Download Crystallization and Determination of Melting and Boiling Points

Experiment
1
Crystallization and Determination of Melting and
Boiling Points
by Anawat Ajavakom
Objectives
1)
2)
3)
To perform a purification of organic compounds by crystallization.
To determine melting point and boiling point of unknown compounds.
To become familiar with general apparatus in organic chemistry laboratory.
Principles
1. Crystallization
Solid organic compounds are usually purified by crystallization. This general
technique involves dissolving the impure material in a minimum amount of hot solvent
and cooling the solution slowly. The dissolved material has lower solubility at lower
temperature and a solid material will form as the solution is cooled down. This process is
called either ‘crystallization’ if the crystal growth is relatively slow and selective or
‘precipitation’ if the process is rapid and yields smaller crystals.
In microscale organic laboratory, there are two common methods for crystallization;
1) Semi-microscale crystallization (for solid material of more than 0.1 g).
2) Microscale crystallization (for solid material of less than 0.1 g)
In this experiment, you will perform a semi-microscale crystallization using 0.5 g of
solid unknowns, which could be either benzoin or benzoic acid.
COOH
O
OH
Benzoin
Benzoic acid
Four main steps in semi-microscale crystallization are;
1)
2)
3)
4)
Dissolving the solid
Removing insoluble impurities (if necessary)
Crystallization
Isolation of crystals
2. Melting Points and Boiling Points
Physical properties that are useful for distinguishing compounds include color,
melting point, boiling point, density, and reflective index. In this experiment, we will learn
how to determine melting and boiling points.
-1-
Melting Points
The melting point is used by organic chemists not only to identify compounds, but
also to verify their purity. To measure the melting point, a small amount of sample is
heated in an apparatus equipped with a thermometer while two temperatures are noted.
The first is the point at which the first drop of liquid forms among the crystals; and the
other is the point at which the whole mass of crystals turns to a clear liquid. The melting
point is recorded as a range of temperatures, for example 180-182 °C. Pure compounds
usually have narrow melting temperature ranges (within 1-2 degree).
Melting point can be used as supporting evidence in identifying a compound as well.
Not only can we compare melting points of two individual compounds, a procedure called
‘mixed melting point’ may be used with the same compound taken from different
sources. Since melting point is a unique physical property, the mixture of two samples
would have a narrow melting range if the mixture composes of just one compound. On
the other hand, the observed melting ranges would be broad if the mixture composes of
two different compounds.
Boiling Points
When a liquid is heated, its vapor pressure increases until it equals the atmospheric
pressure. And at this temperature, the liquid starts to boil. The normal boiling point is
measured at 760 mmHg or 1 atm. However at lower pressures, the vapor pressure
needed for boiling is also lower, and so the liquid boils at lower temperature. (Look at the
reference, fig 6-8 p.606.)
Experimental Procedure
Part A
1)
Obtain a sample from your instructor. Record sample number.
2)
Keep 10 mg (or about 2 grains of rice) in a watch glass for melting point
determination and place the same amount in each of two test tubes.
3)
Add 10 drops of ethanol in one test tube, and 10 drops of water in another.
4)
Gently shake both test tubes and observe the solubility at room temperature.
a) If the sample completely dissolves in just one tube, your solvent for crystallization
is the one that cannot dissolve your sample at room temperature.
b) If the sample does not dissolve in both tubes, place the tubes in a steam bath for
30 seconds and observe the solubility. Your solvent for crystallization is the one
that can dissolve your sample at high temperature.
c) Report the solvent of choice before proceeding to the next step.
5)
Place the rest of your sample in a 50 mL Erlenmeyer flask, follow by 5 mL of your
solvent.
6)
Heat the mixture on a hotplate and swirl occasionally. Do not allow the mixture to
boil vigorously. If sample doesn’t completely dissolve when the solvent starts to boil,
add a small amount of solvent until a clear solution is obtained. However, impurities
or some black particles may still exist.
-2-
7)
Setup a hot filtration kit as shown in the picture below. Filter paper is available in the
supply room. Consult your instructor on how to transfer and filter a hot solution.
Glass funnel
with filter paper
Empty
flask
Solution to be
filtered
Figure 1
8)
When the hot filtration is finished, remove the flask from the hot plate and set aside.
Wait for the crystals to grow and do not move the flask around. You may measure
the melting point of unpurified sample while waiting (see step 10).
9)
Vacuum filter and dry the crystals by placing them on a watch glass heated on a
steam bath. Use a glass rod to gently turn the crystals, ensuring thorough drying.
10) Put the unpurified sample into a capillary tube (about 4-5 mm in height). Attach the
tube to a thermometer with sewing thread and set the apparatus as in Figure 2.
Thermometer
Clamp
50 mL Beaker
Sewing thread
Paraffin Oil
Sample in
capillary tube
Hotplate
Figure 2
-3-
11) Turn on the hotplate and observe the melting point. Use a clean glass rod to stir the
paraffin oil to ensure a uniform heat distribution.
12) Record the temperatures
a) when the sample starts to melt.
b) when the melting process is finished.
13) Allow the paraffin oil to cool down and repeat step 10) to12) with the purified sample.
Part B
1)
Obtain an unknown liquid sample from your instructor. Record the sample number.
2)
Attach a clean and empty test tube to a thermometer with sewing thread. Put an
empty capillary tube in the test tube so that the open end of capillary is down. Set up
the apparatus as in Figure 3.
Thermometer
Clamp
Test tube
50 mL Beaker
Capillary
Close end
Capillary tube
Capillary
tube
Sewing thread
Paraffin Oil
Sample in
test tube
Capillary
Open end
Hotplate
Figure 3
3)
Ensure that the paraffin oil is not hot and place 2-3 mL of sample in the test tube.
4)
Turn on the hot plate and use a clean glass rod to stir the paraffin oil to ensure a
uniform heat distribution.
5)
Record the temperatures when rapid air bubbles come out from the capillary
6)
Turn off the hot plate and carefully insert a ceramic tile between the beaker and the
hotplate.
7)
As the temperature decreases, air bubbling will gradually slow down. Record the
temperature when you see the last bubble comes out and the liquid goes into the
capillary tube
8)
Report the boiling point to your instructor. If a repetition is needed, allow the paraffin
oil to cool, then replace the capillary tube with a new one. Add more liquid sample if
necessary and repeat step 4) to 7).
-4-
Safety Precautions
Wear safety goggles and lab coat at all times.
Reference
D. L. Pavia, G. M. Lampman, G. S. Kriz, R. G. Engel, Introduction to Organic Laboratory
Techniques, A Microscale Approach, Part 5, 577-616.
-5-
Experiment
Extraction and Simple Distillation
2
by Anawat Ajavakom
Objectives
1) To separate neutral, acidic, and basic compounds in a mixture by extraction.
2) To become familiar with separatory funnel and other general apparatus in organic
chemistry laboratory.
3) To perform a simple distillation of organic compounds.
Principles
To isolate pure components from a mixture, many practical techniques can be
chosen depending on the difference in physical and chemical properties. Extraction is a
very simple way for isolation. It can be used with mixtures containing neutral, acidic, and
basic compounds, for example, the isolation of benzoin (a neutral component) and
benzoic acid (an acidic component) from a mixture given to you in this experiment.
COOH
O
OH
Benzoin
Benzoic acid
Both benzoin and benzoic acid are white solid substances which can dissolve in
dichloromethane (CH2Cl2). With the difference in acidity, these two compounds can be
separated by acid-base extraction method as outlined in the flow chart.
Mixtur e of benzoin and benzoic acid
dissolved in CH 2Cl2
Shake with diluted NaOH
Or ganic layer
Aqueous layer
Benzoin
in CH2Cl2
Sodium benzoate
in water
Dry and evaporate
CH2Cl2
Benzoin
Add cold conc. HCl
W hite Pr ecipitate
Filter
Benzoic acid
-6-
-
-
Acidic compounds (HA) react with bases (OH ) to give their conjugated bases (A )
and water, as described in equation (i).
HA
+
OH-
A-
+
H2O
(i)
Experimental Procedure
Part A
1)
Obtain a mixture from your instructor. This mixture consists of approximately equal
weights of benzoin (neutral) and benzoic acid (acidic).
2)
Weigh 1g of the mixture and dissolve with 20 mL of CH2Cl2 in a 50-mL separatory
funnel. Swirl until solid dissolves completely.
3)
Add 8 mL of 10% NaOH into the separatory funnel. Shake the funnel carefully for 10
seconds as demonstrated by your instructor. (*Remember to hold the separatory
funnel with both hands and to vent it frequently with the lower end pointed upward
and away from other people.) Settle for a few minutes and split the layers into two
separate flasks.
4)
Transfer the organic layer into the separatory funnel. Add a new portion of 8 mL of
10% NaOH into the separatory funnel. Shake, settle, and split the layers. Transfer
the lower organic layer in a flask and keep the upper aqueous layer in the funnel.
5)
Combine the first aqueous portion with the solution in the funnel. Add 15-mL of
CH2Cl2. Shake, settle, and split the layers. Combine the CH2Cl2 layers with that from
step 4). Transfer the aqueous layers into another flask for experiment in Part B.
6)
Wash the organic solution by shaking with 10 mL of water. Discard the aqueous
layer. Dry the organic layer over anhydrous sodium sulfate (Na2SO4) (roughly about
2-3 tea spoons). After standing for a few minutes, this organic solution should be
clear. If not, consult your instructor.
7)
Gravity filter the CH2Cl2 solution into a 50-mL round bottom flask and evaporate the
solvent by distillation. The distillation set should be prepared as shown in Figure 1
(Don’t forget to place a lab jack underneath the hot plate so that the heating source
can be instantly removed in case of EMERGENCY.) Consult your instructor before
heating the distillation set.
8)
Observe the temperature of the distillate (solvent) and collect in a conical flask.
9)
Remove the heating source when the content remaining in the flask is about 2-3 mL.
Allow the solvent to evaporate while the flask is cooling to room temperature.
10) Collect and weigh the solid residue of benzoin.
-7-
Thermometer
Thermometer
Adapter
Water out
Condenser
50 mL Round
Bottom Flask
Parafin Oil
Oil Bath
Boiling Stone or
Ceramic Pieces
Water in
Conical Flask
Hot Plate
Figure 1
Part B
1)
Acidify the combined aqueous portions from Part A step 5) by slowly add 6M HCl
until the solution is acidic to litmus paper.
2)
Cool the resulting suspension in ice bath for a few minutes.
3)
Vacuum filter and air dry the benzoic acid for a few minutes.
4)
Collect and weigh the solid benzoic acid.
Safety Precautions
Concentrated HCl is highly corrosive. Safety goggles and lab coat must be worn at all
times.
Reference
D. L. Pavia, G. M. Lampman, G. S. Kriz, R. G. Engel, Introduction to Organic Laboratory
Techniques, A Microscale Approach, Part 5, 617-650.
-8-
Experiment
Thin Layer and Column Chromatography
3
by Pattara Sawasdee
Objectives
1) To perform separation techniques of column chromatography.
2) To analyze the purity of the isolated compounds using TLC technique.
Principles
Chromatography is a laboratory method based on selective adsorption by which
components in complex mixtures can be separated for identification or purification
purposes. (Adsorption is the binding of molecules to the surface of another substance.)
