The second mechanism leading to the lower basicity of aromatic amines is the electron-withdrawing inductive action of aromatic ring sp2 hybridized carbons compared to aliphatic amine sp3 hybridized carbons.

• The unshared pair of electrons on nitrogen in an aromatic amine is drawn toward the ring, making it less accessible for protonation to generate the amine's conjugate acid.

• These are the same two causes that make phenoxide ions less basic than alkoxide ions (as shown in the image attached).

Electron-releasing groups (e.g., methyl, ethyl, and other alkyl groups) enhance the basicity of aromatic amines, whereas electron-drawing groups (e.g., nitro and carbonyl groups) reduce it.

• The electron-withdrawing inductive action of the electronegative halogen causes the drop in basicity with halogen replacement.

• The drop in basicity generated by nitro substitution is caused by a combination of inductive and resonance effects, as demonstrated by comparing the pKa values of 3-nitroaniline and 4-nitroaniline conjugate acids.

Amines are ammonia derivatives in which one or more hydrogens have been replaced with alkyl and/or aryl groups.

• One hydrogen of ammonia is replaced by a carbon in the form of an alkyl or aryl group in primary amines.

• Secondary amines have two ammonia hydrogens replaced by carbon in the form of alkyl and/or aryl groups.

• All three hydrogens of ammonia are replaced with carbon in the form of alkyl and/or aryl groups in tertiary amines.

Four alkyl and/or aryl groups are linked to nitrogen in quaternary ammonium ions, resulting in a positively charged species.

Aromatic amines contain at least one aromatic ring connected to the nitrogen atom, whereas aliphatic amines have solely alkyl groups bound to nitrogen.

• The nitrogen atom is present in heterocyclic amines.

• Aliphatic amines are designated similarly to alcohols in IUPAC, with the exception that the suffix -amine is used and a number is used to indicate the location of the amine group.

• The common term aniline is used by IUPAC for simple derivatives of C6H5NH2, however certain common names, such as toluidine and anisidine, are kept for some substituted anilines.

Secondary and tertiary amines are referred to as N-substituted primary amines, with the biggest group serving as the parent amine; the smaller groups bound to nitrogen are then referred to by the prefix N.

• N-methylaniline and N,N-dimethylcyclopentanamine are two examples.

• Several common heterocycles, such as pyridine, indole, purine, quinoline, and isoquinoline, maintain their common names in IUPAC nomenclature.

The common names are obtained by alphabetically listing the alkyl groups linked to the nitrogen atom.

Amines are polar chemicals, and both primary and secondary amines may form intramolecular hydrogen bonds.

• Primary and secondary amines interact with solutes predominantly through hydrogen bonding, have significantly higher melting and boiling temperatures, and are more soluble in water than similar hydrocarbons.

• Amines have lower boiling points than similar alcohols because H-N hydrogen bonds are weaker than H-O hydrogen bonds.

Because amines are weak bases, their aqueous solutions are basic.

• The conjugate acids of aliphatic amines have pKa values in the 10–11 range.

Because electron-releasing alkyl groups stabilize the alkylammoniun ion, alkyl groups make amines somewhat more basic.

• Near neutral pH and in biological fluids, alkyl amines are protonated and positively charged.

• Aromatic amines are significantly less basic than aliphatic amines, with conjugate acid pKa values in the 4–5 range.

Aromatic amines have a lower basicity because the nitrogen lone pair participates in resonance with the aromatic p system, a stabilizing connection that is lost via protonation.

• This resonance interaction necessitates that the N atom of aromatic amines be nearly or totally sp2 hybridized and so planar, which is not always the case.

The basicity of N atoms in heterocyclic aromatic amines is determined by whether the N lone pair belongs to the aromatic p system.

• Because the lone pair on N is not part of the p system in pyridine, protonation has no effect on aromaticity.

• Because the pyridine lone pair is in a moderately electronegative sp2 orbital, the pKa of the conjugate acid of pyridine is 5.25, which is lower than that of an alkyl amine.

Only one N atom in imidazole can be protonated since the lone pair on the other N atom is part of the aromatic p system and protonation would destroy the aromaticity.

• The aromatic p system includes the lone pair on the ring N atom in pyrrole.

• Because the protonated guanidinium ion is highly stabilized by charge delocalization, pyrrole is a very poor base because protonation on N would disrupt the aromaticity.

• Guanidine groups are very basic organic groups because the protonated guanidinium ion is highly stabilized by charge delocalization.

Amines react with strong acids to form water-soluble salts, which allows amines to be separated from water-insoluble compounds.

• Amines can be synthesized by processes such as epoxide ring opening, addition of nitrogen nucleophiles to carbonyls followed by reduction, amide reduction, nitrile reduction, and arenes nitration followed by reduction.

• In most cases, alkylation of amines leads in overalkylation.

• By reacting a haloalkane with the strong nucleophile (and weak base) sodium or potassium azide, followed by reduction with LiAlH4, primary amines can be produced in high yield.

Azides can also be used to ring open epoxides before reducing them to produce amino alcohols with trans stereoselectivity.

Nitrous acid, which is frequently generated in situ by combining NaNO2 with acid, interacts differently with amines depending on whether they are primary, secondary, tertiary, or aromatic.

• Nitrous acid participates in proton transfer processes and is a source of the nitrosyl cation, a weak but significant electrophile.

• Tertiary aromatic amines can undergo electrophilic aromatic substitution with nitrous acid, while secondary amines react with nitrous acid to form N-nitrosamines.

Because primary amines react with nitrous acid to produce diazonium ion intermediates that lose N2 and produce a range of substitution and elimination products, the reaction is not often effective in synthetic chemistry.

• The Tiffeneau-Demjanov reaction, which yields a one-carbon ring expansion of a cyclic b-aminoalcohol and creates a cyclic ketone, is a synthetically valuable variation of the process.

The Hofmann elimination reaction occurs when a quaternary ammonium halide reacts with damp silver oxide to form a quaternary ammonium hydroxide, which is then heated to produce an alkene.

• Hofmann elimination reactions are stereoselective for anti eliminations and produce mostly the least substituted alkene, which contradicts Zaitsev's rule.

• The steric bulk of the ammonium group is considered to drive deprotonation by base to the least hindered site, resulting in the creation of the less substituted alkene in Hofmann elimination regiochemistry.

• The Hofmann rule is considered to be followed when eliminations generate mostly the least substituted alkene.

When a tertiary amine is treated with hydrogen peroxide, an amine oxide is formed, which when heated yields an alkene and an N,N-dialkylhydroxyamine in a Cope elimination process.

• Unless a conjugated double bond can be formed, the Cope elimination is syn stereoselective and shows no preference for regiochemistry, in which case the conjugated product predominates.