Benedicts Reagent/Test

Oxidation
Mutarotation is a dynamic equilibrium process. As the sugar goes from one cyclic form
to another ( to ) it briefly adopts its straight chain form. From the straight chain,
aldehydes can be oxidized.

Isomerization from ketone to aldehyde and vise versa, goes through an ene-diol
rearrangement as well as several tautomerizations.
Mechanism of isomerization:

Base catalysed isomerization is why we sometimes get a false positive with

Benedicts Test for reducing sugars when testing fructose. The base in the reagent
will cause a fructose to isomerize to glucose and mannose which will result in the
oxidation that causes the colour change.

This is why you cannot use Benedicts Test to discriminate between an aldose and a
ketose. You can however, discriminate between aldose or ketose and a
monosaccharide reduced by NaBH4:

Cellulose
Cellulose, like amylose, is comprised of linear chains of repeating D-glucose units.
Unlike amylose however, the connection between those units are -1,4 (amylose has
-1,4 glycosidic linkages). This has a big structural impact which turn affects the
properties of cellulose.
- the -1,4 bonds allow each unit to rotate in such a way that intramolecular hydrogen
bonds can form making the chain firmly linear and as a whole it lays quite flat.
- because the chain is so linear, H-bonding can also occur intermolecularly between
chains along the entire length

Cellulose can be acetylated:

The acid used for the acetylation in the lab is sulfuric which reacts vigorously with water
releasing heat. This acid and heat may hydrolyse the cellulose before acetylation if
cotton (cellulose) is too wet.

Fatty Acids
Reaction of double bonds with bromine:
Bromine (Br2) is an orangey liquid. As it reacts, it loses this colour and we say that it is
decolourised. We can therefore use the addition of a known volume of Br2 to a
compound to determine how many double bonds that compound had.
1 x Br2 decolourized = 1 x double bond

A mineral acid (HBr, HCl etc) will precipitate a soap as its corresponding fatty acid:

Zyban
The synthesis of Zyban is a one pot procedure, meaning that the substrate remains in a
single reaction vessel throughout the preparation.
A few points to remember:

The HCl salt final product will be soluble in water (as is tert-butylamine
and N-methylpyrrolidinone) but not the intermediates
Intermediates are soluble in ether
The HCl salt final product will precipitate and isolated by filtration
The alpha bromination of a ketone is autocatalytic:

You will know the reaction is occurring as the orange/brown colur of the bromine fades
to light yellow or colourless.

A Couple Definitions
Four specific examples of high-molecular weight biopolymers incorporating
carbohydrates were discussed in lecture.
1. Glycoproteins proteins with short, branched carbohydrate chains bonded to
the side chains of the amino acids
Used for receptors, recognition, and cell-to-cell interactions
Example: blood-group antigens A and B
2. Proteoglycans (mucopolysaccharides) proteins with long, linear
carbohydrate chains bonded to the side chains of the amino acids

Typically found in connective tissue and cartilage

3. Peptidoglycans long, linear carbohydrates crosslinked by short oligopeptides
Typically found in bacterial cell walls
4. Lipopolysaccharides fatty acids linked to carbohydrates
Typically found in the outer envelope of Gram-negative bacteria

Carboxylic Acid Reactivity:

Acids/Bases
For neutral amino acids three forms can exists depending on the environment that
amino acid is in:

It is pretty clear looking at the above structures, that amino acids are amphoteric and
can act as both an acid or a base.
1. At low pH (acidic solution) amino acids are found in their cation form with a
protonated amine and neutral carboxylic acid.
2. At around pH 6 (neutral solution) amino acids with R-groups that are not
basic/acidic, will exist as a dipolar species. Their amine remains protonated but
the carboxylic acid is deprotonated. The combined positive and negative charge
balance out and the overall charge is zero.
3. At high pH (basic solution) amino acids are found in their anion forms with a
neutral amine and deprotonated carboxylic acid.
A weak acid ionizes according to the following:

Using the above equation, we can now titrate to find pKas; they will be found the
pH at which [H-A] = [A-] which we can determine with a titration curve.