The utilization of a moving (or mobile) phase and a stationary phase is common to all
chromatographic separation techniques. A mixture of compounds is introduced into the
chromatographic system as a narrow zone and is partly retained by the stationary phase
while the mobile phase carries the components through the system. Each component in
the mixture will be distributed between the mobile phase and the stationary phase, but not
to the same extent. Components that are more loosely interacted by the stationary phase
will be swept through the column more rapidly, and a separation will be achieved.
When the stationary phase is packed inside a column, the experimental
procedure is called column chromatography. When the stationary phase is planar (e.g.,
a piece of filter paper or a coated glass), the mobile phase is usually liquid and the
techniques are classified according to the stationary phase which is paper or thin-layer
chromatography.
Chromatography is a sophisticated separation method. Its versatility results from
many adjustable factors which include:
1. Types of adsorbent
2. Types of solvent, which relates to the polarity of the mobile phase
3. Column size, both length and diameter, relative to the amount of mixtures
4. Rate of elution or solvent flow
In this experiment, you will use an open column chromatography to separate a
mixture of two compounds (benzil and benzoin). But first, you will have to determine a
suitable solvent system using thin-layer chromatography (TLC). The ideal solvent system
is the one that allows the faster-moving component to have an Rf value of about 0.25-9-
0.35 on the TLC plate while giving a good separation between the two spots (maximum
Rf difference). When you know the best solvent system, use this solvent as the eluent
(mobile phase) for the column chromatography. After the separation of the two
compounds, you will identify them by comparing the Rf with that of the authentic
compounds.
***
Rf stands for ratio of fronts or rate of flow***
Experimental Procedure
Part A: Mobile phase determination by TLC method
1) Obtain four TLC plates from the supply room. By using a pencil, not pen, lightly
draw a line across the short side of each plate, on the silica gel side approximately 1
cm from the bottom. Be careful not to scratch the silica gel as you are drawing the
line.
2) Use small capillary tubes to spot solutions of benzil and benzoin along the line. Keep
a gap (0.8-1 cm) between the two spots. When spotting the solutions, gently and
quickly touch the capillary to the surface of the plate so that the spots are not too
large. Also, write a letter above or below to indicate what is spotted at each position
(e.g. “A” for benzil and “B” for benzoin) as shown in Figure 1.
A
B
Watch glass
Beaker
A B
1 cm
Filter paper
TLC plate
1 cm
A = benzil solution
B = benzoin solution
Fig 1. TLC plate
z
z
Solvent level below the
pencil line on TLC plate
Fig 2. TLC chamber
- 10 -
3) Set up a TLC chamber as shown in Figure 2. Put a piece of filter paper in a 100 mL
beaker. Place a small amount of n-hexane in this beaker. The liquid should cover the
bottom of the beaker but the surface should be below the pencil line when the plate
is placed in the beaker (that is, less than 1 cm in depth). The filter paper lining is
used to saturate the atmosphere within the beaker with solvent fumes.
4) Place one spotted TLC plate in the TLC chamber, cover with a watch glass and
allow the solvent to move through the plate until it is approximately 0.5-1 cm from
the top. Do not disturb the chamber while the plate is being developed!!!
5) Remove the plate from the chamber and mark the solvent front with a pencil. Allow
the plate to dry for a few minutes. Place it under short-wave ultraviolet light (254 nm)
and circle dark spots appear on the plate under the UV light.
6) Repeat step 2) to 5) for other three TLC plates but each time change the mobile
phase from pure n-hexane to a mixture of ethyl acetate and n-hexane; 1:1, 1:2 and
1:4, respectively.
7) From the results, decide which solvent system would be appropriate for the
separation of benzil and benzoin (PART B). Report the result to your instructor.
PART B: Separation of a mixture by column chromatography
1) Prepare a silica gel column as shown in Fig 3, first plugging the column with cotton
and then affix to a clamp stand. Place a beaker under the outlet tap.
Funnel
Cotton
Fig 3. Setting up a
Chromatographic column
Beaker
2) In a clean and dry beaker, mix silica gel (~6 g) with your solvent of choice from
PART A (~30 mL) (CAUTION: Silica gel dust is very harmful if inhaled). Then, slowly
- 11 -
transfer the slurry into the column using a glass funnel until the silica gel level is
about 10-12 cm (when settle). If necessary, gently tap the side of the column with a
rubber tube during the packing process to compact the silica gel.
3) Open the stopcock to allow liquid to drain into the beaker. Adjust the level of liquid
around 2-3 cm above the level of silica gel and close the stopcock.
4) Obtain 0.1 g of solid mixture (benzil+benzoin) from your instructor. Place it in a test
tube and dissolve with a minimum amount of dichloromethane (~1-1.5 mL).
5) Open the stopcock and drain the solvent in the column until it reaches the silica gel
surface, and then close the stopcock. Slowly add the mixture solution into the
column via a pipette. The flat surface of silica gel should be minimally disturbed.
6) Open the stopcock to allow sample adsorption onto the silica gel, and then close the
stopcock.
7) Rinse the inside wall of the column with 1-2 mL of solvent.
8) When the solvent reaches the top of the silica gel surface, carefully add 25 mL (or as
much as your column can contain) of solvent for eluting. It is very important that the
column never be dried out during the eluting process.
9) Collect 10 fractions (2 mL each) in test tubes and label as 1, 2, 3,…..
10) Analyze all of your collected fractions by TLC (Fig 4).
1234
Fig 4. TLC plate for
checking each fraction
5 mm
1 cm
11) Combine the fractions containing pure benzoin in a ceramic evaporating dish and
place the dish on a steam bath until a solid or thick oil is obtained.
12) Allow the dish to cool to room temperature and collect the solid into a pre-weighed
plastic bag.
13) Calculate the weight of isolated benzoin.
14) Calculate recovery percentage.
15) Repeat step 11) to 14) with fractions containing pure benzil.
- 12 -
Safety Precautions
a. Wear safety goggles and lab coat at ALL times.
b. n-hexane and ethyl acetate are flammable. Never use them near open flame or
hot plate.
c. Cover all vessels containing silica dust. It is dangerous if inhaled.
Waste Disposal
Place all organic solvents and chemicals into container marked “Organic Waste”.
Reference
1) D. L. Pavia, G. M. Lampman, G. S. Kriz, R. G. Engel, Introduction to Organic
Laboratory Techniques, 3rd edition, Part 2: technique 10 column chromatography
and technique 11 thin-layer chromatography, pp.593-629.
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Experiment
Preparation of Cyclohexene from Cyclohexanol
4
by Pattara Sawasdee
Objectives
1) To synthesize cyclohexene from cyclohexanol via dehydration reaction of an alcohol.
2) To classify alkanes and alkenes using chemical reaction test
Principles
In this experiment some important properties of hydrocarbons will be studied. You’ll
perform tests which to distinguishing between saturated hydrocarbons (alkanes) and
unsaturated hydrocarbons (alkenes). An alkene (cyclohexene) will be prepared by
dehydration of an alcohol (cyclohexanol).
Alcohol dehydration is an acid-catalyzed elimination reaction, which can be
performed by strong, concentrated mineral acids such as phosphoric acid.
OH
H3PO4
cyclohexanol
b.p. 161oC
+ H2O
cyclohexene
b.p. 83oC
In the reaction above, cyclohexene is the only alkene that can be formed under
these conditions. Cyclohexene and water are removed via azeotropic distillation to drive
the equilibrium to product (Le Chatelier’s Principle). Traces of acid in the crude product
are removed by treatment with sodium carbonate solution. A final wash with water
removes any remaining carbonate.
Cyclohexene is an unsaturated hydrocarbon. In chemistry, a hydrocarbon is any
chemical compound that consists only of the elements carbon (C) and hydrogen (H). The
major classes of hydrocarbons are alkanes, alkenes, alkynes and aromatic hydrocarbons.
The alkanes are the least reactive class, because they contain only carbon and hydrogen
and they have no reactive functional groups. There are a number of useful chemical tests
that can differentiate alkanes from alkenes. These tests are based upon the reactivity of
alkenes with a variety of reagents to which the alkanes are insensitive. In this experiment,
you will distinguish cyclohexene (alkene) from cyclohexane (alkane) using bromine and
permanganate tests.
- 14 -
1) Bromine test using bromine in chloroform (Br2/CHCl3)
R C C
H H
Br H
R C C
H Br
R + Br2
R
A solutions of bromine in CHCl3 has an intense red-orange color. When Br2 in
CHCl3 is mixed with an alkane, no change is initially observed. When it is mixed with
an alkene or alkyne, the color of Br2 rapidly disappears as an addition reaction takes
place.
2) Permanganate Test (Baeyer’s test)
3 R C C
H H
R +
2KMnO4 + 4H2O
OH OH
3R C
C R + 2MnO2 + 2KOH
H
H
The disappearance of the purple color of potassium permanganate and the
formation of brown precipitate (MnO2) is a positive test. The alkenes are readily
oxidized by potassium permanganate to form diols. The alkanes are not reacted with
the potassium permanganate as the purple color remains.
Experimental Procedure
Part A: Preparation of cyclohexene by dehydration of cyclohexanol
OH
H3PO4
heat
1)
2)
3)
Transfer 10 mL (9.4 g.) of cyclohexanol to a 100 mL round-bottomed flask. Add 5 mL
of 85% H3PO4. Thoroughly mix the solution by swirling.
CAUTION: Phosphoric acid is strongly corrosive. If it is in contact with your skin,
rinse with tap water immediately and report the incident to your instructor.)
Add a few pieces of boiling chips, and assemble the flask for fractional distillation
(Figure 1) using a 25 mL graduated cylinder in an ice-water bath as a receiver.
(cyclohexene is very volatile and it will evaporate quite rapidly)
Start circulating the cooling water in the condenser and heat the reaction flask using
a heating mantle (avoid overheating). The temperature of the distilling vapor should
be regulated so that it does not exceed 100°C.
- 15 -
4)
5)
6)
7)
8)
9)
When white fumes appear in the round bottom flask, and a few milliliters of liquid
remains in the reaction flask, discontinue the distillation by turning off the heating
mantle.
Transfer the distillate* to a small separatory funnel and add about 10 mL of 10%
aqueous Na2CO3. Swirl the solution slowly at first and then shake vigorously to
neutralize the solution. Vent frequently to prevent CO2 pressure build up.
Allow the layers to separate, drain and test the pH of the aqueous layer (bottom
layer). Repeat the neutralization until the aqueous layer is basic to litmus. The
aqueous layer can then be discarded.
Wash the organic layer with 10 mL of water.
Transfer the organic layer to a dried 50 mL Erlenmeyer flask. Add anhydrous
Na2SO4 to the flask and swirl occasionally until the solution is dry and clear.
Weigh the cyclohexene product and calculate the total yield.
* distillate = Lliquid condensed from vapor in distillation
distilland = The material in the distillation apparatus that is to be distilled.
Thermometer
Water out
Water in
Condensor
Fractionating
column
Graduate cylinder
ice-water bath
Heating mental
Figure 1: a fractional distillation apparatus
Part B: Test of unsaturation
Samples :
1. Cyclohexane (Alkanes): from the laboratory
2. Cyclohexene (Alkenes): from your synthesis (Part A)
1)
Bromine test: Place 3 drops of samples in dry test tubes. Then, add about 3-4
drops of a bromine solution in chloroform. Stopper each tube, shake, and record
the observation. If decolorization occurs, test for hydrogen bromide with wet
litmus.
