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CHE 1401

Last update: June 2011 1

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Last Update: July 2015

CHE 2401

Last update: June 2011 1

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Section: ________________________

LLAABBOORRAATTOORRYY MMAANNUUAALL FFOORR

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Last Update: July 2015

CHE 2401

Lab Manual i

TTAABBLLEE OOFF CCOONNTTEENNTTSS

Introduction 1

Laboratory safety 4

Laboratory operations 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 61

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Lab Manual 1

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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Lab Manual 2

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-the-

way 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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Lab Manual 3

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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Lab Manual 4

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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Lab Manual 5

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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Lab Manual 6

2. Never smoke in the laboratory or use open flames in operations that involve low-

boiling 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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Lab Manual 7

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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Lab Manual 8

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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Lab Manual 9

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

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

Figure 2: 19/22

standard-taper joint.

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Lab Manual 10

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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Lab Manual 11

Figure 3: Steps in the assembly of a ground-glass apparatus.

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.

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Lab Manual 12

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.

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

Figure 4: Reading the volume

contained in a graduated

cylinder – in this case, 6.0 mL.

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Lab Manual 13

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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Lab Manual 14

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 Figure 7: Making a fluted filter paper

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Lab Manual 15

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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Lab Manual 16

pressures that would be exerted by the separate pure liquids. (PAo and PB

o) at the same

temperature.

P ≈ PAo + PB

o

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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EEXXPPEERRIIMMEENNTT 11

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)

n-butanol (11.5 mL)

conc. sulfuric acid (2 mL)

10 % sodium hydrogenocarbonate solution (10 mL)

anhydrous sodium sulfate (1 g)

heating mantle, Boy elevator

100 mL round-bottomed flask

water condenser

distillation kit

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:

H

O

O

Ethyl methanoate (ethyl formate)

rum flavouring

O

O

Propyl pentanoate (n-propyl n-valerate):

pineapple flavouring

O

O

Ethyl butanoate (ethyl butyrate)

apple odour

O

O

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:

R1

O

OH + R2 OH R1

O

OR2

+ 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

R1

O

OH + H+

R1

O

OH

H

R1

HO

OH

HR2 OH

R1 OH

O OH

H

R2

R1 OH

O OR2

PT

H

H-H2O

R1

HO

OH

R2

R1

O

O

R2

H

-H+

R1

O

O

R2

ester

carboxylic acid

REACTION

HOOH

O+

O

OH2SO4

acetic acid n-butanol n-butyl acetateheat, 1 h

Compound M.W. (g/mol) Density (g/mL) b.p (oC)

Acetic acid 60.05 1.049 117-118

n-Butanol 74.12 0.81 116-118

Sulfuric acid, 98 % 98.08 1.84 ~ 290

n-Butyl acetate 116.16 0.88 124-126

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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.

Figure 1.1 Figure 1.2

Figure 1.3

organiclayer

aqueouslayer

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Experiment 1

Esterification reaction:

Synthesis of n-butyl acetate

Name(s)

Date Laboratory Instructor

REPORT SHEET

HOOH

O+

O

OH2SO4

acetic acid n-butanol n-butyl acetateheat, 1 h

Compound M.W. (g/mol) Density

(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Acetic acid 60.05 1.049 15.0 15.73 261.9

n-Butanol 74.12 0.81 11.5 9.31 125.6

1.84 n-Butyl acetate 116.16 0.88 16.6 14.59 125.6

Mass of product expected: ___________________ g

Mass of product obtained: ___________________ g

Percent chemical yield= 100exp ectedmass

obtainedmass

product

product ___________________ %

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.

CHE 2401

Lab Manual 22


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




salicylic acid (2 g)

acetic anhydride (3 mL)

conc. sulfuric acid (1 drop)

methanol or ethanol (6 mL)


50 mL beaker

thermometer

glass rod


bain-marie

melting point apparatus

CHE 2401

Lab Manual 23

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:

R

O

Cl + R' OH R

O

OR'

+ HCl

R

O

O + R' OH R

O

OR'

+R

O

R

O

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.

