CHE 1401
School of Science & Engineering
LABORATORY MANUAL FOR
ORGANIC CHEMISTRY I
Last Update: July 2015
Last update: June 2011
1
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Name: ________________________
Section: ________________________
LABORATORY MANUAL FOR
ORGANIC CHEMISTRY I
Last Update: July 2015
Last update: June 2011
1
CHE 2401
TABLE OF CONTENTS
Introduction
Laboratory safety
Laboratory operations
1
4
8
Experiment 1:
Esterification reaction: Synthesis of n-butyl acetate
17
Experiment 2:
Esterification reaction: Preparation of aspirin
22
Experiment 3:
Synthesis of benzoic acid and benzyl alcohol
27
Experiment 4:
Nitration of phenol
33
Experiment 5:
Synthesis of triphenylmethanol
37
Experiment 6:
Synthesis of pinacol hydrate and pinacolone
43
Experiment 7:
Synthesis of o-chlorobenzoic acid
49
Experiment 8:
Synthesis of cyclohexanone and adipic acid
54
Appendix
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INTRODUCTION
Getting started
By the end of the first week of your organic chemistry course, you should have read the
"Laboratory Safety" section of this manual and any other safety rules or data provided by
your instructor. Before you begin working in the laboratory, your instructor should
review the safety rules and tell you what safety supplies, such as safety goggles and
protective gloves you will need to use in the lab. During the first laboratory period, the
instructor will show you where safety equipment is located and tell you how to use it. As
you locate each item, check it off the following list and make a note of its location:
 Fire extinguishers
 Fire blanket
 Safety shower
 Eyewash fountain
 First aid supplies
 Spill cleanup supplies
You should also learn the locations of chemicals, consumable
supplies (such as filter paper and boiling chips), waste
containers, and various items of equipment such as balances
and drying oven.
If you find any glassware items with chips, cracks, or star
fractures, you should have them replaced; they may cause
cuts, break on heating, or shatter under stress. If necessary,
clean up any dirty glassware and organize it neatly at this
time.
Figure 1: Glassware defects.
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Working efficiently
Because of wide variations in individual working rates, it is usually not possible to
schedule experiments so that everyone can finish in the alloted time. If all labs were
geared to the slowest student, the objectives of the course could not be accomplished in
the limited time available. If you fall behind in the lab, you may need to put in extra
hours outside your scheduled laboratory period in order to complete the course. The
following suggestions should help you work more efficiently anf finish each experiment
on time.
1. Be prepared to start the experiment the moment you reach your work area. Don't
waste precious minutes at the start of a laboratory period doing calculations,
reading the experiment, washing glassware, or carrying out other activities that
should have been done at the end of the previous period or during the intervening
time. The first half hour of any lab period is the most important – if you use it to
collect the necessary materials, set up the apparatus, and get the initial operation
(reflux, distillation, etc) under way, you should have no trouble completing the
experiment on time.
2. Organize your time efficiently. Schedule a time each week to read the experiment
and operation descriptions and to complete the prelab assignement – an hour
before the lab period begins is too late! Plan ahead so that you know
approximately what you will be doing at each stage of the experiment. A written
experimental plan is invaluable for this purpose.
3. Organize your work area. Before performing any operation, arrange all of the
equipment and supplies you will need during the operation neatly on your
benchtop, in the approximate order in which they will be used. Place small objects
and any items that might be contaminated by contact with the benchtop on a paper
towel, laboratroy tissue, or mat. After you use each item, move it to an out-of-theway location where it can be cleaned and returned to its proper location when
time permits; for example put dirty glassware in a washing trough in the sink.
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Getting along in the laboratory
You will get along much better in the laboratory if you can maintain peace and harmony
with your coworkers – or at least keep from aggravating them – and stay on good terms
with your instructor. Following these commonsense rules will help you do that.
1. Leave all chemicals where you can find them. You will understand the reason for
this rule once you experience the frustration of hunting high and low for a
reagent, only to find it at another's student's station in a far corner of the lab.
2. Take only what you need. Whenever possible, liquids and solutions should be
obtained using pipets, graduated cylinders, or other measuring devices so that it
will take no more than you expect to use for a given operation.
3. Prevent contamination of chemicals. Don't use your own pipet or dropper to
remove liquids directly from stock bottles, and don’t return unused chemicals to
stock bottles. Be sure to close all bottles tightly after use – particularly those that
contain dying agents and other anhydrous chemicals.
4. If you must use a burner, inform your neighbors – unless they are already using
burners. This will allow them to cover any containers of flammable solvents and
take other necessary precautions. In some circumstances, you may have to use a
different heat source, move your operation to a safe location (for instance under a
fume hood), or find something else to do while flammable solvents are in use.
5. Return all community equipment to the designated locations. This may include
ring stands, lab kits, clamps, condenser tubing, and other items. Because such
items will be needed by students in other lab sections, they should always be
returned to the proper storage area at the end of the period.
6. Clean up for the next person. Few experiences are more annoying than finding
that the lab kit you just checked out is full of dirty glassware or that your lab
station is cluttered with paper towels, broken glass, and spilled chemicals. The
last 15 minutes or so of every laboratory period should be set aside for cleaning
up your lab station and the glassware used during the experiment. Put things away
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so that your workstation is uncluttered. Clean off the benchtop with a towel or wet
sponge; remove condenser tubing, other supplies, and debris from the sink; and
thoroughly wash any dirty glassware that is to be returned to the stockroom. Clean
up any spills and broken glassware immediately. If you spill a corrosive or toxic
chemical, such as sulfuric acid or aniline, inform the instructor before you attempt
to clean it up.
7. It is advised to maximize the labor and minimize the oratory while in the
laboratory. This does not mean that all conversation must come to a halt. Quiet
conversation during a lull in the experimental activity is okay, but a constant
stream of chatter directed at a coworker who is performing a delicate operation is
distracting and can lead to an accident. For the same reason, radios, CD or MP3
players and other audio devices must not be brought into the laboratory.
LABORATORY SAFETY
Laboratory instructors are required to see that students know and follow established
safety rules, have access to and know how to use appropriate emergency equipment, and
are aware of hazards of hazards associated with specific experiments. The lab instructor
alone cannot prevent laboratory accidents, however. You also have a responsibility to
follow safe laboratory practices while performing experiments and to be ready to respond
in case of accident.
Protecting yourself
Just as construction workers protect themselves from accidents by wearing hard hats and
steel-toed boots, people who work with chemicals should wear appropriate clothing and
personal protective equipment (such as safety goggles) that reduce the likelihood of
injury in case of an accident.
Eye protection is essential at all times and it should be the rule in every chemistry
laboratory. Safety glasses provide only limited protection because they have no side
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shields, so it is best to wear safety goggles that protect your eyes from chemical splashes
and flying particles from any direction.
In any chemistry lab, you should wear clothing that is substantial enough and covers
enough of your body to offer some protection against accidental chemical spills and
flying glass or other particles. Long-sleeved shirts or blouses and long pants or dresses
are recommended, especially when they are made of denim or other heavy materials .
Some synthetic fabrics can be dissolved by chemicals such as acetone and could melt in
contact with a flame or another heat source. Wear shoes that protect you from spilled
chemicals and broken glass – not open sandals or cloth-topped athletic shoes.
Always wear appropriate gloves when handling caustic chemicals, which can burn the
skin, or toxic chemicals that can be absorbed through the skin. No single type of glove
protects against all chemicals, but neoprene gloves offer good to excellent protection
against many commonly used chemicals, and disposable nitrile gloves are adequate for
use in most undergraduate labs. Latex gloves aren't recommended, because some people
are allergic to latex because they are permeable to many hazardous chemicals.
Preventing laboratory accidents
Most organic lab courses are completed without incident, apart from minor cuts or burns,
and serious accidents are rare. Nevertheless, the potential for a serious accident always
exists. To reduce the likelihood of an accident, you must learn the following safety rules
and observe them at all times. Additional safety rules or revisions of these rules may be
provided by your instructor.
1. Wear approved eye protection in the laboratory at all times. Even when you
aren't working with hazardous materials another student's actions could endanger
your eyes, so never remove your safety goggles or safety glasses until you leave
the lab. Do not wear contact lenses in the laboratory because chemicals splashed
into an eye may get underneath a contact lens and cause damage before the lens
can be removed. Determine the location of the eyewash fountain nearest to you
during the first laboratory session, and learn how to use it.
