BITC 1402 chapters_14-18

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					                                   Chapter 14
                            Alcohols, Ether, and Thiols
Alcohol: The functional group of an alcohol is an –OH (hydroxyl) group bonded to a
tetrahedral carbon atom. When naming an alcohol, change the ending from –e (for the
hydrocarbon) to –ol, and use a number to show the location of the –OH group (the –OH
group always gets the lowest number compared to alkyl, aryl, and halogen groups). For
cyclic alcohols, numbering begins at the carbon bearing the –OH group; this carbon is
automatically carbon-1; for substituents, name and number them in alphabetical order. To
derive common names for alcohols, name the alkyl group bonded to –OH and add the
word ―alcohol‖; for example, ethyl alcohol. Classify alcohols as primary, secondary, or
tertiary depending on the number of carbon groups bonded to the carbon bearing the –OH

Draw the line formulas for ethanol, 2-methyl-1-propanol, cyclohexanol, 2 butanol, 2
methyl 2- propane, 1 butanol, and trans2-methylcyclohexanol. Designate them as
primary, secondary or tertiary alcohols.

Nitroglycerin can be formed when glycerol is reacted with nitric acid in the presence of
sulfuric acid, write the reaction. How does nitroglycerin cause dilation of blood vessels?

Two hydroxyl groups = a diol; three hydroxyl groups = a triol; and common names for
these compounds consist of the parent compound and the word glycol. Draw the line
formulas for ethylene glycol (1,2 ethanediol) and 1, 3, 6, hexanetriol.

Physical Properties of Alcohols
The most important physical property of alcohols is the polarity of their –OH groups.
Because of the large differences in electronegativity between oxygen and carbon and
between oxygen and hydrogen, both the C-O and the O-H bonds of an alcohol are polar
covalent, and therefore alcohols are polar molecules. Thus alcohols have higher boiling
points than alkenes and alkanes. With increasing London dispersion forces between
larger molecules, the boiling points of longer chain alcohols are higher than the boiling
points of smaller chain alcohols. Alcohols are more soluble in water, but with increasing
chain length, solubility decreases. Which is more soluble in water ethanol or heptanol?
Which of these two has the higher boiling point?

Reactions of Alcohols
1) Write an equation demonstrating how alcohol can act as a very weak acid. What is the
pka value for most alcohols?

2) Write an equation showing the acid-catalyzed dehydration of an alcohol to form an
alkene. Why is it easier to catalyze the dehydration of a tertiary alcohol in comparison to
a secondary alcohol, which is easier to catalyze than a primary alcohol? What are the
products of the acid-catalyzed dehydration of 3-hexanol and why? Of 2 methyl
3) Write an equation showing the oxidation of a primary alcohol to an aldehyde to a acid,
of a secondary alcohol to a ketone. Why can‘t tertiary alcohols be oxidized?

Breath-Alcohol Screening
Write the equation that corresponds to the oxidation of a primary alcohol that results in
the reduction of dichromate, which is the basis for the breath analyzer test. Explain how
this reaction is exploited in this test.

The general formula is R-O-R. Draw a line formula for an ether compound and show the
bond angles between the carbon backbone and the oxygen. The common name for ethers
is written by the listing the alkyl groups attached to oxygen in alphabetical order and
adding the word ether. Alternatively the name is given by naming one of the groups on
the oxygen as an alkoxy group for example OCH3 is named methoxy. Show the structure
for cyclohexyl methyl ether (methoxycyclohexane)? For Enflurane? What is Enflurane
used for? How do ethers act as anesthetics?

An Example of a Cyclic Ether: Ethylene Oxide: A Chemical Sterilant
Write the formula for ethylene oxide and explain how it works as a chemical sterilant.
Physical Properties
 Ethers are polar compounds in which the oxygen bears a partial negative charge and
each attached carbon bears a partial positive charge; this leads to weak forces of
attraction between ether molecules in the pure liquid form and hence low boiling points
compared to alcohols (i.e. ethers exhibit dipole-dipole attractive forces whereas alcohols
exhibit hydrogen bonding). What is the boiling point of methoxyhexane vs heptanol,
lower or higher? Ethers resemble long chain hydrocarbons in their reactions; they are not
oxidized, they are not hydrogenated in the presence of metal catalysts, thus they make
excellent inert solvents.

