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.



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.



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.



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.



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:



PRACTICE: Predict the product of the following reactions

a.

b.

c.



CONCEPT: WEAK OXIDATIVE CLEAVAGE

Ozonolysis: Ketones + Aldehydes + Formaldehyde

PRACTICE: Predict the products of the following reaction



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



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: _____________



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: __________________________



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:



CONCEPT: CYANOHYDRINS

Cyanide Addition: Cyanohydrins

Cyanohydrin Hydrolysis: Cyanohydrin Reduction:



PRACTICE: Provide the major product for the following reaction.



CONCEPT: ORGANOMETALLICS

1. Nucleophilic Addition on Ketones and Aldehydes

EXAMPLE: Show the mechanism and predict the product for the following reaction.



PRACTICE: Provide the major product for the following reaction dealing with the Grignard reagent.

Br

Mg

Ether (ROR)

O

H3O+




Br

OH

TMS-Cl

N(Et)3

A

Mg

Ether (ROR)

O

H3O+

B C



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)



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.



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



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



PRACTICE: Provide the chemical steps necessary for the following synthesis.

O

?O O



PRACTICE: Determine the starting materials based on the acetal group present.

O

O



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.




H

NO

H CH3

OO?



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



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:



CONCEPT: ADDITION OF AMMONIA DERIVATIVES

EXAMPLE: Predict the products of the following reaction.



CONCEPT: WOLFF-KISCHNER REDUCTION

This reaction sequence is used to completely remove carbonyls from alkane chains, much like:

a. _______________________________

b. _______________________________

Mechanism:



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




Cl

O

(CH3CH2)2CuLi

Ether



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).



PRACTICE: Determine the carbonyl and ylide that formed the following product.



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



ch. 19 - aldehydes and ketones: nucleophilic...

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