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East West University
Liquid–Liquid Extraction
PHRM 309
Tareq Hasan7/25/2011
Table of Contents
Liquid – Liquid Extraction.......................................2
Introduction..........................................................2
Definition..........................................................2
Properties of Solvents......................................2
Properties of Solute..........................................2
Organic Solute......................................................3
Inorganic Solutes..................................................3
Principles of Liquid – Liquid Extraction.................3
Different Portions of Liquid – Liquid Extraction 3
Feed Phase...........................................................3
Extractant and Extract..........................................3
Raffinate...............................................................4
Theory of Liquid – Liquid Extraction or Nernst Distribution Law 4
Statement and Expression...................................4
Limitation.............................................................4
Effectiveness of Liquid – Liquid Extraction........5
Criterias of Solvent Selection............................6
Miscibility.............................................................6
Density.................................................................6
Density Difference................................................7
Solubility..............................................................8
Factors influencing Liquid – Liquid Extraction. .8
Effect of Temperature..........................................8
Effect of pH..........................................................9
Emulsion Problem encountered in Liquid – Liquid Extraction 9
Factors Influencing Emulsion Stability................10
Finely Divided Powders.................................10
Surfactants....................................................11
Ionic Species..................................................11
Prevention of Emulsion Formation.....................12
Moderate Shaking.........................................12
High Density Difference.................................12
Removal of Finely Divided Solids...................12
Avoiding High pH Range................................12
1 | P a g e
Removal of Surfactant by Using Adsorbents. 13
Processes of Breaking Emulsion.........................13
Mechanical Means........................................13
Centrifugation...............................................13
Addition of Mono – or Di – valent Cations... .13
Addition of Ethanol or Higher Alcohol...........13
Silicone – Defoaming Agent..........................14
Sudden Cooling or Thermal Shock.................14
Alteration of Solvent Ratio............................14
Thin – Bed of Adsorbent................................14
Drying Agents.................................................14
Definition...........................................................14
Classification of Drying Agents...........................14
Magnesium Sulfate (Mg2SO4)........................14
Advantages of Magnesium Sulfate...........15
Disadvantages of Magnesium Sulfate.......15
Sodium Sulfate (Na2SO4)................................15
Advantages of Sodium Sulfate..................15
Disadvantages of Sodium Sulfate.............15
Liquid – Liquid Washing.......................................15
Definition........................................................15
Type of Impurities removed in Liquid – Liquid Washing 15
Steps of Liquid – Liquid Washing....................15
Reaction Work-up in Liquid – Liquid Washing....16
Separation of Target Solute from the Reaction medium 16
Removal of Impurities........................................16
Problem of Sparingly Soluble Solvents...........17
Solution..............................................................18
Difference between Liquid – Liquid Extraction and Liquid – Liquid Washing 18
2 | P a g e
L i q u i d – L i q u i d E x t r a c t i o n
In t roduct ion
Definition
Liquid – Liquid Extraction is a method of
separation where an aqueous solution is
usually brought into contact with another
immiscible organic solvent, so as to affect a
transfer of one or more solute from the
aqueous solution into the organic solvent.
This is a fast, easy and convenient
method of Separation.
It is usually performed by moderately
shaking the 2 liquids inside a separating
funnel for a few minute and can be used for
either large volume or trace level.
Properties of Solvents
Solvents are selected based on the
following criteria –
1. Both Solvents must be immiscible to
each other.
2. Solvent 1 can be aqueous / H2O and
Solvent 2 can be Organic in nature. It is
because –
Most Targeted Compounds (or
Solutes in Solvent 1) are soluble in
Organic Solvents (If the solutes are
organic).
Most organic Solvents has lower
boiling point (E.g. Methanol,
Chloroform, Carbon Tetrachloride
has boiling point 500C, 61.20C and
76.80C respectively) , and Since,
after extraction the solvent 2 is
evaporated to collect the targeted
solute, there will be a less chance
for the targeted solute to be
degraded at high temperature.