Thiols (smelly stuff!)
The functional group of a thiol is an –SH bounded to a tetrahedral carbon atom. The scent
of skunks is due to what two thiols? Draw an example of a simple thiol and show the
bond angle between the S and the C atom. The sulfur analog of an alcohol is called a thiol
or in older literature, a mercaptan, which literally means ―mercury capturing‖. Thiols
react with Hg2+ in aqueous solution to give sulfide salts as insoluble precipitates.
Thiophenol C6H5SH, for example, gives (C6H5S)2Hg. This is the basis for mercury
poisoning!!!! In the IUPAC system, thiols are named by selecting the longest carbon
chain that contains the –SH group as the parent alkane. To show that the compound is a
thiol, we add the suffix –thiol to the name of the parent alkane. We number the parent
chain in the direction that gives the –SH group the lower number. We derive common
names for simple thiols by naming the alkyl group attached to –SH and adding the word
mercaptan. Draw the line structures for ethanethiol and pentyl mercaptan.
Physical Properties
Because of the small differences in electronegativity between sulfur and hydrogen (2.5 –
2.1 = 0.4) we classify the S-H bond as nonpolar covalent. Because of this lack of polarity,
thiols show little association by hydrogen bonding. Consequently, they have lower
boiling points and are less soluble in water and other polar solvents than alcohols of
similar molecular weight.
Reactions of Thiols
They are weak acids (pKa 10). They react with strong bases such as NaOH to form
thiolate salts. The most common reaction of thiols in biological systems in their
oxidations to disulfides (-S-S-).

Problems: 10, 11, 12, 14, 19, 21, 25, 32, 33, 40 63
                                       Chapter 15
A mirror image is the reflection of an object in a mirror. Enantiomers are a pair of
stereoisomers that are nonsuperposable mirror images of each other and a racemic
mixture contains equal amounts of two enantiomers. A good example of enantiomers are
your hands or your feet. An object that is not superposable on its mirror image is said to
be chiral. An achiral object is one that lacks chirality, it is superposable. The most
common cause of chirality in organic molecules is the presence of a tetrahedral carbon
atom with four different groups bonded to it. Such a carbon is called a stereocenter. The
configuration at a stereocenter can be specified using the R,S system. How is this system
     Arrange the groups bonded to it in order of priority, which is based on atomic
        number; the higher the atomic number, the higher the priority (e.g. O is 8 so it is
        higher than C, which is 6).
     If you cannot arrange the groups based on atomic number (e.g. 2 groups with the
        same atom), then find another priority, such as the atom bound to the C atom.
     Orient the molecule in space so that the lowest-priority group is directed away
        from you.
     Read the 3 groups projecting toward you in order from highest (1) to lowest (3)
     If reading the groups 1-2-3 proceeds in a clockwise direction, the configuration is
        designated as R; if reading the groups 1-2-3 proceeds in a counterclockwise
        direction, the configuration is S.

Only one enantiomer of ibuprofen is biologically active and it reaches therapeutic
concentrations in the human body in approximately 12 minutes, whereas the racemic
mixture takes approximately 30 minutes. However, in this case, the inactive enantiomer
is not wasted. The body converts to the active enantiomer, but that process takes time.
Draw the R (inactive) and the S (active) form of ibuprofen.

As we have already seen, (s)-ibuprofen is active while its R enantiomer is inactive. The S
enantiomer of the closely related analgesic naproxen is also the active pain reliever of this
compound, but its R enantiomer is a liver toxin! Draw (s) naproxen.

Light with waves that vibrate in only parallel planes is said to be plane polarized. To
measure optical activity, we use a polarimeter. A compound is said to be optically active
if it rotates the plane of polarized light. If it rotates it clockwise, it is dextrorotatory
(designated +); if it rotates the plane counterclockwise, it is levorotatory (designated -).
Each member of a pair of enantiomers rotates the plane of polarized light by an equal
number of degrees, but in opposite directions. Diagram a polarimeter and an example of
how specific rotation is reported for molecules, as shown in your textbook.

