ORG MED LABORATORY HANDOUT 1

2PH-A

REVIEW IN ORGANIC CHEMISTRY II.Sp2 Hybridization- When carbon atom bound to

 ORGANIC CHEMISTRY- is a chemistry three atoms (two single bonds, one double bond)
subdiscipline involving the scientific study of
the structure, physical and chemical of
organic compounds and organic materials

CARBON
 Group 4A Period 2

III. Sp Hybridization- when carbon is bound to two

other atoms (two double bonds or one single + one
triple bond).

Characteristics of CARBON

1.________- ability to bond successively to other

carbon atoms to form chains and rings of varying
sizes
2. ________-mixing of 2 or more non-equivalent
EXAMPLE: CH3-CH=CH-CH2-C=C-CH=CH-CH2-
atomic orbitals to form new set of equivalent orbital
CH=CH-CH3
TYPES:
o Sp3 - 4 hybrid orbitals - Single bond –
EXERCISE #1: CH2=CH-C=C-CH2-C=C-CH=CH-
Tetrahedral
CH2-CH2-CH3
o Sp2 - 3 hybrid orbitals – Double bonds –
Planar
Examples of Organic Compounds:
o Sp1 - 2 hybrid orbitals – Triple bond –
Diagonal or Linear o DNA
o ¨ table sugar or sucrose, C12H22O11 ¨
HYBRIDIZATION OF CARBON o benzene, C6H6 ¨
o methane, CH4 ¨
I.Sp3 Hybridization- When carbon is bonded to four o ethanol or grain alcohol, C2H6O
other atoms (with no lone electron pairs).
Examples of organic compounds that don't
contain carbon-hydrogen bonds.

