55058
Chemistry basic laboratory II
(Organic chemistry)
Organic chemistry laboratory
Department of Chemistry
University of Helsinki 2016
2
Content
General
Glassware etc.
3
6
Working practices
How to perform a reaction
Heating reaction mixture
Mechanical stirring
Isolation
Suction filtration
Extraction
Purification
Recrystallization
Distillation
Sublimation
Chromatography
Synthesis reports
Synthesis
meso-1,2-Dibromo-1,2-diphenyl ethane
Acetyl salicylic acid
Ethyl propionate
Benzoin
Reduction of benzoin with NaBH4
p-Methyl acetophenone
p-Benzoquinone
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10
10
11
12
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12
13
13
14
18
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21
24
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25
26
27
28
29
30
IR-spectroscopy
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GENERAL
Location: Room B147 and B151 (First floor wing B in Chemicum)
Instructors' room telephone number 02941 50426
The laboratory hours 8.30 - 16.45 daily. The laboratory period lasts 2 weeks.
You must be present on the first day of the course at 8.30 o'clock when the work benches are
allocated. You must check the contents of bench drawers according to the list given by the
technician. You are responsible for the broken or lost glassware and will have to pay for them in the
end of the lab period. When you are finished you must check out your glassware (with the laboratory
technician, see the main stockroom) by the last day of the course. If you fail to do the checking-out
you will be required to pay € 40 fine.
Please print the course material before you come to the laboratory. Mandatory absence due to
exams etc. must be agreed with the teacher of the group in advance. The synthesis form and the
product should be given to the teacher for checking as soon as possible.
The course Chemistry basic laboratory II contains seven synthesis. The theory (reaction mechanism)
and the execution as well as the safety matters of the laboratory work is examined in the morning
group wise led by the assistant. It is therefore important to be present right from the start of the
work session. The participants of the course will be divided into groups in such a way, that every
group works on a different synthesis. The members of the group carry out the same synthesis
individually. The student receives a grade for the four last synthesis. The grade is based on the
product yield and purity.
During the synthetic lab work a test on work methods and laboratory safety will be held, which
consists of questions related to safety at work.
Follow the safety regulations: wear safe glasses at all times, no fire in the lab etc. Keep your working
area clean.
The payments
After you have finished working and checked with the assistant that all the experiments have been
correctly entered on your lab card, you should go to the main stockroom (BK 149, 9-11 and 13-15)
to get the bill for the course fee and the broken glassware etc. This must be paid to a bank. When
you show the receipt of the payment to Leena Kaisalo (B213 or by email to
leena.kaisalo@helsinki.fi the course is entered as passed in the study register of the university
(WebOodi).
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For the course you need
• lab coat
• notebook
Essential safety rules
Check the location of:
• exit routes
• fire-extinguishers
• fire-blankets and safety showers
• waste containers
• Find out the properties of the chemicals you are handling
Always:
Handle all chemicals with great care
Keep you working area clean
Attend to spills immediately
Never:
Eat or drink in the laboratory
Always wear eye protection, gloves and laboratory coat in the laboratory
All experiments must be done in fume hoods
Fire safety
• flammable liquids: ether, acetone, petroleum ether etc.
• danger of fire, danger of explosion, fire-fighting equipment
• electrical safety
• how to handle electrical equipment’s safely
Apparatus
• Never heat a closed apparatus
• When heating use stirring or boiling stones. Don’t heat the oil bath over 200°C, use thermometer
in oil bath
• don’t use flame for heating
• don’t evaporate solvents from open vessels.
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Waste handle and dishwashing
Never pour water immiscible organic solvents down the sink
Waste solvent should be poured into appropriately labelled containers
Water soluble waste like discarded water layers from aqueous-organic extractions, ethanol,
neutralized acids and bases can be poured down the sink
Use acetone to rinse your glassware
Hazardous chemicals
• Corrosive reagents: strong acids and bases, oxidizing, reducing, and explosive chemicals and
carcinogens.
• Br2, Na, AlCl3, KCN, NaOH, KOH, LiAlH4, H2, NaBH4, KBrO3, SOCl2, Hg
• Aniline, methanol, phenol, chloroform, methyl iodide, isoforone
• Sodium hypochlorite, H2O2, benzoylperoxide, silica dust.
Br2 can be neutralized with Na2CO3 (aq) and ethanol
• Cyanides can be neutralized by oxidation. Under basic conditions cyanide ion oxidizes for example
with sodium hypochlorite first to cyanate (OCN-) and further to nitrogen gas and carbon dioxide.