The Significance of Chirality in the Biological World
Except for inorganic salts and a few low molecular weight organics, the molecules in
living systems are chiral. Even though these molecules can exist as a number of
stereoisomers, (2n to be exact with n being the number of stereocenters for any one
molecule), usually only one stereoisomer is found in a system. Why? Because it wastes
energy to synthesize and resources to make more than one stereoisomer when one can do
the job. Plus enzymes recognize the differences between a substrate molecule and its
enantiomer and this confers specificity to a reaction, which is an advantage not a
Problems: 8, 10, 12, 15, 25, 26, 33
                                        Chapter 16

Nitrogen is the fourth most common element of organic compounds. The most important
chemical property of amines is their basicity. They are classified as primary, secondary or
tertiary depending on the number of carbon groups bonded to the nitrogen. Give an
example of a primary, secondary, and tertiary amine.
They can be further classified as aliphatic or aromatic, what does this mean?
Amphetamines or pep pills are examples of amines. They are powerful stimulants of the
central nervous system and are stored and administered as salts (why is that?). Examples
are the sulfate salt of amphetamine is prescribed as Benzedrine, the hydrochloride salt of
the s enantiomer of methamphetamine known as Methedrine, and the hydrochloric salt of
phentermine known as Fastin. Physiologically, they have in common the ability to reduce
fatigue and diminish hunger by raising the glucose level of the blood. They are addictive.
Draw all 3 structures
Nitrogen Containing Rings
An amine in which the nitrogen atom is part of a ring is classified as a heterocyclic
amine. When the ring is saturated, the amine is classified as a heterocyclic aliphatic
amine. When the nitrogen is part of an aromatic ring the amine is classified as a
heterocyclic aromatic amine. The most important of these compounds are pyridine,
pyrimidines, imidazole, and purine. Pyridine and pyrimidines are analogs of benzene in
which first one and then two –Ch groups are replaced by nitrogen atoms. Pyrimidine and
purine serve as the building blocks for the amine bases of DNA and RNA. Draw the four
basic structures for these compounds.
Alkaloids are basic nitrogen-containing compounds found in the roots, bark, leaves,
berries, and fruits of plants. In almost all of these compounds, the nitrogen atom is part of
a ring. Three examples of alkaloids are (s) Coniline, the toxic principal of water hemlock,
(s) Nicotine, which occurs in the tobacco plant, and Cocaine, a central nervous system
stimulant obtained from the leaves of the coca plant. Draw these two structures
IUPAC name for aliphatic amines is derived the same way as for an alcohol. The final e-
of the parent alkane is dropped and replaced by –amine. The location of the amino group
on the parent chain is indicated by a number. Draw 2 Butanamine, Cyclohexanamine, and
1,6 Hexanediamine. IUPAC retains the common name aniline and its derivatives are
named using numbers to locate substutents or the prefixes (o), (m), or (p) are used. Draw
aniline, 4 nitroaniline, and 3 methylaniline.
Unsymmetrical secondary and tertiary amines are commonly named as N-substituted
primary amines. The largest group bonded to nitrogen is taken as the parent amine; the
smaller groups bonded to nitrogen are named, and their locations are indicated by the
prefix N (indicating that they are bonded to nitrogen). Draw the structures for N-
methylaniline and N,N dimethylcyclopentanamine
Common names list the groups bonded to nitrogen in alphabetical order in one word
ending in the suffix –amine. Draw proplyamine, diethylmethylamine, and
When four atoms or groups of atoms are bonded to a nitrogen atom—as in NH4+--the
nitrogen is + charged and is associated with an anion as a salt. The compound is named as
a salt of the corresponding amine and the ending –amine (or aniline etc.) is replaced by –
ammonium (or anilinium etc.). Draw triethylammonium chloride
Physical Properties
     Low molecular weights have sharp odors
     They are polar compounds because of the difference in electronegativity between
         nitrogen and hydrogen (3-2.1 = 0.9)
     Both primary and secondary amines have N-H bonds and they can form H bonds
         with one another (translates into higher boiling points etc.)
     Tertiary amines cannot form H bonds
     An N-H…H hydrogen bond is weaker than an O-H…O hydrogen bond because
         the electronegativity difference between N and H is LESS than O and H. You can
         see this difference in the boiling point for alcohols vs amines.

