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ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

CONCEPT: INTRODUCTION TO SUBSTITUTION

Previously, we discussed the various ways that acids could react with bases:

□ Recall that in these mechanisms, electrons always travel from ________ density to _______ density

Bronsted-Lowry Reactions: When a nucleophile and electrophile react to exchange a ______________

Lewis Acid/Base Reactions: When a nucleophile and electrophile with an empty orbital react to form a covalent bond

Substitution Reactions take place when a nucleophile reacts with an electrophile that does not have an empty orbital.

□ This generates the need to analyze a new type of conjugate base: the leaving group.

EXAMPLE: Predict the product. Identify all of the chemical species in the following reaction.

● In typical acid and base reactions, we used stability of the conjugate base to determine chemical equilibrium

● In substitution, we use the stability of the leaving group to help determine reaction rate.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: LEAVING GROUPS

Leaving groups break a bond with the electrophile to make it reactive. They are molecules that will remain stable after

accepting an extra electron pair.

□ We use factors affecting acidity to determine which atoms will be most stable after gaining extra electrons.

● Recall that the element effect consists of two trends:

EXAMPLE: Predict which of the following pairs of electrophiles possesses the best leaving group

a. b.

c. d.

□ Due to their high electronegativity, __________ ______________ will be the primary leaving groups for this chapter.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE SN2 MECHANISM

□ A negatively charged nucleophile reacts with an accessible leaving group to produce substitution in one-step.

SN2 Properties (Circle One)

● Nucleophile = Strong / Weak

● Leaving Group = Unsubstituted / Highly Substituted

● Reaction coordinate = Transition State / Intermediate

● Reaction = Concerted / Two-Step

● Rate = Unimolecular / Bimolecular

● Rate = k[RX] / k[Nu][RX]

● Stereochemistry = Inversion / Retention / Racemic

● Nickname = ______________________________________

EXAMPLE: Rank the following alkyl halides in order of reactivity toward an SN2 reaction.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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PRACTICE: Provide the mechanism and final products for the following reactions.

a.

b.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE SN1 MECHANISM

□ A neutral nucleophile reacts with an inaccessible leaving group to produce substitution in two-steps.

The more -R groups, the more substituted the carbocation, the more ________________

SN1 Properties (Circle One)

● Nucleophile = Strong / Weak

● Leaving Group = Unsubstituted / Highly Substituted

● Reaction coordinate = Transition State / Intermediate

● Reaction = Concerted / Two-Step

● Rate = Unimolecular / Bimolecular

● Rate = k[RX] / k[Nu][RX]

● Stereochemistry = Inversion / Retention / Racemic

● Nickname = ______________________________________

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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PRACTICE: Provide the mechanism and final products for the following reactions.

□ NOTE: Substitution reactions with neutral nucleophiles require an additional deprotonation step.

a.

b.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: SUBSTITUTION COMPARISON

When given a substitution reaction, use the following two factors to determine the mechanism:

1. Nucleophile Strength SN1 = ___________ SN2 = ___________

2. Leaving Group Substitution SN1 = ___________ SN2 = ___________

EXAMPLE: Provide the mechanism and final products for the following reactions.

a.

b.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE E2 MECHANISM

□ A strong nucleophile reacts with an inaccessible leaving group to produce beta-elimination in one-step.

E2 Properties (Circle One)

● Nucleophile = Strong / Weak

● Leaving Group = Unsubstituted / Highly Substituted

● Reaction coordinate = Transition State / Intermediate

● Reaction = Concerted / Two-Step

● Rate = Unimolecular / Bimolecular

● Rate = k[RX] / k[Nu][RX]

● Stereochemistry = ___________________________

EXAMPLE: Rank the following alkyl halides in order of reactivity toward an E2 reaction.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: RECOGNIZING DIFFERENT β-HYDROGENS

□ Elimination reactions remove β-hydrogens to create double bonds.

● The number of non-equivalent β-carbons with at least one _____ determines the number of possible products.