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Glassware with
conical joints
erlenmeyer (29/32)
erlenmeyer
(14/23)
thermometer
round bottom flask (29/32)
round bottom flask (14/23)
pear shaped
flask
3-necked flask
dropping funnel
condencer (bulp)
condencer (Liebig)
distillation head
Claisen distillation
head
receiving
adapter
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stopper
(29/32))
knee tube
stopper
(14/23)
CaCl2 tube
(14/23)
adapter 29 to 14
Glassware without conical joints
erlenmeyer
flask
beaker
graduated cylinder
suction flask and
its stopper
extraction
funnel
imupullo
imupullon korkki
mortar and
pestle
Büchner-funnel
gasket
glass funnel
evaporation dish
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test tubes and
rack
watch chromatography
glass jar
glass dish
clamps
pincers
magnet bar
CaCl2 tube
spatula
vacuum desiccator
washing bottle
magnetic stirrer
steel pan (oil bath)
plastic tube
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lifting table
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WORKING PRACTICES
How to perform a reaction
Heating reaction mixtures
Heating reaction mixtures (reflux), recrystallization etc. is done with the apparatus on the following
picture. The condenser prevents the evaporation of the liquid during the heating. In the condenser
the solvent vapours condense into a liquid and the liquid returns into the flask. To prevent over
heating the mixture must be stirred or 1-2 boiling stones should be added into the mixture. If the
boiling point of the heated liquid is under 80 ̊C the water bath is used for heating. In case the boiling
point of the liquid is higher silicon oil bath is used. Use thermometer in an oil bath. Never heat an
oil bath over 200 °C. Avoid getting water in the oil bath because it causes splashing of the hot oil.
Never use closed apparatus for heating because closed system may explode.
bulb
condencer
H2O
clamp
flask
heathing
bath
H2O
magnetic
stirrer
lifting
table
support
stand
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Mechanical stirring
If the reaction mixture is stiff mechanical stirring is used for the efficient stirring for example in
Friedel-Crafs reaction. Fix the stirrer firmly to the support stand. Cautiously test run the empty
apparatus before adding the starting materials.
Note! If you use a dropping funnel with a bypass use a stopper instead of CaCl 2 tubing.
Apparatus for Friedel-Crafts reaction (p-Methyl acetophenone)
Mechanical stirrer
Hose
Rod
PVC-hose
Cotton wool
Addition funnel
3-neck flask
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Suction filtration
stopper for suction flask
Büchner funnel
water aspirator
thick wall tubing
clamp
clamp
suction flask
When solid material is isolated from the reaction mixture (like product precipitates from the
reaction mixture) the suction filtration is used (see the apparatus above). Both suction flasks are
connect to the support stands with clamps. In the Bühner funnel a filter paper of correct size should
be used. The paper should not turn up the edges of the Bühner funnel. Moisten the filter paper with
the same solvent which forms the filtrate. Turn the water aspirator tab on completely and close the
suction flask stopper and start filtering. When the filtration is switched off first release the normal
pressure into the apparatus by opening the suction flask stopper. When drying agent is removed
from the solvent use glass funnel with a small amount of cotton wool.
Extraction
In order to move the reaction product from the water solution into the organic solvent the water
solution is shaken with organic solvent e.g. ether in an extraction funnel.
A separatory funnel is usually made of thin glass and it should be handled carefully. The stopcock of
the separatory funnel is either glass or Teflon. Glass stopcock should be lightly greased before use
so that it turns easily. Support the separatory funnel in a metal ring clamped to a stand. Get into the
habit of placing an Erlenmeyer or beaker under the separatory funnel as soon as you put it in its
ring. Check that the stopper fits well for the glass joint. With the stopcock closed (check!) pour the
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mixture to be extracted and the extraction solvent into the separatory funnel. As a general rule,
never fill the separatory funnel more than two-thirds full.
To carry out the extraction, the aqueous and organic layers have to be thoroughly mixed. After
adding the liquids to the funnel, and before inserting the stopper, it is good idea initially to swirl the
separatory funnel gently. This swirling causes some preliminary mixing of the layers, and is
particularly important when aqueous carbonate or bicarbonate is being used to extract or neutralize
acidic components. Preliminary swirling will reduce the problems from excessive pressure building
up during the extraction. After swirling insert the stopper. More vigorous shaking is needed to mix
the layers. Foe holding a separatory funnel the following method is recommended (see the picture
below). Hold the funnel with both hands. Hold the stopper with one hand and hold the funnel
around stopcock with the other hand, so that you van open the stopcock quickly with your fingers.
If doubt, practise your grip with an empty funnel.
To carry out the extraction, lift the separatory funnel of its support, adjust your grip and invert the
funnel. Immediately open the stopcock to release any pressure. When venting a funnel, never point
the stem towards your neighbours or yourself. After the first venting, close the stopcock and swirl
the inverted funnel for few seconds and repeat the venting procedure. Repeat until the pressure
build-up diminishes. Then shake the funnel 10-20 seconds and vent the funnel at least once during
the shaking process.
Allow the funnel to stand until the layers separate. Remove the stopper and run off the lower layer
into the flask. Before removing the lower layer make sure which layer is which. Check the densities
from literature e.g. CRC Handbook of Chemistry and Physics. Label the flask immediately. Pour the
upper layer out though the neck of the funnel into a clean Erlenmeyer flask, which should be
labelled. Always keep both solutions until you have isolated your organic product.
shaking hold
release pressure
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Purification
Recrystallization
Recrystallization is an important purification method for solid organic compounds. The method is
based on the differences of the solubility between purified compound and impurities. The solid
synthesis products or solid isolated organic compounds are always impure. The impurities are
trapped between the crystals. In practice this type of impure material is purified by dissolving the
crystals into a minimum volume of such hot solvent from which the compound recrystallizes upon
cooling. Due to the small amount of impurities present they stay in solvent which is dilute relative
to the impurities. If the hot solution contains undissolved impurities it must be filtered before the
solvent is cooled down. It is possible to remove coloured impurities from the hot solution by active
charcoal. It is important not to cool the solution too fast. With slow cooling the crystals grow bigger
and are more pure.