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2. Never smoke in the laboratory or use open flames in operations that involve lowboiling flammable solvents. Anyone found smoking in an organic chemistry
laboratory is subject to immediate expulsion. Before you light a burner or even
strike a match, inform your neighbors of your intention to use a flame. If anyone
nearby is using flammable solvents, either wait until he or she is finished or move
to a safer location, such as a fumehood. Diethyl ether and petroleum ether are
extremely flammable, but other common solvents, such as acetone and ethanol,
can be dangerous as well. When ventilation is inadequate, the vapors of diethyl
ether and other highly volatile liquids can travel a long way; lighting a burner at
one end of a lab bench that has an open bottle of ether at its other end has been
known to start an ether fire. Learn the location and operation of the fire
extinguishers, fire blankets, and safety showers at the first laboratory session.
3. Consider all chemicals to be hazardous and minimize your exposure to them.
Never taste chemicals, do not inhale the vapors of volatile chemicals or the dust
of finely divided solids, and prevent contact between chemicals and your skin,
eyes and clothing. Many chemicals can cause poisoning by ingestion, inhalation,
or absorption through the skin. Strong acids and bases, bromine, thionyl chloride,
and other corrosive materials can produce severe burns and require special
precautions, such as wearing gloves and labcoats. Some chemicals cause severe
allergic reactions, and others may be carcinogenic (tending to cause cancer) or
teratogenic (tending to cause birth defects) by inhalation, ingestion (swallowing)
or skin absorption. To prevent accidental ingestion of toxic chemicals, don't bring
food or drink into the laboratory or use mouth suction for pipettng, and wash your
hands thoroughly after handling any chemical. To prevent inhalation of toxic or
carcinogenic chemicals, work under an efficient fume hood or use a gas trap to
keep chemical fumes out of the laboratory atmosphere. To prevent contact with
corrosive or toxic chemicals, wear appropriate gloves and a labcoat. Clean up
chemical spills immediately – use a neutralizing agent a plenty of water for acids
and bases, and an absorbent for solvents. In case of a major spill, or if the
chemical spilled is very corrosive or toxic, notify your instructor before you try to
clean it up.
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4. Exercice great care when working with glass and when inserting or removing
thermometers and glass tubing. Among the most common injuries in a chemistry
lab are cuts from broken glass and burns from touching hot glass. Protect your
hands with gloves or a towel when inserting glass tubes or thermometers into
stoppers or thermometer adapaters, and when removing them. Grasp the glass
close to the stopper or thermometer adapter and gently twist it in or out.
5. Wear appropriate clothing in the laboratory. Wear clothing that is substantial
enough to offer some protection against accidental chemical spills, and shoes that
can protect you from spilled chemicals and broken glass. Human hair is very
flammable, to tie up your hair or wear a hair net while using a burner if you have
long hair.
6. Dispose of chemicals properly. For reasons of safety and environmental
protection, most organic chemicals shouldn't be washed down the drain. Except
when your instructor or an experiment's directions indicate otherwise, place used
organic chemicals and solutions in designated waste containers. Some aqueous
solutions can be safely poured down the drain, but consult your instructor if there
is any question about the best method for disposing of a particular chemical or
solution.
7. Never work alone in the laboratory or perform unauthorized experiments. If you
wish to work in the laboratory when no formal lab period is scheduled, you must
obtain permission from the instructor and be certain that others will be present
while you are working.
LABORATORY OPERATIONS
This section describes some of the operations you should need to know to successfully
complete this organic chemistry laboratory course. Although you may already have used
some of them in a general chemistry course, you should still read the descriptions
carefully because an operation may require different equipment or be performed in a
different way in the organic chemistry lab.
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Cleaning glassware
Clean glassware is essential for good results in the organic chemistry laboratory. Even
small amounts of impurities can sometimes inhibit chemical reactions, catalyse
undesirable side reactions, or invalidate the results of chemical tests or rate studies.
Always clean dirty glassware at the end of each laboratory period, or as soon as possible
after the glassware is used. This way, your glassware will be clean and dry for the next
experiment, and you will be ready to start work when you arrive. If you wait too long to
clean glassware, residues may harden and become more resistant to cleaning agents; they
may also attack the glass itself, weakening it and making future cleaning more difficult. It
is particularly important to wash out strong strong bases such as sodium hydroxyde
promptly, because they can etch the glass permanently and cause glass joints to "freeze"
tight. When glassware has been thoroughly cleaned, water applied to its inner surface
should wet the whole surface and not form droplets or leave dry patches. However, used
glassware that has been scratched or etched may not wet evenly.
You can clean most glassware adequately by vigorous scrubbing with water and a
laboratory detergent, using a brush of appropriate size and shape to reach otherwise
inaccesible spots.
Organic residues that can't be removed by detergent and water will often dissolve in
organic solvents such as technical-grade acetone (Never use reagent grade solvents for
washing). For example, it is difficult if not impossible – to scrub the inside porcelain
Büchner or Hirsch funnel, but squirting a little acetone around the inside of the funnel
stem and letting it drain through the porous plate should remove chemical residues that
may have lodged there. Use acetone sparingly and recycle it after use (don't pour it down
the drain), as it is much more costly than water and may harm the environment Be certain
that acetone is completely removed from glassware before you return it in the drawer.
After washing, always rinse glassware thoroughly with water (a final distilled-water rinse
is a good idea) and check it to see if the water wets its surface evenly rather than forming
separate beads of water. If it doesn't pass this test scrub it some more or use a cleaning
solution. Note that some well-used glassware may not pass the test because of surface
damage, but it may still be clean enough to use after thorough scrubbing.
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Lubricating joints
Most specialized glassware components used in organic
chemistry have rigid ground-glass joints called standard-taper
joints. The size of a tapered joint is designated by two
numbers, such as 19/22, in which the first number is the
diameter at the top of the joint and the second is the length of
the taper, measured in millimiters.
Glassware from a commercial organic lab kit, or its equivalent
purshased as separate parts, can be used to construct apparatus
Figure 2: 19/22
standard-taper joint.
for many different laboratory operations.
For some operations, such as vacuum distillation, glass joints should be lubricated with a
suitable joint grease. For most other operations, lubrication of glass joints is unnecessary
and may be undesirable. Your instructor should inform you if lubrication will be
necessary. To lubricate a ground-glass joint, apply a thin layer of joint grease completely
around the top half of the inner (male) joint. Do not lubricate the outer (female) joint. Be
careful to keep grease away from the open end of the joint, where it may come into
contact with and contaminate your reaction mixture or product. When you assemble the
components, press the outer and inner joints together firmly, with a slight twist, to form a
seal around the entire joint with no gaps. Grease should never extend beyond the joint
inside the apparatus.
After disassembling the apparatus, remove the grease completely by using a suitable
organic solvent. You can remove petroleum-based greases with petroleum ether or
hexanes, and silicone greases by thorough cleaning with dichloromethane. An inner joint
can be cleaned by wrapping a small amount of cotton loosely around the end of an
applicator stick, dipping it in the solvent, and wiping the joint with the moist cotton.
Assembling glassware
Standard-taper joints are rigid, so a glassware apparatus must be assembled carefully to
avoid strain that can result in breakage. First, place the necessary clamps and rings at
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appropriate locations on the ring stand (use two ring stands for distillations setups). Then,
assemble the apparatus from the bottom up, starting at the heat source. Position the heat
source on a ring or a Boy elevator so that it can be removed easily when the heating
period is over; otherwise it may continue to heat a reaction mixture or an empty distilling
flask even after it is switched off, causing a danger of breakage, tar formation, or even an
explosion. Clamp the reaction flask or boiling flask securely at the proper distance from
the heat source.
As you add other components clamp them to the ring stand(s) but don't tighten the clamp
jaws completely until all of the components are in place and aligned properly. Use as
many clamps as are necessary to provide adequate support for all parts of the apparatus.
Figure 3 summarizes the steps followed in assembling one kind of ground-glass
apparatus.
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Steps
1.
Position clamps, rings.
2.
Position heat source.
3.
Clamp boiling flask securely.
4.,5. Add
Claisen
adapter
and
connecting adapter.
6.
Clamp West condenser in place.
7.
Attach vaccum adapter with
rubber band or spring clamp.
8.
Attach receiving flask, support
with ring and wire gauze.
9.
Readjust all clamps to align
parts.
10. Press joints together.
11. Tighten clamps.
12. Add stopper.
13. Add thermometer adapter and
position thermometer.
Figure 3: Steps in the assembly of a ground-glass apparatus.
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Graduated cylinder
Graduated cylinders aren't highly accurate, but they are
often used to measure specified quantities of solvents and
wash liquids, or even some liquid reactants that are used
in excess.
To use a graduated cylinder, transfer the liquid being
measured to the cylinder – by pouring it or by using a
Pasteur pipet – until the cylinder is filled to the graduation
mark corresponding to the desired volume. Read the liquid
volume from the bottom of the meniscus, as shown in
Figure 4. In necessary, add or remove liquid with a
Pasteur pipet.