All amines are soluble in water due to H bonding with the higher molecular weight
amines being less soluble.

Amines are weak bases and aqueous solutions of amines are basic. The following acid-
base reaction between an amine and water is written using curved arrows to emphasize
that, in this proton-transfer reaction, the unshared pair of electrons on nitrogen forms a
new covalent bond with H and displaces a –OH ion. The base dissociation constant for
the reaction of an amine with water is as follows.
And the pKb = -log Kb
All aliphatic amines have about the same base strength and are slightly stronger bases
than ammonia. (So at what pH value does ½ of aliphatic amines in a solution form a new
covalent bond with H and displaces a –OH ion?).
Understanding this, predict what form the aliphatic amine, dopamine, predominates in the
blood, which has a pH value of 7.40 (i.e the protonated or conjugatsed acid form?).
Reaction with Acids
The most important chemical property of amines is their basicity. Amines, wether water
soluble or insoluble, react with strong acids to form water-soluble salts. AND as a salt,
amines are less susceptible to oxidation so they retain their effectiveness for a much
longer time. Drug companies exploit this characteristic.
Ephinephrine: A Prototype for the Development of New Bronchodilators
First isolated in pure form in 1897 and its structure determined in 1901. It occurs in the
adrenal gland (adrenalin) as a single enantiomer with the R configuration at its
stereocenter. It is commonly referred to as a catecholamine. It is a vasoconstrictor, a
bronchodilator, and a cardiac stimulant. It became an important treatment for asthma and
hayfever. It is available under several trade names, including Bronkaid Mist Primatine
Mist. Draw epinephrine
One of the most important synthetic catechnolamines was isoproternol, the levorotatory
enantiomer of which retains the bronchodilating effects of epinephrine but is free from its
cardiac-stimulating effects. It was introduced in 1951 and was the drug of choice for
asthma attacks for twenty years. The hydrochloric salt of (s) isoproterenol is marked
under the trade name Sudafed. One of the problems with this compound is that the –OH
groups are inactivated by enzymes in the body so they were replaced by groups that
would not be changed; thus the development of terbutaline and albuterol.
In the search for a longer-acting drug, scientists thought extending the side chain on the
nitrogen might strengthen the binding of the drug to the adrenoreceptors in the lungs.
Salmeterol or Serevent, that is ten times more potent than albuternol and much longer
acting was developed. Show the difference between Sudafed and terbutaline and

Do problems: 10, 12, 16, 19, 21, 27, 28, 42, 44, 50
                                    Chapter 17
                               Aldehydes and Ketones

