MODULE 1: PHARMACEUTICAL CHEMISTRY

Subject: Organic Chemistry

Prepared by : Deanne Marizthel J. Madrio, RPh

❖ ________________-branch of science that deals with the study of compounds containing Carbon
with __, __, __, __, __, & (F, Cl, Br,I - _______).
▪ ___________ - first organic compound synthesized from inorganic matter; discovered by
____________ from heating lead cyanate and ammonia.
▪ Vital force theory – organic substances could only originate from living material; disproved by
Wohler.
❖ CLASSIFICATIONS:

Organic Compounds

Hydrocarbons -compounds of C & H; backbone of organic compounds; Empirical formula

of CxHy
Aliphatic HC Aromatic HC Alicyclic
-HC compounds arranged in -aka __________; presence of ring
-aka ___________; chains that form a ring
linear chain or branched form system with multiple bond; Benzene
without multiple bond; behave like
without any ring system and its derivatives
aliphatic HC
involved. CnH2n - 2
*Polycyclic benzenoids/Polyaromatic
a. Saturated (Alkanes) HC – benzene rings fused together
- aka __________; single bond
only
CnH2n + 2
b. Unsaturated
- Alkenes aka________; double
bond
- Alkynes with triple bond in
structure CnH2n
CnH2n

HC Derivatives

Alkyl group -aliphatic HC loses one H, replaced by another atom, or becomes a substituent;
denoted as ’R’ under condensed structural formula ex. R-OH, R-NH2, R-X

Aryl group -aromatic HC loses one H, replaced by another atom, or becomes a substituent;
denoted as ’Ar’ or ‘Ph’ under condensed structural formula ex. Ar-OH, Ar-
NH2, Ar-X

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 HC DERIVATIVES

OXYGEN-CONTAINING SULFUR-CONTAINING HALOGEN-CONTAINING

NITROGEN-CONTAINING PHOSPHORUS-CONTAINING

❖ OXYGEN- ❖ NITROGEN- ❖ SULFUR- ❖ PHOSPHORUS- ❖ HALOGEN-

CONTAINING CONTAINING CONTAINING CONTAINING CONTAINING
• Alcohols: • Amines (amino group, - • Thiols (-SH) • Phosphate • Alkyl Halides
________ NH) -sulfur analogue of groups • Aryl Halides
• Phenols: • Primary Amines: RNH2 alcohols • Organophosph
_________ -aka “_________” ate
• Aldehydes: • Thioethers (R-S-R)
_________ • Thioesters
• Ketones: • Secondary Amines:
__________ R2NH
• Carboxylic
acids: _______
• Esters: *____________-
_________ • Tertiary Amines: R3N interchangeability of
one atom & another,
provided that they
have the
• Heterocyclic approximately similar
Nitrogenous # & arrangement of
compounds electrons.

Trend of basicity: Secondary >

Primary > Tertiary > NH3
❖ BENZENE Ex. Of Isosteres:
DERIVATIVES -Fluorine vs Hydrogen
-Hydroxyl vs Amino Acids
MONOSUBSITUTED DISUBSTITUTED -Hydroxyl vs Thiol Groups
-Methyl, Methoxyl, Hydroxyl,
Amino groups vs Hydrogen
-Fluoro, Chloro, & Bromo, thiol, vs
Methyl & other small alkyl groups

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 Cresol –o,m,p methylphenol; hydroxytoluene

Toluidine – methylaniline; prilocaine, an amino amide-type local anesthetic, yields o-toluidine when
metabolized by carboxylesterase enzymes. Large prilocaine doses can cause
methemoglobinemia due to oxidation of hemoglobin by o -toluidine.

Xylene- dimethylbenzene

Salicylic acid – 2-hydroxy benzoic acid

Catechol – 1,2 dihydroxybenzene –ortho; parent ring of catecholamines ;

Resorcinol – 1.3 dihydroxybenzene -meta

Hydroquinine – 1,4 dihydroxybenzene

❖ IMPORTANT HETEROCYCLES

A. NITROGEN-CONTAINING

➢ ____________-composed of four fused pyrrole ➢ Imidazole antifungals:

subunits interconnected at their α carbon
atoms via methine bridges; important in the
➢ ____________- imidazoline alpha adrenergic agonist
(Catapress®)
structure of chlorophyll and hemoglobin.