3. Solvent 2 must be chosen accordingly.
So that, The Target Compound must
have higher affinity towards Solvent 2,
so that, during extraction maximum
amount of solute is transferred to
Solvent 2.
4. Density of both of the Solvents must be
known. So, that in the separating funnel
it is possible to know which solvent is at
the lower phase and which one is at the
upper (Usually, the Solvent with higher
density is at the lower phase).
5. Density Difference between Solvent 1
and Solvent 2 should be high, so that
there will be a less chance of emulsion
formation and even if emulsion forms,
it will easy to breakdown.
6. The Kp value / Partition Coefficient of
immiscible solvent pair must be higher,
since it is important for the
effectiveness of extraction.
3 | P a g e
Properties of Solute
Solutes / Target Compounds can be –
Organic Solute
Inorganic Solute
Organic Solute
Most Organic Solutes are soluble in
Organic solvents, which can be
extracted with any organic solvents
(E.g. Extraction Caffeine by Chloroform).
However, for both pharmaceutical and
therapeutical purpose, some organic
solutes are introduced as salts in order
to increase their solubility in Water,
(E.g. Promethazine hydrochloride, a
hydrochloric salt of Promethazine).
So, before performing liquid – liquid
extraction of such organic solutes, they
are converted into their original organic
forms by means of a chemical reaction,
so that they can be extracted by any
organic solvents (E.g. Promethazine
Hydrochloride is converted into
Promethazine before they are
extracted with organic solvents like n –
hexane or Chloroform).
However, it is to say that upon chemical
reaction the concentration of original
compound does not changes.
Inorganic Solutes
Inorganic solutes are frequently
encountered in aqueous solvents either
as Impurities or as Pharmaceutical
Ingredients.
And before their extraction, it is
absolutely necessary to form ion –
association complexes or metal –
chelates (by using organic – ligands), so
that they may be extracted by an
appropriate organic solvent.
For example, Cu (II) can be extracted by
acetyl acetone by forming Cu (II) –
acetyl acetone complex.
Pr incip les of L iquid – L iquid Extract ion
Different Portions of Liquid – Liquid Extraction
Feed Phase
Feed Phase is the initial solution
containing the target compound /
Solute and Solvent 1.
In the feed phase, the solvent 2 added
to perform the extraction.
So,
Feed Phase=Solute+Solvent 1
Extractant and Extract
Extractant is the Solvent 2 that is
added to the Feed Phase for extraction.
4 | P a g e
After extraction, the Extractant is
called Extract which contains the
target compound.
The Extract is evaporated to collect
and measure the amount of the
solute.
So, Before extraction,
Extractant=Solvent2
And, after extraction,
Extractant=Extract=Solvent 2+Solute
Raffinate
Raffinate is generally, termed for the
Feed Phase after extraction.
And if the extraction process is
repeated, the Raffinate becomes the
feed phase to which the Solvent 2 is
added again.
So,
Raffinate=Feed phase after Extraction=Solvent 1+Remaining Solute
And, if the extraction process is
repeated, then
Raffinate=Feed Phase=Solvent 1+Remaining Solute
Theory of Liquid – Liquid Extraction or Nernst Distribution Law
Statement and Expression
Liquid – Liquid extraction follows the theory of Nernst Distribution Law / Partition Co – efficient
Law which states that – “At a Constant / Fixed temperature, the ratio of concentration of
solute in both immiscible phases is found to be a constant.”
The Law can be expressed as –
Kp= Concentrationof Solute∈Organic SolventConcentrationof Solute∈AqueousSolvent
Kp=COrganic Solvent
CWater∨AqueousSolvent
Here, Kp = Partition Co – efficient
Limitation
The Nernst distribution Law comes with
2 limitations –
1. This law is only applicable for very
dilute solutions.
2. The law does not hold good when
the target compound or solute is
freely soluble / distributed in both
solvents. That means, for this law to
be applicable, the solutes must be
affined to either of the Solvent
especially to the Solvent 2.
