Carbonyl group

For carbonyl as a ligand, see Metal carbonyl.
A compound containing a carbonyl group (C=O)

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a carbonyl group is often referred to as a carbonyl compound.

The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex (a metal carbonyl, e.g. nickel carbonyl).

The remainder of this article concerns itself with the organic chemistry definition of carbonyl, where carbon and oxygen share a double bond.

Carbonyl compounds

A carbonyl group characterizes the following types of compounds:

CompoundAldehydeKetoneCarboxylic acidCarboxylate EsterAmide
Structure
General formulaRCHORCOR'RCOOHRCOOR'RCONR'R''
CompoundEnoneAcyl halideAcid anhydrideImide
Structure
General formulaRC(O)C(R')CR''R'''RCOX(RCO)2ORC(O)N(R')C(O)R''

Note that the most specific labels are usually employed. For example, R(CO)O(CO)R' structures are known as acid anhydride rather than the more generic ester, even though the ester motif is present.

Carbon dioxide

Other organic carbonyls are urea and the carbamates, the derivatives of acyl chlorides chloroformates and phosgene, carbonate esters, thioesters, lactones, lactams, hydroxamates, and isocyanates. Examples of inorganic carbonyl compounds are carbon dioxide and carbonyl sulfide.

A special group of carbonyl compounds are 1,3-dicarbonyl compounds that have acidic protons in the central methylene unit. Examples are Meldrum's acid, diethyl malonate and acetylacetone.

Reactivity

Carbonyl resonance chemistry

Because oxygen is more electronegative than carbon, carbonyl compounds often have resonance structures which affect their reactivity. This relative electronegativity draws electron density away from carbon, increasing the bond's polarity, therefore making carbon an electrophile (i.e. slightly positive). Carbon can then be attacked by nucleophiles (e.g. negatively charged ions, like the cyanide ion) or a negatively charged part of another molecule (e.g. the lone pair electrons of nitrogen in the ammonia molecule). During the reaction, the carbon-oxygen double bond is broken, and the carbonyl group may experience addition reactions. This reaction is known as addition-elimination (because a water molecule is often lost) or condensation.[1] The electronegative oxygen also can react with an electrophile; for example a proton in an acidic solution or with Lewis acids to form an oxocarbenium ion.

A carbonyl compound

The polarity of oxygen also makes the alpha hydrogens of carbonyl compounds much more acidic (roughly 1030 times more acidic) than typical sp3 C-H bonds, such as those in methane. For example, the pKa values of acetaldehyde and acetone are 16.7 and 19 respectively,[2] while the pKa value of methane is extrapolated to be approximately 50.[3] This is because a carbonyl is in tautomeric resonance with an enol. The deprotonation of the enol with a strong base produces an enolate, which is a powerful nucleophile and can alkylate electrophiles such as other carbonyls.

Amides are the most stable of the carbonyl couplings due to their high resonance stabilization between the nitrogen-carbon and carbon-oxygen bonds.

Carbonyl reduction

Main article: Carbonyl reduction

Carbonyl groups can be reduced by reaction with hydride reagents such as NaBH4 and LiAlH4, with baker's yeast, or by catalytic hydrogenation. Ketones give secondary alcohols while aldehydes, esters and carboxylic acids give primary alcohols.

Carbonyl alkylation

Carbonyls can be alkylated in nucleophilic addition reactions using organometallic compounds such as organolithium reagents, Grignard reagents, or acetylides. Carbonyls also may be alkylated by enolates as in aldol reactions. Carbonyls are also the prototypical groups with vinylogous reactivity (e.g. the Michael reaction where an unsaturated carbon in conjugation with the carbonyl is alkylated instead of the carbonyl itself).

Carbonyl chemoselectivity

In case of multiple carbonyl types in one molecule, one can expect the most electrophilic carbonyl carbon to react first. Acyl chlorides and carboxylic anhydrides react fastest, followed by aldehydes and ketones. Esters react much more slowly and amides are almost completely unreactive due to resonance of the amide nitrogen towards the carbonyl group. This reactivity difference allows chemoselectivity when a reactant contains multiple carbonyl groups. An instructive example is found in the last part of the total synthesis of monensin by Kishi in 1979:[4]

The left-hand reactant possesses two potential electrophilic sites: an aldehyde (indicated in blue) and an ester (indicated in green). Only the aldehyde, which is more electrophilic, will react with the enolate of the methyl ketone in the other part of the molecule. The methyl ester remains untouched. Of course, other effects can play a role in this selectivity process, including electronic effects, steric effects, and thermodynamic versus kinetic reaction control.

Carbonyl specialty reactions

Other important reactions include:

α,β-Unsaturated carbonyl compounds

Acrolein, an α,β-unsaturated carbonyl compound.

α,β-Unsaturated carbonyl compounds are an important class of carbonyl compounds with the general structure (O=CR)−Cα=Cβ-R; for example enones and enals. In these compounds the carbonyl group is conjugated with an alkene (hence the adjective unsaturated), from which they derive special properties. Unlike the case for simple carbonyls, α,β-unsaturated carbonyl compounds are often attacked by nucleophiles at the β carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.

The carbonyl group draws electrons away from the alkene, and the alkene group is, therefore, deactivated towards an electrophile, such as bromine or hydrochloric acid. As a general rule with asymmetric electrophiles, hydrogen attaches itself at the α-position in an electrophilic addition. On the other hand, these compounds are activated towards nucleophiles in nucleophilic conjugate addition.

Since α,β-unsaturated compounds are electrophiles, many α,β-unsaturated carbonyl compounds are toxic, mutagenic and carcinogenic. DNA can attack the β carbon and thus be alkylated. However, the endogenous scavenger compound glutathione naturally protects from toxic electrophiles in the body. Some drugs (amifostine, N-acetylcysteine) containing thiol group may protect biomolecules from such harmful alkylation

Spectroscopy

See also

References

  1. ↑ http://www.chemguide.co.uk/organicprops/carbonyls/background.html
  2. ↑ Ouellette, R.J. and Rawn, J.D. "Organic Chemistry" 1st Ed. Prentice-Hall, Inc., 1996: New Jersey. ISBN 0-02-390171-3
  3. ↑ Claden, Johnathan; et al. Organic Chemistry. Oxford University Press. ISBN 978-0-19-850346-0.
  4. ↑ Nicolaou, Kyriacos Costa; E. J. Sorensen (1996). Classics in Total Synthesis: Targets, Strategies, Methods. Wiley-VCH. pp. 230–232. ISBN 3-527-29231-4.
  5. ↑ Mayo D.W., Miller F.A and Hannah R.W “Course Notes On The Interpretation of Infrared and Raman Spectra” 1st Ed. John Wiley & Sons Inc, 2004: New Jersey. ISBN 0-471-24823-1.
  6. ↑ "Archived copy" (PDF). Archived from the original (PDF) on 2015-08-24. Retrieved 2015-07-11.

Further reading

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