Chapter 2

Chapter 2: Techniques in Organic Syntheses
Learning Objectives
By the end of this section, you should be able to apply concepts related to basic organic techniques
such as:
1. Reflux
2. Filtration
3. Recrystallisation
4. Distillation
5. Liquid-liquid Extraction
6. Thin-layer Chromatography (TLC)
2.1 Reflux
 Reflux: A technique that involves boiling of a reaction mixture and condensation of
solvent vapour.
 Most organic synthesis preparations are carried out in the liquid phase in a reaction
solvent
 Boiling/ heating is done to increase the rate of a reaction
 Condensation prevents reagents form escaping the system
 However, the reflux set-up is an OPEN system (opening at the top)
Precautions
 Grease joints
 Dry round bottom flask
 Anti-bumping granules (glass beads)
Note components and position

2.2 Filtration
 Filtration: technique that uses a filter to separate solid residue from liquid filtrate in a
mixture
 Liquid collected is known as the filtrate and solid trapped Is the residue
3 methods:
Gravity Filtration Hot gravity filtration Suction Filtration
Efficiency Slow Very slow Fast

Relies on gravity Relies on gravity, time Air is forced through the filter
needed to heat apparatus via the vacuum pump
Application Typically for removing solid Remove solid impurities Isolate a desired solid NOT
impurities during recrystallisation IMPURITY (E.g.
recrystallisation)
Type of filter Cotton wool or Fluted filter paper, Flat filter paper, dampened
conventional/fluted filter dampened with hot solvent with cold solvent
paper
Glassware & funnel Filter funnel, conical flask Hot stemless funnel, hot Büchner filter flask and
required beaker Büchner funnel
Risk level Low High Medium
Limitations Typically useful for Must use hot solvent Requires the use of a vacuum
removing solid impurities pump
Common errors Too much sample is added, Glassware is not hot Failure to wet paper  poor
then filtration is very slow causing premature seal, solids pass under
recrystallisation and Using one piece of filter paper
blockage of funnel  holes in the filter funnel not
covered
Hot gravity filtration procedure

1. Place a hot stemless funnel in a beaker in the fume hood
2. Add a fluted filter paper into the stemless funnel
3. Dampen the entire filter paper with the hot recrystallisation solvent
4. Quickly pour the hot saturated solution through the fluted filter paper and hot,
stemless funnel
5. Transfer both beaker and funnel onto the hot plate once filtration has begun.
6. Once the filtration is complete, remove the beaker and funnel from the hot plate.
2.3 Recrystallisation
 Recrystallisation: Technique used to purify a solid
 Recrystallisation occurs because the solubility of the solid solute increases as the temperature
increases. This means the solute dissolves at high temperatures and solidifies at low
temperatures.
Soluble impurities, even if present in small amounts, will remain dissolved in the solution. So
suction filtration is able to remove the impurities.
Insoluble impurities, if present, can be removed by hot gravity filtration. Obtained crystals
dissolve when heated and are the filtrated, while solid impurities are the residue.
 Requirements:
 Desired compound must be a solid at room temperature
 Solvent must not react with desired compound
 Purified compound must be very soluble in hot and almost insoluble in cold solvent.
 Impurities must be very soluble in cold solvent or almost insoluble in hot solvent
Types of recrystallisation
Single solvent - A single solvent is used
- Heat is required to dissolve the solute
Multi solvent - 2 solvents are used
- Appropriate ratio of good solvent to poor solvent (antisolvent)
- Heat may/may not be used
Hot filtration - Typically a single solvent is used
- Hot filtration is required to remove any insoluble impurities such as
sand, charcoal
Seeding - Initiates recrystallisation by adding a pure crystal or scratching the
inner walls of the flask to create a seeding surface for the crystals to
grow
- Required when recrystallisation is difficult
 Precautions:
 Ensure that the solution is hot and saturated
 Do not heat the crystals as most organic substance will lose their water of crystallisation and
even decompose under direct heating
 Do not cool the solution too quickly or disturb the reaction flask  reduces yield of crystals
 Solutions to difficult recrystallisation:

 Boil the solvent away
 Try scratching inner walls
 Use ice/water bath
 Use another solvent
Steps to recrystallisation
1. Add a small amount of solvent to achieve a saturated solution
2. Heat the suspension, to dissolve the solute (desired product), hot gravity filtration may be
used
3. Cool the solution to recrystallise
4. Suction filtration is used to isolate the solid and dry it
5.4 Distillation
 Apparatus set up to obtain a pure solvent from a solution (2 miscible solns)
 Intermolecular forces in a liquid must be overcome in other to vaporise one of the
solutions to be condensed into another vessel
 Glassware required (note positions as well)

 Round bottom flask
 Glass T-joint
 Condenser
 Collection glass joint
 Collection flask
 Miscellaneous items required

 Heating mantle
 Thermometer
 Retort stand, clamp and bosshead
 Grease, glass beads
 Precautions:
 Don’t over boil as separation will be poor
 Ensure thermometer is at the “T” intersection to record accurate readings
 Ensure the glass joints are greased so seizure does not occur
 Ensure there are no gaps between the glass joints, so no vapour escapes
 Ensure water is running through the condenser
 Angle the condenser correctly so the distillate can be collected
5.4.1 Transition states

1. Vaporisation
 A liquid  a gas; through evaporation or boiling
2. Condensation
 A gas  a liquid through cooling
3. Deposition (or desublimation)
 Gas  a solid without going through the liquid phase
5.4.2 Intermolecular Forces of liquids
Ion-ion forces > Ion-dipole > Hydrogen bond > Dipole-dipole force > Dispersion forces
 Also dependent on the molar mass (if the bonds are the same)  ↑molar mass, ↑B.p.
 Amides: Have an extensive network of hydrogen bonds

 Carb acids: Dimers with trigonal planar arrangement of bonds  makes Hydrogen bonds
more diff to break
 Alcohols: hydrogen bonding due to the presence of OH groups.
 Pri and sec amines: still have hydrogen bonding to N (N-H bond is weaker than OH)
5.5 Liquid-liquid Extraction
 Liquid-liquid extraction: separates 2 components in an (organic) mixture using 2
immiscible solvents (aqueous & organic) in a separatory funnel
 For example, the extraction of Sodium chloride (polar) from cholesterol (non-
polar) using an organic solvent such as ether and an aqueous solvent water
1. The immiscible solvents will form 2 distinct layers due to density difference
2. The polar components dissolves in aqueous Layer, non-polar components dissolve in
organic layer
3. Liquid-liquid extraction is then carried out to separate the 2 layers of liquids using
the separation funnel, thus the components are separated as well.
Precautions:
1. If there is no distinct separation:
 Add NaCl to make the aqueous layer more dense than the organic layer
 Add more aqueous layer / organic layer
2. The liquid does not flow out of the separation funnel
 Ensure the glass stopper is removed from the top of the flask
3. Unsure which layer is organic or aqueous
 Add a few drops of known aqueous or organic solvent and observe which layer it
sets in
4. Solid particles are present
 Choose a different solvent or filter during separation  desired component to be
extracted may be insoluble in both organic and aqueous solvent
5. Effervescence is formed when the layers are mixed
 Wait for effervescence to disappear and ensure the glass stopper at the top is
removed  Acid-base reactions can cause effervescence (CO2)
5.5.1 Acid-Base extraction
 Acid-Base extraction: To separate acids or bases from an organic solvent
 Separate a organic base from a non-base

 Add acid to convert organic base into water-soluble salt (e.g. amine)
 The water-soluble polar salt dissolves in the aqueous layer from the added acid,
while the non-polar non-base components remains in the organic solution.
 Carry out liquid-liquid extraction
 Convert polar salt  non-polar base again by adding a strong base.
 The recovered base separates from the aqueous solution; carry out liq-liq Extraction
 Separate an organic acid from a non-acid

