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ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

CONCEPT: AMINE NOMENCLATURE

The degree of the amine directly determines how it will be named.

1o Amines: Add the suffix –amine is to the name of the alkyl substituent. If the alkyl substituent’s name ends with an –e

replace it with –amine.

EXAMPLE: Name the following 1o Amines.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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If a higher priority functional group is present then the suffix –amine changes into the prefix –amino.

EXAMPLE: Name the following multi-functional amine.

2o and 3o amines: If different alkyl groups are attached the largest alkyl group is chosen as the parent name, and the other

alkyl groups are N-substituents.

EXAMPLE: Name the following amines

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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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 - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: GABRIEL SYNTHESIS

Potassium phthalimide is a secondary diamide that can yield primary amines in much better yield when treated with

1. _______________ (to turn it into a strong nucleophile)

2. _______________ (back-side attack)

3. _______________ (to attack the carbonyls)

Gabriel Synthesis Mechanism:

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: AMINES BY REDUCTION

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: NITROGENOUS NUCLEOPHILES

Three of the reagents used in amines by reduction can be found as excellent nucleophiles.

● They can participate in __________ reactions when there is a good leaving group present.

□ ____________

□ ____________

□ ____________

Additionally, ________ can act on acid chlorides to produce ___________________ (not an SN2 mech, we’ll get to it later!)

□ ____________

EXAMPLE: Provide the major product for the following reaction.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: REDUCTIVE AMINATION

Recall that ketones and aldehydes can react with primary amines in acidic conditions to form imines.

● This mechanism passed through an important intermediate called an iminium cation.

Ketones and aldehydes can be made to form amines instead by using the reducing agent, NaBH3CN on the imine.

● This mechanism starts the same, except for the fact that we reduce the imine instead of deprotonating it

EXAMPLE: Provide the major product for the following reaction.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: CURTIUS REARRAGEMENT

Also known as Reduction of Acyl Azides, it is the result of the thermal formation of a reactive intermediate called a nitrene.

● Heat drives the rearrangement of the acyl group to a molecule called an isocyanate

● Addition of ____________ results in a decarboxylation reaction that liberates ______________ and _________

General Mechanism:

EXAMPLE: Propose a synthesis for the following compound.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: HOFMANN REARRAGEMENT

Also known as Hofmann Degradation, it is a method to turn amides into primary amines.

● The amide rearranges to a molecule called an isocyanate

● Liberates _______________ as a by-product

Hofmann Rearrangement Mechanism:

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: HOFMANN ELIMINATION

Also known as exhaustive methylation or Hofmann Degradation.

● This reaction uses amine polyalkylation to produce a Hofmann Elimination product.

Hofmann Elimination Mechanism:

EXAMPLE: Provide the major product for the following reaction.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: EAS – PROTECTION OF ANILINE DERIVATIVES

Strongly activated rings like aniline can open the ring up to unwanted reactions.

To avoid this, we can reversibly acetylate (protect) the amino group to make it moderately activating.

EXAMPLE: Synthesize the target molecule from nitrobenzene and any other reagents.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: DIAZONIUM COMPOUNDS – REPLACEMENT REACTIONS

Aniline reacts with nitrous acid to form a diazo functional group in a reaction called a diazotization.

● Aryl diazonium salts participate in multiple replacement reactions

List of Diazo Replacement Reactions:

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: DIAZO COMPOUNDS – SEQUENCE GROUPS

Sequence Groups are groups that have the ability to alter the sequence of an aromatic synthesis. These are groups that

can be easily transformed into another type of director:

Blocking Groups are groups that act only to direct other reactions and are then completely removed.

● Hypophosphorous acid (H3PO2) is used to __________ the para position and _________ o-substitution.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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CONCEPT: DIAZONIUM COMPOUNDS – PROPOSING AROMATIC SYNTHESIS

You may be asked to propose an aromatic synthesis starting only from benzene or diazobenzene derivatives.

● We must use our knowledge sequence and blocking groups to plan synthetic steps in the correct order

EXAMPLE: Synthesize the target molecule from toluene and any other reagents.

EXAMPLE: Synthesize the target molecule from the following precursor and any other reagents.

ORGANIC - LOUDON 6E

CH. 23 - THE CHEMISTRY OF AMINES

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