Introduction to

Pharmaceutical
Organic Chemistry
The word “organic” was originally used by eighteenth-
century chemists to describe substances obtained
from living sources – plants and animals. These
chemists believed that nature possessed a certain
vital force and that only living things could produce
organic compounds.

This notion was disproved in 1828 by Friedrich Wohler, a German chemist who prepared urea, an organic compound, from
the reaction between inorganic compounds lead cyanate and aqueous ammonia. Today, over 20 million synthetic and
natural organic compounds are known.

At the end of this unit, you should be able to:

1. Demonstrate understanding of inorganic and organic chemistry and distinguish between inorganic and organic
compounds
2. Demonstrate understanding of organic molecules structure and bonding
3. Demonstrate understanding of structural models and representations of organic molecules

UNIT 1
INTRODUCTION TO ORGANIC CHEMISTRY

The branch of chemistry that deals with carbon compounds is organic chemistry. Nearly all compounds found in living
organisms are still classified as organic compounds, as are many compounds that have been synthesized in the laboratory
and have never been found in a living organism.

As we go further with our subject, you will see that organic compounds are everywhere around us. They are in our foods,
flavors, and fragrances; in our medicines, toiletries, and cosmetics; in our plastics, films, fibers, and resins; in our paints,
varnishes, and glues; and, of course, in our bodies and the bodies of all other living organisms.

A. Organic Chemistry: An Overview

In essence, organic chemistry is the study of the compounds of one element (carbon), and inorganic chemistry is the study
of the compounds of the other 116 elements. There are approximately 7 million organic compounds and only an estimated
1.5 million inorganic compounds, approximately 5:1 ratio between organic and inorganic compounds.

The most remarkable feature of organic compounds is that they involve the chemistry of carbon and only a few other
elements – mainly, hydrogen, oxygen, and nitrogen. Many also contain sulfur, a halogen (fluorine, chlorine, bromine, or
iodine), and phosphorus. However, there is always an exception to the rule. The oxides of carbon, carbonates, cyanides, and
metallic carbides are classified as inorganic rather than organic compounds.

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 Take note: Inorganic carbon compounds always involve carbon atoms that are not bonded to hydrogen atoms (CO,
CO2, Na2CO3, and so on).

A.1. Significance of Organic Chemistry:

1. Abundance
 Chemists have discovered or synthesized more than 10 million of organic compounds, and an estimated 10,000
new ones are reported each year.
 By comparison, chemists have discovered or synthesized an estimated 1.7 million inorganic compounds—
approximately 85% of all known compounds are organic compounds
 They are present daily and are seen in products or cleaning accessories such as soaps, shampoos or perfumes

2. Understanding Biochemistry
 Carbohydrates, lipids, proteins, enzymes, nucleic acids (DNA and RNA), hormones, vitamins, and almost all other
important chemicals in living systems are organic compounds
 These biomolecules give and store energy, that are included in structural formation, that transport other
molecules, or that regulate growth in living organisms

3. Human Health Technology

 Organic chemistry is involved in the development of new drugs and applications in medicinal chemistry
- Scientists apply their chemistry training to the process of synthesizing new pharmaceuticals
- Uses sophisticated analytical techniques to synthesize and test new drug products and to develop the most
cost-effective and eco-friendly means of production
- Alter the structure of compounds for optimum effect and minimum side-effects of newly developed
medications
 The study of materials, e.g. hypoallergenic materials used in prosthesis
 Production of food

4. Industrial Applications
 Organic substances are involved in developing new and innovative materials
 Production of petroleum, and the industry of polymers
 Solvents like degreasers or dry cleaning products, chemical gums for wood like latex or white glue, plastics like
toys or plastic coatings

5. New Tendencies in Technology and Applied Sciences

 Development of alternative energy sources as biofuels that can be produced from plants or organic waste
 Organic photo-sensors that convert light in electrical signals to capture images in cameras

A.2. Sources of Organic Compounds:

1. Isolation from Nature

 Terrestrial, marine, and freshwater plant (flora) and animal (fauna)—even microorganisms such as bacteria—
make thousands of organic compounds by a process called biosynthesis
 Process: extract, isolate, and purify them from biological sources
 Pharmaceutical Products: Vitamin E, Penicillins, table sugar, Insulin, Quinine, and the anticancer drug Paclitaxel
 Industrial Products: natural gas, petroleum, and coal

2. Synthesis in the Laboratory

 Involves more sophisticated methods
 Compounds made in the laboratory are identical in both chemical and physical properties to those found in
nature— assuming, of course, that each is 100% pure.
 Examples: Vitamin C and Ethanol
 Also used to design and synthesize compounds not found in nature
 More than 10 million known organic compounds are purely synthetic and do not exist in living organisms
 Examples: Aspirin, Iburofen, Diazepam (ValiumⓇ), Albuterol (VentolinⓇ), Fluoxetine (ProzacⓇ), Ranitidine
(ZantacⓇ), Sertraline (ZoloftⓇ), Furosemide (LasixⓇ), Sildenafil (ViagraⓇ), and Norethynodrel (EnovidⓇ)