If the recrystallization solvent is not known it must be chosen by testing. The ideal solvent for
recrystallization should not react with the compound to be recrystallized, should have a boiling point
that is lower than the melting point of the compound to be recrystallized and most importantly the
compound should be very soluble in hot solvent and insoluble in cold solvent. Unfortunately there
is no rule of thumb how to choose the solvent for recrystallization. Recrystallization of nonpolar
hydrocarbons can be tested from hexane or light petroleum. In the case of ethers and halogenides
can dichloromethane be the solvent of choice. If the compound to be recrystallized has OH-groups
(alcohols, phenols and carboxylic acids) it is worth to try to use ethanol as solvent. Good alternatives
can be found from the CRC Handbook of Chemistry where the solubilities of organic compounds to
the most common solvents are listed.
If suitable recrystallization solvent cannot be found, then a mixture of solvents may have to be used.
A mixed solvent system is a pair of miscible solvents. The solvents should be chosen so that one of
them dissolves the compound readily, and the other one (poor solvent) does not. One method is to
dissolve the solid in the minimum volume of the hot good solvent, then add the poor solvent
dropwise until the solution starts to become slightly cloudy, and the set the solution aside to
crystallize. You can try the following mixed solvent systems:
Class of compound
carboxylic acid
dicarboxylic acid
phenol
amine
nonpolar compound
polar compound
Suggested solvent (better
dissolving)
ethanol
ether, toluene
ethanol, toluene
ethanol
hexane, dichloromethane
propanol
Additional solvent (poor
solvent)
water
water
water
water
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Recrystallization problems: Crystallization does not always work. What if the solvent has been
correctly chosen but no crystallization occurs after cooling in an ice bath? The reason may be over
saturation of the solution. You can attempt to induce the crystallization by adding a seed crystal (is
available) or scratch the side of the flask with a glass rod when the produced micro-fragments of
glass serve as nuclei to induce crystallization. If this fails, try cooling the solvent in ethanol-solid CO 2
bath (-76 °C), and then scratch the sides of the flask as the solution warms up to room temperature.
If the substance still refuses to crystallize, you can concentrate the solution with a rotavapor- and
hope for the best.
Sometimes during the recrystallization the substance separates as an oil rather than as crystals. This
is known as oiling out, and even if the oil solidifies the compound will not be pure, and the material
should be redissolved by heating the solution. You may need to add a little more solvent at this
stage. In this case the stirring may be left on during the cooling and first a dispersion is formed
before the compound crystallizes. The use of seed crystals is also recommended.
Distillation
Distillation is one of the main techniques for purifying volatile liquids in organic chemistry
laboratory. It involves vaporizing the material by heating and subsequently condensing the vapour
back to liquid, the distillate. There are various ways in which the distillation can be carried out. The
choice of the distillation procedure depends on the properties of the liquid that will be purified
and on the properties of the impurities present. The most common distillation methods are:
simple distillation, fractional distillation, distillation under reduced pressure, steam distillation and
so called Kugelrohr distillation. In addition, sublimation, the purification of a solid, without going
through a liquid phase, is also a kind of distillation.
Distillation under normal pressure
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thermometer with a conical joint
Liebig condencer
distillation head
distillation flask
receiving adapter
water out
water in
receiving flask
Transfer the liquid to be distilled to the distillation flask and warm the liquid until the more volatile
compound starts to boil. At this point the boiling point of the compound is measured from the
thermometer. The vapour finds its way into the condenser where it condenses back to liquid and
drops through the receiving adapter into the receiving flask. After the distillation ends or there is a
risk that the liquid is distilled to dryness the distillation is finished or the receiving flask is changed
for the higher boiling compound. Never distil to dryness. The picture of the apparatus for simple
distillation is above. Choose the distillation flask so that the liquid to be distilled fills at least half of
the flask but no more than 2/3. Use magnetic stirring or boiling stones. When the boiling point of
the liquid is under 120 °C use running water in the condenser. When the boiling point is 120-150 °C
use stagnant water and if the boiling point is over 150 °C remove the water from the condenser (air
cooling). Heat the flask first mildly until the liquid starts to boil. When the liquid starts to distil adjust
the heating so that the distillate drops into the receiving flask in a rate 1 drop/second. Stop the
distillation before the distillation flask is completely dry. Many liquids especially alkenes and ethers
may contain peroxides which concentrate in distillation residue and may explode.
Continuous feed distillation
water out
water in
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Continuous feed distillation is used when a
large volume of solvent is distilled from a small
flask. Usually the situation is like that when the
solvent is separated from the product. During
the distillation the liquid is added to the flask
from the dropping funnel. The size of the
distillation flask is chosen so that it is suitable
for the distillation of the mixture which is left
over when the solvent has been distilled away.
This is how can be avoided the situation when
a small amount of compound should be
distilled from a large volume flask. Instead of
continuous feed distillation rotavapor can be
used to remove the solvent
Fractional distillation
It is possible to separate two liquids by normal
distillation only if their boiling points differ
more than 20-50 ºC. If the difference between
the boiling points is too small it is not possible
to get pure distillates. It is easier to separate
compounds if a fractionating column (Vigreux
column) is inserted between the distillation
flask and the distillation head. As the vapour
from the distillation flask passes up through
the fractional column, it condenses on the
column packing and revaporizes continuously.
