AMINES, AMIDES and ANILINE

Amines An amine is a base as well as a nucleophile Some amines are heterocyclic compounds (or heterocycles) Most drugs, vitamins, and many other natural products are heterocycles A natural product is a compound synthesized by a plant or an animal

Organic bases are amines Amines are derivatives of ammonia N 1s 2, 2s 2 2p 1 2p 1 2p lone pair occupies an sp 3 orbital

Amines are bases because of the lone pair on the nitrogen atom - red litmus paper to blue

The lone-pair electrons on nitrogen allows an amine to turn “inside out” rapidly at room temperature

1,4-butanediamine Some Common Amines Both upper amines are 1 o This amine is are 2 o This amine is 3 o This amine is 1 o

Aniline can be converted into useful diazonium salt

Relative Reactivity of Amine The leaving group of a protonated amine cannot dissociate to form a carbocation or be replaced by a halide ion RCH 2 F > RCH 2 OH ~ RCH 2 OCH 3 > RCH 2 NH 2 most reactiveleast reactive HFH 2 O RCH 2 OH NH 3 pK a = 3.2 pK a = 15.7 pK a = 15.5pK a = 36

Reactions of Amines nucleophilic substitution reactions nucleophilic acyl substitution reactions

Oxidation of Amines oxd a hydroxylamine a nitroso compound

Nitrite Ion, Nitrous Acid, and Nitrosyl Cation H+ –O NO O NO H H+O NO H H + + NO + O HH

Example (CH 3 ) 2 NH NaNO 2, HCl H2OH2OH2OH2O (88-90%) (CH 3 ) 2 N NO CH 3 NH 2 +HNO 2 CH 3 OH+N 2 +H 2 O

Nitrosation of Secondary Alkylamines + NO N H + N NO + H + H + N NO nitrosation of secondary amines gives an N- nitroso amine nitrosation of secondary amines gives an N- nitroso amine

Nitrosation of Primary Arylamines gives aryl diazonium ions gives aryl diazonium ions aryl diazonium ions are much more stable than alkyl diazonium ions aryl diazonium ions are much more stable than alkyl diazonium ions most aryl diazonium ions are stable under the conditions of their formation (0-10°C) most aryl diazonium ions are stable under the conditions of their formation (0-10°C) ArN N + RNRNRNRNN+fast slow R + + N2N2N2N2 Ar + + N2N2N2N2

Example: (CH 3 ) 2 CH NH2NH2NH2NH2 NaNO 2, H 2 SO 4 H 2 O, 0-5°C (CH 3 ) 2 CH N N + HSO 4 –

Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

Azo Coupling Diazonium salts are weak electrophiles. Diazonium salts are weak electrophiles. React with strongly activated aromatic compounds by electrophilic aromatic substitution. React with strongly activated aromatic compounds by electrophilic aromatic substitution. Ar N N+Ar' H + Ar N N Ar' an azo compound Ar' must bear a strongly electron-releasing group such as OH, OR, or NR 2.

ExampleOH+ C6H5NC6H5NC6H5NC6H5N N+ OHN NC 6 H 5 Cl –

Amides Features of a Peptide Bond 1.Usually inert 2.Planar to allow delocalisation 3.Restricted Rotation about the amide bond 4.Rotation of Groups (R and R’) attached to the amide bond is relatively free Not acids or bases