Amines are hydrocarbons with an ammonia-based group attached to it. Since the nitrogen in ammonia is trivalent, there are three classes of amines;
Primary amine: RNH2 ; Secondary amine: (R)2NH and Tertiary amine: (R)3N
Of course the alkyl (R) groups need not be the same.
Like ether the common name for amine consist of stating the different alkyl groups present (in alphabetical order) followed by the suffix amine. So (CH3CH2)NH2 will be known as ethylamine, (CH3)(CH3CH2)NH as ethylmethylamine, and (CH3)(CH3CH2)(CH3CH2CH2)N as ethylmethylpropylamine. But like ether, for more complex amines, it is sometimes clumsy to use this system. The IUPAC or Chemical Abstract nomenclature is friendlier.
Tutorial 10.1
Give the name for the following amines, using whichever system is convenient.
(CH3)2CHCH2−C(NH2)H−CH2CH3 and CH3CH2−C(CH3)H−CH2CH2−NHCH3. Answer
PHYSICAL PROPERTIES
Hydrogen bonding is more important for primary amine than secondary amine, and does not exist with tertiary amine. So the boiling point of CH3CH2CH2CH2NH2 is 77.8�C, while that for [CH3CH2]2NH is 56.3�C. The much larger tertiary amine [CH3CH2]3N, with 6 carbons, is only 89.3�C.
Amines are soluble in water and can be easily taken up by living organisms. They get into the food chain and finally end up in our bodies. It can be a nutrient or a threat to our health. So chemists must not discharge amines indiscriminately into the environment.
CHEMICAL PROPERTIES
        |
 |
   |
|
 |
It is best to consider amines as cousins of ammonia, as they show similar chemical properties.
The energy needed for the molecule to invert itself is only about 40 kJ/mol. This is very low as compared to about 350 kJ/mol needed to break a σ−bond. So the thermal energy at ambient condition is sufficient for the inversion to occur. This means an amine does not have a definite tetrahedral geometrical and consequently does not exhibit optical isomerism.
Note: In our discussion we will only refer to the primary amine. The chemistry is applicable to all the other amines. Of course there are diferences in reactivity.As a BASE
As nitrogen is less electronegative than oxygen, so amines are more basic than water. It will dissolve in water to give hydroxide ions.
RNH2 + H2O � RNH3+ + OH‾
Needless to say they are Lewis bases and react with acids to give ammonium-like compounds.
This property can come in useful in separating amines from non-polar organic compounds. Just add sufficient amount of a 10% dilute hydrochloric acid into the mixture. The quaternary ammonium compound formed will dissolve in water. Isolate the aqueous layer and neutralise the solution with a 10% sodium hydroxide solution to regenerate the amine, which is insoluble in an alkaline medium. The amine can then be extracted with ether.
This is the technique used to isolate amines from plants. These natural occurring amines are known as alkaloids.
As a NUCLEOPHILE in SN Reaction
Ammonia is a nucleophile and will react with alkyl bromide;
NH3 + RBr � RNH2 + HBr
Like ammonia, the primary amine will react further to give the secondary and tertiary amines;
|
RNH2 + RBr R2NH + RBr R3N + RBr |
� � � |
R2NH + HBr R3N + HBr R4N+Br‾ |
R4N+Br‾, as expected, is known as a quaternary ammonium bromide. Quaternary ammonium compounds has a definite tetrahedral configuration and cannot perform a nitrogen inversion. So they will exhibit optical isomerism.
E REACTION
Amines will not undergo base- or acid-catalysed Elimination Reaction, but quaternary ammonium hydroxides will.
RCH2CH2−N(R3)+OH‾ + � RCH=CH2 + R3N + H2O
The favoured product will be the less highly substituted alkene.
Hofmann made use of this reaction to prepare alkenes from amines. An amine can be converted to the quaternary ammonium hydroxide with methyl iodide followed by hydrolysis in the presence of silver oxide.
| RCH2CH2−NH2 | + | 3 CH3I | � | [RCH2CH2−N(CH3)3]+I‾ | H2O � Ag2O |
[RCH2CH2−N(CH3)3]+OH‾ |
The quaternary ammonium hydroxide when heated will give − the alkene, the trimethyl amine and water. This degradation of an amine via this series of reactions came to be known as the Hofmann Degradation of amines.
Tutorial 10.2
give the product from the Hofmann degradation of N-methyl-piperidine. Answer
OXIDATION by NITROUS ACID
Nitrous acid, HNO2, is not stable and is generally prepared in the laboratory by mixing sodium nitrite and hydrochloric acid.
NaNO2 + HCl ⇆ HNO2 + NaCl
More precisely, the nitrous acid exist in equilibrium with the nitrosonium ion, [N=O]+
HNO2 + H+ ⇆ H2O + [N=O]+
Amine is oxidised by the nitrosonium ion in the nitrous acid. The lone-electron pair of the amine favours an attack by the nitrosonium cation.
R3N + +N=O ⇆ [R3N−N=O]+
For tertiary amine this is where the reaction stays. No overall reaction takes place. The equilibrium in is favour of the starting material, the tertiary amine and nitrous acid.
For secondary amine the reaction proceeds with the displacement of the proton on the amine, to give a nitrosoamine.
