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1
UNIVERSITY OF NAIROBI
COLLEGE OF BIOLOGICAL AND PHYSICAL SCIENCES
SCHOOL OF PHYSICAL SCIENCES
SCH 206: ORGANIC ACIDS, ESTERS, PHENOLS AND AMINES
A PRACTICAL MANUAL
FOR
BACHELOR OF EDUCATION (SCIENCE) AND BACHELOR OF
SCIENCE
2
GENERAL LABORATORY GUIDELINES AND SAFETY INSTRUCTIONS
The organic chemistry laboratory is potentially one of the most dangerous of the
undergraduate laboratories. That is why, for your personal safety and those of whom you
work with, it is important that you pay close attention to the general safety regulations
that apply in the lab.
Safety in the laboratory is also an integral part of your practical training. Adherence to
good, safe laboratory practice must be observed at all times. The following guidelines,
though not exhaustive, must be observed:
(1) You must wear a white lab-coat at all times during the laboratory session. Wear
closed shoes while reporting to the lab. No student wearing sandals will be admitted
to the lab.
(2) Punctuality must be observed. Latecomers will be barred from the practical session
and no practical will be repeated for those who either absent themselves or report
late.
(3) Handle the apparatus assigned to you with care. Since the glassware are very
expensive, you will be surcharged for any losses or breakages.
(4) All students must stay in the lab until they have completed their experiment.
Permission to move out of the lab must first be sought from the instructor.
(5) All mobile phones must be switched off during the practical session. Violation will
lead to cancellation of the practical for the offending student.
(6) Drinking, eating or playing in the lab is strictly prohibited.
(7) To avoid mix-ups, clearly label any products you isolate during a practical session
and keep them safely in your locker. Any solid products must be left to dry atleast
overnight before attempting a melting point determination.
(8) Proper waste disposal must be observed. Solid waste should only be disposed in the
solid waste containers located next to your working bench and not in the sink.
(9) Leave your working area clean at the end of the experiment and thoroughly clean
your hands with soap before leaving the lab.
(10) Remember to sign the attendance register at the end of each lab session.
(11) Lab reports are due one week after the completion of the experiment.
3
EXPERIMENT 1
REACTIONS OF ALDEHYDES AND KETONES I
Acetophenone
A. Reduction of Acetophenone to Ethylbenzene
Introduction:
Carbonyl compounds can be reduced by a variety of reagents to their corresponding
alcohols (primary from aldehydes, secondary from ketones).
Other reduction methods are available which convert the carbonyl group to a methylene
group.
The Wolff-Kishner reduction effectively uses hydrazine as the reducing agent. The
carbonyl compound is first converted to its hydrazone which then undergoes a
rearrangement and decomposition, with the loss of nitrogen gas, when heated strongly
with base. The reaction is conveniently carried out in diethylene glycol, which is a good
solvent for the organic material as well as KOH and can be heated to the required high
temperatures.
Experiment:
In a 100 ml flask fitted with a reflux condenser place 4.5 ml (approx 4.6g) of
acetophenone, 15 ml of diethylene glycol, 4.0 ml of 90% hydrazine hydrate and 5 g of
potassium hydroxide pellets. Warm the mixture over a very small flame with continuous
swirling until the KOH pellets dissolve to give a clear solution. Heat the flask over a free
flame under reflux for one hour.
R
R
OR
R
H
OH
2 [H]
R
R
OR
R
H
H
4 [H]
+ H2O
4
Cool the mixture and then fit the flask with a still head, thermometer (with its bulb
dipping into the liquid) and a condenser for distillation. Distill out and collect all the
volatile material in a 10 ml graduated cylinder until the temperature of the liquid rises to
175 ºC. The distillate will consist mainly of ethylbenzene and water.
To aid in the separation, top-up the liquid in the cylinder with distilled water and the
separate the upper hydrocarbon layer from the lower water layer using a dropper.
