Structure and Classification of Amines

1. 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

2. 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

3. 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

4. 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

7. 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

9. 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

10. 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

11. 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)

12. 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

13. 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)