[R2NH−N=O]+ ⇆ R2N−N=O + H+
Nitrosoamines are often coloured, and so their formation is easily visible.
In the case of primary amine, the reaction proceeds even further with the remaining proton of the amine.
RNH−N=O + H+ ⇆ RNH−N=O+H � RN−N−O+H2
RN−N−O+H2 � R+ + N2 + H2O
The carbonium ion will then proceed to give alcohols (with the water), chlorides (with the HCl), or just decompose to give alkenes.
Beside nitrosonium ion, amines can also be oxidised by peroxides and peroxyacids.
The oxidation reaction of amines are of very limited application. However it is important for the fact that burning meat in the open (which is protein, an amine compound) can result in the formation of nitroso compounds which are considered bad for health. So there are some who would advise against eating barbecued meat.
SYNTHESIS of AMINES
Amines are important low volume commercial chemicals (as compared to general purpose chemicals). We will now look at the chemistry of the various processes that are used to prepare them.
AMMONIA with ALKYL BROMIDE
This reaction is not good for preparing amines as it is difficult to control the stage of reaction - primary, secondary, or tertiary. The best we can do is to use it to prepare primary amines. This is done by using an excess of the alkyl bromide and continuously distilling off the amine produced and recycles the unreacted alkyl bromide back into the reaction chamber. This is rather tricky.
Since amines are important health products much research has been conducted to prepare amines in good yield. An example is the Gabriel Synthesis.
This process uses phthalimide to restrict the nucleophilic substitution reaction to just the primary stage;
                  Phthalimide |
− H2O � |
 Resonance Stabilisation |
 |
− Br‾ � |
|
H2O � NaOH |
    Phthalate |
The pthalimide is then recovered for reuse by reacting the phthalate with acid, and then with ammonia.
REDUCTION of NITRILES
Nitriles, RCN, can be easily prepared so it is a good starting material for the preparation of amines. It can be hydrogenated to give primary amines.
| R−C≡N + H2 | Pd/C � |
RCH=NH (an imine) |
H2 � Pd/C |
RCH2NH2 |
The imine can react with the amine to give a secondary amine.
| RCH=NH + RCH2NH2 | − NH3 � |
RCH=NCH2R | H2 � Pd/C |
RCH2NHCH2R |
This by-reaction can be retarded by a high concentration of ammonia according to the Law of Mass Action.
Alternatively we can use an acetic anhydride to block the nucleophilic action of the imine, a "blocking strategy" used in the Gabriel Synthesis.
    |
Ni � |
 |
H2O / OH‾ � |
|
In the laboratory the catalyst of choice would be LiAH4, in place of Ni.
Note: Imines are not particularly stable. They are rapidly hydrolysed by water to give aldehydes (or ketones).REDUCTIVE AMINATION
Secondary amines can be prepared conveniently by reacting aldehyde with a primary amine. This process involves two reactions - a condensation reaction followed by a hydrogenation reaction.(Reactions that produce water as a product are historically known as condensation reaction).
 |
� |   |
H2 / Pt � |
|
Tutorial 10.3
Show by chemical equations how you can prepare diethylamine from acetaldehyde and ammonia, via a hydrogenation process. Answer
ESCHWEILER-CLARKE Reaction
This is also a reductive amination reaction but it does not involve hydrogenation. Instead the imine is reduced by formic acid.
The amine is reacted with formaldehyde along with formic acid at about 100�C. Tertiary amine with a methyl group can be prepared using this reaction.
| R2NH + CH2=O | ⇆ | R2NH−CH2−OH |
| R2NH−CH2−OH + HCOOH | ⇆ | R2N+=CH2 + HCOO‾ + H2O |
| R2N+=CH2 + HCOO‾ | � | R2N−CH3 + CO2 |
The variation here is that instead of an imine intermediate the reaction gave an immonium ion, R2N+=CH2, which can be reduced by the formate ion.
REDUCTION of AMIDES
 |
− H2O � |
|
LiAlH4 � Ether |
|
Organic acids are cheap raw materials for the preparation of amines. One of the most direct route would be to convert the acid into the amide, an easy process, and then reducing the amide to amine.
The reduction can be done with LiAlH4 in an ether solution or diborane in tetrahydrofuran.
|
− H2O � |
|
To prepare secondary and tertiary amines we will have to start with the appropriate amine in place of ammonia.
VIA ISOCYANATE
A different approach to the preparation of primary amine is via alkyl isocyanate. Alkyl isocyanate is easily hydrolysed by water to give a thermally unstable carbamic acid, which decomposes to give a primary amine.
Alkyl Isocyanate |
� |
Carbamic Acid |
∆ � |
|
Curtius found a way to prepare acyl azide, the precursor of isocyanate by reacting acid chloride with sodium azide, while Schmidt uses the acid with sodium azide in the presence of concentrated sulphuric acid.
| Curtius Reaction |
  |
� |
|
Acyl Azide |
| Schmidt Reaction |
|
H2SO4 � |
|
Acyl Azide |
|
− N2 � ∆ |
Acyl Nitrene |
� |
|
Tutorial
How would you prepare N-ethyl-N-methylpropanamide using common laboratory compounds like formaldehyde, acetaldehyde, acetic acid, methyl bromide, ethyl bromide, etc, and other common laboratory reagents?
I would be glad to check your answers if you email them to me.
