Physical Properties
 As it is true for all substances, each organic compound has
certain physical and chemical properties.
 some of the important physical properties of organic
compounds are:
melting point, boiling point, density, and solubility
Melting Point
Melting point for an organic substance is the temperature at
which it changes from solid state to liquid state. This temperature
is also referred to as freezing point at which a compound changes
its state from liquid to solid.
Melting point determinations have importance in various
applications. Such as:
 Making a comparison with the literature data to observe the
same temperature.
 Having a very rough idea on the purity of a substance (there are
much more available and accurate methods applied to decide
it).
 To identify the melting point of a substance that is originally
synthesized.
some compounds have too low melting points, and some of them
have very high melting points. There are lots of factors that affect
the melting point. The chemical structure is the main determinant.
In general;
 Melting points are higher for higher molecular weight
compounds.
 Impurities decrease the melting point. ice-salt mixtures , Salt
and soil , Ethylene glycol.
 Intramolecular and, in particular intermolecular forces, such as
H-bonds, dipole dipole interactions increase the melting point.
 Loosing symmetry decreases the chance of intermolecular
interactions. Solid state formation is deeply affected through
the possibility of interaction among molecules.
 Therefore, loosing symmetry, in particular through branching
lowers the melting point.
 Trans isomers are more stable than cis isomers, therefore they
have higher melting points.
Measuring the Melting Point
Old Fashion Model
 New fashion model
Boiling Point
 Boiling point for an organic substance is the temperature at
which it changes from liquid state to gas (vapor) state. The
vapor pressure of a liquid is also equal to the pressure of the
current environment at its boiling point temperature.
 Unlike the melting point boiling point of an organic compound
varies depending on the change at the environmental pressure.
 The lower atmospheric pressure---the lower the boiling point
 There are structural aspects having effect on boiling point:
 Higher molecular weight ---higher boiling point
 Intermolecular and intramolecular interaction
 Hydrogen bonding,
 Dipole-dipole interaction
 Vanderwals Increase boiling point
 Impurities
 Branching
Density
 A density of a substance is calculated by dividing its
weight to its volume.
 The unit generally employed for density is gr/mL (i.e.,
also referred to as gr/cm3).
 pressure
 Temperature
 Polar groups
 Molecular weight
 Branching
 Double and triple bonds
Measuring of density
 Pycnometers
Measuring the density for liquid sample
𝑑𝑠𝑎𝑚𝑝𝑙𝑒 = 𝑑𝑖𝑛𝑒𝑟𝑡 𝑙𝑖𝑞𝑢𝑖𝑑
𝑤2 − 𝑤1
𝑤3 − 𝑤1
In this equation;
W1= the weight of empty pycnometer
W2= the weight of pycnometer filled with the sample liquid
W3= the weight of pycnometer filled with the inert liquid.
Measuring the density for solid sample
In this equation;
w1 = the weight of pycnometer filled with the inert liquid.
w2 = the weight of empty pycnometer.
w3 = the weight of pycnometer added a little amount of solid
sample.
w4 = the weight of inert liquid filled w3.
Solubility
 Solubility is the degree of dissolution of a substance in a
solvent.
 The solubility of a liquid substance in another liquid matter ---
miscibility and immiscibility,
 See table for solubility page 68
like dissolves like
There are lots of interaction types that might take place in
dissolution of a substance in a liquid. The organic molecules can not
dissolve in water because;
long carbon skeletons,
absence of polar functional groups,
absence of heteroatoms,
absence of ionic structures,
hydrophobic character
 Making salt (ammonium salt, carboxylic acid salt)
These are typically prepared by employing acid base reactions (list
of base and acid are in page 64,65)
 Make hydrogen bond (glucose, resorcinol)
 Having carboxylic, ketone-aldehyde, amine with 5 or less carbon
atoms
 Like dissolves like, organic substances are soluble in organic
solvent, but not all, varying depending on the structure of both the
organic substance and the organic solvent, for instance; see, table
of solubility of naproxen in page 70
 Acetone has the ability of dissolve most of the organic
molecules. For instance, the solubility of naproxen in acetone is
0.726 mol/L, which is quite higher than its solubility in other
solvents.
