aldket2.htm(accessed on February 13, 2011)

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