This makes it possible to separate the lower
boiling compounds from the higher boiling
ones efficiently. Different fractions are
collected in own flasks.
Distillation under reduced pressure
Distillation under reduced pressure is necessary when the boiling point of the liquid is
inconveniently high or the compound to be distilled is solid or when the compound decomposes at
elevated temperatures. In order to get vacuum in the distillation apparatus either water aspirator
or oil vacuum pump is used. When the pressure is reduced the boiling point of the compound to be
distilled reduces. The distillation apparatus is show below. Manometer is used to measure the
pressure and it is incorporated between the receiver adapter and the suction flask. The reduced
pressure within the system is obtained by reading the difference in the mercury levels between the
two halves of the manometer (mmHg). The suction flask is used to prevent water to enter the
receiving flask in case the water aspirator is closed incorrectly before the normal pressure is
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achieved. Always attach the manometer as well as the suction flask with a clamp to support stand.
To prevent over heating during the distillation either stirring or vacuum boiling stones is used. If the
distillation is interrupted new vacuum boiling stones must be added before the distillation is
continued.
The apparatus for vacuum distillation should be tested before the sample is introduced into the
distillation flask. After assembling the apparatus check that all the joints are tight-fitting and that there
are no strains in the apparatus. First open the stopcock of the suction flask, close the stopcock of the
manometer and open the water aspirator completely. After this close the stopcock of the suction flask and
the pressure starts to reduce inside the apparatus. Check the pressure by opening the stopcock of the
manometer. The reduced pressure within the system is obtained by reading the difference in the mercury
levels between the two halves of the manometer (the scale is in mm). Finally close the manometer stopcock
and open the stopcock of the suction flask and you will get normal pressure inside the apparatus.
After testing add the mixture into the distillation flask and add vacuum boiling stones if magnetic
stirring is not used. Repeat the previous steps and start heating after the reduced pressure is stable.
Read the temperature and pressure during the distillation of the compound. Write these values
down for the report. When the compound has distilled stop the heating and let normal pressure
into the system and close the water aspirator.
In the organic chemistry laboratory there are two kinds of vacuum pumps in use: water aspirator is
in each fume hood and there are couple of oil pumps. With the water aspirator 10-20 mmHg can be
reached and with oil pump 0.1-0.001 mmHg (normal pressure is around 760 mmHg). When oil pump
is used the pressure is measured with an electrical pressure meter. Don’t use mercury manometer
with oil pump. In addition when oil pump is used there must be a liquid nitrogen trap between the
distillation apparatus and the oil pump. In order to compare the measured boiling point to the
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literature value the readings must be converted to the same pressure. It can be done by using
graphical nomogram.
Read the boiling point under normal pressure from the scale in the middle and the used pressure
from the scale at the right hand side. Draw a line through these two points and read the boiling
point under reduced pressure from the scale on the left hand side (the point where the line crosses
the scale). For example if a compound boils at 200 °C under normal pressure and the reduced
pressure inside the distillation apparatus is 20 mmHg the boiling point in 20 mmHg is around 80 °C.
There is a boiling point converter in Nettilabra.
Sublimation
Sublimation is closely related to distillation. A solid is converted into a vapour, without going
through liquid phase, which is the recondensed on cold surface in a purified state. Typical
compounds which sublimate are camphor and selenium dioxide. Sublimation is extremely good way
to purify solid compounds which sublimate under normal or reduced pressure.
Sublimation under reduced pressure
Use a sublimator when sublimation is done under reduced pressure. The sample to be sublimed is
placed in the bottom of the outer tube. Use water circulation inside the cold finger. Check that the
stopcock of the suction funnel is open, open the water aspirator (fully open), and close the stopcock
of the suction funnel. Read the pressure from the manometer and close the stopcock of the
manometer. Warm the heating bath to such a temperature that the sublimation occurs. The pure
sublimated compound sticks on the surface of the cold finger and the impurities stay at the bottom
of the outer tube. From time to time the purified solid must be scraped off and to do this you need
to stop heating and open the stopcock of the suction flask in order to introduce normal pressure
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inside the apparatus. Scrap the pure compound from the cold finger with spatula to weighted watch
glass.
Chromatography
Chromatography can be used to separate, purify, or identify compounds. All the chromatography
techniques depend upon differential distribution of various components of the mixture between
two phases – the mobile phase and the stationary phase. The mobile phase may be either a liquid
or a gas and the stationary phase either liquid or solid. Main types of chromatography are column
chromatography, paper chromatography, thin layer chromatography (TLC), gas chromatography
(GC) and liquid chromatography (LC).
TLC-chromatography
Developing tank is a jar with a lid and it should preferably have a flat bottom. The inside of the
development tank is lined with filter paper. Sufficient developing solution (eluent) is placed into the
tank, a 0.5 cm layer in the bottom of the tank is usually sufficient. TLC-plates are usually aluminium
plates covered with stationary phase (e.g. silica gel) as a thin layer. The plates should be cut down
to smaller size (8x2.5 cm is sufficient for 2-3 spots). Handle the TLC-plates with care to avoid
crumbling the delicate absorbent layer.
