Question

Coniine, C8H17N, is the toxic principle of the poison hemlock drunk by Socrates. It can be synthesized from acrylonitrile (H2C=CHCN) and ethyl 3-oxohexanoate.

The synthesis proceeds as follows: Deprotonation of ethyl 3-oxohexanoate to form enolate anion 1; Michael addition to acrylonitrile to form intermediate 2; Protonation to form Michael adduct 3; Ester hydrolysis and decarboxylation to form oxonitrile 4; Reduction to form oxoamine 5; Cyclization to form imine 6; Catalytic hydrogenation to form Coniine.

Draw the structures of imine 6 and Michael adduct 3.

Answer 1

The Michael reaction occurs between the ester and α, β-unsaturated carbonyl compound. It involves the conjugate addition of a resonance-stabilized enolate to the beta carbon of α, β-unsaturated carbonyl compound First the base removes the acidic proton between the two carbonyl groups of an ester and forms a resonance-stabilized enolate. Next by the nucleophilic enolate ion adds to the beta carbon of the acrylonitrile and forms a new C-C bond followed by the protonation gives the Michael adduct, which further undergoes hydrolysis and decarboxylation forms an oxonitrile. Next, the carbonyl group is protected followed by the reduction of cyano group to primarv amine. The protected group undergoes hvdrolvsis and forms oxoamine, which undergoes cyclization and forms an imine. Finally, the double undergoes catalytic hydrogenation and forms the desired product, coniine

OCH CH resonance-stabilized enolate anion Michael adduct intermediate он oxonitrile OH LiAlH NH H30 OH NH2 NH oxoamine mine H2/Pd NH

Therefore, the structures of imine and Michael adduct are as follows: imine Michael adduct