➢ ____________- pyrrolidine anticonvulsant (Keppra®)

B. OXYGEN-CONTAINING

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 C. SULFUR-CONTAINING

❖ Systems of Nomenclature:
1. Common name- uses the name given when
it was discovered
example: Formic Acid (Latin, formica=ants);
simplest carboxylic acid
- Uses prefixes: -n, -iso, -neo; considered in
alphabetizing
2. Derived Names - derived from a parent
compound
3. IUPAC (international Union of Pure & Applied
Chemistry) - most systematic
example: 2-methylhexane, methanoic acid
IUPAC Rules:
1. Name by considering the longest carbon chain
2. Number C atoms consecutively from one end so that the branches or substituents are given the
lowest position numbers
3. Modify the suffix based on the type of formula or the functional group
4. Identify the substituents & indicate the positions by using numbers
5. If there is more than one of the same substituent/ alkyl group on the chain, indicate the number of
groups by using prefixes; di-two; tri-three; tetra-four; & so on. Ignore these prefixes when
alphabetizing.

❖ CARBON
➢ Properties:
1. Atomic & Molecular Orbitals
Electron configuration of Carbon: 1s22s22p2 or (He)2s22p2

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 ELEMENT ELECTRONIC ELECTRONS IN ORBITAL DEDUCTION
CONFIGURATION 1s 2s 2p

Carbon Ground state Divalent with lone pair

Excited state Tetravalent

Nitrogen Trivalent with one lone

pair
Oxygen Divalent with two lone
pairs
Fluorine Monovalent with
three lone pairs

*Note: In the periodic table, from left to right, increasing atomic number, increasing
electronegativity (H<C<N<O<F(Most electronegative element)) ; Down the group, increasing
atomic number, decreasing electronegativity (F>Cl>Br>I)
➢
2. Stability
*Follows the Octet Rule
-chemical rule of thumb that reflects the theory that main-group elements tend to bond in
such a way that each atom has eight electrons in its valence shell, giving it the same
electronic configuration as the nearest noble gas; only applicable to the main group elements
aka ‘__________________’
> 2 ways of achieving this: REDOX or covalent bonding (in the case of carbon interaction
with other atoms – its covalent bonding); Remember that Redox mainly or more commonly
happens in inorganic compounds, especially during formation of ions.
*Covalent bonding - _________ of electrons; Intermolecular or intramolecular force?
____________
3. Catenation – ability of an atom to form multiple bonds to itself in chains or in branching
4. Hybridization – mixing of two or more non-equivalent atomic orbitals to form a new set of
equivalent ‘hybrid orbitals’
HYBRID ORBITAL GEOMETRY BOND ANGLE EXAMPLE
Sp3 (no lone pair) tetrahedral 109.5° methane
(1 lone pair) Trigonal pyramidal 107° NH3
(2 lone pair) Bent 104.5° H2O
Sp2 (no lone pair) Trigonal planar 120° Formaldehyde
(1 lone pair) Bent 118° ozone
Sp Linear 180° HCN

5. Isomerism - refers to the existence of two or more compounds having the same molecular
formula, but different structure
______________- the branch of organic chemistry that is solely dedicated to the study of isomers
➢ Isomers differ in the ff. :
A. Order of Bonding (Constitutional Isomers)
1. Chain Isomers – exhibited by alkanes due to possibility of branching;

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 2. Positional Isomers – compounds that differ only in the position of substituent,
functional group, or multiple bond
2a. Acyclics

2b. Cyclics

3. Functional Isomers – differ in functional group

B. Spatial Orientation (Stereoisomerism)

1. Geometric Isomers – exhibited by alkenes and cycloalkanes; stereoisomers which
differ from each other in the arrangement of groups with respect to the double
bond or ring structure
1a. Ayclic
• Cis/trans isomerism – used for double bonds w/ approximately similar
substituents around it.
________- same side __________- opposite side

• E/Z isomerism – used for double bonds w/ different substituent around it.
_______- same side ________-opposite side
*Rule: Prioritize the substituents using Cahn-Ingold Prelog sequence (the
__________the atomic number means higher priority); analyze whether the
highest priority on each side are on the same side.

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 Case 1:

Case 2:

Case 3:

1b. Cyclic

2. Conformational Isomers – compounds that differ in their rotation along single bond
2a. Acyclic

Stability: Anti-staggered>Gauche>E2>E1

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 2b. Cyclic – rotation along single bond results to ‘ring flipping’

Except: Cyclopropane

Cyclobutane

Cyclopentane

Cyclohexane

Stability:

3. Configurational Isomers – compounds that exhibit optical activity

*Optical activity- ability of a compound to rotate plane polarized light either to the right or
left
a. Dextrotatory (d/ +) – rotate plane polarized light to the right
b. Levorotatory (l/ -) – rotate plane polarized light to the left
*Note: Optical rotation of a compound can only be determined by a polarimeter.
Common mistake: interchanging of D and L isomer with d/+ or l/-.
Requirements for Optical Activity:
1. Chiral Center/ Chiral carbon/ Asymmetric chiral carbon aka __________ - is a carbon to
which four different atoms or group of atoms are attached
2. No symmetric element

