Amines and Amides - StFXpeople.stfx.ca/bjmaclea/CHEM 150/Chapters/Chapter 17.pdf · atoms in organic compounds ... For complicated amine structures, ... polyfunctional carboxylic

Amines and Amides

Chapter 17

Bonding characteristics of nitrogen atoms in organic compounds

• We saw already that carbon atoms (Group 4A) form four bonds to other atoms in organic compounds.

• And oxygen atoms (Group 6A) form two bonds.

• Nitrogen atoms (Group 5A) require three bonds to give them octets. Normally, nitrogen atoms are involved in three covalent bonds to other atoms.

.

...

.

...

. ..

. ..

The important arrangement for this chapter

Structure and classification of amines

• Amines are organic derivatives of ammonia (NH3), in which one or more alkyl, cycloalkyl, or aromatic groups replace hydrogen and bond to the nitrogen atom.

Ammonia (NH3) is a weak base. Amines are also weak bases.

..


• Amines are classified as primary, secondary, and tertiary, as we have seen previously for alcohols.

• For alcohols, the type of carbon atom (1o, 2o, 3o) bound to the –OH group determined whether the alcohol was primary, secondary, or tertiary.

• For amines, it is the number of carbon groups that are bound to the nitrogen atom.

1o amine 2o amine 3o amine

Structure and classification of amines • This is an important difference in the way that 1o, 2o, and 3o

classification is given.

tert-butanola 3o alcohol

tert-butylaminea 1o amine

Nomenclature for amines

• Common and IUPAC systems are used extensively for naming amines.

• In the common system, rules similar to what we have seen for ethers are employed, naming the alkyl/aromatic groups attached to the functional group, and then following these with “amine”

Methylamine Trimethylamine Methylpropylamine

Methylphenylamine CyclohexyldimethylamineFor simple amines, this

is a good naming system

Nomenclature for amines

• The IUPAC system for naming amines is as follows:

– Select the longest carbon chain bound to the nitrogen as the parent chain

– Name the chain by changing the alkane name for this chain: drop the “e” and add “amine”

– Number the chain to give the nitrogen the lowest numbering

– The number and identity of other substituents (including any on the main chain) are indicated at the beginning of the amine name (some are attached to N)

For complicated amine structures, this is probably the better way of naming amines.


• Some examples. First, 1o amines

2-Butanamine

1-Butanamine

# to indicate placement of NH2 group 4-C chain (“butane”; - “e” + “amine”)


• For di- and trisubstituted amines, the non-parent chains are indicated as N-bonded:

N,N-Dimethyl-1-propanamine

N-Ethyl-N-methyl-2-butanamine

longest carbon chain = 4 carbons

longest carbon chain = 3 carbons


• For diamines, the molecule is named as an “alkane-diamine” with NH2 groups numbered.

• …and for cases where NH2-substituted alcohols or other compound cases are involved, the NH2-group is called an “amino” substituent.

1,4-Butanediamine

3-Aminobutanoic acid don’t need to name polyfunctional carboxylic acids

an example of an amino acid


• In cases where substituted parent chains are encountered, the substituents are named at the beginning of the compound’s name:

4,N-dimethyl-2-pentanamine

One CH3 substituent is on the amine’s N and one CH3

substituent is on C#4 of the 2-pentanamine chain.

Doesn’t matter if you write N or 4 first here


• Aromatic amines involve an amine-type nitrogen bound to an aromatic ring. The simplest case for these is aniline.

Aniline 3-Bromo-2-chloroaniline

phenol benzaldehyde benzoic acid

Remember: other aromatic compounds seen so far


• For substituted anilines, the substituent names are treated in a manner similar to what was shown for substituted parent chain cases:

Aniline 3,N-DimethylanilineN-Ethyl-N-methylaniline

Same idea as before. Now the benzene is treated as the “parent” part of the name.

Isomerism for amines

• Skeletal and positional isomers for amines are possible.

• In skeletal isomers, the carbon chain components of the amines differ

3-Hexanamine 2-Methyl-3-pentanamine

C6H15N

Isomerism for amines

• Positional isomers are also possible.

3-Hexanamine 2-Hexanamine

Physical properties of amines

• Amines tend to be gases for low molecular weight cases (e.g. up to (CH3)3N, trimethylamine) and many heavier ones are liquids at room temperature.

• One very noticeable thing about amines is that they tend to exhibit strong odors. For example, some have a “fishy” smell

Cadaverine(1,5-Pentanediamine)

Putrescine(1,4-Buntanediamine)


• Amine boiling points are intermediate of those for alcohols and alkanes of similar molar mass.

• Because of the presence of N-H bond(s) in primary and secondary amines, hydrogen-bonding is sometimes possible; however, because N is not as electronegative as O, the N-H bond is not as polar as an O-H bond (weaker H-bonding).

H-bonding between tertiary amines not possible


• Amines tend to be water-soluble because of H-bonding interactions with water molecules. In fact, amines having fewer than six carbon atoms are infinitely water-soluble.

