Class 21: Kinetics and Mechanism - Substitution Reactions Flashcards
Define the term substitution reaction and identify where the substitution is occurring if given an overall reaction.
- A substitution reaction is a type of reaction where an atom or group of atoms in a molecule is replaced by another atom or group.
- To identify where substitution is occurring in an overall reaction:
- Look for molecule(s) on the reactant side
- Compare to molecule(s) on the product side
- The substituted atom/group is the part that is different between reactants and products
- Common examples:
- Nucleophilic substitution (SN1, SN2)
- Nucleophile replaces a leaving group
- Electrophilic aromatic substitution
- Electrophile replaces H on aromatic ring
- Radical substitutions
- Radical replaces H or other group
- Nucleophilic substitution (SN1, SN2)
- The substituted atom/group is symbolized as “X” in reaction mechanisms
Propose two plausible mechanisms for an overall reaction and a reaction coordinate diagram for each mechanism.
Mechanism 1:
* Step 1: Reactants → Intermediate 1
- Transition state and Ea1
* Step 2: Intermediate 1 → Intermediate 2
- Transition state and Ea2
* Step 3: Intermediate 2 → Products
- Transition state and Ea3
* Draw potential energy diagram
- Y-axis: Energy
- X-axis: Reaction coordinate
- Plot Reactants, Ea1, Int 1, Ea2, Int 2, Ea3, Products
Mechanism 2:
* Step 1: Reactants → Intermediate 3
- Transition state and Ea4
* Step 2: Intermediate 3 → Products
- Transition state and Ea5
* Draw potential energy diagram
- Y-axis: Energy
- X-axis: Reaction coordinate
- Plot Reactants, Ea4, Int 3, Ea5, Products
- Identify rate-determining step based on largest Ea
- Propose evidence to favor one mechanism over the other
State the molecularity of a mechanistic step as unimolecular or bimolecular.
- Molecularity refers to number of molecule particles involved in a single elementary reaction step
- Unimolecular
- One molecule particle undergoing change
- Example: A → Products
- Bimolecular
- Two molecule particles colliding and reacting
- Example: A + B → Products
- Determined by:
- Counting molecule particles on reactant side
- Not the number of atoms/molecules in overall balanced equation
- Never higher than bimolecular
- Due to low probability of simultaneous three-molecule collision
- Important for determining rate law expression
- Unimolecular step: Rate ∝ [A]
- Bimolecular step: Rate ∝ [A][B]
Propose a rate law from a proposed mechanism for an overall reaction based on the rate determining step.
- Identify the rate-determining (slow) step of the mechanism
- This is the step with the highest energy barrier
- The rate law depends on the reactants involved in the rate-determining step
- For an elementary rate-determining step:
- If unimolecular (one reactant): Rate = k[A]
- If bimolecular (two reactants): Rate = k[A][B]
- If rate-determining step is not elementary:
- Apply steady-state approximation to reactive intermediates
- Derive rate law from that step involving reactive intermediates
- The overall reaction order is the sum of the orders for each reactant
- Plug in concentrations to calculated k, the rate constant
- Check proposed rate law against experimental initial rate data
Relate mechanism of a reaction to the order of its rate law.
- Rate law order depends on the rate-determining/slow step
- For an elementary rate-determining step:
- Unimolecular (one reactant): Rate = k[A] (First order in A)
- Bimolecular (two reactants): Rate = k[A][B] (First order in A, first order in B)
- If rate-determining step is not elementary:
- Apply steady-state approximation to derive rate law
- Order depends on which reactants are involved
- Zero-order if reaction is saturated/independent of reactant concentrations
- Examples:
- A → B (slow) Rate = k[A] (First order)
- A + B → C (slow) Rate = k[A][B] (Second order)
- Two A’s react (slow): Rate = k[A]^2 (Second order)
- Overall order is sum of orders for each reactant
- Can be fractional order if derived from steady-state
- Proposed mechanisms must match experimentally determined rate laws
Explain what the S, N, 1 and 2 stand for in SN1 and SN2 reactions.