Mark a line (baseline) about 1 cm from one end of the plate. Make a solution of a small quantity of
your sample in a volatile solvent in which it is soluble (approximately 1 % solution). Dip a TLC-capillar
onto the solution and then touch the loaded capillary onto the silica surface and let dry. Repeat this
with reference compound. Place the TLC plate carefully into the tank making sure that the level of
the solvent does not reach the level of the sample spotted onto the baseline, otherwise the material
will simply be dissolved off the plate instead of being carried up it by the eluent.
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Allow the solvent front to rise in a horizontal straight line up the plate by virtue of capillary action
until it reaches about 1 cm from the top. Finally carefully remove the plate, mark the solvent front
and allow the solvent to evaporate off in the hood. The spots will be visible under UV-light or staining
the plate with a suitable reagent. A useful measurement that can be made from the developed TLC
plate is the relation between the distance moved by the compound spot and the distance moved by
the eluting solvent: this is the retention factor Rf.
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Synthesis reports (Basic chemistry laboratory II)
From each synthesis a synthesis form is filled and it is given in with a reaction mechanism,
interpreted IR-spectrum and melting point printout as well as TLC-plate in.
Read the chapter How to fill in a synthesis form on page x.
Synthesis forms can be found from Nettilabra.
Reaction mechanism: Draw the reaction mechanism clearly to the reversed side of the synthesis
form.
How to interpret IR-spectra:
You can write the interpretations on the printed spectra.
Try to find all the absorptions of the functional groups and bonds present in your
compound.
It is recommended that the fingerprint area (wave number < 1500 cm -1) should not be
interpreted in detail.
Write on the spectrum:
The measured wave number (cm-1)
Interpretation (functional group and bond)
The literature value of the wave number
The intensity of the absorption s, m, w (from the literature)
Literature reference
TLC plates (not from all synthesis):
Draw under UV-light the outlines of the visible spots
Attach the TLC plate on the synthesis form with adhesive plastic so that the plastic
covers the whole plate. This prevents the silica layer to crumble.
Write next to the plate what was the eluent
Calculate the Rf-value
Stable the pages together. The report must be given in as soon as possible.
The synthesis product must be given in to the teacher with the form. Place the synthesis product
into a small vial. Label the vial with your name and the name of the product.
If you get your report back for corrections do them carefully and give the report in within three days.
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HOW TO FILL IN THE SYNTHESIS FORM
Fill in all the applicable parts.
Name of the synthesis product
Literature reference for the procedure and reaction mechanism
Reaction scheme and to the reverse side reaction mechanism
Information about the starting materials and product
Molecular weight M
Mass m
Density r (for liquids)
Volume (for liquids)
Moles
eqv=mole ratio of starting
materials
Yield %
Melting point (Mp)
Boiling point (Bp)
Refractive index (nD20)
Numerical values
Accuracy
integer
one decimal accuracy
accuracy of the literature
value
one decimal accuracy
with two significant
numbers
one decimal accuracy
integer
one degree accuracy
one degree accuracy
if measured under reduced
pressure also mark the
pressure
accuracy of the
refractometer
Unit
g/mol
g
(g/mL)
mL
mol
%
̊C
̊ C / mmHg
e.g. 75 ̊ C /15 mmHg
-
Note! Use precise numerical values when calculating but fill in the form in round numbers.
The yield of a synthesis is the amount of the pure product(s). Theoretical yield (100 % yield) is
calculated according to the equilibrated reaction scheme. Theoretical yield is always calculated from
the starting material which is used least according to the stoichiometry.
The own yield is expressed as per cents from the theoretical yield.
Determination of purity
It is possible to determine the purity per cent and the purity class of crystalline product with the aid
of the melting point. In case of liquid product from the measured refractive index indicates only
whether the purity class is 1 or 2. If needed the exact purity class of a liquid can be determined by
gas chromatography if there are no non-volatile compounds present.
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State of the Difference from the literature
product
value
solid
ΔT ≤ 1 °C
1 °C < ΔT ≤ 3 °C
3 °C < ΔT ≤ 5 °C
ΔT > 5 °C
purity %
99 %
over 97 %
around 95 %
Technical chemicals
Product must be
purified again
purity class n
1
2
3
4
ΔnD20 ≤ 0,001
1
(Basic chemistry lab II ≤0,003)
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ΔnD > 0,001
2
(Basic chemistry lab II >0,003)
Product with purity class n=1 must be of uniform quality and the colour must be the same as in the
literature. Sometimes it is possible to determine by e.g. gas chromatography.
liquid
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SYNTHESIS
meso-1,2-Dibromo-1,2-diphenyl ethane
Reaction mechanism is an electrophilic addition to the double bond
Reagents
1 g trans-stilbene
10 mL of dichloromethane
10 mL 10 % (w/v) solution
of bromine in
dichloromethane bromin
(solution conains 0,1 g Br2/1
mL)
cyclohexene
5 mL dichloromethane
Safety notes
Bromine is extremely
poisonous and corrosive.
It has to be handled in
fume cupboard. Wear
protective gloves.
Equipment
50 ml round-bottomed
flask (14/29)
small graduated cylinder
suction filtration apparatus
watch glass
Procedure
Dissolve 1.0 g of trans-stilbene in 10 mL of dichloromethane in a 50 mL roundbottomed flask. Stir the solution
with magnetic stirrer and add 10 mL of a 10% solution of bromine in dichloromethane (0,10 g of bromine/
1.0 mL). If the colour of bromine disappears completely, add bromine dichloromethane solution in 1 ml
portions until the colour of the bromine stays permanently. The developing dibromocompound precipitates
from the solution. Add to the reaction mixture cyclohexene in drops until the extra bromine is destroyed.