5 | P a g e
Effectiveness of Liquid – Liquid Extraction
Based on the Appropriate Partition
Coefficient of an immiscible solvent pair, it
is possible to calculate the ‘Effectiveness
of Liquid – Liquid Extraction’.
Let us assume that –
An Initial Feed Phase Solution
contains a Solute (Target Compound)
of X mole in an Aqueous Solvent, Aaq
with a volume of V2.
A second Organic Solvent, Borg with a
Volume of V1 is added to the Feed
Phase for extraction of the solute.
After 1st extraction, the amount of
solute remaining in Aqueous Solvent,
Aaq is Y mole.
So, after extraction, amount of solute
transferred to the Organic Solvent,
Borg is (X – Y) mole.
Now according to Nernst Distribution Law,
Kp=COrganic
C Aqueous
Here, COrganic = Concentration of Solute
in Organic Solvent, Borg
And, CAqueous = Concentration of Solute
in Aqueous Solvent, Aaq
And, Kp = Partition Co – efficient
Kp=
(X−Y )V 1
YV 2
[Because, Concentration = Amount of
Substance or Solute / Volume]
Kp=(X−Y )V 1
×V 2
Y
Kp=( XV 1
×V 2
Y )−( YV 1
×V 2
Y ) Kp=( XY ×
V 2
V 1)−V 2
V 1
Kp=V 2
V 1
×( XY −1) Kp×
V 1
V 2
= XY
−1
XY
=Kp×V 1
V 2
+1
YX
=(Kp×V 1
V 2
+1)−1
_______(1)
Since, X mole is the total amount of solute
in Solvent Aaq as Feed Phase and Y mole is
the remaining amount of solute in solvent
Aaq as Raffinate then in Equation 1, value
of Y / X mole will be a fraction or less than
1 and it is the amount of solute remaining
in the Raffinate as the unextracted form.
Since, value of Kp is a constant for a
particular solvent pair and Volume of
solvents V1 and V2 are also known then it is
6 | P a g e
possible to find out value of Y / X even
before performing the extraction. Thus, it is
possible to find out the Effectiveness of the
Solvent Pair used in the Liquid – Liquid
Extraction.
If the extraction process is repeated a
second time by using the same solvents in
the same volume, then equation 1 can be –
YX
=(Kp×V 1
V 2
+1)−2
_____ (2)
And, for n number of extractions the
equation can be –
YX
=(Kp×V 1
V 2
+1)−n
_____ (3)
Criterias of Solvent Selection
Miscibility
Solvents which are miscible to each
other in all proportions (E.g. Water
Alcohol mixture) have no possibility to
be separated into 2 phases; rather they
form a one phase system. And, these
types of Solvent pairs cannot be used in
Liquid – Liquid Extraction Process.
Solvent pairs which are immiscible to
each other and form a 2 phase system
(E.g. Water – Benzene System or Water
– Chloroform System) must be used in
Liquid – Liquid Extraction, so that, the
solute effectively transfers to the
organic phase.
Figure 1: A Water – Alcohol System – A One Phase
System (Not suitable for Liquid – Liquid Extraction)
Figure 2: A Water – Benzene System – A Two Phase
System (A Suitable Solvent Pair for Liquid – Liquid
Extraction)
Density
Density of both of the Solvents must be
known.
So that, in the separating funnel it is
possible to identify which solvent is at
the lower phase and which one is at the
upper.
Usually, the Solvent with higher density
is at the lower phase.
E.g. –
7 | P a g e
Density of water is 0.9982 gm / ml
and of n – hexane is 0.6548 gm / ml.
So, in the separating funnel, Water
will form the lower phase and n –
hexane will be at the Upper phase.
Figure 3: A Water - n - hexane System (Water is at
the lower Phase due to higher density and n -
hexane is at the upper phase due to lower density)
Density Difference
Density difference between the
solvents must be high.