Transfer the hydrocarbon layer into a clean conical flask. Dry the hydrocarbon (organic
layer) with a little anhydrous magnesium sulphate. Carefully decant the dry hydrocarbon
in a dry 50 ml round bottomed flask and redistill. Collect the distillate in a 10 mL
graduated cylinder. Record the boiling point range (observed), the volume of
ethylbenzene obtained and calculate the percentage yield of the reaction. Determine a
more accurate boiling point using the Siwolloboffs method.
B. Addition of a Carbanion-The Preparation of Chalcone (Benzal acetophenone).
Introduction:
Carbonyl compounds undergo aldol condensation if reacted in the presence of a base
under suitable conditions. Aldehydes which contain -hydrogens undergo self
condensation in the presence of a suitable base.
R tertiary
Cross aldol products are formed between non-enolizable aldehydes and ketones.
In this experiment you will prepare a cross aldol product between benzaldehyde, a non-
enolisable aldehyde, and acetophenone.
R H
O
R H
OBase
(e.g. OH-)
R R
O
R R
ORBase
(e.g. OH-)
(2 moles)
R H
O
CH3
R'
O
+
OH-
non-enolisable
R R'
O
a cross aldolproduct
5
Experiment:
In a conical flask mix 10 ml of 10% NaOH solution, 5 ml of 95% ethanol and 1.8 g
(0.017 mole) of benzaldehyde. Cool the mixture in an ice-bath and add dropwise 2 g
(0.017 mole) of acetophenone, while swirling vigorously. Mix the liquids thoroughly by
shaking. Stopper the flask tightly and swirl vigorously for one hour, at 5-10 minute
intervals at RT. A yellow oil will separate. Cool the flask in an ice-bath and induce
crystallisation by scratching the sides of the flask with a glass rod.
When crystallisation is complete, collect the solid precipitate by suction filtration. Wash
the crystals with a little cold water and a little ice-cold 95% ethanol. Weigh the dry
crystals of the crude product. Reserve a few crystals for seeding and recrystallize* the
crude product from 95% ethanol. Let the crystals dry (atleast overnight) and then
determine the melting point of the recrystallized material.
* As you will find out, chalcone is not easy to recrystallize. Allot of patience required.
6
EXPERIMENT 2
REACTIONS OF ALDEHYDES AND KETONES II
Addition of an Amine to an Aldehyde or Ketone- The Preparation of Imines
Introduction:
Aldehydes and ketones can be detected using Brady’s reagent (2,4-dinitrophenyl hydrazine). The product, a
hydrazone, is a yellow solid which precipitates out of solution.
In general, aldehydes and ketones react with primary amines with the loss of water to form imines.
Experiment:
You are supplied with an unknown (aromatic) aldehyde, which is to be identified by
reaction with aniline (phenylamine) to give the anil (phenylimine).
Instructions
Place 1 ml (1 g if a solid) of the unknown aldehyde, 1 ml of phenylamine, 7 ml of
petroleum ether (b.p. 40-60 oC ) and one or two boiling chips in a small flask fitted with
a still head and condenser. Gently heat the flask in a water bath so that the petroleum
ether distils off slowly and collect the distillate in a small measuring cylinder. When all
the solvent has distilled off, continue heating for an additional 30 min and then cool the
flask. Dissolve the contents of the flask in a little methanol (3 ml or less), and transfer
R R
O
+
R = H, alkyl or aryl
NH2
R'N
R'
R
R+ H2O
Imine
R R
O
NNH
NO2
NO2
R
RNH
2
NH
NO2
NO2
+
a 2,4-dinitrophenylhydrazone2,4-dinitrophenylhydrazine
A carbonylcompound
R = H, alkyl or aryl
+ H2O
7
the mixture to a small conical flask or beaker. Cool the mixture in an ice-bath and stir or
carefully scratch the sides of the flask with a glass rod to induce crystallisation. Filter the
crude solid product and rinse the solid residue with a little ice-cold methanol (just a few
sprinkles only). Recrystallize the solid product from a minimum volume of boiling
methanol, but retain a few crystals as “seeds” in case recrystallization proves to be
difficult. Let the filtered crystals dry atleast overnight before attempting a melting point
determination. Compare the melting point obtained against that of anil derivatives of
various aromatic aldehydes listed in Table 1 to identify the unknown aldehyde allotted
to you.