Stop adding the cyclohexene when the colour of the bromine disappears. Cool the solution in an ice bath to
complete the precipitation.
Isolation
Collect the product by suction filtration. Wash it in the funnel with 5 ml of ice cooled dichloromethane. Dry
the product by sucking air though the funnel. Transfer the dry product to a watch glass and weight the dry
product. The yield of the product is 75%. The melting point of the product is 241-243 °C.
Product characterization
Measure the melting point and run an IR-spectrum of the product. Check the purity of the product by TLC
(1:2 dichloromethane:petroleum ether)
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Acetylsalisylic acid (Aspirin)
Reagents
· 5.0 mL of acetic anhydride
· 2.8 g of salicylic acid
· 3-4 drops of conc. sulfuric
acid
Safety Notes
Equipment
Acetic anhydride is volatile
and a strong irritant.
Sulfuric acid is corrosive
· 100 mL roundbottomed
flask (14/29)
· magnetic stirrer
· water and ice baths
· suction filtration apparatus
· Büchner funnel
· rubber stopper
· 2 filter flasks
· roundbottomed
flask,
condenser, oil bath
Procedure
Place 2.8 g of salicylic acid in a dry 100 mL roundbottomed flask, then add 5.0 mL of acetic
anhydride and 3-4 drops of concentrated sulfuric acid. Mix the resulting white slurry with a magnetic
stirrer, and place the flask in a warm water bath (45-50°C) for 15 min. Allow the flask to cool and
add 50 mL of water and break up any lumps with a spatula.
Isolation and purification
Allow the mixture to stand for an additional five minutes, then chill the flask in an ice bath and
remove the crystals by suction. Crystallize the crude aspirin from warm 30% ethanol water mixture
not exceeding 80°C (see experimental note). Allowing the mother liquor to stand overnight may
produce a second crop of crystals. Airdry the crystals and determine the per cent yield and melting
point (mp. for aspirin is 135°C). The yield is 80%.
Experimental note: At temperatures exceeding 80°C, aspirin forms an oil that dissolves organic
impurities from water; in this case it may be difficult to redissolve the aspirin in water.
Product characterization
Measure the melting point and run an IR-spectrum of the product.
27
Ethyl propionate
The reaction in question is an acid catalyzed esterification. Propanoic acid is protonated by the acid
used as a catalyst. The emerging cation is resonance stabilized. Ethanol acts as a nucleophile as it
attacks the cation. This is followed by the transfer of a proton and the loss of water. The reaction is
a nucleophilic substitution.
Reagents
· 10 mL abs. ethanol
· 14 mL propanoic acid
· conc. sulfuric acid
· 40 mL ether
· 2M NaHCO3 solution
· MgSO4
Safety Notes
Concentrated sulfuric acid is
highly corrosive.
Ether is a highly flammable
and volatile liquid.
Ethanol is a highly flammable
and volatile liquid.
Equipment
· reflux apparatus
· extraction/separation
equipment
· apparatus for continuous
feed distillation
Procedure
In a 50 mL roundbottomed flask mix 10 mL of ethanol and 14 mL of propanoic acid. Carefully add
2-3 drops of concentrated sulfuric acid (catalyst) and mix the solution well with magnetic stirrer.
Reflux the mixture for one hour using an oil bath. Let the reaction mixture cool.
Isolation and purification
Pour the cool reaction mixture into a separatory funnel filled with 40 mL of water. Add 40 mL of
ether into the funnel, stopper, and shake it gently (wear safety glasses!). Release any pressure inside
the separation funnel by turning the stoppered funnel upside down and opening the stopcock. Let
the funnel rest (upright, stopcock closed) until the layers are separated. Let the aqueous layer (the
lower one) drain from the funnel into a different vessel. Wash the ether layer that remains in the
funnel with 20 mL of water (shake it with the added water).
Once the layers have separated, the aqueous layer is drained. Wash the ether solution with 2 M
NaHCO3 solution to remove any unreacted acid. It is essential that you are especially careful at this
stage since carbon dioxide is produced when the acid is neutralized. The gas causes pressure inside
the separatory funnel. The pressure is released as described above. The acid is now present in the
aqueous layer as the Na salt. Finally wash the ether solution with 20 mL of water. Remove the
aqueous layer as thoroughly as possible and then dry the ether solution with anhydrous magnesium
sulfate. After 30 minutes of drying, filter the solution through a regular glass funnel fitted with a
clean cotton plug into a dropping funnel. Part of the ether solution is poured into a roundbottomed
28
flask and magnetic stirrer bar is added. The ether is removed by a distillation procedure used for the
removal of large amounts of solvent (bp. of ether = 35°C). The flask can be heated either in a water
or oil bath.
The product is purified by distillation. The boiling point of ethyl propanoate is 99°C (oil bath). The
product yield is 60 %.
Product characterization
Measure the refractive index and run an IR spectrum of the product
Benzoin
Aromatic aldehydes when treated with an alkali cyanide, usually in aqueous solution, undergo
condensation to the hydroxyketone or benzoin (called benzoin condensation). α The best known
example is the conversion of benzaldehyde to benzoin.