o Carbon Tetrachloride
o Urea

Exemption:
o Carbonates ¨ Simple Oxides of Carbon ¨
o Cyanides ¨

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 o Diamond
Note: containing carbon is not sufficient for a
compound to be considered organic!
¨ PHARMACEUTICAL CHEMISTRY
 is best to be defined as an interdisciplinary
research area incorporating different
branches of chemistry and biology in the
research for better and new drugs. (Drug
discovery)
 Generally, it is concerned with healthcare,
and the discovery and design synthesis and
testing of new and better therapeutic
chemicals and development of these
chemicals into new medicines and drugs in
a new era of detailed knowledge of genes
and determining 3-dimentional molecules
 GENERALLY MEDICINAL CHEMISTS
CAN:
o Make a new compound
o Look for structure and alter it
MEDICINAL CHEMISTRY
 - involves in the identification, synthesis and
development of NEW CHEMICAL
ENTITIES suitable for therapeutic use. It
also includes the study of existing drugs,
their biological properties, and their
QUANTITATIVE STRUCTURE-ACTIVITY
RELATIONSHIPS (QSAR). It focused on
quality aspects of medicines and aims to
assure fitness for the purpose of medicinal
products.
DRUG
 defined as an agent intended for use in the
diagnosis, mitigation, treatment, cure or
prevention of disease in man or in other
animals
ORGANIC PHARMACEUTICAL CHEMISTRY
 Study of carbon-based medicinals.
 A scientific discipline at the intersection of
chemistry and pharmacy involved with
designing, synthesizing, and developing
pharmaceutical drugs.
NEW DRUG DEVELOPMENT PROCESS
DISCOVERY PHASE- involves synthesis, isolation,
fermentation, screening, and SAR studies
1. Choosing a disease- Focus is on the financial
return
2. Choosing a drug target- receptor, enzymes,
and nucleic acid.
3. Identifying a bioassay a. _____________-
inducing a clinical condition and treated with the
test drug. b. _____________- drugs activity is
tested on isolated tissues, cells or enzymes.
*HIGH THROUGHPUT SCREENING- involves the
automated testing of large numbers of compounds
against a large number of targets where, typically,
several thousand compounds can be tested in 30-
50 biochemical tests at once.
4. Finding a lead compound
*LEAD COMPOUND- A compound showing a
desired pharmacological property which can be
used to initiate a medicinal chemistry project.
WAYS OF DISCOVERING A LEAD COMPOUND:
1. Screening of natural products
a. Plant Kingdom- morphine, cocaine, quinine,
periwinkle
b. Microbiological world- penicillin, cephalosphorin,
tetracyclines, aminoglycosides, lovastatin
c. Animal sources-PROTEINS (somastatin,
glucagon), POLYSACCHARIDES (heparin), URINE
OF PREGNANT MARE (Hormones)
d. Biological source-vaccines (living or killed
microorganisms) e. Medical folklore
2. Screening synthetic banks
3. Existing drugs
4. Combinatorial synthesis
5. Computer-aided design
6. Serendipity and prepared mind
NEW DRUG DEVELOPMENT PROCESS
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5. Isolate and purify the lead compound
6. Determine the structure by NMR, IR
spectroscopy, X-ray, crystallography
7. Identify the SAR (Structure Activity
Relationship) via invitro.
8. Identify the PHARMACOPHORE * the atoms or
functional groups required for a specific
pharmacological activity, and their relative positions
in space.
9. Improve target interaction and
pharmacokinetic properties
10. Study drug metabolism and test for toxicity
11. Design a manufacturing process
PRE-CLINICAL STUDIES PHASE
 - includes Chemical and physical
characterization, pharmacology,
pharmacokinetics, pharmacodynamics,
pharmaceutics, analytical studies,
toxicology
Pharmacology - the science of properties of
the drugs and its effects in the body.
Pharmacokinetics- the handling of a drug
within the body, it includes the ADME process.
Pharmacodynamics - the study of the
interaction of drugs with cells
11. Design a manufacturing process
PHARMACEUTICS- the general area of study
concerned with the formulation, manufacturing,
stability and effectiveness of a pharmaceutical
dosage form.
*TOXICOLOGY- in vitro and in vivo testing that
involves determination of LD50.
UNDER FDA REQUIREMENT: A sponsor must first
submit data showing that the drug is reasonably
safe for use in initial, small-scale clinical studies.
12. FILE IND Application
 Patent the drug – an exclusive rights to the
use and profits of a novel pharmaceutical
for a limited term
 - special consideration is given on Orphan
drugs
 Orphan drug – used to treat orphan
disease, or disease that affects fewer than
200,000 people in the US
Investigational New Drug Application
 The IND is also the vehicle through which a
sponsor advances to the next stage of drug
development known as CLINICAL TRIALS.
 "Investigational use" suggests the use of an
approved product in the context of a clinical
study protocol. When the principal intent of
the investigational use of a test article is to
 develop information about the product's
safety or efficacy, submission of an IND
may be required.
 The main purpose of an Investigational New
Drug (IND) application is to provide the data
showing that it is reasonable to begin tests
of a new drug on humans.
 The IND is not an application for marketing
approval.
 A sponsor shall submit an IND to FDA if the
sponsor intends to conduct a clinical
investigation with an investigational new
drug A sponsor shall not begin a clinical trial
until the investigation is subject to an
approved IND application.
13. CARRYING OUT CLINICAL TRIALS
14. Market the drug
 Submission of New Drug Application (NDA)
 NDA is submitted for review and approval
after the completion of the clinical trials and
requirements have been met.
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  When the preclinical and clinical studies
have proven the IND’s effectiveness and
safeness by all parameters
DRUG DESIGN APPROACHES
A. STRUCTURE-BASED DESIGN
 One of the first techniques to be used in
drug design
 Refers specifically to finding and
complementing the 3D structure (binding
and/or active site) of a target molecule such
as a receptor protein. Chemists may be
guided to subsets of compounds with
desired features to complement 3-
dimesional shape of the site.
B. COMPUTATIONAL CHEMISTRY
 A method which screens small molecules in
the database and identify potential
candidate compounds.
 Such databases are published or
commercially available, for instance, at MSI
(Molecular Simulations) and other similar
service organizations. In here the best kind
of position and orientation of compounds
are studied for most favourable conformers
based on energy considerations.
 Used to design combinatorial libraries.
Statistical techniques such as QSAR
analysis may be used in order to choose
targeted compounds with required features,
and for diverse libraries, techniques such as
PCA (Principal Component Analysis) may
be used for
ensuring as wide a range as possible of
compounds in the library. The component
here may be activities, properties or
substructures of the molecule.
C. ACTIVE-ANALOG APPROACH
 A method that designs a ligand based on
similarities to a set of compounds known to
possess the desired activity. The affinity
score is calculated to select candidate
compounds with strong binding to the target
site.
 In addition, when the target site is not
known for a ligand, various programs allow
to characterize likely sites through
computational approaches for functional site
mapping that involves repeatedly placing
small functional groups into the possible site
to approximate the shape of the binding
region. Likely sites may also be inferred
from similarity to known site structures.
D. COMBINATORIAL CHEMISTRY
 Combinatorial chemistry is now widely used
to generate vast libraries of molecules that
can be screened for biologically active
compounds. However, combinatorial
chemistry gives rise to an enormous
number and range of compounds that they
are not necessarily synthetically accessible
drug-like molecules.
 Useful new compounds may not emerge
unless intelligently designed in the library
production. Sets of compounds (libraries)
may be well targeted or diversified,
depending on the degree of available
information.
Organic Chemistry
 Study of carbon containing compounds
except carbonates, bicarbonates, cyanides
and oxides.
Catenation
 Ability to bond other carbon atoms to itself
to form very large and complex molecules
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  The purpose of the IUPAC system of
Comparison Between Organic & Inorganic nomenclature is to establish an international
Compounds standard of naming compounds to facilitate
communication. The goal of the system is to
give each structure a unique and
unambiguous name, and to correlate each
name with a unique and unambiguous
structure.