It is because In Liquid – liquid Extraction
for pharmaceutical purpose, a frequent
number of substances are encountered
which are very susceptible to emulsion
formation.
There will be a less chance of emulsion
formation upon shaking and even if
emulsion forms, it will easy to
breakdown.
E.g. –
Density of Water, Benzene and n –
hexane are 0.9982 gm / ml, 0.8765
gm / ml and 0.6548 gm / ml
respectively.
In case of Water – benzene system
there is a very low density
difference (0.1217 gm / ml); so the
system is very susceptible to
emulsion formation even upon
moderate shaking.
But, in case of Water – n-hexane
system, there is a high density
difference (0.3434 gm / ml); so
there is less chance of emulsion
formation.
8 | P a g e
Figure 4: Emulsion formation in water - benzene
system due to low density difference and moderate
shaking
Solubility
Though solvents used in Liquid – Liquid
Extraction are immiscible to each other,
there is chance that the solvents are
soluble / distributable in each other to a
slight percentage. This is called Partial
Solubility or Percentage Solubility.
E.g. –
1. In a CH2Cl2 – Water system, 1.6%
CH2Cl2 is soluble in water and,
0.24% Water is soluble in CH2Cl2.
2. In a Carbon tetrachloride – Water
system, 0.03% of Carbon
tetrachloride is soluble to Water
and 0.03% of Water is soluble in
Carbon tetrachloride.
Figure 5: Distribution of Water and CH2Cl2 in each
other.
So, solvents must be both immiscible
and insoluble to each other at any
volume, otherwise the following
problems will occur –
1. Volume Change may occur which
will give error in the result.
2. Aqueous Contamination in the
Organic Extract may increase its
boiling point close to 1000C, so
during evaporation of the extract
(to collect and measure the solute),
the solute can be degraded due to
9 | P a g e
high temperature, thus resulting in
content loss.
In case of solubility, Partition
Coefficient Law is expressed as
following –
Kp=SOrganicSAqueous
Here, SOrganic = Solubility of Solute in Organic
Solvent
And, SAqueous = Solubility of Solute in Aqueous
Solvents
Factors influencing Liquid – Liquid Extraction
Effect of Temperature
Solubility of a compound changes
according to the changes in the
temperature.
Solubility of a Solute increases with
increasing temperature.
In case of Liquid – Liquid Extraction, this
is crucial because, differences in
temperature at any sequence of the
extraction process may change the
solubility of solute in the both aqueous
and organic phases.
And if the solubility of the solute
decreases in Organic Phase but
increases in Aqueous Phase due to
change in temperature change then, it
will be disastrous, because for the
extraction process to be effective, the
solute must have higher solubility
towards Organic Solvent.
So, temperature must be kept fixed
during the extraction process.
Effect of pH
pH is a measurement of concentration
of proton present in a solution.
It determines whether the solution is
basic, acidic or neutral.
The higher the pH value of a solution
the fewer protons are present in it and
the less acidic or more basic it is, and
vice – versa.
pH value of neutral solution is 7.
pH is expressed as the negative
logarithm of Concentration of Proton.
pH=−log¿
pH is important in Liquid – Liquid
Extraction because, most drugs to be
extracted are either weak acids or weak
bases which donate or accept protons
respectively.
Since, the solvent for extraction is
organic, the solute / Target Compound
must be in their extractable form (A
neutral or unionized form of the solute
regardless whether the solute is a weak
base or a weak acid).
So, pH of the Feed Phase must be
adjusted by using a suitable buffer, so
10 | P a g e
that the solute remains in their
neutral / unionized form.
Emulsion Problem encountered in Liquid – Liquid Extraction
Emulsion can be defined as a dispersed
system where one liquid phase is dispersed
as droplets into another immiscible liquid
phase and the dispersion is stabilized by
using an appropriate emulsifying agent.
In Liquid – Liquid Extraction, the phases are
dispersed in each other through moderate
shaking so that they can come in each
other’s contact for solute transfer.