• Water-solubility decreases as: – Chain length increases, and,

– The degree of N-substitution increases

Basicity of amines • Ammonia is one of the few examples of a weak base we

looked at in the first semester. It reacts with water molecules to produce OH- ions, making the resulting solution basic:

NH3 + H2O D NH4+ + OH-

• The resulting ion (NH4+) is called an ammonium ion.

• Amines react with water to produce ammonium-like species.

CH3NH2 + H2O D CH3NH3+ + OH-

-. . ... .. . ... .

ammonium ion

Basicity of amines

• Naming substituted ammonium ions:

– Named similar to amine, but with the term “ammonium ion” instead of amine

-

+

Methylamine

Methylammonium ion

Others:

Trimethylammonium ion Anilinium ion

Tetraethylammonium ion

Basicity of amines

• Amines are better bases than oxygen-containing compounds.

• A comparison:

-

Ethanoate ion:0.1 M sol'n in water has pH ~ 8.9

Ethylamine:0.1 M sol'n in water has pH ~ 11.9

A carboxylate ion

(from ethanoic acid)

Organic bases • amines • conj. bases of carboxylic acids

Amine salts

• Amines, because they are basic, can react with acids in neutralization reactions. The reaction produces an amine salt, as follows:

R-NH2 + H-Cl D R-NH3+Cl-

amine amine salt

Naming: named as an ammonium chloride

Example: (CH3)3N+Cl- is Trimethylammonium chloride

Amine salts are ionic compounds in which the positive ion comes from the substituted ammonium and the negative ion comes from an acid used to react with the parent amine.

Amine salts

• Amine salts are water-soluble; many amines (having higher molar masses) are not. Thus, in order to introduce an amine-based drug into he body, it is often converted into the salt form.

• Many pharmaceuticals possess nitrogen centers that are protonated to the ammonium form, to make them water-soluble, or to stabilize them (they are often called “hydrochlorides”).

Paxil

·HCl Paxil hydrochloride

(water-soluble, shelf-stable)

Amine salts • The neutral form of an amine drug is often called its “free-

base” form.

• In this neutral form, the drug may be vaporized (because the intermolecular forces that keep it in a condensed state at room temperature can be overcome by heating).

• The ionic form has a very high boiling point and usually cannot be vaporized without decomposing the structure.

+Cl-

cocaine cocaine hydrochloride

free-base form ionic (salt) form

not water-soluble

water-soluble

Heterocyclic amines • Heterocylic compounds involve ring structures that possess

non-carbon atoms. We saw some examples in earlier chapters (cyclic ethers, cyclic esters, etc.)

• Nitrogen heterocycles are frequently encountered in biochemistry. Some examples are:

NicoteneCaffeine

Heterocyclic amines

• The following nitrogen heterocycles are found frequently in biologically relevant structures. For example, the purine structure is present in caffeine (drug), adenine and guanine (DNA).

Heterocyclic amines

• The nitrogen heterocycle shown below is used for oxygen transport in the body. The heme structure (right) is present in the bloodstream as a component of a much bigger molecule (hemoglobin) and acquires/releases O2.

porphyrin ring Heme, a component of hemoglobin

Selected biologically important amines

• Neurotransmitters: substances that are released at the end of a nerve which travel across the synaptic gap to another nerve and trigger a nerve impulse by binding to a chemical receptor site.

Selected biologically important amines

Norepinepherine

Dopamine

Seratonin

Acetylcholine

Alkaloids

• There are some very important nitrogen-containing plant extracts (alkaloids) that are used in medicinal science (all of which are amines):

Morphine Codeine

Heroin

Hydrocodone Oxycodone

Structure and classification of amides

• Amides possess a functional group that consists of a C=O (carbonyl) directly bound to a nitrogen:

• The amide functional group involves a nitrogen atom (and lone pair), but unlike an amine, the nitrogen center is not basic, due to the electron-withdrawing effect of the C=O group.

For amides, R, R’,, and R” can be • carbon-based, or • hydrogen

Structure and classification of amides • Amides may be primary, secondary, or teritary:

1o amide 3o amide2o amide

1o amine 2o amine 3o amine

Remember, for amines:


• In terms of their structure, amines may be aromatic (benzene substituents); for example, benzamide:

• They may also be cyclic, or even involve multiple amide groups in a single ring:


• In Ch-16, we looked at lactones, which were cyclic esters:

• Lactams are cyclic amides (and heterocycles)

-lactone -lactam -lactam-lactam

Lactams

Nomenclature of amides

• IUPAC system for naming amides:

– Like esters, amides are made using carboxylic acids. The portion that comes from the carboxylic acid is named as a carboxylic acid first, before dropping the “-oic acid” from the name and adding “-amide”

– Substituents attached to the nitrogen are prefixed with “N” to indicate their position; other substituents on the parent chain are named as part of the parent chain (unlike for amines)

Ethanoic acid(carboxylic acid)

N-methylethanamide(amide)

Methyl ethanoate(ester)

Ethanamide(amide)

Nomenclature of amides

• Some examples:

• For aromatic cases:

Butanamide N-Methylbutnamide

N,N-Diethyl-3-methylbutanamide

Benzamide N,N-Dimethylbenzamide

N,N,3,5-Tetramethylbenzamide

Ethyl and methyl substituents on a butanamide molecule

Selected amides and their uses

• Urea is one of the simplest amides, formed by reaction between CO2 and ammonia in a series of metabolic reactions.