FUNDAMENTAL PRINCIPLE
 IUPAC nomenclature is based on naming a
molecule’s longest chain of carbons
connected by single bonds, whether in
continuous chain or in a ring. All deviations,
either multiple bonds or atoms other than
carbon and hydrogen, are indicated by
prefixes or suffixes according to a specific
Urea set of priorities.
 1st organic compound synthesized §
 Most abundant organic compound PREFIXES USED BASED ON THE NUMBER
Characteristics: OF CARBON
✔Catenation

✔Isomerism

Functional Groups

TYPES OF NOMENCLATURE
 SYSTEMATIC NAME- refers to
____________. - A name composed wholly
of especially coined or selected syllables. -
Ex:
 TRIVIAL NAME aka ________________. -
Refers to a compound, independent of
structures and sometimes assigned even
before the structure is known. - A name
 no part of which is used in a systematic
sense.
INTRODUCTION - Ex:

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  SEMISYNTHETIC aka ________________.
A name of which only a part is used in a
systematic sense. - Most names in organic
chemistry belong to this class.
 - Ex:
 LOCANT- Denotes the numeral or letter
that indicates the position of an atom or
group in a molecule.

TYPES OF NOMENCLATURE  NUMERAL- is a locant when it indicates the

position of a substituents or bond in a
 VERNACULAR NAME is a name used in a structure
lab, trade or industry that does not
unambiguously describe a single chemical. HYDROCARBONS
Ex: - chain or series of H-C
 ARCHAIC NAME is an older name for a MAIN CLASSES:
chemical that predates the modern naming 1. Aliphatic Hydrocarbon
conventions. a. ___________
Ex: b. ___________
 CAS NUMBER is an unambiguous 2. Aromatic Hydrocarbon
identifier assigned to a chemical by the 3. Alicyclic Hydrocarbon
Chemical Abstracts Service (CAS), a part of
the American Chemical Society A. Aliphatic
- single chain, no ring/s involved
CHEMICAL FORMULA
-It is a format used to express the structure of 1. ________– Single bonds only, Alkane Family
atoms. 2. ________– has multiple bonds, Alkenes &
1. Structural Formula Alkynes
2. Molecular Formula
3. Empirical Formula

Types of Aliphatic Hydrocarbons

TERMINOLOGIES USED IN ORGANIC 1.Alkanes
NOMENCLATURE
 Characterized by single covalent bonds
between carbon atoms.
 RADICAL-A group of atoms common to a
 CnH2n +2 (R-H)
number of compounds ¤ - Such groups are
 sp3 hybrid
 IUPAC Naming ends with -ane
often called radicals in nomenclature CH3 CH3-CH2-CH-CH-CH3 CH3
parlance. Free radicals are always given the
designation “free” in nomenclature work. 2. Alkenes
 Characterized by having double bonds
 FUNCTIONAL GROUP – A group of atoms between carbon atoms.
that defines the “function” or mode of  CnH2n
activity of a compound.  sp2 hybrid
 PRINCIPAL GROUP-  IUPAC Naming ends with -ene Types of
“________________________” - Denotes Aliphatic Hydrocarbons
the group named as suffix use of “principal CH2=CH-CH-CH3
group” CH3
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3. Alkynes
 Having a triple bond between two carbons
 CnH2n-2
 sp hybrid

