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“OXIDATION REACTION OF VARIOUS FUNCTIONAL GROUPS”
A
PROJECT REPORT
FOR ELECTIVE SUBJECT
SUBMITTED TO THE
HEMCHANDRACHARYA NORTH GUJARAT UNIVERSITY, PATAN
IN PARTIAL FULFILLMENT OF THE REQUIREMENT FOR THE DEGREE OF BACHELOR OF PHARMACY
SUBMITTED BY:-
BHARGAV H. PATEL
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
SHREE S.K. PATEL COLLEGE OF PHARMACEUTICAL EDUCATION AND RESEARCH,
GANPAT VIDHYANAGAR, KHERVA, NORTH GUJARAT
2004-2005
gnu.i
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.inCERTIFICATE
This is to certify that the project work for elective subject entitled “OXIDATION
REACTOIN OF VARIOUS FUNCTIONAL GROUPS” Represents the
bonafide work of MR. BHARGAV H. PATEL carried out under my guidance and
supervision in the department of Pharmachemistry of S.K.Patel College Of
Pharmaceutical Education And Research, Ganpat Vidyanagar, during the academic
year 2004-2005. He has collected the literature sincerely and systematically. This
work is up to my satisfaction.
Guide: - Head Of Department: -
Mr. J.R.Patel (M.Phram) Mr. P.U.Patel (M.Pharm) Lec. of Dept. of Pharma.chemistry, Ass.Prof.Of Dept.of Pharma.chemistry, S.K.Patel college of pharmaceutical S.K.Patel college of pharmaceutical Education and Research. Education and Research. Ganpat Vidyanagar, Kherva. Ganpat Vidyanagar, Kherva.
PRINCIPAL (I /C)
Dr. N. J. Patel M.Pharm,Ph.D.
S.K.Patel college of pharmaceutical Education and Research Ganpat Vidyanagar,Kherva
DATE:
PLACE: Ganpat Vidyanagar
gnu.i
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.inACKNOWLEDGEMENT
Success is the progressive realization of worthy goal.
- Earl Nightangle Success in life not determined by how we are doing compare to
others, but by how we are doing compared with what we are capable of doing.
Successful people compete against themselves. They better their own records
and keep improving constantly.
Words are tools of expressing the feelings but they might be
failed miserably when it comes to thanks giving. Therefore I might not able to
do adequate justice in task of acknowledgement to all those who directly as well
as indirectly in complication of my project work.
Knowledge is the antidote to fear.
-Ralph Waldo Emerson
First and foremost, I would like to acknowledge the continuous
encouragement and help extended to me by Mr.J.R.Patel for preparing this
project work. He has been my sole guide & philosopher throughout the period of
my work. His extensive knowledge of the subject and the way he imparted the
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.insame to me has enabled me to develop the thesis in a cohesive manner and
kindled within me a passion for the subject.
I also want to thank Mr.P.U.Patel, Mr.S.A.Patel, Dr.K.I.Molvi,
Mr.M.B.Patel, Mr.B.H.Patel, and Miss D.M.Shankala for providing tremdous
guidance in this project work.
I also want to thank my honorable principle(I/C) Dr.N.J.Patel for
who provides me all facilities and infrastructure for the completion of my project
work.
Friendship always protects, always trusts, always hopes,
always preservers. So Friend lies at the bottom of every heart.
So specially I want to thank Pratik for helping me in the computer
related project work. I also want to thank Sweta, Dipika, Chintan, Deval, Bipin,
Mihir, Nilesh, Ankit, Aashish, Alpesh, Jignesh and Dhaval who help me to
complete my project work without any burden.
Last but not least I heartly thank God and My Family who gives me
courage and confidence to complete this project work.
Last I would like to tell some thing:
The six most important words are:
gnu.i
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.in“ I admit I made a mistake ”
The five most important words are:
“ You need a good job ”
The four most important words are:
“ What is your opinion? ”
The three most important words are:
“ If you please ”
The two most important words are:
“ Thank you ”
The last most important words are:
“ I “
-BHARGAV H. PATEL
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.inINDEX
Sr.
No.
CONTENT
PAGE
NO.
1)
Introduction
1-7
2)
Oxidation of aromatic ring
8-12
3)
Oxidation of alkyl benzene
13-18
4)
Oxidation of alcohol
19-30
5)
Oxidation of ketone
31-40
6)
Oxidation of aldehyde
41-44
7)
Oxidation of other functional groups
45-52
8)
Reference
53
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Oxidation reaction of various functional groups 1
♫ INTRODUCTION ♫
OXIDATION:- “Oxidation is defined as the process in which
compound or molecule or atom loss one or more electron.”
The term oxidation was originally used to describe reactions in which an
element combines with oxygen.
Example: The reaction between magnesium metal and oxygen to form
magnesium oxide involves the oxidation of magnesium.
After electrons were discovered, chemists became convinced that
oxidation-reduction reactions involved the transfer of electrons from one
atom to another. From this perspective, the reaction between magnesium
and oxygen is written as follows.
2 Mg + O2 2 [Mg2+][O2-]
In the course of this reaction, each magnesium atom loses two electrons
to form an Mg2+ ion.
Mg Mg2+ + 2 e-
Chemists eventually extended the idea of oxidation and reduction to
reactions that do not formally involve the transfer of electrons.
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Oxidation reaction of various functional groups 2
Consider the following Reaction:--
CO(g) + H2O(g) CO2(g) + H2(g)
As can be seen in the figure below, the total number of electrons in the
valence shell of each atom remains constant in this reaction.
What changes in this reaction is the oxidation state of these atoms. The
oxidation state of carbon increases from +2 to +4, while the oxidation
state of the hydrogen decreases from +1 to 0.
Oxidation is therefore best defined as follows:
Oxidation occurs when the oxidation number of an atom becomes
larger.
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Oxidation reaction of various functional groups 3
Mechanisms of oxidation
1) Direct electron transfer:
eg: Birch reduction, where Na directly transfers an electron to an
aromatic ring. It is a metal that supplies the electrons.
This kind of mechanism is found largely in three types of Reaction:-
a) The oxidation of a free radical to a positive ion.
b) The oxidation of negative ion to a comparatively stable free
radical.
c) Electrolytic oxidations:
eg: Kolbe Reaction:-
2 R-COO- 2 R-COO. 2 R. R-R
2) Hydride transfer:
e.g.: Cannizaro Reaction:-
2 Ar-CHO Ar-CH2OH + Ar-COO-
3) Hydrogen-atom transfer:
Many oxidation reactions are free radical substitutions and involve
the transfer of a hydrogen atom.
RH + Cl. R. + HCl
4) Formation of ester intermediate:
No. of oxidation involve the formation of an ester intermediate and
then the cleavage of this intermediate.
C
A
BH
ZO
CA B
O
+ Z + H+
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Oxidation reaction of various functional groups 4
5) Displacement mechanism:
In these reaction the organic substrate uses its electrons to cause
displacement on an electrophilic oxidizing agents.
e.g. Addition of bromine to an olefin
C C
H
R1 R2
H
+ Br Br C C
H
R1 R2
H
Br+
+ Br-
R1, R2 =H or Aliphatic chain or Aromatic ring
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Oxidation reaction of various functional groups 5
OXIDIZING AGENTS
Defination:- “They are the agents or chemicals that cause the oxidation
of other compounds by reducing itself.”
e.g. Permanganates
Chromium trioxide
Dichromates
Nitric acid and nitrogen tetroxide
Hypochlorous acid and salts
Sodium chlorite and chlorine dioxide
Chlorates
Peroxides
Potassium permanganate is the most widely used agent for the
oxidation of a wide variety of organic compounds. Permanganate is a
derivative of hexavalent manganese, and is a very powerful oxidant. Its
reactivity depends mainly on whether bit is used under acidic, neutral or
basic conditions. In acidic solution it is reduced to the divalent
manganese П ion, Mn2+, with net transfer of five electrons (Mn VΠ
Mn Π), while in neutral or basic media manganese dioxide,
MnO2, is usually formed, corresponding to a three electron change (Mn
VΠ Mn ІV). Permanganate is generally used in aqueous solution
and this restricts its usefulness since not many organic compounds are
sufficiently soluble in water and only a few organic compounds are
resistant to the oxidizing action of the reagent. Solutions in acetic acid, t-
butanol or dry acetone or pyridine can sometimes be employed.
