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20.7 Chemistry of Nitriles

Objectives

After completing this section, you should be able to

  1. discuss, in detail, the preparation of nitriles:
    1. write an equation to illustrate the formation of a nitrile by the nucleophilic attack of cyanide ion on an alkyl halide.
    2. write an equation to illustrate the formation of a nitrile by the dehydration of a primary amide.
    3. identify the product formed when a primary amide is treated with SOCl2, P2O5, or POCl3.
    4. identify the primary amide, the reagents, or both, needed to prepare a given nitrile by a dehydration reaction.
    5. write a detailed mechanism for the dehydration of a primary amide by thionyl chloride.
  2. discuss, in detail, the reactions of nitriles:
    1. write an equation to describe the (acidic or basic) hydrolysis of a nitrile.
    2. write detailed mechanisms for the acidic and basic hydrolysis of nitriles.
    3. identify the products formed from the (acidic or basic) hydrolysis of a given nitrile.
    4. identify the nitrile, the reagents, or both, needed to obtain a given carboxylic acid from a hydrolysis reaction.
    5. write an equation to describe the reduction of a nitrile to give a primary amine.
    6. identify the product formed from the lithium aluminum hydride reduction of a given nitrile.
    7. identify the nitrile, the reagents, or both, needed to prepare a given amine by direct reduction.
    8. write a detailed mechanism for the reduction of a nitrile to a primary amine using lithium aluminum hydride.
    9. give an example of the reduction of a nitrile with diisobutylaluminum hydride.
    10. write an equation to illustrate the reaction of a nitrile with a Grignard reagent.
    11. identify the product formed from the reaction of a given nitrile with a given Grignard reagent.
    12. identify the nitrile, the Grignard reagent, or both, needed to prepare a given ketone.
    13. write a detailed mechanism for the reaction of a nitrile with a Grignard reagent.

Study Notes

To be able to understand the driving force behind the reactions of nitriles, you must recognize the polarity of this group:

carbon shown to be more electropositive than nitrogen in a nitrile group

You can therefore expect to see similarities between the behaviour of the nitrile group and the similarly polarized carbonyl group:

carbon shown to be more electropositive than oxygen in a carbonyl group

Properties of Nitriles

The electronic structure of nitriles is very similar to that of an alkyne with the main difference being the presence of a set of lone pair electrons on the nitrogen. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two \(\pi\) bond in the triple bond. The R-C-N bond angle in and nitrile is 180o which give a nitrile functional group a linear shape.

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The lone pair electrons on the nitrogen are contained in a sp hybrid orbital which makes them much less basic and an amine.  The 50% character of an sp hybrid orbital close to the nucleus and therefore less basic compared to other nitrogen containing compounds such as amines.

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The presence of an electronegative nitrogen causes nitriles to be very polar molecules. Consequently, nitriles tend to have higher boiling points than molecules with a similar size.  

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Interesting Nitriles

One of the most common occurrences of nitriles is in Nitrile rubber. Nitrile rubber is a synthetic copolymer of acrylonitrile and butadiene.  This form of rubber is highly resistant to chemicals and is used to make protective gloves, hoses and seals.

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Preparation of Nitriles

Addition of cyanide (-:C≡N) to an aldehyde or ketone forms a cyanohydrin

 

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Nitriles are formed by an SN2 reaction between a bromide and sodium cyanide

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1o Amides can be converted to nitriles by dehydration with thionyl chloride (or other dehydrating agents like P2O5, or POCl3).

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Mechanism

1) Nucleophilic attach on thionyl chloride

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2) Leaving group removal

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3) Deprotonation

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4)  Leaving group removal

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Reactions of Nitriles

The carbon in a nitrile is electrophilic because a resonance structure can be drawn which places a positive charge on it.  Because of this the triple bond of a nitrile accepts a nucleophile in a manner similar to a carbonyl.

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Nitriles can be converted to carboxylic acid with heating in sulfuric acid. During the reaction an amide intermediate is formed. 

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Example

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Mechanism

1) Protonation

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2)  Nucleophilic attack by water

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3) Proton Transfer

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4) Resonance

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5) Deprotonation

6) Further hydrolysis of the amide.  This mechanism can be found in Section 21.7

 

Nitriles can be converted to 1° amines by reaction with LiAlH4

During this reaction the hydride nucleophile attacks the electrophilic carbon in the nitrile to form an imine anion. Once stabilized by a Lewis acid-base complexation the imine salt can accept a second hydride to form a dianion. The dianion can then be converted to an amine by addition of water.

General Reaction

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Going from reactants to products simplified

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Example

 

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Mechanism

1) Nucleophilic Attack by the Hydride

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2) Second nucleophilic attack by the hydride.

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3) Protonation by addition of water to give an amine

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Reaction of Nitriles with Organometaliic Reagents

Grignard reagents can attack the electophillic carbon in a nitrile to form an imine salt.  This salt can then be hydrolyzed to become a ketone. 

General Reaction

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Example

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Mechanism

1) Nucleophilic Attack by the Grignard Reagent

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2) Protonation

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3) Protonation

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4) Nucleophilic attack by water

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5) Proton Transfer

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6)  Leaving group removal

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7) Deprotonation

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