Figure 4: Reading the volume
contained in a graduated
cylinder – in this case, 6.0 mL.
Heating under reflux
Most organic reactions are carried out by heating the reaction mixture to increase the
reaction rate. The temperature of a reaction mixture can be controlled in several ways, the
simplest and most convenient being to use a reaction solvent that has a boiling point
within the desired temperature range for the reaction. Sometimes a liquid reactant itself
may be used as the solvent. The reaction is conducted at the boiling point of the solvent,
using a condenser to return solvent vapors to the reaction vessel so that no solvent is lost.
This process of boiling a reaction mixture and condensing the solvent vapors back into
the reaction is known as heating under reflux (or more informally as "refluxing"), where
the word reflux refers to the "flowing back" of the solvent. Usually a reaction time is
specified for a reaction conducted under reflux. That interval should be measured from
the time the reaction mixture begins to boil, not from the time heating is begun.
Round-bottom flasks are used as the reaction vessels for most of the synthetic
experiments. As a rule, the reaction vessel should be the smallest appropriate container
that will be about half-full or less when all of the reactants have been added.
Several different kinds of reflux condensers are available. A water-cooled condenser
consists of two concentric tubes, with cold tap water circulating through the outer tube
and solvent vapors from a boiling reaction mixture rising up in the inner tube. The
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circulating water cools the walls of the inner tube, cooling the vapors and causing them to
condense to liquid droplets that flow back into the reaction vessel. A water-cooled West
condenser is used for most standard scale reactions conducted under reflux (Figure 5).
Figure 5: Apparatus for heating under reflux.
Gravity filtration
Filtration is used for two main purposes in organic chemistry:
- to remove solid impurities from a liquid or solution
- to separate an organic solid from a reaction mixture or a crystallization
solvent
Gravity filtration is generally used for the first purpose, and vaccum filration for the
second. Centrifugation can be used for either. In a gravity filtration, the liquid component
of a liquid-solid mixture drains through a filtering medium (such as filter paper or cotton)
by gravity alone, leaving the solid on the filtering medium. The filtered liquid, called the
filtrate, is collected in a flask or another container. Gravity filtration is often used to
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remove drying agents from dried organic liquids or solutions and solid impurities from
hot recrystallisation solutions.
If the solid being removed is coarse and quite dense, it can sometimes be removed from a
liquid by letting it settle to the bottom of the container (preferably an Erlenmeyer flask)
and then slowly and carefully pouring the liquid into another container, leaving the solid
behind. Some of the liquid may remain behind in the flask, but it can be transferred using
a Pasteur pipet or a filter-tip pipet, if necessary. This process, called decanting, should
not be used with finely divided solids, because some of the solid will inevitably be
poured out with the liquid and contaminate it.
Gravity filtration of moderate to large volumes of organic liquids can be carried out using
a funnel with a short, wide stem (such as a powder funnel) and a relatively fast, fluted
filter paper (Figure 6). Circles of ordinary filter paper can be fluted (folded) as shown in
Figure 7. Glass wool is sometimes used for very fast filtration of coarse solids. A thin
layer of glass wool is placed inside the cone of a short-stemmed funnel, covering the
outer hole, and the mixture to be filtered is poured directly onto the glass wool. Because
fine particles will pass through glass wool fibers, this method is most often used for
prefiltration of mixtures that will be filtered again.
Figure 6: Apparatus for gravity filtration
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Figure 7: Making a fluted filter paper
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Steam distillation
Distillation of a mixture of two (or more) immiscible liquids is called codistillation.
When one of the liquids is water, the process is usually called steam distillation. External
steam distillation is carried out by passing externally generated steam (usually from a
steam line) into a boiling flask that contains the organic material (Figure 8). The
vaporized organic liquid is carried over into a receiver along with the condensed steam.
Figure 8: Apparatus for external steam distillation.
When a homogeneous mixture of two liquids is distilled, the vapor pressure of each
liquid is lowered by an amount proportional to the mole fraction of the other liquid
present. This usually results in a solution boiling point that is somewhere between the
boiling points of the separate components. For example, a solution containing equal
masses of cyclohexane (bp = 81 oC) and toluene (bp = 111 oC) boils at 90 oC.
When a heterogeneous mixture of two immiscible liquids, A and B, is distilled, each
liquid exerts its vapor pressure more or less independently of the other. The total vapor
pressure over the mixture (P) is thus approximately equal to the sum of the vapor
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pressures that would be exerted by the separate pure liquids. (PAo and PBo) at the same
temperature.
P ≈ PAo + PBo
This has several important consequences. First the vapor pressure of a mixture of
immiscible components will be higher than the vapor pressure of its most volatile
component. Because raising the vapor pressure of a liquid or liquid mixture lowers its
boiling point, the boiling point of the mixture will be lower than that of its most volatile
(lowest-boiling) component. Because the vapor pressure of a pure liquid is constant at a
constant temperature, the vapor pressure of the mixture of liquids will be constant as
well. Thus, the boiling point of the mixture will remain constant throughout its
distillation as long as each component is present in significant quantity.
Externally generated steam is preferred for most standard scale steam distillation,
especially those involving solids or high-boiling liquids, because external steam produces
a rapid distillation rate and helps prevent bumping caused by solids and tars.
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EXPERIMENT 1
ESTERIFICATION REACTION:
SYNTHESIS OF n-BUTYL ACETATE
OBJECTIVES
 To become acquainted with general procedures used in an organic chemistry
lab experiment
 Synthesize an ester from its corresponding acid and alcohol (Fischer esterification)
Relates to chapter 11 of “Essential Organic Chemistry, 2nd Ed.”.
APPARATUS AND CHEMICALS
CHEMICALS
APPARATUS & MISC
acetic acid (15 mL)
heating mantle, Boy elevator
n-butanol (11.5 mL)
100 mL round-bottomed flask
conc. sulfuric acid (2 mL)
water condenser
10 % sodium hydrogenocarbonate solution (10 mL)
distillation kit
anhydrous sodium sulfate (1 g)
Büchner funnel, filter paper
separating funnel
boiling chips, grease, gloves
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INTRODUCTION
Esters are derived from carboxylic acids. A carboxylic acid contains the -COOH group,
and in an ester the hydrogen in this group is replaced by a hydrocarbon group of some
kind. This could be an alkyl group like methyl or ethyl, or one containing a benzene ring
like phenyl.
Esters are widespread in nature and are widely used in industry, notably for flavourings.
Below are mentioned a few examples:
O
O
H
O
O
Ethyl methanoate (ethyl formate)
rum flavouring
Propyl pentanoate (n-propyl n-valerate):
pineapple flavouring
O
O
O
O
Ethyl butanoate (ethyl butyrate)
apple odour
Octyl ethanoate (n-octyl acetate)
orange odour
The classic synthesis of esters is the Fischer esterification, which involves treating a
carboxylic acid with an alcohol in the presence of a dehydrating agent:
O
O
R1
OH + R2 OH
R1
O
R2
+ H2O
Strong acids, typically sulfuric acid, catalyze this reaction. Many other acids are also
used. Esterification is highly reversible. The simple reaction of one equivalent each of
acid and alcohol gives a mixture of starting materials and products. The yield of the
product may be improved using le Chatelier's principle:

using the alcohol in large excess (i.e. as a solvent)
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
using a dehydrating agent. Sulfuric acid (H2SO4) not only catalyzes the reaction
but sequesters water (a reaction product)

removal of water by physical means such as an azeotropic distilation with
cyclohexane or toluene.
GENERAL MECHANISM
O
R1
O
+
OH + H
R1
H
HO
OH
R1
H
R2 OH
H
R2 O OH
OH
R1
carboxylic acid
OH
PT
O
1
R
R2
O
-H+
1
R
O
R2
O H
HO
1
R
R2
-H2O
H
R2 O O H
R1
OH
OH
ester
REACTION
O
+
OH
acetic acid
Compound
Acetic acid
n-Butanol
Sulfuric acid, 98 %
n-Butyl acetate
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H2SO4
HO
heat, 1 h
n-butanol
M.W. (g/mol)
60.05
74.12
98.08
116.16
O
O
n-butyl acetate
Density (g/mL)
1.049
0.81
1.84
0.88
b.p (oC)
117-118
116-118
~ 290
124-126
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PROCEDURE
In a 100 mL round-bottom flask, introduce successively acetic acid (15 mL), n-butanol
(11.5 mL) and concentrated sulfuric acid (~ 2 mL). Next, add a few boiling chips and fit a
water condenser lubricated with grease (Figure 1.1). The mixture is refluxed by means of
a heating mantle for 1 hour, time upon which the reaction mixture is transferred into a
separating flask containing 30 mL of water (Figure 1.2). The aqueous layer is isolated
and the organic layer is washed first with a 10 % solution of sodium hydrogenocarbonate
NaHCO3 (1 x 10 mL) and then with water (2 x 10 mL). Then, the organic layer is dried
over anhydrous sodium sulfate Na2SO4 (~ 1 g) and filtered over a Büchner funnel.
