Chapter 16 Amines and Amides

16.1 Occurrence, Names, and Physical Properties of Amines

An amine is basically an ammonia molecule with one or more aliphatic and/or aromatic

organic groups attached. Thus they have the generic formulas NH2R, NHR2, and NR3. If a

carbonyl group lies between the nitrogen and R the compound is called an amide. Amines are

typically named by naming the organic group as a substituent and using the suffix -amine.

This is the old common system and we will use it for the rest of the course. If an -NH2 group is

named as a substituent, it goes by amino-. For example:

O
CH3NH2 (CH3)2NH (CH3)2N(C2H5) CH3CNH2
acetamide
methylamine dimethylamine ethyldimethylamine ethanamide

Aromatic amines are called anilines. When other groups are also attached to the nitrogen in

aniline, they are named as for amines, except that a capital N is placed in front to indicate the

substituent group is bound to the nitrogen, rather than the aromatic ring. A couple of examples

include:

NH2 N(CH3)2

aniline N,N-dimethylaniline

Aromatic amides are analogous to their aliphatic counterparts. Two amines/amides that you

have heard of are:

O H
O
N
HO N N n
H O H
Acetaminophen Nylon-66

N-aceto-4-aminophenol poly(hexamethylene adipamide)

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Many natural products chemicals (these are species extracted from living systems) contain amino

groups. The alkaloids are a class of these materials. If you see a drug end in -ine there is a

good chance of it containing an amino group. Examples include: codeine, morphine, and quinine

(all have pictures in your book on p. 486).

Amines generally have an odor that is ammonia-like to fishy and mildly unpleasant,

although apparently some smell quite bad. A couple of examples of the latter (I assuming here,

never having checked this out for myself) include putricine (1,3-propanediamine) and cadaverine

(1,5-pentanediamine). Amines are weak bases like ammonia, but are frequently little stronger.

Anilines are very weak bases, while amides are not at all basic. Table 16.1 (p. 480) lists the Kbs

of some amines and aniline. For comparison purposes, ammonia has a Kb of 1.8 x 10-5.

Amines tend to form hydrogen bonds like alcohols, but they are weaker. This is because

nitrogen is less electronegative than oxygen, resulting in a decreased attraction between the N

and H on different molecules. Like alcohols their boiling points are higher than is expected from

their molecular size, but because the hydrogen bonding is weaker than in alcohols, the boiling

point increase isnt as large. A table in the right margin on p. 481 of your textbook shows that

the boiling point of methylamine is roughly halfway between those of ethane and methanol.

Likewise, they are much more soluble than comparable hydrocarbons. Also like alcohols, the

effect of the amino group decreases as the size of the molecule increases.

16.2 Chemical Properties of Amines

Since amines are weak bases much like ammonia they react with water much like ammonia.

[ RNH 3+ ][OH - ]
RNH2 (aq) + H2O(l) RNH3+(aq) + OH-(aq) Kb =
[RNH 2 ]
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Anilines engage in the same types of reaction, but since their Kbs are about a million times

smaller than for aliphatic amines, they barely ionize in water. Indeed, the only acid/base reaction

they usually engage in is with strong acids.

Since aliphatic amines are weak bases, their protonation products, RnNH4-n+ (n = 1-3), are

also weak acids. Strong bases react with these ammonium ions to regenerate the parent amines.

RNH3+(aq) + OH-(aq) RNH2 (aq) + H2O(l)

When an amine forms an ammonium-type ion, the product is a solid. It is frequently water

soluble even if the parent amine isnt. Unless the parent amine is miscible with water, the

corresponding ammonium ion will be more water-soluble. These features explain why many

drugs come as the hydrochloride salt. For example, the active ingredient in Sudafed is

pseudephedrine hydrochloride (see below). Do you see where the product name comes from?:

OH H
N+
Cl-
H

As a salt it is easier to package, store, and deliver to the patient. Many pharmaceuticals contain

amino groups and a very large percentage of them are sold as ammonium salts. In fact, any time

you see the phrase hydrochloride following a drugs name, its a good bet that the active form

of the medication is an amine.

As an aside, amines are rarely found free in nature. This is because naturally occurring

water is slightly acidic because of the CO2 that dissolves in it. (Remember that CO2 dissolves in

water to form H2CO3 (carbonic acid which is a weak acid). Therefore amines that are exposed to

environmental water are usually protonated. Amines are found free in restricted environments.

As was just noted, the solubilities of amines in water can be greatly enhanced by converting
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them to ammonium salts (your book calls them amine salts). In this they are much like the

carboxylic acids we learned about in the last chapter (which become more soluble when

deprotonated). In fact, we will see shortly that molecules containing both amine and carboxylic

acid functional groups are quite soluble in water because the latter transfers a proton to the

former yielding an internal double salt.

16.3 Amides of Carboxylic Acids

The bond between the carbonyl carbon and the nitrogen in an amide is called the amide

bond. This bond is a major site of reactivity in the molecule as we shall soon see. Amides with

two hydrogen atoms bound to the nitrogen are called simple amides. Those with one or two

aliphatic or aromatic groups are called amides of amines.

The hydrogen bonding in these molecules is amongst the strongest observed. (See the table

in the margin of p. 487 of your textbook.) A result is that they almost always exist as solids

when pure (as a result of bonding to each other). They are also generally quite water-soluble.

Unlike amines, amides show no measurable basicity. Two factors account for this. Most

importantly, the lone pair of electrons on nitrogen interacts with the carbonyl -bond much like

the -bonds in benzene interact with each other. Also, the electronegative oxygen pulls the lone

pair of electrons towards itself. The effect is to render these electrons unavailable for acid/base

reactions.

Amides are named using the following rule:

Name the corresponding carboxylic acid (i.e. pretend the -NH2 is an OH). Now replace -ic

acid with amide from the common name or replace -oic acid with amide from the IUPAC

name. Thus CH3C(O)NH2 is acetamide or ethanamide, respectively.

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Preparation

In a chemistry lab, the easiest way to make amides is the reaction of an acid chloride with

ammonia or either a primary or secondary amine. For example:

O O
RC-Cl + 2 NH3 RC-NH2 + NH4Cl
O O
RC-Cl + 2 HNR2 RC-NR2 + [NH2R2]Cl

Your book also points out that amides can be prepared from anhydrides but this method is

more difficult and is less commonly used. Since acyl chlorides and anhydrides are far too

reactive to exist in the body, the biochemical production of amides follows a different route. The

molecule transferring the acyl group has the general form:

R O
H2N-CH-CR'

In the reaction the -R group is replaced by an -NH2 group. The product molecule

R O
H2N-CH-CNH2

is called a peptide. Well return to this type of molecule in Chapter 20.

Hydrolysis

In the presence of strong acids or bases amides hydrolyze to carboxylic acids or their salts

respectively.
O O
+ +
RC-NH2 + H2O + H RC-OH + NH4
O O
+ OH-
RC-NR2 RC-O- + NH3

Since strong acids and bases dont exist in the body, enzymes catalyze the hydrolysis
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reaction and permit it to happen in vivo. This enzyme reaction ishowyour body breaks down

proteins.

January 20, 2002