 Utilizing the solubility data to estimate the presence of
functional groups in an unknown molecules (see table in page
71)
pH
Henderson-Hasselbach equation:
pH = pKa + log ([A-] / [HA])
pH=pka---the concentration of ionized and non-ionized forms are
equal
pH>pKa---the concentration of ionized >non-ionized forms
pH<pKa---the concentration of ionized <non-ionized forms
Carboxylic acid ---pKa=4-5
HA, PH=7 more than 99 % AIf an organic molecule is insoluble in a liquid, it precipitates.
precipitation and dissolution might be evaluated as opposite actions
Miscibility
 Miscibility of organic solvents is quite important.
 For instance; Some reactions utilize more than one organic
solvent to conduct a reaction as reagents or to increase the
solubility.
 Some work-up and purification studies also require the
employment of more than one solvent.
Partition Coefficient
Organic compound has different solubility in different organic
solvents have applications in various experiments.
Partition coefficient is the ratio of concentration of an organic
molecule in two immiscible organic solvents. The organic
compound must be at unionized (neutral). It is important to adjust
the pH that guarantees the non-ionized state of a molecule.
Distribution Coefficient
Solubility in water and lipid systems are both required for a drug
molecule to pass through different biological fluid systems to reach
to its active site.
In general, a LogP value in 3-5 range is one of those drug-likely
parameters that shows a good criteria for a drug candidate molecule.
Chloroform is sometimes used as an alternative to n-octacol.
Polar groups, groups tend to make Hydrogen bonds,
ionic bonds definitely trigger solubility in aqueous
systems, therefore resulting in low LogP values
relatively. In contrast, lacking of those structural
features and abundance of hydrophobic groups creating
London London forces positively affect lipophilicity
and high LogP values. (see table in page 75)
Purification and work-up methods
1-Extraction
2-Filteration
3-Distillation
4-Crystallization
Extraction
It is a separation technique; Depending upon the system, extraction
can be categorized into two groups: solid-liquid extractions and
liquid-liquid extractions.
Solid liquid extractions simple aims to extract the material from a
solid mixture into a liquid. For example, the material inside the dried
leaves extracted into hot water. Assume a solid mixture of benzoic
acid and sodium benzoate. If you treat this mixture with water,
sodium benzoate readily dissolves in water, whereas benzoic acid has
very limited solubility.
Liquid-liquid extractions employ the solubility difference of an
organic compound in two immiscible liquids.
The calculation of distribution coefficient is explained previously.
The term ‘extraction coefficient’ is used instead in extraction
studies, although the equation is the same as the one used for
distribution coefficient.
Extraction coefficient depends on several factors. Those are
summarized below:
- solubility in two immiscible solvents
- temperature
- the amount of each solvent used
Separation funnels are utilized for
liquid-liquid extraction.
Immiscible solvents separate in
funnel such that heavier (higher
density) stays at bottom.
There are some quick tips that can be followed to accelerate the phase
separation:
-Hanging the separation funnel on the metal ring support and shaking
it very gently from time to time
-adding little amount of salt
-adding a little amount of either of the solvents utilized.
Extraction Efficiency is the ratio of the concentration of an organic
compound in two immiscible liquids when the system reaches to
equilibrium :
𝐶𝐴
𝐾=
𝐶𝐵
CA is the amount of organic compound in X mL of solvent A, and CB
is the amount of organic compound in Y mL of solvent B.
Drying of liquid
Following the extraction process, in general, the organic phase is
evaporated to gain the organic compound.
In practice, most of the organic solvents have the ability to dissolve
some amount of water as well. The amount of water transferred into
organic phase changes depending on the organic solvent used.
Anhydrous sodium sulfate, and anhydrous magnesium sulfate,
anhydrous calcium chloride, anhydrous cupper sulfate, and anhydrous
calcium sulfate
Therefore, some drying phase changes depending on the agents are
used to have the organic solvent water free.