No. of Isomers = 2n
n = number of chiral centers

Mirror Image? Superimposable

symmetry?
Meso compounds
Diastereomer
Enantiomer

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 ➢ Epimer - special type of diastereomers; identical in all except in one chiral center; differ only in
configuration at one asymmetric carbon atom
▪ D-glucose/ D-mannose - Epimers at carbon 2
▪ D-glucose/ D-galactose - Epimers at carbon 4
➢ Anomer - differ only in configuration at Carbon #1 (carbonyl C or anomeric C); designated as
alpha (OH pointing downward) or beta (OH pointing upward)
*Note: If Fischer Projection is given, and is asking for anomeric configuration, remember that :
OH on the right side will be placed downward on Haworth projection; OH on the left side will
be placed upward.

➢ Absolute configuration of Enantiomers:

Steps:
1. Prioritize the substituents using Cahn-Ingold Prelog sequence.
2. Place the least prioritized group at the back
3. Check the rotation.
Clockwise: ___________ Counterclockwise: ____________

➢ For Fischer Projection:

Case I : The least prioritized group is on the vertical bond.

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

• Racemic mixture – molecule with equal mixture or presence of R & S or D & L isomers;
optically inactive
Ex. Tartaric Acid
Thalidomide:
R isomer - ___________ S isomer - _____________

SUMMARY OF ISOMERISM

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Exercises: 10. Which of the following compounds is not
a phenol?
1. By heating the inorganic substance a. Carbolic acid c. benzyl alcohol
ammonium cyanate, the first organic b. Picric acid d. p-cresol
compound was synthesized. This
compound is _______________. 11. All of the following are true for phenols,
a. Penicillin c. Urea except:
b. Allantoin d. Thiourea a. Have an aromatic nucleus in which one
or more hydrogen atoms have been
2. The covalency of carbon in the ground replaced by a hydroxyl group
state is __________ b. Are tertiary alcohols
a. 1 c.3 c. Are acidic
b. 2 d. 4 d. Are particularly resistant to oxidation

3. Which compound contains double bonds,

does not decolorize bromine water, and 12. Which of the following is not true of
reacts with chlorine in the presence of aspirin?
Lewis acid? a. Has antipyretic activity
a. Butane c. benzene b. Very soluble in water
b. Cyclohexane d. Acetylene c. In the presence of moisture, it is
hydrolyzed to form salicylic acid and
4. Which of the following is least soluble in acetic acid
H2O? d. Has anti-inflammatory activity
a. n-pentyl alcohol c. t-butyl alcohol
b. Butane d. n-butyl alcohol 13. Lactic acid is
a. Ethanedioic acid
5. Which of the following has the highest b. 2-hydroxypropanoic acid
boiling point? c. Dihydroxysuccinic acid
a. Decane c. pentane d. Cis-butanedioic acid
b. Hexane d. butane
14. A compound having an asymmetric
6. CH3CH2COCH3 is a/an: carbon atom exhibits
a. Aldehyde c. Ketone a. chair-boat isomerism
b. Ether d. cyanide b. cis-trans isomerism
c. Optical isomerism
7. A carbon with four different moieties d. All of the above
attached to it
a. Anomeric carbon c. stereocenter 15.
b. Epimeric carbon d. carbonyl carbon

8. 1, 4 positions in the benzene ring a. 3-methyl-3-hexene

a. ortho- c. para- b. 4-methyl-3-hexene
b. Meta- d. tert- c. 3-methyl-3-heptane
d. 4-methyl-3-heptene
9. These are isomers that are not mirror
images of each other and differing only in 16. Number of sp2 hybridized carbons in
the position of moieties at the first carbon acetaminophen
a. Epimers c. enantiomers a. 7
b. Anomers d. tautomer b. 6
c. 5
d. 4

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17. Conformational isomerism is described as 19. Molecular orbital in carbons 3 and 4 in the
a. A form of optical isomerism molecule CH2=CHCH2CH2CH3
b. Cis-trans isomerism a. sp2-sp2
c. Possession of molecules that have the b. sp3-sp3
ability to rotate plane polarized light c. sp3-sp
d. The non-identical spatial arrangement d. sp2-sp3
of atoms in a molecule, resulting from
rotation about one or more single bonds

