[O Chem] Nitrogen Compounds

[PHYSICAL PROPERTIES]

Are the boiling point of amines higher/lower than hydrocarbons with similar M_r?

Higher.

More energy is required to overcome the stronger intermolecular hydrogen bonding/permanent dipole-permanent dipole interactions in amines compared to instantaneous dipole-induced dipole interactions in hydrocarbons.

• (1-2º amines: H-bonding since they have a H atom attached to EN N atom)

• (3º amines: pd-pd because they do not have a H atom attached to EN N atom)

[PHYSICAL PROPERTIES]

Small amines are soluble in water. Why?

Does the solubility of amines increase/decrease as the size of the alkyl group(s) become bulkier?

Energy released by the formation of hydrogen bonds between amine and water molecules is sufficient to overcome hydrogen bonds between amine molecules and between water molecules.

As alkyl groups get bulkier, the molecule becomes less polar and hence less soluble in water.

[BASICITY]

Explain the basicity of amines.

Amines are Lewis bases as they have a

• lone pair of electrons on N

• which is available for donation to form dative bonds

Amines are Bronsted-Lowry bases in water as they

• accept a H+ from water

[BASICITY]

Relative basicities of 1º, 2º and 3ª amines in gaseous phase

Increase in basicity from 1º to 3º.

• More electron donating-alkyl groups on N

• Increases electron density on N, making the lone pair more available for donation

[BASICITY]

Relative basicities of 1º, 2º and 3ª amines in aqueous phase

3º amines may be less basic than 2º amines.

• The presence of more bulky alkyl groups increases the steric hindrance to the lone pair of electrons on the N atom

[BASICITY]

State and explain the relative basicities of ammonia, ethylamine and phenylamine.

Phenylamine < ammonia < ethyleamine

• The electron-donating ethyl group in ethylamine increases the electron density on the N atom, making the lone pair more available for donation to form dative bonds with H+

• The lone pair of electrons on the N atom delocalises into the benzene ring, decreasing the electron density on the N atom, making the lone pair less available for donation to form dative bonds with H+

[BASICITY]

Explain why pyridine has a higher Kb than diphenylamine.

In diphenylamine, the lone electron pair on N resides in the p-orbital, which overlaps side-on with the electron clouds of the adjacent benzene rings, delocalising into the benzene rings and being less available for donation to form dative bonds with H atoms. In pyridine, the p-orbital forms a pi bond with the adjacent carbon atom. Hence the lone pair of electrons on N resides in the sp2 hybrid orbital and is unable to delocalise into the ring, making it more available for donation to form dative bonds with H atoms.

[PREPARATION]

How do you prepare a primary amine from a nitrile?

Reduction

1. LiAlH4 in dry ether

2. H2, Ni catalyst, high pressure

[PREPARATION]

How do you prepare a 1º amine from a halogenoalkane?

Nucleophilic substitution

Excess ethanolic NH3, heat in sealed tube

[PREPARATION]

How do you form an amine from an amide? (Two possible reactions)

For one of the reactions, state the other product that forms.

• Basic hydrolysis, KOH/NaOH, heat under reflux, carboxylate ion

• Reduction, LiAlH4 in dry ether

[PREPARATION]

How do you form phenylamine form nitrobenzene?

Reduction

Sn in excess concentrated HCl, heat under reflux, followed by NaOH (aq)

[PREPARATION]

What is the purpose of adding NaOH after using Sn to reduce phenylamine?

Liberate amine via acid-base reaction (deprotonate)

[REACTIONS]

How do you form 2º amine from 1º amine?

Nucleophilic substitution

Limited R-X in ethanol, heat in sealed tube

[REACTIONS]

Why must the R-X nucleophile be limited in nucleophilic substitution with 1º amines?

Excess R-X will result in polysubstitution

[REACTION]

How do you form an ammonium salt from an amine?

Acid-base/neutralisation

Any acid

[EXTENSION]

Why are amines soluble in acidic medium?

The amine undergoes neutralisation to give an ammonium salt, which forms strong ion-dipole interactions with water molecules, releasing enough energy to overcome hydrogen bonds between water molecules.

[REACTIONS]

How do you form amides from amines?

Condensation

Anhydrous RCOCl

[EXTENSION]

Why does RCOCl need to be anhydrous in the condensation reaction with amine?

RCOCl will undergo hydrolysis with water to form COOH

[EXTENSION]

Why can’t 3º amines undergo condensation reaction with RCOCl to form an amide?

The amine has to lose a hydrogen atom to form the amide. Tertiary amines do not have a H atom bonded to the N atom.

[EXTENSION]

Why can’t RCOCl undergo condensation with COOH to give an amide?

Acid-base reaction will occur between acidic COOH and basic amines to give an ammoniums salt.

[REACTIONS]

Compare the relative susceptibilities of phenylamine and benzene to electrophilic substitution.