Some features required form drying agents are summarized below:
- No solubility in the organic solvent
- high efficiency to dry
- Inert material (i.e., it should not give or catalyze a reaction)
- Easy to find
- Cheap substance
Filtration
Filtration is one of the most applied processes in organic and
pharmaceutical chemistry practices. In general, filtration is
categorized into two groups; gravity filtration and vacuum
filtration
Gravity filtration is the simple form of filtration. It is routinely
applied in training laboratories. Gravity is the only deriving force in
this type of filtration.
A funnel, a filtration paper and a Erlenmeyer are the only required
materials.
One of the most important aspects of the gravity filtration is the
preparation of the filtration paper. The fluting of the filtration paper
changes depending on the aim of the
filtration.
Vacuum Filtration
Suction filtration is another filtration type. The only difference is the
employing of vacuum as a deriving force for filtration. Therefore,
vacuum filtration is much faster than gravity filtration.
Distillation
Distillation is an oldknown separation and
purification technique,
particularly applied for
liquids. It is based on a
system consisting of both
heating and cooling units.
Fractional Distillation
Liquids that have different
boiling points and do not make
azeotrope mixtures can be
separated employing the
fractional distillation
technique. The difference of
fractional distillation from the
simple distillation is the
employment of fractional
condenser.
One important item to keep in mind in separating liquids is that some
liquids can form azeotropes. The boiling point of the azeotropes
might be lower or higher than the boiling point of each components
of the azeotrope mixture. For example:
For instance, 96% ethanol boils at around 78.3 ºC which is lower
than the boiling points of water and ethanol, 100 ºC, and 78.8 ºC,
respectively. Due to the formation of azeotrope, technically it is not
possible to separate ethanol-water mixture employing fractional
distillation. In such a case, another solvent is added to break down
the azeotrope, such as benzene addition to ethanol-water mixture.
Steam Distillation
This type of distillation is generally assayed for liquids that have high
boiling points and decompose at high temperatures less than their
boiling point. The steam distillation system applies the in-situ
generation of steam and applying it directly onto the material to
activate it for distillation.
Vacuum Distillation
It is also referred to as low-pressure distillation. boiling point of an
organic substance depends on several factors including the pressure.
The vacuum application to a distillation unit would be enough to
decrease the pressure inside the system, resulting in the boiling of a
liquid compound at temperatures lower than its regular boiling
temperature.
For instance, dimethylsulfoxide has a relatively high boiling point,
around 190 ºC. Vacuum application to the system physically takes
down the boiling point of dimethylsulfoxide. An effective vacuum can
even take it to less than 100 ºC.
Rotary Evaporator
The main principle in a rotary evaporator is the distillation (in fact to
remove) of an organic solvent in the presence of heat and vacuum that
supplies conditions available to evaporate an organic solvent well
below its boiling point temperature, therefore available to save time
and energy.
Crystallization
Crystallization is one of the oldest purification techniques applied
for solid organic compounds. It has 5 stages of a continuous process
summarized below:
- Dissolution
- Hot filtration
- Crystallization
- Filtration of crystal
- Drying of crystal
The overall technique simply relies on the dissolution of an
organic compound in the presence of impurities in a hot organic
solvent concomitant with its crystallization in the same solvent
during the cooling down of the organic solvent.
A crystal lattice is perfectly ordered for the same type of
molecules. Therefore, crystals physically chemically tends to
form between the same type of molecules. This also means that
impurities are excluded from the crystal lattice.
- Finding an appropriate crystallization solvent is critical:
- It should dissolve the organic compound to be purified at high
temperatures and there should be no dissolution it at low temperatures.
- It should be inert. There should not be any reaction between the
organic compound to be purified and the organic solvent.
- The boiling point of the organic solvent should not be high. In
general, organic solvents that have less than 110°C boiling points
are assayed.
- It should be volatile enough to be removed during the drying
process. This is also in parallel to the statement above.
- It should not be flammable, corrosive, or lachrymator.
There are cases that crystallization process can be accelerated.
Those strategies are summarized below:
- Seeding is a valuable approach to initiate crystallization. Simply,
just a few amount of pure organic substance is added to the cooled
organic solvent involving the organic compound to be purified.
- Scratching the side chains of the vessel triggers the crystallization.
- Cooling the organic solvent below to room temperature.
- Decreasing the amount of solvent used.