Dr. Louis Williams
November 7, 2006
FUNCTIONAL GROUP ANALYSIS
Aldehydes, Ketones, and Amines
Group 1
Problem Set 5E (Week 5)
Stephanie Lao
Thanh Phan
Annie Tran
Dan Truong-Le
Janet Way (Recorder)
I. Introduction
Week five brought us aldehydes, ketones, and amines. The aldehyde and ketone
groups both contain the carbonyl group, in which a carbon is doubly bonded to an oxygen
atom. The carbonyl group is highly polar with a positively charged carbon and negatively
charged oxygen.
O
O
R
C
H
Aldehyde
R
C
R'
Ketone
IUPAC naming of aldehydes begins with choosing a base name from the longest
continuous carbon chain containing the aldehyde at position one. The suffix “-al”
replaces “e” in the alkane base name.
IUPAC naming of ketones gives the lowest number to the carbonyl group, with
the lowest number to remaining constituents being most desirable. The suffix “-one”
along with the ketone position replaces the “e” in the alkane base name.
Due to the carbonyl group, both aldehydes and ketones are polar. Both can
hydrogen bond to water and will dissolve in water to some extent. Longer hydrocarbon
chains reduce solubility very rapidly. The ketone group is relatively nonreactive, while
the aldehyde group is rapidly oxidized and must be protected from oxygen. Both of these
functional groups will react with alcohol in a reversible fashion in acidic conditions.
Addition of alcohol to aldehydes and ketones yields hemiacetals and hemiketals. A
subsequent addition of alcohol will yield acetals and ketals respectively.
Amines are derivatives of ammonia in which one or more hydrogen has been
replaced by an alkyl or aryl group. These functional groups are often added to organic
molecules for the purpose of promoting water solubility in the body. For this reason,
amines are commonly found in pharmaceutical agents. Primary and secondary amines
participate in hydrogen bonding as both donors and acceptors, displaying both acidic and
basic properties.
The IUPAC system considers amines to be substituted alkanes. The longest
continuous alkane chain is used as the base name. The lowest possible number is
assigned to the amine group. Other substituents on the amine group are preceded by “N”.
Whether the group is primary, secondary, or tertiary is determined by how many
substituents are attached to the nitrogen – not the carbon to which the nitrogen is
attached.
Quaternary salts earn their name because they have a central nitrogen bound to
four carbon atoms through covalent bonds. These salts are very stable and are not
converted to amines when treated with base. They are ionic compounds which will be
highly soluble in water if they are capable of dissociation. These compounds are named
as the organic substituents, followed by the word “ammonium”, followed by the salt that
is present.
II. Assigned Problem Set 5E
Spectinomycin is in the family of aminoglycoside antibiotics. It is marketed as a
white powder to be mixed with bacteriostatic sterile water for injection. It is injected
intramuscularly to treat Neisseria gonorrhea.
2o alcohol
acetal
2o amine
H3C
OH
H
HN
R
S
2o alcohol
HO
S
S
O
O
OH
NH
CH3
O
S
S
S
R
H
H
R
H
ketone
O
H3C
hemi-ketal
.2HCl
2o amine
C14H24N2O7 *2HCl *5H2O
Spectinomycin Hydrochloride
.5H
20
1. Identify functional groups along with their acidic, basic or neutral tendencies.
(See diagram for identification of functional groups.)
a. The two secondary amines are basic in nature.
b. Spectinomycin has two secondary alcohols. An alcohol group attached to a
carbon, which in turn is attached to two other carbons, is a secondary alcohol.
These alcohols are generally neutral.
c. Acetals can form two alcohols and an aldehyde. These groups are basic in
nature.
d. Hemiketals are formed when an alcohol group is added to a ketone group.
They can form a ketone and an alcohol. Hemiketals, like acetals, are basic in
nature.
e. Ketones are also basic in nature.
2. Discuss the solubility of spectinomycin in aqueous acid, aqueous base and water.
Using table 18.2, we determined that this molecule is soluble in water ( = -1.5).
Once this determination was made, we were able to reason that this drug is also
soluble in aqueous base and aqueous acid.
3. Discuss the stereochemistry, stability and metabolism of the structure.
(a) Stereochemistry has been labeled in the above diagram. We found nine chiral
centers indicating 29 or 512 isomers, including this molecule.
(b) Stability –In its unmixed, dry powder form, spectinomycin is shelf stable for
36 months.
(c) Metabolism – In the body, this drug is readily metabolized.

The secondary amine groups can undergo dealkylation (removal of the
attached methyl group). The resulting primary amine may undergo the
following reactions:

Deamination – removal of amine group. If catalyzed by pyroxidal 5phosphate, an aldehyde or ketone product results. Monoamine oxidase
(MAO) and diamine oxidase (DAO) are commonly utilized in
deamination reactions. A CYP450 catalyzed dealkylation may also
occur.

Conjugation with sulfuric acid to give sulfates

Conjugation with glucuronic acid to give glucuronides

Acetylation by acetyl CoA to give a less water soluble product. This
occurs most often in primary aryl amines.

The acetal group is highly unstable in aqueous acidic conditions and will
revert to aldehyde and alcohol. Aldehydes are readily oxidized by
xanthine or aldehyde oxidase, and by NAD-specific aldehyde
dehydrogenase to produce a carboxylic acid.

Hemiketals are similar to acetal in aqueous conditions. They will revert to
ketones and alcohols. In this case, the right-most ring will be separated
from the rest of the molecule in the process. The resulting ketone and
alcohol will appear as below:
O
+
OH

HO
OH
O
The secondary alcohols can be oxidized by oxidase enzymes to ketones.
They may also undergo conjugation with glucuronic acid or sulfuric acid
yielding a more soluble substance.

Ketones may undergo reduction to secondary alcohol.
The aldehyde, ketone, and amine functional groups are commonly utilized in the
creation of pharmaceutical products. Aldehydes can generate acetals, which are found in
aminoglycoside antibiotics. Amines are used to solubilize the drug as the free base or as a
water-soluble salt of the amine. It also acts as to maintain the drug in the target site of the
body to produce prolonged activity where it is needed. All of these groups work together
in the metabolism and biosynthesis of amino acids.