Relationship Between Structure and Acidity

In this section we will consider the three general ways that structure can be used to
determine the relative acidity of a given compound.
When we considered the relative acidities of carboxylic acids in a previous organic
lesson it was shown that electronegative substituents close to the acidic proton increase

the acidity of that compound. We can now think of this property in terms of the stability
of that acids conjugate base since a compounds willingness to lose a proton (act as an
acid) is directly related to the stability of the conjugate base it leaves behind. Although
we will discuss the meaning of a pKa shortly, just remember for now that the smaller the
pKa, the stronger the acid.
1. Periodic Trends
Lets consider ethanol, methylamine and ethane. Since we know that the strength of an
acid is related to the stability of its conjugate base, we should start there:

When we look at the conjugate bases of these species we can see that as we go from C
N O (across the row) the atom which bears the negative charge changes. Since
oxygen is an electronegative atom it is much easier for it to carry the additional negative
charge. This property makes the alkoxide conjugate base more stable and ethanol a

stronger acid than methylamine or ethane.

Nitrogen, being somewhat more
electronegative can carry the charge but
much less effectively while the carbon in
ethane is ineffective at bearing and
stabilizing a negative charge.
Electronegativities increase to the right
across the periodic table and so does acid
strength.
In contrast, as we move down a group in
the periodic table electronegativities
decrease but acid strength increases. This
is because atomic radii also increase down
a group and the larger atom is better able to
spread out and carry the excess negative
charge.
In summary, acid strength increases to the right and down the periodic table.
2. Resonance Effects
Resonance effects are very strong in determining relative acidity based on structure.
Instead of delocalizing our electrostatic charge on a single atom based on size and
electronegativity we can spread it out over several atoms.
For example, acetic acid is fairly willing to donate a proton because its conjugate base,
the carboxylate anion, is resonance stabilized:

Consider also a CH2 group between two carbonyls:

In this case not only can we spread our negative charge with resonance, we are also
spreading it across a more electronegative atom and putting the double bonds into
conjugation which further stabilizes this conjugate base.
3. Inductive Effects
In addition to resonance stabilization, a conjugate base can be stabilized by induction
through bonds. Electron withdrawing groups draw electron density toward themselves
weakening the bond to the acidic hydrogen and also serve to stabilize the conjugate
base. The conjugate base is stabilized by delocalizing or spreading out the extra
electron density after the acidic proton is lost. For example, as we substitute
electronegative atoms onto the -proton of acetic acid we observe an increase in
acidity:

Adding more electron withdrawing groups further increases the acidity:

When comparing the acidities of organic compounds based on their substituents we

must consider three things:
1. The nature of the substituent (a monofluoracetic acid will be more acidic than
an monobromoacetic acid)
2. The number of those substituents (trichloro more acidic than dichloro which is
more acidic than monochloro)

3. The proximity of the substituent to the acidic hydrogen; since inductive effects
are through bonds their effects drop off quickly over relatively short distances
(3-4 atoms)
An important example of inductive effects is seen when we consider the acidity of the
carboxylic acid group of an -amino acid. If we take alanine as written, the H atom of
the carboxylic group would be expected to have a pKa between 4-5 and the H atom of
the amino group, leaving an unstable conjugate base, has a pKa of around 36 and is in
fact basic. Having a powerful base and acid in the same molecule results in a kind of
intramolecular acid-base reaction which yield the zwitterion that we expect for an amino
acid.

As we saw in the organic section, the zwitterionic form of an amino acid can be
protonated or deprotonated depending on the environment:

If we look at the zwitterion in an acidic environment we find the pKa of the carboxylic
acid function reduced to around 2 which is substantially more acidic than the pKa of 4-5
that we typically expect. What can account for this reduction? In forming the zwitterion,
the structure of the molecule changed. Once protonated, the amino group can no
longer donate electrons and instead withdraws electron density from the carboxylic acid
inductively. This delocalization stabilizes the conjugate base and therefore increases
the acidity of the carboxylic acid group.