- 16 -
2)
Permanganate test: Place 3 drops of samples in clean test tubes. Add 3-4
drops of 0.1% permanganate solution drop by drop while shaking. Watch for
disappearance of the purple color and formation of a brown precipitate within 1
minute.
Safety Precautions
-
-
Phosphoric acid is a strong acid capable of producing severe burns to skin or eyes.
Cyclohexanol can be irritating to the respiratory system and skin.
Cyclohexene is not particularly dangerous but is highly flammable and has an
unpleasant smell.
Bromine is highly volatile, toxic, and causes severe skin burns.
Waste Disposal
All contents of your test tubes from bromine test reactions go into “HALOGENATED
organic waste”.
Quiz
Quiz will cover this material and the basic knowledge of hydrocarbons.
- 17 -
Experiment
Alkyl Halides
5
by Paitoon Rashatasakhon
Objectives
1) To classify alkyl halides according to their structures and reactivity.
2) To understand the relationship between structures and reactivity of alkyl halides.
3) To distinguish the differences in SN1 and SN2 reactions.
Principles
Alkyl halides are hydrocarbon compounds containing at least one atom of
halogen directly bonded to an alkyl group. With a general formula R-X, the halogen
atom could be F, Cl, Br, or I. If the halogen atom is attached to an aromatic ring, the
compound will be referred to as an aryl halide. In terms of reactivity, aryl halides are
usually less reactive than alkyl halides.
Most of the reactions for alkyl halides are Nucleophilic Substitution reaction.
Nucleophiles are molecules with high electron density or lone pairs of electrons, or
ions with a negative charge. They can form bond by donating electrons to another
molecule having a position of lower electron density (electrophiles). Examples of
nucleophilic species are: water, amines, ammonia, cyanide ion, alkoxide ions, and
hydroxide ion.
Alkyl halides can react with a number of nucleophilic reagents, both organic and
inorganic species. Therefore, alkyl halides are usually good starting materials in the
synthesis of compounds with other functional groups.
The reaction may occur by one of two mechanisms designated SN1 or SN2.
Which mechanism operates depends on the structure of the R group, nucleophile, and
the reaction conditions.
General form of the SN1 mechanism
nuc: = nucleophile
X = leaving group (usually halide)
This mechanism involves the formation of a carbocation as the crucial
intermediate in the rate-determining step. The reaction exhibits unimolecular (or "firstorder") kinetics, because only one molecule is involved in the rate-determining step.
Since the mechanism goes through a carbocation, the leaving group must be attached
- 18 -
to either a tertiary or secondary carbon to stabilize the intermediate. A methyl or primary
leaving group will not form a carbocation.
Because the intermediate carbocation, R+, is planar, the central carbon is not a
stereocenter, even if it was a stereocenter in the original reactant, so the original
configuration at that atom is lost. Nucleophilic attack can occur from either side of the
plane, so the product may consist of a mixture of two stereoisomers. In fact, if the
central carbon is the only stereocenter in the reaction, racemization may occur
General form of the SN2 mechanism
nuc: = nucleophile
X = leaving group (usually halide)
The SN2 reaction involves displacement of a leaving group by a nucleophile. The
rate of an SN2 reaction is second order, as the rate-determining step depends on the
nucleophile concentration, as well as the concentration of alkyl halide. This reaction
works best with methyl and primary halides because bulky alkyl groups block the
backside attack of the nucleophile, but the reaction does work with secondary halides
(although it is usually accompanied by elimination), and will not react at all with tertiary
halides. In the following example, the hydroxide ion is acting as the nucleophile and
bromide ion is the leaving group: Because of the backside attack of the nucleophile,
inversion of configuration occurs.
- 19 -
Experimental Procedure
1. Reaction with NaI in acetone
In this part of the experiment, you will test the reactivity of several alkyl halides in an
SN2 reaction. Iodide ion (I-) is an effective nucleophile in SN2 substitution. In acetone
solution, other alkyl halides (alkyl chlorides or bromides) can be converted to alkyl
iodides easily by this method. Although one might expect such a reaction to be
reversible, it can be driven to formation of R-I by using anhydrous acetone as the
solvent. Sodium iodide (NaI) is soluble in this solvent, but sodium chloride and sodium
bromide are not. If a reaction occurs, a precipitate of sodium chloride or sodium
bromide forms and thus the ion is not available in solution for the reverse reaction.
The mechanism involves a one-step, concerted, SN2 reaction. Therefore, the reaction
occurs most quickly when attack at the carbon that bears the halogen (X) is least
sterically hindered.
1. Place 2 drops of each of the following compounds in five separate clean and
dry test tubes. Label them accordingly.
n-butyl chloride, s-butyl chloride, t-butyl chloride, n-butyl bromide, bromobenzene.
2. Add 1 mL of 18% NaI solution in acetone in each test tube.
3. Stopper, and shake vigorously.
4. Record the time required to observe precipitate.
• If no precipitation takes place after 5 minutes, place the test tube in a
steam bath (45-50°C). Do not allow complete evaporation by adding
acetone to keep the solution at the same level. Record whether the
precipitation take place and the time required.
• If no precipitation takes place after 10 minutes in steam bath, record
data as “no precipitation”.
5. Present the final result to your instructor.
2. Reaction with AgNO3 in ethanol
The silver nitrate test allows for the identification of alkyl halides by observing them in
an alcoholic silver nitrate environment. The rate at which the silver halide salt
precipitate forms is characteristic of different types of alkyl halides. You will test the
reactivity of several alkyl halides in a SN1 reaction. Organic halides may react with
ethanol to form ethyl ethers. When the ethanol contains silver ion, the rate of reaction
increases because the silver ion acts as an electrophile toward the halogen and helps
to break the carbon-halogen bond. Alkyl chlorides yield an observable silver chloride
precipitate, which is insoluble in ethanol and thus provides an indicator that a reaction
has occurred. In this case, the slow step being the breaking of the carbon-halogen
bond. The carbocation then reacts rapidly with alcohol to form the ether. Organic
halide reactivity parallels the stability of the corresponding carbocations.
1. Place 2 drops of each of the following compounds in five separate clean and
dry test tubes. Label the test tubes accordingly.
- 20 -
n-butyl chloride, s-butyl chloride, t-butyl chloride, n-butyl bromide, bromobenzene.
2. Add 1 mL of 1% AgNO3 in ethanol.
3. Stopper, and shake vigorously.
4. Record the time required to observe precipitate. If no precipitation takes place
after 5 minutes, place the test tube in a water bath (45-50°C). Do not allow
complete evaporation by adding ethanol to keep the solution at the same
level. Record whether the precipitation take place and the time required. If no
precipitation takes place after 10 minutes in water bath, record data as “no
precipitation”.
5. Present the final result to your instructor.
3. Comparison of SN1 and SN2
Blank test:
1. Place 1 mL of ethanol, 5 drops of water, and 2 drops of bromophenol blue in a
test tube.
2. Stopper and shake the tube vigorously.
Note:
Bromophenol blue
pH 3 (yellow) – pH 4.6 (blue)
Test A:
1. Place 1 mL of ethanol, 5 drops of water, 2 drops of bromophenol blue, and 5
drops of n-butyl chloride in a test tube.
2. Stopper and shake the tube vigorously.
3. Observe the result and compare with the blank test.
4. Present the final result to your instructor.
Test B:
1. Place 1 mL of ethanol, 5 drops of water, 2 drops of bromophenol blue, and 5
drops of t-butyl chloride in a test tube.
2. Stopper and shake the tube vigorously.
3. Observe the result and compare with the blank test.
4. Present the final result to your instructor.
4. Preparation of alkyl halide
Alkyl halides may be prepared in a variety of ways, the particular method to be
employed depending largely upon the nature of the alkyl group and the halogen.
Some of the general methods which may be used are illustrated in the following
equations:
R-H + Cl2 Æ R-Cl + HCl
R – CH=CH2 + HCl Æ R-CHCl-CH3
R-OH + HCl Æ R-Cl + H2O
ROH + SOCl2 Æ RCl + SO2 + HCl
Replacement of the hydroxyl group of an alcohol is perhaps the most common
method. When the reagent is a hydrogen halide, the ease with which this may be
accomplished increases as one proceeds from a primary to a tertiary alcohol. Tertiary
alcohols are readily converted to the corresponding chlorides simply by shaking for a
few minutes, at room temperature, with concentrated hydrochloric acid.
- 21 -
Synthesis of Tertiary Butyl Chloride
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Place 10 mL of cold concentrated hydrochloric acid in a 125 mL separatory
funnel.
Add 5 mL of tert-butyl alcohol
Without closing the separatory funnel, mix the two components by swirling the
funnel for a few minutes.
Close the separatory funnel with its stopper, shake the separatory funnel at
intervals for 10 minutes. From time to time, relieve any internal pressure by
inverting the funnel and slowly opening the stopcock.
Allow the mixture to stand until two distinct layers separate.
Draw off and discard the aqueous layer (bottom layer) through the stopcock.
Add 15 mL of distilled water, shake the separatory funnel for 30 seconds, put the
funnel on the stand and relieve the pressure by opening the stopper.
Allow the mixture to stand until two distinct layers separate.
Draw off and discard the aqueous layer (bottom layer) through the stopcock.
Add 15 mL of distilled water, shake the separatory funnel for 30 seconds, put the
funnel on the stand and relieve the pressure by opening the stopper.
Allow the mixture to stand until two distinct layers separate.
Draw off and discard the aqueous layer (bottom layer) through the stopcock.
Weigh and record the weight of an empty clean test tube.
Draw off the organic layer (your product) into the test tube. Weigh the tube with
your product.
Calculate and record the weight of your product.
Calculate the % yield of the product.
In order to verify the identity of your product, test the product with both NaI and
AgNO3 (follow the procedures 1-2 above)
Present the final result to your instructor.
- 22 -
Experiment
Alcohols and Phenols
6
by Paitoon Rashatasakhon
Objectives
1) To classify alcohols according to their characteristic chemical reactions.
2) To differentiate phenols and the three types of alcohols using simple chemical tests.
Principles
The alcohols, with a hydroxyl group attached to an alkyl chain, and the phenols,
with the same group attached directly to the aromatic ring, have similar chemical
properties in kind, but may differ considerably in the degree to which these properties are
exhibited. Alcohols are classified as 10, 20 and 30, depending on the number of carbon
atoms connected to the carbon bearing the OH group. The following experiments are
designed to bring out these similarities and differences, as well as to demonstrate the
properties of the hydroxyl group.
Examples of primary alcohols
OH
OH
OH
OH
Examples of secondary alcohols
OH
CH2Ph
H
OH
Cl
H
CH3
OH
OH
Examples of tertiary alcohols
OH
OH
OH
OH
CH3
Examples of phenolic compounds
OH
OH
OCH3
OH
HO
HO
- 23 -
Experimental Procedures
1) Water solubility
The more carbon atoms present in the molecule of alcohols, the less polar and
more hydrophobic they become. However, alcohols with straight chain methylene (-CH2-)
units are generally more hydrophobic than those with branch structure.
