Organic Chemistry Lab: Student Manual

VIET NAM NATIONAL UNIVERSITY – HO CHI MINH CITY
UNIVERSITY OF TECHNOLOGY
FACULTY OF CHEMICAL ENGINEERING
STUDENT MANUAL
ORGANIC CHEMISTRY LAB
Compilers:
Dr. Le Vu Ha
Dr. Le Xuan Tien
Dr. Nguyen Dang Khoa
Assoc. Prof. Le Thi Hong Nhan
HO CHI MINH CITY, 01/2020

STUDENT MANUAL – ORGANIC CHEMISTRY LAB – HCMUT
Table of Contents
Unit 1 – Introduction to organic synthesis laboratory 3
1.1. Lab safety rules 3
1.1.1. Safety guidelines 3
1.1.2. Lab first aid 4
1.1.3. Lab glassware safety 6
1.2. Basic laboratory glassware 7
1.3. Gravity filtration and vacuum filtration 9
1.4. Washing and extraction 10
1.5. Heating and controlled boiling 14
1.6. Cooling 15
1.7. Drying 16
1.8. Distillation 17
1.9. Recrystallization 24
1.10. Calculation of the reaction yield 29
Unit 2 – Synthesis of ß-naphthol orange 30
Unit 3 – Synthesis of dibenzylideneacetone 33
Unit 4 – Synthesis of benzoic acid 37
Unit 5 – Synthesis of ethyl acetate 40
Unit 6 – Synthesis of terpineol 43
Unit 7 – Synthesis of aspirin 46
Unit 8 – Synthesis of soap 49
Unit 9 – Determination of melting point and recrystallization of benzoic acid 53
Unit 10 – Liquid-phase separation techniques 58
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Unit 1 – Introduction to organic synthesis laboratory
1.1. Lab safety rules
The organic chemistry laboratory is potentially one of the most dangerous of undergraduate
laboratories. That is why you must have a set of safety guidelines.
1.1.1. Safety guidelines
● Wear safety glasses always in lab to mitigate or eliminate eye injuries by lab accidents
which can happen anytime, anywhere. To protect your eyes, safety glasses must include
side shields to prevent the inrush of foreign objects and chemicals from the sides.
● Wear long-sleeve safety coat, pants, and safety-toe shoes to protect almost your entire
body from chemical exposures and lab accidents.
● Choose the right glove types for specific works such as leather, latex, rubber, or plastic
gloves when working with chemicals, aluminized or wool gloves when working with heat.
● Never work alone. And don’t work at unauthorized times without your instructor’s
permission. If you are working alone in lab and have a serious accident, you might not be
able to get help before your faint.
● Read and take notes on any experiment carefully before the lab. For example, you’re
unprepared before the lab, so you have a lab book out, and begin reading the start of a
sentence and simultaneously do that operation “Addition of water to concentrated sulfuric
acid”. Probably there is no chance for you to read its rest “is not allowed because high
exothermicity can cause serious accidents”.
● Read the entire chemical label carefully to be sure you will have the right stuff. For
example, the bottle of sodium is close to the place of sodium sulfate. If you are careless, you
will have a good chance of picking up sodium to dehydrate an organic acid. Do not forget to
check material safety data sheet (MSDS) before using any chemical.
● Ask your instructor anytime if you have any question or problem. Remember that your
instructor is always ready to help you and give you important advices. Shyness in asking
questions will make you look foolish and often lead to negative results.
● Never eat, drink, and smoke in lab. Mistakes can be deadly. Eating contaminated
food/drink makes for an embarrassing story for your obituary. Smoking nearby flammable
solvents and gases can blow you up.
● Do not smell and touch any chemical or any product in lab without your instructor’s
permission. Tasting them is absolutely banned.
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● Be always careful. Chemistry is a serious challenge. Lab accidents are never expected but
seldom predicted. If you are be careless or clown in lab, you can hurt yourself and other
people or even burned all down.
● Keep your lab clean. Close all chemical container after using them. Clean up your bench
and allocated places after the lab. Turn off burners, water, and electrical equipment before
your leave. Wash equipment and glassware you have used under your instructor’s guide.
● Remember the locations and proper use of the fire extinguishers, fire blankets, safety
showers, eyewash stations, first-aid boxes, and emergency contacts. This is indeed
useful to diminish accidental damages.
● Learn how and where to dispose of wastes made from different materials or in different
states or with different toxicities or with conflicting reactivities. For example, you cannot pour
an acid into a bases-containing waste bottle.
● Work in the hood. A hood has at the least, a powered vent to suck noxious fumes outside. It
is also an ideal place to carry out many operations of an organic lab due to a safety glass or
plastic panel you can pull down as protection from exploding apparatus.
● Do not place flammable compounds close to flames and heat sources. Heating them by
an open-flame heater is not allowed as well.
1.1.2. Lab first aid
First aid is a set of guidelines which can reduce the damages caused by exposure to chemicals
or injury before expert medical help can be provided. All people working in the lab must be
familiar with first-aid practices as these save valuable time and reduce damages in case of lab
accidents.
First aid kit
First aid kit should be a dedicated cabinet or box and contain essential medicines, antiseptic
lotions, creams, bandages, and sterilized cotton. Maintaining a list of the contents and discarding
the expired medicines and replacement with fresh stocks must be regularly done.
Contact Information
● Names and contact details of employees holding first aid training certificates
● List of blood groups of all laboratory employees
● Names of employees with detailed specific allergies
● Telephone numbers of hospitals
● Emergency contact numbers such as ambulance, fire and rescue services, and police
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Guidelines for first aid providers
● Maintain calm and evacuate the area in case there is danger.

● Start remedial action to save time before expert medical help can be provided. Do not
attempt to move around the victim unless he/she is exposed to smoke, fire, hazardous
chemicals, or vapors. Take proper care in moving to a safe location.
● Ensure that the victim is breathing. If breathing stops, try artificial respiration.
● Do not try to remove deeply embedded metal or glass shreds. Bandage the wounds to
control bleeding till medical help arrives.
● Intense bleeding can be stopped by pressing the wound with your thumb
● In case the victim has fainted turn him/her on the side with the face tilted towards the floor to
prevent choking by the tongue.
Specific first aid tips
● Skin burns: hold the affected skin under a stream of running water for at least 10 – 15 min.
Keep the wound open and do not apply any ointment/cream/iodine/object until expert
medical help can be provided. In case of strong acid burns after washing with water rinse
with dilute ammonia (1 – 2%) or sodium bicarbonate (2 – 3%) solution. Use a 1% acetic acid
solution for strong base burns.
Caution!!! Never apply strong acids or alkalis to neutralize the corrosive liquid on the skin.
Due to heat of reaction, matters can get even more complicated.
● Chemical eye injury: if corrosive liquid gets splashed into the eyes, immediately wash the
eyes thoroughly with fresh water using an eye fountain or eye wash bottle. You can also
flush your eye gently under a running faucet, kitchen sink sprayer, or shower. Move your eye
in all directions during the flushing so that all areas of your eye are rinsed. When flushing,
pull the lower and upper eyelid forward to make sure any solid or liquid chemical caught in
these areas is rinsed away. Keep flushing the eye for at least 30 minutes or longer. After
flushing the eye, do not bandage or put any pressure on the eye and immediately transport
the injured person to a closest hospital.
Caution!!! Never apply any chemical to the injured eyes until expert medical help can be
provided.
● Poisons: If the victim has swallowed any poison, dilute the stomach contents by drinking a
large amount of water or milk and immediately transport the victim to a medical center. In
case of gas poisoning, transfer the victim into the fresh air immediately. If breathing is
stopped or irregular, give artificial respiration and call for an ambulance oxygen cylinder for
taking the victim to the hospital.
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● Cuts and wounds: For a small cut by broken glass, keep bleeding for seconds and clean
the wound with running water to flush dirt and contaminants out of the wound, use ethanol as
an antiseptic and then cover it with a sticking plaster. In other cases, try to stop bleeding as
the first step by covering the wound with clean cloth or sterile gauze and applying direct
pressure. If bleeding is continuous, do not remove dressing but apply further dressing or
pads in the old ones and bandage firmly. Transport the victim to a hospital in serious cases.
1.1.3. Lab glassware safety
Fragile glassware is one of the most used kinds of equipment in science laboratories. Follow all
lab safety rules when using and handling glassware to avoid accidents and injury.
● Do not use laboratory vessels for food or drink.

