PHYSICAL PROPERTIES OF
ORGANIC COMPOUNDS
Mr. Maywan Hariono
Objective Learning
 To understand the physical properties of
organic compounds such as solubility,
melting point, refractive index and boiling
point of organic compounds
 To understand the acid base properties of
organic compounds in order to integrate with
Henderson-Hesselbach concept.
Solubility of Organic Compounds in
Lipid and Water
 Why pharmacist assistant should be able to identify the
solubility of organic compounds in several solvents???
 Please think what you have learned in Basic Formulation &
Introduction to Pharmaceutics Subject.
- When you prepared Paracetamol Syrup, why you have to
dissolve the chemical in alcohol & propylenglicol firstly
before you top up with water?
When you studied about Pharmaceutical Dosage Form why
some drug can be prepared in syrup while the other ones
should be prepared in emulsion or suspension?
-When you studied about Introduction to
Bioavailability, why some drug has a good absorption while
the other ones have a poor absorption so that ones will
effect in”onset”, still remember?
 The solubility of an organic compound can provide
evidence for the presence (or lack) of several important
functional groups, as indicated in the following chart
Solvent
Some solubility or complete
miscibility
water
Alcohols, amines, acids, esters,
ketones, aldehydes (typically only
those with C < 4)
5% NaHCO3
Carboxilic acids
5% NaOH
Carboxilic acids and phenols
5% HCl
Amines
Diethyl ether
Most organic molecules
 Most of organic molecules are usually soluble in organic solvents (e.g.
diethyl ether, dichloromethane, chloroform, petroleum ether, hexanes
etc)
H
H3CH2C
O
CH2CH3
diethyl ether
Cl
C
H
Cl
CH3CH2CH2CH2CH2CH3
n-hexane
dichloromethane
 However, some organic molecules are also soluble in water. This
denotes a rather high ratio of polar group(s) to carbon chain, i.e., a low
molecular weight compound containing an –OH, -NH2, or CO2H group,
or a larger molecule containing more than one polar group
 Solubility is defined as the maximum mass
of a substance that can be dissolved in a
fixed mass of a solvent at a given
temperature.
 A substance will have a different solubility in
different solvents depending on polarity of
both the substance and the solvent.
 Still remember about ”like dissolves like”?
Predict the following organic compounds solubility in
water, ethanol, benzene
 The presence of an acidic CO2H or basic NH2 group in a watersoluble compound can be detected by low or high pH, respectively,
of the solution.
 Compounds which are insoluble in water can dissolve to a
significant extent in aqueous acid or base if they form an ionic
species.
 The solubilty of carboxilic acids (KA= 10-3 to 10-5) and phenols (KA =
10-9 to 10-10) in aqueous hydroxide is due to the formation of the
carboxylate or phenoxide, since they are much stronger acids than
water (KA = 10-7) and the acid equilibria lie far to right.
O
R
C
O
OH
+ OH-
R
C
O- + H2O
carboxylic acid
OH
+
phenol
O-
OH-
+
H2 O
 Carboxylic acids, but phenols, are also stronger
than carbonic acid (KA = 10-7) and they are
therefore soluble also in NaHCO3 solution:
O
R
C
O
OH
+ HCO3-
R
C
O-
+ H2O + CO2
 The solubility of amines in dilute aqueous acid
similarly reflects the fact that they are stronger
bases than water, and are converted to
ammonium ion
NH2
+ H3O+
NH3+
+ H2O
Melting Point
1. Melting point is the temperature range
over which the solid melts to become a
liquid
2. The transition between the solid and the
liquid is so sharp for small samples of pure
substance that melting points can be
measured to ± 1oC
 Melting points of pure compounds are
recorded in The Handbook of Chemistry and
Physics (CRC) or the Merck Index
 Measurement of the melting point of solid
can also provide information about purity of
the substance.
 Pure crystalline solids have a sharp melting
point whereas mixtures melt with a broad
temperature range.
What is the use of melting point
property in pharmacy?
 For the new compounds which no have observed data,
melting point can be used to detect the synthetic product
compared to the starting material.
 Example: 1stly, aspirin is synthesized by reacting salicylic
acid & acetic acid anhydride. How can we ensure that
aspirin has been yielded from the reaction?
 By measuring of melting point the product & the starting
material we can sure that the product has already
obtained.
 Aspirin (m.p. 141-144oC) but salicylic acid (m.p. 158.5161oC)
 In drug analysis, we can identify the
unknown compound and compare to CRC
O
C
O
O
OH
+
HO
C
O
O
C
C
OH
O
OH
O
salycilic acid
m.p. 158.5-161oC
aspirin
m.p. 141-144oC
O
OH
C
+
CH3
CH3
C
OH
Measuring Melting Point
 Using electrothermal Meltpoint tester
Boiling Points
 Likely the melting points, boiling points are a
physical properties
 The boiling point of liquid is affected by the
forces that attract one molecule to anotherionic attraction , dipole-dipole interaction,
hydrogen bonding & van der Waals force.
 A very liquid in a very clean vessel will
superheat and not boil when subjected to a
temperature above its boiling point
 If boiling does occur under these conditions,
it occurs with explosive violence.
Application in Pharmacy
 Such as melting point, boiling point can be
used to identify the unknown drugs.
 We can refer to CRC to compare the
observed boiling point data with the data
from literature
 The difference in boiling point informs the
difference in molecule structure
 Phenol is an antiseptic that has boiling point
higher than ether that was used as general
anesthetic.
O
H
H3C
phenol
H2
C
O
ether
 Why is b.p of phenol higher than ether?
H2
C
CH3
 propylenglicol is an adjunct (co-solvent) has
a boiling point higher than
OH
H3C
C
H
H2
C
propylenglycol
b.p. 188.2oC
OH
H3C
H2
C
H2
C
propanol
b.p. 97.1oC
OH
Refractive index
 The refractive index (or index of refraction) of a
medium is a measure of how much the speed of
light (or other waves such as sound waves) is
reduced inside the medium.
 Since refractive index is a fundamental physical
property of a substance, it is often used to identify
a particular substance, confirm its purity, or
measure its concentration.
Measuring refractive index
acetone
H3C
H2
C
O
O
ethanol
OH
H3C
D. 1.36 (25oC)
refractometer
C
CH3
D. 1.36 (20 C)
o
H3C
C
Ethyl acetate
CH2CH3
D. 1.37 (20oC)
Density
 The density of a material is defined as its
mass per unit volume
 Density can be used to examine the
unknown sample qualitatively
 The measurement can use PICNOMETER
O
O
H3 C
H2
C
OH
= 0.789 g/cm
H3 C
C
CH3
= 0.79 g/cm
H3 C
C
CH2CH3
= 0.897 g/cm
OPTICAL ROTATION
Optical rotation can be used to
identify chirality
OH
OH
H
H
H
H
C
N
C OH
H
CH3
Cl