1. Place 2 drops of each of the following compounds in six separate clean test tubes.
Label them accordingly.
ethanol, 1-butanol, 2-butanol, tert-butanol, cyclohexanol, phenol
2. Add 10 drops of water into each test tube. Shake and let stand.
3. Observe whether the compound is soluble in water.
4. Record the data and present to your instructor.
2) Alkali solubility
Alcohols are weaker acids than water, but the aromatic ring makes phenols more
acidic than water, which means that they may be neutralized by stronger bases such as
sodium hydroxide.
1. Place 2 drops of each of the following compounds in three separate clean test tubes.
Label them accordingly.
1-butanol,
cyclohexanol,
phenol
2. Add 10 drops of 10% NaOH solution into each test tube. Shake and let stand.
3. Observe whether the compound is soluble in NaOH solution.
4. Record the data and present to your instructor.
3) Reaction with metallic sodium
The hydrogen atom of the hydroxyl group can be displaced by active metals such
as sodium. This reaction can be used as an indication of the presence of an –OH group in
an unknown compound. The reaction produces hydrogen gas and the corresponding
sodium alkoxide as shown in the following equation.
O- Na+
OH
+
tert-butanol
+
Na
sodium
sodium tert-butoxide
H2
hydrogen
1. Place 10 drops of each of the following compounds in three separate clean and dry
test tubes. Label them accordingly.
ethanol, 2-propanol,
2.
3.
4.
5.
6.
tert-butanol
Add a very small piece of sodium into each test tube.
Observe the result and note the relative rates of reaction (gas bubbling).
Add a drop of phenolphthalein to the ethanol tube (only one tube).
Observe the result.
Record the data and present to your instructor.
- 24 -
NOTE: Do not discard the waste from the experiment into the sink. Discard the
solution into the bottle or beaker labeled “Sodium Waste”.
4) Reaction with ceric nitrate
Alcohols with less than 10 carbon atoms can form colorful complexes with Ce3+
ion. This is a characteristic feature of alcohols as the positive test results will have
different color compared to the blank test.
1. Place 2 drops of each of the following compounds in four separate clean and dry test
tubes. Label them accordingly.
1-butanol,
2-butanol,
tert-butanol,
phenol
2. Add 1 mL of ceric nitrate reagent into each test tube.
3. Observe the result and compare the color with blank test (ceric nitrate reagent + a
few drops of water)
4. Present the data to your instructor
5) Characteristic reactions of phenol
a) Phenols and compounds with the hydroxyl group attached to an unsaturated
carbon atom, give coloration (purple/violet) upon the addition of ferric chloride
(FeCl3) solution. This is due to the formation of complex between phenolic
compounds and Fe3+ ion.
1. Place 1 mL of water into each of two clean test tubes.
2. Add one drop of phenol in one tube and a few drops of ethanol in the other.
3. Add 5 drops of 1% ferric chloride solution. Note the characteristic color developed in
the phenol tube. This is a standard test for most phenol.
4. Present the data to your instructor
b) The hydroxyl group of the phenols activates the benzene ring to further
substitution. Bromination using bromine water can proceed smoothly under very
mild conditions.
1. Place 1 mL of water into each of two clean test tubes.
2. Add one drop of phenol in one tube and a few drops of ethanol in the other.
3. Add bromine water slowly into each tube. If the color disappears, continue adding
until the color of the bromine just persists.
4. Present the data to your instructor
6) Lucas test –Differentiation of primary, secondary and tertiary alcohols
The Lucas test is a test for the ease of replacement of a hydroxyl group by a
halogen atom, according to the reaction:
R OH + HCl
ZnCl2
R Cl
+ H 2O
Since the product (alkyl halide) is insoluble in water, the solution becomes cloudy
and may separate into two layers when the hydroxyl group is replaced with halogen. This
cloudiness or appearance of a second layer (heterogeneous mixture) is evidence that a
reaction has occurred.
- 25 -
When Lucas reagent (ZnCl2 + conc. HCl) is added to alcohols, H+ from HCl will
protonate the -OH group, so that the leaving group H2O, being a much weaker
nucleophile than OH-, hence can be substituted by nucleophile Cl-. Lucas' reagent offers
a polar medium in which SN1 mechanism is favored. In unimolecular nucleophilic
substitution, the reaction rate is faster when the carbocation intermediate is more stable.
Therefore, tertiary alcohols react immediately with Lucas reagent to produce turbidity
while secondary alcohols do so in about five minutes. Primary alcohols do not react
appreciably with Lucas reagent at room temperature. Hence, the time taken for turbidity to
appear is a measure of the reactivity of the class of alcohol with Lucas reagent, and this is
used to differentiate between the three classes of alcohols
1. Place 3 drops of each of the following compounds in four separate clean and dry test
tubes. Label the test tubes accordingly.
1-butanol,
2.
3.
4.
5.
cyclohexanol,
tert-butanol
Add 1 mL of the Lucas reagent into each tube.
Stopper and shake well.
Observe the result immediately, after 5 min, and again after 30 min.
Present the data to your instructor.
7) The oxidation reaction
The oxidation of the carbon atom is an important reaction for this class of
compounds. When sodium dichromate is used as an oxidizing agent, the orange
dichromate ion is reduced to the green chromic ion. In this reaction a chromate ester of
the alcohol substrate is believed to be an intermediate, which undergoes an E2-like
elimination to the carbonyl product. The oxidation state of carbon increases by 2, while
the chromium decreases by 3 (it is reduced). The progress of these oxidations is easily
observed. Indeed, this is the chemical transformation on which the Breathalyzer test is
based. The secondary alcohols can be oxidized to ketones, while the oxidation of primary
alcohols initially gives aldehydes which are oxidized further to carboxylic acids. Tertiary
alcohols will not be oxidized under these conditions.
1.
2.
3.
4.
5.
6.
Place 0.5 mL of a 10% solution of sodium dichromate in a clean test tube.
Add 2 drops of concentrated sulfuric acid and stir with a glass rod.
Add 5 drops of ethanol and warm gently (~40-50°C).
Observe any change in color of the solution.
Repeat step 1-4 with 2-propanol and tert-butanol.
Present the data to your instructor.
8) Identification of an unknown alcohol.
After presenting the data from part 1-6 to your instructor, you will receive an
unknown alcohol. Identify the possible structure of your unknown based on the data
from ceric nitrate test, FeCl3 test, Lucas test, and oxidation test.
- 26 -
Experiment
7
Aromatic Chemistry –
Nitration of Methyl Benzoate
by Varawut Tangpasuthadol
Objectives
1) To perform nitration reaction of methyl benzoate.
2) To purify the product by recrystallization.
3) To analyze the purity of the product by TLC and melting point determination.
Principles
Nitration of methyl benzoate is a classic example of the electrophilic aromatic
substitution reaction. In general, the electron-rich aromatic ring is attracted to
electrophiles, which in this case is a ‘nitronium’ ion (NO2+). The nitronium ion is
generated from a mixture of concentrated nitric acid and concentrated sulfuric acid as
shown below.
HNO3 +
H 2SO4
NO 2+ + HSO4- + H 2O
nitronium iom
O
O
C
OCH3
+ NO2+
C
H2SO4
OCH3
o
15 C
NO2
Methyl m-nitrobenzoate
The –CO2CH3 group on methyl benzoate is an electron withdrawing group and is
therefore considered as a meta-directing group. If the reaction condition is very well
controlled as directed, methyl m-nitrobenzoate should be the only product obtained from
this reaction, otherwise by-products such as a di-nitro compound may occur. For this
reason, students are also asked to check the purity of the product by performing TLC of
their synthesized product.
Chemicals
Methyl benzoate
10 drops (~200 mg) irritate, flammable
Conc. sulfuric acid 3 mL
corrosive, reacts violently with water
Conc. nitric acid
1 mL
corrosive, oxidizing agent
- 27 -
Experimental Procedure
1)
Withdraw 10 drops of methyl benzoate from a burette into a small conical flask
with known weight. Record the exact weight of methyl benzoate used.
2)
Immerse the flask from step 1 in an ice-water bath. Slowly add 2 mL of
concentrated sulfuric acid dropwise while swirling.
3)
Prepare the nitrating agent by mixing 1.0 mL of conc. sulfuric acid and 1.0 mL of
conc. nitric acid in a test tube that is chilled in an ice-water bath.
4)
SLOWLY add, using a Pasteur pipet, the solution from step 3 into the mixture from
step 2 while being chilled all the time. Stir the mixture regularly. The adding period
should not be less than 15 minutes. If the mixture becomes cloudy, add a few
drops of conc. sulfuric acid until the solution is clear.
5)
Let the reaction mixture stand in a water bath (no ice) at room temperature for 15
minutes.
6)
Add about 10 g of crushed ice into the reaction mixture. Stir the mixture vigorously.
7)
After the ice has melted, isolate the solid product by vacuum filtration and wash
with cool water, 5% NaHCO3, and cool water again until the filtrate is neutral.
8)
Dry the product in a watch glass over a steam bath, weigh and determine yield
percentage of the product (before re-crystallization).
9)
Re-crystallize the product from methanol. (Use a minimum amount of hot methanol
to dissolve the product.)
10) Weigh the re-crystallized product. Calculate yield percentage after recrystalization
and recovery percentage.
11) Check the purity of the product by TLC comparing to the starting material. A
mixture of hexane-ethyl acetate (3:1) is used as the eluent.
12) Determine the melting point of the purified product and compare it with a
reference.
13) Submit the product to your instructor in a labeled plastic bag.
Waste Disposal
All organic solvent wastes are discarded in a container marked, ‘Organic Waste’.
- 28 -
Experiment
Aldehydes and Ketones
8
by Varawut Tangpasuthadol
Objective
To carry out a series of chemical reactions for the classification of aldehydes and
ketones.
Principles
Aldehydes and ketones are organic compounds that contain carbonyl functional groups
connecting to either one hydrogen and one alkyl (or aryl) group or two alkyl (or aryl)
groups, respectively.
O
R
C
O
H
R
C
O
R'
R
C
O
CH R'
R
C
CH3
OH
Aldehyde
ketone
α-hydroxy ketone
methyl ketone
The chemistry of these compounds is primarily due to that of the carbonyl
groups. Identifying methods for aldehydes and ketones can be performed by a number
of chemical reagents listed in Table 1.
Table 1 Classification tests for aldehydes and ketones
Compound
Reagent
Aldehydes and ketones
2,4-Dinitrophenylhydrazine
Aldehydes, α-hydroxy ketones
Tollen’s reagent
Aliphetic aldehydes, α-hydroxy ketones
Benedict’s reagent
Aldehydes
Schiff’s reagent
Aldehydes, α-hydroxy ketones
Potassium permanganate
Methyl ketone, acetaldehyde
Iodoform test
Classification tests
2,4-Dinitrophenylhydrazine (2,4-DNP) reagent
Most aldehydes and ketones give a precipitate, 2,4-dinitrophenylhydrazone. The
color of the precipitate is ranged from yellow-orange-red. The color of any precipitate
must be judged cautiously, since the 2,4-DNP reagent is itself orange-red. Glucose and
other carbohydrates also give positive results for this test but very slowly, therefore,
boiling is also required.