● Do not use glassware when working with hydrofluoric acid, hot phosphoric acid, or strong hot
alkalis.
● Do not use excessive force to tighten glassware to clamps.
● Check all glassware for wetness, cracks, and contamination before use. The glassware must
be dry for water-sensitive steps, reactions, and compounds. Cracked items should be
disposed of. And dirty glassware should be cleaned.
● Discard cracked, broken and other waste glass in a container specially marked to indicate its
contents.
● Do not change glassware temperature (both heating and cooling) suddenly. If such an
operation or heating at high temperature (from 100 oC to 200 oC), borosilicate glassware
(e.g., "Pyrex", “Kimax”) should be applied. Water, oil, and sand baths should be used to heat
glassware indirectly.
● Never heat sealed or stoppered glassware. Also never stopper or seal glassware contains
any hot volatile compound or any mixture that will release gases (e.g., acetic acid + sodium
bicarbonate).
● Use pressure-assistant glassware for vacuum and high-pressure applications.
● Never use a thermometer as a stirring rod.
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1.2. Basic laboratory glassware
(a) (b) (c)
Figure 1.1. a. Glass beaker, b. Erlenmeyer flask, c. Graduated cylinder.
(a) (b) (c)
(d) (e) (f)
(g) (h) (i) (j)
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Figure 1.2. Common flask types: (a) flat-bottom flask, (b) round-bottom flask, (c) pear-shaped
flask, (d, e, f) multi-neck flasks, (g, h) Wurtz distillation flasks, (i) Claisen distillation flask, (j)
Claisen distillation flask with a Vigreux fractionating column.
(a) (b) (c) (d) (e)
Figure 1.3. Common conderser types: a. air condenser, b. Liebig condenser (straight
condenser), c. Allihn condenser (bulb condenser), d. Graham condenser (coolant-jacketed spiral
coil as the vapor–condensate path), e. Coil condenser (spiral coil with coolant flows jacketed by
the vapor–condensate path).
a. b. c. d. e. f.
Figure 1.4. Filtration equipment: a. long-stem funnel, b. short-stem funnel for hot filtration, c.
Büchner funnel, d. Büchner funnel with fritted disc, e. jacketed Buchner funnel, f. Büchner flask
(filter flask).
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(a) (b) (c) (d) (e) (f) (g) (h)
Figure 1.5. Common funnel types: (a, b, c, d) separatory funnels, (e, f) addition funnels (dropping
funnels), (g,h) pressure equalizing dropping funnels
(a) (b)
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Figure 1.6. (a) temperature-controlled reaction apparatus, (b) reflux reaction apparatus.
1.3. Gravity filtration and vacuum filtration
Figure 1.7. Apparatus for gravity filtration
a. b.
Figure 1.8. Preparation of (a) a cone filter paper and (b) a pleated filter paper.
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Figure 1.9. Vacuum filtration apparatus.
1.4. Washing and extraction
Extraction is one of the more complex operations that you’ll do in the organic chemistry lab.
Another term that you’ll see used simultaneously with extraction is washing. That’s because
extraction and washing are indeed the same operation, but lead to very different ends due to
very different purposes.
Extraction is to obtain an expected compound from a mixture/a matrix while washing is to

remove the impurities from the expected compound.
Depending on the mixture type, extraction includes solid-liquid process for dissolving some
components of a solid directly into the solvent (e.g., coffee making, extraction of essential oil
from orange) and liquid-liquid process for pulling some components from solvent A to solvent B
(e.g., extracting morphine from an aqueous solution into ethyl acetate).
Liquid-liquid extraction
Liquid-liquid extraction is more popular in lab as a step of a synthetic procedure based on the
relative solubilities of a compound in two different immiscible liquids, typically water (polar) and
an organic solvent (non-polar). The solvent that is enriched with solute(s) is called the extract
while the feed solution that is depleted of solute(s) is called the raffinate.
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In solvent extraction, a distribution coefficient is often determined as a measure of how efficient

the extraction of a species is. In case of extracting the solute from A to B, the distribution ratio
(Kd) is equal to the concentration of the solute in the extract B divided by its concentration in the
raffinate A (Kd = CB/CA). The distribution ratio can be a function of temperature, the concentration
of chemical species in the system, and many other parameters.
The larger Kd is, the more efficient extraction is. If Kd is smaller than 100, a multiple extraction
procedure is required. Multiple extractions with small solvent amounts are also always more
efficient than one single extraction with a large volume. The solvent for extraction must be
immiscible with the feed solvent, well dissolve the solute and should have a low boiling
temperature for easy solvent removal after the extraction step. Common solvent ideal for
extraction are diethyl ether, petroleum ether, n-hexane, chloroform, dichloromethane, ethyl
acetate, toluene.
Liquid-liquid extraction or washing is usually performed with a separatory funnel including the
following steps:
1. Add liquid phases to the separatory funnel (the stopcock must be closed first!). Two separate
phases should be observed.
2. Place the cap on the separatory funnel.
3. Holding the cap and funnel securely, invert the separatory funnel.
4. Vent the separatory funnel: with the funnel inverted (and cap secured), open the stopcock to
reduce any pressure that has built or release any formed gas (if any).
5. Close the stopcock and gently shake the separatory funnel.
6. Repeat the shaking and venting steps several times.
7. After completing the above steps, it is necessary to collect the phase that has dissolved the
compound targeted for isolation. Deciding which phase this is actually requires knowledge of
the polarity of the target compound. When in doubt, save both phases and consult with the
instructor. Never throw away a phase until absolutel certain it is no longer needed.
8. To remove a phase from the separatory funnel, return the funnel to the ring clamp. Remove
the cap from the separatory funnel and drain the two phases into two different beakers.
9. Decide which solvent contains the target compound. Usually the entire extraction process is
repeated several times to ensure that the maximum amount of the target molecule has been
isolated. For this reason, it is necessary to also save the phase containing the original
mixture.
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Figure 1.10. Liquid-liquid extraction using a separatory funnel.
Solid-liquid extraction
When desired components are extracted from a solid material into a liquid solvent, the process
is called a solid-liquid extraction. Typical examples are the extraction of essential oils from plants
with organic solvents and the extraction of caffeine from coffee or tea with water (coffee or tea
making).
A smaller size of solid materials allows a higher surface contact between the materials and the
extraction solvent, favoring the extraction of the solutes. The best extraction solvent is able to
selectively dissolve the expected compound but cannot dissolve or poorly dissolve unexpected
ones. In lab, a solid-liquid extraction is usually performed using a Soxhlet extraction apparatus.
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Figure 1.11. A Soxhlet extraction system.
Washing
Several common procedures to wash impurities in an organic phase are listed below:
● Wash strong acids (HCl, H2SO4…) with Na2CO3aq (10%), NaHCO3aq, or water
● Wash weak organic acids (RCOOH) with Na2CO3aq (10%) or NaHCO3aq
● Wash very weak organic acids (phenols) with NaOHaq (5-10%)
● Wash strong inorganic bases (NaOH, KOH…) with water
● Wash organic bases (aniline, trimethylamine…) with HClaq (5-10%)
● Wash neutral compounds with immiscible solvents
1.5. Heating and controlled boiling
In organic synthesis, many processes must be carried out at an elevated temperature upon a
heat source. However, except water and several halogenated solvents, most organic liquids are
flammable, easily catching on fire and sustaining combustion. The use of a naked flame (e.g., a
Bunsen burner) is therefore strictly limited in the organic chemistry laboratory because it could
ignite flammable vapors. A flame is never used to directly heat an organic liquid in an open
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beaker or test tube; however, it is useful if water is the solvent or heating is indirect via a water
bath. To use a Bunsen burner in the lab, be sure that there are no flammable solvents nearby.
Common heat sources are a steam bath, a water/mineral oil/silicone oil/glycerol/sand bath
(heated with an electrical hot plate), an electric hot plate, and an electric heating mantle.
Table 1.1. Useful temperature ranges of heat sources.
Heat source Useful range (oC)
Steam bath 25 – 80
Water bath 0 – 70
Silicone oil bath 25 – 230
Glycerol bath 25 – 200
Mineral oil bath 25 – 200
Sand bath 25 – 500
Controlled boiling
Boiling stones (boiling chips) are small pieces of inert porous materials (e.g., silicon carbide,
glass, carbon, calcium sulfate, calcium carbonate, polytetrafluoroethylene) that are added to a
solution or a solvent to control boiling. They contain trapped air that bubbles out when the liquid
phase is heated, and act as nucleation sites (due to their high surface area) for formation of
solvent bubbles. The use of boiling stones does not only help the liquid boil smoothly without
becoming superheated or bumping but also improve mass and heat transfer. Boiling stones are
frequently present in distillation and boiling liquids (solvents, reaction mixture).
Caution!!!
- Never add boiling stones to a liquid that is boiling or near its boiling because this can lead to
violent flash boiling, splash hot material out of a flask and finally cause serious accidents
(burn, fire).
- Just use boiling stones for boiling systems. They are useless for non-boiling ones.
- Do not re-use boiling stones without activation.
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- Be careful with using boiling stones in concentrated solutions of acids or bases. They might
be reactive with such solutions.
- Besides boiling stones, boiling sticks (wood splints) and stirring bar (always used with a
magnetic stirrer) are alternatively used to control boiling. Note that stirring bar is mainly used
for stirring a mixture.
(a) (b) (c)

