MCAT Organic Chemistry > Amines

Background

Amine Nomenclature

In the IUPAC, amines are named by switching the -e ending of the longest possible alkane chain’s name that can be made in the molecule, and replacing it with the suffix -amine. An N is used to label substituents attached to the nitrogen in secondary or tertiary amines. Each substituent is given its own separate N label. When there is a higher priority substituent on the molecule, the prefix -amino is used.

The suffix –amine has the highest priority

The prefix –amino is used when the amine does not have the highest priority

Nitrogen Containing Functional Groups

Amine Properties

The boiling point of amines is between that of alcohols and alkanes.

Certain amines can be optically active if inversion is inhibited by sterics

Amines have lone pairs so they are bases/nucleophiles

A nitrogen double bonded to a carbon (imine) acts just like an oxygen double bonded to a carbon (carbonyl)

Many nitrogen-based functional groups are easily reduced to amines

Nitrogen Inversion

Nitrogen inversion is an inversion of the sp3 orbital occupied by the lone pair. This process causes the chirality of a nitrogen containing molecule to rapidly interconvert, making it impossible to isolate any enantiomers of a nitrogen containing compound. Thus, all nitrogen compounds where the nitrogen contains a lone pair of electrons are racemic mixtures if chirality is even possible.

About the MCAT - Organic Chemistry - Amines - Nitrogen Inversion Image

The nitrogen atom in an amine is effectively sp3 hybridized. The orbitals are made up of three substituents and a lone pair of electrons, creating a tetrahedral hybridized structure. This lone pair of electrons is extremely important in the chemistry of nitrogen. It gives nitrogen containing molecules their basicity and nucleophilic properties.

Since amines are bases, they can readily accept a hydrogen proton and become ammonium ions.

Amine Stereochemistry

Amines are divided up into three degrees based on the number of hydrogens and nitrogen in the molecule. These range from primary to tertiary. Each amine can have different properties and reactivity levels.

Primary and secondary amines can form hydrogen bonds, but nitrogen has a lower electronegativity than oxygen, so amines will have weaker hydrogen bonding than alcohols, and thus lower boiling points.

Tertiary amines cannot hydrogen bond at all, because they have no hydrogen, so the boiling point of tertiary amines will be even lower than primary or secondary amines. Tertiary amines may also be chiral and are always racemic due to spontaneous inversions that occur at room temperature. Tertiary amines undergo nitrogen inversion because the proton gets removed and added during acid-base equilibrium.

Primary (1°) AmineSecondary (2°) AmineTertiary (3°) Amine
Attached to one alkyl groupAttached to two alkyl groupsAttached to two alkyl groups
About the MCAT - Organic Chemistry - Amines - Primary AmineAbout the MCAT - Organic Chemistry - Amines - Secondary AmineAbout the MCAT - Organic Chemistry - Amines - Tertiary Amine

Quarternary ammonium compound is attached to four alkyl groups, carries positive charge and exists as a salt. 4° amine groups may also be chiral and if they are no inversion occurs.

Amines display different characteristic infrared absorption peaks based on the degree of amines.

Primary Amines (R-NH2) contain two N-H bonds which display 2 peaks around 3300 cm-1

Secondary Amines (R2-NH) contain one N-H bond which displays a single peak around 3300 cm-1

Tertiary Amines (R3-N) contain no N-H bonds and do not show up in infrared spectroscopy.

Basicity of Amines

Amines are basic molecules. They prefer to gain a proton and will act as nucleophiles in most circumstances. If an amine is neutral, it will be extremely difficult to strip it of this proton, so on the MCAT, if you see a neutral amine, it will be involved in the reaction as a nucleophile.

R-NH2 → R-NH3+

Amides, however, can much more easily be stripped of a proton. Since the carbonyl group next to the nitrogen on an amide is electron withdrawing, it will distribute any negative charge that forms along its resonance hybrid structure when the nitrogen is stripped. The negative charge is easily placed on the oxygen atom and thus distributed.

Carbocation Stabilization

A carbonium ion adjacent to an amine can be given the amine’s lone pair, stabilizing the resonance structure with a double bond.

Substituent Effects on Basicity

Since amines will donate some of its electron density to any aromatic ring that it is attached to, aromatic amines will essentially be weaker bases than aliphatic amines. The amine can also form stable resonance structures with the aromatic ring, and thus will have a stable hybridized structure.

pKb of alkyl amines = ~4

The pKb of aromatic amines are much less basic than their alkyl counterparts. (ex. Aniline pKb = 9.42) Other substituents on the aromatic ring containing an amine substituent can effect the basicity of the amine substituent. Amines can also function as weak acids. Since the pKas of amines = ~35, a strong base is required to de-protonate amines.

Electron donating groups increase basicity.

Electron donating groups on aromatic amines increase the basicity of the compound. This is due to the fact that the electron donating groups increase the nitrogen's electron density.

Electron withdrawing groups decrease basicity

Any electron withdrawing substituents will reduce the basicity of the aromatic ring because they will further localize electron density away from the amine substituent, making its hydrogens more acidic. Electron donating substituents on the aromatic ring will localize electron density towards the amine substituent, and therefore increase the basicity of the aromatic amine.

Note that any substituent that has an ortho- position with respect to the amine substituent on an aromatic ring will decrease the basicity of the aromatic amine. This is because of steric hinderance caused by ortho substituents next to an amine substituent. Essentially, an ortho substituent will have steric interactions with protonated amines, thus destabilizing the amine and making it easier for the amine to lose a proton.

Amine Reactions

Amide Formation

MCAT Amines - Amide Formation

Amine + Acid Derivative → Amide

When an amine is reacted with any acid derivative that has a good leaving group, such as acid chloride, an amide can be formed. This reaction is extremely important in the biological process of peptide bond formation in proteins

Amine + Carboxylic acid → Amide

Nitrous Acid Reaction

Ar-NH2 + HONO → Ar-N2+ + H2O + OH-

Nitrous acid has the molecular formula HNO2 and its structural formula is HONO. An aromatic amine reacted with nitrous acid creates an Ar-N2+ ion. HONO dissociates in solution to NO+ and OH-, which provides the strong nucleophile NO+ for the reaction.

Alkylation

MCAT Amines - Alkylation

An amine attacks the alpha carbon of an alkyl halide, creating secondary amine. The halide acts as a leaving group and binds with a hydrogen lost when the amine bonds to the alkyl chain, forming an alkyl-halide byproduct. This process can be repeated until four substituents are bonded to the amine, forming a substituted ammonium ion.

Hofmann Elimination

MCAT Amines - Hofmann Elimination

Hofmann elimination is also known as exhaustive methylation. This is the process of the conversion of an amine into an alkene and another amine. First, the amide is converted into a quarternary ammonium iodide, by treating the amide with excess methyl iodide.

The intermediate, in other words, will have methyl groups attached to the amine in all of the places that used to be bonded to hydrogens or lone pairs, and a negative iodide ion, I- will form a complex with the intermediate. Then, the reaction is treated with silver oxide and water, which displaces the iodide ion and turns the intermediate into ammonium hydroxide. After ammonium hydroxide is heated, it breaks down to predominately form the least substituted alkene, and also forms another amine.

Hofmann elimination reactions form a less substituted double bond

MCAT Organic Chemistry

Organic Chemistry Topics