Table 1: Melting points of “Anils” (Phenylimines) derived from Aromatic Aldehydes
Aldehyde m.p. (º C) of the Derived Anils
(Phenylimine)
Benzaldehyde 54-55
p-Methoxybenzaldehyde (Anisaldehyde) 60-62
Cinnamaldehyde 109
o-Hydroxybenzaldehyde (Salicylaldehyde) 51
4-Hydroxy-3-methoxybenzaldehyde (Vanillin) 152-3
o-Nitrobenzaldehyde 69-70
p-Nitrobenzaldehyde 93
p-Chlorobenzaldehyde 66
For your own practice, you may attempt the reactions mechanism of the reactions shown
below. Note however that you are not required to submit the answer to these questions
Questions on mechanisms
1. Work out reaction mechanisms for the following transformations
OO
OH
H
O
O
H
H
NaOH
MeOH
(a)
8
2. Paraldehyde induces sleep when it is administered to animals in large doses, and
consequently it is used as a sedative or a hypnotic. Propose a mechanism for the
formation of paraldehyde.
O
O
Br
Br
O
OO
NaOH
(b)
O
O
O
NaOH(c)
CH3
H
OO
O
O
CH3
CH3
CH3
3H+
Paraldehyde
9
EXPERIMENT 3
PREPARATION OF ESTERS FROM CARBOXYLIC ACIDS AND
ALCOHOLS
Introduction
The esterification reaction between carboxylic acids and alcohols is acid-catalyzed and can be
represented by the equilibrium reaction shown below.
Since carboxylic acids themselves produce a small concentration of protons, the reaction is
spontaneous (though very slow) at room temperature. For example a mixture of acetic acid and 1-
butanol, if left at room temperature for a few days, will develop a sweet smell characteristic of
butyl acetate.
For preparative purposes, the reaction can be speeded up by using higher temperatures and an
additional supply of catalytic protons. Sulphuric acid, hydrochloric acid, phosphoric acid or p-
toluenesulphonic acid are frequently used as acid catalysts. Concentrated sulphuric acid has the
additional advantage that it tends to force the equilibrium reaction to the right by reacting with the
water molecules produced in the reaction.
Other methods of increasing the yield by forcing the equilibrium position to the right include:
- The use of a large excess of either the carboxylic acid or the alcohol reactant (especially
if one happens to be cheap and readily available.)
- Conducting the reaction under distillation conditions. Removing the more volatile
product as it forms.
In the present practical you will be supplied with about 15 ml of any one of the isomers of
butanol (C4H9OH) shown in Table 1. You will be required to use a small portion of this alcohol to
identify the alcohol (qualitatively i.e. determine whether it is a primary, secondary or tertiary
alcohol) and the main portion to prepare its liquid butyrate ester. The final portion of the alcohol
will be used to prepare a solid 3,5-dinitrobenzoate ester derivative, whose melting point should be
matched with those in Table 2 to determine the unknown isomer of butanol allocated to you.
R OH
O
R OR'
O
+ R'OHH+
+ H2O
10
(a) Preparation of Butyrate Ester
Procedure
Measure 6 ml of the unknown alcohol (assume a density of 0.8 gml-1), 6 ml of butanoic (butyric)
acid (bpt 162 oC) and 0.5 ml of concentrated sulphuric acid into a 50 ml round bottom flask. Mix
well, add one or two boiling chips, attach a reflux condenser and heat under reflux for one hour.
While waiting for the reflux period to elapse, start parts b and c of the experiment.