Figure 1.12. Controlled boiling using (a) a boiling stone, (b) a boiling stick, and (c) a stir bar.
1.6. Cooling
Cooling is necessary for crystallization, low-temperature reaction, absorption of heat from an

exothermic reaction or reducing vaporization. In lab, a cooling bath is used to maintain low
temperatures, typically between 13 °C and -196 °C, which usually contains the following cooling
agents/mixtures:
- Water bath: room temperature
- Ice bath (an ice-water slurry has better surface contact than ice alone): 0 oC can be achieved
- Crushed ice + sodium chloride (3:1 by weight): -20 oC can be achieved
- Crushed ice + calcium chloride (4:5 by weight): -50 oC can be achieved
- Dry ice (solid CO2) + diisopropyl ether: -60 oC can be achieved
- Dry ice (solid CO2) + liquid acetone or isopropanol: -78 oC can be achieved
- Dry ice (solid CO2) + liquid ethanol: -72 oC can be achieved
- Liquid N2 + liquid acetone: -94 oC can be achieved
- Liquid N2 + liquid ethanol: -114 oC can be achieved
- Liquid N2: -196 oC can be achieved
1.7. Drying
Drying an organic liquid
To synthesize a liquid organic product, the liquid must be dried before finally distilled and
packaged. Drying agents (desiccants) are usually anhydrous salts that combine with the water in
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the product and hold it as water of crystallization. After drying, simple decantation or gravity
filtration can be performed to remove the hydrated agent from the product.
Table 1.2. Common drying agents.
Organic compounds Drying agents
R-X (X=Cl, Br, I) CaCl2, CaSO4, P2O5, MgSO4
Alcohol CaSO4, MgSO4, K2CO3, CaO

Ether, saturated hydrocarbon, aromatic hydrocarbon CaCl2, CaSO4, P2O5
Aldehyde MgSO4, NaSO4
Ketone CaSO4, MgSO4, Na2SO4
Organic acid MgSO4, Na2SO4, CaSO4
Amine KOH, NaOH, K2CO3, CaO
Anhydrous calcium chloride (CaCl2): this drying agent is a very popular, inexpensive, and
efficient. However, because of slow dehydration, the mixture needs to be gently heated. It
should be noted that commercial CaCl2 which can be contaminated with Ca(OH)2 cannot be
used to dry acids or acidic solution. More importantly, also do not apply CaCl2 for drying
alcohols, phenols, amines, amino acids, amides, ketones, esters, and aldehydes due to its
reactivity with these compounds.
Anhydrous sodium sulfate (Na2SO4): this is a neutral drying agent that has a high capacity for
water, therefore large quantities of water can be removed from very wet samples. Its dehydration
is slow, and not too efficient, but it is cheap, and a granular hydrate will be formed for facile
decantation. However, the solution temperature should be considered as Na2SO4 loses water at
above 32 °C
Anhydrous magnesium sulfate (MgSO4): this is considered as one of the best drying agents
due to its rapid drying and neutrality. However, MgSO4 is often a fine powder, lots of your product
can be trapped on the surface. The product can be washed out of the powder with a little fresh
solvent.
Anhydrous sodium carbonate and potassium carbonate: these drying agents are not
applied to dry acidic products. However, their basicity can be made use of to dehydrate and
neutralize a small amount of acid that may be left in the liquid.
Drying an organic solid
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The solids can be dried in air or in an oven. Vacuum drying can be applied for thermally unstable
compounds. Moisture-sensitive ones should be dried and stored in a desiccator containing silica
gel or the above-mentioned drying agents at the bottom (Figure 1.13).
(a) (b)
Figure 1.13. (a) simple desiccator, (b) vacuum desiccator.
1.8. Distillation
Distillation is a separation process that involves heating a liquid mixture to its boiling point,
transferring the vapor to a different portion of the apparatus, then condensing the vapor and
collecting the condensate in another container. This technique is one of the most useful for
separating a mixture of liquids when the components have different boiling points. After a
distillation process, the residue left in the distilling flask is enriched in the non-volatile or
less-volatile components (related to their higher boiling points) while the distillate has been
enriched in the more-volatile components (related to their lower boiling points).
In industry, distillation is used to separate the economically important components of crude oil
into various hydrocarbon fractions including natural gas, gasoline, kerosene, heating oil, and
lubricants. In the food industry, distillation is used to concentrate the alcohol in wines and other
beverages obtained from the natural fermentation of fruits and vegetables. In the organic lab,
distillation is used for purifying solvents and liquid reaction products.
Successful distillation depends on several factors, including difference in the boiling points of the
materials in the mixture, and therefore difference in their vapor pressures, type of apparatus
used, and experimental skill.
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The most common methods of distillation include:
- Simple distillation
- Vacuum distillation
- Fractional distillation
- Steam distillation (internal steam distillation and external steam distillation)
Simple distillation
Simple distillation involves a single equilibration between the liquid and vapor. This distillation is
referred to as involving one theoretical plate. Simple distillation is usually applied to separate the
components boiling below 150 oC (at 1 atm) from:
- Nonvolatile impurities or solid impurities.
- Another component with a boiling point that differs by at least 25 oC.
In simple distillation, all components in the initial mixture must be miscible and stable at the
boiling points at 1 atm.
Simple distillation procedure
1. Boiling chips should be placed in the distillation flask for two reasons: they will prevent
superheating of the liquid being distilled, leading to a more controlled boil, and eliminating
the possibility that the liquid in the distillation flask will bump into the condenser.
2. Set the distillation apparatus as shown in Figure 1.14.a. (from left to right and from bottom to
top).
3. Fill the distillation flask with the liquid mixture using a long-stem funnel. The funnel stem
must be long enough to make sure that the mixture cannot flow into the condenser. The flask
should be no more than two thirds full. A sufficient clearance above the surface of the liquid
is need so that the liquid will not bump into the condenser when boiling begins.
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Figure 1.14. (a) simple distillation apparatus, (b) right position of thermometer.
4. Place the thermometer and its adaptor at the Y-adaptor top. The entire thermometer bulb is
right below the side arm of the Y-adaptor (Figure 1.15.b), and does not touch the adaptor
wall
5. Place an Erlenmeyer flask for collection under the vacuum adaptor. A beaker, vial or
graduated cylinder could also be used. If the distillate is volatile, the receiving flask should be
cooled.
6. Secure all joints tightly.
7. Have your laboratory instructor check your distillation apparatus.
8. Turn on cool water for the condenser.
9. Heat the distillation flask carefully and slowly until the liquid mixture begins to boil. As the
vapors pass through the condenser, they will condense and drip into the collection receiver.
An appropriate rate of distillation is approximately 10-20 drops per minute. Distillation must
occur slowly enough to make sure all the vapors condense to liquid in the condenser and. As
the lower boiling component is distilled, the boiling point of the mixture in the distillation flask
will increase, meaning that a next component is releasing from the mixture and a new
receiver must be used.
10. After collecting the desired fraction, remove the heat source from the distillation flask before
all of the liquid is vaporized.
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11. Make sure the apparatus is cool before the disassembly in the way opposite to the assembly
described above.
Notes:
- Make sure to have correct placement of the thermometer because the purity of the desired
fraction is dependent on the vapor temperature which is shown on the thermometer. If it is
too low, it will be too close to the boiling liquid and will read higher than the true vapor
temperature. If it is positioned too high, it will be out of the path of the vapors and read lower
than the true temperature.
- Make sure that all joints must be tight. If any vapor escapes at the connection points, it may
come into direct contact with the heat source and ignite
- Never distill to dryness. The residue left in the distillation flask may contain peroxides, which
could ignite or explode after all the liquid has distilled away. Also, when all the liquid has
evaporated, the temperature of the glass of the filtration flask will rise very rapidly, possibly
igniting whatever vapors may still be present in the distillation flask.
- Never heat a closed system, the increasing pressure will lead to apparatus explosion.
- Just record a distillation temperature as the first drop of liquid falls into the receiving flask.
- Determine the desire fraction with a boiling range of a 2 - 3oC accuracy. For example, to
obtain A with the boiling point of 70 oC, keep letting liquid come over until the temperature
stabilizes at about 69°C and then change receiving flasks quickly. The temperature is
expected to slowly increases to ~ 71°C and then starts moving up rapidly. Stop collecting the
fraction of with a boiling range of 69-71 oC.
- Save all fractions of the distillate until the desired compound is correctly chosen.
- Do not apply simple distillation or fractional distillation at atmospheric pressure to separate
an azeotrope (This is a mixture of two or more liquids whose proportions cannot be changed
by simple distillation or extraction, e.g. an azeotropic mixture of 95.63 wt.% of ethanol (bp
78.4 °C) and 4.37 wt.% of water (bp 100 °C) boils at 78.2 °C) To break an azeotrope, many
various methods can be used, including addition of an additional agent for azeotropic
distillation, distillation with changed pressure, selective absorption using molecular sieves,
chemical separation by a reaction selective only with one of components (CaO to remove
water from ethanol), and membrane methods.
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Vacuum distillation
Boiling begins as the vapor pressure of a liquid or solution equals the external or applied
pressure (often the atmospheric pressure). Therefore, the boiling point of the liquid will decrease
with the applied pressure.
Vacuum distillation at a reduced pressure is used to distill compounds that have a very high
boiling point, i.e. above 150 oC, or might be decomposed or be more reactive at their boiling
point at 1 atm. To perform a vacuum distillation, all components in the initial mixture must be
miscible and have a boiling point difference of at least 25 oC.
(a) (b)
Figure 1.16. (a) typical vacuum distillation system, (b) temperature-controlled vacuum distillation
system.
Fractional distillation
Mixtures of miscible liquids whose boiling points are similar (less than 25 °C) cannot be
separated by a single simple distillation. In these situations, a fractional distillation is performed
with a modification of the simple distillation setup, namely insertion of a fractionating column
between the distilling flask and three-way adapter. The process involves repeated distillations
and condensations and the mixture is therefore separated into component parts called fractions.
In industry, fractional distillation is used in oil refineries to separate the complex mixture
containing hydrocarbon with similar molecular weights and therefore similar boiling points into
fractions such as gasoline, diesel fuel, kerosene, and jet fuel.
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Figure 1.17. Fractional distillation setup.
Steam distillation
If the desired component has a boiling point much higher 100 oC but is sensitive to heat, , steam
distillation can be applied to separate this component from a matrix or a mixture. By adding
water or steam, the boiling points of the resulting mixture are depressed, allowing them to
evaporate at temperatures lower than 100 oC.
Consider a typical example for a mixture of bromobenzene (bp 156 °C) and water (100 °C). The
total vapor pressure equal to the sum of the individual vapor pressures. At 95 oC, Ptotal = pwater +
pbromobenzene = 640 mm Hg + 120 mm Hg = 760 mm Hg, and boiling begins since the mixture of
water and bromobenzene has a vapor pressure equal to the atmospheric pressure at this
temperature. Obviously, bromobenzene can be easily distilled at a temperature lower than the
boiling point of either bromobenzene or water.
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After distillation, the vapors of water and the organic compounds is condensed, yielding a
two-phase system of water and the organic compounds, allowing for simple separation.
Therefore, it is important to remember that steam distillation is efficient as if the organic
compound is insoluble/slightly soluble in water and has a has a boiling point much higher 100
o
C. If the substances are very sensitive to heat, steam distillation can also be combined with
vacuum distillation.
Steam distillation is one of the most popular methods used to obtain essential oils from plants.
There are two ways of generating steam: externally and internally. In an external steam
distillation, steam supplied from an external system is led into the flask containing the materials.
In an internal steam distillation, there is only one boiling flask containing the material and liquid
water which will be heated directly and produce the vapor to the condenser.
Figure 1.18. External steam distillation setup.
1.9. Recrystallization
Recrystallization is widely applied to purify impure solid products in a solvent or a mixture of