The -NH2 group in phenylamine strongly activates the benzene ring towards electrophilic substitution. Hence, electrophilic substitution with X(aq) occurs readily at room temperature without the need for a Lewis acid like FeX3 to form a trisubstituted product.

[TESTS]

How do you distinguish between phenol and phenylamine?

Neutral FeCl3 solution

Phenol will give a violet complex, while no violet complex is observed for phenylamine.

[EXTENSION]

Can phenylamine undergo electrophilic substitution with dilute nitric acid like phenol?

No.

• Phenylamine will undergo acid-base reaction with nitric acid as it is a Bronsted-Lowry base.

• The -NH3+ substituent formed is electrophilic, deactivating the ring, a catalyst will hence be needed for electrophilic substitution to occur.

• The -NH3+ substituent is. 3-directing group

[PREPARATION OF AMIDES]

How do you prepare amides?

Condensation

Amine, anhydrous RCOCl

[NEUTRALITY OF AMIDES]

What makes amides neutral?

The parallel adjacent p-orbitals of the N atom and C=O group overlap. The lone pair of electrons on N delocalises into the C=O bond, making it unavailable for donation to form dative bonds with H+

[REACTIONS OF AMIDES]

What are the reagents, conditions and products of acidic and basic hydrolysis of amides?

• Acidic hydrolysis: H2SO4/HCl (aq), heat under reflux, carboxylic acid and ammonium salt

• Basic hydrolysis: KOH/NaOH (aq), heat under reflux, carboxylate ion and amine

[REACTIONS OF AMIDES]

What are the different nitrogen-containing products of acidic and basic hydrolysis of 1º, 2º and 3º amides respectively?

• 1º: Ammonia/ammonium ion

• 2º: Alkylammonia/alkylammonium salt

• 3º: 2º amine/2º ammonium salt

[REACTIONS OF AMIDES]

Considering the products of the acidic and basic hydrolysis of amides, explain why both reactions are irreversible.

• Acidic hydrolysis: The N atom in the protonated ammonium salt has no available lone pairs to undergo nucleophilic attack.

• Basic hydrolysis: The negative charge on the oxygen atom of the carboxylate ion delocalises into the adjacent C=O, making the acyl carbon non-electrophilic and hence non-susceptible to attack by the nucleophilic amine.

[REACTIONS OF AMIDES]

How do you form an amine from an amide?

Reduction

LiAlH4 in dry ether

[TEST FOR AMIDES]

How do you test for the presence of an amide? (there is only one way)

Basic hydrolysis

1. Add NaOH (aq), heat to liberate amine

2. Gas evolved* turned moist red litmus paper blue

*the gas evolved is NH3 ONLY for primary amines

[AMINO ACIDS]

Define ‘zwitterion’

A compound with no overall charge, but contains separate parts which are positively and negatively charged.

[AMINO ACIDS]

Explain the amphoteric nature of zwitterions

• When acid is added, zwitterion acts as a base by accepting a proton with its -COO- group

• When alkali is added, zwitterion acts as an acid by donating a proton from its -NH3+ group

[AMINO ACIDS]

The specific pH at which only the zwitterion of an amino acid is present is…

isoelectric point (pI)

[AMINO ACIDS]

How do you calculate pI when given a range of pKa values?

1. Deduce the structure of the zwitterion and hence the pKa values of the equations that sandwich it

2. pI = (pKa1+ pKa2)/2

[AMINO ACIDS]

Which form of amino acid is present when pH>pI and pH<pI?

• pH>pI: anionic form

• pH<pI: cationic form

• pH=pI: zwitterionic form

[AMINO ACIDS]

At what pH regions can amino acids act as buffers?

pH near pKa

[AMINO ACIDS]

Which COOH group gets deprotonated first?

a-COOH

• The conjugate base of the a-COOH is more stable due to its greater proximity to the electron-withdrawing -NH3+ group, which disperses the negative charge to a greater extent, reducing the intensity of the negative charge.

• The a-COOH can dissociate more, giving a stronger acid.

*usually, a-COOH is more acidic

[AMINO ACIDS]

In the separation of a mixture of amino acids via electrophoresis, what are the direction and distance of migration determined by?

• direction: charge of amino acid

• distance: molecular weight

[AMINO ACIDS]

When do you use ‘peptide bonds’ over ‘amide bonds’?

When referring to protein polymers made up of amino acids

Peptide bonds form between a-COOH and a-NH2 of amino acid molecules.

[AMINO ACIDS]

When deciding if an amine can be further protonated, what is the consideration factor?

Presence of sp2 hybrid orbital to form sigma bond with a H atom.

[AMINO ACIDS]

What makes an N atom sp2-hybridised?

Directly bonded to sp2-hybridised C atom.

[AMINO ACIDS]

Explain the relative basicities of N(a) and N(b).

N(b) is more basic. The lone pair of electrons on N(a) resides in an sp2 hybrid orbital, which has greater s-character than sp3 hybridised N(b). The lone electron pair is more attracted to the nucleus and is hence less available for forming dative bonds.