SolutionsRetrosynthesis
Exercise 1
Propose a retrosynthesis of 2-phenylbutan-2-ol leading to starting materials of two carbons or fewer plus benzene. How many reasonable C–C disconnections does the alcohol carbon have?
The tertiary carbinol has three C–C bonds, and all three can be disconnected by the addition of a Grignard reagent to a ketone: Ph/butan-2-one (PhMgBr + CH3COCH2CH3), methyl/propiophenone (CH3MgBr + PhCOEt) and ethyl/acetophenone (EtMgBr + PhCOCH3). With the stated restriction, the last is the most direct: acetophenone comes from benzene by Friedel–Crafts acylation with acetyl chloride, and ethylmagnesium bromide from bromoethane.
Exercise 2
Why is isobutylbenzene not disconnected into benzene and 1-chloro-2-methylpropane? What product would that Friedel–Crafts alkylation give?
The complex of the primary halide with AlCl3 rearranges by a 1,2-hydride shift to the much more stable tert-butyl cation, and tert-butylbenzene is obtained. In addition, the alkylated product is more reactive than benzene and tends to polyalkylate. Acylation followed by reduction avoids both problems.