At the end of the reflux period, cool the reaction mixture to room temperature under the tap and
pour it into a separating funnel containing 30 mL of water. Shake gently and allow the layers to
separate before running off the aqueous layer. Wash the organic ester successively with 20 ml of
water, 10 ml of 5% sodium bicarbonate and 10 ml of water. Separate the layers as completely as
possible in each successive wash and eventually pour the washed crude ester into a clean conical
flask. Add a small amount of drying agent (anhydrous magnesium or sodium sulphate) into the
flask and stir until the ester is dry as determined by loss of cloudiness in the crude ester. Carefully
decant the dry crude ester into a distillation flask and distil, recording the temperature range over
which the product is collected. Weigh the distillate (butyrate ester) and calculate the percentage
yield of the reaction. Determine a more accurate boiling point of the distillate by the Siwoloboffs
method.
(b) Determination of the Classification of the Unknown Isomer of Butanol
Meanwhile test the remaining sample of the unknown isomer of butanol by the Lucas test to
determine if it is a primary, secondary or tertiary alcohol.
Table 1
Isomers of Butanol Classification of Alcohol
1-Butanol Primary
2-Butanol Secondary
2-Methylpropan-1ol Primary
2-Methylpropan-2-ol Tertiary
Caution: The Lucas test uses the Lucas reagent (A mixture of ZnCl2 and concentrated HCl). This
mixture is very corrosive and can cause serious burns. Inhaling the vapour is also harmful. Use
gloves when using this reagent and perform the test entirely in the fume chamber.
Procedure
Add 1 mL of the unknown alcohol to a test tube containing 2 mL of the Lucas reagent and shake
well. Allow the mixture to stand for about 15 minutes, a period within which you should
periodically monitor for any evidence of reaction (cloudiness) or layer separation (two distinct
11
layers that persist even after shaking). If the alcohol is tertiary, a reaction will occur immediately
(<1 minute) and distinct layer separation occurs within this period. If the alcohol is secondary, the
reaction will take place but at a slower rate; the reaction turns cloudy in about 3 to 5 minutes and
distinct layer separation occurs within 15 minutes. Primary alcohols are essentially inactive and
the mixture remains clear. No layer separation occurs even after standing for more than 15
minutes.
(c) Preparation of 3,5-Dinitrobenzoate Ester of the Unknown Isomer of Butanol
Prepare the 3,5-dinitrobenzoate ester of the unknown alcohol provided and determine its melting
point to aid identify the specific isomer of butanol allocated to you.
Procedure
Warning: Do not inhale pyridine. Caution: PCl5 is moisture sensitive; use dry test tubes only.
Mix 0.25 g of 3,5-dinitrobenzoic acid with 0.5 g of phosphorus pentachloride (PCl5) in a small
dry test tube in the fume cupboard. Warm the mixture gently until the reaction starts (as shown
by the evolution of HCl gas) and then remove it from the flame and allow it to proceed
spontaneously. When the reaction subsides, boil the mixture until all the solid dissolves. Pour the
liquid immediately onto a dry watch glass and allow the product to solidify. Transfer the pasty
mass to a pad of two filter papers, fold them over it and press it dry. This procedure absorbs the
phosphorus oxychloride formed in the reaction and leaves the 3,5-dinitrobenzoyl chloride pure
enough to use directly.
Mix the acid chloride with 0.5 ml of the unknown alcohol and 0.5 ml of pyridine in a dry boiling
tube, cork the tube loosely and heat it in a boiling water bath for ten minutes (If the isomer you
have is a primary alcohol) or for thirty minutes if a secondary or tertiary alcohol is suspected.
Cool the mixture, add 10 ml of 5% sodium bicarbonate solution (CARE! evolution of gas), stir
and filter the solid that forms. Wash the solid with a little cold water, keep a small sample for
melting point determination and recrystallise the bulk from the aqueous alcohol (ethanol).
Determine the melting points of the crude and the recrystallised derivative. Determine the identity
of the derivative you have prepared by referring to Table 2 below.
Melting points of the 3,5-dinitrobenzoate derivatives of various isomers of butanol are as shown
in Table 2.
Table 2
Isomers of Butanol Melting point C of 3,5-Dinitrobenzoate derivative
1-Butanol 64
2-Butanol 76
2-Methylpropan-1ol 36
2-Methylpropan-2-ol 142
12
Questions:
1. Account for the following observations
(c) HCl cannot be used to prepare acid chlorides from carboxylic acids.