Alternatively, oxidation with aqueous solutions of permanganate can be
effected in the presence of crown ethers or phase transfer catalysts.
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Oxidation reaction of various functional groups 6
Chromic acid, a derivative of hexavalent chromium is one of the
most versatile of the available oxidizing agent. It reacts with almost all
types of oxidisable groups. The reactions can be controlled to yield
mainly one product. So it is useful process in organic synthesis. In
oxidation, chromium is reduced from the hexavalent to the trivalent state
(Cr VI Cr III ) with generation of chromium salt. It is used in
solution of acetic anhydride, t-butanol or in pyridine. In these solution the
reactive species present are chromyl acetate, t-butyl chromates and
pyridine in chromium ( VI ) oxide complex.
Potassium or sodium dichromate in presence of dilute sulphuric
acid, is a convenient oxidizing agent for the controlled oxidation of
primary alcohols to aldehydes. To avoid further oxidation to the
corresponding acids, the aldehyde is removed as rapidly as possible by
distillation through a fractionating column. Sodium dichromate is also
used for the oxidation of a side chain. The molecule should not contain
any other groups which are affected by the oxidizing agent.
Nitric acid is a strong oxidizing agent. Unless used under
controlled conditions, it is completely oxidises the organic compound into
carbon dioxide and water. However, as has already been stated, it along
with concentrated sulphuric acid is used for nitration of organic
compounds.
Hydrogen peroxide is a mild oxidizing agent. It is used for the
oxidation of phenolic aldehydes to a hydroxyl group. Hydrogen peroxide
is used for the preparation of paracids, which in turn are used to oxidize
the aldehyde group to phenolic group. It is also used for the oxidation of
easily oxidisable or reactive C=C bond in aromatic compound. Thus,
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Oxidation reaction of various functional groups 7
diphenic acid as obtained when phenanthrene is oxidized with 30%
hydrogen peroxide in glacial acetic acid solution at 85°C. No
phenanthrene is formed under these conditions (compare the oxidation of
phenanthrene with acid dichromate). This hydrogen peroxide oxidation of
phenanthrene is, essentially oxidation by peracetic acid, of the reactive 9-
10 positions in phenanthrene.
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Oxidation reaction of various functional groups 8
♫ OXIDATION OF AROMATIC RING ♫
1) Anthraquinone from anthracene:
It is obtained by the oxidation of anthracene with a solution of
chromium trioxide in glacial acetic acid.
Reaction:-
O
O
anthracene anthraquinone
[o]
CrO3
Anthracene : 5 g
Chromium trioxide : 10 g
Acetic acid (glacial) : 100 ml
Procedure:-
A solution of chromium trioxide (10 g) in water (10 ml) and glacial
acetic acid (25 ml) is added drop wise to a well stirred solution of
anthracene (5 g, 0.028 mole) in glacial acetic acid (75ml) (the anthracene
solution is obtained by gentle warming). The reaction is carried out in a
three necked R.B. flask fitted with sealed stirrer, a reflux condenser and a
dropping funnel. The chromium trioxide solution is added at such a rate
that the mixture continues to reflux (10-15 minutes). When all the
solution has been added, the reaction mixture is refluxed for 10 minutes.
The cooled mixture is poured into cold water (250 ml) and mixture
stirred. The separated anthraquinone is filtered under gentle suction,
washed with water, hot sodium hydroxide solution (N) and finally with
cold water. It is crystallized from glacial acetic acid using decolorizing
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Oxidation reaction of various functional groups 9
carbon. The yield is 5.5 g (94.2 %); m.p. is 285-2850°C. Alternatively, it
can be purified by sublimation.
2) Phenanthraquinone from phenanthrene:
It is obtained by the oxidation of phenanthrene with potassium
dichromate and dilute sulphuric acid.
Reaction:-
O O
K2Cr2O7/H2SO4
[O]
Phenanthrene phenanthraquinone
Phenanthrene : 3 g
Potassium dichromate : 18 g
Conc. Sulphuric acid : 30 ml
Procedure:-
To a suspension of phenanthrene (3g, 0.017 mole) in dilute acid
(obtained by cautiously adding 30 ml concentrated sulphuric acid to 60
ml water with stirring) is added at 90-95°C (water bath), potassium
dichromate (18 g) in small lots (0.5-1 g) until a vigorous reaction sets in.
the external heating is removed and the temperature of the mixture is
approximately 110-115°C. Addition of potassium dichromate is
continued. The temperature of the reaction mixture is heated on boiling
water 85°C (hot water bath is used if necessary). Finally, the reaction
mixture is heated on a boiling water bath for 30 minutes. It is cooled,
water (200 ml) is added, and the crude product filtered and washed with
water until it is free from chromium salts. It is purified by suspending in
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Oxidation reaction of various functional groups 10
rectified spirit (30 ml) and stirring with saturated sodium bisulphate
solution (30 ml). The mixture is stirred for 10 minutes, diluted with water
(175 ml) and the clear solution (filter if necessary) containing the
bisulphate addition product is treated with saturated sodium carbonate
solution. The precipitated phenanthraquinone is filtered, washed with
water and crystallized from glacial acetic acid. The yield is 2 g (57 %);
m.p. is 206-207°C.
3) Diphenic acid (biphenyl-2,2'-dicarboxylic acid) from
phenanthrene :
It is obtained by the oxidation of phenanthrene with hydrogen
peroxide in glacial acetic acid medium.
Reaction:-
COOHCOOH
[O]
H2O2, CH3COOH
phenanthrene diphenic acid
Phenanthrene : 17.8 g
Acetic acid (glacial) : 200 ml
Hydrogen peroxide (30 %) : 71 ml
Procedure:-
Hydrogen peroxide ( 30 %, 71 ml, 2 mole) is added slowly during
40-45 minutes to a stirred solution of phenanthrene (17.8 g, 0.1 mol) in
glacial acetic acid (200 ml, 85°C) contained in a three necked flask (1
liter capacity) fitted with a sealed stirrer, a reflux condenser and
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Oxidation reaction of various functional groups 11
thermometer. After the addition is complete, the temperature falls to
80°C, the mixture is heated on a water bath with stirring for 3-4 hours.
The solution is concentrated to approximately half by distillation under
reduced pressure and then cooled. The precipitated diphenic acid is
filtered; the filtrate is evaporated almost to dryness under reduced
pressure. The residue is extracted with sodium carbonate solution (10 %,
175 ml) by warming on a water bath. The alkaline extract is boiled with a
little decolorizing carbon, filtered and the filtrate acidified with dilute
hydrochloric acid to pH 4.5. The solution is cooled to 0°C, any tarry
material separated is filtered and the clear solution acidified with dilute
hydrochloric acid. The separated diphenic acid is filtered and washed
with cold water. Total yield is 16.6 g (69 %). It is crystallized from
glacial acetic acid, m.p. 229-230°C.
4) Cyclohexanol from Cyclohexene:
Reaction:-
OH
1. conc. H2SO4
2. boil
cyclohexene cyclohexanol
Mechanism of Reaction:-
O
cyclohexene
conc. H2SO4
S OH
O
OH2O
boil
cyclohexyl hydrogen sulfate
OH
cyclohexanol
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Oxidation reaction of various functional groups 12
Procedure:-
Cautiously add 7.0 ml (0.126 mole) of concentrated sulfuric acid to
3.4 ml (3.4 g; 0.19 mole) of water in a 50 ml round-glass stoppered
Erlenmeyer flask. Cool the solution to room temperature. Add 10.1 ml
(8.2 g; 0.10 mole) of cyclohexene. Stopper the flask and shake to mix; the
mixture should be shaken or stirred until a clear homogeneous solution is
formed (note 1).