The carbonyl group =O is present in aldehydes, ketones and carboxylic acids. Draw the
simplest structure for an aldehyde and a ketone.
To name an aldehyde, change the suffix –e of the parent alkane to –al. The carbon
attached to the C=O is always the number 1 carbon. For unsaturated aldehydes, show the
presence of the C=C and an aldehyde by changing the ending of the parent alkane from –
ane to enal: ―en‖ to show the C=C bond and ―al‖ to show the aldehyde. Show the
structure for hexanal and 2-propenal.
For ketones, change the –e to –one, and number from the direction that gives the lowest
number for the group. If there is a second or third substituent, list them alphabetically
numbered by position. Show the structure for 2-amino, 3 hydroxyl hexanone,
benzaldehyde, 2, 6 dimethyl, 2 octenal
Common names are derived from the common name of the corresponding carboxylic
acid. The word ―acid‖ is dropped, and the suffix ―ic‖ or ―oic‖ is changed to ―aldehyde‖.
Write the formulas for formaldehyde and formic acid.
Common names for ketones are derived by naming each alkyl or aryl group bonded to the
carbonyl group as a separate word, followed by the word ―ketone‖. The alkyl or aryl
groups are generally listed in order of increasing molecular weight.
Physical Properties
Oxygen is more electronegative than carbon therefore a C=O is polar with O slightly
negative and the C slightly positive. Based on this differential, there is some attraction
between the molecules. However, since H bonding is not possible, the boiling point of
these compounds is less than alcohols or carboxylic acids. The oxygen of the carbonyl
group can be a hydrogen bond acceptor so low molecular weight ketones and aldehydes
are very water-soluble. Most have strong odors ranging from pleasant to obnoxious.
Aldehydes are oxidized to acids by a variety of oxidizing agents including dichromate ion
in the presence of strong acid. They are also oxidized to acids by the oxygen in the air, in
fact, aldehydes that are liquid at room temperature must be protected from air to prevent
oxidation. Ketones, in contrast, resist oxidation, and based on this difference, one can
easily determine if one has an aldehyde or a ketone (e.g. use Tollen‘s reagent, a mild
oxidizing agent). This reaction is used for making mirrors.
Aldehydes can be reduced to primary alcohols. Ketones are reduced to secondary
alcohols. Show these two reactions.
The reduction of a C=O bond under the same condition as the reduction of a C=C bond is
slower, thus if the same molecule contains both bonds, the C=C is reduced first before the
C=O. The most common reagent used for accomplishing this reaction in the laboratory is
sodium borohydride. This reagent contains hydrogen in the form of hydride ion, H:-. The
hydride ion is attracted to and then adds to the partially positive carbonyl carbon, which
leaves a negative charge on the carbonyl oxygen. Reaction of this intermediate with
aqueous acid gives the alcohol. Show this reaction. Note, this reaction does not reduce
C=C because there is no POLARITY on double bonds.
In biological systems, the agent for the reduction of aldehydes and ketones is the reduced
form of the coenzyme nicotinamide adenine dinucleotide. Abbreviated NADH. This
reducing agent, like sodium borohydride, delivers a hydride ion to the carbonyl carbon of
the aldehyde or ketone, Reduction of pyruvate by NADH, for example, gives lactate;
show this reaction. Pyruvate is the end product for what series of reactions in the cell?
Addition of Alcohols
Addition of a molecule of alcohol to the carbonyl group of an aldehyde or ketone forms a
hemiacetal (a half-acetal). The functional group of a hemiacetal is a carbon bonded to one
–OH group or one –OR group. The H of the alcohol adds to the carbonyl oxygen and the
OR adds to the carbonyl carbon.
Hemiacetal are unstable and are minor components of an equilibrium mixture, except in
one very important type of molecule. When a hydroxyl group is part of the same
molecule that contains the carbonyl group and a fix or six membered ring can form, the
compound exists almost entirely in a cyclic hemiacetal form. In this case, the –OH groups
adds to the C=O group of the same molecule. This is how sugars (like glucose) form ring

Hemiacetals can react further with alcohols to form acetals plus water in an acid-
catalyzed reaction.

Keto-Enol Tautomerism
A carbon atom adjacent to a carbonyl group is called an a-carbon and a hydrogen atom
bonded to it is called an a-hydrogen.
A carbonyl compound that has a hydrogen on an a-carbon is in equilibrium with a
constitutional isomer called an enol. The name enol is derived from the IUPAC
designation of it as both an alkene (en) and an alcohol (ol). Keto and enol forms are
examples of tautomers, constitutional isomers in equilibrium with each other that differ in
the location of a hydrogen atom relative to an oxygen atom. This type of isomerism is
called keto-enol tautomerism. The keto form generally predominates at equilibrium.

Draw the keto form of acetone that is equilibrium with the enol form of acetone.

