FG2

This set of flashcards covers the key terms related to nucleophiles, electrophiles, and the mechanisms of SN1 and SN2 reactions along with factors affecting these reactions.

Nucleophile

• A species that donates electrons,

• possessing a lone pair,

• a negative charge,

• or a high-energy HOMO.

Electrophile

• A species that accepts electrons,

• possessing empty atomic orbitals,

• low-energy antibonding orbitals,

• or polar bonds to electronegative atoms.

Nucleophillic sites

• Lone pairs on heteroatoms (O, N, S)

• Anionic centres

• π-bonds (alkenes, aromatic rings)

• Hydride donors (BH₄⁻)

Electrophillic sites

• Carbonyl carbon (C=O π* LUMO)

• Alkyl halides (C–X σ* LUMO)

• Carbocations (empty p orbital)

• Activated alkenes (e.g., conjugated systems)

SN2 mechanism

• One-step, concerted mechanism.

• Nucleophile attacks as the leaving group departs.

• Backside attack → walden inversion of stereochemistry.

SN1 mechanism

• Two-step mechanism:

  • Leaving group departs → carbocation (rate-determining step)

  • Nucleophile attacks carbocation

Racemic mixture formed at chiral centres.

Factors affecting SN1

• Tertiary carbons

• Stable carbocations (allylic, benzylic, heteroatom-stabilised)

• Polar protic solvents

• Good leaving groups

Factors affecting SN2

• Strong nucleophiles

• Primary or methyl electrophiles

• Good leaving groups

• Aprotic solvents

Preferable routes of SN2

methyl > primary > secondary > tertiary

Explain steric accessibility trend

• less steric hindrance allows for better nucleophile attack

• Nucleophile approaches at 180 to leaving group

• Bulky groups blocks the carbon from being attacked

Preferable route for sn1 reaction

tertiary>secondary >primary>methyl

Why do SN1 reactions occur by this

favour carbocation stability

How are carbocations stabilised

• Hyperconjugation- extra stabilization from C–H σ donation into empty p orbital of planar carbocation

• resonance

• adjacent lone pairs

Good leaving groups

 I⁻ > Br⁻ > Cl⁻ >> F⁻.

Why is I^- the best leaving group

• its large size,

• which stabilizes the negative charge,

• low electronegativity,

• allowing it to easily break away from the substrate. HI has the weakest bond

Why is F^- the worst leaving group

• small size

• high electronegativity,

• holds its electrons more tightly and makes it less stable as a negative ion.

Strong nucleophiles

RS⁻, RO⁻, and R₃N, important for SN2

Polar protic solvents

Solvents that stabilize carbocations and are favorable for SN1 reactions.

Polar aprotic solvents

Solvents that enhance nucleophile strength, favored for SN2 reactions.

CYP450 oxidation

A metabolic process that generates electrophilic intermediates leading to enzyme alkylation, akin to SN1/SN2 processes.

What is a protic solvent

A protic solvent is a solvent that can donate or accept protons (H+)

What is an Aprotic solvent

Can accept H-bonds but cannot donate protons.