At this point, pour the mixture into a 250 ml boiling flask and rinse
the Erlenmeyer flask with a total of about 120 ml of water, adding the
rinsing to the boiling flask. Fit the flask with a distillation adapter and a
condenser set for distillation. Heat the mixture to hydrolyze the
intermediate and to distill the product. Continue the distillation until 50 or
60 ml of distillate has been collected.
Saturate the distillate with sodium chloride and separate the
cyclohexanol by extracting it with ether. Dry the ethereal extracts over
anhydrous potassium carbonate, filter, and remove the ether by
distillation on the steam bath. Distill the residue and collect the fraction
boiling between 155 and 162°c as cyclohexanol.
Note:
1) Some time can be saved by allowing the mixture to stand between
laboratory periods.
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Oxidation reaction of various functional groups 13
♫ OXIDATION OF ALKYL BENZENE ♫
1) Aromatic acids by oxidation by permanganate:
Reaction:-
Ar RKMnO4 Ar C OH
O
Procedure:-
Add 1 gram of the hydrocarbon to a solution of 3 grams of
potassium permanganate and 1 gram of sodium carbonate in 75 ml of
water, and heat the mixture under reflux until the permanganate colour
has disappeared (in 15 minutes to 4 hours; note 1). Cool the solution to
room temperature and acidify it cautiously by the addition of 50%
sulfuric acid (note 2). Remove the manganese dioxide by the addition of a
concentrated solution of sodium bisulfite (while stirring well and possibly
heating on the steam bath) and, after cooling the mixture thoroughly in an
ice bath, collect the acid by suction filtration. It can be recrystallized from
water.
Notes:
1. potassium permanganate can be detected by dipping a stirring rod into
the mixture and touching the rod to a piece of filter paper; a pink colour
in the ring around the dark spot of manganese dioxide indicates the
presence of permanganate.
2. 50% sulfuric acid can be prepared by cautiously pouring 5 ml
concentrated sulfuric acid over 10 grams ice.
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Oxidation reaction of various functional groups 14
2) p-nitrobenzoic acid from p-nitrotoluene:
It is obtained by the oxidation of p-nitrotoluene with sodium
dichromate and dilute sulphuric acid.
Reaction:-
O2N CH3 O2N COOH[O]
Na2Cr2O7/H2SO4
p-nitrotoluene p-nitrobenzoic acid
p-nitrotoluene : 14 g
Sodium dichromate : 40 g
Conc. Sulphuric acid : 49 ml
Procedure:-
Concentrated sulphuric acid (49 ml) is added slowly (dropping
funnel) to a stirred mixture of p-nitrotoluene (14 g, 0.1 mole), sodium
dichromate (40 g) and water (90 ml). Considerable heat is evolved, the p-
nitrotoluene melts and oxidation proceeds. The reaction mixture is
refluxed by gentle boiling on a wire gauge for 15 minutes. It is cooled
and poured into cold water (130 ml). The separated product is filtered and
washed with water (60-70 ml). It is digested by heating on a water bath
with dilute sulphuric acid (5%, 75 ml obtained by adding 2.7 ml
concentrated sulphuric acid to 75 ml water) with stirring for 20 minutes
(to remove the chromium salts). The mixture is cooled and filtered. The
crude product is treated with dilute sodium hydroxide solution (5%, 100-
120 ml) until the liquid is alkaline. The mixture is warmed to 50°C with
decolorizing carbon, stirred for 5 minutes and filtered. The clear alkaline
filtrate is added to well stirred dilute sulphuric acid is filtered, washed
with water and dried. It is crystallized from benzene or glacial acetic acid.
The yield is 13.2 g (77.4%); m.p. is 238-239 °C.
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Oxidation reaction of various functional groups 15
3) Terephthalic acid from p-xylene:
It is obtained by oxidation of p-xylene with sodium dichromate and
dilute sulphuric acid.
Reaction:-
CH3
CH3
COOH
COOH
p-xylene terephthalic acid
[O]
Na2Cr2O7/H2SO4
p-xylene : 15 ml
Sodium dichromate : 70 ml
Conc. Sulphuric acid : 170 g (92.5 ml)
Procedure:-
A mixture of p-xylene (12.5 g, 15 ml, 0.118 mole), sodium
dichromate (70 g) and water (300 ml) is placed in a three necked one liter
R.B. flask fitted with a sealed mechanical stirrer, a reflux condenser and a
dropping funnel. Concentrated sulphuric acid (170 g, 92.5 ml) is added
drop wise (dropping funnel) to the well stirred mixture (35-40 minutes).
When all the acid has been added, the temperature begins to fall, and the
mixture is gently refluxed for 30 minutes. The reaction mixture is poured
into water (600 ml) and allowed to stand for one hour. The separated
terephthalic acid is filtered, washed with cold water (30 ml) and then by
ether (30 ml). It is purified by dissolving in sodium hydroxide solution (5
%, 70 ml) and the clear filtrate (obtained by filtration) is added to well
stirred dilute sulphuric acid (15 %, 225 ml obtained by cautiously adding
20 ml concentrated sulphuric acid to 200 ml water). The yield is 9 g (46
%). It sublimes at 300°C without melting.
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Oxidation reaction of various functional groups 16
4) o-chlorobenzoic acid from o-chlorotoluene:
Reaction:-
CH3
Cl
COOH
Cl
[O]
KMnO4
O-chlorotoluene o-chlorobenzoic acid
o-chlorotoluene :25 g
potassium permanganate :75 g
Procedure:-
A mixture of potassium permanganate (37.5 g), o-chlorotoluene
(25 g,0.2 mol) and water (600 ml) is stirred and refluxed in a three necked
flask (1 liter capacity) fitted with a sealed stirrer and a reflux condenser.
The mixture is refluxed with stirring till the permanganate colour has
disappeared (1.5-2 hours). A second lot of potassium permanganate
(18.75 g) is added and the mixture refluxed with stirring until the
permanganate colour disappears (1.5-2 hours). Finally, a third lot of
potassium permanganate (18.75 g) is added and refluxing continued until
the permanganate colour has disappeared (2-2.5 hours). The precipitated
manganese dioxide is destroyed by passing a current of sulphur dioxide
gas. The separated o-chlorobenzoic acid is filtered and washed with cold
water. It is purified by dissolving in sodium bicarbonate solution and
acidification of the clear alkaline solution. It is finally crystallized from
hot water. The yield is 21 g (68%); m.p. is 139-140°C.
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Oxidation reaction of various functional groups 17
5) p-nitrobenzaldehyde form p-nitrotoluene:
It is obtained by the oxidation of p-nitrotoluene with chromium
trioxide in acetic anhydride.
Reaction:-
O2N O2N O2NCH3 CH(OCOCH3)2 CHO
[O]
CrO3/(CH3CO)2OH3O+
p-nitrotoluenep-nitrobenzaldehyde
p-nitrotoluene : 12.5 g
Acetic anhydride : 225 ml
Conc. Sulphuric acid : 20 ml
Chromium trioxide : 25 g
Procedure:-
Acetic anhydride (100 g, 92.5 ml, 1 mol) and p-nitrotoluene (12.5
g, 0.09 mol) are taken in a three necked flask (500 ml capacity) fitted
with a mechanical stirrer and a dropping funnel. The mixture is cooled to
00 C (ice-salt mixture) and concentrated sulphuric acid (20 ml) is added
drop wise to the stirred solution. A solution of chromium trioxide in
acetic anhydride (obtained by adding 25 g, 0.25 mol chromium oxide
portion wise to well cooled 125 ml acetic anhydride) is added at such a
rate that the temperature does not exceed 100 °C. The mixture is stirred
for 2 hours more and poured over crushed ice water (approx. 1 kg). The
separated p-nitrobenzylidene diacetate is filtered and washed with cold
water until the washings are colourelss. It is suspended in cold sodium
carbonate solution (2% ), stirred for 5 minutes, filtered and washed with
cold water and finally with cold alcohol (5 ml). It is crystallized from
alcohol. The yield is 15 g (65%); m.p. is 125-1260°C.
