11.S: Reactions of Alkyl Halides - Nucleophilic Substitutions and Eliminations (Summary)
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- Dietmar Kennepohl & Layne Morsch
- University of Illinois Springfield
Concepts & Vocabulary
- Alkyl halides react as electrophiles and undergo nucleophilic substitution and elimination reactions.
11.2 The Discovery of Nucleophilic Substitution Reactions
- Some nucleophilic substitution reactions invert stereochemistry at the reactive carbon.
- Reaction steps with two molecules involved in the rate determining step are called bimolecular.
- A substitution mechanism that has the nucleophile entering at the same time the leaving group leaves, in a concerted step, is called S N 2 - substitution nucleophilic bimolecular.
- Concerted substitution mechanisms (S N 2) occur via backside attack, which causes inversion of the carbon where the reaction occurs.
- Rates of S N 2 reactions depend on concentration of nucleophile and alkyl halide.
11.4 Characteristics of the S N 2 Reaction
- S N 2 reactions are concerted.
- Sterically hindered substrates reduce S N 2 reaction rate.
- A transition state in a reaction mechanism is the highest energy point on a pathway from reactants to an intermediate or products.
- Larger groups (such as alkyl vs. hydrogen) cause greater steric repulsion in S N 2 transition states , reducing rates of S N 2 reactions.
- Groups that have electron-rich atoms are typically good nucleophiles.
- In general, stronger bases are better nucleophiles.
- Polar aprotic solvents increase rates of S N 2 reactions.
- Polar protic solvents decrease rates of S N 2 reactions.
- As basicity of leaving groups decreases, their ability to leave increases.
- A substitution mechanism that occurs with the leaving group leaving in the first step, creating a carbocation intermediate, followed by the nucleophile entering is called S N 1 - substitution nucleophilic unimolecular.
- S N 1 reactions occur through a stepwise mechanism.
- The first step (dissociation) of an S N 1 mechanism is rate limiting.
- In S N 1 reactions the nucleophile is not involved in the rate limiting step, therefore nucleophile strength or concentration do not affect the rate.
- The intermediate for S N 1 mechanisms contains a planar carbocation. The nucleophile can then enter from either side of the molecule giving racemic products with no additional stereocenters in the molecule.
11.6 Characteristics of the S N 1 Reaction
- Polar solvents increase rates of S N 1 reactions.
- Better leaving groups increase rates of S N 1 and S N 2 reactions.
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Predicting whether a reaction will follow an S
N
1 or S
N
2 mechanism requires analysis of:
- Electrophile - primary favor S N 2, tertiary (and allyl or benzyl) favor S N 1, secondary depends on other factors
- Nucleophile - strong favor S N 2, weak favor S N 1
- Solvent - polar aprotic favor S N 2, polar protic favor S N 1
11.7 Biological Substitution Reactions
- When biological substitution reactions occur, the electrophiles are often different though the mechanisms are primarily the same.
11.8 Elimination Reactions - Zaitsev's Rule
- The major product of Elimination reactions is the product with the more substituted double bond. This is known as Zaitsev's rule.
11.9 The E2 Reaction and Deuterium Isotope Effect
- The E2 mechanism is concerted with the base removing a proton and the leaving group leaving at the same time.
- Since E2 mechanisms are concerted, both the base and the electrophile are present in the rate equation.
- E2 reactions require strong bases and polar aprotic solvents.
- Kinetic Isotope Effects can provide evidence for E2 mechanisms since they can show when breaking of the C-H bond is part of the rate-determining step.
11.10 The E2 Reaction and Cyclohexane Conformation
- E2 reactions of cyclic structures show necessity for anti orientation of the proton being removed and the leaving group.
11.11 The E1 and E1cB Reactions
- E1 mechanisms begin with a leaving group leaving which forms a carbocation intermediate, which is then deprotonated in a second step.
- E1 mechanisms are step-wise.
- More substituted electrophiles are more reactive in E1 reactions.
- Zaitsev products are preferred, similarly to E2 reactions.
- E1 and S N 1 proceed via the same carbocation intermediate and the same rate-determining step so typically happen concurrently.
- E1cB reactions begin with deprotonation (usually resulting in a resonance stabilized carbanion), followed by loss of the leaving group in the second step.
11.12 Biological Elimination Reactions
- There are many important examples of biological elimination reactions.
11.13 A Summary of Reactivity - S N 1, S N 2, E1, E1CcB, and E2
Skills to Master
- Skill 11.1 Draw S N 1/S N 2 mechanisms showing appropriate stereochemistry.
- Skill 11.2 Explain when S N 1/S N 2 mechanisms are likely to occur.
- Skill 11.3 Describe/draw the intermediate for an S N 1 mechanism and transition state(s) for S N 1/S N 2 mechanisms.
- Skill 11.4 Write out rate laws for S N 1/S N 2 mechanisms.
- Skill 11.5 Differentiate between which mechanism is more likely between S N 1/S N 2.
- Skill 11.6 Draw reaction coordinate diagrams for S N 1/S N 2 mechanisms.
- Skill 11.7 Explain how the electrophile, nucleophile, leaving group, and solvent affect S N 1/S N 2 mechanisms.
- Skill 11.8 Recognize use of nucleophilic substitution and elimination reactions in biological systems.
- Skill 11.9 Draw E1/E2 mechanisms showing appropriate stereochemistry.
- Skill 11.10 Explain when E1/E2 mechanisms are likely to occur.
- Skill 11.11Describe/draw the intermediate for an E1 mechanism and transition state(s) for E1/E2mechanisms.
- Skill 11.12 Write out rate laws for E1/E2 mechanisms.
- Skill 11.13 Differentiate between which mechanism is more likely between E1/E2.
- Skill 11.14 Draw reaction coordinate diagrams for E1/E2 mechanisms.
- Skill 11.15 Explain how kinetic isotope effects can be used to support or refute a proposed mechanism.
- Skill 11.16 Draw an E1cB mechanism and explain when it is a viable option.
- Skill 11.17 Differentiate between which mechanism is more likely between S N 1/S N 2 and E1/E2.
Memorization Tasks (MT)
MT 11.1 Memorize the order of good leaving groups.
MT 11.2 Memorize which solvents are polar protic and polar aprotic.
MT 11.3 Memorize the stability order of carbocations.