Alkenes as Electrophiles

Are alkenes good nucleophiles?

Yes

Alkenes undergo…

electrophilic addition reactions

Are aromatics good nucleophiles?

Not really due to stability

Can aromatics be electrophiles?

Yes

S_NAr

What are α, β - unsaturated carbonyls called?

Enone

Are α, β - unsaturated carbonyls toxic?

Yes. Since they are readily reactive to nucleophiles (e.g. R-OH, R-SH, R-NH₂), they will alkylate DNA, amino acids, proteins (which have these nucleophiles) and stop their function

Are enone electrophilic?

Yes

1. There’s electronegativity difference

2. The electrons in the double bond can move across and help delocalise that positive charge

The electrophilic positions are carbonyl C and the other place due to allylic cation. Nucleophiles can attack 1 or the other.

1,2-Addition in enone

The numbering is 1 to 4, with 1 being oxygen.

The nucleophile attacks the 2 C which then attacks the 1 O. Therefore it is called 1,2-addition.

Also known as direct addition

1,4-Addition in Enone

The numbering is 1 to 4, with 1 being oxygen.

The nucleophile attacks 4 C. The pi bond breaks because the pi bond is weaker. A bond is formed between the nucleophile and 4 C. A double bond is formed between 2 and 3 and then the carbonyl double bond is broken. An enolate is formed.

Also known as conjugate addition and Michael addition

What factors influence where the addition is 1,2 or 1,4 in enone?

Are ketones electrophilic?

Yes

Acrylamide

Toxic

Thiol group

Q) Show how acrylamide is toxic:

The product formed is a chemically modified enzyme. It’s no longer a thiol, but a thioether, it has another alkyl group attach. We have lost potential hydrogen bond interactions, lost the ability to make disulphide bridges, and the enzyme will no longer work.

Glutathione

Made up of glutamate, cysteine, glycine

GSH

Why is glutathione important in detoxifying α, β - unsaturated carbonyls?

Because α,β-unsaturated carbonyls are electrophilic Michael acceptors, they readily react with cellular nucleophiles like DNA and proteins. Glutathione (GSH) detoxifies them by donating its thiol group (–SH) to perform a Michael addition, forming a stable, non-toxic GSH-conjugate that can be safely excreted