SolutionsDisconnection
Exercise 1
Give the best disconnection of: a) benzyl acetate; b) benzyl methyl ether; c) N-methylbenzamide. State the reagents of the synthesis.
a) The O–C(O) bond of the ester: benzyl alcohol + acetyl chloride (or acetic anhydride) with pyridine. b) The O–CH2Ph bond: sodium methoxide + benzyl bromide (Williamson synthesis; the other disconnection, phenylmethoxide + methyl iodide, also works). c) The N–C(O) bond: benzoyl chloride + methylamine.
Exercise 2
4-Hydroxy-4-phenylbutan-2-one is a 1,3-dioxygenated compound. Disconnect it and propose the synthesis. What selectivity problem arises?
The C3–C4 bond (between the α carbon and the carbinol) is disconnected: acetone enolate + benzaldehyde, a crossed aldol. Benzaldehyde is not enolizable, but acetone can react with itself, and the aldol tends to dehydrate to benzylideneacetone. An excess of acetone, dilute base and low temperature are used, or better the preformed lithium enolate with LDA at −78 °C (directed aldol).