Do Problems: 9, 10, 15, 17, 18, 19, 22, 23, 26, 31, 41, 45, 50, 59
                                Chapter 18
             Carboxylic Acids, Anhydrides, Esters, and Amides
What are their general formulas? Draw them

The acid              The anhydride          The ester             The amide

Carboxylic Acids: Draw the 3 ways it can be represented
The name of an acyclic carboxylic acid comes from the name of the longest carbon chain
that contains the carboxyl group. The final –e is dropped and replaced y –oic acid. The
numbering begins with the C of the carboxyl group and therefore it doesn‘t need a
number. Draw heptanoic acid

What if it contains a hydroxy- or an amino-? Draw 4 Amino 5 hydrox heptanoic acid

To name dicarboxylic acids, ad the suffix –dioic acid to the name of the parent alkane
that contains both carboxyl groups. Why aren‘t they numbered? (Because it is assumed
that the acid functional groups are at the ends of the molecule) Draw Pentanedioic acid

Many of the common names were known long before the development of the IUPAC
nomenclature and are often derived from the name of the natural substance from which
the acid can be isolated. When common names are used, the Greek letters alpha, beta and
gamma etc. are often added as a prefix to locate substituents. Draw propanoic acid and
label which carbons are gamma, beta and alpha.

Physical Properties
A major feature of acids is the polarity of the carboxyl group. This group contains 3
polar covalent bonds: C=O, C-O and O-H. Acids have significantly higher boiling points
than other types of organic compounds of comparable weight. Not only can acids form
hydrogen bonds with water etc. –hydrogen bonding can also occur between 2 carboxyl
groups of two acids creating a dimmer that behaves as a higher-molecular wt compound.
Draw two molecules of a carboxylic acid and show how they hydrogen bond to each

Carboxylic acids are more soluble in water than are alcohols, ethers, aldehydes and
ketones of comparable molecular weight. This increase in solubility is due to their strong
association with water molecules by hydrogen bonding through both their carbonyl and
hydroxyl groups. Two other properties that bear mentioning is their disagreeable odors
(‗Locker room smell‖, ―goat smell‖) and second, their sour taste (limes, lemons, pickles
and sauerkraut). Which acid has a higher boiling point, butanoic acid or butanal?

They are weak acids. Values of ka for most unsubstituted aliphatic and aromatic acids
fall within the range of 10-4 to 10-5 (pKa = 4-5).
Substituents of high electronegativity (especially –OH, -Cl and –NH3+) near the carboxyl
group increase the acidity of carboxylic acids, often by several orders of magnitude.
Compare the acidities of the compounds listed on the line below.
Acetic acid, chloroacetic acid, dichloroacetic acid, and trichloroacetic acid

Reaction with Bases?
All acids, WHETHER soluble or insoluble in water, react with strong bases to form
WATER-soluble salts.
Show the reaction between benzoic acid and sodium hydroxide.

Salts of the acids are names in the same manner as the salts of inorganic acids: the cation
is named first and then the anion. We derive the name of the anion from the name of the
carboxylic acid by dropping the suffix –ic acid and adding the suffix –ate. Name the salt
that is formed in the reaction above.

The form in which an acid exists in an aqueous solution depends on the solution‘s pH.
Review the equation given on page 444 and be able to determine what form of benzoic
acid is present in solution with a pH value of 3, of 7 and of 9.

Anhydrides, Esters and Amides
The functional group of an anhydride consists of two carbonyl groups bonded to the same
oxygen atom. The anhydride may be symmetrical (from two identical acyl groups) or
mixed (from two different acyl groups). To name it, we drop the word ―acid‖ from the
same of the carboxylic acid from which the anhydride is derived and add the word
―anhydride‖. Draw acetic anhydride

The functional group of an ester is a carbonyl group bonded to an –OR group. Both
IUPAC and common names are derived from the names of the parent carboxylic acids.
The alkyl group bonded to oxygen is named first followed y the name of the acid in
which the suffix –ic acid is replaced by the suffix –ate. Draw ethyl ethanoate

Cyclic esters are called lactones. (note the oxygen atom counts as one atom of the ring)
Draw a five-membered lactone

Esters are slightly polar compounds because of the presence of the C=O and C-O-C
bonds. Because they have no available hydrogens for hydrogen bonding, however, they
are generally insoluble in water. Almost all low molecular wt esters are liquids. Draw
the line structure for ethyl –3 methybutanoate