EXAMPLE: Identify the number of unique products that could be obtained through elimination.

a.

b.

c.

d.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE ANTI-COPLANAR REQUIREMENT

□ E2 reactions require an anti-coplanar arrangement in order for the orbitals to overlap and create a new pi bond.

● When this occurs on cyclohexane, the leaving group and beta-proton must be DIAXIAL to each other.

EXAMPLE: Identify which of the following E2 mechanisms would react to completion. Do not draw final products.

a.

b.

c.

d.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE E1 MECHANISM

□ A weak nucleophile reacts with an inaccessible leaving group to produce beta-elimination in two-steps.

E1 Properties (Circle One)

● Nucleophile = Strong / Weak

● Leaving Group = Unsubstituted / Highly Substituted

● Reaction coordinate = Transition State / Intermediate

● Reaction = Concerted / Two-Step

● Rate = Unimolecular / Bimolecular

● Rate = k[RX] / k[Nu][RX]

● Stereochemistry = ___________________________

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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PRACTICE: Provide the full mechanism and draw the final product for the following reactions.

a.

b.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: SOLVENTS

Solvents are mostly inert compounds that provide a medium for the reaction to take place in.

□ Although extremely important in lab, they rarely affect the outcome of a written reaction in Orgo 1

Classification of Solvents

● Polar solvents are solvents which contain a ______ ________________

● Aprotic solvents are solvents that cannot display __________________ ____________

● Protic solvents are solvents that display ____ ______________ (stabilize carbocations, hinder nucleophiles)

□ Therefore, we will prefer to run _____ & _____ in protic solvents, and _____ & _____ in aprotic solvents.

EXAMPLE: Identify the following solvents as apolar, polar aprotic or polar protic

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: LEAVING GROUPS AND NUCLEOPHILES

Leaving Groups: Alkyl halides are the most common leaving groups of organic chemistry, but there are others.

□ Sulfonate Esters are the name given to a group of leaving groups with the general formula -SO3R

□ Water is also a common leaving group, usually formed after alcohol is protonated with a strong acid

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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Nucleophile: Molecule that can easily donate electrons Base: Molecule that can easily remove a proton

□ Relative Strength Rules:

1. A negative charge will always be a stronger nucleophile than its neutral counterpart.

2. The bulkier the substrate, the more ______________ and less ____________________ it is.

3.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: THE BIG DADDY MECHANISM FLOWCHART

Mechanisms are rarely given. We use nucleophile and leaving group information to determine the favored mechanism.

ORGANIC - EGE 5E

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PRACTICE: Predict the mechanism for the following reactions. Provide the full mechanism and draw the final product.

a.

b.

c.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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PRACTICE: Predict the mechanism for the following reactions. Provide the full mechanism and draw the final product.

d.

e.

f.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: CARBOCATION INTERMEDIATES — STABILITY

□ Carbocations are stabilized by a phenomenon called _________________________________

● Hyperconjugation is the delocalization of charge by the interaction of an empty p-orbital with an adjacent, eclipsed σ-bond

● Since this is only possible with -R groups, the more substituted the carbocation, the more ________________

EXAMPLE: Which of the following alkyl halides would generate the most stable carbocation?

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: ACID-CATALYZED DEHYDRATION

□ Alcohols are terrible leaving groups, but in the presence of acid, they can be converted into an awesome leaving group

● The more –R groups on the alcohol, the easier to dehydrate: _________________________________

● The specific elimination mechanism depends on how easily the molecule will form a ______________________.

E2 Dehydration: 1o Alcohol Mechanism:

● Protonation:

● E2 β-Hydrogen Elimination:

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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CONCEPT: ACID-CATALYZED DEHYDRATION

□ Alcohols are terrible leaving groups, but in the presence of acid, they can be converted into an awesome leaving group

E1 Dehydration: 2o and 3o Alcohol Mechanism:

● Protonation:

● Carbocation Formation:

● E1 β-Hydrogen Elimination:

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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PRACTICE: Provide the mechanism and major product for the following dehydration reactions:

a.

b.

ORGANIC - EGE 5E

CH. 7 - NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS

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