2. Work out the reaction mechanisms for the following transformations:
R
R' COOH
COOH
R
R'
COOH
COOH
R
R'COOH
O
R
R'
O
O
H+
Heat
Heat
(a)
(b)
R OH
O
R Cl
O
+ HCl + H2O
CO2Et
CO2Et
CN
CO2H
CO2H
OOO
O CO2H
Conc HCl
AlCl3
(a)
(b)
13
EXPERIMENT 4
IDENTIFICATION OF ESTERS. (2 weeks)
Introduction:
Shown below are the common reaction pathways used for forming esters.
R C
O
OH + R'OH R C
O
OR' + H2OH
R C
O
Cl + R'OH R C
O
OR' + HCl
Carboxylic Acid Ester
Acid chloride Ester
A common method used for identification of esters is the hydrolysis or saponification
with alkali to give an alcohol and a carboxylic acid salt. The alcohol can then be
converted to a 3,5-dinitrobenzoate ester derivative while the carboxylic acid salt to a p-
bromophenacyl ester derivative; two compounds with characteristic melting points.
The saponification reaction can be carried out quantitatively using a standard alkali
solution to give the saponification equivalent of the ester (that weight of the ester that
reacts with one mole of the alkali). In a monofunctional ester, the weight is equal to the
molecular mass and can thereby assist in the identification of the ester. (N.B> in industry,
a different term, the saponification value, is used which is the number of milligrams of
KOH required to saponify one gram of fat or oil. Other physical properties e.g. the
refractive index also assist identification of esters.
Saponification of esters.
For simple esters saponification by aqueous alkali proceeds rapidly and completely. The
alcohol component can be obtained by distilling off a small proportion of the reaction
mixture and collecting the distillate. The alcohol will either separate from the distillate as
an oily layer, or after saturation with potassium carbonate and can be identified in the
usual way. The acid, as its salt, is left in the distillation flask and can be converted to a p-
phenacyl derivative.
14
Many esters have low solubility in water and their saponification by aqueous alkali is
excessively slow. The use of an alcoholic alkali, in which the ester is more soluble,
speeds up the saponification but because of the presence of the alcoholic solvent,
identification of the alcohol component becomes difficult or impossible although the acid
component can be readily identified.
A method which enables both components of an ester to be identified employs the high
boiling point, water soluble solvent, diethylene glycol (HOCH2CH2OCH2CH2OH). The
base, potassium hydroxide, is also readily soluble in this solvent. Its high boiling point
allows the lower boiling point alcohol (obtained from the saponification) to be distilled
out and identified.
If no distillate is obtained in this experiment, either the alcohol component of the ester is
a non-volatile polyhydric alcohol or the original ester was a phenolic ester, the resultant
phenol being retained in the distillation flask as its potassium salt. Separation will then
require acidification of the whole reaction mixture, extracting with ether and then
application of the usual method for separating the mixture of acid and phenol produced
(bicarbonate method).
If a distillate is obtained, only a solution of the potassium salt of the acid component of
the ester will remain in the distillation flask. This solution can be neutralised and a
derivative of the acid prepared directly from the neutral salt.
Experimental Procedure.
You are supplied with three unknowns of which two are esters. Identify the esters among
the unknowns by the hydroxamic acid test (procedure (a) below). Do not forget to record
the serial numbers of your unknowns.
(a) Add 2 drops of the unknown to 0.5 ml of a solution of hydroxylamine hydrochloride
in methanol (5%) and follow it by a dilute solution of potassium hydroxide until the
solution is just alkaline (test with litmus paper to determine this). Boil the solution
for one minute in a water bath, cool and just acidify with dilute hydrochloric acid.
Add a few drops of ferric chloride solution and observe the colour change. A red
colour indicates the presence of a hydroxamic acid, and therefore identifies the
unknown as an ester.
15
(b) Having determined which unknowns are esters, determine the boiling points of the
unknown esters by the Siwoloboff method (if the boiling point is above 180 C, just
record this- do not try to heat the oil bath above this level!).