solvents. The process efficiency is dependent on the product purity, the solubility of the product
and impurities in the used solvent, the temperature range, and the experimental skills.
Successful recrystallization of a solid compound depends on finding a right solvent which must
satisfy the following properties:
25
- Well dissolve the substance at high temperatures (e.g., at the boiling point of the solvent).
- Poorly dissolve or cannot dissolve the substance at lower temperatures. Either insolubility of
impurities in the solvent at high temperatures (in this case, the next step is hot filtration to
remove impurities from the solution) or very good solubility of impurities in the solvent at low
temperatures (in this case, impurities cannot simultaneously crystallize with the substance) is
expected.
- Unreactive with the substance.
- Have a boiling point at least 10-15 oC lower the melting point of the substance.
- Should be volatile, inexpensive and have a low toxicity.
In case the solubilities of the product and impurities in the used solvent are similar,
recrystallization works best when the quantity of impurities is small so that at low temperature,
the solution of the desired substance earlier becomes saturated, leading its crystallization in a
purer form while the impurities will not crystallize in their unsaturated solution yet, therefore
leaving the impurities behind in the solution.
Find a right solvent to recrystallize an impure compound usually requires prediction, experience,
and practice. Solubility of that compound in different solvent must be screened first. Generally, a
compound might be soluble in solvents with a similar polarity, e.g., a very polar compound will be
easily dissolved in a polar solvent but insoluble in a non-polar solvent.
However, note that a solvent with a slightly different polarity compared to the solute is preferable
for prediction because if their polarities are too closely matched, the solute might be fairly
soluble in the solvent at a reduced temperature, leading to recrystallization with difficulty.
Commonly used solvents are arranged in order of increasing polarity, including: hexane <
cyclohexane < tetrachloromethane < toluene < benzene < diethyl ether < dichloromethane <
chloroform < ethyl acetate < acetone < ethanol < methanol < water
However, note that a solvent with a slightly different polarity compared to the solute is preferable
for prediction because if their polarities are too closely matched, the solute might be fairly
soluble in the solvent at a reduced temperature, leading to recrystallization with difficulty. A good
single solvent will ideally have a high solubility at high temperatures and at least a five times
lower solubility for the compound at lower temperatures. If no solubility data is found, solvent
selection will be experimentally investigated with the following steps.
Procedure to find a good recrystallization solvent
26
1. Place 0.10 g of the solid in a test tube.

2. Add 3 mL of a solvent, stopper the tube, and shake it well. If all (or very much)
of the solid is soluble at room temperature, do not use this solvent as a recrystallization
solvent.
3. If none (or very little) of the solid dissolved at room temperature, unstopper the tube. Heat
and shake it respectively and repeatedly until the solvent begins boiling. If it does not
dissolve at all, do not use this as a recrystallization solvent.
4. If the sample dissolved when hot, and did not dissolve at room temperature,
One last test left.
5. Place the test tube (no longer hot) in an ice-water bath, and cool it about 5 °C
or so. If lots of crystals come out, this is the solvent of choice.
6. If the crystals don’t come back at a low temperature. Get a glass rod into the test tube, stir
the solution, rub the inside of the tube with the glass rod, and agitate that solution. If crystals
still don’t come back, another solvent should be tested.
7. In case no single recrystallization solvent is found. Try with a mixture of two or more
miscible solvents. For example, the compound is completely soluble in ethanol at room
temperature and insoluble in water. Ethanol and water are miscible. A mixed-solvent
recrystallization would be performed.
Procedure to recrystallize an impure compound in a solvent
1. Put the solid into an Erlenmeyer flask. If a beaker is used, the solid might climb the beaker
walls and the boiling solvent is quickly vaporized. The flask size is decided base on a
predicted total solvent volume. In particular, the flask should not be filled more than one-fifth
to one-fourth full.
2. Heat a large quantity of the solvent selected before to the boiling point. Do not heat the
container of the flammable solvent directly on a hot plate or using naked flames. A
steam/water/sand bath should be used to avoid accidents.
3. Slowly add small amounts the hot (boiling) solvent to the sample in the flask to JUST
dissolve it. This step is to obtain a saturated solution of the major substance, depending on
experimental skill. Indeed, if the flask is added with very small solvent amounts or with cool
solvent, dissolving is difficult. In contrast, too much hot solvent used will give an unsaturated
solvent.
4. Check the appearance (color and transparency) of the resulting solution to decide the next
steps:
4.1 The solution is transparent and has the same color to the major substance
27
- Slowly cool the saturated solution to room temperature and then to 5-10 oC for the slow
recrystallization of the major substance.
- Collect crystals by vacuum filtration and wash them with small amounts of the cold solvent.
- Caution!!!
+ The solution must be saturated or nearly saturated (better !!!) before cooling. Otherwise,
the solution needs to be concentrated to saturated (the solution turns cloudy or the first
crystals are observed).
+ The crystals quality (purity, size, morphology) is dependent on cooling and recrystallization
rate. If recrystallization occurs so fast due to rapid cooling, obtained crystals might be small,
contaminated, and usually in a powder form.
+ Organic solvents are easily vaporized even when cooled, leading a bad recrystallization.
Close the flask (using a holed stopper to keep open to the atmosphere, avoiding a pressure
difference) to diminish their vaporization.
+ If too much solvent is used to wash the crystals, probably there will be nothing on the filter
paper to collect.
4.2 The solution has insoluble solids
- Mark the solution volume on the Erlenmeyer flask wall.
- Dilute the solution with the hot solvent (20-30 mL) to ensure that the solution state is far
away from the saturated point.
- Perform a hot gravity filtration using a stemless or short-stem funnel
- Wash the flask and the filter paper with small amounts of the hot solvent until no crystals are
observed there
- Concentrate the obtained solution to the marked volume (saturation state). If marking the
volume is missed, simply concentrate it to saturated.
- Caution!!!
+ See Part 4.1 above.
+ Hot filtration should be conducted on a hot plate to keep the setup hot and diminish
crystallization on the filter paper and in the funnel stem (Figure 1.19).
4.3 The solution has an unexpected color (different from the major substance color)
- Mark the solution volume on the Erlenmeyer flask wall.
- Dilute the solution with the hot solvent (20-30 mL) to ensure that the solution state is far
away from the saturated point.
28
- Move the flask from the hot plate. Add activated carbon (the use amount depending on the
color difference). Bring the flask back to the hot plate for boiling for 5 mins.
- Perform a hot gravity filtration using a stemless or short-stem funnel.
- Wash the flask and the filter paper with small amounts of the hot solvent until no crystals are
observed there.
- Concentrate the obtained solution to the marked volume (saturation state). If marking the
volume is missed, simply concentrate it to saturated.
- Caution!!!
+ See Parts 4.1 & 4.2 above
Figure 1.19. Hot gravity filtration setup.
Procedure to recrystallize an impure compound in a mixed-solvent system
- Two or more solvents must be miscible, such as ethanol-water, methanol-water, ethyl

acetate-dichloromethane. The solute is soluble in one of these solvents (called solvent A) but
insoluble in another (called solvent B).
- Dissolve the compound in the smallest amount of hot solvent A.
- Add hot solvent B until the solution turns cloudy.
- Make sure that this cloudiness is stable on a hot plate or in a hot water bath.
- Add some drops of hot solvent A to make the solution transparent again
29
- Slowly cool and collect crystals on a Buchner funnel. Wash the crystals with cold solvent B.
1.10. Calculation of the reaction yield
Theoretical yield
xA + yB → iC + jD
The theoretical yield is the amount predicted by a stoichiometric calculation based on the
number of moles of the limiting reactant which is totally consumed when the chemical reaction is
completed (not working with the excess reactants!!!). This calculation assumes that only one
reaction occurs and that the limiting reactant reacts completely.
For example, the limiting reactant is A, and the theoretical yield (weight) of C is
𝑖 𝑀𝐶
𝑚𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 = 𝑥 𝑀𝐴
×𝑎 (1.1)
where a is the molar number of A, M A and MC are the molecular weight of A and C, respectively.
Percentage yield
However, the actual yield is always smaller (less than 100%)

