17uch09 - Organic Chemistry-Ii

ORGANIC CHEMISTRY-II
AVS College of Arts & Science

(Recognized under Section 2(f) & 2 (B) of UGC Act 1956 and Accredited by NAAC)
(Affiliated to Periyar University, Salem)
Attur Main Road, Ramalingapuram, SALEM – 636106
DEPARTMENT OF UG CHEMISTRY
Students Study Material
2020-2021
Title of the Subject ORGANIC CHEMISTRY
Paper Code 17UCH09
Year & Class III B.Sc CHEMISTRY
Batch 2018-2021
Semester EVEN
Subject In-charge HOD PRINCIPAL
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SYLLABUS
ORGANIC CHEMISTRY
UNIT I Carbohydrates
1.1.Classification, Reactions of Glucose and Fructose- Constitution of glucose and fructose-open
chain structure- Configuration and ring structure-mutarotation, epimerisation Conformations of
glucose and fructose.
1.2.Interconversion of monosaccharides- conversion of pentose to hexose and vice-versa ,aldose
to ketose and vice-versa
1.3.Disaccharides-structural elucidation of sucrose and maltose, Polysaccharides-structure of
starch and cellulose - derivatives of cellulose.
UNIT II Vitamins and antibiotics

2.1. Vitamins-occurrence and biological importance of Vitamin A, Thiamine, Riboflavin,
Pyridoxin and Ascorbic acid. – Synthesis and structural elucidation of ascorbic acid.
2.2. Antibiotics-structural elucidation of penicillin G and chloromycetin.
UNIT III Molecular rearrangements

3.1. Classification as anionotropic, cationotropic , intermolecular and intramolecular.
3.2.Mechanisms of pinacol-pinacolone, Beckmann, benzidine, Hofmann, Curtius, Lossen,
Schmidt, benzilic acid, Fries and Cope rearrangements.
UNIT IV Important reagents and their applications in organic chemistry

AlCl3, BF3, LiAlH4, NaBH4, PCl5 ,P205,Na/ethanol, alcoholic KOH, H2/Ni, H2/Pd-BaS04,
Zn/Hg-HCl, H2N-NH2/C2H5ONa, Ag2O, HIO4, Lead tetra acetate and Osmium tetroxide.
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UNIT V Green Chemistry

5.1.Green Chemistry- Principle & Greener Reactions- Definition, need of green chemistry,
Twelve basic principles of green chemistry- Planning a green synthesis in a chemical laboratory-
Solvent-less reactions, Selection of appropriate solvent .
5.2. Use of microwaves- Fundamentals of closed-vessel heating and sonication- Water as green
solvent- reactions in ionic-liquid, Solid support organic synthesis, Phase transfer catalyst (PTC)
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UNIT-I
CARBOHYDRATES
Classification of Carbohydrates
The carbohydrates are divided into three major classes depending on the number
of simple sugar units present in their molecule. In other words the basis of
classification of carbohydrates will be will be the number of simple sugar,
molecules produced on hydrolysis.
Chemical reactions of glucose
a) Oxidation
With weak oxidising agent:
On treatment With a weak oxidising agent such as bromine water, CHO of
glucose is oxidised to COOH and gluconic acid results.
For the same reason, glucose reduces Tollen’s reagent, Ag+ (ammonia
complex), and Fehling’s solution, Cu2+(tartarate complex),to give metallic silver
and cuprous oxide, Cu2O respectively. These reactions are used as tests for the
presence of glucose.
Ag+ + Glucose Ag + (Gluconic acid)

Cu2+ + Glucose Cu2O + (Gluconic acid)
With strong oxidising agent:
A strong oxidising agent like nitric acid oxidises both the CHO and CH2OH
groups of glucose, yielding glucaric acid.
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b) Reduction
Glucose on reduction with sodium borohydride, NaBH4, or catalytic
reduction (H2/Pd) gives the corresponding alcohol D – Glucitol.
The reduction of glucitol with hydrogen iodide and red P at 100 , gives n –
hexane. This proves the straight chain structure of glucose.
c) Acetylation:
Glucose reacts with acetic anhydride in the presence of anhydrous zinc
chloride, to form penta acetyl glucose.
This gives a clue to the presence of five OH groups in glucose molecule.

d) Addition of HCN:
Aldehydes hydrogen cyanide reacts by addition at the aldehyde carbonyl
group. Since this creates new asymmetric carbon, two isomeric cyanohydrins
differing only in configuration at the aldehydic carbon are obtained.
f) Oxime formation.
Reaction with hydroxylamine:
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Glucose condenses with hydroxylamine, NH2OH, to form Glucose oxime.
g) Fermentation:
A solution of glucose is readily fermented by the enzyme zymzse present in
yeast, in the absence of air, to form ethanol and carbon dioxide.
C6H12O6 2C2H5OH + 2CO2
This reaction called alcoholic fermentation is the basis of manufacture of
wines and alcohol.
OPEN – CHAIN FORMULA
1. Molecular formula:
Molecular formula of glucose is C6H12O6.
2. Presence of 6 C un branched chain:
The complete reduction of glucose with conc. hydrogen iodide and red P
gives n – hexane. This proves that glucose molecule is made of an un branched six
– carbon chain.
3. Presence of 5 OH groups:
Glucose reacts with acetic anhydride to form a penta acetyl derivative. This
shows a presence of five hydroxyl groups. Since glucose is a stable compound, no
two OH groups are attached to the same carbon. In other words, the five OH
groups are on different carbons.
4. Presence of C=O group:
Glucose reacts with hydroxylamine to form an oxime. It suggests the
presence of a carbonyl group.
5. Presence of terminal CHO function:
On mild oxidation with bromine water, glucose is converted to gluconic
acid which when reduced with excess of HI yields n – hexanoic acid.
C5H11O5.CHO C5H11O5.COOH CH3(CH2)4COOH
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This shows that glucose contains a six carbon straight chain with CHO at
one end which has been oxidised to COOH.
6. Construction of open chain formula:
Glucose has a straight 6 – carbon chain with a terminal CHO, the five OH
groups can be placed one each on the remaining five carbons. Supplying
hydrogen atoms to satisfy their tetra covalency, the open – chain structure of
glucose
Occurrence and preparation of D – Glucose

Occurrence:
Glucose is the most common monosaccharide. It is known as Dextrose
because it occurs in nature principally s the optically active dextrorotatory isomer.
Glucose is found in most sweet fruits, especially grapes (20 – 30 ), and
honey. It is an essential constituent of human blood. The blood normally contains
65 to 110 mg (0.06 to 0.1 ) of glucose per 100 ml.
In diabetic persons the level may be much higher. In the combined form
glucose occurs in abundance in cane sugar and polysaccharides such as starch
and cellulose.
Preparation:
Glucose is produced by the hydrolysis of starch with dilute hydrochloric
acid at high temperature under pressure.
(C6H10O5)n + n H2O n C6H12O6

An aqueous suspension of starch obtained from corn is acidified with
hydrochloric acid. It is then heated with high – pressure steam in an autoclave.
When the hydrolysis is complete, the liquid is neutralised with sodium carbonate
to a pH of 4 – 5. The resulting solution is concentrated under reduced pressure to
get the crystals of glucose.
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Prepare Penta acetyl glucose by using glucose

Glucose reacts with acetic anhydride in the presence of
anhydrous zinc chloride, to form penta acetyl glucose.
CHO CHO
CHOH) +5(CH3CO)2O (CHO.COCH3)4+5CH3COOH

CH2OH CH2O.COCH3
D–Glucose Penta acetylglucose
Distinguish Glucose from Fructose
Glucose can be differentiated from fructose by performing Seliwanoff test.
Fructose gives positive test with Seliwanoff reagent, where as glucose gives
negative test with Seliwanoff reagent.
A dark red or cherry red colour is observed when fructose is heated with
Seliwanoff reagent for 60 seconds, whereas light pink or peach colour is observed
when glucose is heated with Seliwanoff reagent for 60 seconds.
Glucose react with phenyl
Hydrazine
When warmed with excess phenylhydrazine, glucose first forms
phenylhydrazone by condensation with CHO group. The reaction does not stop
at this stage. The adjacent CHOH group is then oxidised by a second molecule of
phenylhydrazine which itself is reduced to aniline and ammonia. The resulting
carbonyl group reacts with a third molecule of the reagent to yield the final
product Glucosazone.
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Uses of glucose
• Glucose is a source of energy, and all the cells and organs in your body
need glucose to function properly.
• Glucose as a medication is given either by mouth (orally) or by injection.
• Glucose is used to treat very low blood sugar (hypoglycaemia), most often
in people with diabetes mellitus.
• As a sweetening agent in syrups and confectionery.
• As food for infants.
• As a reducing agent in silvering of mirrors and to convert indigo blue to
indigo white in vat dyeing .
• As a raw material for wine and alcohol manufacture.
Conformation of Fructose
When fructose is component of a saccharide as in sucrose, it usually occurs
in its furanose form (5 – membered hemiketal). Thus - D – fructose is assigned
the name D – fructofuranose.
The generic name of the Haworth structure for 5 – membered sugars arose
because of its similarity with the hetero cycle furan.
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Pyranose Ring Structure of Glucose

He introduced the hexagonal representations resembling the hetero cycle
pyran which contains five carbons and one oxygen in the ring. He claimed the
names - D – glucopyranose and – D – glucopyranose for the hexagonal
structure of - D – glucose and - D – glucose.
It may be noted that in Haworth formula, all the OH group on the right in
Fischer formula are directed below the plane of the ring, while those on the left go
above the plane. The terminal CH2OH projects above the plane of the ring.
Inter conversion of glucose to fructose.

Conversion of aldose to isomeric ketoses:
An aldose may be converted to the isomeric ketose by the following steps:
✓ Formation of Osazone by treating with excess phenyl hydrazine.
✓ Hydrolysis of osazone to ozone with dil.HCl.
✓ Reduction of ozone to ketose with zinc and acetic acid, when – CHO is
reduced in preference to C = O.
✓ For example, D – glucose may be converted to D – fructose.
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Glucose react with Tollen’s reagent and fehling’s solution.

With weak oxidising agent:
On treatment With a weak oxidising agent such as bromine water, CHO of
glucose is oxidised to COOH and gluconic acid results.
For the same reason, glucose reduces Tollen’s reagent, Ag+ (ammonia
complex), and Fehling’s solution, Cu2+(tartarate complex),to give metallic silver
and cuprous oxide, Cu2O respectively. These reactions are used as tests for the
presence of glucose.
Ag+ + Glucose Ag + (Gluconic acid)
Cu2+ + Glucose Cu2O + (Gluconic acid)
Establish the structure of fructose.
Open – chain Formula:
1. Molecular formula: The molecular formula of fructose is C6H12O6.
2. Presence of 6 – C chain: Fructose on complete reduction with HI and red P
forms n – hexane. Therefore, it contains n unbranched 6 – carbon chain.
3. Presence of 5 OH group: Fructose react with acetic anhydride to give
pentaacetyl derivative. It indicates the presence of five hydroxy groups,
each attached to separate carbon.
4. 4. Presence of C=O: It forms an oxime with hydroxylamine and hence
contains a carbonyl group, C = O.
5. C=O is ketonic: On oxidation with HNO3, fructose yields a mixture of
tartaric acid (4C) and glycolic acid (2C), both containing fewer carbon atom
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than six. Therefore, fructose behaves like a simple ketone and the C=O is
ketonic.
6. Carbonyl is on C – 2 : Fructose forms cyanohydrins which upon hydrolysis
and subsequent reduction with HI and red P yields 2 – methyl hexanoic
acid. Since the COOH has appeared in place of CN the latter is bonded to C
– 2 in the cyanohydrins. Hence the carbonyl is at position 2 on the six
carbon chain.
7. Open – chain formula: The open chain structure of fructose can be

constructed.
Configuration:
Formation of Glucosazone
Fructose react with excess phenyl hydrazine, C6H5NHNH2, to form
glucosazone. The ozasone formed by fructose is identical with that obtained from
D – glucose. This shows that the configuration of asymmetric carbon atoms C-3,
C-4, and C-5 in D – fructose is the same as in D – glucose.
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Cyclic structure of D – Fructose:

A six – membered hemiketal ring structure was proposed for D – fructose.
Since D – Fructose also exhibits mutarotation, the and forms in equilibrium
via the open – chain form.
Configuration of D – Glucose:
1. Construction of four possible D – pentose:
Taking the configuration of D – glyceraldehydes as standard two possible D
– aldotetroses may be constructed by adding a CHOH just below CHO, placing
OH to the right and then to the left.
Similarly each of the two D – tetroses gives two D – aldopentoses. Thus four
possible D – aldopentoses.
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2. D – Arabinose has configuration II and IV:

Oxidation of D – arobinose with nitric acid oxidises the terminal CHO and
CH2OH groups yielding two optically active dicarboxylic acids. The forms II and
IV can form two optically active diacids, while I and III can give meso acids only
that have a plane of symmetry. Therefore D – arabinose is either II or IV.
3. Configuration II confirmed for D – arabinose:
D – Arabinose by Killiani Fischer synthesis yields two epimeric aldohexoses, D-

glucose and D – mannose. These on oxidation with nitric acid form two optically
active dicarboxylic acids. This is theoretically possible only if D – arabinose has
the configuration II and not IV.
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4. Ruff degradation of D – glucose and D – mannose produces D – arabinose

in each case:
In ruff degradation the CHOH below CHO is destroyed. Therefore, the
configuration of the two aldohexoses, D – glucose and D – mannose, can be
derived by adding new CHOH below CHO in form II of D – arabinose.
5. D- Glucose and L – glucose yield the same dicarboxylic acid:

Two sugars differ only in respect of the position of the terminal groups
(CHO and CH2OH). Therefore, the exchange of the terminal groups in D –
glucose should be able to give a different aldohexose .
If VII is rotated through 180 in the plane of the paper, it gives an aldohexose VIII,
different from V. A similar procedure with formula VI does not give rise to a
different sugar.
Cyclic structure of D – Glucose:
1. Open – chain structure not wholly true:
Fischer realised that the open – chain pentahydroxy aldehyde structure of
glucose did not wholly explain its chemical behaviour. Unlike simple aldehydes,
glucose did not form the crystalline bisulphite compound and failed to give the
Schiff’s test. The penta – acetate and pentamethyl – ether derivatives of glucose
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are not oxidised by Tollen’s reagent or Fehling’s solution, indicating the absence
of CHO group.
2. Cyclic structure suggested to explain mutarotation:
The existence of two crystalline forms of glucose, - glucose and –
glucose. - glucose had specific rotation +112 , while - glucose +19 . The
optical rotation of each of these forms changed gradually with time till finally a
constant value +53 was reached.
The concentrations of – D – glucose, - D – glucose and the open chin
glucose at equilibrium are 36 , 64% and less than 0.01%respectively. This
explains why D – glucose can react both as an aldehyde and a cyclic hemiacetal in
which CHO is absent.
3. Glycoside formation confirms cyclic structure:

Glucose when treated with methanol in the presence of dry HCl gives two
isomeric acetals or glycosides. These crystalline glycoside methyl - D –
glucoside and methyl - D – glucoside have been actually isolated. These are
optically active but do not give any of the reactions of free CHO group. The two
glycosides are the methyl derivatives of - and - D – glucose formed as a result
of the reaction between the hemiacetal OH of these forms and methanol.
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4. Ring size:
So far we have represented structures of cyclic hemiacetals or anomers of D –
glucose as having a ring of six members five carbons and one oxygen. It prepared
tetra – O – methyl – D – glucose by treating methyl – D – glucoside with dimethyl
sulphate and subsequent acid hydrolysis of the penta methyl derivative formed.
The oxidation of tetra – O – methyl – D – glucose with nitric acid yielded
trimethoxy glutaric acid.
Epimerisation.
1. An aldose can be converted to its epimer with opposite configuration at C –
2 by the following steps:
2. Oxidation of aldose with bromine water to give the aldonic acid.
3. Heating the aldonic acid with pyridine, C6H5N, to give an equilibrium
mixture of original and its epimeric acid.
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4. Separation of the epimeric acid and reduction of its lactone to yield the
epimer aldose.
Ex:
D – glucose may be converted to its epimer D – mannose.
Establish the structure of maltose.

It is obtained from starch. It is composed of two - D – glucose units joined
by glycosidic linkage b/w C – 1 of one unit and C – 4 of the other unit.
C – 1 of the second glucose unit in the maltose structure is a hemiacetal
carbon. Consequently it is equilibrium with the open – chain aldehyde form. Thus
maltose can exist in and forms. Since it has a potential aldehyde group,
maltose shows mutarotation forms osazone and reduces Fehling’s solution
(Maltose is a reducing sugar)
Reducing and non-reducing sugars

Those saccharides which reduce Fehling’s reagent and Tollen’s reagent are
called Reducing sugars, and those which do not, Non – Reducing Sugars. The
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ability to reduce or not to reduce Fehling’s and Tollen’s reagents depends on

certain characteristics structural features.
Structural features of Reducing Sugars:
1. They contain hydroxyaldehyde or hydroxyketone functions.
2. They contain cyclic hemiacetal or hemiketal structures in equilibrium with

the open – chain form having a free CHO or C=O groups as the case may
be. Such sugars, therefore, reduce Fehling’s and Tollen’s reagents. Reducing
sugars also exhibit mutarotation.
Structural Features of Non – Reducing sugars:

1. They do not contain free aldehyde or ketone groups with OH on the carbon
adjacent to the carbonyl group.
2. They contain acetal or ketal structure that is stable. Their cyclic structures
cannot be opened into an open – chain form having a free carbonyl group.
Thus they are unable to reduce Fehling’s or Tollen’s reagent. For the same
reason, non – reducing sugars do not exhibit mutarotation.
Examples:
All monosccharides contain free or potential CHO or C= O functions and are
reducing sugars.
Ex: D – glucose and D – fructose.Of the disaccharides, sucrose is non – reducing
because the anomeric carbons of both monosaccharides are involved in glycoside
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or acetal formation. Maltose and lactose are reducing sugars, because in one of the
monosaccharides units there is a hemiacetal group that can be opened to give free
OH function.
Inversion of cane sugar
The hydrolysis of sucrose by boiling with a mineral acid, or by the enzyme
invertase, produces a mixture of equal molecules of D – fructose and D – glucose.
C12H22O11 + H2O C6H12O6 + C6H12O6

Sucrose solution is dextrorotatory but during hydrolysis it becomes laevorotatory.
The specific rotation of sucrose is + 66.5 . D – Glucose has specific rotation +52
and D – Fructose - 92 . Therefore, the net specific rotation of an equimolar mixture
of D – fructose and D – glucose . = -20
The specific rotation changes from +66.5 to - 20 . The sign of specific rotation
changes from (+) to (-), or said to invert. Hence the hydrolysis of sucrose to D –
glucose and D – fructose, is termed inversion and the hydrolysis mixture is called
invert sugar.
Sucrose D – glucose + D – Fructose Specific rotation +66.5

Invert sugar specific rotation-20
STRUCTURE AND PROPERTIES OF CELLULOSE
Cellulose is the main structural material of trees and other plants. Wood is
50% cellulose, while cotton wool is almost pure cellulose. Other sources of
cellulose are straw, corncobs, bagasse and similar agricultural wastes.
Manufacture:
Cotton wool is about 97 percent cellulose. It is ready for use after washing
away the waxes and fats associated with it. The cellulose required for making
paper is obtained from wood. Lignin and resinous substances present along with
cellulose, are removed by digesting the wood chips under pressure with a
solution of calcium hydrogen sulphite, Ca(HSO3)2. The cellulose separates as
insoluble fibres which are washed with water, bleached and dried.
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Structure:
Cellulose is a straight – chain polysaccharide composed of D – glucose
units. These units are jointed by - glycosidic linkages b/w C – 1 of one glucose
unit and C – 4 of the next glucose unit. The number of D – glucose units in
cellulose ranges from 300 – 2500.
Properties:
✓ Cellulose is a colourless amorphous solid having no melting point.
✓ It decomposes on strong heating.
✓ It is insoluble in water and most organic solvents.
✓ It dissolves in Schweitzer’s reagent which is ammoniacal solution of cupric
hydroxide.
Derivatives of Cellulose
Each glucose unit in cellulose molecules has three –OH groups. Thus
cellulose gives industrially important derivatives involving one or more of these
three – OH groups.
1. Nitrated Cellulose:
Cellulose reacts with nitric acid in the presence of sulphuric acid to form an ester
Cellulose Nitrate, called Gum Cotton or Cordite.
Cell – OH + HNO3 Cell – ONO2

Gun Cotton, which looks like ordinary cotton is highly explosive. It is used in the
manufacture of smokeless gunpowder or propelling powder.
By partial nitration, cellulose gives cellulose dinitrate, known as pyroxylin. When
dissolved in ether or alcohol, it forms a transparent film called Collodion.
Collodion is used as a covering over cuts and skin and abrasions.
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2. Cellulose acetate:
Cellulose when acetylated with acetic anhydride and sulphuric acid, forms
Cellulose acetate or triacetate.
Cell – OH + (CH3CO)2O Cell – O – COCH3

The cellulose acetate in acetone solution is passed through a spinnerette into a
stream warm air to evaporate the acetone, a product called Acetate Rayon is
obtained. The acetate fabrics accept colour well and are wrinkle resistant.
Cellulose acetate is also used in making motion picture film.
3. Cellulose Xanthate:
When cellulose is treated with sodium hydroxide solution and then with
carbon disulphide, a xanthate is formed.
The cellulose xanthate dissolves in sodium hydroxide solution to give a viscose

solution and is named as Viscose. When the viscose is passed through a
spinnerette into a dilute acid bath, xanthate is decomposed, the regenerate
appearing in the form of Viscose Rayon. These threads are wound and processed
into fabric.
Structure of Sucrose
1. Molecular formula of sucrose is C12H22O11.
2. Sucrose react with acetic anhydride in the presence of of sodium acetate to
form sucrose octa acetate. This reaction indicates the presence of eight
hydroxyl groups in a sucrose molecule. Since sucrose is a stable compound,
the eight OH groups must be present on separate carbon atoms.
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3. Hydrolysis of sucrose with dilute acids yields an equimolecular mixture of

D – glucose and D – fructose. This indicates that the sucrose molecule is
made up in one unit of these monosaccharides.
4. Sucrose does not reduce Tollen’s reagent or Fehling’s solution , does not
form an osazone, when glucosazone is formed . It does not form methyl
glucosides, and does not undergo mutarotation.
All these observations indicate that the cyclic forms of glucose and fructose are
joined together glycosidic linkage at points where the carbonyl groups would
otherwise become available that is C – 1 in glucose and C – 2 in fructose.
(5)Sucrose reacts with dimethyl sulphate in an alkaline solution to form octa
methyl sucrose, which on hydrolysis yields a mixture of 2,3,4,6 – tetramethyl – D
– glucopyranose and 1,3,4,6 – tetramethyl – D – fructofuranose. The formation of
these compounds indicates that the glucose unit in sucrose has a pyranose form,
and the fructose unit in the furanose form.
C12H14O3(OH)8 + (CH3)2SO4 C12H14O3(OCH3)8
(6) Sucrose is hydrolysed by maltase, an enzyme that hydrolyses only -

Glycosides. It is also hydrolysed by invertase, an enzyme that hydrolysis but
not fructofuranosides. These observations indicate that sucrose is both an -
glucoside and a fructoside.
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Properties of Sucrose
Physical properties:
❖ Sucrose is a colourless, odourless, crystalline substance, m.p 185 – 186 .
❖ It is very soluble in water, slightly soluble in alcohol, and insoluble in ether.
❖ An aqueous solution of sucrose is dextrorotatory, its specific rotation being
66.5 .
Chemical properties:
Sucrose molecule is made of one D – glucose and one D – fructose unit
joined by a glycosidic bond. It gives all the reactions of glucose and fructose,
minus those due to free or potential carbonyl group.
Thus it fails to reduce Fehling’s solution, and doesnot react with hydrogen
cyanide or phenylhydrazine. At the glycosidic bond it reacts by hydrolysis to
generate the component units, the D – glucose and D – fructose.
The hydrolysis of sucrose by boiling with a mineral acid, or by the enzyme
invertase, produces a mixture of equal molecules of D – fructose and D – glucose.
C12H22O11 + H2O C6H12O6 + C6H12O6