For the mechanism see: A. Streitwieser, C. H. Heathcock and E. M. Kosower, Introduction to
Organic Chemistry, 4. edt.; Macmillan, New York 1992, p. 867.
Reagents
· 2.5 mL of benzaldehyde
· 35 mL of techn. alcohol
· 0.25 g of potassium cyanide
Safety Notes
Potassium cyanide is a
poisonous and corrosive solid.
For the disposal of cyanide
compounds see (in Finnish):
P. Tilus, ja T. Asikainen,
Turvallinen työskentely
laboratoriossa, Helsingin
Yliopisto 1996, p.40.
Benzaldehyde is an irritant.
Equipment
· reflux apparatus
· water bath
· Erlenmeyer flask
· suction filtration apparatus
Procedure
In a 50 mL roundbottomed flask place 5 mL alcohol, 2.5 mL purified benzaldehyde and 0.25 g
potassium cyanide dissolved in 4ml of water (CARE! This preparation must be done in the hood!
29
Assumed purity of KCN is 96-98%). Attach a reflux condenser and heat on a boiling water bath for
30 minutes. Cool the flask in icewater, filter the crude benzoin and wash it with water and drain dry.
Isolation and purification
Recrystallize the crude product from ethanol; the benzoin is obtained as a white crystalline solid,
m.p. 137 °C, the yield of the pure product being 2.1 g.
Product characterization
Measure the melting point and run an IR spectrum of the product.
Reduction of benzoin with sodium borohydride –
1,2-Diphenylethane-1,2-diol
The stereochemical course of ketone reductions can be influenced by the presence of hydroxyl
groupsclose to the carbonyl function. This experiment illustrates the stereoselective reduction of
benzoin using sodium borohydride as reducing agent.
For the mechanism see the course folder Orgaanisen kemian perustyöt I in the assistant room.
Reagents
· 2.00 g benzoin
· 0.40 g sodium borohydride
· ethanol
· hydrochloric acid (6 M)
Safety Notes
Benzoin is irritant
NaBH4 is corrosive, flammable
Etanoli is flammable,
HCl is corrosive
Equipment
· magnetic stirrer
· suction filtration apparatus
· recrystallization apparatus
Procedure
Dissolve the benzoin in 20 mL of ethanol in a 100 mL Erlenmeyer flask. 1 Stir the solution magnetically
and add the sodium borohydride in small portions over 5 min using a spatula. 2 If necessary, rinse in
the last traces of sodium borohydride with 5 mL of ethanol. Stir the mixture at room temperature
for a further 20 min. and then cool it in an ice bath whilst adding 30 mL of water followed by 1 mL
of 6 M hydrochloric acid.3 Add a further 10 mL of water, and stir the mixture for a further 20 min.
1) Warming may be necessary; solution need not be complete.
2) Care! Exothermic
30
3) Foaming may occur!
Isolation and purification
Collect the product by suction filtration, and wash it thoroughly with 100 ml water. Dry the product
by suction for 30 min, and record the yield. Recrystallize from ethanol-water
(1:1). Yield 90 %.
Product characterization
Check the purity by tlc (silica plates; eluent ethyl acetatehexane1:1). Measure the melting point and
run a IR spectrum of the product.
p-Methyl acetophenone
Mechanism: A. Streitwieser, Jr., C. H. Heathcock and E. M. Kosower, Introduction to Organic
Chemistry, 4. p.; Macmillan, New York 1992, s. 696.
Reagents
15 g AlCl3
25 mL toluene
4,8 mL acetic anhydride
anhydrous MgSO4
Safety Notes
Aluminium chloride produces
HCl when it comes into
contact with dampness of the
air and reacts violently with
water. AlCl3 dust is harmful
when inhaled.
Toluene: flammable.
Acetic anhydride:lachrymator,
corrosive.
Equipment
· 100 mL 3-necked
roundbottomed flask
· dropping funnel
· CaCl2tube
· mechanical stirrer
· reflux condenser
· PVC-tube
· glass funnel
· 250 mL beaker
· oil bath
· separation/extraction
apparatus
· vacuum distillation apparatus
Procedure
(A. I. Vogel, A TextBook of Practical Organic Chemistry, 3. edt., Longman, London 1970, p. 730)
In a 100 mL 3-necked flask, equipped with a separatory funnel carrying a calcium chloride tube, a
mechanical stirrer, and an efficient reflux condenser attached to a gas absorption device, place 15
g of finelypowdered, anhydrous aluminium chloride and 25 mL of toluene. Set the stirrer in motion
and add 5.1 g (4.8 mL) of acetic anhydride slowly through the addition funnel; the addition requires
31
15 minutes, during which time the temperature rises to about 90°C and much hydrogen chloride is
evolved. Heat the mixture on a water bath, with stirring, for 30 minutes or until there is practically
no evolution of gas. Cool the reaction mixture to room temperature and pour it into a mixture of 30
g of crushed ice and 30 mL of concentrated hydrochloric acid: stir until the aluminium salts dissolve
completely.
Isolation and purification
Separate the toluene layer, wash it with water, then with 10 per cent sodium hydroxide solution
until the washings remain alkaline, and finally with water: dry over anhydrous magnesium sulphate.