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A.3. Inorganic vs. Organic Compounds:

The terms organic and inorganic continue to be used in classifying compounds, but the definitions of these terms no longer
reflect their historical origins. As mentioned, Organic Chemistry is the study of hydrocarbons (compounds of carbon and
hydrogen) and their derivatives. While, Inorganic chemistry is the study of all substances other than hydrocarbons and their
derivatives. A table below is provided for you to show the differentiation of inorganic from organic compounds.

B. PRINCIPLES OF ORGANIC CHEMISTRY: CARBON AS THE PRINCIPAL ELEMENT

“What makes carbon so special? Why are there so many carbon-containing compounds?”

 Carbon is in the center of the second row of elements.

 Atoms to the left of carbon have a tendency to give up electrons, whereas the atoms to the right have a tendency
to accept electrons.
 Because carbon is in the middle, it neither readily gives up nor readily accepts electrons. Instead, it shares electrons.
 Carbon can share electrons with several different kinds of atoms, and it can share electrons with other carbon atoms.
 Carbon is able to form millions of stable compounds with a wide range of chemical properties simply by sharing
electrons.

B.1. Physical Properties of Carbon

 Carbon is a unique element. It occurs in many forms. Some of the examples of the pure form of carbon are coal and
soot.
 One of the most important compounds of carbon is the charcoal, which is formed when carbon is heated in the
absence in of air.
 It occurs in a number of allotropic forms. Allotropes are nothing but forms of an element with varying physical as well
as chemical properties.

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 What are the Physical Properties of Carbon?

Allotropes Two allotropes of carbon have different crystalline structures: diamond and graphite
The physical properties of carbon vary widely with the allotropic form.

Forms of Carbon Graphite, diamonds and coal are all nearly pure forms of carbon

Color Diamond is highly transparent. Graphite is opaque and black

Hardness Diamond is one of the hardest substances known to man. Graphite is soft and often used as the
"lead" in lead pencils

Conductivity Diamond has a very low electrical conductivity. Graphite is a very good conductor

Brittleness Very brittle, and cannot be rolled into wires or pounded into sheets

Phase Solid

B.2. Chemical Properties of Carbon

 Carbon compounds generally show four reactions. They are the combustion, oxidation, addition, and substitution
reaction.

a. Combustion reaction:
As we all know that carbon in all forms needs oxygen, heat, and light and forms carbon dioxide. When it is burned
in air to give carbon dioxide, it is called as combustion.
Example: Methane (CH4) is burnt in the presence of oxygen

b. Oxidation reaction:
Carbon and its compounds get easily oxidized when subjected to combustion. For example alcohol on oxidation
is converted to carboxylic acid. Carbon burns in the presence of oxygen and gets oxidized to carbon dioxide
and carbon monoxide depending upon the availability of oxygen and the extent of reaction. Most compounds
of carbon get oxidized when reacted with strong oxidizing agents.

c. Addition reactions:
Addition reaction is observed only for those compounds that have unsaturation that is the compounds that
contain multiple bonds (double bond, triple bond) in them. Industrially, hydrogenation of vegetable oils is an
example of addition reaction in which hydrogen is added to unsaturated vegetable oil in presence of a catalyst
to convert it into a saturated compound.

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 d. Substitution reaction
The reactions in which a less reactive element or molecule is replaced by a more reactive element or molecule
are known as substitution reactions. Substitution reaction is mainly observed in case of saturated hydrocarbons.
The reaction of saturated hydrocarbons in presence of sunlight with chlorine is an example of substitution
reaction. Chlorine being more reactive has the ability to displace the hydrogen atom from the saturated
hydrocarbons.

What are the Chemical Properties of Carbon?

Chemical Formula C

Oxidation Combines with oxygen to produce carbon dioxide (CO 2 ) and carbon monoxide
(CO)

Reactivity Carbon does not dissolve in, or react with, water or acids

Chains of Atoms Carbon has the ability to make long strings, or chains, of atoms

Compounds Carbon forms more compounds than all other elements combined; several million
carbon compounds are known

Buckminsterfulleren - C60 Carbon also occurs in a newly discovered form known as fullerenes or buckyballs. A
fullerene is any molecule composed entirely of carbon. Fullerenes are similar in
structure to graphite