Sucrose solution is dextrorotatory but during hydrolysis it becomes laevorotatory.
The specific rotation of sucrose is + 66.5 . D – Glucose has specific rotation
+52 and D – Fructose - 92 . Therefore, the net specific rotation of an equimolar
mixture of D – fructose and D – glucose .
= -20
The specific rotation changes from +66.5 to - 20 . The sign of specific

rotation changes from (+) to(-), or said to invert. Hence the hydrolysis of sucrose
to D – glucose and D – fructose, is termed inversion and the hydrolysis mixture is
called invert sugar.
Sucros D – glucose + D – Fructose Specific rotation +66.5

Invert sugar specific rotation-20
Structure of starch.
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Starch is actually a mixture of two structurally different polysaccharides,

Amylose, (20%) and Amylopectin (80%). When starch is heated with hot water, it
can be separated into these components. The part that is soluble in water is
amylose and remaining fraction is amylopectin.
Both amylose and amylopectin are composed of D – glucose units. The
amylose molecule is made up of D – glucose units jointed by - glycosidic
linkages b/w C – 1 of glucose unit and C – 4 of the next glucose unit. The number
of D – glucose units in amylase ranges from 60 – 300.
Amylopectin has a branched – chain structure. It is composed of chains of

25 to 30 D – glucose units joined by - glycosidic linkages b/w C – 1 of one
glucose unit and C – 4 of the next glucose unit. These chains are in turn connected
to each other by 1,6 – linkages. The number of D – glucose units in amylopectin
ranges from 300 to 6000.
Properties and uses of starch
Starch is a colourless amorphous, powder having no definite melting point.
It gives colloidal solutions in water.
1. Hydrolysis:
The hydrolysis of starch with hot dilute acids yields a syrupy mixture of
glucose, maltose, and high – molecular weight saccharides. The mixture is called
Dextrin and marketed as Corn Syrup.
The digestive enzymes in humans convert starch ultimately to glucose
which is the source of energy. In the presence of the enzyme amylase starch is
converted to maltose, an important step in the manufacture of alcohol from
starch.
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2. Iodine test:
It is amylase which gives a blue colour when treated with iodine, it is
believed that amylase forms a helical structure and iodine is lodged in it.
Starch does not reduce Tollen’s reagent and Fehling’s solution . It does not
form an osazone with phenylhydrazine.
Uses:
• Textile chemicals from starch: warp sizing agents are used to reduce
breaking of yarns during weaving. Starch is mainly used to size cotton based
yarns. Modified starch is also used as textile printing thickener.
• In oil exploration, starch is used to adjust the viscosity of drilling fluid,
which is used to lubricate the drill head and suspend the grinding residue in
petroleum extraction.
• Starch is also used to make some packing peanuts, and some drop
ceiling tiles.
• In the printing industry, food grade starch is used in the manufacture
of anti-set-off spray powder used to separate printed sheets of paper to avoid
wet ink being set off.
• For body powder, powdered corn starch is used as a substitute
for talcum powder, and similarly in other health and beauty products.
• Starch is used to produce various bio plastics, synthetic polymers that are
biodegradable. An example is poly lactic acid based on glucose from starch.
• Glucose from starch can be further fermented to bio fuel corn ethanol using
the so-called wet milling process. Today most bio ethanol production plants
use the dry milling process to ferment corn or other feedstock directly to
ethanol.
• Hydrogen production could use glucose from starch as the raw material,
using enzymes.
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UNIT-II
VITAMINS AND ANTIBIOTICS
Vitamin ‘A’
Occurrence:
Sea and fresh water fish, liver oils of sheep,calf,ox, halibut, shark, apples,
oranges, carrots, mint, sweet potato, papaya, yellow pumpkin, cabbage. Tomato
contains carotenoids. ‘A’ group of Vitamins are called caroteniods as it includes α,
peta, Gama carotenoides and retinols.
Biological importance of vitamin A:
❖ Vitamin A is essential for growth, reproduction of cells and normal
metabolism.
❖ Vitamin A regulates the growth of bones in the growing animal. Excess
vitamin A is harmful to growth of bones.
❖ It plays a significant role in the biosynthesis of glycogen and some steroids.
❖ Moderates and massive doses of vitamin have been used in pregnancy
lactation.
Deficiency symptoms:
❖ Deficiency may cause night-blindness and keratomalacia (eye disorder that
results in a dry cornea).
❖ It affects the vision , the skin and immune functions adversly
Uses:
❖ Vitamin A is produced synthetically for medical purposes.
❖ Vitamin A is available in concentrated solution form (or) in tablet form. Cod
liver oil capsules are available.
❖ In the treatment of night blindness, Vitamin A is administered in the dose of
50,000 to 75,000 units usually in the form of halibut liver oil.
26
Vitamin C (Ascorbic acid)

Occurrence:
Tomato, leafy vegetable, citrus fruits, cabbage, paprika etc.
Biological importance:
❖ It regulates oxidation-reduction potential inside the cell by acting as a
hydrogen carrier.
❖ It regulars carbohydrates metabolism.
❖ It plays a major role in wound healing by producing connective tissue.
❖ It involves in the maturation of RBC.
❖ It helps in the absorption of iron from the intestine.
❖ It provides resistance power against toxins, cold and stress conditions.
❖ It is essential for the synthesis of adrenal hormones and gonadal hormones.
❖ In man deficiency of this vitamin causes scurvy. It is characterised by
internal bleeding. Bleeding is more common in the gums. It is due to
fragility of capillaries.
❖ It causes malfunction of bones and teeth.
❖ It causes increased brittleness of bones leading to fracture.
❖ It causes delayed blood clotting.
❖ It also causes anaemia.
❖ Increased susceptibility to infections.
❖ Wound healing is delayed.
❖ It also causes disturbances in carbohydrate metabolism.
Uses:
❖ It is used in the treatment of scurvy when it is administered in the dose of
100 to 500 mgs per day.
❖ Infertile scurvy can be prevented by giving 5 mg of this vitamin per day.
❖ Vitamin helps in absorption of iron from the intestine as it facilitates the
conversion of ferric into ferrous ions.
27
❖ Vitamin C is effective against cold, though its role in the treatment of

common cold is still controversial.
SYNTHESIS AND STRUCTURAL ELUCIDATION OF ASCORBIC ACID (VITAMIN C)

General methods of preparation:
❖ The molecular formula of vitamin C is C6H8O6.
❖ Presence of keto-enol system.
❖ Ascorbic acid undergoes ozonolysis without produsing fragments,shows
that it contains one double bond.
❖ With phenyl hydrazine ascorbic acid gives phenyl hydrazone. This shows
the presence of keto group.
❖ It forms a phenyl hydrazone and gives a violet colour with ferric chloride.
Therefore a keto enol system is present.
❖ C6H8O6 + NaOH ————> Mono sodium derivative .

❖ It was thought to be a monocarboxylic acid.
28
❖ It behaves as an unsaturated compound and as a strong reducing agent.

❖ Presence of 5-carbon atoms in a straight chain.
Inter conversion of oxidation –reduction process is
because the reaction is carried out with mild reagent.(i.e)
dehydro ascorbic acid is a lactone.
All these reactions can be explained by the presence of a
α-hydroxy ketone group in ascorbic acid.
❖ Dehydro ascorbic acid on oxidation with sodium hypoiodite gives oxalic

acid and L-Threonic acid. Formation of these products shows ascorbic acid
contains four carbon system joined to two carbon system by a double
bond.(i.e)C-C=C-C-C-C.
Size of the lactone ring:

If lactone is gama-lactone ring.
29
30
Synthesis of Ascorbic acid:
General methods of preparation of ascorbic acid:
Synthesis from glucose:
31
RIBOFLAVIN
Riboflavin (Vitamin B2 )
Occurrence:
❖ It occurs in yeast, green vegetables, milk, meat etc.,
❖ Chemically vitamin B2 is closely related to the yellow, water soluble
pigments known as flavins and since it was first isolated from milk, vitamin
B2 is also known as lactoflavin.
❖ Riboflavin is a component of two important enzymes, namely flavin
mononuleotide (FMN) and flavin adenine dinucleotide (FAD). They play
major roles in various enzyme systems.
❖ It is essential for the metabolism of growth.
❖ It is an important of acyl-co a dehydrofenase.
❖ It is characterised by the development of fissures developing in the lips and
the corners of the mouth (Cheilosis).
❖ Sore tongue.
❖ Dermatitis affecting the face (ears, nose, and fore head).
❖ Eye becomes itchy,photophobia,vision become poor in dim light and leads
to severe interstitial keraitis
32
❖ The skin loses hair, it becomes dry and scaly.

❖ Growth is arrested.
Uses:
❖ Riboflavin is administered either orally or parenterally.Riboflavin tablets
containing 2 mg of the vitamin are administered.5 to 10 mg daily in
therapeutic doses.
❖ Riboflavin injection contains 10 mg of riboflavin per ml.It is usually given
with other members of vitamin B group.
Thiamine: ( Vitamin B1)
Occurrence:
It is present in cereals. This vitamin is concentrated in the outer, germ and
bran layers. During milling and polishing, this vitamin is discarded. Hence,
unpolished rice is the richest source. Rice polishing and yeast have been the usual
source of thiamine. Eggs are also a rich source. Thiamine occurs in all cells as its
pyrophosphate ester.
❖ It undergoes reaction with ATP in which two terminal phosphates from
ATP are transferred to the thiamine molecule to form thiamine
pyrophosphate (TPP). This acts as a coenzyme in glycolytic pathway as well
as kerbs cycle.
❖ Thiamine activates carboxylase which is essential for the oxidative
decarboxylation pyruvic acid, ketoglutaric acid and other keto acids.
❖ TTP acts as a coenzyme for certain trans-ketolase reactions.
❖ Thiamine helps the enzyme system which is responsible for the synthesis of
facts from carbohydrates and proteins.
The deficiency of this vitamin causes beri-beri in man. Beri-Beri is
characterised by oedema in the legs. Thus, this vitamin is the antineuritic factor
and hence the name aneurin.
33
Uses:
❖ Thiamine hydrochloride tablets containing 5 to 50 mg of the drugs is given
for therapeutic use.
❖ Thiamine hydrochloride injections are available containing 25 mg of the
vitamin per ml.vit B1 deficiency can be prevented by taking proper diet like
cereals particularly rice, beans, peas etc.
Pyridoxine (VitaminB6)
Occurrence:
The richest sources are yeast, rice polishing, germs of grains and cereals,
leafy vegetable, liver, eggs, meat, etc.,
❖ Pyridoxol phosphate acts as a coenzyme.
❖ It helps in the synthesis of fats from carbohydrates and proteins.
❖ It is involved in the active transport of amino acids and certain metallic ions
across cell membranes.
❖ It is linked with the metabolism of central nervous system.
In rats deficiency of this vitamin cause a specific type to dermatitis called
acrodynia anemia and convulsions. The deficiency disease produced in main is
not known.
Uses:
❖ It is used in the treatment of convulsion due to pyridoxine deficiency in
infants.
❖ It is also used in the treatment of pellagra.
❖ Pyridoxine in the daily dose of 20 to 100 mgs is used in vomiting of
pregnancy and in radiation sickness.
❖ It is also used in treating abnormal G.T.T. and mental depressions.
34
Antibiotics
The term Antibiotic is defined as a drug derived from living matter of
micro-organism which either prevents the growth of other micro organism or
destroy them.
Antibiotics are obtained from micro organisms such as fungi, actinomycetes,
bacteria etc.
Conditions:
❖ It should be effective even at low concentration.
❖ It should kill one or more species of the micro-organism.
❖ It should not have significant toxic side effect.
❖ It must be effective against a pathogen.
❖ It must be stored for a long time without appreciable loss of its activity.
❖ Antibiotics should be completely eliminated from the body after its
administration has been stopped.
Classification:
Approximately 6000 antibiotics substances have been described by now and
it would be very difficult to handle such great variety of antibiotics unless they
are, systematized properly.
They are several approaches to classification based on the spectrum of
biological action of antibiotics.
1. Broad spectrum antibiotics:
An antibiotic which is active against gram +ve and gram –ve bacteria.
Example: Ambicillin.amoxicillin, tetracycline, chloramphenicol.
2. Narrow spectrum antibiotics:
An antibiotic which is active against one type of bacteria only.
Example: PenicillinG, streptomycin, Erythromycin.
35
STRUCTURAL ELUCIDATION OF PENICILLIN G