Finally, the filtrate is distilled slowly and the boiling point recorded (Figure 1.3). Weigh
the mass of product (n-butyl acetate) obtained.
organic
layer
Figure 1.1
aqueous
layer
Figure 1.2
Figure 1.3
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Experiment 1
Esterification reaction:
Synthesis of n-butyl acetate
Name(s)
Date
Laboratory Instructor
REPORT SHEET
O
+
OH
Acetic acid
n-Butanol
n-Butyl acetate
n-butyl acetate
n-butanol
M.W. (g/mol)
60.05
74.12
116.16
O
heat, 1 h
acetic acid
Compound
O
H2SO4
HO
Density
(g/mL)
1.049
0.81
1.84
0.88
volume
(mL)
15.0
11.5
16.6
mass
(g)
15.73
9.31
14.59
n
(mmol)
261.9
125.6
125.6
Mass of product expected: ___________________ g
Mass of product obtained: ___________________ g
Percent chemical yield=
mass product obtained
mass product exp ected
100  ___________________ %
QUESTIONS
1) Why do we use a small amount of mineral acid?
2) What is the reactant in excess? Justify your answer.
3) What is the role of sodium hydrogenocarbonate?
4) Write the equation of the chemical reaction and the associated mechanism.
5) What is the role of the distillation?
6) Compare the recorded boiling point with the literature data.
8) Propose another synthetic method for the preparation of n-butyl acetate.
Lab Manual
21
CHE 2401
EXPERIMENT 2
ESTERIFICATION REACTION:
PREPARATION OF ASPIRIN
OBJECTIVES
 Synthesize aspirin from its corresponding acid anhydride and alcohol
 Compare two different synthetic routes for the preparation of esters
Relates to chapter 11 of “Essential Organic Chemistry, 2nd Ed.”.
APPARATUS AND CHEMICALS
CHEMICALS
APPARATUS & MISC
salicylic acid (2 g)
50 mL beaker
acetic anhydride (3 mL)
thermometer
conc. sulfuric acid (1 drop)
glass rod
methanol or ethanol (6 mL)
Büchner funnel, filter paper
anhydrous sodium sulfate (1 g)
bain-marie
melting point apparatus
Lab Manual
22
CHE 2401
INTRODUCTION
The classic synthesis of esters is the Fischer-Speier esterification, employed in
experiment 1. However, several other methods are available, one being often favored
other another depending on the problems needing to be tackled. The method used in this
experiment is the alcoholysis of an acid anhydride. Alternative methods are the
following:
-
alcoholysis of acyl chlorides
-
Steglish esterification
-
transesterification
-
Favorskii rearrangement of α-haloketones in presence of base
-
nucleophilic displacement of alkyl halides with carboxylic acid salts
-
Baeyer-Villiger oxidation of ketones with peroxides
-
Pinner reaction of nitriles with an alcohol
Alcohols react with acyl chlorides or acid anhydrides to give esters:
O
O
R
O
R
Cl
+ R' OH
R
R'
+ HCl
O
O
O
O
'
R + R OH
R
O
O
R'
+ R
OH
These reactions are irreversible, thus simplifying workup. Since acyl chlorides and acid
anhydrides react also with water, anhydrous conditions are preferred. The analogous
acylation of amines that produces amides is less sensitive towards water because amines
are stronger nucleophiles and react more rapidly.
Lab Manual
23
CHE 2401
GENERAL MECHANISM
O
R1
O
O
R1
O
H+
R1
O
R1
O
H
acid anhydride
R2 OH
O
R1
R2
O
O
-H+
2
R
O
O
H
R1
+
R1
OH
ester
REACTION
httpwww2.volstate.edu/chem/1110/Labs/Synthesis_of_Aspirin.htm
O
O
OH
O
+
O
O
H2SO4
OH
O
OH
acetic anhydride
Compound
Salicylic acid
Acetic anhydride
Sulfuric acid, 98 %
Aspirin
Lab Manual
+
50-60 oC, 15 min
OH
salicylic acid
O
O
M.W. (g/mol)
138.12
102.09
98.08
180.16
acetylsalicylic acid
(aspirin)
Density (g/mL)
/
1.08
1.84
/
acetic acid
b.p (oC)
211
138-140
~ 290
/
24
CHE 2401
PROCEDURE
In a 50 mL beaker, introduce salicylic acid (2 g) and acetic anhydride (3 mL). Then, add
1 drop of concentrated sulfuric acid and stir the mixture. Heat by means of a bain-marie
for 15 min while strirring continually with a glass rod.
Add 35 mL of water, swirl the mixture and carry out a vacuum filtration. Weigh the
mass of crude product (aspirin) obtained.
The crude acetylsalicylic acid is purified by recristallisation. It is dissolved in hot
methanol or ethanol (6 mL). The resulting solution is poured into 20 mL of hot water. If a
precipitation occurs, heat the mixture until complete dissolution and then let it cool down
slowly (in the air, next water, then ice water). After recrystallisation, the solid is filtered
and dried. Weigh the mass of pure product (aspirin) obtained.
Lab Manual
25
CHE 2401
Experiment 2
Esterification reaction:
Preparation of Aspirin
Name(s)
Date
Laboratory Instructor
REPORT SHEET
O
O
OH
O
+
O
H2SO4
O
+
50-60 oC, 15 min
Compound
Salicylic acid
Acetic anhydride
Aspirin
OH
O
OH
salicylic acid
O
O
OH
acetic anhydride
M.W.
(g/mol)
138.12
102.09
180.16
acetylsalicylic acid
(aspirin)
Density
(g/mL)
/
1.08
/
volume
(mL)
/
3
/
Mass of pure product expected:
_______________ g
Mass of crude product obtained:
_______________ g
Mass of pure product obtained:
_______________ g
Percent yield in crude product =
Percent yield in pure product =
masscrude product obtained
masspure product exp ected
masspure product obtained
masspure product exp ected
acetic acid
mass
(g)
2.00
3.24
2.61
n
(mmol)
14.5
31.7
14.5
100  _______________ %
100  _______________ %
QUESTION
 Give an alternative method of synthesis of aspirin, using salicylic acid as a starting
material. Give the mechanism.
Lab Manual
26
CHE 2401
EXPERIMENT 3
SYNTHESIS OF BENZOIC ACID
AND BENZYL ALCOHOL
OBJECTIVE
 Perform the reaction of dismutation of an aldehyde (Cannizzaro reaction)
APPARATUS AND CHEMICALS
CHEMICALS
APPARATUS & MISC
benzaldehyde (7.5 g)
100 mL beaker
sodium hydroxyde (4.5 g)
50 mL beaker
dichloromethane (50 mL)
bain-marie
sodium bisulfate solution NaHSO3 (5 mL)
separating funnel
anhydrous sodium sulfate (1 g)
funnel, filter paper
conc. hydrochloric acid
Büchner funnel, filter paper
pH paper
ice
Lab Manual
27
CHE 2401
INTRODUCTION
As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and
ketones, not of carboxylic acid derivatives. The reason for the difference of is structural;
the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid
derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution
reaction. The tetrahedral intermediate produced by addition of a nucleophile to an
aldehyde or ketone, however, has only alkyl or hydrogen substituents and thus can't
usually expel a leaving group. One exception to this rule, however, is the Cannizaro
reaction, discovered in 1853.
The Canizzaro reaction takes place by nucleophilic addition of OH- to an unenolizable
aldehyde (bearing no α H) to give a tetrahedral intermediate, which expels hydride ion as
a leaving group and is thereby oxidized. A second aldehyde molecule accepts the hydride
ion in another nucleophilic addition step and is thereby reduced.
GENERAL MECHANISM
O
R
OH
H
O O H
R
O O
H
R
H
aldehyde
tetrahedral
dianion
O
R
H
O
R
Lab Manual
O H
O
+
R
H
28
CHE 2401
REACTION
O
O
NaOH
H
2
OH +
heat, 30 min
benazaldehyde
Compound
Benzaldehyde
Sodium hydroxyde
Benzoic acid
Benzyl alcohol
M.W. (g/mol)
106.12
40.00
122.12
108.14
benzoic acid
OH
benzyl alcohol
Density (g/mL)
b.p (oC)
PROCEDURE
In a 50 mL beaker introduce benzaldehyde (7.5 g) and a saturated solution of sodium
hydroxyde (4.5 g of pellets in the minimum amount of water). Heat the mixture by means
of a bain-marie for 30 min while stirring vigorously (Figure 3.1).