B.3. Stability
 Carbon is the chemical element with the symbol C and atomic number 6.
 It is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds.
 The variety of covalent bonding that is possible for carbon atoms is related to carbon’s electron configuration. If you
recall from your Inorganic Chemistry, carbon is a member of Group IVA of the periodic table, so carbon atoms possess
four valence electrons.
 RECALLING THE OCTET RULE: Atoms lose, gain, or share electrons in order to have a full valence shell of eight electrons.
Hydrogen is an exception because it can hold a maximum of two electrons in its valence level.
 The octet rule is the understanding that most atoms seek to gain stability in their outer most energy level by filling the
s and p orbitals of the highest energy level with eight electrons.
 Carbon has an electron configuration of 1s²2s²2p² this means that carbon has four valence electrons.
 In compound formation, four additional valence electrons are needed to give carbon atoms an octet of valence
electrons. These additional electrons are obtained by electron sharing. The sharing of four valence electrons requires
the formation of four covalent bonds.
 Carbon can meet this four-bond requirement in three different ways:
 By bonding to four other atoms. This situation requires the presence of four single bonds.

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Pharm 122 – Organic Chemistry
  By bonding to three other atoms. This situation requires the presence of two single bonds and one double
bond.

 By bonding to two other atoms. This situation requires the presence of either two double bonds or a triple bond
and a single bond.

 Remember: Carbon seeks out four additional electrons to fill the p orbital and gain the stability of a noble gas.
Example: Carbon tetrachloride

B.4. Hybridization: A Recall

 Hybrid orbital vs. pure atomic orbital:
 Hybridization is the mixing of at least two nonequivalent atomic orbitals, for example, s and p orbitals.
Therefore, a hybrid orbital is not a pure atomic orbital.
 Hybrid orbitals and pure atomic orbitals have very different shapes.
 The number of hybrid orbitals generated is equal to the number of pure atomic orbitals that participate in
the hybridization process.
 The table below provides you the important hybrid orbitals and their shapes:

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Pharm 122 – Organic Chemistry
 To assign a suitable state of hybridization to the central atom in a molecule, we must have some idea about the
geometry of the molecule. The steps are as follows:
1. Draw the Lewis structure of the molecule.
2. Predict the overall arrangement of the electron pairs (both bonding pairs and lone pairs) using the VSEPR model.
Recall: Valence-shell electron-pair repulsion (VSEPR) model, accounts for the geometric arrangements of
electron pairs around a central atom in terms of the electrostatic repulsion between electron pairs.
3. Deduce the hybridization of the central atom by matching the arrangement of the electron pairs with those of
the hybrid orbitals.

 Below is an example that illustrates the procedure:

 Determine the hybridization state of the central (underlined) atom of the inorganic molecule: BeH2
 Describe the hybridization process and determine the molecular geometry of the molecule.
 Strategy: The steps for determining the hybridization of the central atom in a molecule are:

Determine the
Draw the Lewis Use VSEPR to determine the
hybridization
Structure of the electron pair arrangement
state of the
molecule surrounding the central atom central atom

 Solution:
(a) The ground-state electron configuration of Be is 1s²2s² and the Be atom has two valence electrons. The
Lewis structure of BeH2 is:

(b) There are two bonding pairs around Be; therefore, the electron pair arrangement is linear. We conclude
that Be uses sp hybrid orbitals in bonding with H, because sp orbitals have a linear arrangement. The
hybridization process can be imagined as follows. First, we draw the orbital diagram for the ground state of
Be:

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Pharm 122 – Organic Chemistry
 (c) By promoting a 2s electron to the 2p orbital, we get the excited state:

(d) The 2s and 2p orbitals then mix to form two hybrid orbitals:

(e) The two Be-H bonds are formed by the overlap of the Be sp orbitals with the 1s orbitals of the H atoms.
Thus, BeH2 is a linear molecule.

 Remember:
 Hybridization is the idea that atomic orbitals fuse to form newly hybridized orbitals, which in turn, influences molecular
geometry and bonding properties.
 Hybridization is also an expansion of the valence bond theory.
 The concept of hybridization is not applied to isolated atoms. It is a theoretical model used only to explain covalent
bonding.
 Covalent bonds in polyatomic molecules and ions are formed by the overlap of hybrid orbitals, or of hybrid orbitals
with unhybridized ones. Therefore, the hybridization bonding scheme is still within the framework of valence bond
theory; electrons in a molecule are assumed to occupy hybrid orbitals of the individual atoms.

B.5. Catenation
 Carbon is unique among the elements in the almost infinite capacity of its atoms to bond to each other in long chains,
a process called catenation. (Latin catena, chain).

 This characteristic reflects the strength of the bond between adjacent carbon atoms in the molecule, both in
relationship to similar bonds involving other elements of the carbon family and in relationship to bonds between
carbon atoms and atoms of many other elements.