- 29 -
NO 2
NO2
O
R
C
R'
+ H2N
H
N
NO 2
H+
R
N
NH
NO 2
+ H2O
R'
2,4-dinitrophenylhydrazine
2,4-dinitrophenylhydrazone
Tollen’s test
Most aldehydes, α-hydroxy ketone and more carbohydrates can reduce silver
nitrate (AgNO3) solution in ammonia to give silver metal (Ag). The silver may precipitate
as ‘silver mirror’ along the side of a test tube or as gray powder. The aldehyde is
oxidized to a carboxylic acid:
2 Ag(s) + RCOO-NH4+ + H2O + NH3
RCHO + 2 Ag(NH3)2OH
Benedict’s test
Only aliphatic aldehydes and α-hydroxy ketone can be oxidized by copper (II) ion
(Cu2+) to give orange-red precipitate of cupric oxide (Cu2O). For some compounds,
green, blue or brown precipitate can also be expected. Reducing sugars such as
glucose, fructose, mannose, lactose and maltose can also be oxidized by the Benedict’s
test.
RCOO- + Cu2O(s) + 3 H2O
RCHO + 2 Cu2+ + 5 OH-
Schiff’s test
Schiff’s reagent is a solution of pararosaniline hydrochloride which is reacted with
sulfuric acid to give a colorless solution. This solution will turn light purple or pink when
reacting with an aldehyde.
Potassium permanganate test
Potassium permanganate solution contains manganese (VII) ion (Mn7+) that can
oxidize aldehydes and α-hydroxy ketone to carboxylic compounds and di-ketone,
respectively. A brown precipitate of manganese dioxide (MnO2) is observed.
Iodoform test
Methyl ketone and acetaldehyde form a precipitate of iodoform (CHI3) when
treated with a basic solution of iodine. The iodoform is yellow in color and may be
produced in a very small amount. Therefore, the testing result should be carefully
observed since the yellow precipitate usually sinks to the bottom of the test tubes.
O
CH3 C
O
I2
R'
NaOH
CI3
C
OHR'
O
-O
C
R'
+ CHI3
iodoform
Test samples
Acetaldehyde, acetone, benzaldehyde, glucose (1% solution in water), benzoin (1%
solution in ethanol), and one UNKNOWN sample
- 30 -
Experimental Procedure
Note- A blank test should be performed in every test.
1) Reaction with 2,4-dinitrophenylhydrazine (2,4-DNP)
Place one drop of a test sample in a test tube and add 1 mL of 2,4-DNP. Shake the
solution well. If no precipitation is observed, gently heat the sample test tube about 15
minutes. Compare the appearance of the precipitate and the time required for the
precipitation of all test samples.
2) Tollen’s reagent
Place 2 drops of a test sample in a test tube. Add 1 mL Tollen’s reagent. Shake the
solution well. If a mirror of silver is deposited on the inner walls of the test tube, the test
is positive. Otherwise heat the test tube for 1 minute, let it cool down to room
temperature. Record the change in appearance.
3) Schiff’s reagent
Place 1 mL Schiff’s reagent in a test tube. Add 1 drop of a test sample. Shake the
solution. Record the result.
4) Benedict’s test
In a test tube, place 1 mL Benedict’s solution and add 1 drop of a test sample. Shake
the solution well. If there is no change, warm up the test tube for about 5 minutes.
Record the result.
5) Oxidation with KMnO4
Place 4 drops of test sample in a test tube. Add 2 drops of 0.1% KMnO4 solution. Shake
the solution well. Record the result.
6) Iodoform test
Use only acetaldehyde, acetone and benzaldehyde for this test.
Place 1 mL distilled water in each of 4 test tubes. Add one drop of the test sample in
each tube. Add 1 mL of 5% NaOH solution. Add iodine-potassium iodide (I2-KI) solution
one drop at a time until a permanent pale yellow solution is obtained. Shake the tube
well after each addition. Allow the test tube to stand for 2-3 minutes. If the test is
positive, the yellow solution will decolorize and a yellow precipitate of iodoform will form.
If the color of the solution is discharged but no precipitation, add some more I2-KI
solution until the pale yellow color returns. Allow the solution to stand for 2 more
minutes. It may be necessary to warm the solution in a water bath (~60 °C) to aid in the
discharge of the color.
7) Classification test for an unknown compound
Obtain an unknown sample from the instructor. Record the sample number. Perform the
tests according to the procedure. From the results, try to identify the detailed structure
of the unknown. Consult with your instructor and write down the structure in the report.
- 31 -
Experiment
Synthesis of Esters and Reactions of
Carboxylic Acids and their Derivatives
9
by Warinthorn Chavasiri
Objectives
1) To synthesize an ester using acid-catalyzed esterification reaction.
2) To study the reactions of carboxylic acids and their derivatives.
Principles
Carboxylic acid is an important class of organic compounds. Acid derivatives differ
from their parent compound in that the hydroxyl (-OH) portion is replaced by another
group. Important acid derivatives include acid halides, anhydrides, esters, and amides.
O
R
C
OH
carboxylic acid
O
R
C
O
X
R
acid halide
C
O
O
anhydride
C
O
R
R
C
O
OR'
R
ester
C
NH2
amide
Carboxylic acids can be converted into their salts by treatment with base. Because
these salts are ionic and usually water-soluble, acids have low solubility in the presence
of base in water can be extracted from a solution into an organic solvent.
O
R
C
O
OH
less soluble
in water
+ NaOH
R
C
O-Na+
+ H2O
more soluble
in water
Acid halides are usually prepared by reacting the corresponding acid with an
inorganic halide such as PCl3, PCl5 or thionyl chloride (SOCl2). Acid anhydrides can be
prepared by dehydration of the corresponding carboxylic acids. The acid-catalyzed
reaction of an alcohol with a carboxylic acid is the most commonly used method for ester
preparation. Amides can be prepared by heating ammonium salts of acids or by the
reaction of ammonia, primary-, or secondary-amines with various acid derivatives. Most
reactions of acid derivatives involve nucleophilic attack on the carbonyl carbon.
- 32 -
Preparation of an ester
Background
Esters are found in many natural products, contributing to the scent of banana,
orange, pineapple, and other fruits. The structure of ester determines its scent. By
reacting different alcohols with carboxylic acids, you can produce esters of different
scents. There are many different methods for synthesizing esters. However, the two
most common ones are 1) acid-catalyzed Fischer esterification using a carboxylic acid
and an alcohol; and 2) condensation of acid chloride with an alcohol.
The Fischer esterification is an equilibrium reaction in which an acid and an alcohol
combine to produce the ester and water. For example, the acid catalyzed reaction for
the formation of ethyl acetate from acetic acid and ethanol.
O
O
H+
H3C
C
OH + CH3CH2OH
H3C
C
OCH2CH3 + H2O
To drive the equilibrium towards completion, either the starting carboxylic acid or the
alcohol is used in excess. Alternatively, if the ester has a significantly different boiling
point than the alcohol or acid, it can be separated from the acid and alcohol by
distillation.
The second synthetic route to esters employs an acid chloride, which has to be
prepared in an additional step. The reaction requires a base such as K2CO3 or
triethylamine to destroy the hydrochloric acid by-product.
O
O
H3C
C
Cl + CH3CH2OH
base
H3C
C
OCH2CH3
Techniques
Reflux
Extraction using separatory funnel
Simple distillation
- 33 -
Experimental Procedure
Part A Preparation of fruity ester (CARE: extremely corrosive)
Each group will obtain an unknown carboxylic acid and an unknown alcohol. You will
then synthesize an ester from the two starting materials, identify the scent of the ester
product, purify the product by distillation, and predict the identity of the two starting
materials based on the scent of the ester and its boiling point.
Procedure
1. Pour all of the unknown alcohol and carboxylic acid into a 50 mL round bottom
flask. The alcohol was accurately measured to be 0.046 mol and the carboxylic
acid was measured to be 0.12 mol.
2. Carefully add 1.5 mL of concentrated sulfuric acid to the reaction flask. Add
boiling stones to the mixture.
3. Assemble the reflux apparatus. Bring the mixture to boil using a heating mantle
and heat the mixture under reflux for 1 hour. During this time, you may proceed
to Part B.
4. Remove the heating source and allow the mixture to cool to room temperature.
5. Pour the cooled mixture into a separatory funnel and carefully add 20 mL of
distilled water. Rinse the reaction flask with 5 mL of distilled water and pour the
rinsing into the separatory funnel.
6. Stopper the funnel and shake it several times. Separate the lower aqueous layer
from the upper organic layer. Label the unwanted aqueous layer and put it aside.
7. The crude ester in the upper organic layer still contains some unreacted acid
which can be removed by extraction with NaHCO3 solution. Carefully add 10 mL
of 5% NaHCO3 to the organic layer in the separatory funnel. Without the stopper,
swirl the funnel gently until carbon dioxide gas no longer evolved.
8. Place the stopper, shake the funnel, relief the internal pressure, and settle the
funnel to allow phase separation to occur, then remove and discard the lower
layer.
9. Add 10 mL of 5% NaHCO3 to the organic layer in the separatory funnel. Place
the stopper, shake the funnel, relief the internal pressure, and settle the funnel to
allow phase separation to occur.
10. Remove the lower layer and check whether it is basic to litmus paper. If it is not
basic, repeat step 9 until the aqueous layer is basic.
11. Add 10-mL portion of water. Place the stopper, shake the funnel, relief the
internal pressure, and settle the funnel to allow phase separation.
12. Add 10 mL of saturated sodium chloride to aid in layer separation.
13. Carefully separate and discard the lower layer.
- 34 -
14. Transfer the organic layer into an Erlenmeyer flask. Add about 2 g of anhydrous
MgSO4 to dry the solution.
15. Assemble a simple distillation apparatus and carefully decant the ester solution
into the distillating flask.
16. Add boiling stones and distill the ester. Collect the fraction and observe the
boiling range.
17. Weigh the product.
18. Report the scent and boiling point of your ester product to your instructor. Also,
identify the unknown starting carboxylic acid and alcohol.
19. Calculate the percentage yield based on the molecular weight of your product.
- 35 -
Table of selected ester flavors and fragrances
Complete this table before starting the experiments.
Draw the structures of the carboxylic acids, alcohols and esters.
Find out the boiling range of the esters from the references.
Carboxylic
acid
Acetic acid
Alcohol
Ester
Scent
Isoamyl alcohol
Isoamyl acetate
Propionic acid
Isobutyl alcohol
Isobutyl propionate
rum
Anthranilic
acid
Methyl alcohol
Methyl anthranilate
grape
Acetic acid
Benzyl alcohol
Benzyl acetate
peach
Butyric acid
Methyl alcohol
Methyl butyrate
apple
Butyric acid
Ethyl alcohol
Ethyl butyrate
pineapple
Acetic acid
Octyl alcohol
Octyl acetate
orange
Acetic acid
n-Propyl alcohol
n-Propyl acetate
b.p.
banana
pear
- 36 -
Part B
Reactions of carboxylic acids and their derivatives
Samples:
O
O
O
OH
OCH3
HN
O
O
H
O
OH
H3C
Formic acid
O
OH
Acetic acid
CH3
OH
OH
Oxalic acid
Benzoic acid
Methyl benzoate
Acetanilide
1. Solubility Experiments
a) In water
Add approximately 2 drops of liquid sample or 0.1 g of solid sample into water
(3 mL). Shake well, observe the solubility, and record your observation.
b) In 5% NaOH solution
Use the same amount of sample as above, and use 3 mL of 5% NaOH solution.
Observe the solubility in 5% NaOH solution and record your observation.
c) In 5% NaHCO3 solution
Use the same amount of sample as above, and use 5% NaHCO3 solution.