Structure of penicillin – G:
❖ The general molecular formula of penicillin is C9H11N2O4SR .
❖ The penicillins are all strong monobasic acids as they form salts.
❖ From various studies it is found that no free amino group and free thiol
group are present.
❖ They are hydrolysed by hot dilute inorganic acids; one carbon atom is
eliminated as CO2 and two products are obtained in equimolecular
amounts- one being an amine, penicillamine and therefore an aldehyde,
penilloaldehyde. All the penicillins gives the same amine, but different
aldehydes. It is the latter which contain the R group.
❖ C9H11N2O4SR+2H2O————>C5H11NO2S+ C3H4NO2R + CO2
Structure of penicillamine:
❖ The molecular formula is C5H11NO2S.
❖ This compound gave colour reactions with sodium nitroprusside and ferric
chloride were characteristic of the thiol (-SH) group.
❖ Electrometric titration showed three pKa values. These correspond to
carboxyl, α-amino and thiol groups i.e., the penicillamine is a cysteine
derivative.
❖ Since penicillamine combined with acetone to give an isopropylidine
derivative which no longer contained as free amino or free thiol group and
was reconverted into penicillamine on hydrolysis. This suggested that these
two groups were attached carbon atoms.
❖ Oxidation of penicillamine with bromine water gave a sulphonic acid. This
reaction is characteristic of a thiol.
❖ The Kuhn- Roth determination of methyl side chains gave a very low value.
This suggested that the amine contained an isopropyl end group and not a
methyl end group.
36
❖ It was therefore proposed on the foregoing evidence that penicillamine was

β,β – dimethyl cystein.
Penicillin G. Confirm the same by its synthesis
Structure:
1. Molecular formula:
C9H11N2O4SR
Presence of a carboxyl group:Penicillins form mono salts, this shows that these
contain a carboxyl group.
3. By the usual tests, it has been shown that penicillin do not possess a free amino
or thiol group.
4. Hydrolysis:
When penicillin are hydrolysed by hot dilute inorganic acids, they lose one
carbon atom in the form of carbon dioxide and they are also degraded to the
equimolecular amounts of an amine, penicillamine and an aldehyde
penilloaldehydes.
C9H11N2O4SR +2H2O CO2 + C5H11NO2S + C3H4NO2R
Structure of D – penicillamine:
1. Molecular formula of penicillamine is C5H11NO2S
2. As penicillamine responds to the indigo colour reaction with sodium
nitroprusside, this show that D – penicillamine contains thiol group.
3. It is revealed that there are three pKa values 1.8, 7.9 and 10.5 corresponding to
carboxylic, - amino and thiol groups respectively.
4. The chemical reactions are parallel to those of cysteine. For example like
cysteine D – penicillmine also reacts with acetone to yield an isopropylidene
derivative.
Synthesis:
37
Structure of penilloaldehyde:
1. Molecular formula of penilloaldehyde is C3H4NO2R
2. When hydrolysed vigorously all penilloaldehydes yield a substituted acetic
acid and amino acetaldehyde. This reaction reveals that penilloaldehydes are acyl
derivatives of amino acetaldehyde.
RCONHCH2CHO(Or C3H4NO2R) + H2O RCOOH + NH2CH2CHO
The above structure of penilloaldehydes has been confirmed by its from the
corresponding acid chloride and amino acetal.
RCOCl+NH2CH2CH(OC2H5)2 RCONHCH2CH(OC2H5)2 RCONHCH2CHO

An acid is a – keto acid and hence penilloaldehyde – carboxylic acid should be
formed as an intermediate in the hydrolysis of penicillin.
38
Mode of linking of penicillamine and penilloaldehyde It may explain the

formation of penaldic acid. To explain the formation carbon dioxide When
penicillin is hydrolysed with dilute alkali or with enzyme penicillonase it yields
penicilloic acid which is a dicarboxylic acid and readily eliminates a molecule of
carbon dioxide to yield a monocarboxylic acid penilloic acid.
CHLOROMYCETIN (CHLORAMPHENICOL)
❖ The molecular formula of chloramphenicol is C11H12Cl2N2O5.
❖ UV spectrum of the antibiotic in water λ max 278nm and loge-3.98.UV
spectrum of Para nitro toluene λmax 285nm, logE3.97.These two are similar.
❖ Presence of a –NO2 group is shown by the following sequence of reactions,
❖ Chloramphenicol ————> product ————>(i)Diazotisation &coupling
with beta naphthol.
❖ Chloramphenicol ————> product with UV spectrum similar to that of p-

toluidine-2,3 and 4 confirm the presence of nitro phenyl group in
chloramphenicol.
39
❖ Chloramphenicol ————> CHCl2COOH + C9H12N2O4

Dichloro acetic acid + optically active base
The UVspectrum of this base is similar to that of chloramphenicol and
nitrobenzene.Therefore p-nitro phenol group should be present in this base.
❖ Chloramphenicol ————> a diacetyl derivative
******R.RAMESH, M.Phil.*****
40
UNIT-III
MOLECULAR REARRANGEMENT
1. Curtius rearrangement
Thermal rearrangement of acid azides in non aqueous solvents such as
isocyanate, is known as Curtius rearrangement. Isocyanate on hydrolysis gives
primary amine. The reaction converts acid azide into amine with loss of a carbon.
The acid azide required as starting materials may be prepared either by action
of sodium azide on an acid chlorides or by action of nitrous acid upon
hydrazides. The acid hydrazide can be obtained by treatment of an ester or acid
chloride with hydrazine.
The rearrangement of acid azide to isocyanate is similar to the hofmann

rearrangement. In curtius rearrangement, however, the intermediate isocyanate
may be isolated by performing reaction in an inert aprotic solvent, such as
benzene, chloroform.
Mechanism:
Acid azide loses molecular nitrogen when heated in inert solvent or when
irradiated and rearranges to the isocyanate. The reaction probably occurs via a
concerted rearrangement without involving intermediate nitrene.
41
There is evidence to support the existence of nitrene intermediate when

tertiary alkyl azides undergo curtius rearrangement to form imines.
Hydrolysis of isocyanate gives primary amine. Isocyanate are unstable and

attack by water on the carbonyl group gives a carbamic acid, which decomposes
to an amine.
When acid azide is decomposed in the presence of alcohol, the isocyanate

formed initially, reacts with alcohol to form a carbamate ester gives the amines.
2. Fries rearrangement
Esters of phenols on heating with anhydrous aluminium chloride undergo
rearrangement to give phenolic ketones. This is known as fries rearrangement.
Phenyl acetate to give mixture of o – and p – hydroxy acetophenone.
42
Low temperature the formation of the p – isomer and higher temperatures the
formation of the o – isomer. The mixture of o- and p – isomers resulting from the
fries reaction can be separated by steam distillation. The o – isomers are intra
molecularly hydrogen bonded (chelated) and have greater volatility.
Mechanism:
Intermolecular:
Intra-molecular:
43
3. Explain Beckmann rearrangement

The rearrangement of oximes under the influence of a varity of acidic reagents
to N – substituted amides is known as Beckmann rearrangement. Phosphorous
pentachloride is used as a catalyst in Beckmann rearrangement but conc.
sulphuric acid, polyphosphoric acid, formic acid, thionyl chloride, silica have
been used successfully. Rearrangement of benzophenone oxime to benzanilide in
the presence of phosphorous pentachloride.
Mechanism:
Treatment of oxime with acid generates a good leaving group on the nitrogen
atom. Loss of the leaving group generates an electron deficient species, which is
accompanied by migration of a group from adjacent carbon to the electron
deficient nitrogen.
As the migrating group is always approaching the nitrogen atom on the side
opposite to the oxygen atom, this rearrangement is highly stereo specific.
44
4. Benzidine rearrangement
The acid catalysed rearrangement of hydrazobenzene to 4,4’ –
diaminobiphenyl (p – benzidine) is known as benzidine rearrangement.
The major product is benzidine, but other side products called semidines and
diphenyline are also formed in low yield.
Mechanism:
A number theories have been given to explain the mechanism of benzidine
rearrangement.
Ex: caged radical mechanism, - complex mechanism and polar transition state
mechanism. It is believed that the mechanism involves the intra molecular
rearrangement.
When two different hydrazobenzenes are rearranged in same solution. Only

two benzidines are obtained and cross coupling product are not formed.
45
5. Benzilic acid rearrangement

- diketones (benziles) undergo a base – catalysed reaction called benzyl –
benzilic acid rearrangement.
The salts of - hydroxyl carboxylic acids initially formed on acidification yield
the hydroxy carboxylic acids.
Benzil on treatment with KOH followed by acidification yields benzilic acid.
Mechanism:
The reaction is analogous to intra molecular Cannizaro reaction of glyoxal. The
mechanism of benzyl – benzilic acid rearrangement starts with a reversible
nucleophilic addition addition of hydroxide ion to benzyl.
The resulting hydrate anion undergoes rearrangement by migration of aryl

group, followed by shift of proton to give resonance stabilized carboxylate anion.
The formation of resonance stabilized carboxylate anion from after 1,2 – phenyl
shift provides the driving force for the reaction. In the last step benzilic acid is
obtained by acidification.
6. pinacol – pinacolone rearrangement.
Acid – catalysed dehydration of 1,2 – diols usually leads to rearrangement with
the formation of ketones. When 2,3 dimethyl butane -2,3 – diol is treated with hot
30% sulphuric acid, 3,3 – dimethyl – 2-butanone is formed.
46
This type of acid – catalysed dehydration reactions involving rearrangement of

