Structure and Classification of Amines

Structure and Classification of Amines • Amines are derivatives of ammonia, the same way that alcohols are derivatives of water • Amines have a nitrogen, with hydrogens and/or alkyl groups attached • The shape around the nitrogen is pyrimidal and there is a lone pair of electrons on the nitrogen • Amines can be classified as 1º, 2º or 3º, just like carbons, based on how many alkyl groups are attached to the nitrogen

Naming Amines • Most simple amines are named by their common names (which are accepted by IUPAC) • For common names, the alkyl groups attached to the N are named alphabetically, and amine is added to the end • IUPAC rules are more often used for more complicated amines - find the longest chain bonded to N, and replace -e in alkane name with amine - number at end nearest N and give number for position of N - the prefixes di, tri etc. are used for multiple amines - when amines are with other functional groups they are called amino groups

Naming Aromatic and Heterocyclic Amines • Aromatic amines are named as analines • When alkyl groups are attached to the aromatic N, they are written as N-alkyl at the beginning of the name • As substituents on the ring they are named as amino groups • Heterocyclic amines have one or more nitrogens as part of the ring and are usually named by their common names - know those that are boxed

Structure & Classification • heterocyclic amine: an amine in which the nitrogen atom is part of a ring • heterocyclic aliphatic amine: a heterocyclic amine in which the ring is saturated (has no C=C bonds) • heterocyclic aromatic amine: the amine nitrogen is part of an aromatic ring

Nomenclature • Amine salts • when four atoms or groups of atoms are bonded to a nitrogen atom, as for example CH3NH3+, nitrogen bears a positive charge and is associated with an anion as a salt • name the compound as a salt of the corresponding amine • replace the ending -amine (or aniline or pyridine or the like) by -ammonium (or anilinium or pyridinium or the like) and add the name of the anion

Physical Properties • Like ammonia, low-molecular-weight amines have very sharp, penetrating odors • trimethylamine, for example, is the pungent principle in the smell of rotting fish • two other particularly pungent amines are 1,4-butanediamine (putrescine) and 1,5-pentanediamine (cadaverine)

Physical Properties of Amines • Primary and secondary amines can H-bond with themselves, so have relatively high boiling points • However, because the N-H bond is less polar than the O-H bond, amines have lower boiling points than alcohols • Primary and secondary amines have boiling points similar to aldehydes and ketones • Tertiary amines can’t H-bond with themselves, and so have boiling points near those of ethers and hydrocarbons • Smaller amines (less than 5 carbons) are soluble in water - primary and secondary amines are more soluble than tertiary because they have more H-bonding with water

an N-H---N hydrogen bond is weaker than an O-H---O hydrogen bond because the difference in electronegativity between N and H (3.0 - 2.1 = 0.9) is less than that between O and H (3.5 - 2.1 = 1.4)

Basicity of Amines and Amine Salts • Amines are weak bases that partially ionize in water to form ammonium ions and hydroxide ions • When treated with acids, amines form salts, without the formation of water • Quaternary ammonium ions have 4 alkyl groups attached to the nitrogen, and have a permanent positive charge on the N (no H attached to N, so can’t react with bases) • Amine salts are solids at room temperature and are soluble in water, making them much more useful as medicines

Reactions of Amines • The most important chemical property of amines is their basicity • amines, whether soluble or insoluble in water, react quantitatively with strong acids to form water-soluble salts

Basicity of Amines • Like ammonia, amines are weak bases, and aqueous solutions of amines are basic • the acid-base reaction between an amine and water involves transfer of a proton from water to the amine

Basicity of Amines • aliphatic amines have about the same base strength, and are slightly stronger bases than NH3 • aromatic and heterocyclic aromatic amines are considerably weaker bases than aliphatic amines • note that while aliphatic amines are weak bases by comparison with inorganic bases such as NaOH, they are strong bases among organic compounds

Basicity of Amines • Given the basicities of amines, we can determine which form of an amine exists in body fluids, say blood • in a normal, healthy person, the pH of blood is approximately 7.40, which is slightly basic • if an aliphatic amine is dissolved in blood, it is present predominantly as its protonated (conjugated acid) form

Alkaloids • Alkaloids are naturally occurring compounds that contain nitrogen and have basic properties • They have a wide variety of structures, including simple amines, aromatic amines, and heterocyclic amines • Some examples of alkaloids are caffeine and the opiates

Amides • The functional group of an amide is a carbonyl group bonded to a nitrogen atom

Structure and Naming of Amides • Amides are considered derivatives of carboxylic acids • They have an amino group attached to the carbonyl • Most simple amides are known by their common names • For common names the -ic acid is changed to -amide • For IUPAC names the -oic acid is changed to -amide • Alkyl groups attached to the amide nitrogen are indicated by writing N-alkyl or N,N-dialkyl before the amide name

Amides • a cyclic amide is called a lactam • the penicillins are referred to as b-lactam antibiotics

Physical Properties and Stability of Amides • Primary and secondary amides can H-bond with themselves, and so have high melting and boiling points • Tertiary amides can’t H-bond with themselves, so have lower melting and boiling points than primary or secondary • Amides have higher melting and boiling points than carboxylic acids because they are more flat (due to delocalization of electrons), so they stack better • Amides (except formamide) are solids at room temperature • Smaller amides (5 carbons or less) are soluble in water • Unlike amines, amides are not basic • They are also very stable (unreactive) compared to esters • This is due to the delocalization of the nonbonded pair of electrons (through resonance)

Preparation of Amides from Carboxylic Acids • Amines (except tertiary) can react with carboxylic acids to produce amides (amidation) • The reaction is similar to esterification • Unfortunately, the reaction is of little synthetic use - amines are bases and will remove a proton from a carboxylic acid, making the acid carbonyl unreactive - primary amides can be formed using ammonia this way, but yields are not great - amides are generally prepared by other methods

Preparation of Amides • In principle, we can form an amide by treating a carboxylic acid with an amine and removing -OH from the acid and an -H from the amine • in practice what occurs if the two are mixed is an acid-base reaction to form an ammonium salt • if this salt is heated to a high enough temperature, water is eliminated and an amide forms

Hydrolysis of Amides • Amides can be hydrolyzed to carboxylic acids using either acid or base, similar to the hydrolysis of esters • However, amides are much more resistant to hydrolysis than esters, which is what makes proteins so stable • In the stomach, hydrolysis of amide bonds in proteins is facilitated by enzyme catalysts • Amide bonds are much more common in medicines than esters due to this resistance to acid-catalyzed hydrolysis (the drugs are more likely to make it through the stomach)

Hydrolysis of Amides • amides require more vigorous conditions for hydrolysis in both acid and base than do esters • hydrolysis in hot aqueous acid gives a carboxylic acid and an ammonium ion • hydrolysis is driven to completion by the acid-base reaction between ammonia or the amine and the acid to form an ammonium ion • each mole of amide requires one mole of acid

Hydrolysis of Amides • hydrolysis of an amide in aqueous base gives a carboxylic acid salt and ammonia or an amine • hydrolysis is driven to completion by the acid-base reaction between the carboxylic acid and base to form a salt • each mole of amide requires one mole of base

Structure and Classification of Amines