18. Example of a cumulated diene 20. D-glucose and L-glucose are :

a. 1,2 - pentadiene a. Epimer
b. 1,3 – pentadiene b. Enantiomer
c. 1,4- pentadiene c. Diastereomer
d. 2,4-hexadiene d. Anomer

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ORGANIC REACTION

➢ MUST KNOW BASICS:

• Electrons → particles of the atom that participate in bonding or any other type of chemical
reactions.
• Bonds consist of electrons; multiple bond means higher number of electrons.
• Chemical change is defined as a process in which bonds are broken and/or formed.
• Therefore, when chemistry takes place, electron move, then atoms follow.
• Curved arrow (↷) shows the “flow” of an electron pair from its point of origin, usually a lone
pair or a covalent bond.

Reaction 1: Dissociation of polar covalent bond into ions

• Polar covalent bonds is made from sharing electrons of polar compounds
o Non-Polar: 0-0.4
o Polar: 0.5-1.9
o Ionic: ≥ 2.0

*Arrow points toward the atom

that is more electronegative

Reaction 2: Formation of a covalent bond from ions

Reaction 3: Simultaneous making and breaking of two bonds: substitution reactions

Reaction type 4. Reactions involving double (or triple) bonds: additions

Electrophile - electron loving; electron poor

Nucleophile - nucleus loving; electron rich; there is a double or triple bond

• Protonation – movement of one electron pair of a double bond towards a proton; proton is
acting as an electrophile, attacking an electron pair in the double bond
• Carbocation - species with a positively charged carbon atom.

O R G A N I C R E A C T I O N 1 | 15
 • Functional groups - controls the reactivity of a molecule; the higher the
number of functional groups and electronegative atoms on the FG=
higher reactivity = lower stability
• This explains why hydrocarbons are unreactive/lowly reactive generally,
because they do not have FGs with electronegative atoms.

❖ REACTIONS OF ALKANES
A. Combustion reaction – alkanes react w/ molecular oxygen; depends on the availability of
oxygen in environment.
CnH2n+2 + O2 → CO2 + H2O (abundance of O2)
CnH2n+2 + O2 → CO2 + H2O + Csoot (low level of O2)
*The completeness of the reaction depends on oxygen level*

B. Halogenation reaction
• Attachment of halogens to alkane; carried out by free-radical substitutions
• There should be present of UV light, because it is the one that will trigger homolytic
cleavage.

HOMOLYTIC CLEAVAGE → Breaking of bond in such a way that the two bonding electrons divide
equally between the two participating atom or fragments; formation of radicals

Radicals - species that have unpaired electrons that are very reactive and usually cannot be
isolated; they trigger oxidation very harmful in human because they can trigger oxygen,
production of diseases.

MECHANISMS:

I. Chain initiation – production of radicals; radical is on the product side

II. Chain propagation – radical is both on the reactant and product side of reaction

III. Chain termination – production of non-radical; radical is on the reactant side

O R G A N I C R E A C T I O N 2 | 15
❖ REACTIONS OF ALKENES
• PRINCIPLE FOR REACTIVITY: Electrophilic addition reaction
• Alkene is a nucleophile
• Sigma bond is stronger than pi bond because it is the primary bond
Ex of electrophile: H2, and
halogen

A. Catalytic Hydrogenation
OXIDATION REDUCTION
▪ simplest reaction of the double bond is its
Addition of O2 Removal of
saturation with hydrogen; addition of Hydrogen oxygen
(reduction) Formation of Cleaving of
▪ principle involved in the manufacture of bonds bonds
margarine Removal of Addition of
▪ exothermic reaction hydrogen hydrogen
▪ requires metal catalyst to cleave the strong H-
bond between H2 molecule

B. Halogenation
▪ addition of hydrogen halide (HX)
▪ NOTE: Bromine and chlorine add to alkenes to give 1,2-dihalides, an industrial important
process. F2 is too reactive and I2 does not add
Two types: Major – Follows Markovnikov’s rule
Minor – does not follow Markovnikov’s rule

REACTION 1: using organic solvents

Product: Alkyl dihalides and vicinal dihalides

REACTION 2: using H2O

Product: Halohydrin

O R G A N I C R E A C T I O N 3 | 15
C. Hydrohalogenation - addition of hydrogen halide (HX)
MARKOVNIKOV’S RULE
▪ Two types: Major – Follows Markovnikov’s rule
The electrophile (H) adds to the
Minor – does not follow Markovnikov’s rule
carbon w/ greater number of H
substituents. The nucleophile (X)
adds to the carbon w/ lesser
number of H substituents

