Α-Halo ketone

A haloketone in organic chemistry is a functional group consisting of a ketone group with a α-halogen substituent. The general structure is RR'C(X)C(=O)R where R is an alkyl or aryl residue and X any one of the halogens. The preferred conformation of a haloketone is that of a cisoid with the halogen and carbonyl sharing the same plane as the steric hindrance with the carbonyl alkyl group is generally larger ^[1].

Organic synthesis

• Haloketones and halo carbonyl compounds in general are synthesized by reaction of carbonyl compounds with halogenation agents:
  • halogens, bromine and chlorine give monosubstitution, fluorine gives polysubstitution
  • Tetrabutylammonium tribromide
  • N-Bromosuccinimide

• In the Hell-Volhard-Zelinsky halogenation a carboxylic acid reacts with bromine in presence of phosphorous tribromide.

Reactions of haloketones

Haloketones take part in several reaction types. In reaction with a nucleophile 2 electrophilic sites are available and in reactions with a base several acidic protons exist due to the presence of two electron withdrawing groups. The carbon halogen bond experiences increases polarity from the inductive effect of the carbonyl group making the carbon atom more electropositive.

• In nucleophilic aliphatic substitution reactions with potassium iodide in acetone, 1-chloro-2-propanone reacts faster than n-propylchloride by a factor of 36000.

• In the Favorskii rearrangement a base abstacts first an acidic α-proton and the resulting carbanion then displaces the halogen.

• The same sequence is observed in the Bingel reaction with fullerenes

• In crossed Aldol reactions between haloketones and aldehydes the initial reaction product is an halohydrin which can subsequently form a oxirane in the presence of base.

• Haloketones are important in heterocyclic chemistry. An example is the use of haloketones in the Hantzsch Pyrrole Synthesis and the Hantzsch thiazole synthesis.

References

• ^ The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis Ayman W. Erian, Sherif M. Sherif and Hatem M. Gaber Molecules 2003, 8, 793-865 Online Article