SN1, SN2, E1, and E2 Reaction Mechanisms

• Understanding primary, secondary, and tertiary substrates is crucial for predicting SN2, SN1, E1, and E2 reaction mechanisms.

Substrates

• Primary substrates have one carbon atom directly bonded to another carbon atom.
• SN2 reactions are favored by primary substrates due to less steric hindrance.
• Primary substrates do not favor SN1 reactions because the carbocation intermediate is unstable.
• Secondary substrates have one carbon atom bonded to two other carbon atoms.
• Secondary substrates can undergo both SN2 and SN1 reactions, depending on conditions.
• SN2 reactions are still quite favorable for secondary substrates.
• SN1 reactions become more competitive for secondary substrates because the secondary carbocation intermediate is more stable.
• Tertiary substrates have one carbon atom bonded to three other carbon atoms.
• SN1 and E1 reactions are strongly favored by tertiary substrates because they stabilize the carbocation intermediate through hyperconjugation and inductive effects.
• SN2 reactions are hindered in tertiary substrates due to severe steric hindrance around the carbon center.

Reaction Mechanisms

• SN2 (Substitution Nucleophilic Bimolecular) involves a concerted, one-step process with simultaneous nucleophile attack and leaving group displacement.
• SN2 reactions are favored by primary substrates and require a strong nucleophile.
• SN1 (Substitution Nucleophilic Unimolecular) reactions proceed via a two-step mechanism.
• The leaving group leaves first in SN1, forming a carbocation intermediate, which is then attacked by a nucleophile.
• SN1 reactions are favored by tertiary substrates due to the carbocation intermediate's stability.
• E2 (Elimination Bimolecular) reactions occur in a single step where a base abstracts a proton adjacent to the leaving group.
• This leads to double bond formation and leaving group expulsion in E2 reactions.
• E2 reactions are favored by secondary substrates, balancing accessibility and transition state stability.
• E1 (Elimination Unimolecular) reactions proceed via a two-step mechanism similar to SN1.
• The leaving group first departs, forming a carbocation intermediate; then, a base abstracts a proton to form a double bond in E1 reactions.
• Like SN1, E1 reactions are favored by tertiary substrates because of the stability of the carbocation intermediate.
• Understanding these relationships aids prediction of major products and reaction conditions in organic chemistry.

Steric Hindrance

• Steric hindrance refers to physical crowding around a molecule, hindering reactions.
• Bulky groups surrounding a reactive center physically prevent other molecules from approaching and reacting efficiently.

Causes and Effects of Steric Hindrance

• Large groups attached to a molecule take up space, creating a barrier if they surround a reaction site.
• This barrier makes it harder for molecules to reach and react with the molecule.
• SN2 reactions suffer from steric hindrance because the nucleophile needs to attack the carbon directly, which bulky groups block.
• SN1 reactions are less affected because they don’t require a direct attack; the leaving group departs first, creating an open carbocation.
• E2 reactions need a base to extract a proton from a β-carbon; bulky groups block access, making E2 harder.
• E1 reactions, like SN1, involve a carbocation intermediate, so steric hindrance is less of an issue.

Steric Hindrance Summary

• Less steric hindrance = Easier for direct attack (good for SN2).
• More steric hindrance = Harder for direct attack, favoring SN1 and E1 mechanisms.
• Tertiary carbons are the most sterically hindered, while primary carbons are the least.

Primary Unhindered

• The carbon attached to the leaving group is not surrounded by bulky groups.
• This allows easy access for nucleophiles or bases, making reactions like SN2 and E2 more favorable.

Example: Methyl Bromide (CH₃Br) or Ethyl Bromide (CH₃CH₂Br)

• No bulky groups around the reaction site.
• Nucleophiles can easily attack from the backside (favored for SN2).
• A strong base can abstract a proton if needed (possible E2, but less common).
• SN2 is highly favored because there's minimal steric hindrance.
• SN1 is unlikely because a primary carbocation is too unstable.
• E1 is also unlikely due to the same reason.

Primary Branched

• Although the carbon bonded to the leaving group is still primary, there are bulky groups nearby that can block nucleophilic attack.

Example: Isobutyl Bromide (CH₃)₂CHCH₂Br or Neopentyl Bromide (C(CH₃)₃CH₂Br)

• The carbon directly attached to the leaving group is still primary.
• However, nearby bulky groups (like extra methyl groups) block access to the nucleophile.
• SN2 becomes much slower due to steric hindrance.
• SN2 is hindered because the nucleophile struggles to attack.
• SN1 is still unlikely because the primary carbocation is unstable.
• E2 may happen if a strong base is used, but it depends on the branching.

Neopentyl Halides (C(CH₃)₃CH₂X)

• SN2 is almost completely blocked due to extreme steric hindrance.
• SN1 is still bad because a primary carbocation is unstable.
• E2 might happen with a strong base, but elimination isn’t very favorable.

Summary

• Primary Unhindered = Ideal for SN2; easy for nucleophiles to attack.
• Primary Branched = Steric hindrance slows SN2, might lead to E2 instead with a strong base.
• Neopentyl substrates = Almost completely block SN2 but still don't favor SN1.

Protic Solvents

• A protic solvent has hydrogen atoms bonded to electronegative atoms like oxygen or nitrogen, allowing it to form hydrogen bonds with nucleophiles.
• Protic solvents contain O-H or N-H bonds and can hydrogen bond.
• They stabilize ions, especially carbocations.
• Reduces nucleophilicity by surrounding the nucleophile in a solvent cage.

Examples of Protic Solvents

• Water (H₂O)
• Methanol (CH₃OH)
• Ethanol (CH₃CH₂OH)
• Acetic acid (CH₃COOH)
• Ammonia (NH₃)
• Favors SN1 reactions by stabilizing the carbocation intermediate.
• Slows SN2 reactions because the nucleophile gets solvent-caged, reducing its strength.
• Favors E1 reactions by stabilizing the carbocation similarly to SN1.
• E2 can still happen, but it depends on the base strength.

Aprotic Solvents

• An aprotic solvent does not have O-H or N-H bonds and thus cannot form hydrogen bonds with nucleophiles.
• Aprotic solvents cannot hydrogen bond, leaving nucleophiles “free” and highly reactive.
• Favors strong nucleophiles, increasing reaction speed.

Examples of Aprotic Solvents

• Acetone (CH₃COCH₃)
• Dimethyl sulfoxide (DMSO, (CH₃)₂SO)
• Dimethylformamide (DMF, HCON(CH₃)₂)
• Tetrahydrofuran (THF, C₄H₈O)
• Ethyl acetate (CH₃COOCH₂CH₃)
• Favors SN2 reactions by keeping nucleophiles reactive and strong.
• Is not ideal for SN1 Reactions because does not stabilize the carbocation well
• Favors E2 reactions because strong bases remain effective.
• Is not ideal for E1 Reactions because carbocation formation is not well supported

Choosing the Right Solvent

• If you want SN1 or E1, use a protic solvent (stabilizes carbocations).
• If you want SN2 or E2, use an aprotic solvent (keeps nucleophiles/reactive bases strong).