MODULE 1: ORGANIC CHEMISTRY

FUNCTIONAL GROUPS

A. HALOGEN-CONTAINING
R – X (alkyl halide)
Ar – X (aryl halide)
B. OXYGEN-CONTAINING
 R-OH (Alcohol)
 Ph-OH (Phenols)
 RC=OH (Aldehydes)
 RC=OR (Ketones)
 RCO=OH (Carboxylic Acids and Derivatives)
o Derivatives of CA
 RCOOR’ (Esters) TECHNIQUE IN HYBRIDIZATION: In determination, count
 ROR (Ethers) the number of bonds. Take note that the DOUBLE and
TRIPLE bonds are counted as one bond.
Methoxyethane – ROR (ether)
In example,
H3C-O-CH2CH3
ETHYLENE (H2C=CH2)  3 bonds (sp2) – TRIGONAL
Meth – 1 carbon (R)
PLANAR
Oxy – means with Oxygen

Ethane – Alkyl group (R)

C. NITROGEN CONTAINING FUNCTIONS

ACETYLENE  2 bonds (sp) -- LINEAR
R- NH2 (amines)

BENZENE  3 bonds (sp2) – TRIGONAL PLANAR “flat

planar molecule”

D. HETEROCYCLIC COMPOUNDS
E. SULFUR-CONTAININGING
R-SH (Thiols)
R – S – R (Thioethers)

PROPERTIES OF CARBON
CYCLOPENTANE  4 bonds (sp3) – TETRAHEDRAL
Carbon - central of organic chemistry

1. Stability
- TETRAVALENT, 4 bonds needed
2. Catenation- the stability of C to form
chains/structure
3. Mixing of 2 or more non-equivalent atomic
orbitals to form a new set of equivalent atomic
orbitals called “HYBRID ORBITALS”; process:
HYBRIDIZATION 4. ISOMERISM

HYBRIDIZATION MOLECULAR BOND ISOMERISM

GEOMETRY ANGLE
sp Linear 180 deg  2 or more compounds having the same molecular
sp2 Trigonal planar 120 deg formula but different structure/structural formula
(flat)
sp3 Tetrahedral 109.5 deg STRUCTURAL/CONSTITUTIONAL ISOMERISM - Differ
based on the ORDER OF BONDING
 o Chain Isomers “Skeletal Isomers” Draw:
 Existence of BRANCHING
form of carbons (Carboxylic Acid) (Ester)
 Ex. C4H10 (Butane)
 STEREOISOMERISM – difference In SPATIAL
ORIENTATION
o Geometric Isomers – involved rigid
bonds such as double bonds and ring
system
 Occurs in ALKENES, CYCLIC
ALKANES
 Gives rise to “cis/trans” and
“E/Z isomers’
 Stability: Cis > trans
o Positional Isomer  CIS TRANS – used only for
 Difference in the position of SIMILAR (approximately)
substituents, difference in the substituents around the double
position of multiple bonds/in bond
the position of FG  “cis = same side” ; “trans:
 Ex. Isoproterenol and opposite side”
Metoproterenol (difference in Draw:
OH position)

 E/Z Isomerism – used for

double bonds with different
substituents around it
 Dihydroxybenzene
 Z – zame side ; E – eppesite
 Classical: “ortho”,
side
“meta”, “para”
 IUPAC: 1, x- Draw:
disubstitution”

o Conformational Isomers – rotation

along the SINGLE BOND
 can be combined “SUMMATION”  Main driving force of stability:
*CRESOL exists in three isomeric forms (ortho, “STERIC EFFECT” – the
meta, para) presence of bulky groups (ie. R
groups/Alkyl groups ; aromatic
o Functional Isomerism – difference in rings)
functional groups but same molecular  Stability: Anti>Syn
formula  Antistaggered (Anti) – 2
o Ex. C2H6O bulky substituents are
completely opposite to each
Draw: other
(Alcohol) (Ether)  LOW steric effect,
more stable
 Eclipse (Syn): two bulky
substituents are adjacent
o Ex. C3H6O (eclipsing) to each other
 HIGH steric effect,
Draw: less stable
(Aldehyde) (Ketone) Conformations:

