gnu.inflibnet.ac.in BHARGAV H. PATELgnu.inflibnet.ac.in/bitstream/123456789/2346/1/33-Bhargav...

gnu.i

nflibn

et.ac

.in

“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

nflibn

et.ac

.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

nflibn

et.ac

.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

gnu.i

nflibn

et.ac

.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

nflibn

et.ac

.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

gnu.i

nflibn

et.ac

.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

gnu.i

nflibn

et.ac

.in

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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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+

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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,

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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.

gnu.i

nflibn

et.ac

.in


2) p-nitrobenzoic acid from p-nitrotoluene:

It is obtained by the oxidation of p-nitrotoluene with sodium


Reaction:-

O2N CH3 O2N COOH[O]

Na2Cr2O7/H2SO4

p-nitrotoluene p-nitrobenzoic acid

p-nitrotoluene : 14 g

Sodium dichromate : 40 g


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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

gnu.i

nflibn

et.ac

.in


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


Reaction:-

CH3CH2CH2CH2OH CH3CH2CH2CHO + H2O[O]

Na2Cr2O7+H2SO4

n-butyl alcohol n-butyraldehyde

n-butyl alcohol :25.5 ml

Sodium dichromate : 28 g


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in



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

gnu.i

nflibn

et.ac

.in


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)

gnu.i

nflibn

et.ac

.in



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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


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)

gnu.i

nflibn

et.ac

.in



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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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

gnu.i

nflibn

et.ac

.in


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.

gnu.i

nflibn

et.ac

.in


♫ 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.

gnu.inflibnet.ac.in BHARGAV H. PATELgnu.inflibnet.ac.in/bitstream/123456789/2346/1/33-Bhargav...

Documents

Transcript of gnu.inflibnet.ac.in BHARGAV H. PATELgnu.inflibnet.ac.in/bitstream/123456789/2346/1/33-Bhargav...