(c) For one of the two esters, choose the one with the lower boiling point and assume it
is an aliphatic ester, identify the alcohol component qualitatively using the exchange
reaction (transesterification) with 3,5-dinitrobenzoic acid:
To accomplish this transesterification, dissolve 2-drops of conc. Sulphuric acid in 1
ml of the unknown ester in a 5- or 10 ml flask. Add 0.75 g of 3,5-dinitrobenzoic acid
and heat the mixture under gentle reflux for thirty minutes. Caution: Do not overheat;
decomposition of the product may occur. Cool the reaction mixture and dissolve in
25 ml ether (NO FLAMES). Remove the acidic products in the reaction mixture by
washing with 5% Na2CO3, (8 mL), wash the ether layer with water (8 mL) and then
evaporate the ether on a hot water bath (Do this in the fume hood to avoid inhaling
ether vapour). Recrystallize the product from aqueous ethanol and determine its m.pt.
Deduce from this melting point, the alcohol component of the unknown ester of low
boiling point.
(d) For the other ester (high boiling ester), attempt to identify both components (acid
and alcohol) by the method of hydrolysis in the high boiling point solvent by the
procedure given below.
Place 1 g of potassium hydroxide pellets, 3 ml of diethylene glycol and 1 ml of water in a small flask.
Warm gently over a flame with swirling until the alkali dissolves, then cool the solution. Add 2 ml of the
unknown ester, mix well and fit the flask with a reflux condenser. Heat the flask in a boiling water bath
with gentle shaking until the ester has dissolved to give a clear solution (some crystalline solid, the
potassium salt of the acid, may separate) and continue to heat for fifteen minutes.
(i) The alcohol component of the high boiling ester
Cool the reaction mixture, then fit the still head and small condenser and heat over a
small flame until the alcohol derived from the ester distils over (Note that diethylene
glycol boils at 240 C and few alcohols will be encountered with boiling point as high as
16
this). The distillate should be dried with a small amount of anhydrous potassium
carbonate and identified by the preparation of a 3,5-dinitrobenzoate derivative as in
experiment 3 (page 6). A boiling point determination by the Siwoboloff’s method can
also be carried out if sufficient material is available.
(ii) The acid component of the high boiling ester
If a volatile alcohol has been obtained, the residue in the distillation flask will contain
the potassium salt of the acid suspended or dissolved in diethylene glycol. Add 20 ml
of water to dissolve the salts. Take a small portion (about 5 mL) of the solution and
acidify to Congo red with dilute sulphuric acid. If an insoluble solid acid is
precipitated, filter it off, wash with water, let dry. Determine its melting point as an
additional aid in the identification of the acid component of the unknown ester.
The remainder of the solution can be used to form a derivative of the acid directly as
follows: The alkaline solution must first be neutralised by the addition of two drops of
phenolphthalein followed by dilute mineral acid (dilute hydrochloric acid) drop-wise
until the colour is just discharged. This serves to neutralize the KOH initially used for the
saponification. Do not add excess mineral acid as this would acidify the mixture and
prevent the next step from proceeding. The resultant solution of the neutral salt of the
acid can then be used to prepare a p-bromophenacyl ester as a solid derivative (see the
procedure below), whose m.pt. will assist in the identification of the acid.
R C O
O
+ R CO
O
p-Bromophenacyl ester
BrCH2 C
O
p-Bromophenacyl bromide
O
K Br
Heat
+ KBr
Br
Preparation of p-Bromophenacyl Esters of the Acid Component of High Boiling
Ester
Take about one-half of the neutralised solution from d(ii) above, add 0.5 g of p-
bromophenacyl bromide and heat the solution to boiling under reflux. If the solution is
not homogeneous, add ethanol dropwise until the reagent is in solution. Reflux for one
hour, cool and collect the precipitated derivative by filtration. Recrystallise from ethanol
or aqueous ethanol. From the m.p. of the two derivatives, and any other data you may
have, deduce the structure of the original ester.