 Chair and Boat (w/ flag pole

position – eclipsing): Cyclohexane
o Ex. C3H6O2
 Banana Bonds- Cyclopropane
 Butterfly – Cyclobutane
  Envelope - Cyclopentane Draw (Case 2): R – enantiomer (The original molecule said to
o Configurational/Optical Isomers – be counterclockwise is the opposite, meaning clockwise. )
involved the existence of CHIRAL
CENTER/S; gives rise to “R&S” isomers,
aka ENANTIOMERS
 OPTICAL ACTIVITY – the
ability of the compound to
rotate plane-polarized light
either to the right/left
 Dextrorotatory (d/+)-
clockwise Draw (Case 3): NEITHER
 Levorotatory (l/-) -
counterclockwise
REQUIREMENTS FOR OPTICAL ACTIVITY:
(1) The compound must have an asymmetry
carbon or CHIRAL CENTER
o Sp3 hybridized carbon w/ four
different groups attached

Draw (Case 4): PROPRANOLOL

(2) No symmetry

ENANTIOMERS – optically active compound

and comes in pair ; same physical properties
and only DIFFER in the ROTATION of plane
polarized light
Represented as:
a. Dash (away; back) and Wedged
(towards; front) Draw (Case 5): CHLORAMPHENICOL

b. Fischer Notation – uses TWO

PERPENDICULAR lines with the
intersection representing the chiral
center.

ABSOLUTE CONFIGURATION OF ENANTIOMERS

(1) Prioritize the substituents using Cahn-Inlog Prelog FISCHER NOTATION

sequence
Tip: On Fischer notation, always find H since it is the least
(2) Place the least prioritized group at the back
prioritized group (S/R depends whether the H is on vertical or
(3) R – clockwise ; S – counterclockwise
horizontal bond).
Tip: Always find the H (must be dashed). If on the solid line, H
Case 1: The prioritized group is on the vertical bond.
must be put at the back.
(Counterclockwise – S ; Clockwise – R)
Draw (Case 1): S-Enantiomer

Case 2: The least prioritized group is on the horizontal bond.

((Counterclockwise – R ; Clockwise – S)
*ISOSTERES – interchangeability of one atom w/ another
atom of approximately similar properties (Ex. Alcohols and
Thiols)

- If O and S are changed, it changes PK

properties (i.e making the drug
rapid/short/long acting)

FISCHER-ROSANOFF NOTATION

 D- & L- configuration
Draw (Case 4): ”Z-Toremifene”
 Used for configuration of Amino acids and
monosaccharides

CAHN- INGOLD-PRELOG SEQUENCE

 Used for naming enantiomers and diastereomers

 The higher the atomic # of the substituent atom =
HIGHER PRIORITY

Draw (example from E/Z):

Technique: (1) Divide double bond in half, determine the

priority. Between C and H, choose the one with highest atomic
number. :

(2) On the next half, determine the priority. Choose the one NOMENCLATURE
with highest atomic number.
- Always determine the longest continuous
Draw (Case 1): Carbon chain (number the chain such that
your substituents should have the lowest
possible number)
- Substituents are listed in ALPHABETICAL
order
o Prefixes: di, tri, tetra, etc. (ignored in
alphabetized order)
- Possible substituents:
o Alkyl group (R) – “kyl”
o Halides (X) – “halo” (in general)

Ex. CH3CH2CH2CH=CH2 (1-pentene/pentene)

FORMATION OF ESTERS (RCOOR’)

Draw (Case 2):
RCOOH (carboxylic acid) + R-OH (alcohol)

First to be named is alcoholic part “alkyl” then CA “ic acid” 

“ate” to denote ester

General Naming Patter: “ALKYL ALKANOATE”

Draw (Case 3):
a.
 “Butyl pentanoate” aka Butyl valerate

b.

