ch. 19 - aldehydes and ketones: nucleophilic...
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ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
CONCEPT: ALDEHYDE NOMENCLATURE
Replace the suffix of the alkane “-e” with the suffix __________
● On the parent chain, the carbonyl is always terminal, and ____________ receive a location
● As substituents, they receive the name ______________________________ and _____ receive a location
EXAMPLE: Correctly name the following aldehyde.
EXAMPLE: Correctly name the following aldehyde.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: KETONE NOMENCLATURE
Replace the suffix of the alkane “-e” with the suffix __________
● Ketones have higher priority than most groups in Orgo 1, including alcohols
● When assigning common names to ketones, name both R-groups alphabetically, ending with “______________”
EXAMPLE: Correctly name the following ketone.
1.
EXAMPLE: Correctly name the following ketone.
2.
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CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: INTRO TO REDOX
● Oxidation reactions involve an increase in the ______________ content of a molecule
● Reduction reactions involve an increase in the ______________ content of a molecule
EXAMPLE: Label the following transformations as oxidation or reduction.
a.
b.
c.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: OXIDATION
□ Oxidizing agents are used to oxidize molecules
● Most oxidizing agents add as much oxygen as possible while not breaking ANY C-C bonds.
EXAMPLE: Which of the following compounds could be oxidized?
□ These are called strong oxidizing agents. They include KMnO4 and the Cr6+ reagents (H2Cr2O4, CrO3, K2Cr2O7, etc.)
EXAMPLE: Draw the products of the previous molecules with a strong oxidizing agent
□ PCC is a weak oxidizing agent. It reacts similar but can only add ____ equivalent of oxygen to 1º alcohols.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: OXIDATION MECHANISMS
□ One of the most popular oxidizing agents is the Jones Reagent.
● It can be generated through combination of a strong acid with a Cr6+ reagent.
Mechanism:
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CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Predict the product of the following reactions
a.
b.
c.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: WEAK OXIDATIVE CLEAVAGE
Ozonolysis: Ketones + Aldehydes + Formaldehyde
PRACTICE: Predict the products of the following reaction
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: REDUCTION
□ Reducing agents are used to reduce molecules
● These reagents add hydrogens across π-bonds. Unsaturated hydrocarbons and carbonyls can be reduced.
General Mechanism: Nucleophilic addition of hydrogen
□ Reducing agents add to ALL π-bonds present. Multiple equivalents of hydrogen will react if possible.
● LiAlH4 is a strong reducing agent. It is able to reduce ANY carbonyl compound into alcohol
EXAMPLE: Draw the products of the following molecules reacted with LiAlH4
□ NaBH4 is a weak reducing agent. It can only add ____ equivalent of oxygen and can only reduce CHO and ketones
EXAMPLE: Draw the products of the following molecules reacted with NaBH4
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: ALDEHYDES VIA REDUCING AGENTS
All of the reducing agents we have learned so far are so powerful that they yield alcohols.
● We need to use milder reducing agents to yield aldehydes.
1. Typical strong reduction of carbonyls is accomplished via the use of ____________________
2. We can reduce the power of the reducing agent by making it sterically hindered: _________________________
3. There is another reagent we can use to only induce one equivalent of hydrogen to a carbonyl: _____________
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: ALKYNE HYDRATION
□ Vinyl alcohols are uniquely reactive due to a phenomenon called tautomerization.
● They reversibly swap the positions of a ___________ and a _____ bond.
Oxymercuration of Alkynes
□ Product: __________________________
Hydroboration of Alkynes
□ Product: __________________________
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: NUCLEOPHILIC ADDITION
□ One of the most important ways that carbonyl compounds react is through nucleophilic addition.
● The carbonyl carbon is _____________________________
Nucleophilic Addition General Mechanism:
Nucleophilic Addition General Reactions:
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CONCEPT: CYANOHYDRINS
Cyanide Addition: Cyanohydrins
Cyanohydrin Hydrolysis: Cyanohydrin Reduction:
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PRACTICE: Provide the major product for the following reaction.
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CONCEPT: ORGANOMETALLICS
1. Nucleophilic Addition on Ketones and Aldehydes
EXAMPLE: Show the mechanism and predict the product for the following reaction.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent.
Br
Mg
Ether (ROR)
O
H3O+
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent.
