Download Amines: Nitrogen is the fourth most abundance element…

Amines: Nitrogen is the fourth most abundance element…
Biologically active amines:
Alkaloids are amine compounds that are naturally derived from plant sources. Notice
the similarity in structures. New drug therapies are typically developed by taking a
drug with known capabilities and changing the structure in subtle ways to mimic or
increase the activity of the drug without negative side effects.
CLASSIFICATIONS: Primary
RNH2
Secondary
R2NH
Tertiary
R3N
Quaternary Ammonium Salt
Å
R4N
Xy
Example of formation of Quaternary Ammonium Salt:
IUPAC Rules:
1. Simple Amines – Name alkyl groups (alphabetically) and end with “amine”
2. Complex Amines – Similar rules to alcohols
Suffix for an amine : “-amine”
If the amine is secondary or tertiary (i.e. has more than one alkyl group attached to
nitrogen), the largest alkyl group is considered to be the parent and the others are
substituents on nitrogen (N-substituents).
In terms of priorities, the amine group is below that of the alcohol, and above alkenes
and alkynes. If the amine group is not the highest priority functional group than the
amine group becomes a substituent (prefix) and is named as an “amino” group.
Physical properties of amines:
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•
•
Amines generally tend to have a “fishy” smell.
Like alcohols, amines with fewer than five carbons are generally water-soluble
because the compound is still more polar than non-polar.
Compounds are highly polar resulting in higher boiling points than alkanes or alkenes.
Amines are also capable of hydrogen bonding, which increases the boiling points.
Nitrogen is less electronegative than oxygen. The bond is not as strong and the
boiling point is therefore lower than that of a similar alcohol.
Structure and Bonding in Amines:
What if you have three different groups bonded to the nitrogen atom? The molecule is
chiral, lacking a plane of symmetry. The enantiomers cannot be isolated though because
of a rapid inversion (pyramidal inversion) that occurs at room temperature.
The
3
tetrahedral amine has a sp hybrid orbital that contains a lone pair of electrons. This
molecule can go through a flattening process, to form a planar transition state, where
2
Nitrogen is sp hybridized. The bond angles are now 120°. The molecule then continues
3
the inversion process, reforming the sp hybridization for nitrogen. The barrier to this
inversion for simple amines is typically 5-6 kcal/mol, thus isolation of enantiomers is
difficult, even at low temperatures.
Acid-Base chemistry of amines:
Factors that affect basicity:
1.
2.
3.
4.
5.
Sterics – the more sterically hindered the Nitrogen atom is, the more difficult it
will be for the nitrogen atom to deprotonate a molecule. Tertiary amines are less
basic than secondary amines, which are less basic than primary amines.
Solvation – the more solvation can occur, the more stable the ammonium cation that
can form will be (similar to sterics). Polar solvents solvate the cation better.
Resonance - amines that are involved in resonance are less basic. Aromatic amines,
such as aniline and pyrrole are much less basic.
Hybridization – the more s character an atom has, the tighter it holds onto lone pair
2
3
electrons (less basic). Sp hybridized nitrogens are less basic than sp hybridized
nitrogens.
Inductive effect – presence of EWG will decrease basicity by pulling electron
density away from nitrogen with lone pair but EDG will increase basicity by pushing
electron density at the nitrogen with the lone pair!
Acid-Base Chemistry – Useful in the laboratory for separation of compounds in
extractions
Consider a mixture of three compounds: naphthalene, benzoic acid and pyridine.
three compounds are organic and soluble in an organic solvent, such as ether.
All
We can use acid-base chemistry to separate them. Consider their characteristics:
naphthalene is a neutral organic compound without any acidic nor basic functionality.
Benzoic acid has an acidic proton that reacts with bases. Pyridine is a base that reacts
with acids. Let’s separate them. Add aqueous acid to the three compounds. What
happens to each? Nothing happens to naphthalene, as it is neutral and non-reactive in
acid. Nothing happens to benzoic acid, as it does not react with acid. Pyridine, though,
is protonated. Once it is protonated, it becomes an ammonium salt, polar, and is watersoluble. Off it goes, into the aqueous acid layer.
Now you are left with naphthalene and benzoic acid. How would you separate these two
compounds? Consider adding a base this time, such as sodium hydroxide in water. What
happens this time? Nothing happens to naphthalene again, since it has no functional
groups that react with base. Benzoic acid, though, has an acidic proton, which is
removed by the base, forming a charged compound. It is then water-soluble and off it
goes into the aqueous base layer.
At the end of this process, you are left with three layers (a) the original ether layer,
still containing the neutral naphthalene, (b) the aqueous acidic layer, containing the
protonated pyridine, and (c) the aqueous basic layer, containing the deprotonated
benzoic acid. What would you add to get the pyridine back, uncharged? Base. What
would you add to get the benzoic acid back, uncharged? Acid.
By utilizing acid-base characteristics, you can separate organic compounds during the
extraction process.
Tetraalkylammonium salts are commonly used as Phase Transfer Catalysts:
Ex. Benzyltrimethylammonium hydroxide – used as an organic base because it has
a large number of carbons and thus is very soluble in organic solvents (non-polar) but it
is also a charged complex so it may also dissolve in aqueous solutions.
For reactions that need to have water present but have compounds that will not
dissolve, may use organic solvent and aqueous solution and a phase transfer catalyst to
cause reaction to occur across both phases!