CHE 2401

Lab Manual 24

GENERAL MECHANISM

H+

R2 OH

R1

O

O

R2

ester

acid anhydride

R1 O R1

OO

R1 O R1

OO

H

R1 OH

O

+R1

O

OR2

H

-H+

REACTION httpwww2.volstate.edu/chem/1110/Labs/Synthesis_of_Aspirin.htm

+ O

OO H2SO4

50-60 oC, 15 min

OH

O

OH

O

O

OH

O

salicylic acid acetic anhydride acetylsalicylic acid(aspirin)

+OH

O

acetic acid


Salicylic acid 138.12 / 211

Acetic anhydride 102.09 1.08 138-140

Sulfuric acid, 98 % 98.08 1.84 ~ 290

Aspirin 180.16 / /

CHE 2401

Lab Manual 25

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.

CHE 2401

Lab Manual 26

Experiment 2

Esterification reaction:

Preparation of Aspirin

Name(s)


REPORT SHEET

+ O

OO H2SO4

50-60 oC, 15 min

OH

O

OH

O

O

OH

O

salicylic acid acetic anhydride acetylsalicylic acid(aspirin)

+OH

O

acetic acid

Compound M.W.

(g/mol)

Density

(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Salicylic acid 138.12 / / 2.00 14.5

Acetic anhydride 102.09 1.08 3 3.24 31.7

Aspirin 180.16 / / 2.61 14.5

Mass of pure product expected: _______________ g

Mass of crude product obtained: _______________ g

Mass of pure product obtained: _______________ g

Percent yield in crude product = 100exp ectedmass

obtainedmass

productpure

productcrude _______________ %

Percent yield in pure product = 100exp ectedmass

obtainedmass

productpure

productpure _______________ %

QUESTION

Give an alternative method of synthesis of aspirin, using salicylic acid as a starting

material. Give the mechanism.

CHE 2401

Lab Manual 27


SYNTHESIS OF BENZOIC ACID

AND BENZYL ALCOHOL

OBJECTIVE

Perform the reaction of dismutation of an aldehyde (Cannizzaro reaction)



benzaldehyde (7.5 g)

sodium hydroxyde (4.5 g)

dichloromethane (50 mL)

sodium bisulfate solution NaHSO3 (5 mL)


conc. hydrochloric acid

100 mL beaker

50 mL beaker

bain-marie

separating funnel

funnel, filter paper


pH paper

ice

CHE 2401

Lab Manual 28

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

R H

OOH

R H

O O H

R H

O O

dianionaldehyde

R H

O

R O

O

+R H

O H

tetrahedral

CHE 2401

Lab Manual 29

REACTION

H

O

benazaldehyde

NaOHOH

O

+OH

benzoic acid benzyl alcohol

heat, 30 min2


Benzaldehyde 106.12

Sodium hydroxyde 40.00

Benzoic acid 122.12

Benzyl alcohol 108.14

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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Lab Manual 30

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.

Figure 3.1 Figure 3.2 Figure 3.3

organiclayer

aqueouslayer

CHE 2401

Lab Manual 31

Experiment 3

Synthesis of benzoic acid and benzyl alcohol

Name(s)


REPORT SHEET

H

O

benazaldehyde

NaOHOH

O

+OH

benzoic acid benzyl alcohol

heat, 30 min2

Compound M.W.

(g/mol)

Density

(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Benzaldehyde 106.12 / / 7.50 70.7

Sodium hydroxyde 40.00 / / 4.50 112.5

Benzoic acid 122.12 / / 4.31 35.34

Benzyl alcohol 108.14 1.045 3.65 3.82 35.34

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 = 100exp ectedmass

obtainedmass

acid

acid _______________ %

Percent chemical yield in alcohol = 100exp ectedmass

obtainedmass

alcohol

alcohol _______________ %

QUESTIONS

1) Why do we acidify the aqueous layer? Give the chemical equation of the reaction.

CHE 2401

Lab Manual 32

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.