Next, cool the beaker down and the minimum amount of cold water to dissolve the solid.
Then, transfer the mixture into a separating flask, extract with dichloromethane
(2x20 mL) and collect the organic layers in a 100 mL beaker (Figure 3.2). The content of
the beaker is mixed vigorously with a solution of sodium bisulfate (5 mL) in order to
remove the unreacted benzaldehyde. If a precipitate is formed, filter through a Büchner
funnel (Figure 3.3) and wash it with dichloromethane (10 mL); finally dry it and weigh it
out. The organic layer is washed consecutively with a dilute solution of sodium
hydroxyde (5 mL) and water until a neutral pH is reached.
The resulting organic layer is dried over anhydrous sodium sulfate (~1g) and evaporated
by means of a rotary evaporator. Weigh the mass of product (benzyl alcohol) obtained.
The remaining aqueous phase is cooled down in an ice bath and treated with concentrated
HCl until pH = 1. The resulting solid is filtered through a Büchner funnel, washed twice
with cold water and finally dried over filter paper.
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29
CHE 2401
Recrystallization
Dissolve the solid completely in hot water (30 mL) and let the solution cool down slowly
until benzoic acid crystallizes in the form of white needles. The solid is isolated by
filtration and dried over filter paper. Weigh the mass of product (benzoic acid)
obtained.
organic
layer
Figure 3.1
Lab Manual
aqueous
layer
Figure 3.2
Figure 3.3
30
CHE 2401
Experiment 3
Synthesis of benzoic acid and benzyl alcohol
Name(s)
Date
Laboratory Instructor
REPORT SHEET
O
O
NaOH
H
2
OH +
heat, 30 min
benazaldehyde
Compound
Benzaldehyde
Sodium hydroxyde
Benzoic acid
Benzyl alcohol
benzoic acid
M.W.
(g/mol)
106.12
40.00
122.12
108.14
Density
(g/mL)
/
/
/
1.045
benzyl alcohol
volume
(mL)
/
/
/
3.65
Mass of benzoic acid expected:
_______________ g
Mass of benzoic acid obtained:
_______________ g
Mass of benzyl alcohol expected:
_______________ g
Mass of benzyl alcohol obtained:
_______________ g
Percent chemical yield in acid =
OH
massacid obtained
100 
massacid exp ected
Percent chemical yield in alcohol =
massalcohol obtained
100 
massalcohol exp ected
mass
(g)
7.50
4.50
4.31
3.82
n
(mmol)
70.7
112.5
35.34
35.34
_______________ %
_______________ %
QUESTIONS
1) Why do we acidify the aqueous layer? Give the chemical equation of the reaction.
Lab Manual
31
CHE 2401
2) How would you isolate the alcohol from the organic layer that contains also the
portion of unreacted aldehyde?
3) Why is the organic layer washed with a dilute sodium hydroxyde solution?
4) Give the mechanism of the reaction between sodium bisulfate and benzaldehyde.
5) Calculate the mass of unreacted benzaldehyde.
6) What is the difference between the Canizzaro reaction and an aldol reaction? Give an
example.
Lab Manual
32
CHE 2401
EXPERIMENT 4
NITRATION OF PHENOL
OBJECTIVE
 Synthesis and isolation of o-nitrophenol by nitration of phenol followed by steam
distillation.
Relates to chapter 8 of “Essential Organic Chemistry, 2nd Ed.”.
APPARATUS AND CHEMICALS
CHEMICALS
APPARATUS & MISC
phenol (6.5 mL)
250 mL beaker
conc. sulfuric acid (7 mL)
condenser
sodium nitrate NaNO3 (10 g)
ice
magnetic stirrer, stirrer bar
thermometer
separating flask
Bunsen burner, hot plate, oil bath
heating mantle, Jack elevator
septum with 2 holes, glass tubes (water
boiler)
Büchner funnel, filter paper
Lab Manual
33
CHE 2401
INTRODUCTION
o-nitrophenol is a compound that has numerous applications in the chemical industry. It
is notably used in the synthesis of dyes and as an intermediate in the production of
pigments, rubber and preservatives. o-nitrophenol can be prepared directly from phenol
in a reaction known as "nitration", a type of electrophilic aromatic substitution reaction.
Phenol reacts with hot concentrated nitric acid to give nitrophenol. This sluggish reaction
is hazardous because a hot mixture of concentrated nitric acid with any oxidizable
material might explode. A safer and more convenient procedure uses a mixture of nitric
acid and sulfuric acid. Sulfuric acid is a catalyst, allowing nitration to take place more
rapidly and at lower temperatures.
Sulfuric acid reacts with nitric acid to form the nitronium ion (+NO2), a powerful
electrophile. As resonance contributors of phenol indicate, the aromatic ring in phenol
possesses electron rich areas in the o and p position, thus producing o-nitrophenol and
p-nitrophenol in an electrophilic substitution reaction with +NO2.
REACTION MECHANISM
NaNO3 + H2SO4
NaHSO4 + HNO3
HSO4- + H2NO3+
H2SO4 + HNO3
H2NO3+
NO2+ + H3O+ + HSO4-
+ H2SO4
NO2+ + H3O+ + 2 HSO4nitronium
ion
H
O
H
HNO3 + 2 H2SO4
O
H
O
H
O
H
O
NO2
H
NO2
-H+
o-nitrophenol
NO2
O
H
phenol
OH
-H+
H
Lab Manual
OH
NO2
p-nitrophenol
NO2
34
CHE 2401
REACTION
OH
OH
+ NaNO3
phenol
Compound
Phenol
Sodium nitrate
Sulfuric acid
o-nitrophenol
OH
NO2
H2SO4
+
T < 25oC, 30 min
sodium
nitrate
M.W. (g/mol)
94.11
84.99
98.08
139.11
o-nitrophenol
NO2
p-nitrophenol
Density (g/mL)
b.p (oC)
PROCEDURE
Nitration of phenol
Place a 250 mL round-bottom flask containing a solution of sodium nitrate (10 g) in
water (25 mL) in an ice bath, and introduce cautiously concentrated sulfuric acid (7 mL).
Next, a suspension of phenol (6.5 mL) in water (2 mL) is added dropwise to the
sulfonitric mixture while stirring at low temperature (ice bath). Once the addition is
complete, the mixture is stirred for 30 min, time upon which water (~100 mL) is added.
Finally the mixture is transferred into a separating flask, the aqueous layer isolated and
the oily dark organic layer washed a second time with water (~100 mL).
Separation of o-nitrophenol by steam distillation
A round-bottom flask containing the oily dark organic layer obtained previously is placed
in an external steam distillation setup (cf "Laboratory Operations" section of the manual)
and is heated by means of a heating mantle to minimize the condensation of water. If the
distilled product crystallizes inside the condenser (yellow solid), stop feeding the water
condenser temporarily until the solid melts again. Finally, stop the distillation once no
more product is distilled, filter through a Büchner funnel and dry over filter paper several
times. Weigh the mass of product (o-nitrophenol) obtained.
Lab Manual
35
CHE 2401
Experiment 4
Nitration of phenol
Name(s)
Date
Laboratory Instructor
REPORT SHEET
OH
OH
+ NaNO3
phenol
Compound
Phenol
Sodium nitrate
o-nitrophenol
OH
NO2
H2SO4
+
T < 25oC, 30 min
sodium
nitrate
M.W. (g/mol)
94.11
84.99
139.11
o-nitrophenol
Density
(g/mL)
1.071
/
/
volume
(mL)
6.5
/
/
NO2
p-nitrophenol
mass
(g)
6.96
10.00
10.30
Mass of o-nitrophenol expected:
_______________ g
Mass of o-nitrophenol obtained:
_______________ g
Percent chemical yield =
massproduct obtained
massproduct exp ected
n
(mmol)
74.0
117.7
74.0
100  _______________ %
QUESTIONS
1) What products will be obtained if the concentration of the sulfonitric mixture
employed is increased?
2) The reaction produced also p-nitrophenol; suggest a method to isolate it.
3) Suggest a synthetic method for the preparation of m-nitrophenol from benzene.
4) Explain why during the steam distillation we isolate mainly the o-nitrophenol and only
trace amounts of p-nitrophenol.
