SolutionsAlkylation of ketones and carboxylic acid derivatives
Exercise 1
Propose how to prepare 2-benzylcyclohexanone, and ethyl 2-methylpropanoate bearing an allyl group on C2, from simple carbonyl compounds.
2-Benzylcyclohexanone: cyclohexanone + LDA (THF, −78 °C), then benzyl bromide. Ester: ethyl 2-methylpropanoate (isobutyrate) + LDA (THF, −78 °C), then allyl bromide; ethyl 2,2-dimethylpent-4-enoate is obtained. Both electrophiles are primary and very reactive in SN2.
Exercise 2
Why does the attempt to prepare 2-tert-butylcyclohexanone by treating the lithium enolate of cyclohexanone with tert-butyl chloride fail? What is obtained?
Tertiary halides do not undergo SN2 reactions: the carbon is too hindered. The enolate, a strong base, brings about E2 elimination of HCl, giving 2-methylpropene (isobutene) and, after workup, the starting cyclohexanone.
Exercise 3
In the manganese-catalysed alkylation of acetophenone with ethanol, which intermediates are formed? What is the by-product?
The catalyst dehydrogenates ethanol to acetaldehyde (becoming a metal hydride); acetaldehyde condenses with acetophenone under basic conditions (aldol with dehydration) to give the enone PhCOCH=CHCH3; the metal hydride reduces the C=C double bond, giving butyrophenone, PhCOCH2CH2CH3. The only by-product is water.