Observe the solubility in 5% NaHCO3 and look for evolution of gas.
2. Ferric hydroxamate reaction
Place a drop of methyl benzoate in a test tube and add 0.5 M NH2OH.HCl in
ethanol (1 mL). Add 20% NaOH until the solution becomes basic to litmus. Warm
up the mixture on the water bath for 5 min and then cool down to room
temperature. Add 1M HCl until the solution becomes acidic or the brown
precipitate dissolves. Add 5% FeCl3 until a permanent color is observed. Record
your observation and then repeat with benzoic acid.
3. Reaction with Tollens’ reagent
Place approximately 4 mL of Tollens’ reagent in each of 5 test tubes and add in
the samples in the first four tubes as listed in the table below. The last tube is
used as a blank test.
Tube #
Tollens’s reagent (mL)
1
2
3
4
5
4
4
4
4
4
Sample
Formic acid (5 drops)
Acetic acid (5 drops)
Oxalic acid (0.1 g)
Benzoic acid (0.1 g)
= blank test
Place the tubes in water bath for 5 min and compare with the blank test. Record
your observation.
- 37 -
4. Reaction with KMnO4
Place approximately 1 mL of distilled water in each of 5 test tubes and add in the
reagents and samples as listed in the table below. The last tube is used as a
blank test.
Tube
#
Water (mL)
Conc.
H2SO4
(drop)
0.3%
KMnO4
(mL)
Sample
1
2
3
4
5
4
4
4
4
4
1
1
1
1
1
1
1
1
1
1
Formic acid (5 drops)
Acetic acid (5 drops)
Oxalic acid (0.1 g)
Benzoic acid (0.1 g)
None (= blank test)
Gently shake and place the tubes in water bath for 1 min and compare with the
blank test. Record your observation.
Caution: Extreme care must be exercised to avoid contact with concentrated sulfuric
acid (safely goggles must be worn at all times). If it comes in contact with the skin or
clothes, it must be washed off immediately with excess water. In addition, sodium
bicarbonate may be used to neutralize the acid. Clean up all spills immediately.
Reference
1. “Introduction to Organic Laboratory Techniques: A Small Scale Approach”, Pavia,
Lampman, Kriz and Engel, Brooks/Cole, 2nd Ed, 2005.
2. “Theory and Practice in the Organic Laboratory” Landgrebe, Brooks/Cole, 5th Ed,
2005.
3. “Microscale and Miniscale Organic Chemistry Laboratory Experiments” Schoffstall,
Gaddis, Druelinger, McGraw Hill, 2nd Ed, 2004.
4. “Organic Chemistry”, Solomon and Fryhle, John Wiley & Sons, 8th Ed, 2004.
- 38 -
Experiment
Oxidation and Reduction of Benzoin
10
by Sumrit Wacharasindhu
Objectives
1)
2)
To understand oxidation-reduction processes in organic reactions.
To perform simple oxidation and reduction reactions of benzoin and related
techniques in laboratory-scale synthesis.
Principles
Focusing on the functional groups in a molecule allows us to recognize patterns
in the behavior of related compounds. Consider what we know about the reaction
between sodium metal and water, for example;
H2(g) + 2 Na+(aq) + 2 OH-(aq)
2 Na(s) + 2 H2O(l)
We can divide this reaction into two half-reactions. One involves the oxidation of sodium
metal to form sodium ions.
Oxidation: Na
Na+ + e-
The other involves the reduction of an H+ ion in water to form a neutral hydrogen atom
that combines with another hydrogen atom to form an H2 molecule.
Reduction:
2
H
2H
O
H
2e
H
2H
+
OH
H2
Once we recognize that water contains an -OH functional group, we can predict what
might happen when sodium metal reacts with an alcohol that contains the same
functional group. Sodium metal should react with methanol (CH3OH), for example, to
give H2 gas and a solution of the Na+ and CH3O- ions dissolved in this alcohol.
2 Na(s) + 2 CH3OH(l)
H2(g) + 2 Na+(alc) + 2 CH3O-(alc)
Because they involve the transfer of electrons, the reactions between sodium metal and
either water or alcohol are examples of oxidation-reduction. But what about the
following reaction, in which hydrogen gas reacts with an alkene in the presence of a
transition metal catalyst to form an alkane?
- 39 -
H
H
+
C C
H
H
H2
Ni
H H
H C C H
H H
There is no change in the number of valence electrons on any of the atoms in this
reaction. Both before and after the reaction, each carbon atom shares a total of eight
valence electrons and each hydrogen atom shares two electrons. Instead of electrons,
this reaction involves the transfer of atoms in this case, hydrogen atoms. There are
so many atom-transfer reactions that chemists developed the concept of oxidation
number to extend the idea of oxidation and reduction to reactions in which electrons
aren't necessarily gained or lost.
Oxidation involves an increase in the oxidation number of an atom.
Reduction occurs when the oxidation number of an atom decreases.
During the transformation of ethene into ethane, there is a decrease in the oxidation
number of the carbon atom. This reaction therefore involves the reduction of ethene to
ethane.
-2
H
H
C C
+
H
H
H2
Ni
H H
H C C H
H H
-3
Reactions in which none of the atoms undergo a change in oxidation number are called
metathesis reactions. Consider the reaction between a carboxylic acid and an amine,
for example.
CH 3CO2 H +
CH 3NH2
CH 3CO2
+
CH 3NH 3
Or the reaction between an alcohol and hydrogen bromide.
CH 3CH 2OH
+
HBr
CH 3CH2 Br
+
H 2O
These are metathesis reactions because there is no change in the oxidation number of
any atom in either reaction. The oxidation numbers of the carbon atoms in a variety of
compounds are given in the following table.
- 40 -
Typical Oxidation Numbers of Carbon
Oxidation Number of
Carbon in the Example
CH4
-4
CH3Li
-4
H2C=CH2
-2
CH3OH
-2
CH3OCH3
-2
CH3Cl
-2
CH3NH2
-2
HC CH
-1
H2CO
0
RCHO
+1
+3
RCO2H
CO2
+4
Functional Group Example
Alkane
Alkyllithium
Alkene
Alcohol
Ether
Alkyl halide
Amine
Alkyne
Formaldehyde
Aldehyde
Carboxylic acid
Carbon dioxide
In this experiment, benzoin having both a secondary alcohol and a ketone
functional group can be oxidized to a diketone, benzil, or reduced to a diol, hydrobenzoin.
In this reaction, the commonly used reducing agent, sodium borohydride, is used for the
reduction. The oxidation can be accomplished with any of several oxidizing agents, such
as nitric acid.
O
OH
HNO3
O
Benzoin
MW 212.24
NaBH4
OH
O
Benzil
MW 210.23
OH
Hydrobenzoin
MW 214.26
- 41 -
Experimental Procedure
Part I Oxidation of benzoin to benzil (step 1-3 must be carried out in fume hood)
1. Place 1.0 g of benzoin into a 50 mL Erlenmeyer flask and carefully add 7 mL of
concentrated nitric acid.
2. Heat the mixture on a steam bath with occasional slow swirling for 30 min or until the
brown-red nitric oxide gas longer evolves. Make sure that the fume hood safety
shield is pulled down.
Caution: Concentrated nitric acid is highly corrosive and can cause severe burns.
Nitric oxide (NO2) fume is highly toxic and can damage the lungs.
3. Pour the reaction mixture into 25 mL of cool water and stir to coagulate the
precipitated product.
4. Collect the yellow solid by suction filtration and wash the precipitate twice with 5 mL
of cool water to remove trace amount of nitric acid.
5. Air dry the product on the filtration set for 1 min and transfer it onto a watch glass.
6. Remove trace amount of water in the product by placing another piece of dry filter
paper over and pressing with the bottom of a small beaker or round-bottom flask.
7. Recrystallize the product by adding 5 mL of 95% ethanol, heating the mixture in the
steam bath to make a clear solution, and adding water dropwise until cloudiness
occurs. Allow the solution to cool to room temperature and then place in an ice bath.
8. Collect the yellow solid by suction filtration.
9. Air dry the product on the filtration set for 1 min and transfer onto a watch glass.
10. Weigh the product, record the yield, and determine the melting point.
Part II Reduction of benzoin to hydrobenzoin
1. Place 1.0 g of benzoin into a 50 mL Erlenmeyer flask and dissolve it with 10 mL of
95% ethanol.
2. Carefully add, in small portions, over 5 minutes, 0.20 g of sodium borohydride while
swirling. This reaction is exothermic. Do not add sodium borohydride too rapidly.
3. Allow the reaction to proceed at room temperature for 20 min with frequent swirling.
4. Cool the reaction in an ice bath, add 15 mL of water, then 0.5 mL of 6 M HCl.
5. Add another 5 mL of water and allow the mixture to stand for 20 min at room
temperature with frequent swirling.
6. Collect the product by suction filtration and rinse with 50 mL of water.
7. Recrystallize the product by adding 5 mL of 95% ethanol, heating the mixture in the
steam bath to make a clear solution, and adding water dropwise until cloudiness
occurs. Allow the solution to cool to room temperature and then place in an ice bath.
8. Collect the yellow solid by suction filtration.
9. Air dry the product on the filtration set for 1 min and transfer onto a watch glass.
10. Weigh the product, record the yield and determine the melting point.
- 42 -
Experiment
Amines
11
by Duangamol Nuntasri
Objectives
1. To classify amines according to their characteristic chemical reactions
2. To use the chemical characteristics to identify amine sample
Principles
Amines are organic compounds that resemble ammonia but at least one hydrogen
atom is replaced by organic substituents like alkyl (alkane chain) and aryl (aromatic
ring) groups.
Types of Amines
Amines can be classified as primary, secondary or tertiary. If there is only one carboncontaining group (such as in CH3NH2) then it is considered primary. Two carboncontaining groups make it secondary, and three groups make it tertiary. The lone pair of
electrons on the nitrogen is sometimes donated to form a fourth carbon-containing
group to the amine. In this case, quaternary ammonium salt (R4N+X-) is obtained.
Primary amine
Secondary amine
H
N
H
R1
R1
R1
H
Tertiary amine
R3
N
R2
N
R2
An organic compound with multiple amine groups is called a diamine, triamine,
tetraamine and so forth, based on the number of amino groups on the molecule. The
formula for the simplest diamine, for example, is
H2N-CH2-NH2
Aromatic amines
Aromatic amines have the nitrogen atom directly bonded to an aromatic ring. Due to its
delocalization properties, the aromatic ring greatly decreases the basicity of the amine this effect can be either enhanced or offset depending on the substituents on the ring
and on nitrogen. The presence of the lone pair electrons from the nitrogen has an
opposite effect on the electron density of the ring. It causes the ring to become much
more reactive, particularly towards electrophiles.
- 43 -
Naming conventions
Generally amines are named for their carbon structures with the amine functionality
included as either a prefix (amino-) or a suffix (-amine"). Generally, smaller molecules
will use the suffix form, while larger chains will list amine functionality as if it were any
other type of functional group. Examples include methlyamine (CH3NH2), and 2aminopentane (CH3NH2CH(CH2)2CH3).
as prefix: "amino-"
as suffix: "-amine"
the prefix "N-" shows substitution on the nitrogen atom (in the case of secondary,
tertiary and quaternary amines)
•
•
•
Systematic names for some common amines:
small amines are named
with the suffix -amine.
large amines have the prefix
amino as a functional group.