 Add base to convert organic acid into water-soluble salt (e.g. hydroxyl, carboxylic)
 The water-soluble polar salt dissolves in the base, while the non-polar non-acid
components remains in the organic solution.
 Carry out liquid-liquid extraction
 Convert polar salt  non-polar acid again by adding a strong acid.
 The recovered acid separates from the aqueous solution; carry out liq-liq Extraction
 NOTE:
 Memorise the functional group of COOH carboxylic acids
 Memorise the functional group of OH, amines are bases
5.6 Thin-layer chromatography
 Thin layer chromatography: Technique that separates and identifies components in a

sample by distributing them between a stationary phase and a mobile phase, based on
difference in polarity
 Polar Stationary phase (solid), Non-polar Mobile phase (liquid/gas)
 Components distribute based on sorption (sticking) and desorption (unsticking)
processes
distance travelled by component
 Retention factor (Rf): ratio
distance travelled by mobile phase
 Separation of components depends on:

1. Component affinity for stationary phase
o Polar solutes are distributed preferentially in the polar stationary phase it will
pass through the system slower and ↓Rf
2. Component affinity for mobile phase
o Non-Polar solutes are distributed preferentially in the nonpolar mobile phase
it will pass through the system faster and ↑Rf
3. Mobile phase affinity for and competing for the stationary phase
o Mobile phase polarity ↑, more polar mobile phase molecules attach to the
stationary phase, forcing other components to climb higher and ↑Rf.
4. Grain size, water content and thickness of absorbents on Stationary phase
Characteristic TLC
Application Separate and identify
Sample size Small diluted sample
Flow direction Against gravity
Speed Fast
Mobile phase Relatively nonpolar solvent
Stationary Phase Highly polar silica gel on inert solid
Position trends of Polar-bottom, non-polar top
components
5. Material spotted and temperature
 Precautions:
 Don’t use too much sample
 Ensure the mobile phase isn’t too polar  more competition for components
 Ensure the sample does not develop past solvent front  inaccurate Rf values
5.6.1 TLC visualisation technique
 TLC visualisation techniques: allow invisible component spots to be seen
 Ultraviolet light:
 used to detect UV-active substances with extended conjugation (i.e., alternating, or
adjacent double bonds and single bonds; NOT ISOLATED), AND aromatics
 non-destructive; need to circle violet spots as they are impermanent (they disappear
in the absence of UV light)
 Iodine coated on silica powder:

 used to detect presence of multiple saturated bonds and aromatics (with benzene
ring)
 semi-destructive; need to circle brown spots as they are often impermanent
 Potassium permanganate solution:

 used to detect presence of any oxidizable compound such as alcohol (pri, sec), ether,
ester, alkene, alkyne(mains), alkyl aromatic, aldehyde, carboxylic acid, amine, amide
and almost all the rest will show up as brown-yellow spots (MnO2).
 KETONES, TERT-ALCOHOLS, ALKANES, AROMATICS CANNOT unless there is
another functional grp in the compound that can be oxidised
 For alcohol and amines mild heating is required.
 destructive; yellow/brown spots are permanent, so there is no need to circle these
spots
5.6.2 TLC Flash Column Chromatography
 A type of chromatography where instead a plane (flat) stationary phase, a column is
used, and is effective in separating mixtures of organic compounds

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Chapter 2: Techniques in Organic Syntheses

Note components and position

Efficiency Slow Very slow Fast

Hot gravity filtration procedure

 Solutions to difficult recrystallisation:

 Glassware required (note positions as well)

 Miscellaneous items required

5.4.1 Transition states

 Amides: Have an extensive network of hydrogen bonds

 Separate a organic base from a non-base

 Separate an organic acid from a non-acid

 Thin layer chromatography: Technique that separates and identifies components in a

 Separation of components depends on:

 Iodine coated on silica powder:

 semi-destructive; need to circle brown spots as they are often impermanent

 Potassium permanganate solution:

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