CHE 2401

Lab Manual 33


NITRATION OF PHENOL

OBJECTIVE

Synthesis and isolation of o-nitrophenol by nitration of phenol followed by steam

distillation.




phenol (6.5 mL)


sodium nitrate NaNO3 (10 g)

250 mL beaker

condenser

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)


CHE 2401

Lab Manual 34

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

OH

OH

OH

OH

NO2

OH

H

NO2

OH

NO2-H+

OH

H NO2

-H+

OH

NO2

o-nitrophenol

p-nitrophenol

phenol

H2SO4 + HNO3 HSO4- + H2NO3

+

H2NO3+ + H2SO4 NO2

+ + H3O+ + HSO4-

HNO3 + 2 H2SO4

NaNO3 + H2SO4 NaHSO4 + HNO3

NO2+ + H3O+ + 2 HSO4

-

nitroniumion

CHE 2401

Lab Manual 35

REACTION

H2SO4

T < 25oC, 30 min

OH

phenol

NaNO3+

OH

o-nitrophenol

+

NO2

OH

NO2

p-nitrophenol

sodiumnitrate


Phenol 94.11

Sodium nitrate 84.99

Sulfuric acid 98.08

o-nitrophenol 139.11

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.

CHE 2401

Lab Manual 36

Experiment 4

Nitration of phenol

Name(s)


REPORT SHEET

H2SO4

T < 25oC, 30 min

OH

phenol

NaNO3+

OH

o-nitrophenol

+

NO2

OH

NO2

p-nitrophenol

sodiumnitrate


(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Phenol 94.11 1.071 6.5 6.96 74.0

Sodium nitrate 84.99 / / 10.00 117.7

o-nitrophenol 139.11 / / 10.30 74.0

Mass of o-nitrophenol expected: _______________ g

Mass of o-nitrophenol obtained: _______________ g

Percent chemical yield = 100exp ectedmass

obtainedmass

product

product _______________ %

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.

CHE 2401

Lab Manual 37


SYNTHESIS OF TRIPHENYLMETHANOL

OBJECTIVE

Perform the addition of a Grignard reagent to a ketone substrate.



bromobenzene (4.2 mL)

magnesium turnings (0.9 g)

benzophenone (4.8 g)

anhydrous diethylether Et2O (40 mL)

diethylether (technical grade – 20 mL)

Calcium chloride

3N HCl solution (60 mL)

sodium sulfate (16 g)

sodium carbonate (2 g)

250 mL two/three neck round-bottomed

flask

addition funnel

condenser

CaCl2 guard

300 mL beaker

rotary evaporator

filter paper

CHE 2401

Lab Manual 38

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.

CHE 2401

Lab Manual 39

MECHANISM

Br

Mg, Et2O

Mg

BrEt2O..

.. OEt2.... O

O

MgBr

bromobenzene Grignardreagent

alkoxideion

H+

OH

triphenylmethanol

REACTION

O

benzophenone

Br

1) Mg, Et2O

2)bromobenzene

3) HCl

triphenyl methanol

OH

, 35 oC, 20 min


Bromobenzene 157.01

Benzophenone 182.22

Magnesium 24.31

Triphenyl methanol 260.33

CHE 2401

Lab Manual 40

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).

.................................... ........................................................................

CaCl2guard

bromobenzene+ ether

magnesiumturnings

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.

CHE 2401

Lab Manual 41

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.

CHE 2401

Lab Manual 42

Experiment 5

Synthesis of triphenylmethanol

Name(s)


REPORT SHEET

O

benzophenone

Br

1) Mg, Et2O

2)bromobenzene

3) HCl

triphenylmethanol

OH

, 35 oC, 20 min

Compound M.W.

(g/mol)

Density

(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Bromobenzene 157.01 1.491 4 5.96 37.98

Benzophenone 182.22 / / 4.80 26.34

Magnesium 24.31 / / 0.90 37.02

Triphenylmethanol 260.33 / / 6.86 26.34

Mass of trimethylmethanol expected: _______________ g

Mass of trimethylmethanol obtained: _______________ g

Percent chemical yield = 100exp ectedmass

obtainedmass

product

product _______________ %

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.