𝑚𝑎𝑐𝑡𝑢𝑎𝑙
Percentage yield (%) = 𝑚𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙
×100% (1.2)
In case of reversible reactions, the theoretical yield should be calculated at the equilibrium state.
For example, in the reversible esterification
Initial: a b 0 c (mol)
Equilibrium: a-x b-x x x+c (mol)

𝑥(𝑥+𝑐)
𝐾= (𝑎−𝑥)(𝑏−𝑥)
= 4. 1 (1.3)
𝑥'
Percentage yield (%) = 𝑥
×100% (1.4)
where K is the equilibrium constant
a, b, and c are the molar numbers of acetic acid, ethanol, and water at the beginning of
the reaction
30
x is the theoretical molar number of the ester determined using the equation (1.3)
x’ is the actually obtained molar number of the ester
Unit 2 – Synthesis of ß-naphthol orange
Introduction
ß-Naphthol orange (chemical formula: C16H11N2SO4Na, IUPAC name: sodium

4-[(2E)-2-(2-oxonaphthalen-1-ylidene)hydrazinyl]benzenesulfonate, commercial names: acid
orange 7, Orange II, or C.I. 15110) is an orange crystalline solid, melting at 164 oC and much
soluble in water (116 g/l at 25 oC). ß-Naphthol orange is commonly used as an azo dye for wool.
This dye could be synthesized via azo coupling of β-naphthol with diazonium salt of sulfanilic
acid.
Figure 1. Synthesis of ß-naphthol orange from sulfanilic acid.
Major chemicals
No. Chemical Amount
1 Sulfanilic acid 2g
2 β-Naphthol 1.4 g
3 concentrated HCl 2.5 ml
4 NaOHaq 2N 5 ml
5 NaOHaq 5% 16 ml
31
6 NaNO2 1g
7 NaCl 5g
Equipment
No. Equipment Quantity
1 Beaker - 100 ml 3
2 Graduated cylinders - 5 ml 1
4 Büchner funnel 1
5 Plastic rod 2
6 Thermometer (up to 100 °C) 1
7 Stainless steel spatula 1
8 Filter flask - 250 mL 1
9 Plastic bath 2
Experimental skills
- Prepare a cooling bath by mixing a cooling agent with an additive

- Monitor azo couping via adjusting the reaction mixture pH
Experimental procedure
- Dissolve sulfanilic acid in 5 mL of NaOH 2 N in a small beaker, yielding a solution of sodium

sulfanilate.
- Dissolve sodium nitrite in 10 mL of water in another beaker. Approximately two-third of this
solution is then added to the sodium sulfanilate solution.
- Cool the resulting mixture to ~ 0 oC by using a 3:1 mixture of crushed ice and salt. Slowly add
1.5 mL of concentrated HCl to the mixture and keep vigorous stirring in 5 mins.
- Add remaining amounts of concentrated HCl and NaNO2 respectively to the reaction mixture.
The acidic environment of reaction mixture is indicated by pH paper. Diazonium salt crystals
would be formed under vigorous stirring at the low temperature.
32
- Dissolve β-naphthol is in a solution of NaOH 5% in a small beaker. The resulting solution

content is cooled to ~ 0 oC.
- Slowly add the diazonium salt phase to the β-naphtholate salt solution. The mixture is stirred
for 30 mins before added with 5 g of sodium chloride. Finally, the reaction mixture is kept
static in cooling bath in 1 hour.
- Collect the dye solid by vacuum filtration and wash the filter cake with small amounts of cold
water.
- Observe and explain the product color change after one-week drying in air.
33
Unit 3 – Synthesis of dibenzylideneacetone
Introduction
Dibenzylideneacetone (chemical formula: C17H14O, other names: dibenzalacetone, DBA) is a

pale-yellow solid insoluble in water, but well soluble in organic solvents. The melting point of
trans-trans isomer is ~ 107-113 oC.
Figure 1. Structural formula of DBA.
With a long-conjugated system (Figure 1), DBA is able to absorb UV light, protecting the skin
from the sun's damaging rays. DBA is therefore used as an active component in sunscreens and
also a ligand in organometallic chemistry.
Trans-trans DBA isomer could be obtained with a selectivity up to 90% via sodium
hydroxide-catalyzed Claisen-Schmidt condensation between acetone and two equivalents of
benzaldehyde in a water/ethanol medium (Figure 2).
Figure 2. Condensation reaction of benzaldehyde and acetone (2:1) under basic conditions.
It should be noted that several side reactions simultaneously occur under such basic conditions,
including self-condensation of acetone, Cannizarro reaction of benzaldehyde, and formation of
monobenzalacetone only, depending on reaction conditions and experimental techniques.
34
Major chemicals
No. Chemical Amount
1 Acetone 1.3 ml
2 Benzaldehyde 3.6 ml
3 NaOH 3.5 g
Equipment
1 Beaker - 10 or 50 ml 1
2 Beaker - 100 ml 1
3 Erlenmeyer flask - 100 ml 1
5 Büchner funnel 1
6 Filter flask - 250 ml 1
7 Graduated cylinder - 100 ml 1
8 Thermometer 1
9 Stirring rod 1
11 Stirring bar (30 mm in length) 1
12 Holed rubber stopper 1
13 Plastic bath 1
14 Steel bath 1
15 Stirring plate (flexibly used) 1
35
16 Heating plate (flexibly used) 1
Experimental skills
- Store and use unstable or volatile chemicals

- Improve the reaction selectivity to the desired product
- Purify a solid organic product by washing with water and recrystallizing in another
solvent
PART 1
Figure 3. Reaction apparatus for the synthesis of DBA.
- Dissolve NaOH in a mixture of water (35 mL) and ethanol (28 mL). This solution is
continuously stirred and kept in the range from 20 oC to 25 oC (Figure 3).
- Prepare a mixture of benzaldehyde and acetone in a small beaker. Reduce the volatility of
acetone by sealing and cooling the beaker. Add ~ a haft of this solution to the above NaOH
solution. The resulting mixture is vigorously stirred at 20-25 oC in 15 mins. The remaining
reactants is then added to the reaction. ~ 5 mL of ethanol should be added to the beaker for
washing and also transferred to the reaction).
- After stirred for another 30 mins at 20-25 oC, the reaction mixture is cooled in an ice bath for
15 mins. The product is collected by vacuum filtration and then washed with water.
- Re-disperse the solid in 150 mL of water in a 250-mL beaker and re-collect the washed
product by vacuum filtration.
- Dry the raw product at room temperature for a week. Record its mass.
PART 2
36
- Recrystallize the raw product in ethanol (Attention!!! dissolve DBA with the minimal
amount of boiling ethanol in a small Erlenmeyer flask on a hot plate).
- The recrystallized product is collected by vacuum filtration and washed with small amounts of
cold ethanol.
- Dry the raw product at room temperature for a week. Determine the yield.
- Determine the melting point of recrystallized DBA using the Thiele setup.
Attention!!!
- A clean and dry small beaker has to be placed in an ice bath for containing
benzaldehyde and acetone.
- Benzaldehyde and acetone will be added to this beaker by your instructor. This
mixture has to be sealed and kept at low temperature to prevent oxidation and
volatility.
37
Unit 4 – Synthesis of benzoic acid
Introduction
Benzoic acid (C6H5COOH) is the simplest aromatic carboxylic acid. In nature, it could be
commonly found in many plants as an intermediate compound of the biosynthesis of many
secondary metabolites. Moreover, benzoic acid is an important substrate for the large-scale
synthesis of many organic compounds. Benzoic acid and its salt are widely used in food industry
as food preservatives because of their antibacterial activity (abbreviated E210 and E211,
respectively)
Benzoic acid is a white or colorless solid with poor solubility in cold water (1.7 g/L in water at
0 oC) but good solubility in organic solvents and hot water (56.3 g/L in water at 100 oC).
Benzoic acid is commercially produced by the partial oxidation of toluene by oxygen with high
selectivity due to catalyzation of cobalt salts or manganese salts. In lab, many different
procedures could be applied to prepare benzoic acid, including i) hydrolysis of benzonitrile
(C6H5CN) or benzamide (C6H5CONH2), ii) partial oxidation of toluene, benzaldehyde or benzyl
alcohol, iii) hydrolysis and oxidation of benzyl chloride, and iv) carboxylation of
phenylmagnesium bromide (derived via a Grignard reaction of phenyl bromide).
C6H5CH3 + 2KMnO4 🡪 C6H5COOK + 2MnO2 + KOH + H2O
3C6H5CH2OH + 4KMnO4 🡪 3C6H5COOK + 4MnO2 + KOH + 4H2O
Figure 1. Partial oxidation of toluene or benzyl alcohol by potassium permanganate to yield

