ch.7 - alkyl halides: nucleophilic …lightcat-files.s3.amazonaws.com/packets/organic-2...concept:...
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ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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PRACTICE: Provide the mechanism and final products for the following reactions.
a.
b.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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CONCEPT: DOUBLE BOND ISOMERISM
□ Cis and trans are names given to particular arrangements of double bonds or ____________
● These isomers exist because free rotation around π bonds is ______________________
● When two groups are on the “same side of the fence”, we call them ___________
● When two groups are on “different sides of the “fence” we call them ___________
EXAMPLE: How are the different substituents related to each other?
□ E and Z isomers are similar designations given to _______________________________ alkenes
EXAMPLE: Assign cis/trans isomerism to the following alkenes
The E/Z naming system allows us to assign unique names to _______ and __________substituted alkenes.
● Choose the highest priority groups on both corners of the double bond. How are they related to each other?
- If ___________, assign the letter (E)
- If ___________, assign the letter (Z)
EXAMPLE: Assign an (E) - (Z) designation to the following alkenes if applicable.
a. b.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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PRACTICE: Determine the IUPAC names of the following molecules
a.
b.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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.
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CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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PRACTICE: Provide the full mechanism and draw the final product for the following E2 reactions.
a.
b.
c.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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
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CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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.
a.
b.
c.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: 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.
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CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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CONCEPT: STABILITY OF ALKENES
□ Alkenes are also stabilized through _________________________________
● Since this is only possible with -R groups, the more substituted the alkene, the more ________________
EXAMPLE: Rank the following alkenes in order of lowest to highest heat of combustion.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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CONCEPT: ELIMINATION AND ZAITSEV’S RULE
□ We often find that an elimination reaction can yield more than one unique alkene as a product.
● The most stable product = ________________ ● The least stable product = ________________
Zaitsev’s Rule explains that we will always favor the more substituted, thermodynamically stable product
□ UNLESS we are using a bulky base. A bulky base promotes the formation of a less substituted, kinetic product
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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PRACTICE: Predict ALL of the products of the following reactions. Label them as either major or minor if necessary.
a.
b.
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CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: 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 - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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PRACTICE: Provide the mechanism and major product for the following dehydration reactions:
a.
b.
ORGANIC - KLEIN 3E
CH.7 - ALKYL HALIDES: NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
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