But, they must not form emulsion and after
shaking they must form separate layers
again.
It is to remember that a good emulsion may
destabilize into –
1. Coalescence
2. Flocculation
3. Creaming
4. Breaking
Figure 6: Instabilities in an Emulsion
Factors Influencing Emulsion Stability
Emulsion formation is a problem when
dealing with the extraction of drugs
from biological or pharmaceutical
formulations which tend to emulsify
even upon moderate shaking due to
presence of emulsion stabilizers in the
formulation.
These Emulsion Stabilizers are –
11 | P a g e
1. Finely Divided Powders
2. Surfactant
3. Ionic Species
Finely Divided Powders
Finely Divided Powders have a
tendency to coat the droplets
formed in an emulsion which
ultimately prevent them from
forming coalescence.
They are used as emulsifying agents
and as binders in pharmaceutical
liquid and solid dosage forms
respectively.
Such examples are –
Albumin
Gelatin
Natural Gums (Such as Acacia)
Figure 7: Coating of Finely Divided Powders on the
Droplets which prevents Emulsion Breaking
Surfactants
Surfactants are used to increase
H2O solubility of a compound which
can either be solid / liquid.
Presence of such surfactants is very
frequent in pharmaceutical
formulations which prevent
coalescence by surrounding the
droplets formed.
Examples of such surfactants are –
Cetosteryl alcohol
Glyceryl Monooleate
Figure 8: Surfactants Molecules Surrounding the
Droplets
Ionic Species
Ionic Species get absorbed at the
interface of the droplets resulting in
a net charge on the droplets.
Because all droplets essentially bear
the similar charge, they will repel
one another thereby preventing
coalescence.
12 | P a g e
Figure 9: Anionic Species Absorbed at the Interface
of Droplets builds up a net charge on the Droplets
and repelling each other preventing Coalescence
Prevention of Emulsion Formation
Moderate Shaking
The solvents must be shaken
moderately, so that the phases are
dispersed in each other for solute
transfer but then again forms
separate layers.
It is because vigorous shaking can
form emulsion.
High Density Difference
Density Difference between the
solvents chosen must be high so
that they do not form emulsion
upon dispersion.
E.g. –
Density of Water, Benzene and
n – hexane are 0.9982 gm / ml,
0.8765 gm / ml and 0.6548 gm /
ml respectively.
In case of Water – benzene
system there is a very low
density difference (0.1217 gm /
ml); so the system is very
susceptible to emulsion
formation even upon moderate
shaking.
But, in case of H2O – n-hexane
system, there is a high density
difference (0.3434 gm / ml); so
there is less chance of emulsion
formation.
Figure 10: Formation of Emulsion in water -
benzene system due to low density difference
Removal of Finely Divided Solids
Finely divided Solids tend to
stabilize the emulsion Formation by
coating the droplets.
13 | P a g e
So, before extraction these solids
must be removed from feed phase
by filtration.
Avoiding High pH Range
Since, Emulsification occurs more
frequently and easily in Extreme pH
range (i.e. below 4 – Extremely
Acidic and above 9 – Extremely
Basic); these ranges should be
avoided and kept between 4 to 9.
Removal of Surfactant by Using Adsorbents
To remove Surfactants, a thin bed
of adsorbents (E.g. Alumina, Silica
Gel) can be used through which the
feed phase can be passed through.
However, use of such adsorbents
must be avoided which can adsorb
the solute.
Processes of Breaking Emulsion
Mechanical Means
In case of simple emulsion,
coalescence can be achieved by
mechanically creating turbulence
on the surface of the droplets by
stirring with a glass rod.
Figure 11: Emulsion Breaking by Mechanical Means
Centrifugation
Centrifugation is a process of
separation by the application of
Centrifugal Force based on the
density difference between the
phases.
So, when the density difference
between the phases / solvents is
considerably high, centrifugation
can be applied to break the
emulsion.