Draw (Case 1):

“Phenyl propanoate”

HALOGENATION REACTION OF ALKANES

*Radicals (.A.) – unpaired electron, highly reactive ; HALOGENATION OF ALKENE

resulted from HEMOLYTIC CLEAVAGE (equal partitioning
presence of organic solvent (ie. Methylene, Carbon
of e-)
tetrachloride, Chloroform
Mechanism: FREE RADICAL SUBSTITUTION

A. Chain Initiation Step – formation of radicals in

which it is located on the PRODUCT side

HETEROLYTIC Cleavage – unequal partitioning of

e- (Electrophiles – “e- poor” ; Nucleophilic – “e –
rich” HYDRATION OF ALKENE

Cl2 -- UV 2 . Cl addition of water (water is nucleophile) and is on ACIDIC

B. Chain Propagation Step – radical is on the ENVIRONMENT
REACTANT and PRODUCT side
Product: Alcohol
.Cl + CH4  .CH3 + HCl

C. Chain Termination Step – formation of non

radical product (radical is on REACTANT side)
.Cl + .Cl  CI2
.Cl + .CH3  CH3
. H3C + .CH3  H3CCH3
D. Chain Radical Step
HYDROXYLATION OF ALKENE
Other mechanisms:
Baeyer’s Test (Rgt: KMnO4) in either basic/neutral on cold
Nucleophilic addition: Aldehydes and Ketones environment.
Nucleophilic substitution: CA and derivatives - Product: Vicinal diol + MnO2 (brown)
Electrophilic Substitution: Aromatic Compounds

(without this mechanism, ring deactivators cause

substitution at META position “meta deactivators”
ie. Nitro, SO3H, -CN)

ring activators – ortho & para (ie. -OH, -NH2, R-

group, -CH=CH2 (VINYL). phenyl)

Electrophilic Addition: Alkenes and Alkynes

HYDROGENATION OF ALKYNES
PRODUCT OF HYDROGENATION OF ALKENES
- Lindlar’s Rgt (catalyst)
Common Catalyst used: Pd, Pt, Ni o Product: Alkene
Product: Alkane Draw:

- Catalyst: Pt/Pd/Ni
 o Product: Alkane Example: Test for Aromaticity

Draw:

6 π e- = 4n
HYDRATION OF ALKYNE
6-2 = 4n
Addition of water in the presence of ACID
n=1 (aromatic)
PRODUCT: Enol (is in equilibrium with Ketone)
Anti-aromaticity rule – the number of pi electorns must be
equal to 4n, where n= 1,2,3….
Equilibrium is known as “TAUTOMERIZATION” - KETO-
ENOL TAUTOMERIZATION Zaitsev’s rule – applicable for ELIMINATION type of rxn
Stability: Ketone (stable) : Enol (unstable)
Application for Markovnikov’s Rule:
Draw:
Major product for CH3CH=CH2 + HCl 
(24) Product: Butanone

RESONANCE

- Overall charge of the system remains the

same
- Involves delocalization of pi bonds
Other: - Bonding is expressed by MULTIPLE Lewis
formula
Alkyl Halides: Hydrohalogenation of Halides

Alcohol: Hydration of Alkenes

Diol: Hydroxylation Reaction

Markovnikov’s rule – ELECTROPHILE adds to the carbon

w/ GREATER number of H-substituents ; NUCLEOPHILES
adds to the carbon w/ LESSER number of H-substituents
BENZENE
Huckel’s rule “Aromaticity Rule / 4n+2 Rule” – the
number of pi electrons must be equal to 4n + 2.

CHARACTERISTICS OF AROMATIC COMPOUNDS:

1. Planar (ie. Benzene) and cyclic

- Benzene Reactivity – Electrophilic
substitution
2. Sp2 hybridization
3. Follows Huckel’s Rule
Catechol – benzene 1,2 diol (ortho)
4. Conjugated double bond system (alternating
double and single bonds) Hydroquinone – benzene 1,4 diol (para)

Resorcinol – benzene 1,3 diol (meta)

Cumulated vs Isolated

- Cumulated – 2 adjacent double

bonds
- Isolated – 2 double bonds away
from each other
 !!! ONLY REVERSIBLE RXN OF BENZENE

FRIEDEL-CRAFTS ACYLATION OF BENZENE

Xylene – dimethylbenzene

Cresol – methylphenol

Anisole – methoxybenzene

Anthranilic acid
Reacts with benzene: ACYLIUM ION (RC+=O)