The functional group of an amide is a carbonyl group bonded to a nitrogen atom.
Amides are names by dropping the suffix –oic acid from the IUPAC name of the parent
acid, or –ic acid from its common name, and adding –amide. If the nitrogen atom of the
amide is bonded to an alkyl group, the group is named and its location on nitrogen is
indicated by N-. Two alkyl groups are indicated by N,N, -di –Draw the structure for N,N

Cyclic amides are called lactams. For example, 4-membered lactam, which is important
to the function of the penicillin and celphalosporin antibiotics.
The B Lactam Antibiotic Story
Penicillins were discovered in 1928 by the Scottish bacteriologist Sir Alexander Fleming.
Backing by work by Sir Howard Florey, an Austrian pathologists, and Ernst Chain, a
German chemist who fled Nazi Germany, penicillin G was introduced into the practice of
medicine in 1943. They were awarded the Nobel Prize for medicine and physiology in
1945. The original mold, Penicillium notatum, was replaced in commercial production
by P chrysogenum, which was discovered growing on a grapefruit in a market in Peoria,
Illinois. This antibiotic inhibits the tetrapeptide crosslinking of peptioglycan in growing
bacteria, particularly gram + bacteria.
Draw Penicillin G                                       Draw Amoxicillin

Once penicillin-resistant strains of bacteria, new derivatives were made (usually different
in the side chains). Another approach is to search for newer, more effective B lactam
antibiotics. The most effective of these agents discovered so far are the cephalosporins,
the first of which was isolated from the fungus Cephalosporium acremonium. This class
of antibiotics has an even broader spectrum of antibacterial activity than the penciling
and is effective against many penicillin-resistant bacterial strains. Cefalexin (Keflex) is
presently one of the most widely prescribed of this type of antibiotic.
Draw Cefalexin

Preparation of Esters-Fischer Esterification
Carboxylic acid + alcohol –(acid catalyst) -> ester + water
First the alcohol adds to the carbonyl group of the carboxylic acid to form a tetrahedral
carbonyl addition intermediate. (Note how closely his step resembles the addition of an
alcohol to the carbonyl group of an aldehydes or ketone to form a hemiacetal) Then the
intermediate loses a molecule of water to give an ester.
Draw the reaction between ethanoic acid and ethanol to form ethyl ethanoate (what is the
reaction you do in lab that is a Fisher Esterification?)

Fisher Esterification is reversible, and generally at equilibrium, the quantities of
carboxylic acid and alcohol present are appreciable. To drive the ration to the right, one
can add and excess of alcohol and/or remove the water formed.

Preparation of Amides
Carboxylic acid + amide -> an ammonium salt –(heat) -> an amide + water Draw the
reaction between acetic acid and ethylamine
Anhydride + amine -> amide + acid (Draw a representative reaction)
The story of Aspirin
The Greek physician Hippocrates recommended chewing bark of the willow for pain to
his patients. Why? Willow bark contains salicin. Later it was found that hydrolysis of
salicin in aqueous acid followed by oxidation gave salicylic acid, which was better at
relieving pain compared to salicin. However, salicylic acid was hard on the stomach. In
the search for a less irritating but effective derivative of salicylic acid, chemists at the
Bayer division of I.G. Farben in Germany in 1883 treated it with acetic anhydride and
prepared acetylsalicylic acid. They gave his new compound the name aspirin. (more
effective than salicylic acid but still somewhat irritating). In the 1960‘s in a search for
even more effective and less irritating analgesics and nonsteriodal anti-inflammatory
drugs (NISADs), chemists at the boots Pure Drug Company in England, discovered
ibuprofen. Soon thereafter, Syntex Corporation in the US Developed naproxen (Aleve).
For both ibuprofen and naproxen, the active form is the s enantiomer.
Draw aspirin, (s) ibuprofen, and (s) naproxen

In the 1960s researchers discovered that aspirin acts by inhibiting cyclooxygenase (CDX)
a key enzyme in the conversion of arachidonic acid to prostaglandins. Only the s
enantiomer of each has the correct handedness to bind COC and inhibit its activity.

