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

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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

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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.

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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.

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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.

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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

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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. –

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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.

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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

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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

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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 –

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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.

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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

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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.

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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.

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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

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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.

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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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