benzoic acid.
Chemicals
No. Chemicals Amount
1 Toluene/benzyl alcohol 4 mL
38
2 KMnO4 12 g for toluene and 9 g for benzyl alcohol
3 Concentrated HCl 6 mL
Equipment
1 Two or three-neck flask – 250 mL 1
2 Rubber stopper 2
3 Allihn (bulb) condenser + rubber stopper 1
4 Stirring bar (25 mm in length) 1
5 Beaker - 250 mL 2
6 Büchner funnel 1
7 Filter flask - 250 ml 1
8 Separatory funnel - 250 mL 1
9 Support ring 1
10 Stirring rod 1
12 Sand bath 1
13 Plastic bath 1
14 Pipette 1
15 Graduated cylinders - 100 mL 1
39
17 Hotplate magnetic stirrer (flexibly used) 1
Experimental skills
- Assemble a reflux reaction apparatus

- Use strong oxidants in organic synthesis
- Monitor an oxidation reaction via color change
- Dissolve KMnO4 in 70 mL of water in a 2-neck round flask before a bulb condenser is

connected to the main neck of the round flask.
- Add toluene or benzyl alcohol to the solution via the side neck of the round flask. Use rubber
stoppers to close the side neck d heated to boiling point.
- The oxidation reaction is refluxed and vigorously stirred for 2 hours for toluene and 1 hour for
benzyl alcohol.
- Stop heating in 10 mins to decrease the reaction
temperature below the boiling point.
- Use a glass rod to transfer a drop of the reaction mixture to
a filter paper piece via the side neck for testing the mixture
color (Figure 2).
- If the mixture is pink, 1-2 mL of ethanol should be quickly
added to the flask. After 5 mins under vigorous stirring,
repeat color testing until no pink spot is observed.
- Collect the liquid containing benzoate salt by hot vacuum filtration. Wash brown precipitate
with small amounts of hot water.
- If the collected liquid consists of 2 immiscible phases, a further separation using a
separatory funnel is required for removal of the organic phase.
- Transfer the aqueous phase to a 250-mL beaker containing 1-2 boiling stones. The solution
is concentrated to 50 mL before cooled to 5-10 oC.
- Acidify the solution by slowly adding 6 mL of concentrated HCl under stirring.
- After cooling in 15 min, the solid product is collected by vacuum filtration and washed with
small amounts of cold water.
- Dry the product in a week in air and determine the reaction yield.
- Store the product in a plastic bottle labelled “Benzoic Acid” for the second lab round.
40
Caution!!!
- Carefully apply a strong oxidant (KMnO4) and concentrated HCl to the procedure.
- Any accident and doubt must be reported to your instructor immediately.
- Do not use plastic film to seal the flask necks. Do not open the flask at the boiling
point.
- After adding ethanol to the reaction mixture, the flask must be closed immediately due
to strongly exothermic reaction.
Unit 5 – Synthesis of ethyl acetate
Introduction
Ethyl acetate (CH3COOC2H5) is one of the most popular carboxylate esters. This colourless
liquid has a sweet, fruity, and pleasant odour similar to pear drops. It is often employed as a
common solvent for paints, varnishes, lacquers, cleaning mixtures, and perfumes. In lab, ethyl
acetate is a solvent used for extraction, column and thin-layer chromatography. Ethyl acetate is
unstable in acid and base due to hydrolysis. Ethyl acetate is poorly soluble in water, but good
miscible with ethanol, diethyl ether, very soluble in acetone and benzene. At atmospheric
pressure, azeotrope points are observed for the mixture of ethyl acetate, ethanol, and water and
the mixture of ethyl acetate and ethanol.
Ethyl acetate is produced via the esterification reaction between ethanol and acetic acid. Such a
reversible esterification can reach a point of equilibrium after several days. In the presence of
acids as catalysts, the time to obtain an equilibrium state could be shortened.
Table 1. Ethyl acetate-containing azeotrope data.
Azeotrope composition (wt%) Azeotrope boiling point (oC)
69.2% ethanol + 30.8% ethyl acetate 71.8
7.8% water + 9.0% ethanol + 83.2% ethyl acetate 70.3
Major chemicals
No. Chemical Amount
41
1 Acetic acid 7.5 mL
2 Absolute ethanol 10.0 mL
3 H2SO4 98% 1 mL
Equipment
1 Round-bottom flask - 100 mL 1
2 Distillation flask - 100 mL 1
3 Erlenmeyer flask - 100 mL 3
5 Liebig condenser 1
8 Thermometer + rubber stopper 1
10 Support ring 1
11 Long-stem funnel 1
12 Plastic bath 1
Experimental skills
- Assemble a reflux reaction apparatus

- Improve the yield of reversible esterification based on Le Chatelier's principle
42
- Obtain the desired fraction by simple distillation

- Wash and dehydrate an organic liquid phase
- Separate the product from two immiscible liquid phases using a separating funnel
Figure 1. (a) reflux reaction apparatus, (b) simple distillation system, (c) liquid-liquid extraction
system.
- Add acetic acid, ethanol, and sulfuric acid respectively to a round-bottomed flask. Connect
the flask to a Liebig condenser. The reaction mixture is refluxed in 1 hour.
o
- Cool the reaction apparatus to 5-10 C before transferring the reaction mixture to a
simple-distillation apparatus. The first distillation process is slowly carried out to collect a
liquid phase boiling below 90 °C.
- Wash the condensed liquid with 5 mL of Na2CO3 10% in a separatory funnel. Collect the
organic phase in an Erlenmeyer flask containing 1.25 g of anhydrous Na2SO4.
- Slowly distill the dehydrated organic phase to collect the product boiling below 72 °C.
43
Unit 6 – Synthesis of terpineol
Introduction
Terpineol has four common isomers including α-, β-, γ-, and terpinen-4-ol, in which α-terpineol is
the major constituent (Figure 1). Terpineol isomers are monocyclic monoterpene tertiary
alcohols, which have a pleasant odor like lilac and are widely applied in perfume, cosmetic,
personal care and cleaning products.
Terpineol could be found in various plants such as cannabis, lilacs, lime blossoms, eucalyptus
sap, and pine trees.
Figure 1. Four most common isomers of terpineol.
It is a viscous colorless flammable liquid with the high boiling point of 214 ~ 224 oC. Terpineol is
insoluble in water, but well soluble in organic solvents.
Terpineol could be chemically synthesized by hydration of limonene or dehydration of terpin.

Commercial terpin referred to as terpinhydrat containing a water molecule, is able to dehydrate
at high temperature in the presence of acids (H2SO4, HCOOH, phthalic acid, KHSO4, ZnCl2…) to
yield a mixture of terpineol isomers.
44
Figure 2. Dehydration of terpin to terpineol.
Major chemicals
No. Chemical Amount
1 Terpin hydrate 8g
2 H2SO4 2.5% 64 mL
Equipment
5 Glass tubes for steam distillation + rubber stopper 2
7 Support ring 1
8 Graduated cylinder - 100 mL 1
9 Graduated cylinder - 10 mL 1
11 Steel bath containing sand 2
Experimental skills
- Set up a reflux reaction apparatus

- Set up an external steam distillation apparatus
- Extract an organic compound from water (if any)
45
- Connect a 250 mL round-bottomed flask containing terpin hydrate and H2SO4 2.5% to a bulb
condenser. The reaction is refluxed in 1 hour.
- Cool and transfer the reaction mixture into a separatory funnel. The organic layer is extracted
and washed two times with water. However, such washing steps could be skipped. After
the reaction, the cooled mixture is transferred directly to an external steam distillation
apparatus.
- Collect liquids condensed from steam distillation in an Erlenmeyer flask until the reaction
mixture is transparent.
- Collect the upper terpineol layer using a separatory funnel.
Attention!!!
- Terpineol is able to form a stable emulsion with water. To avoid this problem, the
liquid phases obtained from steam distillation should not be shaken.
- A saturated solution of sodium chloride could be used to break the emulsion (if any).
46
Unit 7 – Synthesis of aspirin
Introduction
Aspirin (o-HOOC-C6H4-OCOCH3, IUPAC name: 2-acetoxybenzoic acid) is a derivative of salicylic

acid. It is known as a non-steroidal anti-inflammatory drug (NSAID) and widely used to reduce
pain, fever, or inflammation. Using low doses of aspirin in the long-term can reduce the risk of
death from a heart attack and prevent the formation of the blood clots in the blood vessels.
Moreover, some evidences show that aspirin has positive effects in decreasing the risk of certain
types of cancer, particularly colorectal cancer. However, side impacts, including stomach ulcers,
stomach bleeding, and worsening asthma, are also found. It is also not recommended for
pregnants and children with infections because of the risk of Reye syndrome.
Aspirin is a white, crystalline, weakly acidic substance with a melting point of 136 °C. It shows a
poor solubility in water at low temperatures, and a good solubility in acetone, ethanol, ethyl
acetate, and other organic solvents.
Aspirin is obtained via esterification reaction of salicylic acid with acetic anhydride in the
presence of an acid catalyst.
Figure 1. Synthesis of aspirin via esterification between salicylic acid and acetic anhydride.
Major chemicals
No. Chemical Amount
1 Salicylic acid 5g
2 Acetic anhydride 7 mL
3 H2SO4 98% 3 drops (~ 0.5 mL)
47
Equipment
2 Beaker - 100 ml 2
4 Büchner funnel 1
5 Thermometer 1
6 Stirring rod 1
8 Steel bath 1
Experimental skills
- Indirectly predict and control reaction temperature