Lab Manual
36
CHE 2401
EXPERIMENT 5
SYNTHESIS OF TRIPHENYLMETHANOL
OBJECTIVE
 Perform the addition of a Grignard reagent to a ketone substrate.
Relates to chapter 12 of “Essential Organic Chemistry, 2nd Ed.”.
CHEMICALS
APPARATUS & MISC
bromobenzene (4.2 mL)
250 mL two/three neck round-bottomed
magnesium turnings (0.9 g)
flask
benzophenone (4.8 g)
addition funnel
anhydrous diethylether Et2O (40 mL)
condenser
diethylether (technical grade – 20 mL)
CaCl2 guard
Calcium chloride
300 mL beaker
3N HCl solution (60 mL)
rotary evaporator
sodium sulfate (16 g)
filter paper
sodium carbonate (2 g)
Lab Manual
37
CHE 2401
INTRODUCTION
Because they resemble carbanions, Grignard and organolithium reagents are strong
nucleophiles and strong bases. Their most useful nucleophilic reactions are additions to
carbonyl (C=O) groups. The carbonyl group is polarized, with a partial positive charge on
carbon and a partial negative charge on oxygen. The positively charged carbon is
electrophilic; attack by a nucleophile places a negative charge on the electronegative
oxygen atom.
The product of this nucleophilic attack is an alkoxide ion, a strong base. Addition of water
or dilute acid in a second step protonates the alkoxide to give the alcohol.
Either a Grignard or an aluminium reagent can serve as the nucleophile in this addition to
a carbonyl group.
Lab Manual
38
CHE 2401
MECHANISM
..
..
Et2O
Br
.
Br ...OEt2
Mg
O
MgBr
O
Mg, Et2O
Grignard
reagent
bromobenzene
alkoxide
ion
H+
OH
triphenylmethanol
REACTION
Br
OH
1) Mg, Et2O
O
bromobenzene
2)
, 35 oC, 20 min
triphenyl methanol
benzophenone
3) HCl
Compound
Bromobenzene
Benzophenone
Magnesium
Triphenyl methanol
Lab Manual
M.W. (g/mol)
157.01
182.22
24.31
260.33
Density (g/mL)
b.p (oC)
39
CHE 2401
PROCEDURE
Preparation of the Grignard reagent
To a flame dried 250 mL one-neck round-bottomed flask fitted with an addition funnel
and a water condenser (Figure 5.1), are introduced magnesium turnings (0.9 g).
..........
..............
.............
...
..
.....
......
........
CaCl2
guard
bromobenzene
+ ether
magnesium
turnings
Figure 5.1: Reaction setup of the Grignard addition to benzophenone.
Next, the glassware is flame dried again to eliminate moisture and a CaCl2 guard is fitted
over the condenser. The setup is allowed to cool down to room temperature before
charging the addition funnel with bromobenzene (4.0 mL) and ether (1 mL). Then add the
bromobenzene solution and the reaction should take place without external heating
required. Within a few minutes time the reaction mixture should get cloudy, turn milky
and finally turn dark brown, time upon which ether is boiling. At this time, pour the rest
of the bromobenzene solution dropwise at a rate such as ether can boil slowly without
external heating. Once the addition is complete keep the reaction mixture under reflux for
20 min time upon which most of the magnesium should be consumed.
Lab Manual
40
CHE 2401
Grignard addition reaction – preparation of triphenylmethanol
Cool down the flask and load the addition flask with benzophenone (4.8 g) dissolved in
anhydrous ether (15 mL). Add the solution to the Grignard reagent dropwise; the mixture
should then turn red. Once the addition is complete, heat under reflux for 5 min until a
large amount of a pink precipitate is obtained.
Pour the content of the round-bottomed flask in a 300 mL beaker containing a 3N HCl
(60 mL) and ice, and rinse the flask with a few mL of regular ether. Next transfer the
mixture in a separatory funnel, extract the organic phase, wash it with water and dry it
over sodium sulfate. Ether is then evaporated with a rotary evaporator and the resulting
precipate is flitered and dried.
Weigh the mass of product (triphenylmethanol)
obtained.
Lab Manual
41
CHE 2401
Experiment 5
Synthesis of triphenylmethanol
Name(s)
Date
Laboratory Instructor
REPORT SHEET
Br
OH
1) Mg, Et2O
O
bromobenzene
2)
, 35 oC, 20 min
triphenylmethanol
benzophenone
3) HCl
Compound
Bromobenzene
Benzophenone
Magnesium
Triphenylmethanol
M.W.
(g/mol)
157.01
182.22
24.31
260.33
Density
(g/mL)
1.491
/
/
/
volume
(mL)
4
/
/
/
mass
(g)
5.96
4.80
0.90
6.86
Mass of trimethylmethanol expected:
_______________ g
Mass of trimethylmethanol obtained:
_______________ g
Percent chemical yield =
massproduct obtained
massproduct exp ected
n
(mmol)
37.98
26.34
37.02
26.34
100  _______________ %
QUESTIONS
1) By dissolving triphenylmethanol in concentrated sulfuric acid, a yellow-orange
coloration is obtained. Explain why by giving the reaction(s) taking place. Explain
why the subsequent addition of water does make the color disappear.
2) Describe a method to prepare an anhydrous solvent.
Lab Manual
42
CHE 2401
EXPERIMENT 6
SYNTHESIS OF PINACOL HYDRATE AND PINACOLONE
OBJECTIVES
 Synthesize an α-glycol from a ketone by a radical reaction.
 Synthesize pinacolone by dehydration of the synthesized α-glycol.
CHEMICALS
APPARATUS & MISC
magnesium turnings (4 g)
250 mL two neck round-bottomed flask
mercury (II) chloride HgCl2 (4.5 g)
100 mL Erlenmeyer flask
anhydrous acetone (38 mL)
50 mL Erlenmeyer flask
anhydrous xylene (60 mL)
condenser
conc. sulfuric acid (10 mL)
CaCl2 guard
sodium sulfate
Bunsen burner
addition funnel
heating mantle, Jack elevator
funnel, ring, stand
Büchner funnel, filter paper
ice
boiling chips
distillation kit
Lab Manual
43
CHE 2401
INTRODUCTION
The synthesis of α-glycols (1,2-diols) can be carried out with a number of methods. It can
either be done from olefins or insaturated aldehydes and ketones. The addition of
halogens (mainly Br2), hypohalogenous acids (HOX) and peroxyacids followed by a
hydrolysis leads to the formation of α-glycols (Scheme 6.1).
C C
OH
C C
X
XOH
C C
C C
X
C C
X
X2
R
O
C
OOH
C C
O
2 OH-
2 OH-
2 H2O
OH
C C
OH
+ 2 X-
OH
C C
OH
+ X-
OH
C C
OH
+ H+
Scheme 6.1 Preparation of glycols from α-olefins and
halogens/hypohalogenous acids/peroxyacids.
Also, the addition to alkenes of metallic oxides, such as dilute MnO4- and OsO4, leads
after hydrolysis to the formation of α-glycols (Scheme 6.2).
C C
C C
1) MnO42) H2O
1) OsO4
2) H2S or
NaHSO3
OH OH
C C
OH OH
C C
Scheme 6.2 Preparation of glycols from α-olefins and metal oxides
Lab Manual
44
CHE 2401
MECHANISM
O
O
Mg
O
Mg 2+
OH
H2O
heat
, 6 H2O
+ Mg(OH)2
pinacol
OH hydrate
O
acetone
H+
heat
H
H
O
O
H
HO
OH
OH
-H+
O
pinacolone
The pinacol rearrangement is formally a dehydration. The reaction is acid-catalysed, and
the first step is protonation of one of the hydroxyl oxygens. Loss of water gives a tertiary
carbocation, as expected for any tertiary alcohol. Migration of a methyl group places the
positive charge on the carbon atom bearing the second –OH group, where oxygen’s
nonbonding electrons help to stabilize the positive charge through resonance. This extra
stability is the driving force for the rearrangement, which converts a relatively stable
tertiary carbocation into an even better resonance-stabilized carbocation. Deprotonation of
the resonance-stabilized cation gives the product, pinacolone.
Lab Manual
45
CHE 2401
REACTION
O
2
acetone
1) Mg/HgCl2
xylene
reflux, 45 min
2) H2O
reflux, 20 min
Compound
Acetone
Magnesium
Mercury (II) chloride
Xylene
Sulfuric acid
Diethylether
Pinacol anhydrous
Pinacol hydrate
Pinacolone
O
, 6 H2O
OH OH
pinacol
M.W. (g/mol)
58.08
24.31
271.50
/
98.08
/
118.17
226.3
100.16
H2SO4
heat
Density (g/mL)
0.714
pinacolone
b.p (oC)
34.5
PROCEDURE
Preparation of pinacol hydrate
To a flame dried 250 mL one-neck round-bottomed flask fitted with an addition funnel
and a water condenser (Figure 6.1), are introduced magnesium turnings (4.0 g).
