Comprehensive Notes: SN1 and SN2 Mechanisms (Based on Transcript)
Good Attacking Groups for SN2
Nucleophiles (attacking groups) with relative speeds (higher = faster):
HS⁻:
CN⁻:
I⁻:
OH⁻:
Cl⁻:
NH₃:
H₂O:
Implication: Faster nucleophiles and stronger nucleophiles promote SN2; weak nucleophiles slow SN2 down.
Good Leaving Groups for SN2
Leaving groups, ordered by relative ease of departure (higher = faster):
I⁻:
Br⁻:
Cl⁻:
F⁻:
OH⁻:
NH₂⁻:
OR′ (ether):
Implication: I⁻ > Br⁻ > Cl⁻ in SN2 leaving ability; OH⁻, NH₂⁻, OR′ are poor leaving groups in SN2.
SN2 vs SN1: Quick Mechanistic Overview
SN2 mechanism:
Nucleophile attacks the carbon at the end of the molecule (a primary carbon) in a backside attack.
Results in inversion of stereochemistry at the reacting carbon (Walden inversion).
Applicable to iodoalkanes, bromoalkanes and chloroalkanes to form alcohols and nitriles (in some contexts).
Attacking group affects reaction rate; leaving group and substrate shape also matter; solvent matters too.
If the reactant is an alcohol, SN2 is slow/ineffective.
SN1 mechanism:
Nucleophile attack occurs after the leaving group departs, forming a carbocation intermediate.
The rate-determining step is the ionization to form the carbocation; nucleophile involvement occurs after.
Works best when the leaving group is attached to a tertiary carbon (3 Carbon substituents around the reactive center).
Attacking nucleophile does not affect the rate (unlike SN2).
Often requires polar protic solvents to stabilize the carbocation intermediate.
Chirality and Mechanism
SN2 and chirality:
All product from SN2 has the opposite chirality at the reacting center (inversion).
Example: SN2 on a chiral haloalkane leads to inversion of configuration.
SN1 and chirality:
SN1 typically gives racemic mixture if the product is chiral, because the carbocation intermediate is planar and can be attacked from either face equally.
Substrate Preferences: When Each Mechanism Dominates
SN2 works best when attaching something to a primary carbon (leaving group on a carbon attached to only 1 other carbon).
SN1 works best when attaching something to a tertiary carbon (leaving group on a carbon attached to 3 other carbons).
Side-by-Side: SN2 vs SN1 Capabilities
SN2:
Product often has opposite chirality (inversion).
Best when nucleophile attacks a carbon at the end of the molecule.
Can convert iodoalkanes, bromoalkanes and chloroalkanes into alcohols and nitriles.
Attacking group influences rate; the nucleophile is important for the rate.
If starting material is an alcohol, SN2 is slow.
SN1:
Product can be racemic if chiral (equal enantiomer formation).
Best when nucleophile attacks a carbon not at the end of the molecule (middle carbon).
Can convert alcohols, ethers, fluoroalkanes and amines into haloalkanes, alcohols & nitriles.
Attacking group does not affect rate; leaving group, substrate structure, and solvent do.
Water is a common solvent for SN1; polar protic solvents stabilize carbocations.
SN1 Mechanism: Step-by-Step
Step 1: Leaving group departs first (ionization) to form a carbocation (R⁺).
Step 2: Nucleophile attacks the carbocation to form the product.
Step 3: Any subsequent deprotonation/proton transfer if needed to give the final neutral product.
Key example: CBr(CH₃)₃ + OH⁻ → HOC(CH₃)₃ + Br⁻
Mechanistic depiction:
Ionization:
Nucleophilic attack:
Another classic example: Convert C(CH₃)₃Br into C(CH₃)₃OH via SN1.
Curly-arrows notation is used to illustrate the electron flow (X = Br in the example; nuc = OH⁻).
Special Names: Carbocations and Formation
Ions like C(CH₃)₃⁺ are called carbocations.
Carbocations are formed through heterolytic fission (one bond breaks and both electrons go to one atom).
Heterolytic fission example (illustrative in slides): bond breaking leading to a positively charged carbon species and a leaving group anion.
In contrast, homolytic fission yields two identical radicals (e.g., Cl₂ → Cl• + Cl•).
Carbocations: What They Are and How to Identify Them
Three things must be true for something to be a carbocation:
1) The ion must have a charge of +1.
2) The ion must contain a carbon atom near the center of the molecule.
3) There must be 3 bonds coming off the carbon atom (it can be 3 single bonds, or 2 single + 1 double, or 1 triple bond + 0 or more single bonds on adjacent sites).Quick summary: a +1 charged carbon center with three substituents (or equivalent multiple bonds that still generate three substituents) defines a carbocation.
Carbocation Stability and Its Consequences
Stability hierarchy (based on branching around the carbocation center):
(CH₃)₃C⁺ is more stable than (CH₃)₂CCH₂⁺; (CH₃)₂CH⁺ is more stable than (CH₃)CH₂⁺; CH₃⁺ is least stable.
Carbocation stability increases with substitution (more alkyl groups donate electron density via hyperconjugation and inductive effects).
Comparison: (CH₃)₃C⁺ > (CH₃)₂CCH₂⁺ > (CH₃)CH₂⁺ > CH₃⁺.
Additional note: (CH₃)₃C⁺ is more stable than (CH₃)₂CCH₂⁺; similar trends apply to other branching patterns around the positive carbon.