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Oxidation reaction of various functional groups 18
The crude p-nitrobenzylidene diacetate is refluxed in a mixture of
ethanol (25 ml), water (35 ml) and concentrated sulphuric acid (3.5 ml)
for 30 minutes. The mixture is filtered and cooled. The yield is 7.5 g
(55%); m.p. is 1060°C.
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Oxidation reaction of various functional groups 19
♫ OXIDATION OF ALCOHOL ♫
Oxidation of an alcohol involves the loss of one or more hydrogen
(α-hydrogen) from the carbons bearing the –OH group. The kind of
product that is formed depends upon how many of this α-hydrogen the
alcohol contains, that is, upon whether the alcohol is primary, secondary,
or tertiary.
A primary alcohol contains two α-hydrogen, and can either lose
one of them to form an aldehyde,
C
H
R OH
H
CR
H
O
1o
alcohol aldehyde
or both of them to form a carboxylic acid.
C
H
R OH
H
CR
OH
O
1o
alcohol carboxylic acid
(Under the proper conditions, as we shall find, an aldehyde can itself be
oxidized to a carboxylic acid.)
A secondary alcohol can lose its only α-hydrogen to form a ketone.
C
H
R OH
R1
CR
R1
O
2o
alcohol ketone
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Oxidation reaction of various functional groups 20
A tertiary alcohol contains no α-hydrogen and is not oxidized. (An
acidic oxidizing agent can, however, dehydrate the alcohol to an alkene
and then oxidize this.)
C
R2
R OH
R1
3o
alcohol
no oxidation
Some of the oxidation reactions of the alcohol functional group are
given below with the procedure of that particular reaction.
1) n-butyraldehyde from n-butylalcohol:
It is obtained by the oxidation of n-butyl alcohol with sodium
dichromate and dilute sulphuric acid.
Reaction:-
CH3CH2CH2CH2OH CH3CH2CH2CHO + H2O[O]
Na2Cr2O7+H2SO4
n-butyl alcohol n-butyraldehyde
n-butyl alcohol :25.5 ml
Sodium dichromate : 28 g
Conc. Sulphuric acid : 20 ml
Procedure:-
n-butyl alcohol (20.5 g, 25.5 ml, 0.279 mole) is taken in a two
necked R.B. flask (250 ml capacity) fitted with a dropping funnel and a
fractionating column(6”) with a distillation arrangement. A solution of
sodium dichromate in dilute sulphuric acid (obtained by adding
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Oxidation reaction of various functional groups 21
cautiously with stirring, 20 ml concentrated sulphuric acid to a
suspension of 28 g sodium dichromate in 100 ml water) is added during
15 minutes to the warm n-butylalcohol. The rate of addition should be
such that the temperature does not rise above 80-85°C. Since the
oxidation proceeds with evolution of heat the reaction flask has to be
cooled in ice. However, the temperature of the reaction mixture should
not be allowed to fall below 75°C (if necessary the flask has to be heated
with a small flame). After the addition of dichromate solution is
complete, the reaction mixture is heated with a small flame for 15
minutes. The fraction that passes over below 90°C is collected. It is dried
and distilled. The yield is 9 g (45%); b.p. is 74-75°C.
2) Oxalic acid from cane sugar:
It is obtained by oxidation of cane sugar with concentrated nitric
acid.
Reaction:-
C12H12O11 + 18 OConc. HNO3
Oxidation6(COOH)2 + 5H2O
cane sugar oxalic acid
Cane sugar : 20 g
Conc. nitric acid : 100 g ( 70 ml, sp.gr.1.42)
Procedure:-
Cane sugar (20 g, 0.058 mole) is added in one lot to concentrated
nitric acid (100 g, 70 ml, sp.gr.1.42) contained in a conical flask (500 ml
capacity). The mixture is warmed in a water bath till the reaction starts.
Subsequently, it is allowed to proceed with the application of external
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Oxidation reaction of various functional groups 22
heat. In case the reaction becomes too violent with evolution of brown
fumes of oxides of nitrogen, it is cooled in water. The mixture is finally
kept for 24 hours at room temperature. The separated oxalic acid is
filtered (sintered funnel). Further quantity is obtained by concentration of
the mother liquor on a water bath and subsequent cooling. Total yield 5 g
(16 %). It is crystallized from hot water as a hydrate; m.p. is 101.5°C.
3) Cyclohexanone from Cyclohexanol:
Reaction:-
OH
acetic acid
NaOCl
cyclohexanol cyclohexanone
O
Procedure:-
Place 5.0 grams (5.2 ml; 0.050 mole) of cyclohexanol, 12 ml of
glacial acetic acid, and a magnetic stirring bar in a 125 ml Erlenmeyer
flask. Clamp the flask into position on a magnetic stirring motor. Place 80
ml of a 5.25% solution of sodium hypochlorite (0.055 mole NaOCl; note
1) in an addition funnel (Note 2) , and clamp the funnel into position over
the neck of the 125 ml Erlenmeyer flask so that the bleach solution can be
gradually added while the mixture in the flask is stirred by the magnetic
stirrer. Position a thermometer in the Erlenmeyer flask so that the bulb
touches the bottom of the flask but does not interfere with the magnetic
stirring bar. While the solution is magnetically stirred, add the bleach at
such a rate that the temperature of the reaction mixture does not rise
much above 35°C.
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Oxidation reaction of various functional groups 23
After the addition is complete, test the reaction mixture with
potassium iodide-starch test paper (Note 3). If the test is not positive (not
blue), add an additional 2 ml of bleach and stir the reaction mixture at
room temperature for another 15 minutes; an excess of bleach solution
should then be present, as indicated by a greenish-yellow colour, and the
oxidation of all the alcohol is thereby assured. Reduce the excess bleach
by adding concentrated sodium bisulfite until the greenish-yellow colour
is gone and the solution no longer gives a positive potassium iodide-
starch test (Note 3; between 1 and 5 ml will be needed).
Transfer the contents of the Erlenmeyer flask to a 250 ml boiling
flask, and distill the solution until about 25 ml of distillate have been
collected in a 125 ml Erlenmeyer flask (Note 4). Add about 3.5 grams of
anhydrous sodium carbonate to the distillate to neutralize the acetic acid
that has distilled along with the cyclohexanone and water; swirl or stir the
mixture until all of the sodium carbonate has dissolved.
Transfer this solution from the Erlenmeyer flask to a separatory
funnel, rinse the flask with 15 ml of ether, and add the ether to the
separatory funnel. Extract the cyclohexanone into the ether and separate
the layers. Dry the ether extract over the anhydrous magnesium sulfate,
and distill. Collect as a cyclohexanone the portion of the distillate that
boils between 150°C and 155°C. Yield: about 4 grams (80%).
Notes:
1) A commercial bleach, available at the super market, can be used.
2) You should use your seperatory funnel as an addition funnel.
3) When sodium hypochlorite is present, it will oxidize iodide to iodine.
In the present of starch, iodine gives an intense blue colour. Perform the
test by transferring a drop of the reaction mixture to the test paper with a
stirring rod.
4) This is a steam distillation.
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Oxidation reaction of various functional groups 24
4) Adipic acid from cyclohexanol:
It is obtained by the oxidation of cyclohexanol with nitric oxide.
Reaction:-
OH
H2C
C
C C
COOH
COOH
H
H
H
H
H
H
O
HNO3
Cyclohexanol Adipic acid
Procedure:-
Nitric acid (96 ml, 95%, sp. gr. 1.32) is taken in a two necked
round bottom flask (500 ml capacity) fitted with a reflux condenser and a
dropping funnel. Cyclohexanol (30 gram, 0.3 mole) is added drop wise to
the nitric acid, which has been previously heated just to the boiling point.
A vigorous reaction with the evolution of nitrous oxide fumes sets in.
addition of cyclohexanol is continued drop wise (fresh drop of
cyclohexanol is not added till the previous drop has reacted). The addition
is so controlled so as to keep the reaction mixture at the boiling point.
