Chapter 10: Amines

Amines Nitrogen containing compound Nitrogen is a group 5A element with 5 valence electrons Nitrogen has 3 bonds and 1 lone pair Ammonia derivatives where at least one H is replaced by an alkyl, cycloalkyl, or aryl group

Amines are organic nitrogen compounds, formed by replacing one or more hydrogen atoms of ammonia (NH3) with alkyl groups. Amines are classified as 10, 20, or 30 based on the number of alkyl groups bonded to the nitrogen atom.

Amines Introduction Like ammonia, the amine nitrogen atom has a nonbonded electron pair, making it both a base and a nucleophile. As a result, amines react with electrophiles to form quaternary ammonium salts—compounds with four bonds to nitrogen.

Amines Structure and Bonding An amine N atom is sp3 hybridized and trigonal pyramidal, with bond angles of approximately 109.50. Since an amine nitrogen has four different groups around it, it is technically a stereocenter.

Amines Structure and Bonding However, the chirality of the amine nitrogen can be ignored because the two enantiomers interconvert by passing through a trigonal planar (achiral) transition state.

Amines Structure and Bonding In contrast, the chirality of a quaternary ammonium salt with four different groups cannot be ignored. Because there is no nonbonded electron pair on the nitrogen atom, interconversion cannot occur, and the N atom is just like a carbon atom with four different groups around it.

Structure of Amines CH NHCH CH3 CH | NCH N C H N H Aliphatic amines N bonded to alkyl groups Aromatic Amines N bonded to one or more aryl groups CH 3 NHCH 2 CH3 N C H 3 N H 2 CH 3 | 2 NCH 8

Heterocyclic Amines Heterocyclic aromatic amines When nitrogen is part of an aromatic ring Heterocyclic aliphatic amines Ring is saturated and N is part of a non aromatic ring 9

Naming Amines Amines may be named using either common or IUPAC rules For common names, list the alkyl groups attached to the N in ABC order and use the suffix –amine, which is written as one word Prefixes di- and tri- are used if identical groups are present 10

IUPAC Naming of 1o Amines 1. Select the longest carbon chain that contains the N as the parent 2. Name parent as an alkan-amine by removing the –e of the alkane and replacing it with the suffix –amine 3. # the parent from the end nearest the N 4. The location of the amino group comes before the parent 5. If the parent is substituted, its name and # comes before the parent 11

Nomenclature

IUPAC Naming 1o Amines Compounds with 2 amino groups are named by adding suffix -diamine. The final ‘e’ of the parent hydrocarbon is retained 3 N H 2 | CH CHCH2NH2 1,2- propanediamine H2NCH2CH2CH2CH2CH2CH2NH2 1,6-hexanediamine 13

IUPAC Naming 2o and 3o Amines 2o and 3o amines are named as N-substituted primary amines The largest alkyl chain is considered the parent The other alkyl chains are placed in front of the parent using the prefix N- to denoted that it is attached to the N N,N-dimethylcyclohexanamine CH3NHCH2CH3 N- methylethanamine N(CH3)2

HN—CH3 | CH3—CH2—CH2—NH—CH3 CH3—CH—CH2—CH3 3 2 1 1 2 3 4 N-Methyl-1-propanamine N-Methyl-2-butanamine

C H 2 ( d CH — NH N - methylmethanamine imethylamine ) Aniline 3 CH — NH N - methylmethanamine imethylamine ) Aniline methylaniline H 2 C

Nomenclature Priority If other functional groups are present on an amine, the –NH2 group is a substituent and is called –amino Priority List from highest to lowest: carboxylic acid, aldehyde, ketone, alcohol, amine

Learning Check Give the name and classify: A. CH 3 NHCH 2 B. | NCH 19

Solution A. CH NHCH N-methylethanamine , 2° | B. NCH 3 NHCH 2 N-methylethanamine , 2° | B. NCH N,N- dimethylethanamine , 3° 20

Solution A. 1 - pentanamine CH - NH B. 1,3 - cyclohexanediamine N H 2 21

Physical Properties Amines are polar compounds Both 1° and 2° amines form hydrogen bonds Boiling points are higher than corresponding alkanes but lower than the corresponding alcohols Are soluble if 6 or less carbons are present 23

Boiling Points N-H less polar than O-H. Weaker hydrogen bonding. Tertiary amines cannot hydrogen bond. 24

Physical Properties of Amines Boiling points of amines are higher than those of alkanes but lower than those of alcohols Compound Formula Mass BP(oC) CH3CH3 30 -89 CH3NH2 31 -6 CH3OH 32 65

Basicity of Amines Lone pair of electrons on nitrogen can accept a proton from an acid All amines are weak bases and aqueous solutions of amines are basic Hydroxide ion Methyl- ammonium ion Methylamine + •• - H C 3 N O 26

Amines Interesting and Useful Amines Many low molecular weight amines have foul odors. Trimethylamine [(CH3)3N], formed when enzymes break down certain fish proteins, has the characteristic odor of rotting fish. Putrescine (NH2CH2CH2CH2CH2NH2) and cadaverine (NH2CH2CH2CH2CH2CH2NH2) are both poisonous diamines with putrid odors. They too are present in rotting fish, and are partly responsible for the odors of semen, urine, and bad breath. Naturally occurring amines derived from plant sources are called alkaloids.

Amines Interesting and Useful Amines Histamine, a rather simple triamine that is present in many tissues, is responsible for a wide variety of physiological effects. Understanding the physiological properties of histamine has helped chemists design drugs to counteract some of its undesirable effects. Antihistamines bind to the same active site as histamine in the cell, but they evoke a different response. Examples are brompheniramine and cimetidine.

Amines Interesting and Useful Amines A large number of physiologically active compounds are derived from 2-phenethylamine (C6H5CH2CH2NH2). These compounds include adrenaline, noradrenaline, methamphetamine, and mescaline. Each contains a benzene ring bonded to a two-carbon unit with a nitrogen atom (shown in red).

Neurotransmitters Neurotransmitter – chemical substance that is released at the end of a nerve, travels across the synaptic gap, and then bonds to a receptor site on another nerve, causing a nerve impulse 31

Amines Natural and Synthetic Dyes Three natural dyes known for centuries are indigo, tyrian purple, and alizarin.

Amines Sulfa Drugs In 1935, Gerhard Domagk first used a synthetic dye, prontosil, to kill bacteria. Prontosil and other sulfur containing antibiotics are collectively known as sulfa drugs. Prontosil is not the active ingredient itself—In cells, it is metabolized to sulfanilamide, the active drug.

Amines Sulfa Drugs To understand how sulfanilamide functions as an antibacterial agent, we must examine folic acid, which microorganisms synthesize from p-aminobenzoic acid. Sulfanilamide and p-aminobenzoic acid are similar in size and shape and have related functional groups.

Amines Sulfa Drugs When sulfanilamide is administered, bacteria attempt to use it in place of p-aminobenzoic acid to synthesize folic acid. Derailing folic acid synthesis means that the bacteria cannot grow and reproduce. Sulfanilamide only affects bacterial cells, because humans do not synthesize folic acid, and must obtain it from their diets.