Difficulty: Intermediate | Prerequisites: Functional group identification, acid-base chemistry, pKa concepts
Amines are nitrogen-containing organic compounds named using IUPAC rules that specify substituents on nitrogen with an "N-" prefix. Amino acids exist as zwitterions at physiological pH, and their isoelectric point (pI) is calculated by averaging the two pKa values that flank the neutral (zwitterionic) form. Basicity of amines depends on how available the nitrogen lone pair is, which is reduced by resonance delocalisation, electron-withdrawing groups, and incorporation into aromatic systems.
Amine
An organic compound containing a nitrogen atom bonded to one or more carbon groups (and possibly hydrogen). Think of it as ammonia (NH3) with one or more hydrogens swapped for carbon chains.
Primary amine (1°)
Nitrogen bonded to one carbon group and two hydrogens (R-NH2). In simple terms, one arm of the nitrogen is attached to a carbon chain, the other two hold hydrogens.
Secondary amine (2°)
Nitrogen bonded to two carbon groups and one hydrogen (R2-NH). Two of nitrogen's arms reach carbon chains.
Tertiary amine (3°)
Nitrogen bonded to three carbon groups (R3-N). All three available bonds go to carbon, none left for hydrogen.
Zwitterion
A molecule carrying both a positive and a negative charge simultaneously, with a net charge of zero. In simple terms, one end of the molecule has donated a proton and the other has accepted one, so both charges coexist.
Isoelectric point (pI)
The pH at which a molecule (typically an amino acid) has no net electrical charge, meaning it exists predominantly in its zwitterionic form. Calculate it by averaging the two pKa values that bracket the neutral species.
pKa
A measure of acid strength: the lower the pKa, the stronger the acid (the more readily it gives up a proton). Think of it as a number telling you how tightly a group holds onto its proton.
Basicity
The tendency of a species to accept a proton. A stronger base has a more available lone pair of electrons and accepts protons more readily.
Conjugate acid
The species formed when a base accepts a proton. The stronger the base, the weaker its conjugate acid (and the higher the conjugate acid's pKa).
Resonance delocalisation
The spreading of electrons (particularly a lone pair) across multiple atoms through overlapping p-orbitals. When nitrogen's lone pair is delocalised, it is less available to accept a proton, making the amine a weaker base.
Amine nomenclature follows the same backbone-identification logic as other functional groups, with a few nitrogen-specific conventions.
Identify the longest carbon chain attached to nitrogen. This becomes the parent chain, and the suffix changes to "-amine" (e.g. pentanamine, butanamine).
Number the parent chain so that the carbon bearing the nitrogen gets the lowest possible locant.
Substituents directly on nitrogen are prefixed with "N-" to distinguish them from substituents on the carbon chain.
If nitrogen carries two identical substituents, use "N,N-di" (e.g. N,N-dimethyl).
If nitrogen carries two different substituents, list them alphabetically, each with its own "N-" prefix.
The full name is assembled alphabetically by substituent, followed by the parent chain name with its "-amine" suffix.
Worked examples from the exam review:
A tertiary amine with ethyl, propyl, and a dimethyl-pentane backbone: N-ethyl-3,4-dimethyl-N-propyl-2-pentanamine.
A secondary amine with a butyl group on a four-carbon chain: N-butyl-1-butanamine.
Zwitterion formation
At physiological pH, an amino acid does not exist as a fully protonated or fully deprotonated species. Instead, the carboxyl group (-COOH) loses its proton to become -COO⁻, while the amino group (-NH2) picks up a proton to become -NH3⁺. The result is a dipolar ion (zwitterion) with no net charge.
When drawing a zwitterion from a neutral amino acid structure, move the proton from the carboxylic acid oxygen to the nitrogen.
Calculating the isoelectric point (pI)
The isoelectric point is the pH at which the amino acid carries zero net charge. To find it:
Identify which form of the amino acid is the zwitterion (net charge = 0).
Find the two pKa values that sit on either side of that neutral form, i.e. the pKa for the protonation that would make it +1, and the pKa for the deprotonation that would make it -1.
Average those two pKa values: pI = (pKa1 + pKa2) / 2.
Worked example from the exam review:
An amino acid with three ionisable groups has pKa values of 2.52, 9.84, and 10.62. The zwitterion (net charge 0) sits between the first and second deprotonation events. The two flanking pKa values are 2.52 and 9.84.
pI = (2.52 + 9.84) / 2 = 6.18
For amino acids with a side-chain that ionises (like serine's -OH or an extra -NH2), you still average the two pKa values flanking the zwitterionic form. The trick is identifying which two those are, since the side-chain adds a third equilibrium.
Basicity reflects how readily the nitrogen lone pair can be donated to a proton. Anything that makes that lone pair less available reduces basicity.
Factors that decrease basicity (in order of typical impact):
Aromaticity of the nitrogen lone pair. If nitrogen's lone pair is part of an aromatic pi system (as in pyrrole), it cannot be donated without destroying aromaticity. This makes pyrrole-type nitrogens extremely weak bases.