Catalyst: AlCl3 / FeCl3

Product: Aromatic ketone

A. NITRATION OF BENZENE reaction principle

behind GUN COTTON/PYROXYLIN COLLODIN
(Polynitrated compound)

Titration of Benzene: Nitric Acid in the presence

of concentrated sulfuric acid

Reacts to benzene: NITRONIUM ION

FRIEDEL-CRAFTS ALKYLATION OF BENZENE

Reacts with benzene: Alkyl halide  “CARBOCATION”

Product: Alkylated benzene

HALOGENATION OF BENZENE
Catalyst: AlCl3 / FeCl3

ALCOHOLS
Ferric Halide / Aluminum Halide – Lewis acid catalyst
carbinol group:
Electrophile produced: (+X) “HALONIUM ION”

Product: Halobenzene / Halogenated benzene basis in

determining the
SULFONATION OF BENZENE types of alcohol
(location)
Titration of benzene: Sulfur trioxide in the presence of
concentrated sulfuric acid

Reacts with benzene: SULFONIUM ION

LUCAS TEST (HCl and ZnCl2) 1. Symmetrical Ether – same R groups on both
sides
Reactivity: 3 > 2 > 1 > Methanol - Ex. Dipropyl Ether

(+) result: Milky white immiscible liquid

2. Asymmetrical Ether – different R groups (ie.

Ethylmethyl ether)
3. Oxiranes/Epoxides/oxacyclopropanes – cyclic
ethers in w/c the ether oxygen is part of a 3-
Alkyl chloride ( R - Cl) membered ring system (ie. Ethylene oxide)

OXIDATION OF ALCOHOLS Ethylene oxide – gas sterilant

STOPS OXIDATION: PCC (Pyridiniumchlorochromate) Diethyl ether: gas anesthetic

K Dichromate

Eugenol (clove): antiseptic; component of Zn-Eugenol

cement
Partial oxidation Full oxidation
K Dichromate
Monobenzone: skin depigmentation

Test for ketones

K Dichromate ALDEHYDE AND KETONES “IODOFORM TEST”

A. NUCLEOPHILIC ADDITION REACTION Yellow crystalline ppt

EXAMPLE: Oxidation of benzyl alcohol using PCC will

produce benzALDEHYDE.

R- MgX “Actual Grignard” - used for the synthesis of

different types of alcohol *Cyanohydrin – precursor in the synthesis of Amino
acids
 Adding this to an aldehyde of 2 carbon or above
yields secondary alcohol B. NITROGEN NUCLEOPHILES
 if primary alcohol, the aldehyde must be
FORMALDEHYDE
 tertiary alcohol – rxn w/ ketone + R-MgX (ie.
Acetone)

DEHYDRATION OF ALCOHOL

Common dehydrating acid: H2SO4

Alkene

FORMATION OF IMINE DERIVATIVES: Reaction

between an aldehyde/ketone with hydroxylamine
STRUCTURAL PRINCIPLE OF ALCOHOLS: (NH2OH) produces R-C = N – OH.
Draw (48): OXIME
 Increase carbon chain length = increased VDW =
dec. H bonding = dec. water solubility
 Inc. polarity = Inc. water solubilty due to inc. OH-
groups
 Inc branching = Dec. VDW = Inc. solubility

Not an alcohol (Menthol, Sorbitol, Eucalyptol, Terpin Rxn with Hydrazine  Hydrazone
hydrate) Eucalyptol is said to be an ETHER.
Rxn with Phenylhydrazine 
ETHERS Phenylhydrazone

Classification of Ethers: Rxn with 2,4 – DNPH – 2,4

dinitrophenylhydrazone (yellow crystalline ppt
– carcinogenic)
 BENEDICT’S TEST – test for the presence of reducing sugars; (+) DIAZOTIZATION – principle behind the production of azo
for aliphatic aldehyde and ketones (brick red ppt) dyes
TOLLEN’S TEST/Silver Mirror Test – used to determine Draw:
Aldehyde

SELIWANOFF’S TEST

REACTIONS OF ALDEHYDES & KETONES w/ ALCOHOL

Partial reaction of Aldehydes with alcohol produced

HEMIACETAL. REDUCTION TOF AZO GROUPS

If first mole reacts with aldehyde/ketone, it forms  Reduction (addition of Hydrogen)