Under no circumstances is cyclohexanol allowed to accumulate in the
flask, otherwise an explosive reaction may occur. The addition of
cyclohexanol takes about 100 minutes. The reaction mixture is finally
refluxed for 15 minutes. The separated adipic acid is filtered (sintered
funnel) and washed with cold water (20 ml). It is crystallized from
concentrated nitric acid (25-30 ml). The yield is 25 gram (56.3%);
melting point is 152°C.
Note:
Adipic acid is also obtained from cyclohexene by oxidation of potassium
dichromate and dilute sulfuric acid.
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Oxidation reaction of various functional groups 25
5) p-benzoquinone from hydroquinone:
Reaction:-
OH
OH
O
O
Hydroquinone p-benzoquinone
O
KBrO3/H2SO4
Procedure:-
A mixture of hydroquinone (10 gram, 0.09 mole), potassium
bromate (5.6 gram, 0.33 mole), sulphuric acid (1N, 5 ml) and water (100
ml) is slowly heated to 60°C on a water bath. After a few minutes, the
temperature is raised to 80°C and maintained for 10 minutes. The reaction
mixture is cooled in an ice bath. The separated quinine is filtered, washed
with cold water and dried in a vacuum desiccator over fused calcium
chloride. The yield is 7 gram (71.4%); melting point is 115°C. It is
crystallized from petroleum ether; melting point is 117°C.
6) Benzil from Benzoin:
Reaction:-
O OO OH
H
benzoin
HNO3
benzil
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Oxidation reaction of various functional groups 26
Procedure:-
Place 4.2 gram (0.02 mole) of benzoin in a 125 ml ground-glass-
stoppered Erlenmeyer flask and then add 11 ml (20 gram; 0.22 mole) of
concentrated nitric acid. Heat this mixture in hood (Note 1) on a steam
bath for 10-12 minutes. During the heating period, swirls the mixture
occasionally (Note 2).
At the end of the heating period, add to the flask 75 ml of cold
water, and swirl the flask to mix the contents. Then add seed crystals of
benzil, stopper the flask, and shake it to cause the oily product to solidify
in small lumps.
Collect the bright yellow solidified benzil by suction filtration, and
wash it thoroughly with water to remove the nitric acid. Yield: about 4
gram (about 95%). Benzil can be recrystallized from 95% ethanol, using
5.7 ml per gram.
Notes:
1) Nitrous oxide fumes are evolved.
2) The solid will gradually dissolve, and an oil (molten benzil) will form.
7) Oxidation of alcohol with benzimidazolium
fluorochromate (BIFC) under solvent free condition:
Reaction:-
N
H
N
CrO3 / HF
0oC , acetone
N
H
N
+
[HCrO3]F -
BIFC
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Oxidation reaction of various functional groups 27
CH2OH
CH3
BIFC
Solvent free
CHO
CH3
P-methyl benzyl alcohol P-methyl benzaldehyde
Procedure for preparation of BIFC:-
Benzimidazole (23.6 gram; 0.2mole) was dissolved in hot acetone.
A solution of chromium trioxide (20 gram; 0.2mole) in water (25 ml) was
cooled to 0°C and to this 40% hydrofluoric acid (4 ml; 0.23 mole) was
slowly added with vigorous stirring. The mixture was added drop wise
during 15 minute to the solution of benzimidazole and then cooled for 2
hour. The resulting yellow orange crystals were collected on a sintered
glass funnel and washed with small portions of acetone, kept under
suction until moderately dry.
Yield 35 gram (80%) and melting point 195°C. The structure was
confirmed by FTIR and elemental analysis.
General procedure for oxidation:-
A mixture of substrate (1 mmole) and BIFC (1mmole) was placed
in clean mortar and thoroughly ground with a pestle for 3 hour. The
progress of reaction was monitored by TLC or GC. The mixture was
extracted with CH2Cl2 or ether and filtered through a silica gel or alumina
pad. The solvent was evaporated and the resulting crude material was
purified on a silica gel column with appropriate eluent to afford the pure
product.
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Oxidation reaction of various functional groups 28
8) 5α,6β-Dibromocholestane-3-one from cholesterol
dibromide:
Reaction:-
H
HO
CH3
Br
H
H
CH3
H3C
CH3
CH3
H
Br
CH3
Br
H
H
CH3
H3C
CH3
CH3
H
BrO
cholesterol dibromide
Na2Cr2O7 in acatic acid
5a,6ß-Dibromocholestane-3-one
Procedure:-
Add the moist cholesterol dibromide to 40 ml of glacial acetic acid
in a 125 ml Erlenmeyer flask. To this, add, all at once, 40 ml of solution
of sodium dichromate in acetic acid that has been preheated to 105°C.
(Note 1; sufficient dichromate to oxidize 60 mmoles of secondary alcohol
to the corresponding ketone). After the mixture has been swirled briefly,
the temperature should rise to between 55°C and 60°C. The temperature
of the mixture must be maintained between 55°C and 58°C for as long as
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Oxidation reaction of various functional groups 29
it takes the solid to dissolve (3-5 minutes) and then for 2 minutes more
(Note 2).
After allowing the solution to stand at room temperature for about
20 minutes, add 8 ml of cold water, swirl to mix, and then cool the
suspension of dibromoketone to about 15°C by means of a cold water or
ice bath.
Collect the product by suction filtration, using 10-12 ml of cold
methanol for rinsing & washing. Transfer the crude product to a 100 ml
of beaker containing 25 ml of ice cold methanol. Stir the mixture to
thoroughly wash the crystals and then collect the product by suction
filtration.
Notes:
1) The solution can be prepared by dissolving 16 grams of sodium
dichromate dehydrate (0.054 mole) in 400 ml of glacial acetic acid. This
is enough reagent for 10 runs of the scale described.
2) If the temperature fails to reach 55°C or shows signs of falling below
55°C, the mixture should be heated briefly to reach or maintain the
specified temperature.
9) Oxidation of secondary alcohol by using a butyltriphenyl
phosphonium chlorochromate as oxidizing agent:
Reaction:-
CH
R1
R2
OH + BuPPh3CrO3Cl C
R1
R2
O
Alcohol Ketone
Butyltriphenyl phosphonium chlorochromate
BTPPCC
MeCN
Reflux
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Oxidation reaction of various functional groups 30
Preparation of Butyltriphenyl phosphonium chlorochromate:-
A solution of butyl triphenyl phosphonium bromide (18 gram, 45
mmole) in 100 ml of water was prepared, then CrO3 (4.5 gram, 45
mmole) in HCl 6N (12 ml) was added drop wise to the above solution and
stirred for 30 minute at room temperature. The resulting orange
precipitate was filtered and washed with cool distilled water (50 ml), and
dried in a desiccator under vacuum over calcium chloride to afford an
orange powder (18 gram, 88% yield), which decomposed at 190-191°C to
a dark brown material.
Procedure for oxidation:-
In a round bottom flask, a solution of alcohol (1 mmole) in
acetonitrile (10 ml) was treated with reagent BTPPCC (0.46 gram, 1
mmole) and refluxed for 10-150 minute until TLC (cyclohexane :
ethylacetate, 80:20) showed disappearance of starting alcohols. The
reaction mixture was cooled to room temperature and the solid was
filtered off and washed with acetonitrile (10 ml). The filtrates were
evaporated on a rotary evaporator and the resulting crude material was
purified by column chromatography on a silica gel with cyclohexane:
ethylacetate (80:20) as eluent or distillation in vacuum to afford pure
carbonyl compounds in 75-100% yields.
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Oxidation reaction of various functional groups 31
♫ OXIDATION OF KETONE ♫
1) Iodoform test:
This test useful for the identification of methyl ketones and
secondary methyl carbinols.