Practical implication: More stable carbocations form more readily and thus lead to faster SN1 reactions.
Carbocation Stability: Examples and Implications
If the central carbon has many branches, the resulting carbocation is more stable, increasing the rate of SN1 for the corresponding haloalkane.
Examples discussed include comparisons like tert-butyl cation vs secondary or primary carbocations, illustrating that stability correlates with substitution degree and branching.
Stability Consequences for Reaction Rates
Since more stable carbocations form more readily, SN1 reactions proceed faster when the substrate can form a highly substituted carbocation (e.g., tertiary halides).
Conversely, less-stable carbocations (primary) form slowly, slowing SN1 considerably or making SN1 unlikely.
Rate Laws and Kinetics: SN1 vs SN2
SN1 rate law (rate-determining step is ionization):
The concentration of the nucleophile does not affect the rate.
Example given: rate = k [\text{CBr(CH₃)_3}] for tert-butyl bromide with OH⁻ (illustrative).
SN2 rate law (bimolecular in substrate and nucleophile):
The nucleophile and substrate both influence the rate; the attacking group matters as well as leaving group and solvent.
Practice point: SN1 and SN2 have different rate-determining steps and therefore different rate dependencies on reactant concentrations.
Solvent Effects
SN1:
Works best in polar protic solvents (solvents with O–H or N–H bonds that can donate H-bonds).
Rationale: such solvents stabilize carbocation intermediates through solvation, increasing carbocation lifetime and allowing more time for nucleophilic attack.
Examples in slides: water (H₂O) and ammonia (NH₃) as protic solvents.
SN2:
Solvent effects also matter, but the main requirement is nucleophile accessibility and substrate structure; polar aprotic solvents can favor SN2 by not heavily solvating the nucleophile.
What Each Mechanism Lets You Do
SN2 and SN1 can both transform iodo-, bromo-, and chloroalkanes into alcohols and nitriles under suitable conditions.
SN2 is preferred when you want to add your substituent to an end carbon (terminal carbon).
SN1 is preferred when you want to add to a middle carbon (internal carbon) where carbocation stabilization is feasible.
If you want to convert alcohols, ethers, fluoroalkanes or amines into haloalkanes, alcohols and nitriles, SN1/SN2 pathways can be used depending on conditions.
Important practical point: the wrong solvent or reagent can lead to elimination products instead of substitution products (see Eliminations below).
Enantiomeric Outcomes and Stereochemistry
SN1: produces equal amounts of both enantiomers if the product is chiral (racemic mixture) because the carbocation is planar.
SN2: produces inversion of configuration at the reacting stereocenter (Walden inversion) due to backside attack.
Eliminations: E1 and E2 as Side Reactions
Relationship to SN1/SN2: depending on solvent and base, elimination can compete with substitution.
Examples from slides:
2-bromo-2-methylpropane with NaOH in water or ethanol yields propene; other conditions yield 2-methylpropan-2-ol (substitution).
2-bromopropane with weak base yields propene; with strong base yields propan-2-ol.
1-bromopropane with base in ethanol yields propene; with base in water yields propan-1-ol.
Practical takeaway: choosing the wrong solvent or base can give an unintended product (elimination vs substitution).
Rate Expression Example for SN1 (Illustrative)
For the tert-butyl bromide example:
The rate is independent of the nucleophile concentration because the rate-determining step is ionization to form the carbocation:
\text{Rate} = k [\text{CBr(CH₃)_3}]
Note: the concentration of OH⁻ does not affect the rate in this SN1 case.
Self-Quiz References (From Slides)
Question: Would CH₃(CH₂)₅I be more likely to react via SN1 or SN2?
Answer provided elsewhere in slides: for a leaving group (I⁻) at the end of the chain, SN2 is more likely.
Additional question: Would CH₃(CH₂)₅I be more likely to react via SN1 or SN2?
Answer: SN2 is favored when the leaving group is on a terminal carbon; SN1 is favored for more substituted/benzylic/tertiary-like centers (context provided in slides).
Conceptual Takeaways: Why Substrate Structure Matters
Carbocation stability drives SN1: more substituted (branched) centers stabilize the carbocation and speed up SN1.
Substrates that form less stable carbocations react slowly by SN1 or require harsher conditions.
For SN2, a less hindered substrate (primary) is favored because backside attack is easier; highly substituted carbons hinder SN2.
Hallmarks of SN2 vs SN1 (Recap)
SN2:
Nucleophile attacks the carbon at the end of the molecule.
Inversion of configuration (if chiral).
Rate depends on substrate and nucleophile.
SN1:
Leaving group departs first to form a carbocation intermediate.
Product distribution may be racemic if chiral (no net inversion or retention).
Rate depends only on the substrate (leaving group, substrate structure, and solvent determine rate).
Stabilizing carbocation (tertiary > secondary > primary) dramatically enhances rate.
Final Connections and Real-World Relevance
SN1 and SN2 concepts underpin many synthetic strategies in organic chemistry, including how to introduce nucleophiles at specific carbons, control stereochemistry, and avoid unwanted eliminations.
Understanding leaving group ability and solvent effects helps in planning reactions and selecting reagents for desired products.
The balance between substitution and elimination is a common consideration in industrial and laboratory synthesis, influencing yields, selectivity, and reaction conditions.