 Only the carbon–hydrogen, carbon–fluorine, and carbon–oxygen single bonds (C―H, C―F, and C―O) are stronger
than the carbon–carbon single bond (C―C), and each of these is weaker than the carbon–carbon multiple bonds
(C=C or C≡C).

 Catenation, via single or multiple bonds or both, combined with several other factors allows carbon to form more
compounds than any other element. These factors are:
1. the stability of certain carbon bonds, in particular of the C―H bond;
2. the existence of carbon in both sp2 and sp3 hybridizations;
3. the ability of carbon to form both chain and cyclic compounds
4. the capability of many carbon compounds to exist in isomeric

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C. MODELS AND REPRESENTATIONS IN ORGANIC CHEMISTRY

C.1. Structural Formula: A two-dimensional structural representation that shows how the various atoms are bonded, and is
more useful than only writing the molecular formula for a compound

a. Displayed formula (a.k.a “Expanded formula”)

 Shows all the bonds in the molecule as individual lines with each atom written at the end of each line using its
elemental abbreviation from the periodic table.

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Pharm 122 – Organic Chemistry
 Example: a) CH2Cl2

b) C2H2Cl

 An expanded structural formula is a structural formula that shows all atoms in a molecule and all bonds connecting
the atoms. When written out, expanded structural formulas generally occupy a lot of space, and condensed structural
formulas represent a shorthand method for conveying the same information.
 In order to guide you further, the expanded structural formulas for methane, ethane, and propane are shown below:

b. Condensed formula

 Simplified form of Displayed Formulae to prevent taking up too much space

Example: Ethanoic Acid (C2H4O2)

 Partially condensed structure: provides a very clear picture of where each of the atoms is bonded in space
 Fully condensed structure: contains more information about bonding order than the molecular formula

 A condensed structural formula is a structural formula that uses groupings of atoms, in which central atoms and the
atoms connected to them are written as a group, to convey molecular structural information.
 The condensed structural formulas for methane, ethane, and propane are shown below:

 Expanded vs. Condensed: It is important to note that expanded structural formulas show all bonds within a
molecule and that condensed structural formulas show only certain bonds—the bonds between carbon atoms.
Specifically, the bond line in the condensed structural formula denotes the bond between the fi rst carbon atom
and the second carbon atom; it is not a bond between hydrogen atoms and the second carbon atom.

c. Line and Skeletal formula

 All the hydrogen atoms are not shown and all the carbons are not labeled but rather are indicated at the end or
bend in every line, leaving just a carbon skeleton with functional groups attached to it
 Any heteroatoms (any other atom than carbon or hydrogen) and hydrogens attached to heteroatoms are shown
in condensed form

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 Example: Butanol (C4H10O)

 In a line or skeletal diagram, the following assumptions can be made:

 There is a carbon atom at each line junction and at the end of each line.
 There are enough hydrogen atoms attached to each carbon to make the total number of bonds on that carbon
equal to 4.
 All heteroatoms (and hydrogens attached to heteroatoms) are shown in condensed format on the skeletal
structure.

 The skeletal structural formula still represents a unique alkane because we know that each carbon atom shown
must have enough hydrogen atoms attached to it to give the carbon four bonds.

C.2. Empirical formula:

 The simplest types of chemical formulas are called empirical formulas, which indicate the ratio of each element in
the molecule. The empirical formula is the simplest whole number ratio of all the atoms in a molecule.

 Example:
 The molecular formula for glucose is C6H12O6. The molecular formula indicates the exact number of atoms in
the molecule.
 The empirical formula expresses the smallest whole number ratio of the atoms in the element. In this case, the
empirical formula of glucose is CH2O.

C.3. Molecular formula:

 A molecular formula is not a chemical name, and it contains no words. Although a molecular formula may imply
certain simple chemical structures, it is not the same as a full chemical structural formula.
 Molecular formulas are more limiting than chemical names and structural formulas. Below is are the common
molecular formulas used in organic chemistry.

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C.4. Molecular Models

a. Wedge-Dash formula

 Allows the visualization of the precise 3-D arrangement in parts of some molecules
 Conventional symbols used:

Example: 2-butanol

b. Ball and Stick Models

 Displays both the three-dimensional position of the atoms and the bonds between them
 Atoms are represented by spheres, connected by rods which represent the bonds; double and triple bonds are
usually represented by two or three curved rods, respectively, or alternately by correctly positioned sticks for
the sigma and pi bonds

Example: Methane

Three different representations of CH4: On the left is the ball and stick model, in the center is the displayed formula,
and to the right is the space-filling model.

c. Space Filling Models

 Atoms are shown as spheres whose diameters are proportional to their atomic radii
 The center-to-center distance between the spheres is proportional to the corresponding bond lengths

Example: Methane

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