MAJOR MINOR

D. Hydration - addition of water (H2O)

- requires acidic environment

E. Oxidation - addition of O2
a. Hydroxylation/Glycol formation – principle involved in Baeyer’s test for unsaturation
(brown ppt (+)); requires the use of MnO4- or OsO4
▪ Environment: basic/neutral and cold

b. Oxidative cleavage
▪ Environment: Acidic and requires Heat

O R G A N I C R E A C T I O N 4 | 15
❖ REACTIONS OF ALKYNES
o One sigma bond and two pi bonds (4 pi bonds electron)

PRINCIPLE FOR REACTIVITY: Electrophilic addition

reaction

A. Catalytic Hydrogenation

Case I: Using Hg2+

Case II: Using Na in liquid NH3

❖ Sequential one-electron reductions of alkynes produce trans alkenes

❖ Elemental sodium in liquid ammonia acts as a powerful electron donor (i.e., a
reducing agent)
❖ Ex: 3-heptyne is reduced to trans-3-heptene

Case III: Using Lindlar’s Catalyst

• Product: Cis-alkene

B. Hydration/Keto-enol Tautomerization - addition of H2O

• Tautomerization - interconverts two isomers by simultaneous proton and double-
bond shifts. Keto form is more stable.
• Hydration of a terminal alkyne gives
methylketone; gives a positive result
to Iodoform test

O R G A N I C R E A C T I O N 5 | 15
 *Conjugated – double bond is alternating
❖ AROMATIC COMPOUNDS *Cumulated – double bond is coinciding
*Isolated – the double bonds are separated
Requirements for aromaticity: with 2 or more single bonds
1. Cyclic, Planar/Flat =sp2
2. Conjugated double bond system
3. Follows the Huckel’s rule for aromaticity

HUCKEL’S RULE
4n + 2 rule; where n = whole number/integral

Pyrrole: Furan: Pyridine:

*lone pair is counted as 1 pi
bond in 5-membered ring ONLY
*Only 1 lone pair can participate
for 1 pi bond; if 2, will already
form cumulated double bond
which is against the requirement
for aromaticity

Example of anti-aromaticity rule (4n rule): cyclobutadiene

PRINCIPLE FOR REACTIVITY: Electrophilic aromatic

substitution

A. Nitration reaction – important in nitration of benzene and in the production of pyroxylin

collodion (gun cotton; nitrocellulose)
• Reagents: conc. Nitric acid + conc. H2SO4
• Electrophile: Ntronium ion (+NO2)
• Product: nitrated benzene or nitrobenzene

O R G A N I C R E A C T I O N 6 | 15
 B. Halogenation
• Reagents: halogens (X2) and FeX3 or ALX3 (Lewis-acid catalysts)
• Electrophile: Halonium ion (+X)
• Product: halobenzene or halogenated benzene

C. Friedel-Craft’s Alkylation – attachment of alkyl groups

• Reagents: alkyl halides (RX) and Lewis-acids catalyst
• Electrophile: carbocation
• Product: alkynylated benzene or alkyl benzene

D. Friedel-Craft’s Acylation – attachment of acyl or acid halides

• Reagents: acid/acyl and Lewis-acid catalyst
• Electrophile: acylium ion
• Product: Aromatic ketone NOTE: Addition of substituents in an
aromatic compound
➢ Ortho-para directing: -OH, -
CH3, -X
➢ Meta-directing: -NO2, -SO3H,
-CN, -CHO

E. Sulfonation
• Reagents: Sulfur trioxide gas (SO3 g) + conc. SO4
• Electrophile: sulfonium ion
• Product: Benzene sulfonic acid

❖ ALCOHOLS
• R-OH
• Nomenclature: Determine the longest continuous carbon chain + root word + suffix –‘ol’
• OH groups can form ion-dipole & H-bonds
• OH groups enhance water solubility
• esterified to form prodrugs
• metabolism: Oxidation, Glucuronidation or sulfate conjugation

Classification of Alcohols:
A. Based on the number of alkyl groups (R) attached to the carbinol group (C-OH)

2. Primary alcohols 1. Secondary alcohols 3. Tertiary alcohols

O R G A N I C R E A C T I O N 7 | 15
 B. Based on the number of OH groups attached
1. Monohydric alcohol: Alcohol that has one hydroxyl group attached
Ex. Ethanol, Methanol, Isopropyl Alcohol

2. Dihydric alcohol: Alcohol containing two hydroxyl group

Ex. Ethylene glycols, propylene glycol

3. Trihydric alcohol: Alcohol containing three hydroxyl group

Ex. Glycerol (in triglycerides) & Glycerin (in Nitroglycerin)

