Reactivity of Enols:a-Substitution Reactions Common a-substitution reaction in the laboratory is halogenation of aldehydes and ketones at their a positions by reaction with Cl2,Br2,or 12 in acidic solution Br2 Acetic acid Acetophenone q-Bromoacetophenone(72%)
Common a-substitution reaction in the laboratory is halogenation of aldehydes and ketones at their a positions by reaction with Cl2 , Br2 , or I2 in acidic solution Reactivity of Enols: α-Substitution Reactions
Reactivity of Enols:a-Substitution Reactions Acid-catalyzed a-halogenation (Cl2,Br2,and 12)of aldehydes and ketones is a common laboratory reaction a-Halogenation occurs in biological systems a-Halogenation of ketones in marine alga Br、 CH3 CH3 Br Br H Br Br From the Hawaiian alga Asparagopsis taxiformis
Acid-catalyzed a-halogenation (Cl2 , Br2 , and I2 ) of aldehydes and ketones is a common laboratory reaction a-Halogenation occurs in biological systems ▪ a-Halogenation of ketones in marine alga Reactivity of Enols: α-Substitution Reactions
Reactivity of Enols:a-Substitution Reactions Mechanism of H-B acid-catalyzed H3C CH3 bromination of The carbonyl oxygen atom is protonated by acid catalyst. o acetone HaC-CCH Br Loss of an acidic proton from the alpha carbon takes place in the normal way to yield an enol o intermediate. C0-4 一8r Enol HsC-CH An electron pair from the enol attacks bromine,giving an intermediate cation that is stabilized by resonance between two forms. Loss of the-OH proton then gives the alpha-halogenated product and generates more 0 acid catalyst. +HBr CH2Br
Mechanism of acid-catalyzed bromination of acetone Reactivity of Enols: α-Substitution Reactions
Reactivity of Enols:a-Substitution Reactions Isotopic labeling experiments support reaction mechanism of acid-catalyzed halogenation For a given ketone,the rate of deuterium exchange is identical to the rate of halogenation Enol intermediate involved in both processes D30+ Fast H30+(D30t) Slow, rate-limiting X2 Ketone/aldehyde Enol X=Cl,Br,or I
Isotopic labeling experiments support reaction mechanism of acid-catalyzed halogenation ▪ For a given ketone, the rate of deuterium exchange is identical to the rate of halogenation ▪ Enol intermediate involved in both processes Reactivity of Enols: α-Substitution Reactions
Reactivity of Enols:a-Substitution Reactions a-Bromoketones are dehydrobrominated by base to yield a,B unsaturated ketones E2 reaction mechanism 2-Methylcyclohexanone gives 2-methylcyclohex-2-enone on heating in pyridine CH3 CH3 CH3 Br2 Pyridine HBr CH3CO2H Heat 2-Methylcyclo- 2-Bromo-2-methyl- 2-Methylcyclo- hexanone cyclohexanone hex-2-enone (63%) Cng Learing Al Pights Rearvd
a-Bromoketones are dehydrobrominated by base to yield a,bunsaturated ketones ▪ E2 reaction mechanism ▪ 2-Methylcyclohexanone gives 2-methylcyclohex-2-enone on heating in pyridine Reactivity of Enols: α-Substitution Reactions