1,2 – diols is called Pinacol – Pinacolone rearrangement .
Mechanism:
The first step is the addition of a proton to one of the hydroxyl groups in
pinacol to give oxonium ion , followed by loss of water from the oxonium ion.
The result is a carbocation, which undergoes rearrangement through the
migration of a methyl group from the carbon adjacent to the carbon that bears the
positive charge.
The carbocation thus formed is at once stabilized by a shift of the charge from
carbon to oxygen.
The final step of the reaction is the loss of proton from to give the ketone. The
driving force for the 1,2 – methyl shift comes from the tendency of initially
formed carbocation intermediate to form a stable oxonium ion.
7. Cope rearrangement
The thermal isomerisation of 1,5 – dienes by a 3,3 – sigmatropic shift is known
as cope rearrangement. In the equilibration of 3,4 – dimethyl – 1,5 – hexadiene to
2,6 – octadiene.
47
A disadvantages of the cope rearrangement from a preparative standpoint is the

high temperature are required. Thermal cope rearrangement requires high
temperatures and the reaction is less stereoselective.
Mechanism:
Cope rearrangement proceeds a chair like transition state which is energetically
preferred over the boat like transition state by 5.7 kcal/ mol. If the chair transition
state is inaccessible then the rearrangement proceeds via the boat like transition
state.
8. Hofmann rearrangement
There is a group of closely related rearrangements, which convert N –
substituted amides to isocyanates. These reactions involve a migration of akyl or
aryl group from adjacent carbon to electron – deficient nitrogen. Although these
reactions have a common mechanism and intermediate but their starting
materials are different, therefore they are treated individually.
48
The Hofmann rearrangement refers to the conversion of primary amides into

primary amines by the action of sodium hypohalite . The most important features
of the rearrangement is that the amine formed has one less carbon atom in the
molecule than the original amide. Propanamide gives ethylamine on treatment
with sodium hypobromite or bromine and KOH.
CH3CH2CONH2 + Br2 + 4 KOH CH3CH2NH2 + 2KBr + K2CO3 + 2H2O
Mechanism:
➢ The first step N – bromoamide is formed by the action of alkaline
hypobromite on the amide. The N – hydrogen atom of N – bromoamide
becomes acidic because it has electron withdrawing acyl and
electronegative halogen functions.
➢ The second step in the reaction of the acidic hydrogen from N – haloamide
by the basic hydroxide ion.
➢ Removal of proton by base gives the trasit nitrogen anionic species which is
unstable and loses bromide ion with the simultaneous migration of aryl or
alkyl group from the adjacent carbon atom to the nitrogen.
➢ The resulting isocyanate is hydrolysed under the reaction conditions to N –
substituted carbamic acid which is unstable and finally decarboxylates into
the primary amine.
49
When the reaction is carried out in methanol the intermediate isocyanate is

converted into methyl carbamate, which may be isolated and hydrolysed
subsequently. Hydrolysis of methyl carbamate yields amine.
9. Lossen rearrangement
The rearrangement of acyl derivative of hydroxamic acid to isocyanate
followed by hydrolysis to corresponding amine is known as Lossen
rearrangement.
This is the another variation of Hofmann rearrangement. The only difference

between Hofmann rearrangement and Lossen rearrangement is that in latter case
50
the acyl derivative of hydroxamic acid is decomposed in the presence of base and
the leaving group is a carboxylate anion rather than bromide ion as in Hofmann
rearrangement.
Lossen rearrangement has little synthetic importance because hydroxamic acids

are not readily available.
Hydroxamic acid itself may undergo the lossen rearrangement, by the action of
strong inorganic acids, to primary amine.
10.Schmidt rearrangement
The conversion of carboxylic acid to primary amine having one carbon less is
accomplished by Schmidt reaction. Schmidt reaction is mechanically related to
Curtius reaction.
The conversion of carboxylic acid to primary amine occurs in one step by
reaction with hydrazoic acid in the presence of conc. sulphuric acid.
Hydrazoic acid is toxic and explosive and hence it is generated in situ by
adding sodium azide gradually to the carboxylic acid in the presence if sulphuric
acid.
RCOOH + HN3 RNH2 + CO2 + N2

Mechanism:
The addition of hydrazoic acid to a protonated carboxylic acid produces
protonated acyl azide, which loses nitrogen to give the intermediate. Subsequent
removal of proton and rearrangement in produces isocyanate, which is
hydrolysed under the reaction conditions to amine and carbon dioxide.
51
52
UNIT-IV
LiAlH4:
Use in organic chemistry
➢ Lithium aluminium hydride is widely used in organic chemistry as

a reducing agent. It is more powerful than the related reagent sodium
borohydride owing to the weaker Al-H bond compared to the B-H bond.
➢ Often as a solution in diethyl ether and followed by an acid workup, it will
convert esters, carboxylic acids, acyl chlorides, aldehydes, and ketones into
the corresponding alcohols (see: carbonyl reduction).
➢ Similarly, it
converts amide, nitro, nitrile, imine, oxime, and azide compounds into
the amines (see: amide reduction). It reduces quaternary ammonium
cations into the corresponding tertiary amines.
➢ Reactivity can be tuned by replacing hydride groups by alkoxy groups.
➢ Due to its pyrophoric nature, instability, toxicity, low shelf life and handling
problems associated with its reactivity, it has been replaced in the last
decade, both at the small-industrial scale and for large-scale reductions by
the more convenient related reagent sodium bis (2-
methoxyethoxy)aluminium hydride, which exhibits similar reactivity but
with higher safety, easier handling and better economics.
➢ LAH is most commonly used for the reduction of esters and carboxylic
acids to primary alcohols; prior to the advent of LiAlH4 this was a difficult
conversion involving sodiummetal in boiling ethanol (the Bouveault-Blanc
reduction).
➢ Aldehydes and ketones can also be reduced to alcohols by LAH, but this is
usually done using milder reagents such as NaBH4; α, β-unsaturated
ketones are reduced to allylic alcohols. When epoxides are reduced using
53
LAH, the reagent attacks the less hindered end of the epoxide, usually
producing a secondary or tertiary alcohol.
➢ Epoxycyclohexanes are reduced to give axial alcohols preferentially.
➢ Partial reduction of acid chlorides to give the corresponding aldehyde
product cannot proceed via LAH, since the latter reduces all the way to the
primary alcohol. Instead, the milder lithium aluminium tri(t-
butoxy)hydride, which reacts significantly faster with the acid chloride than
with the aldehyde, must be used.
➢ For example, when isovaleric acid is treated with thionyl chloride to give
isovaleroyl chloride, it can then be reduced via lithium aluminium tri(t-
butoxy)hydride to give isovaleraldehyde in 65% yield.
➢ Lithium aluminium hydride also reduces alkyl halides to alkanes, . Alkyl
iodides react the fastest, followed by alkyl bromides and then alkyl
chlorides.
➢ Primary halides are the most reactive followed by secondary halides.
Tertiary halides react only in certain cases.
➢ Lithium aluminium hydride does not reduce
simple alkenes or arenes. Alkynes are reduced only if an alcohol group is
nearby.
Inorganic chemistry
➢ LAH is widely used to prepare main group and transition metal
hydrides from the corresponding metal halides. For example, sodium
hydride (NaH) can be prepared from sodium chloride (NaCl) through the
following reaction:
o LiAlH4 + 4 NaCl → 4 NaH + LiCl + AlCl3
➢ LAH also reacts with many inorganic ligands to form coordinated alumina
complexes associated with lithium ions.
o LiAlH4 + 4NH3 → Li[Al(NH2)4] + 4H2
o NaAlH4 + LiCl → LiAlH4 + NaCl
54
o KAlH4 + LiCl → LiAlH4 + KCl

➢ "Magnesium alanate" (Mg(AlH4)2) arises similarly using MgBr2:
o 2 LiAlH4 + MgBr2 → Mg(AlH4)2 + 2 LiBr
NaBH4:
➢ The principal application of sodium borohydride is the production

of sodium dithionite from sulfur dioxide: Sodium dithionite is used as a
bleaching agent for wood pulp and in the dyeing industry.
➢ Sodium borohydride reduces aldehydes and ketones to give the

related alcohols. This reaction is used in the production of various
antibiotics including chloramphenicol, dihydrostreptomycin,
and thiophenicol. Various steroids and vitamin A are prepared using
sodium borohydride in at least one step.
➢ Sodium borohydride is used as reducing agent in the synthesis of

gold nanoparticles.
➢ Sodium borohydride has been considered as a solid state hydrogen

storage candidate. Although practical temperatures and pressures for
hydrogen storage have not been achieved, in 2012 a core–
shell nanostructure of sodium borohydride was used successfully to store,
release and reabsorb hydrogen under moderate conditions.
➢ Sodium borohydride can be used to reduce foxing in old books and

documents.
Osmium tetraoxide
Preparation:
OsO4 is formed slowly when osmium powder reacts with O2 at ambient

temperature. Reaction of bulk solid requires heating to 400 °C.
Addition of oxygen (oxidation) is possible by burning the metal at 800°C.

Os + 2 O2 OsO4
55
An alternative preparation is the oxidation of osmium salts with con.HNO3. This

is a widely used method to recover osmium via the volatile osmium tetroxide.
Properties:
Physical Properties:
➢ Osmium(VIII) oxide forms monoclinic crystals. It has a characteristic
acrid chlorine-like odor.
➢ The element name osmium is derived from osme, Greek for odor.
➢ OsO4 is volatile: it sublimes at room temperature. It is soluble in a wide
range of organic solvents.
➢ It is also moderately soluble in water, with which it reacts reversibly to form
osmic acid .
➢ Pure osmium(VIII) oxide is probably colourless and it has been suggested
that its yellow hue is due to osmium dioxide (OsO2) impurities.
➢ The osmium tetroxide molecule is tetrahedral and therefore non-polar. This
nonpolarity helps OsO4 penetrate charged cell membranes.
➢ OsO4 is 518 times more soluble in carbon tetrachloride than in water.
Uses:
Organic synthesis
In organic synthesis OsO4 is widely used to oxidise alkenes to

the vicinal diols, adding two hydroxyl groups at the same side (syn addition).
See reaction and mechanism above. This reaction has been made both
catalytic (Upjohn dihydroxylation) and asymmetric (Sharpless asymmetric
dihydroxylation).
Osmium(VIII) oxide is also used in catalytic amounts in the Sharpless

oxyamination to give vicinal amino-alcohols.
In combination with sodium periodate, OsO4 is used for the oxidative

cleavage of alkenes (Lemieux-Johnson oxidation) when the periodate serves both
56
to cleave the diol formed by dihydroxylation, and to reoxidize the OsO3 back to
OsO4.
The net transformation is identical to that produced by ozonolysis. Below

an example from the total synthesis of Isosteviol
Polymer staining
It is also used to stain copolymers preferentially, the best known example being
block copolymers where one phase can be stained so as to show
the microstructure of the material.
For example, styrene-butadiene block copolymers have a

central polybutadiene chain with polystyrene end caps. When treated with OsO4,
the butadiene matrix reacts preferentially and so absorbs the oxide.
The presence of a heavy metal is sufficient to block the electron beam, so the
polystyrene domains are seen clearly in thin films in TEM.
Osmium ore refining
OsO4 is an intermediate in the extraction of osmium from its ores. Osmium-

containing residues are treated with sodium peroxide (Na2O2) forming
Na2[OsO4(OH)2], which is soluble.
When exposed to chlorine, this salt gives OsO4. In the final stages of
refining, crude OsO4 is dissolved in alcoholic NaOH forming Na2[OsO2(OH)4],
which, when treated with NH4Cl, to give (NH4)4[OsO2Cl2].
This salt is reduced under hydrogen to give osmium.
PCl5
Phosphorus pentachloride is the chemical compound with the formula
PCl5. It is one of the most important phosphorus chlorides, others
being PCl3 and POCl3. PCl5 finds use as a chlorinating reagent. It is a colourless,
water-sensitive and moisture-sensitive solid, although commercial samples can be
yellowish and contaminated with hydrogen chloride.
57
Structure:
The structures for the phosphorus chlorides are invariably consistent
with VSEPR theory. The structure of PCl5 depends on its environment.
Gaseous and molten PCl5 is a neutral molecule with trigonal
bipyramidal geometry and (D3h) symmetry. The hypervalent nature of this
species (as well as for PCl−6, see below) can be explained with the inclusion of
non-bonding molecular orbitals (molecular orbital theory) or resonance (valence
bond theory).
This trigonal bipyramidal structure persists in nonpolar solvents, such
as CS2 and CCl4. In the solid state PCl5 is an ionic compound, formulated PCl+
4PCl 6.
−
In solutions of polar solvents, PCl5 undergoes self-ionization.[8] Dilute solutions

dissociate according to the following equilibrium:
PCl5 ⇌ PCl+4 + Cl−
At higher concentrations, a second equilibrium becomes more prevalent:
2 PCl5 ⇌ PCl+4 + PCl−6
The cation PCl+4 and the anion PCl−6 are tetrahedral and octahedral,
respectively. At one time, PCl5 in solution was thought to form a dimeric
structure, P2Cl10, but this suggestion is not supported by Raman
spectroscopic measurements.
Related pentachlorides
AsCl5 and SbCl5 also adopt trigonal bipyramidal structures. The relevant
bond distances are 211 pm (As−Cleq), 221 pm (As−Clax), 227 pm (Sb−Cleq), and
233.3 pm (Sb−Clax). At low temperatures, SbCl5 converts to the dimer,
dioctahedral Sb2Cl10, structurally related to niobium pentachloride.
Preparation:
58
PCl5 is prepared by the chlorination of PCl3. This reaction is used to produce

around 10,000 tonnes of PCl5 per year (as of 2000).
PCl3 + Cl2 ⇌ PCl5 (ΔH = −124 kJ/mol)
PCl5 exists in equilibrium with PCl3 and chlorine, and at 180 °C the degree
of dissociation is about 40%. Because of this equilibrium, samples of PCl 5 often
contain chlorine, which imparts a greenish coloration.
Reactions:
Hydrolysis
In its most characteristic reaction, PCl5 reacts upon contact with water to
release hydrogen chloride and give phosphorus oxides. The first hydrolysis
product is phosphorus oxychloride:
PCl5 + H2O → POCl3 + 2 HCl
In hot water, hydrolysis proceeds completely to orthophosphoric acid:
PCl5 + 4 H2O → H3PO4 + 5 HCl

