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ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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PRACTICE: Provide the mechanism and final products for the following reactions.
a.
b.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: CONVERSION OF ALCOHOLS TO GOOD LEAVING GROUPS
□ Alcohols are terrible leaving groups. If we want to react with them, they need to be transformed.
●They can be converted into ____________ _________________ or ______________ _______________
2o and 3o Alcohols with HX: SN1 mechanism
1o alcohols with HX: SN2 mechanism
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: CONVERSION OF ALCOHOLS TO GOOD LEAVING GROUPS
□ SOCl2 and PBr3 are two of the most commonly used reagents to transform alcohols into alkyl halides
●They always proceed with __________________________ of configuration.
1o and 2o Alcohols to RX: SN2 mechanism
EXAMPLE: Determine the mechanism for the following reaction. Draw the final product.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: CONVERSION OF ALCOHOLS TO GOOD LEAVING GROUPS
□ Alcohols can attack sulfonyl chlorides to create sulfonate esters.
●They always proceed with __________________________ of configuration.
Alcohols to Sulfonate Esters:
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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Alcohol Conversion Summary:
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 = ______________________________________
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 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 - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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PRACTICE: Provide the mechanism and major product for the following dehydration reactions:
a.
b.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: DEHYDROHALOGENATION
□ The name given to an E2 reaction of an alkyl halide. The major product will depend upon the type of base used.
Mechanism:
EXAMPLE: Supply the mechanism and major/minor products for the following dehydrohalogenation reaction:
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: DOUBLE DEHYDROHALOGENATION (ALKYNE SYNTHESIS)
□ When two equivalents of halide are present, bases can eliminate twice, creating alkynes as products
VICINAL: Adjacent to each other (aka “Vicinity”) GEMINAL: On the same carbon (aka “Gemini – Twins”)
EXAMPLE: Supply the mechanism and major/minor products for the following dehydrohalogenation reactions:
a.
b.
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CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: AMINE AKLYATION
Alkyl halides are susceptible to nucleophilic attack by amines. This mechanism is called ___________
However, this reaction has little synthetic value because multiple alkylations will usually occur:
● The only way to avoid is will excessive amounts of amine.
Amine Polyalkylation Mechanism:
EXAMPLE: Propose a synthesis for the following compound.
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: SYNTHESIS OF ETHERS
1. Williamson Ether Synthesis (SN2 of 1o or 0o RX)
● Substitution with an oxide base. 2o and 3o alkyl halides will favor _______
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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PRACTICE: Predict the product for the following reaction
PRACTICE: Predict the product for the following reaction
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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CONCEPT: CLEAVAGE OF ETHERS
□ Ethers are very combustible, but unreactive. They contain two strong C—O bonds that are not easy to break.
● They only undergo one synthetically useful reaction: cleavage in the presence of strong acid.
Mechanism:
EXAMPLE: Predict the product of the following reaction
ORGANIC - JONES 5E
CH. 7 - SUBSTITUTION REACTIONS: THE SN2 AND SN1 REACTIONS
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