Next, the glassware is flame dried again to eliminate moisture and a CaCl2 guard is fitted
over the condenser. The setup is allowed to cool down to room temperature before
charging the addition funnel with a solution of HgCl2 (4.5 g) in anhydrous acetone
(38 mL). One fourth of the HgCl2 solution as well as anhydrous xylene (20 mL) are
poured into the round-bottomed flask. Once the reaction is started 20 mL of xylene is
added to the rest of the HgCl2 solution and the mixture is added to the reaction mixture
dropwise over a period of 60 min.
Lab Manual
46
CHE 2401
..
............
.....
....
......
.........
.....
......
........
.....
CaCl2
guard
bromobenzene
+ ether
magnesium
turnings
Figure 6.1: Reaction setup of the preparation of pinacol.
Once the addition is complete, heat under reflux for 45 min. Then, cool down the reaction
mixture, add 10 mL of water and heat under reflux again for 20 min while stirring.
Finally let the reaction mixture cool down to about 50 oC, let it settle and filter it; the
resulting filtrate is pinacol and the residue which is kept in the round-bottomed flask is
the unreacted excess of magnesium. The residual pinacol left in the flask is then extracted
by pouring 20 mL of xylene and heating under reflux for 10 min; the mixture is allowed
to cool down and settle before carrying out another filtration. Finally, the 2 solutions of
pinacol (filtrates containing xylene) are mixed and 10 mL of water is added to them.
Cool down the mixture in an ice bath, observe the precipitation of pinacol hydrate, filter
over a Büchner funnel and dry over filter paper. Weigh the mass of crude pinacol
obtained. Weigh the mass of crude product (pinacol hydrate) obtained.
Preparation of pinacolone
Lab Manual
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CHE 2401
In a 100 mL Erlenmeyer flask containing 15 mL of water, add cautiously 10 mL of
concentrated sulphuric acid H2SO4. A portion of previously prepared pinacol (6 g) is then
added and dissolved into the sulfuric acid solution. Finally the content of the Erlenmeyer
flask is transferred into a round bottomed flask to be distilled. The product of the
distillation is allowed to settle and is then dried. Weigh the mass of product
(pinacolone) obtained.
Lab Manual
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CHE 2401
Experiment 6
Synthesis of pinacol hydrate and pinacolone
Name(s)
Date
Laboratory Instructor
REPORT SHEET
1) Mg/HgCl2
xylene
reflux, 45 min
O
2
acetone
Compound
Acetone
Magnesium
Pinacol anhydrous
Pinacol hydrate
Pinacolone
2) H2O
reflux, 20 min
M.W. (g/mol)
58.08
24.31
118.17
226.3
100.16
O
H2SO4
, 6 H2O
heat
OH OH
pinacol
Density
(g/mL)
0.791
/
/
/
0.801
pinacolone
volume
(mL)
38.0
/
/
/
20.6
mass
(g)
30.06
4.00
19.44
37.23
16.48
n
(mmol)
517.5
164.5
164.5
164.5
164.5
Mass of pure pinacol expected:
_______________ g
Mass of crude pinacol obtained:
_______________ g
Percent crude yield in pinacol =
masscrude pinacol obtained
masspure pinacol exp ected
100  _______________ %
Mass of pure pinacolone expected:
_______________ g
Mass of pure pinacolone obtained:
_______________ g
Percent yield in pinacolone =
Lab Manual
masspure pinacolone obtained
masspure pinacolone exp ected
100  _______________ %
49
CHE 2401
EXPERIMENT 7
SYNTHESIS OF o-CHLOROBENZOIC ACID
OBJECTIVES
 Carry out a diazotization reaction on anthranilic acid to prepare the corresponding
diazonium salt.
 Carry out a Sandmeyer reaction on the diazonium salt to prepare an aryl halide.
CHEMICALS
APPARATUS & MISC
CuCl2, H2O (4.7 g)
100 mL Erlenmeyer flask
copper turnings (3.5 g)
250 mL Erlenmeyer flask
anthranilic acid (5.5 g)
ice-salt water bath
conc. hydrochloric acid (25 mL)
heating mantle, Jack elevator
conc. nitric acid (30 mL)
thermometer
sodium nitrate (2.8 g)
500 mL beaker
glass rod
Büchner funnel, filter paper
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CHE 2401
INTRODUCTION
Primary arylamines react with nitrous acid, HNO2, to yield stable arenediazonium salts,
Ar N N
X,
a process called diazotization reaction. Alkylamines also react with nitrous
acid, but the corresponding alkanediazonium products are so reactive they can’t be
isolated. Instead they lose nitrogen instantly to yield carbocations. The analogous loss of
N2 from an arenediazonium ion to yield an aryl cation is disfavored by the instability of
the cation.
Arene diazonioum salts are useful because the diazonio group (N2) can be replaced by a
nucleophile in a substitution reaction. Many different nucleophiles – halide, hydride,
ccyanide, and hydroxide among others – react with arenediazonium salts, yielding many
different kinds of substituted benzenes. The overall sequence of (1) nitration, (2)
reduction, (3) diazotization, (4) nucleophilic substitution is perhaps the single most
versatile method of aromatic substitution.
Aryl chlorides and bromides are prepared by reaction of an arenediazonium salt with the
corresponding copper(I) halide, CuX, a process called the Sandmeyer reaction.
MECHANISM
Mechanistically, the diazonio replacement reaction occur through radical rather than polar
pathways. In the presence of a copper(I) compound, for instance, it’s thought that the
arenediazonium ion is first converted to an aryl radical plus copper(II), followed by
subsequent reaction to give product plus regenerated copper(I) catalyst.
Lab Manual
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CHE 2401
.
O.
N
H N H
..
H N H
CO2H
+
O N
O
CO2H
N O
+ NO2-
anthranilic acid
NaNO2 + HCl
NaCl + HNO2
fast
2 HNO2
OH
N
.
H N.
H2O + N2O3
CO2H
H
N
Cl
N
CO2H
O
N
.
N.
H
..
OH
N
H N
CO2H
(+ H2O)
CO2H
diazonium
salt
CuCl2, HCl
N
CuCl2
N
Cl
.
CO2H
CO2H
CO2H
CuCl2
(+ CuCl)
radical
(+ N2 + CuCl2)
o-chlorobenzoic acid
N2
Cl
REACTION
NH2
Cl
CO2H
NaNO2, HCl
CO2H Cu/CuCl
2
CO2H
T < 0 oC
anthranilic acid
Compound
Anthranilic acid
Sodium nitrite
Hydrochloric acid
Copper turnings
Copper (II) chloride, dihydrated
o-Chlorobenzoic acid
Lab Manual
o-chlorobenzoic acid
M.W. (g/mol)
137.14
69.00
36.46
63.55
170.48
156.57
Density (g/mL)
b.p (oC)
52
CHE 2401
PROCEDURE
In a 100 mL Erlenmeyer flask introduce CuCl22H2O (4.7 g), 20 mL of water and stir
until complete dissolution. Next, add 15 mL of concentrated HCl, copper turnings (3.5 g)
and heat the mixture until it boils gently. Keep boiling for about 15 min, time after which
a decoloration should be observed. Meanwhile, carry out the diazotization process.
Diazotization
In a 250 mL Erlenmeyer flask containing a mixture of concentrated HCl (10 mL) and
water (50 mL), dissolve anthralinic acid (5.5 g) by heating slightly. Next, cool the
solution in an ice-salt bath. Then, while monitoring the temperature, a solution of sodium
nitrate, containing NaNO2 (2.8 g) and water (10 mL), is added dropwise to the anthranilic
acid solution. The temperature of the mixture should not exceed 0 oC. Once the addition
is over, keep the Erlenmeyer flask in the ice-salt bath.
Sandmeyer reaction
In a 500 mL beaker, add the CuCl2 solution and cool it down quickly below 0 oC. Next,
add the diazonium salt gradually while stirring vigorously with a glass rod. A large
amount of foam is produced due to the release of nitrogen gas. Keep stirring for 30 min.
Then, filter over a Büchner funnel and wash the precipitate, first with cold ~8 M HNO3
(3x20 mL), then with cold water until the filtrate gets colorless. Dry the precipitate over
vacuum. Weigh the mass of crude product (o-chlorobenzoic acid) obtained.