4. Polyhydric alcohol: Alcohol containing more than three hydroxyl group

Ex. Sorbitol, mannitol (product of reductive metabolism of our sugars)

❖ Qualitative Tests for Alcohols

1. Lucas Test – differentiating test for alcohols

▪ REAGENT: conc. HCl + ZnCl2
▪ REACTION: R--OH + HCL -----→ R—Cl (alkyl chloride) + H2O
▪ Visible result: formation of milky white immiscible layer
▪ Reactivity: Tertiary (most reactive and fastest to show visible result) > Secondary >
Primary > Methanol

2. Reaction w/ Active Metal

▪ Alkoxide is used as a component of Williamson’s reagent which is used in the
synthesis of ethers
▪ Reactivity: Methanol > Primary > Secondary > Tertiary
▪ R—OH + Na ---→ R—O---Na+ (alkoxide) + H2↑

3. Dehydration – removal of water

▪ Product: Alkene
▪ The dehydration of alcohol is the opposite of the hydration of alkene

4. Oxidation – addition of oxygen

▪ Reagent: Potassium dichromate (K2Cr2O7) → very powerful oxidizing agent

O R G A N I C R E A C T I O N 8 | 15
 K2Cr2O7
➢ Primary alcohols [RCHO] RCOOH
o Pyridinium chlorochromate (PCC) - stops the oxidation of primary alcohols to
produce RCHO; NOT VERY POWERFUL OXIDIZING AGENT
PCC
1º alcohol RCHO
K2Cr2O7
➢ Secondary alcohols ketones
K2Cr2O7
➢ Tertiary alcohols No reaction

SUMMARY OF REVERSIBLE OXIDATION OF PRIMARY ALCOHOL

PCC

NaBH
4
K2Cr2O K2Cr2O
7 7 Ester DIBAL
LiAlH4

• Methanol -> formaldehyde ->formic acid = metabolic acidosis (blindness)

Antidote: ethanol/ ethyl alcohol
• Ethanol -> acetaldehyde -> acetic acid = liver damage
• Ethylene Glycol -> oxalate + CA2+ = hypocalcemia + CaC2O4 (kidney stones)

IMPORTANT ALCOHOLS:
1. Methanol - aka “Wood Alcohol” (because it was formerly obtained from destructive distillation) used
to produce formaldehyde, a starting material for many plastics; a good denaturant for ethyl alcohol
(makes ethyl alcohol unfit for drinking) because of its taste & poisonous properties.
2. Ethanol - aka “Grain Alcohol”, “wine Sprit”,” Spiritus vini rectificatus”; alcohol present in alcoholic
beverages; obtained from fermentation of sugars & starch; used as antiseptic (70% solution of
ethanol); used as solvent in medicinal preparations (tinctures); unfit for use in intoxicating beverages
by addition of Denatured alcohol (contains Methanol & Benzene)
3. Isopropyl Alcohol - component of rubbing alcohol; solvent; intermediate in the production of acetone
4. Cholesterol - a complex alcohol that occurs in nature, a sterol found in a cell membrane of animal
cells; used as precursor for the synthesis of sex hormones & bile acids
5. Glycerol - used in the manufacture of certain plastics; used as solvent in liquid medications being
nontoxic ingredient in cosmetics formulation due to its moisturizing property main constituent of
suppositories
6. Ethylene Glycol - antifreeze for automobiles solvent humectants aids in retaining moisture
7. Phenol - aka “Carbolic Acid” - used as disinfectant for surgical instruments & utensils etc,: starting
material in the manufacture of aspirin, detergents, dyes, herbicides, explosives, etc.
8. Cresol - saponated cresol (aka “Lysol”) – used as disinfectant which is better & less toxic than phenol
9. Resorcinol - also used as antiseptic but not as good as phenol
10. Hexyl Resorcinol - a much better antiseptic & germicide, commonly used in mouthwash
11. Menthol - from oil of Peppermint
12. Geraniol - from Rose Oil
13. Glucose - a carbohydrate basic unit

O R G A N I C R E A C T I O N 9 | 15
 ❖ ETHERS
• R1-O-R2; Ar-O-R; Ar-O-Ar

Nomenclature for Ethers:

1. IUPAC Rules -use alkoxy as a prefix; position is indicated by number -“oxy” ; ex. CH3OCH3
(Methoxymethane)
2. Derived Name -alkyl groups + Ether; ex. CH3OCH3 (Methyl ether)