17
Acid Component m.pt. of Acid m.pt. of p-Bromophenacyl
ester of Acid
m.pt. ºC of p-phenyl-
phenacyl ester of Acid
Acetic acid liq 85 111
Propionic acid liq 59 102
n-Butyric acid liq 63 82
Isobutyric acid liq 77 89
Benzoic acid 122 119 167
m-Toluic acid 108 108 137
o-Toluic acid 103 57 95
p-Toluic acid 180 153 165
Phthalic acid 195 153 -
Phenylacetic acid 76 89 -
Cinnamic acid 133 183 145
Valeric acid Liq 75 64
Isovaleric acid liq 68 76
Alcohol m.pt. of 3,5-dinitrobenzoate ester (ºC) of Alcohol
Methanol 109
Ethanol 94
n-Propanol (1-Propanol) 74
tert-Butanol (2-methyl-2-propanol) 142
Benzyl alcohol 112
Cinnamyl alcohol 121
Cyclohexanol 113
1-Phenylethanol 95
2-Phenylethanol 108
18
Questions
1. Suggest a suitable synthesis of the following compounds:
2. A synthesis of a lactone is shown below:
(a) Work out the structure of (I) and (II)
(b) Suggest a reaction mechanism for the formation of (III) from (II).
O
O Ph
CO2H CO
2H
CO2H
OH
Phfrom and
(a)
CO2Me
COCl CO2H
CO2H
from(b)
R
Br
CO2Et
R CN(c)
from
OOPh
Ph CO2H
Ph
Ph(d) from
H
O
CN
O
n-Oct
O
n-Oct-BrMg
Et2On-Oct-MgBr (I)
(I)OH-
H2O, heat(II)
H+
(III)n-Oct = C8H17 (straight chain)
19
EXPERIMENT 5
CHARACTERISATION AND IDENTIFICATION OF PHENOLS (2
Weeks)
Introduction
Phenols are aromatic alcohols. They have some similar reactions with aliphatic alcohols
like ester formation (rates are slower) but in most other reactions they are different and
are studied as a different group of alcohols. Acidity of phenols (pKa ~10) is intermediate
between that of carboxylic acids (pKa ~5) and that of alcohols (pKa 16-19). They can be
distinguished from the stronger carboxylic acids by dissolving in aqueous sodium
hydroxide to form phenoxides but not reacting with potassium bicarbonate with the
formation of CO2 (i.e. they are weaker than carbonic acid (pKa 6.4).
O H OH O
H2O
_
pKa 10 Phenoxide
_
+
RC
O
O
H C
O
OHO RC
O
O
C
O
OHOH
O C OR
CO
O
_
unstable
H2O+(CO2)
_
+
Carboxylic acid bicarbonate
carboxylate
_
O H
C
O
OHOO__
Phenoxide
20
Note: Simple phenols are fairly soluble in water to give a weakly acidic solution. These
are best recognized by their ferric chloride colours. Polynitrophenols are more acidic than
simple phenols and may be stronger than carbonic acid (pKa < 6.4). They are usually
yellow in colour.
Other tests for phenols are:
(1) Ferric chloride colours. Most phenols in aqueous or alcoholic solution give bright
colours with neutral FeCl3. The colour may fade rapidly.
(2) Rapid bromination. Most phenols decolourize bromine water almost
instantaneously.
(3) Phenols form brightly coloured azo-dyes on coupling with diazotized aniline.
Warning: All Phenols are liable to burn skin and should not be handled with bare hands.
Derivatives of Phenols:
The most suitable derivatives of phenols are benzoates and p-toluene-suphonates. These
are made by reacting phenol, in the presence of base, with the appropriate acid chloride.
Examine each of the six unknowns as follows and determine which ones are phenols:
1. Test for solubility in cold water, cold or hot aqueous NaOH and cold aqueous
bicarbonate. Record your observations and conclusions in tabular form.
2. If a phenol is suspected, test an aqueous (or aqueous alcoholic) solution with
neutral FeCl3. Record your observation and conclusion.
