Source: Organic Chemistry, The Ohio State University
Difficulty: Intermediate | Prerequisites: Functional groups, Lewis acid/base theory, SN2 mechanism basics, conformational analysis (Newman projections), pKa concepts.
Amines are nitrogen-containing organic compounds and one of the most important functional group families in organic chemistry. Chapter 22 covers how amines are named, classified, and how their structure determines their physical properties and basicity. This material builds directly on your knowledge of Lewis acids and bases, nucleophilic substitution, and conformational analysis. If you are comfortable drawing Newman projections and understand pKa, you are ready for this.
This is Part 1 of 3 covering Alkyl and Aryl Amines. Part 2 covers Preparation of Amines. Part 3 covers Reactions of Amines (Hoffmann Elimination, Diazonium Salts, Azo Coupling).
Amines are organic derivatives of ammonia, classified as primary (1°), secondary (2°), or tertiary (3°) depending on how many carbon groups are bonded to nitrogen. They are named using either the "amino" prefix or the "amine" suffix. Amines are basic because of the nitrogen lone pair, but arylamines (nitrogen on a benzene ring) are weaker bases than alkylamines because the lone pair delocalises into the ring. Nitrogen in amines is sp3-hybridised and pyramidal, but it inverts rapidly, so you cannot isolate individual enantiomers at room temperature.
Tags: amine, amino, primary amine, secondary amine, tertiary amine, quaternary ammonium salt, arylamine, alkylamine, nitrogen inversion, pKa, basicity, lone pair
Primary amine (1°)
A nitrogen bonded to one carbon group and two hydrogens (R-NH2). In simple terms, one R group on nitrogen.
Secondary amine (2°)
A nitrogen bonded to two carbon groups and one hydrogen (R2NH). Think of it as two R groups sharing a nitrogen.
Tertiary amine (3°)
A nitrogen bonded to three carbon groups and no hydrogens (R3N). All three positions on nitrogen are taken by carbon groups.
Quaternary ammonium salt
A positively charged nitrogen bonded to four carbon groups (R4N+). No lone pair remains, so no inversion is possible. This is the one case where a nitrogen centre can be a stable stereogenic centre.
Aliphatic amine (alkylamine)
An amine where nitrogen is bonded to sp3 carbon(s). These are more basic than arylamines.
Arylamine
An amine where nitrogen is bonded directly to an aromatic ring (e.g. aniline). The lone pair on nitrogen delocalises into the ring, making it less available for protonation and therefore less basic.
Nitrogen inversion
The rapid "umbrella flip" of the nitrogen lone pair through a planar transition state. The barrier is only about 6 kcal/mol, so amines racemise at room temperature.
Aniline
The simplest arylamine: an NH2 group bonded directly to a benzene ring. The parent compound for understanding arylamine basicity and reactivity.
Pyridine
A six-membered aromatic ring with one nitrogen atom replacing a CH. The nitrogen lone pair is in an sp2 orbital in the plane of the ring, not part of the aromatic system.
Piperidine
The fully saturated (non-aromatic) version of pyridine. A six-membered ring with one NH.
Pyrrole
A five-membered aromatic ring with one NH. Here the nitrogen lone pair is part of the aromatic pi system, which makes pyrrole an extremely weak base.
Pyrrolidine
The fully saturated version of pyrrole. A five-membered ring with one NH.
LDA (lithium diisopropylamide)
A very strong, non-nucleophilic base made by treating diisopropylamine with n-BuLi. Used to deprotonate at positions adjacent to carbonyls without adding to the carbonyl itself.
There are two naming conventions, plus many common names you need to memorise.
"Amino" as a substituent prefix. When the amine group is not the highest-priority functional group, name it as an amino substituent on the parent chain. Example: 1-amino-2,4-dimethylcyclohexane.
"Amine" as a parent suffix. When the amine is the principal functional group, name the compound as an alkylamine. Example: cyclohexylamine (same molecule as aminocyclohexane).
N,N- prefix for substituents on nitrogen. If the nitrogen carries alkyl groups beyond the parent chain, label them with N,N-. Example: N,N-dimethylaminocyclohexane (both methyl groups sit on nitrogen, not the ring). Example: N,N-dimethylaniline (nitrogen on benzene with two methyl groups).
Common names to memorise. Pyridine (six-membered aromatic ring, one N), piperidine (saturated version of pyridine), pyrrole (five-membered aromatic ring, one NH), pyrrolidine (saturated version of pyrrole). These appear constantly in biological chemistry and pharmaceuticals.
By degree of substitution. Count the number of carbon groups directly bonded to nitrogen. One carbon group = 1° (primary). Two = 2° (secondary). Three = 3° (tertiary). Four (with a positive charge) = quaternary ammonium salt.
Aliphatic vs. aromatic. If nitrogen is bonded to an sp3 carbon, the amine is aliphatic. If nitrogen is bonded directly to an aromatic ring carbon, it is an arylamine.