Reaction:-
C CH3R
OC OHR
O
+ CHI3NaOH
I2
Ketone carboxylic acid
Mechanism of Reaction:-
C CH3R
O
Ketone
C OHR
O
carboxylic acid
NaOH + I2 NaOI + HI
+ 3NaOI C CI3R
O
C O-Na
+R
O
+ CHI3H2O
NaOH
-3NaOH
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Oxidation reaction of various functional groups 32
Procedure:-
Dissolve 4 drops of a liquid or 100 mg of a solid in 5 ml of dioxane
(use 1 ml of water in place of this dioxane if the compound is soluble in
water to this extent). Add 1 ml of the sodium hydroxide solution and then
the iodine/potassium iodide solution with shaking until the definite dark
colour of iodine persists. If less than 2 ml of the iodine/potassium iodide
solution was consumed, place the test tube in a beaker of water at 60°C. If
the dark colour of iodine now disappears, continue to add the
iodine/potassium iodide solution until the dark colour that represents an
excess of iodine is not discharged by heating at 60°C for 2 minutes. Now
add 10% sodium hydroxide solution drop wise until the dark iodine
colour is gone, remove the tube from the heating bath, add 15 ml of
water, and allow the mixture to cool to room temperature. Collect by
suction filtration any solid formed and determine its melting point.
Iodoform melts at 119-121°C. If the iodoform is reddish, dissolve it in 3
or 4 ml of dioxane, add 1 ml of 10% sodium hydroxide solution, and
shake the mixture until the reddish colour gives way to the lemon-yellow
colour of iodoform. Slowly dilute the mixture with water and collect the
precipitated iodoform by suction filtration.
Methyl ketone (and acetaldehyde) and methyl carbinols including
ethanol (compounds that can be oxidized to methyl ketone by the reagent)
give iodoform under these conditions; acetic acid does not. Compounds
that can react with the reagent to generate one of these functional groups
will also give iodoform; conversely, it is possible that the functionality
that might be expected to result in the formation of iodoform can be
removed by hydrolysis before iodoform formation is complete.
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Oxidation reaction of various functional groups 33
2) Tolan (Diphenylethyne) from benzil:
Step 1: Benzil hydrazone
Reaction:-
C C
O O
C6H5 C6H5 C C
N
N
C6H5 C6H5
NH2
NH2
+ 2NH2NH2H2O
benzill benzil dihydrazine
+ 4H2O
Benzil : 8.4 g
Hydrazine hydrate : 6.1ml
Ethanol (absolute) : 15 ml
n-propyl alcohol : 25 ml
Procedure:-
Hydrazine hydrate (85%, 6.1 ml) is added to a solution of benzyl
(8.4 g, 0.04 mole) in n-propyl alcohol (25 ml) in a R.B. flask ( 100 ml
capacity) fitted with a reflux condenser. The monohydrazone separated,
which redissolves on heating. The mixture is refluxed for 50 hours,
cooled and the separated product filtered. It is washed with water and
then with absolute alcohol (15 ml). The yield is 8.9 g, (93.7 %); m.p. is
150-151°C.
Step 2: Tolan (diphenylethyne):-
Reaction:-
C C
N
N
C6H5 C6H5
NH2
NH2
benzil dihydrazine
C CC6H5 C6H5[O]
2HgO2N2 2H2O+ + + 2Hg
Tolan
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Oxidation reaction of various functional groups 34
Benzildihydrazone : 5 g
Benzene : 30 ml
Yellow mercuric oxide : 12 g
Procedure:-
Yellow mercuric oxide (0.5 g) is added to a suspension of benzyl-
dihydrazone (5g, 0.02 mole) in benzene (30 ml) in a three necked R.B.
flask (100 ml capacity) fitted with a sealed stirrer and reflux condenser.
The reaction mixture is warmed on a water bath. Evolution of nitrogen
takes place and the mixture turns grey. The remaining yellow mercuric
oxide (11.5 g) is added in small lots so as to keep the reaction mixture
gently refluxing. The reaction mixture is stirred for one hour, left
overnight and filtered. The residual mercuric oxide is washed with
benzene (5 ml). The combined benzene solution is dried (anhydrous
sodium sulphate) and distilled. The residual product is distilled under
reduced pressure (0.2-0.3 mm). The fraction between 95-105°C is
collected. It solidifies on cooling and is crystallized from alcohol. The
yield is 2.4 g (67.4 %); m.p. is 60-61 °C.
3) Benzilic acid from benzoin:
Reaction:-
HC C
OOH
C
OH
COOH
benzoin benzillic acid
NaBrO3
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Oxidation reaction of various functional groups 35
Mechanism of Reaction:-
HC C
OOH
C C
O
benzoin
NaBrO3
C
OH
COOH
benzillic acid
alkali
O
benzill
C
OH
COO-Na+H
+
Benzoin : 4 g
Potessium bromate : 5.6 g
Sulphuric acid (1 N) : 5 ml
Procedure:-
Benzoin (4 g, 0.019 mole) is added in portions to a stirred solution
of sodium hydroxide (3.7 g) and potassium bromate (1 g) (or sodium
bromate 0.9 g) in water (7 ml) at 85-90°C in an evaporating dish. The
temperature should not exceed 90°C. A small quantity of water is added
from time to time to prevent the mixture from becoming too thick. The
heating the stirring is continued (1.5-2 hours) until a test portion is almost
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Oxidation reaction of various functional groups 36
completely soluble in water. To the reaction mixture is added water (30
ml) and the mixture is cooled in ice-water. The separated benzhydrol
(byproduct) if formed is filtered. A little of the filtrate (1-2 ml) is kept
aside and the remaining filtrate is acidified with dilute sulphuric acid (1:3
by volume, 13 ml) added slowly with stirring to a point just short of
liberation of bromine. If more acid has been added, then the filtrate kept
separately is added and then sufficient sulphuric acid added to the end
point. The separated benzillic acid is filtered and washed with water. The
yield is 3.1 g, (72 %); m.p. is 149-150°C.
4) 2,2-Dimethylpropionic acid (trimethyl acetic acid) from
pinacolone:
It is obtained by the oxidation of pinacolone with hypobromite.
Reaction:-
C
O
(H3C)3C CH3 C
O
(H3C)3C OH(i) NaOBr
(ii) H3O+ + CHBr3
pinacolone Trimethyl acetic acid
Pinacolone : 40 g
Sodium hydroxide : 128 g
Bromine : 192 g (62.6 ml)
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Oxidation reaction of various functional groups 37
Mechanism of Reaction:-
C
O
R CH3
C
O
R O-
+ CHBr3
2OH- + Br2 O-Br + Br- + H2O
O-Br+ RCOCH2
-+ HOBr
RCOCH2 + Br OH RCOCH2Br + OH-
RCOCH2Br RCOCBr3OH-
Procedure:-
Bromine (62.6 ml, 1.2 mole) is added drop wise to a stirred and
well cooled (0°C) solution of sodium hydroxide (128 g, 3.2 mol) in water
(1220 ml) contained in a three necked R.B. flask fitted with a mechanical
stirrer and a dropping funnel. During the addition of bromine, the solution
is continuously stirred and the temperature is not allowed to rise above 10
°C (15-20 minutes). The mixture is cooled again to 0°C (ice-salt bath)
and pinacolone (40g, 0.4 mole) is added keeping the temperature below
10°C. After the colour of bromine has disappeared (one hour) the mixture
is stirred for 3 hours more at room temperature. The reaction mixture is
steam distilled to remove any carbon tetrachloride and bromo form. The
reaction mixture is heated with a Bunsen flame during steam distillation.
It is cooled and concentrated sulphuric acid (160 ml) added cautiously
though a dropping funnel. The reaction mixture is heated again in the
distillation assembly. Trimethyl acetic acid passes over with about 200 ml
of water. Triethyl acetic acid is in the upper layer, when a substance
heavier than water distils (brominated pinacolone), the distillation is
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Oxidation reaction of various functional groups 38
stopped. The upper layer of trimethylacetic acid is separated, dried
(anhydrous sodium sulphate) and distilled. The yield is 26.4 g (55%); b.p.
is 75-80°C/20 mm; m.p. is 34-35°C.
5) 2-Naphthoic acid from 2-acetyl napthalene:
It is obtained by the oxidation of 2-acetyl naphthalene with sodium
hypochlorite.