OH
NN
R
NN
R
OH
(a diazonium compound)
diazolised aniline
+
an azo compound(highly conjugated)
phenol
+
21
Having recognised the phenols among the unknowns, identify each by forming a derivative. Make at least
one benzoyl derivative and one p-toluene-suphonyl derivative. Note that for some of the simpler phenols
benzoyl derivatives are rather low melting and therefore unsuitable as derivatives for identification.
Benzoyl Derivative (The Schotten-Baumann Procedure).
Dissolve (by warming and cooling again, if necessary) 0.5 g (or 0.5 ml) of the phenol and
5 ml of 3N NaOH in a well corked boiling tube. Add 1 ml of benzoyl chloride (fume
cupboard) and shake vigorously for 10 minutes. Check that the solution is still alkaline
(benzoyl chloride if present, would be hydrolysed by water to carboxylic acid!), cool in
ice and filter the solid derivative, wash the solid with water and recrystallise from dilute
alcohol (use only a minimum of boiling alcohol to dissolve the derivative, then add water
dropwise to lower the solubility).
p-Toluenesuphonyl Derivatives.
Warning: Pyridine causes sterility in men (you have been warned!)
Reflux 0.5 g (or 0.5 ml) of the phenol with 1 g of p-toluenesulphonyl chloride and 3 ml of
pyridine for 15 minutes. Cool, pour into the 10 ml ice-cold water, stir vigorously and
filter the solid derivative. Wash and recrystallize as for the benzoyl derivative.
Some Common Phenols and their Derivatives
Phenol m.p.
( C)
m.p. of
benzoate
( C)
m.p. of
p-toluenesulphonate
( C)
FeCl3
Colour
Phenol 42 69 95 Violet
o-Cresol 30 Liquid 55 Violet
m-Cresol 11 54 50 Blue
p-Cresol 35 71 69 Violet
o-Chlorophenol 7 Liquid 74 Violet
m-Chlorophenol 33 72 - -
p-Chlorophenol 43 87 79 Violet
o-Nitrophenol 45 59 83 -
m-Nitrophenol 96 95 112 Red-violet
p-Nitrophenol 114 142 97 Violet
2,4-Dinitrophenol 113 132 121 -
2-Naphthol 123 106 125 Green
Catechol 105 84 Green
Resorcinol 110 117 80 Violet
Hydroquinone 172 199 159 brown
22
Draw full structural formulae of your phenols and their derivatives.
Questions
1. Write the reaction mechanisms for the benzoate and p-toluene-sulphonyl derivatives
that you prepared.
2. Suggest how chemical reaction can be used to separate a mixture of 2,4,6-
trinitrophenol and 2,4,6-trimethoxyphenol.
3. Explain each of the following observations:
(a) 4-Iodophenol is a stronger acid than 4-fluorophenol
(b) o-Hydroxyacetophenone has a lower boiling point than p-hydroxyacetophenone.
(c) Addition of a few drops of phenol to a coloured solution of bromine water gives a
yellow precipitate and a decolourised solution, while addition of a few drops of
toluene to the same solution has no effect.
4. Phenols form esters on reaction with acid chlorides. They do not react directly with
acids (contrast with alcohols). Why?
5. Show by a series of chemical reactions how benzene can be converted to the
following:
(a) 2,4-dihydroxybenzoic acid
(b) 3-hydroxybenzylamine
(c) 4-(N,N-dimethylamino)-phenyl benzoate
6. Ambucaine (J) is used as a local anaesthetic.
23
What reagents would you use to convert:
(i) (A) to (B)
(ii) (C) to (D)
(iii) (F) to (G)
(iv) (G) to (H)
Write down the structure of all the intermediates.
CO2Me CO
2H
NO2
NH2
CO2H
OH
CO2H
OH
CO2H
NO2
OH
NO2
CO2Et
O
CO2Et
NO2
O
NO2
O Cl
O
O ONEt
2
NO2
O
NH2
O ONEt
2
OHNEt
2
(A) (B) (C)(D)
(E) (F) (G)
(H) (I)
(J)
H2/Nickel
?
?EtOH
HCl
HNO3
?H2/Pd?