Recrystallize in a mixture water/methanol 90:10 (~ 60 mL), filter out and dry. Weigh the
mass of pure product (o-chlorobenzoic acid) obtained.
Lab Manual
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CHE 2401
Experiment 7
Synthesis of o-chlorobenzoic acid
Name(s)
Date
Laboratory Instructor
REPORT SHEET
NH2
Cl
CO2H
N2
Cl
CO2H Cu/CuCl
2
NaNO2, HCl
CO2H
T < 0 oC
anthranilic acid
o-chlorobenzoic acid
Compound
Anthranilic acid
Sodium nitrite
Copper turnings
Copper (II) chloride, dihydrated
o-Chlorobenzoic acid
M.W.
(g/mol)
137.14
69.00
63.55
170.48
156.57
mass
(g)
5.50
2.80
3.50
4.70
6.28
n
(mmol)
40.1
40.6
55.1
27.6
40.1
Mass of pure o-chlorobenzoic acid expected:
_______________ g
Mass of crude o-chlorobenzoic acid obtained:
_______________ g
Mass of pure o-chlorobenzoic acid obtained:
_______________ g
Percent yield in crude product =
Percent yield in pure product =
masscrude product obtained
masspure product exp ected
masspuree product obtained
masspure product exp ected
100  _______________ %
100  _______________ %
QUESTIONS
1) What is the purpose of washing the anthranilic acid with a HNO3 solution.
2) Give another example of nucleophile that could react with the diazonium salt. Write
the equation.
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CHE 2401
EXPERIMENT 8
SYNTHESIS OF CYCLOHEXANONE AND ADIPIC ACID
OBJECTIVES
 Prepare a ketone by oxidation of an alcohol.
 Observe the difference of oxidizing power of different acids.
Relates to chapter 10 of “Essential Organic Chemistry, 2nd Ed.”.
CHEMICALS
APPARATUS & MISC
cyclohexanol (15 mL)
100 mL Erlenmeyer flask (x 2)
acetic acid (25 mL)
250 mL round-bottomed flask
K2Cr2O7, 2H2O (5 g)
50 mL round-bottomed flask
diethylether (20 mL)
100 mL beaker
dichloromethane (20 mL)
heating mantle, Jack elevator (2x)
anhydrous sodium sulfate (4 g)
thermometer
conc. nitric acid (35 mL)
condenser (2x)
dichloromethane (20 mL)
filter paper
saturated Na2CO3 solution (20 mL)
separating funnel
sodium sulfate
rotary evaporator
conc. nitric acid (17.5 mL)
addition funnel
ice
bain-marie
Lab Manual
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CHE 2401
INTRODUCTION
Cyclohexane is an organic liquid which is consumed worldwide mainly in the production
of precursors to nylon. About half of the world's supply is converted to adipic acid, one of
two precursors for nylon.
By far the majority of the 2.5 billion kg of adipic acid produced annually is used as
monomer for the production of nylon by a polycondensation reaction with hexamethylene
diamine forming 6,6-nylon. Other major applications also involve polymers: it is a
monomer in the production of polyurethane and its esters are plasticizers, especially in
PVC.
Alcohols can be oxidized by dehydration in presence of an acid. Primary alcohols can be
oxidized into aldehydes (mild conditions) or carboxylic acids (harsh conditions).
Secondary alcohols (such as cyclohexane) can be oxidized into ketones (mild conditions)
or carboxylic acids (harsh conditions). Finally, tertiary alcohols are resistant to oxidation
and cannot undergo oxidation whatsoever in acidic media.
REACTION
OH
O
HO
OH
HNO3
reflux, 15 min
acetic acid
70 oC
cyclohexanol
cyclohexanone
O
adipic acid
Compound
Cyclohexanol
Potassium dichromate
dihydrated
Nitric acid
aCyclohexanone
Adipic acid
Lab Manual
O
K2Cr2O7
M.W. (g/mol)
100.16
330.22
Density (g/mL)
b.p (oC)
63.01
98.14
146.14
56
CHE 2401
MECHANISM
H
..
OH
H
H+
H
O H
O
O
Cr
HO
+
O
H
O
O Cr OH
O
..
+ H2O
O
O
+ H3O+ + HO
cyclohexanol
H
H
O
Cr
O
cyclohexanone
NO3
O NO2
O
O
..
H2O
2 HNO3
HO
OH
O
cyclohexanone
+
(+ H3O +
NO2-)
adipic acid
(+ 2 NO + H2O)
PROCEDURE
Oxidation of cyclohexanol with a sulfochromic mixture
In a 100 mL Erlenmeyer flask dissolve potassium dichromate (5 g) in acetic acid (20 mL)
while heating. Once the dissolution is complete, cool the reaction mixture down to 15 oC
by using running cold tap water. Label the flask “Solution 1”.
In another 100 mL Erlenmeyer flask introduce cyclohexanol (10 mL) and acetic acid
(5 mL), stir and cool down in an ice bath for about 10 min. Label the flask “Solution 2”.
Then, pour solution 2 in solution 1, stir to make the mixture homogeneous, and remove
the flask from the ice bath. Insert a thermometer to monitor the temperature which should
not exceed 70 oC. Cool down with running cold tap water is necessary. If no raise in
temperature occurs, heat with a bain-marie while making sure not to exceed 90 oC.
Once the reaction mixture gets green and that the temperature decreases (= end of the
reaction), transfer the reaction mixture in a round bottomed flask, add 30 mL of water,
and distil (Figure 8.1). Transfer the distillate in a separatory funnel, extract the organic
layer with CH2Cl2 (20 mL) (Figure 8.2) and wash it with a solution of saturated Na2CO3
Lab Manual
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CHE 2401
(20 mL) and water (10 mL). Dry, filter and collect the organic layer in a 50 mL round
bottomed flask. Finally, dichloromethane is evaporated off with a rotary evaporator.
Weigh the mass of pure product (cyclohexanone) obtained.
organic
layer
Figure 8.1
aqueous
layer
Figure 8.2
Oxidation of cyclohexanol with nitric acid
This operation MUST be carried out under the fumehood.
In a 250 mL one-neck round-bottomed flask fitted with an addition funnel and a water
condenser (Figure 8.3), introduce nitric acid (17.5 mL) and heat gently until boiling is
about to be reached. Then, stop the heating, add cyclohexanol (5 mL) in the addition
funnel, and add 2 drops to the flask. A vigorous reaction takes place and nitrous vapors
are released. Continue the addition of cyclohexanol dropwise, for 1 hour. During the
addition, the temperature of the reaction mixture should remain close to the boiling point.
Once the addition is over, the mixture is refluxed for 15 min and then transferred into a
100 mL beaker. Cool down at room temperature for 5 min and then at 0 oC in an ice bath.
Filter out the crystals obtained and wash with 10 mL of ice water. Dry over filter paper.
Weigh the mass of pure product (adipic acid) obtained.
Lab Manual
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CHE 2401
Cyclohexanol
Nitric acid
Figure 8.3
Lab Manual
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CHE 2401
Experiment 8
Synthesis of cyclohexanone and adipic acid
Name(s)
Date
Laboratory Instructor
REPORT SHEET
OH
O
K2Cr2O7
acetic acid
70 oC
cyclohexanol
cyclohexanone
Compound
Cyclohexanol
aCyclohexanone
M.W.
(g/mol)
100.16
98.14
Density volume
(g/mL)
(mL)
0.948
10.0
0.947
9.8
mass
(g)
9.48
9.28
n
(mmol)
94.6
94.6
Mass of cyclohexanol acid expected:
_______________ g
Mass of cyclohexanol acid obtained:
_______________ g
Percent yield in cyclohexanone =
Lab Manual
masscyclohexanone obtained
masscyclohexanone exp ected
100  ______________ %
60
CHE 2401
OH
O
HNO3
HO
reflux, 15 min
adipic acid
cyclohexanol
Compound
Cyclohexanol
aAdipic acid
M.W. (g/mol)
100.16
146.14
OH
O
Density
(g/mL)
0.948
/
volume
(mL)
5.0
/
mass
(g)
4.74
6.91
n
(mmol)
47.3
47.3
Mass of adipic acid expected:
_______________ g
Mass of adipic acid obtained:
_______________ g
Percent yield in adipic acid =
Lab Manual
massadipicacid obtained
massadipicacid exp ected
100 
_______________ %
61
CHE 2401
APPENDIX
Lab Manual
62
CHE 2401
APPENDIX
Laboratory equipment
Hardware
Lab Manual
63
CHE 2401
APPENDIX
Chemical glassware
Lab Manual
64
CHE 2401
APPENDIX
Lab kit components
Lab Manual
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CHE 2401
APPENDIX
Lab Manual
66