2. Ag2O
Silver(I) oxide is the chemical compound with the formula Ag2O. It is a fine
black or dark brown powder that is used to prepare other silver compounds.
Preparation:
Silver oxide can be prepared by combining aqueous solutions of silver

nitrate and an alkali hydroxide. This reaction does not afford appreciable
amounts of silver hydroxide due to the favorable energetic for the following
reaction:
2 AgOH → Ag2O + H2O (pK = 2.875)

US patent 20050050990 describes the preparation of Ag2O with properties
suitable for use as a fine grained conductive paste filler.
Structure and properties:
Ag2O features linear, two-coordinate Ag centers linked by tetrahedral
oxides. It is iso structural with Cu2O. It "dissolves" in solvents that degrade it. It is
59
slightly soluble in water due to the formation of the ion Ag (OH) 2

− and possibly
related hydrolysis products. It dissolves in ammonia solution to give soluble
derivatives. Slurry of Ag2O is readily attacked by acids:
Ag2O + 2 HX → 2 AgX + H2O
Where HX = HF, HCl, HBr, or HI, HO2CCF3. It will also react with solutions of
alkali chlorides to precipitate silver chloride, leaving a solution of the
corresponding alkali hydroxide.
Like many silver compounds, silver oxide is photosensitive. It also

decomposes at temperatures above 280 °C.
Applications:
✓ This oxide is used in some silver-oxide batteries, as is the silver (I, III) oxide,
Ag4O4.
✓ In organic chemistry, silver oxide is used as a mild oxidizing agent.
✓ For example, it oxidizes aldehydes to carboxylic acids.
✓ Such reactions often work best when the silver oxide is prepared in
situ from silver nitrate and alkali hydroxide.
Lead tetra acetate
Lead tetraacetate is a strong oxidizing agent, a source of acetyloxy groups and a
general reagent for the introduction of lead into organolead compounds. Some of
its many uses in organic chemistry:
❖ Acetoxylation of benzylic, allylic and α-oxygen ether C-H bonds, for example
the photochemical conversion of dioxane to 1,4-dioxene through the 2-acetoxy-1,4-
dioxane intermediate and the conversion of α-pinene to verbenone .
❖ An alternative reagent to bromine in Hofmann rearrangement
❖ Oxidation of hydrazones to diazo compounds for example that of hexafluoroacetone
hydrazone to bis(trifluoromethyl)diazomethane
❖ Aziridine formation, for example the reaction of N-aminophthalimide and stilbene
❖ Cleavage of α-hydroxy acids or 1,2-diols to their
corresponding aldehydes or ketones, often replacing ozonolysis; for instance,
60
❖ The oxidation of di-n-butyl d-tartrate to n-butyl glyoxylate.
❖ Reaction with alkenes to form γ-lactones
❖ Oxidation of alcohols carrying a δ-proton to cyclic ethers.
❖ Oxidative cleavage of certain allyl alcohols in conjunction with ozone
❖ Conversion of acetophenones to phenyl acetic acids
❖ Decarboxylation of carboxylic acids to alkyl halides in the Kochi reaction
Rosenmund reduction.
❖ The Rosenmund reduction is a hydrogenation process in which an acyl

chloride is selectively reduced to an aldehyde. The reaction was named
after Karl Wilhelm Rosenmund, who first reported it in 1918.
❖
❖ The reaction, a hydrogenolysis, is catalysed by palladium on barium sulfate,
which is sometimes called the Rosenmund catalyst.
❖ Barium sulfate has a low surface area which reduces the activity of the
palladium, preventing over-reduction. However, for certain reactive acyl
chlorides the activity must be reduced further, by the addition of a poison.
Originally this was thioquinanthrene although thiourea has also been used.
❖ Deactivation is required because the system must reduce the acyl chloride
but not the subsequent aldehyde.
❖ If further reduction does take place it will create a primary alcohol which
would then react with the remaining acyl chloride to form an ester.
❖ Rosenmund catalyst can be prepared by reduction of palladium(II) chloride

solution in the presence of BaSO4. Typical reducing agent is formaldehyde.
❖ While Rosenmund reduction method can be used to prepare several

aldehydes, formaldehyde cannot be prepared, as formyl chloride is unstable
at room temperatures.
61
Periodic acid
PAS staining is mainly used for staining structures containing a high

proportion of carbohydrate macromolecules
(glycogen, glycoprotein, proteoglycans), typically found in e.g. connective
tissues, mucus, the glycocalyx, and basal laminae.
PAS staining can be used to assist in the diagnosis of several medical conditions:
❖ Glycogen storage disease (versus other storage disorders).

❖ Adenocarcinomas, which often secrete neutral mucins.
❖ Paget disease of the breast.
❖ Alveolar soft part sarcoma.
❖ Staining macrophages in Whipple's disease.
❖ It can be used to diagnose α1-antitrypsin deficiency if periportal liver
hepatocytes stain positive.
Borantriflouride
❖ Unlike the aluminium and gallium trihalides, the boron trihalides are all
monomeric. They undergo rapid halide exchange reactions:
❖ BF3 + BCl3 → BF2Cl + BCl2F
❖ Because of the facility of this exchange process, the mixed halides cannot
be obtained in pure form.
❖ Boron trifluoride is a versatile Lewis acid that forms adducts with

such Lewis bases as fluoride and ethers:
❖ CsF + BF3 → CsBF4

❖ O(C2H5)2 + BF3 → BF3O(C2H5)2
Tetrafluoroborate salts are commonly employed as non-coordinating anions. The
adduct with diethyl ether, boron trifluoride diethyl etherate, or just boron
trifluoride etherate, (BF3·O(Et)2) is a conveniently handled liquid and
consequently is widely encountered as a laboratory source of BF3. It is stable as a
60
solution in ether—an excess of ether compared to BF3—but not as a pure

stoichiometric substance. Another common adduct is the adduct with dimethyl
sulfide (BF3·S(Me)2), which can be handled as a neat liquid.
Oxofluorides:
Osmium forms several oxofluorides, all of which are very sensitive to

moisture. Purple cis-OsO2F4 forms at 77 K in an anhydrous HF solution:
OsO4 + 2 KrF2 → cis-OsO2F4 + 2 Kr + O2
OsO4 also reacts with F2 to form yellow OsO3F2:
2 OsO4 + 2 F2 → 2 OsO3F2 + O2
OsO4 reacts with one equivalent of [Me4N]F at 298 K and 2 equivalents at 253 K:
OsO4 + [Me4N]F → [Me4N][OsO4F]

OsO4 + 2 [Me4N]F → [Me4N]2[cis-OsO4F2]
Oxidation of alkenes
Alkenes add to OsO4 to give diolate species that hydrolyze to cis-diols. The net
process is called dihydroxylation. This proceeds via a cycloaddition reaction
between the OsO4 and alkene to form an intermediate osmate ester which rapidly
hydrolyses to yield the vicinal diol. As the oxygen atoms are added in a concerted
step, the resulting stereochemistry is cis.
Idealized depiction of the cis-dihydroxylation of alkenes.
OsO4 is expensive and highly toxic, making it an unappealing reagent to use in

stoichiometric amounts. However its reactions are made catalytic by adding
reagents to reoxidise the Os(VI) by-product back to Os(VIII).
61
Typical reagents include H2O2 (Milas hydroxylation), N-methylmorpholine N-

oxide (Upjohn dihydroxylation) and K3Fe(CN)6, as these will not react with the
alkenes on their own. Other osmium compounds can be used as catalysts,
including osmate(VI) salts ([OsO2(OH)4)]2−, and osmium trichloride hydrate
(OsCl3·xH2O). These species oxidise to osmium(VIII) in the presence of such
oxidants.
Lewis bases such as tertiary amines and pyridines increase the rate of
dihydroxylation. This "ligand-acceleration" arises via the formation
of adduct OsO4L, which adds more rapidly to the alkene.
If the amine is chiral, then the dihydroxylation can proceed with
enantioselectivity (see Sharpless asymmetric dihydroxylation). OsO4 does not
react with most carbohydrates.
The process can be extended to give to aldehydes in the Lemieux–Johnson
oxidation, which uses periodate to achieve diol cleavage and to regenerate the
catalytic loading of OsO4. This process is equivalent to that of ozonolysis
62
UNIT-V
GREEN CHEMISTRY
Green Chemistry & Principle
1. Green chemistry is defined as environmetally benign chemical synthesis.
2. It focuses on a process (whether carried out in industry or chemical laboratory) that
reduces the used and generation of hazardous substances or by-products.
3. Interest in green chemistry was first initiated in the United States after the passage
of the pollution prevention Act of 1990.
4. Green synthesis were developed for existing products by using starting material that
use biomass rather than petrochemicals which were derived from non-renewable
natural sources.
5. It was advantageous to use catalyst rather than stoichiometric reagents.
6. Special care was taken to see that the products obtained were less toxic and
biodegradable.
TWELVE PRINCIPLES OF GREEN CHEMISTRY:
1. It is better to prevent waste than to treat or clean up waste after it is formed.
2. Synthetic methods should be designed to maximize the incorporation of all
materials used in the process into the final product.
3. Wherever practicable, synthetic methodologies should be designed to use and
generate substances that possess little or no toxicity to human health and the
environment.
4. Chemical products should be designed to preserve efficicy of function while
reducing toxicity.
5. The use of auxiliary substances (e.g.,solvents, separation agents, etc.) should be
made unnecessary wherever possible and innocuous when used.
6. Energy requirements should be recognized for their environmental and economic
impacts and should be minimized. Synthetic methods should be conducted at
ambient temprature and pressure.
7. A raw material of feedstock should be renewable rather than depleting wherever
technically and economically pacticable.
63
8. Unnecessary derivatization (blocking group, protection/deprotection, and temporary
modification of physical/chemical processes) should be avoided whenever possible.
9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
10.Chemical products should be designed so that at the end of their function they do
not persist in the environment and break down into innocuous degradation products.
11.Analytical methodologies need to be further developed to allow for real-time,

inprocess monitoring and control perior to the fomation of hazardous substances.
12.Substances and the fom of a substance used in a chemical process should be chosen
so as to minimize the potential for chemical accidents, including releases,
explosions, and fires.
PLANNING A GREEN SYNTHESIS IN A CHEMICAL LABORATORY

Basic Principles:
❖ In view of the pollution caused to the environment by chemical industries , there is
urgent need to develop environmentally benign or green synthesis. We have known
that a number of ways are now available to reduce the impact on the environment of
a large scale process.
❖ These include correct choice of starting material, use of green solvents and using
appropriate reagent. The reaction should be conducted in safer aqueous system
instead of hazardous organic solvents.
64
❖ The reactions as far possible should be carried out at ambient temperature instead of
using heat energy. If possible, the material should be recycled.
❖ The pathways for synthesis be selected so that the generation of toxic materials is
avoided.
❖ It is best to carry out reactions in aqueous media. Water is the cheapest abundantly
available solvent and the reactions in aqueous media are generally environmentally
benign.
❖ The objective of green chemistry is not only to design new green synthesis but also
to devise green methods for the synthesis already existing products, whose
synthesis are responsible for environmental pollution.
❖ Following are some examples of green synthesis.
Synthesis of Catechol
❖ Catechol(1,2- dihydroxybenzene) is an industrial chemical and is required in large
quantities for a variety of purposes. It was conventionally obtained from benzene,
which is responsible for environmental and health problems. Also benzene is
produced from petroleum oil, which is non-renewable source. Various steps
involved in the conventional synthesis of catechol are given below.
65
Synthesis of Methyl Methacrylate:
Methyl Methacrylate is used in large quantities for the manufacture of polymers. It was
earlier synthesised by the method given below
The above synthesis (scheme-41) has 47% atom economy. The new synthesis (developed
by shell corporation) which employs a palladium catalyst (Scheme -42) enjoys 100%
atom economy.
Organic synthesis in solid state: (Solventless process)