Addition of Mono – or Di – valent Cations
Saturated Solution of Mono –
valent or Di – valent Salts (E.g. NaCl
or CaCl2) can be added to break
down the emulsion by increasing
14 | P a g e
the ionic strength of Water /
Aqueous Phase / Feed Phase.
Upon increasing the ionic strength
of Feed Phase, solubility of organic
solute or Complex / Chelate of
inorganic solute in aqueous phase /
Feed Phase decreases and they will
return to their own more soluble
organic phase.
Addition of Ethanol or Higher Alcohol
Addition of Ethanol or higher
alcohol increases coalescence in
emulsion by increasing the
interfacial tension between phases.
Silicone – Defoaming Agent
Addition of Silicone Defoaming
Agent helps in breaking the
emulsion.
Sudden Cooling or Thermal Shock
Sudden temperature drop or
freezing (i.e. giving a thermal shock)
of emulsion mostly enhances the
interfacial tension between the two
immiscible phases thereby causing
coalescence.
Alteration of Solvent Ratio
Coalescence of an emulsion can be
achieved by altering the ratio of
solvents prevailing in the dispersed
phase.
It can be done by slowly adding
solvents.
Thin – Bed of Adsorbent
A thin bed of adsorbents (E.g.
Alumina, Silica Gel) can be used
through which the feed phase can
be passed through to break the
emulsion.
Drying Agents
Definition
Drying Agents are compounds that are
used to absorb H2O from the extract,
since presence of H2O in the extract can
cause –
Volume Change giving error in the
result.
Water in the Organic Extract may
increase its boiling point close to
1000C, so during evaporation of the
extract (to collect and measure the
solute), the solute can be degraded
due to high temperature, thus
resulting in content loss.
Upon addition of drying agents and
following stirring, they will react with
water present in the extract to form a
clump and settle to bottom.
15 | P a g e
When there will be no water in the
extract, drying agents will float on the
surface of the extract, since there is no
water to react with.
Classification of Drying Agents
Drying Agents used in Liquid – Liquid
Extraction can be of 2 types –
1. Magnesium Sulfate (Mg2SO4)
2. Sodium Sulfate (Na2SO4)
Magnesium Sulfate (Mg2SO4)
Mg2SO4 can be used as Drying Agent
to remove Water from the extract,
in Liquid – Liquid Extraction
If water is present in the extract,
then, Mg2SO4 will form Magnesium
Sulfate – Water complex
(Mg2SO4.2H2O).
Advantages of Magnesium Sulfate
Magnesium Sulfate is granule
type material, so it has large
surface area.
As a result it provides quick
absorption of H2O from the
extract.
Disadvantages of Magnesium Sulfate
Magnesium sulfate is acidic in
nature, so it easily reacts with
basic target solutes.
Sodium Sulfate (Na2SO4)
Na2SO4 can be used as Drying Agent
to remove Water from the extract,
in Liquid – Liquid Extraction
If water is present in the extract,
then, Na2SO4 will form a clump of
Sodium Sulfate – Water complex
(Na2SO4.2H2O) which will settle at
the bottom.
Advantages of Sodium Sulfate
Sodium Sulfate is neutral
compound, so it can be used
with any type of solute.
Disadvantages of Sodium Sulfate
Sodium Sulfate is a granular
compound, so it has low surface
area.
As a result, it absorbs water
slowly from the extract.
L i q u i d – L i q u i d W a s h i n g
Definition
Liquid – Liquid Washing is a process of
separation of impurities from the extract or
reaction medium containing the target
solute and also the impurities.
The process can be used to remove
impurities from a reaction medium.
16 | P a g e
Type of Impurities removed in Liquid – Liquid Washing
Impurities to be removed via Liquid – Liquid
Washing can be of 2 type –
Byproduct
Catalyst
For example, all of A and B reacts to form C
and D which is catalysed by X. So, here the
impurities are the byproduct D and catalyst
X.