Do not confuse amine classification with alcohol/halide classification. For alcohols and halides, you classify by the carbon the group is attached to. For amines, you classify by what is on the nitrogen itself. A nitrogen bonded to a tertiary carbon but carrying two hydrogens is still a primary amine.
Amines adopt staggered and eclipsed conformations around the C-N bond, just as alkanes do around C-C bonds. The energy difference between staggered and eclipsed conformations depends on the molecule. Bond lengths decrease in the order C-C > C-N > C-O, which slightly affects the torsional strain per hydrogen interaction going from ethane to methylamine to methanol.
Nitrogen in a simple amine has four groups around it (three bonds plus one lone pair), giving sp3 hybridisation and a pyramidal shape.
The lone pair can "flip" through a planar (sp2) transition state to the other side of the nitrogen. The barrier to this inversion is only about 6 kcal/mol.
Because the barrier is so low, if R, R', and R'' are all different (making nitrogen a potential stereogenic centre with four distinct groups), the amine racemises far too rapidly at room temperature to isolate individual enantiomers.
When nitrogen carries four carbon groups and a positive charge (R4N+), there is no lone pair and no inversion is possible. Quaternary ammonium salts with four different groups can therefore exist as stable, isolable enantiomers.
Although you cannot resolve a free amine at nitrogen, you can resolve amines using chiral acids (forming diastereomeric salts). The source PDF shows the classic method: reacting a racemic amine with a single enantiomer of a chiral carboxylic acid to produce diastereomeric ammonium carboxylate salts, which can then be separated.
Amines can hydrogen bond, but not as effectively as alcohols or water.
Boiling point trend (CH4 < NH3 < H2O). Methane has no hydrogen bonding, ammonia has moderate hydrogen bonding, and water has the strongest. The electronegativity of nitrogen is less than oxygen, so N-H bonds are less polarised than O-H bonds.
Primary amines hydrogen-bond better than secondary amines. A primary amine (R-NH2) has two N-H bonds available for hydrogen bonding, while a secondary amine (R2NH) has only one. Tertiary amines (R3N) have no N-H bonds at all, so they cannot donate hydrogen bonds (though they can accept them via the lone pair).
Molecular weight matters too. When comparing amines of similar substitution, the heavier molecule will generally have the higher boiling point, all else being equal.
This is one of the most exam-tested parts of the chapter.
The nitrogen lone pair can accept a proton from water: NH3 + H2O ⇌ NH4+ + OH-. The pKa of a protonated amine (R3NH+) is roughly 10 to 11, making R3N a good base. The pKa of a protonated amide ion (R2NH) is roughly 35 to 38, making R2N- a very strong base.
Compounds of the form RC(O)-NR2 (amides in the carbonyl sense) are not basic at nitrogen. Two reasons:
Resonance. The nitrogen lone pair delocalises into the carbonyl, making it unavailable for protonation. If protonation does happen, it occurs on oxygen, where resonance structures can stabilise the positive charge.
Inductive effect. If nitrogen were protonated, the positive charge would sit right next to the partially positive carbonyl carbon. That is electrostatically unfavourable.
Strong bases such as alkyl lithiums (R-Li) can deprotonate amines. n-BuLi reacting with diisopropylamine in THF produces LDA (lithium diisopropylamide), a bulky, non-nucleophilic base widely used in enolate chemistry, plus butane as a byproduct.
The nitrogen lone pair on an arylamine (Ar-NH2) delocalises into the aromatic ring through resonance. This makes the lone pair less available for protonation, so arylamines are less basic than alkylamines.
Electron-donating groups (CH3, OCH3, NH2) on the ring increase basicity. They push electron density toward nitrogen, making the lone pair more available.
Electron-withdrawing groups (CN, CHO, COOR, NO2) on the ring decrease basicity. They pull electron density away from nitrogen through the ring.
Amine basicity equilibrium: R3N + H2O ⇌ R3NH+ + OH-
pKa of protonated alkylamines (R3NH+): roughly 10 to 11
pKa of protonated amine anion (R2NH): roughly 35 to 38
Barrier to nitrogen inversion: approximately 6 kcal/mol
Bond length order: C-C > C-N > C-O
Boiling point trend (hydrogen bonding strength): H2O > NH3 > CH4
LDA formation: diisopropylamine + n-BuLi (in THF) → LDA + butane
Amines are everywhere in biology and medicine. Amino acids, the building blocks of proteins, are amines. Many pharmaceutical drugs contain amine functional groups (antihistamines, antidepressants, local anaesthetics like lidocaine). The basicity of amines is exploited in drug design: a protonated amine is water-soluble, which matters for how a drug is absorbed and distributed in the body.