Br
OH
TMS-Cl
N(Et)3
A
Mg
Ether (ROR)
O
H3O+
B C
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: NUCLEOPHILIC ADDITION OF SOLVENTS
These are reactions that are induced primarily by the extraordinary reactivity at the carbonyl carbon
● The carbonyl carbon is so reactive that it even reacts with some _________________
● Most of these mechanisms are acid-catalyzed — all are fully reversible in mild acid (H3O+).
□ Protonation is always the first step, deprotonation is always the last (restores the catalyst)
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: HYDRATES
Carbonyl + Water
● In carbonyls with large –R groups, the equilibrium is greatly shifted to the ____________
EXAMPLE: Show the mechanism and predict the equilibrium for the following reaction.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: HEMIACETALS
Technically, an __________ is the product of alcohol and aldehyde, while ____________ is alcohol and ketone.
● We will simply use the word “acetal” to represent these gem-diether structures in general
● Hemiacetals are only stable when they are ________________.
Carbonyl + 1 Eq. Alcohol
● Acid-Catalyzed Hemiacetal Formation
● Base-Catalyzed Hemiacetal Formation
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: ACETALS
Acetals are stable in ____________ and are easily hydrolyzed back to carbonyls using _________
● Cyclic acetals are formed by reacting carbonyls with a ______________
Carbonyl + 2 Eq. Alcohol
● Acid-Catalyzed Hemiacetal Formation
● Acid-Catalyzed Acetal Formation
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the chemical steps necessary for the following synthesis.
O
?O O
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the chemical steps necessary for the following synthesis.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Determine the starting materials based on the acetal group present.
O
O
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: ACETALS AS PROTECTING GROUPS
There is a huge difference in reactivity between a carbonyl and an acetal. Which do you think is more reactive?
Acetals are used to protect sensitive aldehydes and ketones from reaction with other reagents, since they are reversible.
EXAMPLE: Propose a reagent to perform the following transformation. More than one reagent may be required.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the chemical steps necessary for the following synthesis.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the chemical steps necessary for the following synthesis.
H
NO
H CH3
OO?
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: THIOACETALS AND RANEY NICKEL REDUCTION
Via an almost identical mechanism, thiols can react with aldehydes and ketones to produce thioacetals
The Raney nickel catalyst is a convenient way to _____________________ carbonyls altogether
EXAMPLE: Predict the products of the following reaction
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: IMINES AND ENAMINES
Primary Amine Addition: Imines Secondary Amine Addition: Enamines
□ All products produce iminium cation, where the deprotonation step will depend on type of amine used.
Imine Mechanism:
Enamine Mechanism:
ORGANIC - MCMURRY 9E
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CONCEPT: ADDITION OF AMMONIA DERIVATIVES
EXAMPLE: Predict the products of the following reaction.
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CONCEPT: WOLFF-KISCHNER REDUCTION
This reaction sequence is used to completely remove carbonyls from alkane chains, much like:
a. _______________________________
b. _______________________________
Mechanism:
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CONCEPT: KETONES FROM ACID CHLORIDES
When a good leaving group is present on a carbonyl, organometallics tend to react twice, yielding disubstituted alcohols.
Nucleophilic Acyl Substitution on Esters and Acid Chlorides
From Acid Chlorides:
We can reduce the power of the organometal by using a Gilman to yield _________ from RCOCl
□ This reagent stops after the first nucleophilic addition
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction.
Cl
O
(CH3CH2)2CuLi
Ether
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: THE WITTIG REACTION
The Wittig forms new carbon-carbon bonds between carbonyl and reactive intermediate called an “ylide” to yield
regiospecific _____________
Formation of the Ylide:
● STEP 1 – Alkyl Halide + Triphenylphosphine
● STEP 2 – Deprotonation with a Strong Base
● STEP 3 – Form Oxaphosphetane (mechanism) or Box-Out Method (product).
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Determine the carbonyl and ylide that formed the following product.
ORGANIC - MCMURRY 9E
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PRACTICE: Provide the major product for the following reaction.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the chemical steps necessary for the following synthesis.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent.
ORGANIC - MCMURRY 9E
CH. 19 - ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION
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CONCEPT: CONJUGATE ADDITION OF ENONES
Once an aldol condensation is completed, an electrophilic carbonyl still remains.
● Enones remain susceptible to nucleophilic attack, however they now have two electrophilic regions:
● Also known as 1,2 vs. 1,4 addition of enones, or nucleophilic addition vs. conjugate addition of carbonyls.
Nucleophilic Addition vs. Conjugate Addition
ORGANIC - MCMURRY 9E
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