Steps of Liquid – Liquid Washing
Steps involved in the Liquid – Liquid
Washing are –
1. Reaction Work – up
2. Separation of Target Solute from the
Reaction medium by adding Organic
Solvent
3. Removal of Impurities
Reaction Work-up in Liquid – Liquid Washing
Reaction of Phenol and Acetic
anhydride results in the formation of
Phenol acetate and Acetic Acid which is
catalysed by Triethylamine.
Figure 12: Reaction of Phenol and Acetic anhydride
So, after the reaction of all of Phenol
and Acetic anhydride, the compounds
that remain in the reaction medium are
–
Phenol acetate
Acetic Acid the Byproduct
Triethylamine the Catalyst
Here, Acetic Acid the Byproduct and
Triethylamine the Catalyst are the
impurities and Phenol acetate is the
product or Target Compound.
Separation of Target Solute from the Reaction medium
17 | P a g e
Before performing the separation, it
must be considered that solubility of
the target compound in organic solvent
must be higher than the solubility of
impurities.
So, solvent should be selected in such a
way.
In case of this reaction, the target
compound Phenol acetate is insoluble
in water and soluble in Ether which is
higher than that of both Acetic Acid and
Triethylamine.
So, Ether can be the organic solvent of
choice to separate Target Solute from
the Reaction medium.
Removal of Impurities
Selection of Solvents to remove
impurities depends on the properties of
impurities.
Impurities of acidic nature can be
removed by adding saturated aqueous
solution of a Strong Base in the organic
extract. E.g. Acetic Acid (A Weak Acid)
can be removed by adding saturated
aqueous solution of NaHCO3 in Ether
extract of Phenol acetate. As a result,
Sodium acetate will form which is salt
of Acetic Acid and soluble in water from
the saturated aqueous solution of
NaHCO3.
Figure 13: Removal of Acetic Acid
Impurities of basic nature can be
removed by adding dilute solution of
Strong Acids in the organic extract. E.g.
Triethylamine (A base) can be removed
by adding 10% HCl aqueous solution in
Ether extract of Phenol acetate. As a
result, Triethylamine hydrochloride will
form which is salt of Triethylamine and
soluble in water.
18 | P a g e
Figure 14: Removal of Triethylamine
Problem of Sparingly Soluble Solvents
Use of sparingly soluble solvents must be
avoided.
It is because, severe content loss of target
compound occurs upon using sparingly
soluble solvents especially when the organic
solvent is soluble in water (E.g. Solubility of
Ether in water is 5.6 mg / 100ml).
So, an amount of target compound that is
soluble in organic solvent is lost every time,
when the separation is performed, since an
amount of organic solvent is sparingly
soluble in water. Thus resulting in content
loss of target compound.
Solution
The problem of content loss is solved by
adding Brine solution / Saturated
Solution of NaCl in water before
performing separation of impurities
which incorporates a high
concentration of Na+ and Cl- ions in the
water, thus increasing its ionic strength.
As a result, the solubility of organic
compound in aqueous phase will
decrease.
So, the organic compound will transfer
to its own organic phase.
Difference between Liquid – Liquid Extraction and Liquid –
Liquid Washing
Difference between Liquid – Liquid
Extraction and Liquid – Liquid Washing
is as followed –
Table 1: Difference between Liquid - Liquid
Extraction and Liquid - Liquid Washing
Topic Liquid – Liquid Extraction
Liquid – Liquid Washing
Target Compound
Extracted by Organic Solvent
Remains in the Organic Solvent
Solvent Evaporation
Performed to collect and measure the Target solute
Not required because Impurities are removed
Solubility of Target Solute
Solubility of the target compound
Solubility of the target compound
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Topic Liquid – Liquid Extraction
Liquid – Liquid Washing
in organic solvent must be higher than in aqueous solvent
in organic solvent must be higher than the solubility of impurities
Selection of Solvents
Depends on Miscibility, Solubility and Density of the solvent pair
Depends on the properties of impurities
Contents in the extract
Only Target Solute
Target Solute + Impurities (Byproduct + Catalyst)
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