- Recrystallize a solid product using 2 solvents
- Add salicylic acid, acetic anhydride, and sulfuric acid respectively to an Erlenmeyer flask.
- Carry out the reaction under vigorous stirring (shake if the phase is liquid, use a stirring rod if
the phase is solid) in a warm water bath (the water temperature is controlled to be ~ 65-70 °C
using a thermometer) in 15 mins.
- Keep stirring while cooling the flask to room temperature.
- Add 60 mL of water to the flask and keep stirring in 5 mins.
- Collect the raw product by vacuum filtration and wash the solid with cold water
- A small amount of raw aspirin (Sample 1) is kept for the second lab round (ask your
instructor for more details).
- Recrystallize raw aspirin using ethanol and water in a warm water bath. In detail, the product
is first completely dissolved in a minimal amount of hot ethanol in an Erlenmeyer flask and
slowly added with hot water until the solution turns stably cloudy or the first aspirin crystals
48
appear. Afterwards several drops of hot ethanol should be added to make the solution
transparent again.
- Slowly cool the flask to room temperature and then place it in an ice bath for lower
temperature.
- Recrystallized aspirin is collected by vacuum filtration and washed with cold water
- Dry the product in a week in air
- After determining the reaction yield, collect a small amount of recrystallized aspirin
(Sample 2) for the second lab round.
Figure 1. Simple apparatus for the synthesis of aspirin.
49
Unit 8 – Synthesis of soap
Introduction
Soaps are sodium or kalium salts of various fatty acids (RCOOH) with long hydrocarbon chains
(from 12 to 18 carbons). Solid soap is often sodium salts of fatty acids (RCOONa), while the
liquid form is a result of hydrolysis in the presence of potassium hydroxide (RCOOK).
Soap is one of the most well-known surfactants, also referred to as an amphiphile, containing
both hydrophobic groups (their oil-soluble tails) and hydrophilic groups (their water-soluble
heads) (Figure 1).
Hydrophobic part Hydrophilic part

(soluble in oil) (soluble in water)
Figure 1. An example of soap - sodium stearate.
When a non-polar liquid, poorly soluble in water, exposes with an aqueous solution of soap, the
hydrophobic tail of soap would be strongly attracted by these non-polar molecules while its
hydrophilic heads are towards the polar environment. Therefore, the soap molecules tend to
surround the non-polar droplets with their non-polar part extending into the oil phase and their
polar head groups facing the water. In other words, the non-polar liquid phase would be divided
into smaller droplets and distributed into the aqueous solution due to reducing surface tension.
Soap therefore plays a role as an emulsifier and a cleansing agent.
Soap is industrially produced either by hydrolysis of triglyceride (oil or animal fat) under basic
conditions, which is called saponification, or by neutralization of fat acid.
Figure 2. Synthesis of soap from fatty oil (saponification).
Coconut oil
50
Coconut oil is extracted from coconut flesh with a density of 0.86-0.90 g/mL at 15oC. The major
component in coconut oil is triglyceride of lauric acid. More valid unsaturated fatty acid such as
oleic acid and linoleic acid occupy less than 10% (Table 1). Coconut oil is a cheap and abundant
feedstock to synthesize soap.
Table 1. Fatty acid tails present in coconut oil triglyceride.
No. Fatty oil Chemical formula %
1 Caproic CH3(CH2)4COOH 0.5
2 Caprilic CH3(CH2)6COOH 8.0
3 Capric CH3(CH2)8COOH 7.0
4 Lauric CH3(CH2)10COOH 48.0
5 Myristic CH3(CH2)12COOH 17.0
6 Palmitoleic CH3(CH2)5CH=CH(CH2)7COOH 0.2
7 Oleic CH3(CH2)7CH=CH(CH2)7COOH 6.0
8 Linoleic CH3(CH2)4CH=CH-CH2-CH=CH(CH2)7COOH 2.3
9 Palmitic CH3(CH2)14COOH 9.0
10 Stearic CH3(CH2)16COOH 2.0
Major chemicals
No. Chemical Amount
1 Coconut oil 5g
2 NaOH 10% 25 mL
51
Equipment
1 Beaker - 500 mL 1
2 Beaker - 250 mL 2
4 Büchner funnel 1
6 Stirring rod 2
8 Test tube 4
9 Steel bath 1
10 Heating plate 1
Experimental skills
- Carry out a reaction including two immiscible liquid phases

- Evaluate the as-synthesized product quality and compare with a commercial
product.
52
Figure 1. Reaction system for the synthesis of soap.
Part 1. Preparation of soap

- Add coconut oil, NaOH 10% respectively to a 500 mL beaker.
- Carry out saponification under vigorous stirring in a warm water bath (~ 60 oC) for 90 mins
(Figure 1).
- Add 40 mL of a saturated sodium chloride solution to the beaker and keep stirring for 5 mins
to separate the soap layer from the reaction mixture.
- Cool the beaker to room temperature.
- Collect soap by vacuum filtration and wash the product with water.
Part 2. Evaluation of soap quality

● Emulsion in deionized water
- Prepare a 0.5 wt.% solution of your as-synthesized soap in deionized water.

- Add 10 mL of the obtained solution, 10 mL of coconut oil to a test tube.
- Shake the mixture well (30 times) at room temperature.
- Measure the height of the unemulsified solution.
- Apply the identical procedure to a commercial soap sample.
- Compare the height results and give your conclusion.
● Emulsion in hard water
- Apply the identical procedure to your soap and the a commercial one in a 5% solution of
CaCl2.
- Compare the height results with the ones in deionized water and give your conclusion.
● pH of the soap solutions
- Estimate pH of the above solutions in deionized water using pH indicator paper
53
- Compare pH values and explain the results.
Unit 9 – Determination of melting point and recrystallization