Hydrolysis of Anhydrides, Esters and Amids
Carboxylic anhydrides + water -> 2 carboxylic acids

They are hydrolyzed slowly –even when the water is boiled HOWEVER, when they are
heated in aqueous acid or base, they are hydrolyzed rapidly. Excess water drives the
reaction to the right.
Hydrolysis of an ester can also be carried out using hot aqueous base, such as aqueous
NaOH. This is known as saponification and is how soaps are made. Each mole of ester
hydrolyzed requires one mole of base, draw the reaction.

Ultraviolet Sunscreens and Sunblocks
UV radiation penetrating the earth‘s ozone layer is arbitrarily divided into two regions:
UVB (290-320nm) and UVA (320-400nm). UVB is more energetic and therefore creates
more free radicals that can cause cancer. UVA causes tanning and is less effective at
damaging the skin. Commercial sunscreen products are rated according to their sun
protection factor (SPF). Two types of active ingredients are found in commercial
sunblocks: 1) titanium dioxide (reflects and scatters UV irradiation) and 2) the
compounds listed below which are designed to absorb UVB rays, they do not screen for
UVA. Draw a commercial sunscreen active ingredient.

In 1864, Adolph von Bayer discovered that heating the diethyl ester of malonic acid with
urea in the presence of sodium ethoxide gives a cyclic compound that he name barbituric
Nembutal is the sodium salt of pentobarbital. Draw it
Effects: In small doses, barbiturates are sedatives and in large doses they induce sleep.
Hydrolysis requires more vigorous conditions compared to an ester ACID (products:
carboxylic acid and an ammonium ion)
Draw the reaction between butanamide, water, and hydrochloric acid to form the acid,
ammonium, and chloride

BASE (products: carboxylic acid salt and ammonia or an amine) Show a representative

Phosphoric Anhydrides and Esters
The functional group of a phosphoric anhydride consist of two phosphoryl (P=O) groups
bonded to the same oxygen atom. Draw the structural formulas for two anhydrides of
phosphoric acid ad the ions derived by ionization of the acidic hydrogens of each

Phosphoric Esters
Phosphoric acid and three –OH groups. It forms mono, di- and triphosphoric esters,
which we name by giving the name(s) of the alkyl group(s) bonded to oxygen followed
by the word ―phosphate‖. In more complex phosphoric esters, it is common practice to
name the organic molecule and then indicate the presence of the phosphoric ester by
including either the word ―phosphate‖ or the prefix phosphor-. Dihydroxyacetone
phosphate for example is an intermediate in glycolysis and pyridoxal phosphate is an
enzymatic cofactor. Draw pyridoxal phosphate

Step-Growth Polymerizations
Step growth polymers form from the reaction of molecules containing two functional
groups, with each new bond being created in a separate step. Three types are polyamides,
polyesters and polycarbonates.

In the early 1930s, chemists at E.I. DuPont de Nomours & Company began fundamental
research into the reactions between dicarboxylic acids and diamines to form polyamides
(recognize the similarity to peptide bond formation in proteins?). In 1934 they
synthesized nylon -66 the first purely synthetic fiber. Nylon-66 is so named because it is
synthesized from two different monomers, each containing 6 carbon atoms.
In the synthesis of nylon-66, hexanedioic acid and 1,6 hexanediamine are dissolved in a
aqueous ethanol and then heated in an autoclave to 250C and internal pressure of 15atm.
Under these conditions, -COOH and –NH2 groups react by loss of water to form a
They reasoned that a polyamide containing benzene rings would be even stronger which
led to the discovery of Kevlar. Draw the reaction showing the formation of Kevlar.

The first polyester developed in the 1940s involved the polymerization of benzene 1,4
dicarboxylic acid with 1,2 ethanediol to give poly (ethylene terephthalate) or PET. Draw
the reaction that represents the synthesis of PET.
The crude polyester can be melted, extruded and then drawn to form the textiles fiber
Dacron polyester.
The most familiar is Lexan, which is formed from the reaction of the disodium salt of
bisphenol A and phosgene. What is Lexan used for?

Stitches that Dissolve (Lactomer) What is it a polymer of?

Do Problems: 9, 11, 13, 19, 22, 24, 27, 29, 31, 37, 47, 49, 50, 61, 63

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