• Acetominophen is an aromatic amide

• Barbiturates derive from barbituric acid (sedatives/tranquilizers) are cyclic amides, made from urea and malonic acid:

Urea

Barbituric acid

UreaPentanedioic acid

Malonic acid

2H2O

Preparation of amides

• Amides are prepared in a manner similar to what we’ve already seen for esters. A condensation reaction involving a carboxylic acid is needed, this time with an amine:

H2O100 oC

catalyst

amidification (like esterification)

amide functional group


• For amide formation to happen, the temperature must be high (at room temperature, an acid-base neutralization reaction happens instead).

• Also, the amine used in the reaction must be either a primary or secondary amine (can’t be a tertiary amine).

100 oC

catalyst

Room Temp. -

acid base carboxylate salt


Ammonia + carboxylic acid 1o amide

1o amine + carboxylic acid 2o amide

2o amine + carboxylic acid 3o amide

H2O100oC

catalyst..

100oCH2O

catalyst..

100oCH2O

catalyst..

Preparation of amides • Reactions that make esters from carboxylic acids and alcohols

are called esterification reactions.

• Reactions that make amides from carboxylic acids and amines (or ammonia) are called amidification reactions. Thus amidification reactions are condensation reactions.

• In the condensation, the carboxylic acid loses the OH and the amine loses a H atom:

carboxylic acid amine amide

H2O100 oC

catalyst

H+(cat)

H2O

alcoholcarboxylic acid ester

amidification

esterification

Hydrolysis of amides

• Like esters, amides can undergo hydrolysis. This reaction results in the amide being broken up into amine and carboxylic acid starting materials:


Amidification

Amide hydrolysis


hydrolysis and saponification of amides

This bond was created by amidification. The same one breaks during hydrolysis.


• The products of the hydrolysis reaction will depend on the acidity/basicity of the reaction conditions.

heat

Amide hydrolysis

carboxylic acid(derivative?)

amine(derivative?)

amide acidic/basic conditions used

Remember what an acid does: donates protons (H+ ions); bases accept protons. Acids react with bases, not with other acids.


• Under basic conditions, the carboxylic acid is produced as an carboxylic acid salt:

H2Obasic pH (NaOH)

heat

Amide hydrolysis

carboxylic acid amineamide

Remember,: carboxylic acids are acids amines are bases

Amide hydrolysis carried out under basic conditions is called amide saponification.

H2O

NaOH

-Na+

carboxylic acid salt


• Overall, the reaction would look like this:

• Example:

H2O

NaOH

Na+-heat

carboxylic acid salt amineamide

NaOH

H2ONa+-heat

carboxylic acid salt amineamide

Hydrolysis of amides • Under acidic conditions, the amine is produced as an

ammonium salt:

H2Oacidic pH (HCl)

heat

Amide hydrolysis

carboxylic acid amineamide

Remember,: carboxylic acids are acids amines are bases

HCl

Cl-

ammonium salt


• Overall, under acidic conditions, the reaction would look like this:

• Example:

H2O Cl-HCl

heat

carboxylic acid

ammonium salt

amide

H2O Cl-HCl

heat

carboxylic acid

ammonium salt

amide

Physical properties of amides

• The simplest amides (methanamide, N-methyl, and N,N-dimethyl derivatives) are liquids at room temperature, and all unbranched amides having 2 or more carbons on their C-chain side are solids.

• The secondary and teritary amides have lower melting points, with tertiary amides having lower melting points than secondary amides (less opportunity for H-bonding).

Methanamide

N-Methylmethanamide N,N-Dimethylmethanamide

Primary amides have higher boiling points than carboxylic acids that have the same number of carbons. In order of increasing amide boiling points (for a given molar mass): 3o < 2o < 1o.

Boiling points

Polyamides • Like we saw for esters, amide condensation reactions can be

used to make polymers (another polycondensation reaction).

• As for polyesters, di-functional reactants are needed for polymerization (i.e. a diamine and a dicarboxylic acid):

......

n

a dicarboxylic acid a diamine

a polyamide

heat

Polyamides

• Nylon-6,6 is a polyamide. It can be synthesized from Hexanedioic acid and 1,6-Hexanediamine:

Nylon-6,6a polyamide

n

Polyamides

• Kevlar (bullet-proof

vests) is also a

polyamide:

Documents

Amines and Amides - StFXpeople.stfx.ca/bjmaclea/CHEM 150/Chapters/Chapter 17.pdf · atoms in organic compounds ... For complicated amine structures, ... polyfunctional carboxylic