of benzoic acid
Introduction
Melting-point experiment
A melting point (abbreviated mp) is the temperature at which the first crystals begin melting until
the temperature at which the last crystals turn liquid. Thus, the melting point is actually a melting
range and should be reported as such, for example, mp 147–149 °C, even though it is called a
melting point. Melting process is observed and recorded using a Thiele tube or other compact
electric devices.
Generally, melting points are taken for two reasons.
1. Prediction of purity
If the recorded melting range of a compound is narrow and identical to its known theoretical
data, a high purity could be obtained
For an unknown compound, a narrow melting range (smaller than 3 °C) also usually indicate its
high purity. Note that there are a few exceptions (e.g., a eutectic point).
2. Prediction of an unknown compound.
Again, for an unknown organic solid, compare its narrow melting range with melting point data of
known compounds and choose compounds with the same data.
Mix the unknown solid with the chemical predicted to be the unknown and take a melting point
+ If the mixture melts at a lower temperature, over a broad range, they are different.
54
+ If the mixture melts at the same temperature, same range, they can be the same compound.
Try another run with a different ratio of the mixture to be sure the unknown and this compound
just to be sure.
Recrystallization of an impure solid (including decolorization and hot filtration)
See Part 1.9 of Unit 1
Major chemicals
No. Chemical Amount
1 Raw benzoic acid 2g
2 Activated carbon 0.02-0.05 g
3 Raw aspirin (Sample 1)
4 Recrystallized aspirin (Sample 2) Collected after dried
5 Recrystallized dibenzylideneacetone
Equipment
1 Thiele tube 1
2 Alcohol burner (spirit lamp) 1
3 Beaker - 250 mL 1
5 Büchner funnel 1
7 Short-stem funnel 1
8 Support ring 1
9 Thermometer (up to 250 oC) and holed rubber stopper 1
10 Glass capillary tube 1
55
12 Plastic bath 1
13 Steel bath containing sand 1
14 Magnifying glass 1
15 Lighter 1
Experimental skills
- Determine the melting point of solid organic compounds using a Thiele tube
- Use a mercury thermometer and clean up mercury spills
- Perform decolorization, hot filtration and recrystallization of a solid organic compound
Part 1. Recrystallization of benzoic acid in water
- Step 1: Use a minimal amount of boiling water to completely dissolve raw benzoic acid in a
150 mL Erlenmeyer flask (Solution A).
- Step 2: Check the appearance (color and transparency) of Solution A to decide the next
steps: i) If Solution A is colorless and transparent, go to Step 8; ii) If Solution A is colorless
and has insoluble solids, go to Step 6; iii) If Solution A is unexpectedly colored, go to Step 3.
- Step 3: The volume of A solution is marked on the Erlenmeyer flask wall.
- Step 4: Dilute Solution A with boiling water (20-30 mL).
- Step 5: Move the flask from the hot plate. Add 0.02-0.05 g of activated carbon (depending on
the color difference). Bring the flask back to the hot plate for boiling for 5 mins.
- Step 6: Perform a hot gravity filtration. Solution A should be unsaturated (See Step 4).
- Step 7: Wash the flask and the filter paper with small amounts of boiling water until no
product crystals are observed.
- Step 8: Concentrate the obtained solution to the marked volume (saturation state). Slowly
cool the saturated solution to room temperature and then to 5-10 oC for recrystallization of
benzoic acid.
- Step 9: Collect benzoic acid crystals by vacuum filtration and wash them with small amounts
of cold water.
- Step 10: Extract some crystals, quickly dry for melting point determination.
- Step 11: Dry the product in a week in air and determine the recrystallization yield.
- Step 12: Store the product in a plastic bottle labelled “Benzoic Acid” for disposal.
56
Part 2. Determination of melting point of solid organic compounds
Preparation of a sample-containing tube
- To take melting points, thin, closed-end tubes called capillary tubes (melting-point tubes,
melting-point capillaries). Sometimes, tubes with both open ends are supplied. Simply, light
a burner, touch an end of the tube to the side of the flame, and hold it there for seconds until
it is close (Figure 1).
- Take melting points only on dry, solid substances, never on liquids or solutions of solids in
liquids or on wet solids.
- Place a small amount of the dry solid on a new filter paper. Thrust the open end of the
capillary tube into the middle of the pile of material. Some solid should be trapped in the
tube. Carefully turn the tube over, drop the tube, closed end down, through a length of glass
tubing (Figure 2).
- Use the smallest amount of material that can be seen to melt (2-3 mm in sample height).
- If there is not enough material in the tube, thrust the open end of the tube into the material
and pack it down again.
Figure 1. Closing off a melting-point tube with a flame.
57
Figure 2. Loading a melting-point tube.
Heating the setup
- Set a Thiele tube apparatus (Figure 3) using glycerol or mineral oil (make sure no water
inside!!!) as a heat transfer fluid, place a spirit lamp at the tube corner and slowly heating
the tube (~ 5 °C/min).
- Use a magnifying glass to observe the sample. At the same time, another member has to
observe the sample temperature shown on the thermometer.
- Record the temperature at which the crystals begin melting and the temperature at which
the entire sample is liquid. Such a temperature range is called the melting range of that
substance. It is noted that most pure organic compounds usually have a narrow melting
range of 1-2 oC if heated slowly enough, for example 139.5-140 oC or 169-170 oC while
impure samples of the same compounds often melt over a wider range, for example
134-138 oC or 166-169 oC.
- Cool the setup, remove the glass capillary tube and apply the identical procedure for the
next samples.
- Compare the results for raw and recrystallized aspirin samples, compare the results with
reference values. Give your explanation and conclusion in the lab report.
58
Figure 3. Determination of melting point using a Thiele tube.
Unit 10 – Liquid-phase separation techniques
Introduction
See Part 1.3.2, 1.3.5, and 1.4.1 of Unit 1
Major chemicals
No. Chemical Amount
1 A mixture of acetic acid and cyclohexane 15 mL
Equipment
2 Distillation flask - 100 mL 1
59
8 Thermometer + rubber stopper 1
10 Support ring 1
11 Long-stem funnel 1
12 Plastic bath 1
Experimental skills
- Liquid-phase separation techniques including distillation, washing, extraction, and

drying
- Separation of an azeotropic mixture
- Given that a mixture at a cyclohexane/acetic acid molar ratio of 87/13 is azeotropic (bp = 78.8
o
C), suggest the most appropriate distillation fraction to obtain cyclohexane from a supplied
mixture of cyclohexane and acetic acid.
- Use wet pH paper to determine composition of the collected fraction.
- Suggest an appropriate procedure to remove acetic acid from such an azeotrope.
- Use wet pH paper again to determine composition of the organic phase after completing the
above procedure and evaluate its efficiency.
60
REFERENCES
1. James W. Zubrick, The Organic Chem Lab Survival Manual: A Student’s Guide to
Techniques - 8th edition, JohnWiley & Son, 2011.
2. Brian S. Furniss et al., Vogel’s Practical Organic Chemistry - 5th edition, Longman
Scientific & Technology, 1989.
3. Steven F. Pedersen and Arlyn M. Yers, Understanding the Principles in Organic
Chemistry: A Laboratory Course, Cengage Learning, 2011.
4. Jerry R. Mohrig et al., Techniques in Organic Chemistry - 3rd edition, W. H. Freeman and
Company, 2010.
5. Donald L. Pavia et al., A Small Scale Approach to Organic Laboratory Techniques - 3rd
edition, Cengage Learning, 2011.
6. https://www.healthlinkbc.ca/health-topics/tw9187
7. https://www.pharmaguideline.com/2008/02/sop-for-first-aid.html
8. https://lab-training.com/2014/10/27/essentials-laboratory-first-aid/
9. https://www.labmanager.com/lab-health-and-safety/2010/03/glassware-safety-in-the-lab#.
Xia4XcgzY2w
10. http://www.crscientific.com/properheating2.html
61
11. https://www.labmanager.com/lab-health-and-safety/2010/03/glassware-safety-in-the-lab#.
Xia4XcgzY2w
12. http://www.wiredchemist.com/chemistry/instructional/laboratory-tutorials/distillation
13. https://learning.hccs.edu/faculty/paul.clemens/copy4_of_chem2423-1/laboratory-manual-
provided-as-handouts/experiment-7-distillation-2013-separation-of-a-mixture
14. http://chemistry.bd.psu.edu/halmi/chem213distillf09.pdf
15. https://people.chem.umass.edu/samal/267/owl/owldist.pdf
16. https://orgchemboulder.com/Technique/Procedures/Distillation/Distillation.shtml
17. http://www.chem.ucalgary.ca/courses/351/laboratory/distillation.pdf
18. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemist
ry_Lab_Techniques_(Nichols)/5%3A_Distillation
19. http://ochemlabtechniques.blogspot.com/p/how-steam-distillation-works.html
20. http://www.pitt.edu/~ceder/add_info/recrystallization.html
21. http://www.wiredchemist.com/chemistry/instructional/laboratory-tutorials/recrystallization
62

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VIET NAM NATIONAL UNIVERSITY – HO CHI MINH CITY

ORGANIC CHEMISTRY LAB

Dr. Le Xuan Tien

Dr. Nguyen Dang Khoa

Assoc. Prof. Le Thi Hong Nhan

HO CHI MINH CITY, 01/2020

Unit 1 – Introduction to organic synthesis laboratory

1.1. Lab safety rules

1.1.1. Safety guidelines

1.1.2. Lab first aid

First aid kit

Guidelines for first aid providers

● Maintain calm and evacuate the area in case there is danger.

Specific first aid tips

1.1.3. Lab glassware safety

● Do not use laboratory vessels for food or drink.

1.2. Basic laboratory glassware

(a) (b) (c)

Figure 1.1. a. Glass beaker, b. Erlenmeyer flask, c. Graduated cylinder.

(a) (b) (c)

(d) (e) (f)

(g) (h) (i) (j)

(a) (b) (c) (d) (e)

(a) (b) (c) (d) (e) (f) (g) (h)

1.3. Gravity filtration and vacuum filtration

Figure 1.7. Apparatus for gravity filtration

Figure 1.9. Vacuum filtration apparatus.

1.4. Washing and extraction

Extraction is to obtain an expected compound from a mixture/a matrix while washing is to

In solvent extraction, a distribution coefficient is often determined as a measure of how efficient

Figure 1.10. Liquid-liquid extraction using a separatory funnel.

Figure 1.11. A Soxhlet extraction system.

1.5. Heating and controlled boiling

Table 1.1. Useful temperature ranges of heat sources.

Heat source Useful range (oC)

Silicone oil bath 25 – 230

Glycerol bath 25 – 200

Mineral oil bath 25 – 200

Sand bath 25 – 500

(a) (b) (c)

Cooling is necessary for crystallization, low-temperature reaction, absorption of heat from an

Drying an organic liquid

Table 1.2. Common drying agents.

Organic compounds Drying agents

R-X (X=Cl, Br, I) CaCl2, CaSO4, P2O5, MgSO4

Alcohol CaSO4, MgSO4, K2CO3, CaO

Ketone CaSO4, MgSO4, Na2SO4

Organic acid MgSO4, Na2SO4, CaSO4

Amine KOH, NaOH, K2CO3, CaO

Drying an organic solid

Figure 1.13. (a) simple desiccator, (b) vacuum desiccator.

The most common methods of distillation include:

Simple distillation procedure

Figure 1.17. Fractional distillation setup.

Figure 1.18. External steam distillation setup.

Recrystallization is widely applied to purify impure solid products in a solvent or a mixture of

Procedure to find a good recrystallization solvent

1. Place 0.10 g of the solid in a test tube.

Procedure to recrystallize an impure compound in a solvent