CHE 2401

Lab Manual 43


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.


magnesium turnings (4 g)

mercury (II) chloride HgCl2 (4.5 g)

anhydrous acetone (38 mL)

anhydrous xylene (60 mL)


sodium sulfate

250 mL two neck round-bottomed flask

100 mL Erlenmeyer flask


condenser

CaCl2 guard

Bunsen burner

addition funnel


funnel, ring, stand


ice

boiling chips

distillation kit

CHE 2401

Lab Manual 44

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 CX2 C

X

C

X

2 OH-

C

OH

C

OH

+ 2 X-

C CXOH

C

OH

C

X

2 OH-

C

OH

C

OH

+ X-

C C2 H2O

C

OH

C

OHR

C

O

OOH C C

O+ 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

OH

C

OH

C C

1) MnO4-

2) H2O

C

OH

C

OH1) OsO4

2) H2S or NaHSO3

Scheme 6.2 Preparation of glycols from α-olefins and metal oxides

CHE 2401

Lab Manual 45

MECHANISM

Mg

O

O

Mg

O

O

2+ H2O

heat

OH

OH

, 6 H2O + Mg(OH)2

acetone

pinacolhydrate

H+

heat

O

OH

HH

OH

-H+

O

pinacolone

HOO

H

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.

CHE 2401

Lab Manual 46

REACTION

O

1) Mg/HgCl2xylene

22) H2O

OH OH

pinacolacetone

H2SO4

heat

O

pinacolone

reflux, 45 min

reflux, 20 min

, 6 H2O


Acetone 58.08

Magnesium 24.31

Mercury (II) chloride 271.50

Xylene /

Sulfuric acid 98.08

Diethylether / 0.714 34.5

Pinacol anhydrous 118.17

Pinacol hydrate 226.3

Pinacolone 100.16

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.

CHE 2401

Lab Manual 47

.................................... ........................................................................

CaCl2guard

bromobenzene+ ether

magnesiumturnings

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

CHE 2401

Lab Manual 48

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.

CHE 2401

Lab Manual 49

Experiment 6

Synthesis of pinacol hydrate and pinacolone

Name(s)


REPORT SHEET

O

1) Mg/HgCl2xylene

22) H2O

OH OH

pinacolacetone

H2SO4

heat

O

pinacolone

reflux, 45 min

reflux, 20 min

, 6 H2O


(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Acetone 58.08 0.791 38.0 30.06 517.5

Magnesium 24.31 / / 4.00 164.5

Pinacol anhydrous 118.17 / / 19.44 164.5

Pinacol hydrate 226.3 / / 37.23 164.5

Pinacolone 100.16 0.801 20.6 16.48 164.5

Mass of pure pinacol expected: _______________ g

Mass of crude pinacol obtained: _______________ g

Percent crude yield in pinacol = 100exp ectedmass

obtainedmass

pinacolpure

pinacolcrude _______________ %

Mass of pure pinacolone expected: _______________ g

Mass of pure pinacolone obtained: _______________ g

Percent yield in pinacolone = 100exp ectedmass

obtainedmass

pinacolonepure

pinacolonepure _______________ %

CHE 2401

Lab Manual 50


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.


CuCl2, H2O (4.7 g)

copper turnings (3.5 g)

anthranilic acid (5.5 g)

conc. hydrochloric acid (25 mL)

conc. nitric acid (30 mL)

sodium nitrate (2.8 g)



ice-salt water bath


thermometer

500 mL beaker

glass rod


CHE 2401

Lab Manual 51

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.

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NaNO2 + HCl NaCl + HNO2

2 HNO2 H2O + N2O3

fast

N

O NO

N O

H H..

CO2H

+

NH H

CO2H

N

O

+ NO2-

NH

CO2H

N

OH

NH

CO2H

N

OH

N

CO2H

N

OH H

N

CO2H

N

(+ H2O)

diazoniumsalt

..

..

..

..

anthranilic acid

CuCl2, HCl

Cl

N

CO2H

N

CuCl2

CO2H

(+ N2 + CuCl2)

CuCl2CO2H

Cl

(+ CuCl)

o-chlorobenzoic acid

.

radical

REACTION

NH2

CO2H NaNO2, HCl

N2

CO2HCl

Cu/CuCl2

Cl

CO2H

T < 0 oC

anthranilic acid o-chlorobenzoic acid


Anthranilic acid 137.14

Sodium nitrite 69.00

Hydrochloric acid 36.46

Copper turnings 63.55

Copper (II) chloride, dihydrated 170.48

o-Chlorobenzoic acid 156.57

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PROCEDURE

In a 100 mL Erlenmeyer flask introduce CuCl22H2O (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.