HEMIACETAL/HEMIKETAL.  Produces 2 amines

If hemiacetal/hemiketal reacted to the second moles of SOLUBILZATION IN WATER – must be in ACIDIC media
alcohol, it will become ACETAL/KETAL. and protonated amine (ionized form, enhanced solubility)

CARBOXYLIC ACID HINSBERG TEST – (Rgt: Benzyl sulfonyl chloride)

Nomenclature root word: “-oic acid” ie. 5C – Valeric acid Result: Formation of Sulfonamide precipitate

Reactivity: Acyl Halide > Acid Anhydride > Ester > Amide  Primary amine: soluble in alkali
 Secondary amine: insoluble in alkali
Ex. Which of the following is the most reactive: (Acetyl  Tertiary amine: no ppt
Chloride, Acetic Acid, Acetic Anhydride, Ethyl acetate)
Other:
SAPONIFICATION
Jones Oxidation – Chromic acid (rgt)
Base-catalyzed hydrolysis of esters (Alcohol and CA)
Janovski Test – Polynitration test
The product of the reaction of water with acetic anhydride is 2
moles of acetic acid.

Draw:

SOX2 (Thionyl halide) – reagent used to convert carboxylic

acid into acyl halide.

Draw (Conversion to Acid Derivative):

LiAlH4 (Lithium Aluminum Hydride) - reagent used for

REDUCTION of CA.

Draw (Reduction of COOH):

AMINE

The lone pair of e- in amine allow them to be a good LEWIS

BASE (e- pair donor)

Acidity: 2 > 3 > 1 > NH4

 Principle: Basicity of amine depends on the lone

pair of Nitrogen. If lone pairs are available  MORE
BASIC. (!!! ALKYL GROUPS ARE ELECTRON
REPELLING)
ACIDITY and STABILITY Infrared Spectroscopy For determination of
functional group
Acidity Principle: the higher the e- withdrawing (Cl, F, OH Atomic Absorption For QT determination of
and NO2 groups), the higher the acidity but has reduced Spectroscopy heavy metals
stability Mass Spectroscopy For analysis of gaseous
ions / MW determination
 Most acidic (Acetic acid, Chloroacetic acid, The arrow head denotes the number of electrons transferred.
Trichloroacetic acid, Trifluoroacetic acid)
 Fish hook arrow “half arrow head”: 1 electron
Stability Principle: electron donation improves stability (ex. has been transferred
Methyl groups – e- repelling group)  Full arrow head: 2 electrons have been transferred

 Reduces carbon stability: presence of Least to most water soluble: Toluene < Acetone < Methanol
electronegative atoms, lack of carbon and steric
hindrance  Toluene – benzene with CH3 (lipophilic/non polar)
 A methyl substituent located in the ortho position  Acetone – CH3O (carbonyl group – relatively polar)
usually causes STERIC EFFECT.  Methyl – CH3OH (polar due to OH group)

FORCES OF ATTRACTION What will happen to the Nitro group in this structure:

 ETOH and SA Draw:

o LDF happens between C chain-
interaction to benzene ring
o Intermolecular forces in between-
o Intramolecular forces
A. the nitro group will form H-bond with CH3 hydrogens (due
to the electronegativity, it is not interchangeable)

B. will be out of the plane (to relieve congestion of steric

effect)

C. the Nitro group will donate e- to the ring (Nitro is e-

withdrawing)

D. the Nitro group will cause CH3 to be out of the plane (steric
effect – due to methyl group)

The molecule presented contain which of the ff: functions:

DISULFIDE BONDS

- oxidation of sulfhydryl groups (-SH)

- Responsible for protein folding
o Protein – peptide bonds (amide FG)
- -SH + SH-  -S-S (disulfide)

Other macromolecules:

o Glycosidic bonds (ether): CHO

A. Lactone (cyclic ester)
ASA “Aspirin” – ester FG (process: HYDROLYSIS)  if B. Lactam (cyclic amide)
exposed to water, has VINEGAR ODOR C. Carbamate
D. Guanidine

ANALYTICAL METHODS
NMR Spectroscopy For structure elucidation
(ie. Proton and Carbon 13)