Blessie Mae R. EncilaIV-B.S Chemistry for TeachersAdvance Organic Chemistry

NITRILER-CN

WINTERTemplateNitrile

History

Nomenclature

01

• A nitrile is any organic compound that has a -C≡N functional group.

• The prefix cyano- is used interchangeably with the term nitrile in industrial literature.

• Nitriles are found in many useful compounds, including– methyl cyanoacrylate

• used in super glue– nitrile butadiene rubber

• a nitrile-containing polymer used in latex-free laboratory and medical gloves.

Nitrile

• Organic compounds containing multiple nitrile groups are known as cyanocarbons.

• Inorganic compounds containing the -C≡N group are not called nitriles, but cyanides instead.

• Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.

Nitrile

Nitrile• C.W. Scheele in 1782

-He synthesized the first compound of the homolog row of nitriles, which is the nitrile of formic acid, and hydrogen cyanide.

• J. L. Gay-Lussac in 1811

-He was able to prepare the very toxic and volatile pure acid.

• Friedrich Wöhler and Justus von Liebig

-They prepared the nitrile of benzoic acids, but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested.

History

Nitrile• Théophile-Jules Pelouze in 1834

-He synthesized propionitrile suggesting it to be an ether of propionic alcohol and hydrocyanic acid.

• Hermann Fehling in 1844

-The synthesis of benzonitrile, by heating ammonium benzoate, was the first method yielding enough of the substance for chemical research. He determined the structure by comparing it to the already known synthesis of hydrogen cyanide by heating ammonium formate to his results. He coined the name nitrile for the newfound substance, which became the name for the compound group.

History

NitrileTwo systems have been adopted by IUPAC:

1. Nitriles derived from open-chain alkanes are named by adding –nitrile as a suffix to the alkane name, with the nitrile carbon numbered C1:

CH3 5 43

2

CH3

CN1

CH3 6 54

CH3

CH3

32

CN1

4-Methylpentanenitrile4,5-dimethylhexanenitrile

Nomenclature

NitrileTwo systems have been adopted by IUPAC:

2. Nitriles are named as derivatives of carboxylic acids by replacing the –ic acid or –oic acid with –onitrile, or replacing –carboxylic acid with -carbonitrile.

Acetonitrile Benzonitrile

CH3C

N C N

3

4

2

5

1

6

CH3

CH3NC

3,3-Dimethylcyclohexanecarbonitrile

Nomenclature

02

NitrileGeneral Reactions of Nitrile

Chem

istry

of N

itrile

s

General Reactions of Nitriles

Nitrile

Amine

Amide Carboxylic Acid

Ketone

R N

O

H2R OH

O

RC

N

HH

H2 R R'

O

R

C

N

H2O

H2O

LiAlH4 R’MgX

Chem

istry

of N

itrile

s

A nitrile can be hydrolyzed in either basic or acidic aqueous solution to yield a carboxylic acid and ammoniz or an amine

Hydrolysis: Conversion of Nitriles into Carboxylic Acids

H3O+

Basic hydrolysis of a nitrile

Amide

C NROr NaOH, H2O

R OH

O

+ NH3

C NR

RC

N-

OH

RC

N

OH

H

+--OH

NH

RC

O

H

--OH

RC

N

O-

O-

H2

RC

N

OHO-

H2+

H2O

O-

RC

O+NH2

-

Carboxylate

--OH

OH H

Dianion

Chem

istry

of N

itrile

s

A nitrile can be reduced with LiAlH4 to give a primary amine

Reduction: Conversion of Nitriles into Amines

R C NLiAlH4

etherR

CH

N-

LiAlH4

etherH2O

RC

N

HH

H2RC

N2-

HH

Nitrile Imine anion Dianion Amine

Chem

istry

of N

itrile

s

A nitrile can add a Grignard reagent to give an intermediate imine anion that is further hydrolyzed by water to yield a ketone:

Reaction of Nitriles with Organometallic Reagents

R C N:R’- +MgX H2O

Nitrile Imine anion Ketone

R'RC

N-

RC

R'

O

+ NH3

03

NitrileApplication

• Over 30 nitrile-containing pharmaceuticals are currently marketed for a diverse variety of medicinal indications with more than 20 additional nitrile-containing leads in clinical development.

Nitrile

• Structure of periciazine, an antipsychotic studied in the treatment of opiate dependence.

Nitrile

• Structure of citalopram, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class.

• Structure of cyamemazine, an antipsychotic drug.

Nitrile

• Structure of fadrozole, an aromatase inhibitor for the treatment of breast cancer.

• Structure of letrozole, an oral non-steroidal aromatase inhibitor for the treatment of certain breast cancers.

Nitrile

04

NitrileJournal

Nifurtimox Activation by Trypanosomal Type I

Nitroreductases Generates Cytotoxic

Nitrile MetabolitesBelinda S. Hall, Christopher Bot, and Shane R. Wilkinson

From the School of Biological and Chemical Sciences, Queen Mary University of London, United Kingdom

• The aim of this work was to determine the role of NTRs (trypanosomal type I nitroreductase) in nifurtimox action.

05

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