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Experiment 7

Synthesis of o-chlorobenzoic acid

Name(s)


REPORT SHEET

NH2

CO2H NaNO2, HCl

N2

CO2HCl

Cu/CuCl2

Cl

CO2H

T < 0 oC

anthranilic acid o-chlorobenzoic acid

Compound M.W.

(g/mol)

mass

(g)

n

(mmol)

Anthranilic acid 137.14 5.50 40.1

Sodium nitrite 69.00 2.80 40.6

Copper turnings 63.55 3.50 55.1

Copper (II) chloride, dihydrated 170.48 4.70 27.6

o-Chlorobenzoic acid 156.57 6.28 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 = 100exp ectedmass

obtainedmass

productpure

productcrude _______________ %

Percent yield in pure product = 100exp ectedmass

obtainedmass

productpure

productpuree _______________ %

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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SYNTHESIS OF CYCLOHEXANONE AND ADIPIC ACID

OBJECTIVES

Prepare a ketone by oxidation of an alcohol.

Observe the difference of oxidizing power of different acids.



cyclohexanol (15 mL)

acetic acid (25 mL)

K2Cr2O7, 2H2O (5 g)

diethylether (20 mL)



conc. nitric acid (35 mL)


saturated Na2CO3 solution (20 mL)

sodium sulfate

conc. nitric acid (17.5 mL)

100 mL Erlenmeyer flask (x 2)



100 mL beaker

heating mantle, Jack elevator (2x)

thermometer

condenser (2x)

filter paper

separating funnel

rotary evaporator

addition funnel

ice

bain-marie

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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

cyclohexanol cyclohexanoneadipic acid

O

OH

O

HO K2Cr2O7HNO3

reflux, 15 min acetic acid70 oC


Cyclohexanol 100.16

Potassium dichromate

dihydrated

330.22

Nitric acid 63.01

a Cyclohexanone 98.14

Adipic acid 146.14

http://en.wikipedia.org/wiki/Polyurethane

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MECHANISM

OHH

H+

..OH

H

H CrO O

HO O+

OH Cr

O

O

OH

+ H2O..

O

+ H3O+ +

cyclohexanonecyclohexanol

H NO3

OH NO2

H2O..

O

(+ H3O+ + NO2-)

cyclohexanone

2 HNO3

O

OH

O

HO

(+ 2 NO + H2O)

adipic acid

CrO O

HO O

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

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(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.

organiclayer

aqueouslayer

Figure 8.1 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.

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Nitric acid

Cyclohexanol

Figure 8.3

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Experiment 8

Synthesis of cyclohexanone and adipic acid

Name(s)


REPORT SHEET

OH O

cyclohexanol cyclohexanone

K2Cr2O7

acetic acid70 oC

Compound M.W.

(g/mol)

Density

(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Cyclohexanol 100.16 0.948 10.0 9.48 94.6

a Cyclohexanone 98.14 0.947 9.8 9.28 94.6

Mass of cyclohexanol acid expected: _______________ g

Mass of cyclohexanol acid obtained: _______________ g

Percent yield in cyclohexanone = 100exp ectedmass

obtainedmass

onecyclohexan

onecyclohexan ______________ %

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OH

cyclohexanol adipic acid

O

OH

O

HOHNO3

reflux, 15 min


(g/mL)

volume

(mL)

mass

(g)

n

(mmol)

Cyclohexanol 100.16 0.948 5.0 4.74 47.3

a Adipic acid 146.14 / / 6.91 47.3

Mass of adipic acid expected: _______________ g

Mass of adipic acid obtained: _______________ g

Percent yield in adipic acid = 100exp ectedmass

obtainedmass

acidadipic

acidadipic _______________ %

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APPENDIX

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Laboratory equipment

Hardware

APPENDIX

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Chemical glassware

APPENDIX

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Lab Manual 65

Lab kit components

APPENDIX

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APPENDIX

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