A. Open Chain Ethers

1. Symmetrical Ethers – same R groups on both side of ether oxygen

2. Asymmetrical / Mixed ethers – different R groups

B. Cyclic ethers
1. Epoxide/ Oxiranes/ Oxacyclopropanes – oxygen is part of a 3-membered ring system

2. Cyclic ethers w/ more than 3-membered ring system

IMPORTANT ETHERS:

1. Diethyl Ether - once widely used as general anesthetic because it is safe even in long surgical
procedures; ADR: Irritation of mucous membranes, nausea & vomiting; dangerous because it is
explosive; solvent for waxes & fats

2. Ethylene oxide - gas sterilant; used to fumigate textiles & grains; raw material in the synthesis of
another organic compound

3. Monobenzone - depigmenting agent in cases of excessive melanin formation; reduce melanin

formation can be seen in whitening preparation

4. Eugenol- from Clove Oil; when mixed with ZNO forms a cement used by dentist as temporary
fillings

5. Naproxen - NSAID

6. Gemfibrozil

O R G A N I C R E A C T I O N 10 | 15
 ❖ ALDEHYDES
• undergone Cannizaro Reaction
• are oxidized to carboxylic acids & reduced to primary alcohols
• terminal functional group
Nomenclature IUPAC:
• Naming/Nomenclature:
1. Aldehyde: Parent chain contains the –CHO,
▪ Identify/determine the longest C chain/parent same pattern as alkane, change –e to –al;
chain Example: Methanal (formaldehyde) & Ethanal
▪ Add the suffix “-al” (acetaldehyde)
2. Ketone: Parent chain has the –C=O group
(given the lowest number); Change –e to –
❖ KETONES one;
• product of oxidation of Secondary alcohol Example: Propanone (acetone)- as substrate,
• non-terminal functional group can be used to synthesize tertiary alcohol;
• *Test for methyl ketone: Iodoform test (+) yellow simplest ketone
• Naming/Nomenclature:
▪ Identify/determine the longest C chain/parent chain
▪ Add the suffix “-one”

REACTION OF ALDEHYDE (RCHO) & KETONE (RCOR)

PRINCIPLE FOR REACTVITY: Nucleophilic addition reaction

A. Reaction w/ HCN – product is used as precursor for amino acid synthesis

• Product: Cyanohydrin – used as precursor for the synthesis of Amino Acids

B. Reaction w/ Grignard Reagent - Used to produce different types of alcohol

• RMgX (alkyl magnesium halide)

i. Formaldehyde – simplest aldehyde; methanal; only formaldehyde among all the aldehyde
is able to produce primary alcohol when react to Grignard reagent.

ii. Higher Aldehydes – produce secondary alcohol

iii. Ketones – produce tertiary alcohol

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 C. Reaction w/ Alcohol

Partial Reaction: Hemiacetal/Hemiketal

Complete Reaction: Acetal/ Ketal

D. Reaction w/ Amines

1. Reaction w/ primary amines – 1 alkyl group attached to the amino group

2. Reaction w/ secondary amines – 2 alkyl group attached to the amino group

3. Formation of Imine Derivatives

IMPORTANT ALDEHYDES:
1. Formaldehyde - preservative for anatomical specimens because it causes skin hardening effective
disinfectant used in hospital as embalming fluid –(FORMALIN); creates a “silver mirror” on the walls of a
test tube w/ Silver Nitrate (Tollen’s test)
2. Acetaldehyde - intermediate in the manufacture or acetic, ethyl acetate, vinyl acetate which in turn
are used on the production of synthetic rubber & water-based paints.
3. Chloral - starting material for the manufacture of insecticides (e.g., DDT)
4. Chloral Hydrate - “knockout drops”; dissolves Starch, Resins, Proteins; metabolite: Trichloroacetic Acid
5. Butanal - a constituent of the aroma of fresh bread
6. Benzaldehyde - once called “Oil of Bitter Almond” because of its presence in almond seed; used as
Flavoring Agent; intermediate in the manufacture of drugs, dyes, & other organic products
7. Cinnamaldehyde - chief constituent of the oil of cinnamon bark
8.Vanillin - fragrant component of vanilla beans; flavoring agent
9. Citral - major component of lemon grass oil