Reaction:-
COCH3 COOH[O]
(i)NaOH
(ii)HCl2-Acetylnaphthalene 2-Naphthoic acid
2-acetyl naphthalene : 22.25 g
Sodium hypochlorite : 37.5 g (see note)
Procedure:-
Sodium hypochlorite solution (containing about 37.5 g, 0.5 mole)
(see note) is taken in a three necked R.B flask (2 liter capacity) fitted with
the stirrer, a thermometer and a reflux condenser. 2-acetyl naphthalene
(22.5 g, 0.125 mole) is added to the stirrer solution of sodium
hypochlorite solution at 55°C. An exothermic reaction commences. The
reaction mixture is maintained at 60-70°C by cooling in ice bath if
necessary (30 minutes). The mixture is stirred for 30 minutes more and
excess hypochlorite destroyed by adding sodium metabisulphite solution
(25 %, 50 ml). It is to be ascertained that know hypochlorite remains, by
testing a solution with acidified potassium iodide solution. The reaction
mixture is acidified with concentrated hydrochloric acid (50 ml). The
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Oxidation reaction of various functional groups 39
product obtained is filtered, washed with water and crystallized from
alcohol. The yield is 18.75 g (87%); m.p. is 184-185°C.
Note:-
Sodium hypochlorite solution is obtained by diluting 600 ml of
commercially available chlorox (contains about 5% chlorine) with 150 ml
water.
6) 2-Hydroxy-4-Methoxybenzoic acid from 2-hydroxy-4-
methoxyacetophenone:
It is obtained by the oxidation of 2-hydroxy-4-
methoxyacetophenone with iodine-pyridine.
Reaction:-
OCH3
COCH3
OH
OCH3
COOH
OH
2-Hydroxy-4-methoxyacetophenone
2-hydroxy-4-methoxybenzoic acid
(i) I2-C5H5N
(ii) NaOH
(iii) H+
2-hydroxy-4methoxyacetophenone : 2 g
iodine : 3 g
pyridine : 20 ml
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Oxidation reaction of various functional groups 40
Procedure:-
2-hydroxy-4methoxyacetophenone (2 g, 0.012 mole), iodine (3 g,
0.012 mole) and dry pyridine (20 ml) is heated under anhydrous
conditions on a steam bath for one hour. The solution is kept at 0°C for
24 hours. The separated pyridinium iodine adduct is filtered and washed
with cold water. It is heated on a steam bath with aqueous potassium
hydroxide (2%, 120 ml). The clear, cooled alkaline solution is acidified
with hydrochloric acid. The separated product is filtered and purified by
dissolving in sodium carbonate solution and acidifying the clear alkaline
solution. It is crystallized from dilute alcohol. The yield is 1.2 g (60%);
m.p. is 160-161°C.
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Oxidation reaction of various functional groups 41
♫ OXIDATION OF ALDEHYDE ♫
1) Veratric acid (3,4-dimethoxybenzoic acid) from
veratraldehyde (3,4-dimethoxybenzaldehyde):
Reaction:-
CHOH3CO
H3CO
COOHH3CO
H3CO[O]
KMnO4
Veratraldehyde veratric acid
3,4-dimethoxybenzaldehyde
(verataldehyde) :25 g
potassium permanganate :35.5 g
Procedure:-
Verataldehyde (25 g, 0.15 mole) is suspended in water (150 ml)
and the suspension warmed to 50-60°C (water bath). A solution of
potassium permanganate (35.5 g, 0.225 mol in 350 ml water) is then
added drop wise during 2.5-3 hours to the stirred suspension. The mixture
is stirred for one hour more and the precipitated manganese dioxide is
destroyed by passing a current of sulphur dioxide gas. The separated
crystalline product is filtered and dried. The yield is 25 g (91.5%); m.p. is
179-180°C.
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Oxidation reaction of various functional groups 42
2) Tollen’s reaction:
Reaction:-
3R CHO + 2AgNO3 + NH4OH + 2NaOH
Aldehyde
2Ag + 3R COOH + 2NaNO2 + 2H2O + NH3
Carboxylicacid
Procedure:-
Clean a test tube thoroughly, preferably in it a 10% solution of
sodium hydroxide and rinsing the test tube with distilled water. To the
clean tube, add 2 ml of the silver nitrate solution and 1 drop of the sodium
hydroxide solution. Add the ammonium hydroxide solution drop wise and
while shaking well until the dark precipitated sliver oxide just dissolves.
Add 1 drop of the liquid or 30-50 mg of the solid to be tested,
shake the tube to mix, and allow it to stand at room temperature for 20
min. if nothing happens, heat the tube in a beaker of water at 35°C for 5
min.
Aldehyde and other substance that can be oxidized by the sliver
ammonia complex iron will reduced the sliver iron to metallic sliver,
which will precipitate as a “mirror” on the test tube if it is sufficiently
clean, or black colloidal suspension if the test tube is not clean.
The solution should not be allowed to stand after the test is
completed but should be discarded down the drain immediately, as the
highly explosive sliver fulminate may be formed on standing. Rinse the
test tube with dilute nitric acid.
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Oxidation reaction of various functional groups 43
Substances that can be oxidize by means of the sliver ammonia
complex iron include most aldehyde, “reducing sugars,” hydroxylamines,
aceloins, aminophenols, and polyhydroxyphenoles.
3) Vanillic acid (3-methoxy-4-hydroxybenzoic acid) from
vanillin:
Potash Fusion:-
On the fusion of compound with potassium hydroxide, the –CHO
is oxidized to –COOH. However, on fusion with a mixture of sodium
hydroxide and potassium hydroxide at a comparatively higher
temperature (190-195°C), vanillin is converted into 3,4-dihydroxy
benzoic acid (protocatechuic acid); in this case there is simultaneous
oxidation of the –CHO group and demethylation of the methyoxyl group.
Reaction:-
CHOHO
H3CO
COOHHO
H3CO[O]
(i)KOH fusion (140-180o)
(ii)H+
vanillin vanillic acid
Vanillin : 20 g
Potassium hydroxide : 56 g
Procedure:-
A mixture of potassium hydroxide (56 g, 1.0 mole) and water (8ml)
is place in a nickel dish set in a deep send bath and heated by the Bunsen
burner. The alkali is heated to 120°C with stirring. To the viscous mass is
added vanillin (20 g, 0.30 mole) in small portion during 10 minutes. The
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Oxidation reaction of various functional groups 44
reaction mixture is stirred after each addition. Considerable evolution of
hydrogen takes place during the reaction. The temperature rises to 140°C
and the mixture becomes fluid. After all the vanillin has been added, the
pasty mixture is cooled, dissolved in water (80 ml). The clear red solution
thus obtained is acidified with hydrochloric acid. The separated product is
filtered, washed with water and crystallized from alcohol. The yield is 22
g (99.5 %); m.p. is 208-209°C.
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Oxidation reaction of various functional groups 45
OXIDATION OF
♫ OTHER FUNCTIONAL GROUP ♫
Amino group:
1) Ethyldioxyazobenzene from p-Phenetidine:
Reaction:-
H3CH2CO NH2
H3CH2CO N N+
H3CH2CO N N OH
OH
p-phenetidine
HNO2; diazotize
p-ethoxydiazonium ion
phenol
ethyldioxyazobenzene
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Oxidation reaction of various functional groups 46
Procedure:-
Place 3.2 ml (3.43 grams; 0.025 mole) of para-Phenetidine in a 125
ml of Erlenmeyer flask. To this, add 5 ml of water and then 4.1 ml (0.049
mole) of concentrated HCl. Swirl this mixture until the amine has
dissolved.
Next, prepare a solution of 1.73 gram (0.025 mole) of sodium
nitrite in 12 ml of water. Finally, in a 250 ml Erlenmeyer flask, prepare a
solution of 2.35 gram (0.025 mole) phenol and 5.3 grams (0.05 mole) of
sodium carbonate in 90 ml of water.
Now, add the solution of sodium nitrite to the solution of the
amine; swirl to mix (Note 2). After allowing this mixture to stand for
about 60 seconds, pour it slowly while mixing well into the solution of
phenol and sodium carbonate. A voluminous precipitate of
ethyldioxyazobenzene forms immediately.