 IUPAC Naming ends with -yne 1. Hydroxy Derivatives

CH3-CH=-CH2
B. AROMATIC HYDROCARBON
 presence of ring/s, specifically Benzene
Ring and its derivatives.
Alcohols
 With –OH functional group
 R-OH
 IUPAC Naming ends with –ol
Classifications of Alcohols

1. According to the number of alkyl groups attached

to the carbon bearing the hydroxyl groups. Ø
 1º CH3-CH2-OH
 2º OH
CH3-CH-CH3
 3º CH3`
CH3-C-CH3
OH
HUCKEL’S RULE
`-used to determine if a compound is aromatic
or not. 2. According to the number of hydroxyl groups.
FORMULA: 4n + 2 = Pe- (electrons in double
bond)  Monohydric - CH3-CH2-CH2-OH
RULE: His rule states that if a cyclic, planar  Dihydric - CH2-OH
molecule has 4n+2 π electrons, it is considered CH2-OH
aromatic.  Polyhydric
Example: Benzene CH2-OH
CH -OH
AROMATIC OR NOT? CH2-OH

1. Hydroxy Derivatives

Phenol
 the –OH group is bonded to a conjugated
cyclic planar system
 Ar-OH

2. Ethers

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  Formed by the reaction of alcohol with CH3-CO-CH2-CH2-CH3
sulfuric acid that removes water from two
molecules of alcohol. 4. Carboxylic Acids
 R-O-R § IUPAC Naming ends with –oxy +
Alkane series  Results from the oxidation of aldehyde
CH3-O-CH2-CH3  R-COOH
 IUPAC Naming ends with -oic acid
Classification of Ethers
CH3-CH2-CH2-COOH

1. Open Chain
 Symmetrical
CH3OCH3
 Asymmetrical
2. Cyclic Ethers

3. Carbonyl Compounds

a.ALDEHYDES
 Formed by the oxidation of primary alcohol
 RCH=O
 IUPAC Naming ends with -al
CH3-CH2-CH2-CHO

5. Amides

b) KETONES  Formed by the reactions of organic acids

 formed by the oxidation of secondary with ammonia or with amines
alcohol.  R-CO-NH2
 R-CO-R  IUPAC Naming ends with -amide
 IUPAC Naming ends with -one CH3-CO-NH2

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 6. Esters
 Produced by the reaction of organic acid
with an alcohol.
 R-COO-R`
 IUPAC Naming the alkyl group R` is named
1st followed by the name of RCOO ending
with –oate.
CH3-COO-CH2-CH2-CH3

7. Nitrogen Containing Compounds 8. Alkyl Halides

a) Amines  Derivatives of alkanes in which one

 Organic compound derived from ammonia.
 R-NH2
 IUPAC Naming ends with -amine
Classifications of Amines
hydrogen atom in an alkane has been
replaced by a halogen atom.
 R-X
 Where R is any alkyl radical and X is any
halogenide (F, Cl, I, Br)

1. Primary Amine (1R) CH3-NH2

2. Secondary Amine (2R) CH3-NH-CH2-CH3 Types of Alkyl Halides

3. Tertiary Amine (3R) CH3-N-CH3 1. Primary Alkyl Halide (R-X)

CH3 CH3-CH2-CH2-CH2-Br
2. Secondary Alkyl Halide (R-CHX)
Br
CH3-CH-CH2-CH3
3. Tertiary Alkyl Halide (R-CX)
4. Quaternary Amine (4R) Br
CH3-C-CH3
CH3

Sulfur-Containing Compounds

7. Nitrogen Containing Compounds Nitriles 1. Mercaptans- CH3SH

2. Thioethers- CH3CH2SCH3
 Alkyl derivatives of hydrogen cyanide, HCN
3. Disulfides- CH3CH2CH2SSCH2CH3
 R-CN
 Named by giving the name of the alkyl 4. Thiocyanates- CH3CH2CH2SCN
group and ends with –nitrile 5. Thiophenol-
CH3-CH2-CN

Nitrogen-Containing Compounds