Distill the residue using a Claisen adapter at atmospheric pressure until the temperature rises to
about 125°C, then allow to cool and distil under reduced pressure. Alternatively, toluene may be
removed with a rotary evaporator. Collect the p-methylacetophenone at 93-94° C/7 mm (the b.p.
at atmospheric pressure is 225°C); the yield is 5.8 g.
Product characterization
Measure the refractive index and run an IR spectrum of the product.
p-Benzoquinone
Reagents
· 2.5 g of hydroquinone
· 1.4 g of potassium bromate
· 1.2 mL of sulfuric acid (2 M)
Safety Notes
Hydroquinone is harmful
KBrO3 is oxidative,
explosive
NOTE! The product is highly
toxic and flammable as an
airdust mixture.
Equipment
· 100 mL flask (14/29) +
stopper
· suction filtration apparatus
· sublimation apparatus
Procedure
Place potassium bromate (1.4 g), 2 M sulfuric acid (1.2 mL), water (25 mL) and hydroquinone (2.5 g)
into a 100 mL roundbottomed flask. Close the flask with a stopper and stir the mixture for about 30
minutesat room temperature. The reaction is over when the initially black mixture turns yellow
(yellowish green).
Isolation and purification
32
Filter by suction filtration, wash with ice cold water and spread the product on filter paper until it is
dry. Purify the obtained crude product by sublimation under vacuum. p-Benzoquinone gives a yield
of 1.3 g and has its melting moint at 115°C.
Note: The product is water soluble. This means that over eager washing will diminish the amount of
product that is left in the funnel. The impure product in particular decomposes easily so that it is
important that there is no delay in the isolation and purification of the compound.
Product characterization
Measure the melting point and run an IR spectrum of the product.
33
Infrared spectroscopy
Interpretation of IR spectrum
Most of the functional groups absorb IR radiation in the region between 4000-1500 cm- 1. This region
should be interpreted first by comparing observed absorptions with literature tables. Polar groups
absorb often in smaller frequency and the absorption bands are broad due to hydrogen bonding (e.g.
hydroxyl and amino groups). Absorptions in the region between1400-900 cm-1 (so called fingerprint
region) are usually hard to interpret because in this region there are a large variety of different kind
of absorptions. Absorptions in this region should be interpreted with caution. The substitution pattern
of aromatic ring can be found under 900 cm-1.
Try to find from the spectrum functionalities like hydroxyl groups (alcohols, phenols), amino group
(amines, amides), carbonyl groups (aldehydes, ketones, esters, amides, carboxylic groups (broad OH
and carbonyl group). Also try to find out if there is absorptions from the aromatic compound.
On the table below there is a short list of the most common IR-absorptions of organic compounds.
Literature:
T. Hase, Tables for Organic Spectroscopy, Otatieto, Espoo
E. Pretsch, P. Bühlmann, C. Affolter, Structure Determination of Organic Compounds, Springer
2000.
D.H. Williams, I.Flemming, Spectroscopic methods in organic chemistry, 5. ed. , McGraw-Hill Book
Company Limited, Maidenhead, 1989.
34
Compound
Alkane
Alkene
Aromatic
Alcohol &
phenol
Amine
Aldehyde &
ketone
Carboxylic acid
& derivatives.
Nitriles
Most common IR-absorptions for organic compounds.
Band (cm-1)
Size
Bond
2850-3000
s
CH3, CH2 & CH
2 or 3 peaks
1350-1470
m
CH2 & CH3
1370-1390
m
CH3
3020-3100
m
=C-H & =CH2
1630-1680
v
C=C (symm. weak)
3030
v
C-H
1600 & 1500
m-w
C=C (ring)
690-900
s-m
C-H (ring)
substitution:
730-770 ja 630-710
s
5 adjacent H
735-770
s
4 adjacent H
750-810
s
3 adjacent H
800-860
m-s
2 adjacent H
860-900
m
isolatedH
3580-3650
v
3200-3550
s
1330-1430
970-1250
m
s
3400-3500
3300-3400
1550-1650
2690-2840 (2 piikkiä)
1720-1740
1710-1720
1690
1675
2500-3300 (acids)
peittää C-H –
värähdykset
1705-1720 (acids)
1210-1320 (acids)
1785-1815 (COX)
1750 & 1820
(anhydrides)
1735-1750 (esters)
1000-1300 (esters)
1630-1695 (amides)
1590-1650
1500-1560
2240-2260
w
w
m-s
m
s
s
s
s
s
s
m-s
s
s
s
s
m
m
m
m
O-H (vapaa), sharp
O-H (H-sit.), broad
O-H
C-O
N-H (prim.)2 peaks
N-H (sek.) 1 peak
NH2
C-H (aldehydes)
C=O (aldehydes)
C=O (ketones)
Arylketone
a,b-unstaur.
O-H (very broad)
Absorption type
n
d
d
n
n
n
n
d
d
d
d
d
d
n
n
d
d
n
n
d
n
n
n
n
n
n
C=O (H-bonded.)
C-O
C=O
C=O (2 peaks)
n
n
n
n
C=O
C-O (2 peaks)
C=O (amide I)
N-H (amide II)
N-H (amide II)
n
d
n
Size: s=strong, m =medium, w= weak, v=variable.Absorption type: n=stretsing, d=bending