Students often classify amines the same way as alcohols or halides, by looking at the carbon the group is attached to. For amines, you classify by what is bonded to nitrogen itself. A primary amine has one R group on nitrogen, regardless of whether that R group is a primary, secondary, or tertiary carbon.
Students sometimes assume that because nitrogen has four groups around it (three bonds + lone pair), a chiral amine should be resolvable. It is not, because nitrogen inversion is too fast at room temperature. Only quaternary ammonium salts can hold chirality at nitrogen.
Students frequently forget that amide nitrogen (RC(O)-NR2) is not basic. The lone pair is tied up in resonance with the carbonyl. This is a different use of the word "amide" from the strongly basic amide anion (R2N-).
Confusing pyrrole and pyridine basicity: pyridine is a reasonable base (its lone pair is in an sp2 orbital in the plane of the ring, not part of the aromatic system). Pyrrole is an extremely weak base because its nitrogen lone pair is part of the aromatic pi system, and protonating it would destroy aromaticity.
⚠️ Classifying amines as 1°, 2°, 3° by the nitrogen (not the carbon) is a classic exam trick question.
⚠️ Nitrogen inversion and why you cannot resolve simple amines at room temperature comes up on nearly every exam covering this chapter.
⚠️ Explaining why arylamines are less basic than alkylamines (resonance delocalisation of the lone pair into the ring) is a standard short-answer or multiple-choice question.
⚠️ Distinguishing amide basicity (not basic at nitrogen) from amine basicity (basic) is heavily tested. Be ready to draw resonance structures showing why the amide lone pair is unavailable.
⚠️ Substituent effects on arylamine basicity (electron-donating groups increase it, electron-withdrawing groups decrease it) are commonly tested with a "rank in order of basicity" question.
True or false: A tertiary amine has three hydrogen atoms bonded to nitrogen. Answer: False. A tertiary amine has three R groups and zero hydrogens on nitrogen.
Fill in the blank: The barrier to nitrogen inversion in amines is approximately ___ kcal/mol. Answer: 6 kcal/mol.
True or false: Aniline is a stronger base than cyclohexylamine. Answer: False. Aniline (an arylamine) is a weaker base because the lone pair delocalises into the ring.
True or false: Quaternary ammonium salts can be chiral at nitrogen. Answer: True. No lone pair means no inversion, so four different groups give a stable stereogenic centre.
Fill in the blank: In amide bonds (RC(O)-NR2), protonation preferentially occurs on ___ rather than nitrogen. Answer: Oxygen.
Q: Classify the following amine as primary, secondary, or tertiary: (CH3)3C-NH2.
A: Primary. There is only one carbon group bonded to nitrogen (the tert-butyl group). The fact that the carbon is tertiary is irrelevant; amine classification is based on nitrogen's bonds.
Q: Explain why the nitrogen atom in a simple amine (where R ≠ R' ≠ R'') is not a stable stereogenic centre at room temperature.
A: The barrier to nitrogen inversion is only about 6 kcal/mol. The nitrogen rapidly flips through a planar sp2 transition state (which has a mirror plane), interconverting the two enantiomeric forms. This means the amine racemises too quickly to isolate either enantiomer.
Q: Rank the following in order of increasing basicity: aniline, cyclohexylamine, p-nitroaniline.
A: p-nitroaniline < aniline < cyclohexylamine. The nitro group is electron-withdrawing, further reducing the availability of the nitrogen lone pair. Aniline is less basic than cyclohexylamine because the lone pair delocalises into the aromatic ring.
Q: Why is an amide (RC(O)-NH2) not basic at nitrogen, even though it contains an NH2 group?
A: The nitrogen lone pair is delocalised into the carbonyl by resonance, making it much less available for protonation. In addition, protonation at nitrogen would place a positive charge next to the already partially positive carbonyl carbon (inductive destabilisation). Protonation occurs preferentially on oxygen instead.
Q: What reagent combination produces LDA, and why is LDA useful?
A: n-BuLi reacting with diisopropylamine in THF produces LDA plus butane. LDA is useful because it is a very strong base (pKa of the conjugate acid is about 36) but is too bulky to act as a nucleophile, making it ideal for generating enolates without addition to the carbonyl.
Amine basicity connects directly to acid-base chemistry from earlier in the course (pKa, conjugate acid-base pairs). The resonance argument for why arylamines are weaker bases is the same reasoning used to explain why carboxylate anions are stabilised: delocalisation of a lone pair or charge across multiple atoms.
Nitrogen inversion and stereochemistry link back to conformational analysis (Chapter 4) and chirality (Chapter 5). The resolution of amines using chiral acids is an application of diastereomer separation, the same principle used for resolving any racemic mixture.
The basicity and nucleophilicity of amines set up the preparation and reaction chapters that follow. Understanding why amines are good nucleophiles (lone pair on nitrogen) is essential for SN2 alkylation, reductive amination, and acyl substitution reactions.
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