H 3C
H2 N
CH3
CH3
NH2
Methylamine
2-Aminopentane
Physical properties
1. Basicity
1.1 Solubility and 1.2 Indicator testing
All three classes of amines form hydrogen bonds with water.
N
+
H
OH
N
H
OH
For this reason, low-molecular weight amines are water soluble. Borderline water
solubility is observed when the amine has about six carbon atoms. Aqueous solutions of
amines are alkaline (basic).
N
H
OH
N
H
+
OH
Like ammonia, amines act as reasonably strong bases (see the provided table for some
examples of conjugate acid Ka values). The basicity of amines varies by molecule, and
it largely depends on:
•
The availability of the lone pair electrons on the nitrogen
- 44 -
Ions of compound
Kb
ammonia NH3
1.8 × 10-5
methylamine CH3NH2
4.4 × 10-4
propylamine CH3CH2CH2NH2
4.7 × 10-4
2-propylamine (CH3)2CHNH2
5.3 × 10-4
diethylamine (CH3)2NH2
9.6 × 10-4
+I inductive effect of alkyl groups raises the energy of the lone pair of electrons, thus
elevating the basicity.
•
The electronic properties of the attached substituent groups (e.g., alkyl groups
enhance the basicity, aryl groups diminish it, etc.)
Ions of compound
Kb
ammonia NH3
1.8 × 10-5
aniline C6H5NH2
3.8 × 10-10
4-methylphenylamine 4CH3C6H4NH2
1.2 × 10-9
+M mesomeric effect of aromatic ring delocalizes the lone pair electron into the ring,
resulting in decreased basicity.
•
The degree of solvation of the protonated amine, which depends mostly on the
solvent used in the reaction
The nitrogen atom of a typical amine features a lone electron pair which can bind a
hydrogen ion (H+) in order to form an ammonium ion -- R3NH+. The water solubility of
simple amines is largely due to the extent of hydrogen bonding that occurs between
protons of water and N lone pairs.
Amine protonation VS water solubility:
Ions of compound
Maximum number of H-bond
NH4+
4 Very Soluble in H2O
RNH3+
3
R2NH2+
2
R3NH+
1 Least Soluble in H2O
- 45 -
1.3 Salt Formation
Amines are weak organic bases that form salts with strong acids.
H+ Cl-
+
N
N
H Cl
Like ordinary salts, ammonium salts are readily dissociate into ions and are therefore
water soluble. The salts can be reconverted to amines by making their solutions
alkaline.
N
H Cl
+
Na+ OH-
+ Na+ Cl- + H2O
N
2. Reaction with bromine in water
The amino functional group in aniline works as electron donating group to the benzene
ring via resonance effect, making electrophilic aromatic substitution reaction more
favorable than for non-substituted aromatics. For the bromination of aniline, bromine
acts as electrophile which gets directed to substitute hydrogen atoms at ortho- and
para- positions, producing 2-4-6-tribromoaniline. With, aliphatic amines this type of
reaction cannot occur.
NH2
NH2
Br
Br
+
+
3 Br2
3 HBr
Br
3. Reaction with nitrous acid
Nitrous acid (HNO2) is unstable, and so a mixture of NaNO2 and dilute acid is usually
used to produce nitrous acid in situ. Primary aliphatic amines with nitrous acid give very
unstable diazonium salts which spontaneously decompose by losing N2 gas, forming a
carbonium ion. The carbonium ion goes on to produce a mixture of alkenes, alcohols or
alkyl halides, with alcohols as the major product. This reaction is of little synthetic
importance because the diazonium salt formed is too unstable, even under quite cold
conditions.
NaNO2 + HCl → HNO2 + NaCl
H2 C
R
NH2
HCl
NaNO2
R
R
C
H2
N
R
CH2
+ N
N
H2C
OH
N
Primary aromatic amines, such as aniline (phenylamine) form a more stable diazonium
ion at 0–5°C. Above 5°C, it decomposes to give phenol and N2. Diazonium salts can be
isolated in the crystalline form but are usually used in solution and immediately after
preparation, due to rapid decomposition on standing even with little ambient heat. Solid
diazonium salts can be explosive on mild warming.
- 46 -
NH2
N
N
HCl / NaNO2
5 oC
If the primary amine is readily converted to a diazonium salt and loses nitrogen, bubbles
will be visible in a very short period of time. If no bubbles of nitrogen appear, you can
assume that the amine is secondary or tertiary rather than primary.
At low temperatures, diazonium salts are stable and will couple with the alpha position
with the sodium salt of β-naphthol to form a red colored precipitates.
OH
Cl
N
OH
N
N
+
N
Azo compound
(red)
β-naphthol
(colorless)
4. Hinsberg test
The reaction between primary or secondary amines and benzenesulfonyl chloride in the
presence of sodium hydroxide solution yields the corresponding substituted
benzenesulfonamide, whereas tertiary amines do not react with this combination of
reagents.
With primary amines the sulfonamide formed is acidic and dissolves in the excess base
used to yield a solution of the corresponding anion. Addition of excess hydrochloric acid
converts the anion into the water-insoluble sulfonamide.
RNH2
+
SO2Cl
NaOH
SO2NHR +
NaCl
+
H2O
Insoluble in water
excess
HCl
excess
NaOH
SO2NRNa
+
H2O
Solubility in water
Secondary amines react with benzenesulfonyl chloride but the sulfonamide lacks an
amide hydrogen and is insoluble in the both aqueous basic and acid reagents.
- 47 -
R2NH
+
SO2Cl
NaOH
SO2NR2
+
NaCl
+
H2 O
Insoluble in water
excess
NaOH
No reaction
Tertiary amines react differently with benzenesulfonyl chloride; the intermediate
ammonium ion does not have a proton to lose and reacts rapidly with hydroxide ion to
displace the benzenesulfonate anion and regenerate the tertiary amine.
R3 N
+
SO2Cl
NaOH
SO2NR3 Cl
water soluble
excess
NaOH
SO3
+ NR3 +
Cl
water soluble
The overall reaction amounts to an amine-catalyzed hydrolysis of the benzenesulfonyl
chloride. With tertiary amines there can be a side reaction between the amine and the
intermediate ammonium ion to produce a complex mixture of water-insoluble products,
which could lead to confusion with the results for a secondary amine. This complication
can be minimized by keeping the concentration of the amine low. If there is any doubt
regarding the interpretation of the results, carry out the test on known compounds and
compare the results with those of the unknown.
5. Rimini’s test, Simon’s test, modified Rimini’s test and modified Simon’s test
Rimini’s reagent (sodium nitroprusside and acetone) and Simon’s reagent (sodium
nitroprusside and acetaldehyde) can be used as to distinguish primary amines from
secondary aliphatic ones. When amines react with Rimini’s reagent, different colors are
produced, according to Table 1. Modified versions of Rimini’s reagent and Simon’s
reagent, however work well for identifying aryl amines. i.e. primary, secondary and
tertiary aromatic amines.
- 48 -
Table 1 The developed color of Rimini’s test, Simon’s test, modified Rimini’s test and
modified Simon’s test
Reagent
1o aliphatic
2o aliphatic
1o aromatic
2o aromatic
3o aromatic
Rimini
purple
deep red
-
-
-
Simon
pale yellow
to
red brown
deep blue
-
-
-
Modified
Rimini
-
-
Blue green
blue green
Modified
Simon
-
-
purple
blue green
orange red
to
red brown
orange red
to
red brown
Amine samples for chemical reaction testing
Aliphatic amine
C4H7
C4H7 NH
di-n-butylamine
C4H7 NH2
n-butylamine
Aromatic amine
NH2
Aniline
CH3
CH3
NH
N CH3
N-methylaniline
N,N-dimethylaniline
- 49 -
Experimental Procedure
1. Basicity testing
1.1 Water solubility
Test with n-butylamine, di-n-butylamine and N,N-dimethylaniline
To 2 mL of distilled water in a test tube, add 5 drops of amine and note its solubility.
Test the resulting solution with pink litmus paper.
1.2 Indicator test
Test with n-butylamine and aniline
Add 2 drops of amine to each of two test tubes containing 1 ml of distilled water. To one
tube add a drop of phenolphthalein indicator and to the other add a drop of
bromothymol blue solution. Interpret the results observed on the basis of the following
information: bromothymol blue; below pH 6 the color is yellow, at pH 7 it is yellow-green,
and above pH 7.5 the color is blue. Phenolphthalein is colorless at pH 8.4 and red
above pH 8.6.
1.3 Salt formation
Test with n-butylamine and aniline
To 10 drops of 6M HCl, add 2 drops of amine and shake. Note whether the amine is
soluble in aquous acid. Add 6M NaOH dropwise until the solution becomes alkaline, and
observe.
2. Reaction with bromine in water
Test with n-butylamine and aniline
To 1 ml of distilled water in test tubes, add 1 drop of amine then bromine water
dropwise until excess of bromine and shake.
3. Reaction with nitrous acid (Azo dye)
Test with n-butylamine and aniline
To 1 mL of conc. HCl and 1mL of water, add amine 5 drops. Stir the solution while
cooling in ice bath (ensure temperature does not exceed 5oC). Dissolve 0.2 g NaNO2 in
1 mL distilled water and cool in ice bath at the same temperature. Add NaNO2 solution
dropwise with stirring or shaking to the cold amine hydrochloride. The endpoint can be
determined by putting a drop of the solution on starch-KI paper. A blue color is observed
when excess nitrite is present. Observe whether bubbles appear or not.
Compare the result between n-butylamine and aniline.
Remove about 1 mL of the aniline diazonium chloride solution into test tube and heat on
water bath at 50oC. Observe the change and odour.
To another portion of the cold aniline diazonium solution, add a pre-chilled solution of
0.1 g of β-naphthol in 1 mL of 5% NaOH. Observe the result.
- 50 -
4. Hinsberg Test
Test with aniline, N-methylaniline and N,N-dimethylaniline
To 2 drops of amine in test tube with 1 mL of water, add 1 mL of 10% aqueous NaOH
and 2 drops of benzenesulfonyl chloride (in hood). Close test tube tightly with stopcock
and vigorously shake the tube for 5 mins and note any reaction. If unreacted
benzenesulfonyl chloride is left as an oil drop at bottom of tube. In this case, warm the
mixture do not boil in hood with shaking for 10 min. The reaction mixture should still be
strongly alkaline at this point. Cool the test tube to room temperature, shake well, and
note whether any solid or liquid separates. Do not confuse any separated material with
unreacted benzenesulfonyl chloride. Observe the result.
Separate half amount of reaction mixture (both liquid and solid) into new test tube. Add
2M of HCl until solution turns acidic. Observe if a precipitate forms. If so, this indicates
that the unknown was a primary amine. However, if the organic material does not
dissolve in the hydrochloric acid, it indicates a secondary amine (acid- and baseinsoluble secondary sulfonamide). If the organic material is soluble, it indicates a tertiary
amine (acid soluble, unreactive toward benzenesufonyl chloride).
5. Rimini test, Simon test, modified Rimini test and modified Simon test
5.1 and 5.2 test with aliphatic amine (n-butylamine and di-n-butylamine)
5.3 and 5.4 test with aromatic amine (aniline, N-methylaniline and N,N-dimethylaniline)
5.1 Rimini test
To 1 mL of sodium nitroprusside reagent A (0.13 M in 50% aq. methanol) in test tube
with 1 mL of water, add 5 drops of acetone and 3 drops of amine. Shake the tube and
observe result within 2 min.