- S = Substitution
- Refers to a substitution reaction mechanism
- N = Nucleophilic
- The reaction involves a nucleophile (nucleophilic reagent)
- 1 = Unimolecular
- The rate-determining step is a single molecule breaking apart
- 2 = Bimolecular
- The rate-determining step involves two molecules colliding
So in summary:
- SN1 = Unimolecular Nucleophilic Substitution
- SN2 = Bimolecular Nucleophilic Substitution
The numbers indicate the molecularity (1 or 2) of the rate-determining/slow step involving the nucleophile substituting a group.
Draw diagrams of the LUMO for the SN1 and SN2 reactions and explain how they affect the stereochemical outcome of a reaction.
SN1:
* LUMO is sp hybridized and trigonal planar
* Nucleophile can attack from either face
* Results in racemic mixture (both R and S products)
* SN1 proceeds through planar carbocation intermediate
SN2:
* LUMO is sp3 hybridized and tetrahedral
* Nucleophile attacks 180° from leaving group
* Inversion of configuration at substituted carbon
* Stereochemistry is retained if nucleophile attacks from backside
* Stereochemistry is inverted if nucleophile attacks from front
Key Points:
- SN1 results in racemic mix due to planar carbocation
- SN2 can give inverted or retained due to tetrahedral geometry
- LUMO geometry dictates the stereochemical outcome
Define and apply the stereochemical terms of “racemization” and “inversion.”
Here are the concise bullet points defining and applying the stereochemical terms “racemization” and “inversion”:
Racemization:
- Conversion of an optically pure enantiomer into a 50:50 mixture of both enantiomers
- Occurs via formation of a planar or rapidly racemizing intermediate
- Common in SN1 reactions, which proceed through planar carbocations
- Results in loss of optical activity
Inversion:
- Change in configuration of a tetrahedral stereocenter
- R goes to S or S goes to R
- Occurs with backside nucleophilic attack in SN2 reactions
- Stereochemistry is inverted relative to starting material
- No loss of optical activity if starting with optically pure isomer
Retention:
- No change in configuration of a tetrahedral stereocenter
- Occurs if nucleophile attacks from front in SN2
- Stereochemistry is retained relative to starting material
Applying the terms:
- Racemic mixture contains equal amounts of R and S enantiomers
- Inversion of configuration results from backside SN2 attack
- Retention occurs from frontside SN2 attack
Define the term substitution reaction and identify where the substitution is occurring if given an overall reaction.
Substitution reaction: A substitution reaction is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group.
State the molecularity of a mechanistic step as unimolecular or bimolecular.
Unimolecular: singular substrate (ex. SN1)
Bimolecular: 2 substrates (ex. SN2)
Propose a rate law from a proposed mechanism for an overall reaction based on the rate determining step.
What is a part of the rate determining step? Conc of nucleophile? Or only the electrophile becoming a carbocation
SN2 v SN1
Relate mechanism of a reaction to the order of its rate law.
SN1: rate=k[electrophile]
First order overall
SN2: rate=k[electrophile][nucleophile]
Second order overall
Explain what the S, N, 1 and 2 stand for in SN1 and SN2 reactions.
S: Substitution
N: nucleophilic
2: bimolecular
1: unimolecular
Define and apply the stereochemical terms of “racemization” and “inversion.”
Racemization: equal concentrations of R & S enantiomers
How to determine R & S
Put lowest in the back (4)
Order based on priority (based on atomic number or number of atoms)
Counterclockwise: S
Clockwise: R
Chiral center: carbon connected to 4 different things
Inversion: R→S or S→R
Hyperconjugation is a stabilizing interaction in organic chemistry that occurs when electrons in a sigma bond interact with an adjacent unpopulated non-bonding p or antibonding orbitals.