Resonance with adjacent pi systems. An aniline-type nitrogen (NH2 bonded to a benzene ring) has its lone pair partially delocalised into the ring. This reduces availability compared to a simple alkylamine, but the lone pair is not required for aromaticity, so it is still more basic than pyrrole.
Electron-withdrawing groups. Groups like -CF3 on the ring pull electron density away from nitrogen through induction, further reducing basicity.
Alkyl groups increase basicity by donating electron density to nitrogen through induction (hyperconjugation), making the lone pair more available.
Worked ranking from the exam review:
Four amines ranked in order of increasing basicity: D < C < A < B
D (pyrrole-type nitrogen): lone pair is part of the aromatic sextet, making it the weakest base by a wide margin.
C (aniline with a -CF3 group): resonance into the ring plus the electron-withdrawing CF3 both reduce basicity.
A (aniline, no extra substituents): resonance into the ring reduces basicity, but no electron-withdrawing group.
B (simple aliphatic amine): no resonance effects, alkyl group donates electron density. Strongest base of the set.
"All nitrogen-containing compounds are basic." They are not. Pyrrole's nitrogen lone pair is locked into the aromatic system and is essentially unavailable for protonation. Amides are also very weak bases because the lone pair is delocalised into the carbonyl.
"pI is just the average of all pKa values." Only for amino acids with two ionisable groups. When a side-chain adds a third pKa, you must identify which two flank the zwitterion and average only those two.
"Aniline is a strong base because it has an NH2 group." The NH2 is on a benzene ring, so its lone pair is partially delocalised. Aniline's pKb is much higher than a simple alkylamine like methylamine.
"N- in a name means the substituent is on the second carbon." The "N-" prefix specifically means "on nitrogen," not on any carbon in the chain. Carbon substituents never carry the N- prefix.
⚠️ IUPAC naming of amines is a staple exam question. You will be given a structure and asked to produce the name, or vice versa. Practise placing the "N-" prefix correctly.
⚠️ Isoelectric point calculations appear frequently. The most common error is averaging all three pKa values instead of identifying the two that flank the zwitterion.
⚠️ Basicity ranking questions test whether you can distinguish resonance effects (aniline vs alkylamine), inductive effects (CF3 withdrawal), and aromatic lone-pair involvement (pyrrole). Expect four or five structures to rank.
⚠️ Drawing zwitterions from neutral amino acid structures is a quick-marks question. Remember: carboxylate loses its proton, amine gains one.
True or False: A tertiary amine has three hydrogens bonded to nitrogen. (False, it has zero hydrogens on nitrogen.)
Fill in the blank: The isoelectric point is calculated by averaging the two pKa values that ______ the zwitterionic form. (flank / bracket)
True or False: Pyrrole is a stronger base than aniline. (False, pyrrole is much weaker because its lone pair is part of the aromatic pi system.)
Fill in the blank: Substituents on nitrogen in IUPAC names carry the prefix ______. (N-)
True or False: An electron-withdrawing group on the ring increases amine basicity. (False, it decreases basicity.)
Q: An amino acid has pKa values of 2.34 (carboxyl), 9.60 (alpha-amino), and 12.48 (side-chain guanidinium). What is its isoelectric point?
A: The zwitterion (net charge 0) exists between the second and third deprotonations. pI = (9.60 + 12.48) / 2 = 11.04. This amino acid is arginine.
Q: Rank the following in order of increasing basicity: pyrrole, aniline, cyclohexylamine.
A: Pyrrole < aniline < cyclohexylamine. Pyrrole's lone pair is aromatic, aniline's is partially delocalised into the ring, and cyclohexylamine's is fully available on an sp3 nitrogen.
Q: Give the IUPAC name for a secondary amine where nitrogen bears a methyl group and is attached to C-2 of butane.
A: N-methyl-2-butanamine.
Q: Why is the conjugate acid of an aliphatic amine (pKa around 10 to 11) much stronger than the conjugate acid of pyrrole (pKa around 0)?
A: Protonating pyrrole destroys aromaticity, making the protonated form extremely unfavourable. The equilibrium lies far to the left, so pyrrole barely accepts a proton. Aliphatic amines have no such penalty.
Q: Draw the zwitterion of glycine (H2N-CH2-COOH).
A: The carboxyl loses its proton to give -COO⁻, and the amino group gains a proton to give -NH3⁺. The structure is ⁺H3N-CH2-COO⁻.
This material connects directly to acid-base chemistry from earlier in the course. The pKa reasoning used for basicity ranking is the same framework applied to alcohol acidity, carboxylic acid strength, and later to enolate stability. Zwitterion and pI concepts reappear in biochemistry when discussing protein charge at physiological pH, gel electrophoresis, and buffer systems.
Related Terms / Search Tags
amine nomenclature, IUPAC amine naming, N-prefix, primary secondary tertiary amine, amino acid zwitterion, isoelectric point calculation, pI formula, pKa averaging, basicity ranking, pyrrole basicity, aniline basicity, electron-withdrawing group basicity, resonance and basicity, conjugate acid pKa, organic chemistry I exam 4, UMN organic chemistry