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IMPORTANT KETONES:
1. Acetone - used as a solvent for such products as paints, lacquers, & cellulose acetate because
of its miscibility with both water & non polar; nail polisher remover
2. Testosterone - major constituent of the male sex hormone; responsible for the development of
the secondary sex characteristics; steroidal ketone
3. Muscone - odorous principal component of musk (sex attractants); valued for its ability to
enhance fragrances even when present in minute amounts; present in many of the expensive
perfumes as fixative
Musk -natural substance w/ a strong sweet smell
4. Pheromones - produce by musk to attracts sex; (Scents)
5. Muscaline - pheromone produce by house flies
6. Chloroacetophenone - lacrimator (irritates eye); is used as a Tear Gas (produce stinging pain in
the eyes &streaming from the eyes & nose)
7. Pepper spray - contain capsaicin (sili)
8. Acetophenone - has been used as a hypnotic but newer & safer drugs are now available
9. Methyl Ethyl Ketone (MEK) solvent for lacquers, paints, plastics

❖ CARBOXYLICA ACIDS
• Always a terminal functional group; most prioritized functional group
• Can be aliphatic or aromatic COOH
• product of hydrolysis of anhydrides
• product of further oxidation of Primary Alcohol

Nomenclature:
1. Common name - Uses Greek letters to indicate the positions of substituents
• Ex. C-C-C-C-C-COOH
• Alpha carbon = C next to COOH; Beta, Gamma, Sigma, Epsilon
• Often derived from Latin Greek name indicating the original source of the acid
2. IUPAC - Parent chain contains the –COOH, carboxyl C is #1; Change –e to –oic
• Ex: methane -> Methanoic acid

PRINCIPLE OF REACTIVITY: Nucleophilic Substitution reaction

NOTE: COOH reaction will

always follow this principle of
reactivity except
neutralization/salt formation

• Neutralization/Salt Formation – reaction of an acid with a base to produce a salt

Nomenclature: The name of the

cation is stated first, followed by
the name of the acid w/ ‘-ic
acid’ replaced by ‘-ate’
Ex. Sodium carboxylate

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• Carboxylic acid derivatives

I. Conversion to acyl/acid halides – can be either chloride or bromide

Nomenclature: The name of the
acid ‘-oic acid’ is replaced by the
term ‘amide’
Ex. 2-ethylhexanamide from 2-
ethylhexanoic acid

II. Conversion to acid anhydride – needs 2 molecules of RCOOH undergoing

dehydration process.

III. Conversion to esters – RCOOH reacting w/ alcohol Nomenclature: The name of the R’
portion (alkanol) is stated first,
followed by the name of the acid w/
‘-ic acid’ replaced by ‘-ate’
Ex. Methylhexanoate from methanol
and hexanoic acid

IV. Conversion to amides

Two-step process:
Nomenclature: The name of the
1. Conversion to acyl halide first acid ‘-oic acid’ is replaced by
the term ‘amide’
Ex. 2-ethylhexanamide from 2-
ethylhexanoic acid

2. Convert the acyl halide to amide

3. Reduction of carboxylic acids

• Reagent: Lithium aluminum hydride (LiAlH4); very powerful reducing agent

4. Hydrolysis – reaction with H2O

• *Note: RCOOH derivatives will always react with H2O molecules back to the original
RCOOH
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 I. Acyl Halide

II. Acid anhydride – form by condensation or dehydration of two carboxylic acid

III. Ester

IV. Amide

B. SUSCEPTIBILITY TO HYDROLYSIS: acyl halide > acid anhydride > ester > thioester >
amide > carbamate > ureides (least susceptible/most difficult to hydrolyze)

IMPORTANT ACIDS:
• Salicylic Acid - Monoprotic Acid; used for treatment of fungal infection & removal of
warts & corns; used as a keratolytic agent (for the removal of dead skin cell)
* Whitfield’s Ointment ® (antifungal) = Benzoic Acid + Salicylic Acid
2. Acetylsalicylic Acid (ASPIRIN)- analgesic, antipyretic, treatment of colds, headache,
minor aches & pains
3. Acetaminophen USP (Paracetamol BP) substitute for aspirin
4. Citric Acid - found in citrus fruits; Triprotic Acid
5. Lactic Acid - found in sour milk; formed during fermentation of milk sugar, lactose, &
responsible for souring of spoiled milk; product of fermentation milk sugar
6. Tartaric Acid - found on several fruits particularly grapes; Diprotic Acid
Salt of tartaric acid:
*Potassium Hydrogen Tartrate (Cream of Tartar)- used in making baking powder
*Potassium Sodium Tartrate - used as a mild cathartic
7. Benzoic Acid - Monoprotic Acid; used as Antifungal Agent; its sodium salt, sodium
benzoate is used as a food preservative
8. Para-aminobenzoic Acid - used in suntan lotions to prevent the dangerous UV rays from
reaching the skin
9. Acetic Acids - vinegar, spermatocidal; considered as a universal precursor for fatty
acids, lipids, & other organic plant products
10. Glacial Acetic Acid - Ethanolic Acid

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