5.2 Simon test
To 1 mL of sodium nitroprusside reagent A (0.13 M in 50% aq. methanol) in test tube
with 1 mL of water, add 5 drops of 2.5 M acetaldehyde solution and 3 drops of amine.
Shake the tube and observe result within 2 min.
5.3 Modified Rimini test
To 1 mL of sodium nitroprusside reagent B (0.13 M in 80% aq. dimethyl sulfoxide) in
test tube with 1 mL of saturated ZnCl2 aqueous solution, add 5 drops of acetone and 3
drops of amine. Shake the tube and observe result within 2 min.
5.4 Modified Simon test
To 1 mL of sodium nitroprusside reagent B (0.13 M in 80% aq. dimethyl sulfoxide) in
test tube with 1 mL of saturated ZnCl2 aqueous solution, add 5 drops of 2.5 M
acetaldehyde solution and 3 drops of amine. Shake the tube and observe result within 2
min.
6. Classification test for an unknown compound
Obtain an unknown sample from your instructor. Record the sample number. First,
determine if the unknown is an alkyl or aryl amine and then determine whether the
amine is primary, secondary, or tertiary. Consult with your instructor and write down the
answer in your report sheet.
Caution
- Carefully dispose the red azo compound and reaction mixture from reaction with
nitrous acid by washing down the drain without contact to your skin.
- 51 -
Experiment
Identification of Organic Compounds
12
by
Duangamol Nuntasri
and Paitoon Rashatasakhon
Objectives
1. To classify organic compounds to the corresponding solubility classes.
2. To determine functional groups of organic compounds by chemical tests
Principles
Qualitative organic analysis, the identification and characterization of organic
compounds, is an important part of organic chemistry. In this experiment you will be
issued an unknown compound and asked to identify it through chemical methods. Your
instructor will give you an unknown, you must first determine the class of compound to
which the unknown belongs. Then identify its main functional group and determine the
specific compound in the class that corresponds to the unknown. Unknown compounds
are restricted to include only eight possible important functional groups: aldehydeketone, carboxylic acid, phenol, amine, alcohol, alkyl halide, unsaturated, and
ester. The experiment presents all of the chemical methods of determining the main
functional groups, and it includes methods for verifying the presence of the subsidiary
functional groups as well.
How to proceed
1. Preliminary classification by physical state.
2. Determination of solubility in different solvents
3. Application of relevant chemical classification tests
Preliminary classification
Note the physical characteristics of the unknown. These include its color, its
odor, and its physical state (liquid, solid, crystalline form). Compounds with a high
extent of conjugation are frequently yellow to red. Amines often have a fishlike odor.
Esters have a pleasant fruity or floral odor. Acids have a sharp and pungent odor. As a
note of caution, many compounds have distinctly unpleasant or nauseating odors.
Some have corrosive vapors. Any unknown substance should be smelled with the
greatest caution. Initially, open the unknown container, holding it away from you. Then,
using your hand, carefully waft the vapors toward your nose.
Solubility behavior
Solubility tests are important in determining the nature of the main functional
group of the unknown compound. These a tests are simple, require only small amounts
of unknown, and can reveal whether the compound is a base (amine), an acid (phenol),
a stronger acid (carboxylic acid), or a neutral substance (aldehyde, ketone, alcohol,
ester). Common solvents used to determine solubility include water, 5% NaOH, 5%
NaHCO3, 5% HCl, and conc. H2SO4.
- 52 -
The solubility tests and solubility classes (Table 1) provides a useful and logical
approach to determining compound class from solubility observations. The possible
functional groups for each solubility class are listed in Table 2.
Chemical classification tests
The solubility tests usually suggest or eliminate several possible functional
groups. The chemical classification tests listed in Table 3 allows one to distinguish
among these possible choices. You should choose to perform only those meaningful
tests; time is wasted doing unnecessary tests. The solubility and the main chemical
tests will be possible to identify the class of compound. Solubility tests automatically
eliminate the need for some of the chemical tests. Each successive test will either
eliminate the need for another test or dictate its use. Many possibilities may be
eliminated on the basis of logic alone.
Experimental Procedure
Part 1 Solubility tests
Five unknowns (A to E) will be used for this experiment. The order of solvents for
this test should be as follows:
Water Æ 5% NaOH Æ 5% NaHCO3 Æ 5% HCl Æ concentrated H2SO4
Place about 1 mL of the solvent in a test tube. Add two drop or 50 mg (about the
size of one grain of rice) of an unknown directly into solvent. Shake the test tube to
ensure good mixing, and then observe whether the unknown is soluble. The
disappearance of the liquid or solid, or the appearance of the mixing lines, indicates that
dissolution is taking place. Add several more drops of the liquid, or a few more crystals
of the solid, to determine the extent of the compound’s solubility. A common mistake in
determining the solubility of a compound is testing with a quantity of the unknown too
large to dissolve in the chosen solvent. Use small amounts. It may take several minutes
to dissolve solids. Compounds in the form of large crystals will need more time to
dissolve than powders or very small crystals. In some cases it is helpful to first pulverize
a compound composed of large crystals. Sometime gentle heating helps, but strong
heating is discouraged, as it often leads to reaction. When colored compounds dissolve,
the solution often assumes the same color.
By the above procedure, the solubility of the unknown should be determined in
each of the following solvents: water, 5% NaOH, 5% NaHCO3, 5% HCl, and
concentrated H2SO4. With sulfuric acid, a color change may be observed rather than
dissolution. A color change should be regarded as a positive solubility test.
If compound is found to dissolve in water, the pH of the aqueous solution should
be estimated with pH paper or litmus. Compounds soluble in water are usually soluble
in all the aqueous solvents. If a compound is only slightly soluble in water, it may be
more soluble in acid or alkali. For instance, a carboxylic acid may be only slightly
soluble in water but very soluble in dilute base. It will often not be necessary to
determine the solubility of the unknown in every solvent.
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Part 2 Solubility test and determine functional group of specific unknown
-
Obtain your specific unknown from the instructor
Record the unknown number
Report the physical character of the unknown
Classify unknown into the solubility class, and check your answer before
proceed to the next step
Examine unknown functional group using appropriate chemical tests as shown in
Table 3
Report the answer of unknown in your report sheet
Ref. Pavia, D.L.; Lampman, G.L.; Kriz, G.S. Introduction to Organic Laboratory
Techniques, 3rd ed., W.B. Saunders Company, New York.
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Table 1
Solubility tests and Solubility classes
Solvent (1 ml) : unknown (2 drops or 1 grain of rice)
Water
Soluble and
change blue
litmus into red
Soluble but does
not change blue
litmus into red
Soluble and
change red
litmus into blue
Soluble but does
not change red
litmus into blue
5%
NaHCO3
5%
HCl
conc.
H2SO4
5%
FeCl3
-
Produces
CO2 gas
-
-
-
-
No gas
evolves
-
-
Change color of
Water soluble weak acid
FeCl3 solution
-
Produce redbrown precipitate
Water soluble base
-
-
Does not change
color of FeCl3
solution
Water soluble neutral
compound
-
-
-
Strong acid
-
-
Weak acid
-
-
Basic compound
-
-
-
Insoluble
Soluble
Insoluble
Slightly
soluble
Insoluble
Insoluble
Slightly
soluble and
produces
CO2 gas
Insoluble
-
Insoluble
Solubility class
5%
NaOH
Insoluble
-
-
Soluble
(contains N
atoms)
Insoluble
(contains N or
S atoms)
-
-
Water soluble strong
acid
Miscellaneous neutral
compound
(this class of compounds is not
available in this course)
Insoluble
Insoluble
-
Insoluble
(no N or S
atom)
Soluble
-
Neutral compound
Note 1. “ - ” = unnecessary.
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Table 2
Functional group tests for compounds in each solubility class
Functional groups
Solubility class
Neutral
(see note 1)
Water soluble strong acid
Water soluble weak acid
Water soluble base
Water soluble neutral compound
Strong acid
Weak acid
Basic compound
Neutral compound
Phenol
√
√
Carboxylic
acid
Amine
√
√
√
√
√
√
√
√
Note :
1.
The following functional groups are possible for this class of compounds.
1.1. carbonyl compounds (aromatic or aliphatic aldehyde, α-hydroxy ketone, methyl ketone,
or other ketone)
1.2. alcohol (primary, secondary, or tertiary alcohol)
1.3. ester
1.4. unsaturated hydrocarbon (alkene or alkyne)
1.5. alkyl halide (primary, secondary, or tertiary alkyl halides)
1.6. nitro compound
(not available in this course)
1.7. thiol
(not available in this course)
1.8. amide
(not available in this course)
1.9. ether
(not available in this course)
The solubility flow-chart below provides a summary of information from Table 1 and Table 2.
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low MW
amines
turn red litmus to blue
low MW
carboxylic acids
turn blue litmus to red
soluble
Unknown
No change with
litmus
H 2O
soluble
insoluble 5%NaHCO3
strong acids
insoluble
soluble
weak acids
bases
5%NaOH
insoluble
neutral, hydrogen
bonding or neutral but
polar
carboxylic acids
some phenols
phenols
amines
soluble
5%HCl
insoluble
neutral
compounds
soluble
conc.H2SO4
alkenes
esters
alkynes
ethers
alcohols amides
ketones
thiols
aldehydes
alkyl halides
nitro compounds
insoluble
inert
compounds
alkanes
aromatic
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Table 3
Functional group
Aldehyde, ketone
(see exp. 8)
Functional group tests and required reagents
Sub-functional group
Aldehyde: aliphatic,aromatic
Ketone: α-hydroxy ketone,
methyl ketone, other ketones
Alcohol
(see exp. 6)
Ester
1°, 2°, 3° alcohol
Reagents
(see note 1)
Solvent for solid
unknown
1. 2,4-DNP
Ethanol
2. Schiff’s reagent
Ethanol
3. Tollens’ reagent
Ethanol
4. Benedict’s reagent
Ethanol
5. Iodoform test
Ethanol
1. Ceric nitrate reagent
(positive results= red or orange)
2. Lucas reagent
3. Oxidation test
-
-
Ferric hydroxamate test
-
Unsaturation
(see exp. 4)
-
1.
2.
-
Carboxylic acid
-
5% NaHCO3
-
1.
2.
3.
(see exp. 9)
KMnO4
Br2/CCl4
-
(see exp. 9)
Phenol
(see exp. 6)
Amine
(see exp. 11)
Alkyl halides
(see exp. 5)
Aliphatic, aromatic amine
1°, 2°, 3° amine
1°, 2°, 3° alkyl halide
5% FeCl3
Ceric nitrate reagent
Br2/H2O
1. 2 M HCl
2. Sodium Nitroprusside Test
(Ramini, Simon, Modified
Ramini and Simon)
3. Diazotization & Coupling
4. Br2/H2O
1. AgNO3 / EtOH
2. NaI / actone
Ethanol
Dioxane or acetone
Ethanol
-
-
Note:
1. For liquid unknown, perform the tests without any solvent.
2. For solid unknown which is soluble in water, perform the tests using a solution of the
unknown in water.
3. For solid unknown which is insoluble in water, perform the tests using a solution of the
unknown in solvent listed in Table 3.
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