After allowing the resulting suspension to stand for 10 minutes or
so, collect solid by suction filtration, using some cold water to rinse the
material into the suction funnel and to wash the product on the funnel.
The filtered cake should be sucked free of as much water as possible so
that it can be easily dried. Yield of dried material: 5.95 gram (98%).
Notes:
1) If the solution is highly coloured, it can be treated with decolorizing
carbon, which can be removed by gravity filtration; most of the colour
can be removed in this way.
2) The diazotization of this amine can be done at room temperature.
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Oxidation reaction of various functional groups 47
Oxime group:
1) Quinolinium chlorochromate as an efficient reagent for
oxidative cleavage oximes via the use of microwave
irradiation and pestle / mortar:
Reaction:-
HC CHONOH QCC
1)MWI,PLS,1 MIN.
2)Pestle/mortar
3)Heat
Oxime Benzaldehyde
QCC = Quinolinium chlorochromate
MWI =Microwave irradiation
Procedure:-
1) Typical procedure utilizing microwave irradiation:
A mixture of aldoxime / ketoxime (4 mmoles) and Quinolinium
chlorochromate (10 mmoles) in dry CH2Cl2 (5 ml) was impregnated on a
neutral alumina (1.3 gram). The solvent was evaporated under vacuum to
efford a free flowing solid which was transferred to a 50 ml Erlenmeyer
flask, covered with a watch glass and subjected to MWI at power level 5
(310 W) for 1 minute. The reaction mixture was cooled, taken up in
CH2Cl2 (3 × 5 ml) and filtered. The filtrate was passed through a silica gel
column (5 gram) followed by evaporation of the solvent to furnish pure
aldehyde / ketone.
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Oxidation reaction of various functional groups 48
2) Typical procedure using pestle / mortar:
A mixture of aldoxime / ketoxime (4 m moles) , QCC (10 m
moles) and activated molecular sieves (4 Å, 4 grams) in dry CH2Cl2 (5
ml) were stirred in a 25 ml round bottomed flask followed by evaporation
of the solvent over a hot water bath. The mixture was transferred to a
mortar and ground for the 30 minutes. On completion of the reaction as
monitored by TLC, the mixture was taken up in CH2Cl2 (2 ×15 ml) and
passed through a silica gel column (7 grams). Evaporation of the solvent
in vacuo provided pure aldehyde /ketone.
Heterocyclic ring:
1) Oxidative cyclization of arenecarbaldehyde 4-methyl
quinolin-2-yl hydrazones to 3-aryl-9-methyl-1,2,4-triazolo
(4,3-a) quinolines using nitrous acid:
Reaction:-
N
CH3
NH
NHC C6H5 N
CH3
N
NCC6H5
NaNO2
ACOH
(1) (2)
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Oxidation reaction of various functional groups 49
Mechanism of Reaction:-
N
CH3
NH
NHC C6H5
N
CH3
N
NCC6H5
N
CH3
N NHC C6H5
NO
-H+
NO
N
CH3
N N C C6H5
-NO
H-H
N
CH3
N N C C6H5
N
CH3
N
N
C
C6H5
Procedure:-
To a solution of hydrazones (0.01 mole) in acetic acid (10 ml) was
added a solution of sodium nitrite (0.03 mole) in water (1 ml) and
resulting mixer was refluxed for 2 hr. The reaction was cooled to room
temperature and was slowly added to water. The aqueous mixer was
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Oxidation reaction of various functional groups 50
extracted with CH2Cl2 (3×50 ml), washed with saturated NaHCO3
solution followed by water and dried (Na2SO4). The solvent was removed
at reduced pressure and the residue was purified by passing through a
small column of basic alumina to afford 3-aryl-9-methyl-1,2,4-triazolo
(4,3-a)quinoline.
Using microwave irradiation:
To a solution of 4-methyl quinolin-2-yl hydrazones (0.01 mole) in
acetic acid (10 ml) was added sodium nitrite (0.03 mole) in water (1 ml)
and reaction mixture was subjected to microwave irradiation for 5-7
minute. After usual work up as above, the compound was purified as
described above.
2) Photosensitized oxidation of 1,4-dihydroxypyridine
derivatives:
Reaction:-
N
H3C H
COOEt
CH3H3C
EtOOC
HN
CH3
COOEt
CH3H3C
EtOOC
HN
H
COOEt
CH3H3C
EtOOC
H
+
hvSensitizer
o2
(1) (2)
(1) 2,4,6-trimethyl- 3,5-propionate 1,4-dihydroxypyridine
(2) 2,4,6-trimethyl- 3,5-propionate pyridine
Procedure:-
A CH3CN solution containing 1 millimole of each of (1) and 4
millimoles of each sensitizer was irradiated for the period mentioned
below with a 150 W Hg-high pressure with cooling of samples by
running water until total disappearance of starting material has been
observed. The products were isolated and identified by comparison of
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Oxidation reaction of various functional groups 51
spectroscopic and physical data with those of authentic samples. A
comparison of the UV spectra of starting material with those of the
sensitizers used in this project indicates that almost all of the light λ ≥ 280
nm has been absorbed by sensitizers only be using of 1:4 mole ratio of
(1) to sensitizer.
Sensitizer Time (min.); yield
(Rose Bengal) in CH3CN 80; 77
Methylene blue (MB) 65; 75
Tetraphenylporphine (TPP) 90; 78
Oxidation of Alkene:
1) Baeyer's Test:
This test is useful for indicating the presence of most olefinic or
acetylenic functional groups.
As a test for unsaturation, it should be used in conjunction with a
similar test with a solution of bromine in carbon tetrachloride.
Reaction:-
C C
H
R1 R2
H
+ Br Br C C
H
R1 R2
H
Br+
+ Br-
R1, R2 =H or Aliphatic chain or Aromatic ring
Procedure:-
Dissolve 0.2 ml of a liquid or 0.1 gram of a solid in 2 ml of water
or acetone. Add the potassium permanganate solution drop wise while
shaking the mixture well. If more than 1 drop of the permanganate
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Oxidation reaction of various functional groups 52
solution is consumed, as shown by the loss of the characteristic purple
colour, the presence of an olefin or acetylene or other functional group
that can be oxidized by permanganate under this conditions is indicated.
Such other groups include phenols and aryl amines, most aldehyde (but
not benzaldehyde or formaldehyde) and formate esters, primary and
secondary alcohols, mercaptans and sulfides, and thiophenols. Aryl-
substituted alkenes are oxidized by permanganate under these conditions.
Certain carefully purified alkenes are not oxidized under the
conditions of this test (acetone solvent), but can be oxidized if ethanol is
used instead; ethanol does not react with potassium permanganate within
5 minutes at room temperature.
In this test, you must take care not to be misled by the limited
reaction of impurities.
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Oxidation reaction of various functional groups 53
♫ REFERENCE ♫
1) Comprehensive practical organic chemistry; Preparation and Quantitative analysis; V. K. Ahluwalia, Renu Aggarwal.
2) Techniques and Experiments for organic chemistry; ADDISON
AULT; sixth edition.
3) Organic chemistry; sixth edition; Robert Thornton Morrison and Robert Neilson Boyd.
4) Indian Journal of medicinal chemistry; volume 44B; January
2005;pp.148-151.
5) Advanced organic chemistry; Reactions, Mechanisms and Structures; Jerry March; Fourth edition.
6) Unit processes in organic synthesis; P.H. Groggins; Fifth edition.
7) Name reactions; A collection of detailed reaction mechanism; Jie
Jack Li; Second edition.
8) Organic chemistry; Second edition; Maitland Jones, Jr.
9) Indian journal of chemistry; vol.42B; February 2003; pp. 405-407.
10) Indian journal of chemistry; vol.42B; June 2003; pp. 1456-1459.
11) Indian journal of chemistry; vol.40B; June 2001; pp. 508-509.
12) Indian journal of chemistry; vol.37B; January 1998; pp. 144-145.