It has been formed that a large number of reactions occur in solid state withoutbany
solvent. In fact, in a number of cases, such reactions occur more efficiently and with more
selectivity compared to reactions carried out in solvents. Such reactions are simple to
handle, reduce pollution, comparatively cheaper to operate and are especially important in
industry. A large number of organic reactions have been reported in solid state.
The solid state reaction can be conducted by heating the reactant. Alternatively, a solution
of the reactant in a suitable solvent (like water, alcohol, methylene chloride etc..,). After
stirring, the solvent is removed in vacuo and the dried solid support on which the reactants
have been adsorbed are used for carrying out the reaction under microwave irradiation. A
typical example of an organic reaction in dry state is the Claisen rearrangement of
allylphenyl ether to allylphenol. Using such procedures a number of reactions like
bromination, Micheal addition, Aldol condensation, Dieck mann condensation, Nitration,
Synthesis of amines, Beckmann rearrangements have been carried out. Besides these
synthesis of Oxazolidines, azomethines, Homoallylic alcohols, Cyclopropane derivatives,
66
disulphides, secondary and tertiary halides, ethers from alcohols and high molecular
weight polypeptides has also been affected.
An example of organic reaction in solid state on adsorbent is given in scheme-13.It
involves the condensation reaction of ortho- esters with o-phenylenediamines ai presence
of KSF clay under solvent free conditions using microwave.
Solvent reaction:
Solvent-less reactions realize 100% yield of one product without involvement of
any added solvent for reaction and workup. They occur in virtually all reaction types by
proper choice of the states of aggregation and reaction technique. This article is
subdivided into melting, kneading, dry milling, gas–solid reactions, and gas–liquid
reactions. The choice depends on the crystal packing, melting points, and eutectic
temperatures during a reaction. Temperature control is essential for achieving the full
benefit of crystal packing or the maximal concentration in the absence of deactivating
solvation. The reaction temperatures are decreased as a result of the most favorable
kinetics that leads to complete conversions and mostly avoid catalysis. An additional
advantage is the direct and perfect exclusion of moisture. A decreased reaction
temperature often enables staying below the eutectic temperature, or allows for obtaining
otherwise non accessible new products that directly crystallize without involving a liquid
phase. If the yield is also quantitative with the product directly crystallizing from the melt,
it may be easier to perform melt reactions with slight heating. The so-called “solvent-free”
(rather than solvent-less) reactions are mostly not quantitative and often not free of
auxiliaries, which requires solvent-consuming chromatography and separation of the
auxiliary with usually difficult recovery (eg, catalysts or supports). The hype surrounding
catalysis from “green chemistry” to perform reactions in “green-solvents” or “solvent-
free” is counterproductive. Solvent-less reactions without catalyst and with 100% yield of
67
pure product are the better choice. It is therefore necessary to report the broad application
and variability of solvent-less techniques, for the sake of sustainability.
Selection of solvents:
If the solvent is not specified, you will need to test a variety of solvents to
determine what will work best for the solute you are trying to recrystallize. This testing
can be accomplished by putting a small amount of your solute (about the size of a pea)
into three small test tubes. In each test tube, place 0.5 mL of each potential solvent. Use a
stirring rod to agitate the solute or "flick" the bottom of the test tube with one finger while
holding the top with the other hand. If the solute dissolves at room temperature with
stirring, the solvent should be discarded as a potential recrystallization solvent. If the
sample does not dissolve at room temperature, place the test tube in a hot water bath and
stir the contents. If the solute partially dissolves add more solvent and continue stirring. If
the solute dissolves completely, remove it from heat and place it in an ice-water bath. If
crystals do not form, try to scratch the inside of the test tube with a stirring rod. If crystals
form, you have found an appropriate recrystallization solvent; if no crystals form, keep
looking for the right match between solvent and solute.
If no solvent can be found, perhaps you will need to use a mixed solvent. If two
solvents in which the solute has different solubility characteristics are mixed, sometimes
an appropriate solvent can be found. For instance, if your solute is insoluble in water but
soluble in ethanol at room temperature, a mixture of the two solvents may produce an
appropriate solvent in which the solute is insoluble at room temperature but very soluble
at a significantly higher temperature. To find the proper proportion of water to ethanol in
this example, first, completely dissolve your solute in ethanol at room temperature. Then,
begin to add water until the solution becomes cloudy (this is because all of the solute is no
longer held in solution). Add just enough ethanol to make your solution clear and begin
your recrystallization procedure.
68
Commonly Used Solvents
Solvent B.P. Dielectric Safety Concerns

Constant*
Water 100 78.4 None
Ethanol 78 24.5 Flammable; irritating to the

eyes, respiratory system, and
skin
Acetone 56 20.6 Flammable; Irritating to the

eyes; Vapors may cause
drowsiness or dizziness
Tetrahydrofuran 66 7.58 Flammable; Harmful if

swallowed; Irritating to the
eyes, skin, and respiratory
system
Ethyl acetate 78 6.02 Flammable; Irritating to the

eyes; Vapors may cause
drowsiness or dizziness
Cyclohexane 81 1.89 Flammable; May damage lungs

if swallowed; Vapors may
cause drowsiness or dizziness
*The dielectric constant is a measure of the solvent's ability to separate ions. In general,
ionic compounds are more soluble in solvents with high dielectric constants.
69
Use of Microwaves:
The microwaves as we know, are used for heating purposes. The mechanism of how
energy is given to a substance which is subjected to microwave irradiation is complex.One
view is that the microwave reactions involve selective absorption of electromagnetic
waves by polar molecules, non-polar molecules being inert to microwaves. When a
molecules with a permanent dipoles are subjected to electric field, they become aligned
and as the field qscillates,their orientation changes; this rapid reorientation produces
intense internal heating.
The Main difference between classical heating and microwave heating, lies in core and
homogeneous heating associated with microwaves; on the other hand , in classical heating
heat transfer takes place by preheated molecules.
The preferred reaction – vessel for microwave induced organic reaction is a tall beaker
(particularly for small scale preparations in the laboratory) loosely covered and the
capacity of the beaker should be greater than the volume of the reaction mixture.
Alternatively teflon and polystyerene containers can be used.
These materials are transparent to microwaves. Metallic containers should not be used as
reaction vessels.The microwaves induced organic reactions can be carried out in a solvent
or on a solid support in which no solvent is used.
For carrying out the reaction in a solvent,the choice of the solvent is very important.The
solvent selected must have a dipole moment so that microwaves are absorbed and the b.p.
of the solvent should be 20-300 C higher than the desired reaction temperature.
An excellent solvent in a domestic microwave oven is N, N- dimethyl formamide (DMF).
This solvent can also retain water formed in the reaction. This obviates the need for water
separation. Some other choices of solvents are given below:
Solvent B.P(0C) Dielectric constant(ɛ)
Formamide 216 11.1

Methanol 65 32.7
Ethanol 78 24.6
Chlorobenzene 214 5.6
1,2- Dichlorobenzene 180 1.53
70
1,2,4-Trichlorobenzene 214 1.57

1,2-Dichloroethane 83 10.19
Ethylene glycol 196 37.7
Dioxane 101 2.20
Diglyme 162 7.0
Triglyme 216 1.42
Microwaves are considered as a more efficient source of heating than conventional steam
(or oil heated vessels), Since the energy is directly imparted to the reaction mixture rather
than through the walls of the reaction vessel. In fact, the rapid heating capability of the
microwaves leads to considerable saving of energy and reduction in time for completion
of the reaction. This decreases the overall cost of Production and also diminishes the
waste disposal problem.
71
Sonication:
The term sonication or “Sonochemistry” is used to describe the effect of ultra sound
waves on chemical reactivity. The ultrasound is generated with the help of an instrument
having an ultrasonic transductor, a device by which electrical or mechanical energy can be
converted in to sound energy. These electrochemical transductors are mostly made of
quartz and are commonly based on the piezoelectric effect. When equal and opposite
electrical charges are appled to opposite faces of a crystal of quartz, expansion or
contraction occurs. Applications of rabidly reversing charges sets up a vibration that emits
ultrasonic waves called the piezoelectric effect. When a sound wave propagated by a
series of compression and refraction cycles, pass through a liquid medium, It causes the
molecules to oscillate around their mean path.
During the compression cycle, the average distance between the molecules is reduced and
during refraction, the average distance between the molecules is increased. In the
refraction cycle, under appropriate conditions, the attractive forces of molecules of the
liquid may overcome, causing formation of bubbles. In case the internal forces are great
enough to ensure collapse of these bubbles, very high temperature (around 5000 0C) and
pressure ( Over 1000 bar) may be created. It is this very high temperature and pressure
that initiates chemical reactions. Using Sonication, a large number of reactions like Diels-
alder reaction, Simmons-smith reactions, Cannizaro reactions, Strecker synthesis,
Reformatsky reaction have been carried out.
Following are given some other reaction which can be carried out by ultra sound .
72
Water as green solvents:
The use of water as green solvent is largely restricted due to poor solubility of
organic substrates. Various efforts have been expended for creating micro environments
where in the solubility of the substrate would be increased.
In this connection, a surfactant plays an important role in not only increasing the
solubility but also forming a micellar protective shield from external agents for sensitive
substrates. A clever use of a surfactant-type Bronsted acid, which would form stable
dispersion system with organic substrates and thus would act both as a catalyst and a
hydrophobic protector, has been made in the condensation of OPD with ketone in aqueous
environment using dodecyl sulfonic acid leading to benzodiazepines.
The reaction proceeded at room temperature and the products were obtained in
very good to excellent yield.
The reaction of aniline with 2,5-dimethoxytetrahydrofuran and
dimethyl acetylene dicarboxylate proceeded in low yield in water.
The yield of the product azepines proved to be better in the presence of β-
cyclodextrin (92%), which provided a template for supramolecular catalysis.
73
Cyclodextrins possessing hydrophobic cavities are well-known supramolecular catalysts,
which by reversible formation of host–guest-type complex activate the organic molecule
and catalyze the reaction.
Substitution in the aromatic ring played an important role in governing the yield of the
product. EDGs on the aromatic ring gave better yields.
Ionic liquids as green solvents:

Ionic liquids implies a material that is fluid at ambient temperature, is colourless, has a
low volatility and easily handled. It is a material with attractive properties as a solvent.
As such these are used as industrial solvents are replacement for volatile organic solvents
traditionally used. Their uses reduce the environmental problems and human health
hazards created due to routine organic solvents.
Ionic liquids are made up of at least two components (The cation and the anion) which can
be varied. The solvent can be designed with a particular end use in mind or to possess a
particular set of properties.
Hence these are also known as “designer solvents”. Different aspects of ionic liquids have
been reviewed by a number of authors. Some examples of ionic liquids are given below:
74
The reactions in ionic liquids are easy to perform and need no special apparatus or
methodologies. Also the ionic liquids can be recycled and this leads to reduction of the
costs of the process.
Ionic liquids find application in alkylation, allylation, hydroformylation, epoxidations,
synthesis of ethers, Friedel craft reaction,Diels – alder reaction.
Phase Transfer Catalysis
Definition of a Phase Transfer Catalyst:
• A phase transfer catalyst is a catalyst which facilitates the migration of a reactant in
a heterogeneous system from one phase into another phase where reactions can take
place. Ionic reactants are often soluble in an aqueous phase but are insoluble in an
organic phase unless the phase transfer catalyst is present.
• Phase transfer catalysis or PTC refers to the acceleration of the reactions by the
phase transfer catalyst.
• PTC for anions reactant areoftenquaternary ammonium salts. PTC for cations is
often crown ethers.
Types of Phase-transfer Catalysts:
Phase-transfer catalysts for anionic reactants are often quaternary ammonium and
phosphonium salts. Typical catalysts include benzyltrimethylammonium chloride and
hexadecyltributylphosphonium bromide.
E.g.C8H17Cl + NACN (in presence of H2O) give No Reaction.
The 1-chlorooctane and sodium cyanide solution form two separate layers. Heating of
this mixture under reflux and vigorous stirring for 1-2 days gives no reaction.
C8H17Cl + NACN (in presence of R4N+) givesC8H17CN + NaCl
When an appropriate quaternary ammonium salt is added, tetrahexylammonium chloride,
the displacement occurs rapidly in near 100% in 2-3hr.
In this process the ammonium salt catalyst:
❖ Transfers the cyanide into the organic phase.
❖ Activates the transferred cyanide for the reaction with the alkyl halide.
❖ Transfers the displaced chloride anions back to the aqueous phase to start a new
catalytic cycle.
75
An alternative to the use of “quat salts” is to convert alkali metals cations into
hydrophobic cations . In the research lab , crown ethers are used for this purpose.
Polyethyleneglycols are more commonly used in practical applications. These ligands
encapsulate alkali metal cations (typically Na+ and K+ ) affording large lipophilic cations.
These polyethers have a hydrophilic “interiors” containing the ion and a hydrophobic
exterior.
Principle of Phase-Transfer Catalysis:
The principle of PTC is based on the ability of certain “phase-transfer agents” (the PT
catalysts) to facilitate the transport of one reagent from one phase into another
(immiscible) phase wherein the other reagent exists. Thus the reaction made possible by
bringing together the reagents which are originally in different phases. However, it is also
necessary that the transferred species is in an active state for effective PT catalytic action
and that it is regenerated during the organic reaction.
Mechanism:
According to Starks‟ original work, a quaternary ammonium halide dissolved in the
aqueous phase (Q+X-) undergoes anion exchange with the anion of the reactant dissolved
in the aqueous solution. The ion-pair formed (Q+X-) can cross the liquid-liquid interface
due to its lopophilic nature and diffuses from the interface into the organic phase, this step
being the „phase-transfer‟. In the organic phase, the anion of the ion-pair being quite
nucleophilic undergoes a nucleophilic substitution reaction with the organic reagent
forming the desired product (RY). The catalyst subsequently returns to the aqueous phase
and the cycle continues.
Aqueous phase:Q+Y- + X- → Y- + Q+X-
Organic phase: QY + RX → RY + QX
A prerequisite for a substance to function as a PT-Catalyst is to form ion-pairs soluble in
the organic phase and to be transferred in a highly active state.
Advantages of PTC :
• Elimination of organic solvents.
• Use of simple and inexpensive reactants (NaOH,KOH, K2CO3 etc. instead of NaH,
KHMDS t-BuOK etc).
• High yields and purity of products.
76
• Simplicity of the procedure.

• Highly scalable.
• Low energy consumption and love investment cost.
• Minimization of Industrial waste.
Applications:
▪ PTC is particularly useful for reaction of organic anions with nonpolar organic
reactants.
▪ PTC is also applicable for numerous reactions in which anions are intermediates for
generation other active species such as carbenes,nitrenes and organometallic
reagents.
▪ Reactions have been done in the following areas :
Alkylations Substitutions.
Aldol and related condensationsCarbenes reactionsOxidations and
reductions.Organometallic transformations.
Conclusion:
In the recent years, a lot of research has gone into developing new techniques for reaction
rate enhancement. Usually, these techniques are more chemistry-intensive than what
traditionally chemical engineers have been used to. The present paper has thus
concentrated on the methods of modelling PTC reactions, using both soluble and
immobilized forms of the catalyst. PTC is “green chemistry”, for this reason industrial
applications are expanding.
77
UNIT – I
CARBOHYDRATES
2 Marks
1. What are Oligosaccharides? Give example. (A – 16)
2. How will you prepare penta acetyl glucose by using glucose?(A – 16)
3. Define: Non – reducing sugar.(N – 14)
4. Define: Epimerisation.(N – 14)
5. Define: Anomericarbon.(N – 15)
6. How will you distinguish Glucose from Fructose? Explain.(A – 16)
7. What are carbohydrates? How are they classified? (N – 15,14)
8. What happens when glucose react with phenyl hydrazine?(N – 15)
9. What is epimerisation? (N – 16)
10.Write the uses of glucose. (N – 16)
5 Marks
1. Write a note on mutarotation.(A – 16)
2. Explain the occurrence and preparation of D – Glucose.(N – 14)
3. Write note on killaini – Fischer synthesis.(A – 16)
4. Discuss the conformation of fructose.
5. Explain the pyranose ring structure of glucose.
6. Explain the inter conversion of glucose to fructose.
7. How is glucose react with Tollen‟s reagent and fehling‟s solution.
10Marks
1. Establish the structure of fructose.(A – 16)
2. Write a chemical reactions of glucose.(N – 14)
3. Establish the structure of glucose.
4. Draw the structure of sucrose.(A – 16)
5. What is meant by inversion of cane sugar?(A – 16)
6. Explin why sucrose is not a reducing sugar.
7. How will you prepare ethyl cellulose?
8. Write the uses of sucrose.
**********
78
UNIT – II
VITAMINS AND ANTIBIOTICS
2 Marks
1. Draw the structure of pyridoxine.(A – 16)
2. What are antibiotics? (A – 16)
3. How will you classify the vitamins?(N – 14)
4. What is Ascorbic acid? Sketch its structure.(A – 16)
5. Point out the biological importance of thiamine.(A – 16)
6. What are vitamins?(N - 15)
7. Write the structure of riboflavin.
8. What are chemotherapeutic agents?
9. Bring out the biological importance of vitamin A.
10.Write the properties of penicillins.
5 Marks
1. Write about the biological importance of vitamin A.(A – 16)
2. How will you synthesis ascorbic acid?(A – 16)
3. Write short notes on Riboflavin.(N – 14)
4. Write short notes on chloromycetin (or) Chlorampheicol. (N–14)
5. Tabulate the classification and sources of vitamins.(A – 16)
6. How are antibiotics classified?
7. Discuss the biological functions of thiamine.
8. Explain the sources, biological importance and draw the structure of pyridoxine.
9. Write about penicillin G.
10 Marks
1. Discuss the structure of chloromycetin.(A – 16)
2. Elucidate the structure of Penicillin G. Confirm the same by its synthesis.(A – 16)
**********
79
UNIT –III
MOLECULAR REARRANGEMENT
2 Marks
1. What happen when methyl phenyl ketoxime react with acid.(A – 16)
2. Define: Intramolecular rearrangement.(N – 14)
3. Define:Cationotropic rearrangement.(N – 14,A - 16)
4. What is Fries rearrangement (N – 16)
5. Write pinacol – pinacolone rearrangement.(N – 16)
6. What is mean by benzilic acid rearrangement?
7. Define intermolecular rearrangement.
8. Write the types of molecular rearrangement.
5 Marks
1. Write down the mechanism of curtius rearrangement. (A -16,N – 14)
2. Discuss about the mechanism of fries rearrangement. (A – 16)
3. Explain Beckmann rearrangement.(N – 14,A - 16)
4. Write down the mechanism of Benzidine rearrangement.(A – 16)
5. Discuss the mechanism of benzilic acid rearrangement.
6. Explain pinacol – pinacolone rearrangement.
10 Marks
1. Discuss the mechanism of the following rearrangements. (A – 16)
a) Cope rearrangement b) Hofmann rearrangement
2. Explain: Lossen and Schmidt rearrangement and its mechanism.(N – 14)
*********
80
UNIT – IV
REAGENTS
2 Marks
1. Write any one synthetic application of NaBH4.(A – 16)
2. Write the preparation of lead tetra acetate.(N – 14)
3. Write the uses of periodic acid(N – 14)
4. Define Raney Nickel catalyst.(N – 15)
5. What is Rosenmund reduction?(N – 15)
5 Marks
1. Give synthetic applications of OsO4. (A – 16)
2. Write synthetic applications of lead tetra acetate. (A – 16,A - 16)
3. Write the preparation and mechanism of sodium borohydride. (N – 14)
4. Write any five reactions of Borantriflouride.(N -14)
5. Discuss the various reactions for osmium tetraoxide.
10 Marks
1. Discuss the synthetic applications of LiAlH4 and NaBH4. (A – 16)
2. Write the preparation, properties and uses of Osmium tetraoxide. (N – 14)
3. Write an elaborate account on the applications of following reagents. (A – 16)
a) PCl5 b) Ag2O
**********
81
UNIT –V
GREEN CHEMISTRY
2 Marks
1. Solvent reaction.
2. Use of microwaves.
3. Water as green solvents.
4. Ionic liquids as green solvents.
5. Phase transfer catalysis.
6. Definition of a phase transfer catalyst:
5 Marks
1. Green chemistry & principle.
2. Twelve principles of green chemistry.
3. Synthesis of methyl methacrylate.
4. Types of phase-transfer catalysts.
10 Marks
1. Organic synthesis in solid state: (solventless process)
2. Principle of phase-transfer catalysis Advantages and Applications:
3. Planning a green synthesis in a chemical laboratory.
82

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ORGANIC CHEMISTRY-II

AVS College of Arts & Science

Attur Main Road, Ramalingapuram, SALEM – 636106

Paper Code 17UCH09

Year & Class III B.Sc CHEMISTRY

Subject In-charge HOD PRINCIPAL

UNIT II Vitamins and antibiotics

UNIT III Molecular rearrangements

UNIT IV Important reagents and their applications in organic chemistry

UNIT V Green Chemistry

Ag+ + Glucose Ag + (Gluconic acid)

This gives a clue to the presence of five OH groups in glucose molecule.

Glucose condenses with hydroxylamine, NH2OH, to form Glucose oxime.

C5H11O5.CHO C5H11O5.COOH CH3(CH2)4COOH

Occurrence and preparation of D – Glucose

(C6H10O5)n + n H2O n C6H12O6

Prepare Penta acetyl glucose by using glucose

CHOH) +5(CH3CO)2O (CHO.COCH3)4+5CH3COOH

Pyranose Ring Structure of Glucose

Inter conversion of glucose to fructose.

Glucose react with Tollen’s reagent and fehling’s solution.

7. Open – chain formula: The open chain structure of fructose can be

Cyclic structure of D – Fructose:

2. D – Arabinose has configuration II and IV:

D – Arabinose by Killiani Fischer synthesis yields two epimeric aldohexoses, D-

4. Ruff degradation of D – glucose and D – mannose produces D – arabinose

5. D- Glucose and L – glucose yield the same dicarboxylic acid:

3. Glycoside formation confirms cyclic structure:

Establish the structure of maltose.

Reducing and non-reducing sugars

ability to reduce or not to reduce Fehling’s and Tollen’s reagents depends on

2. They contain cyclic hemiacetal or hemiketal structures in equilibrium with

Structural Features of Non – Reducing sugars:

C12H22O11 + H2O C6H12O6 + C6H12O6

Sucrose D – glucose + D – Fructose Specific rotation +66.5

Cell – OH + HNO3 Cell – ONO2

Cell – OH + (CH3CO)2O Cell – O – COCH3

The cellulose xanthate dissolves in sodium hydroxide solution to give a viscose

3. Hydrolysis of sucrose with dilute acids yields an equimolecular mixture of

C12H14O3(OH)8 + (CH3)2SO4 C12H14O3(OCH3)8

(6) Sucrose is hydrolysed by maltase, an enzyme that hydrolyses only -

C12H22O11 + H2O C6H12O6 + C6H12O6

The specific rotation changes from +66.5 to - 20 . The sign of specific

Sucros D – glucose + D – Fructose Specific rotation +66.5

Starch is actually a mixture of two structurally different polysaccharides,

Amylopectin has a branched – chain structure. It is composed of chains of

Vitamin C (Ascorbic acid)

❖ Vitamin C is effective against cold, though its role in the treatment of

SYNTHESIS AND STRUCTURAL ELUCIDATION OF ASCORBIC ACID (VITAMIN C)

❖ C6H8O6 + NaOH ————> Mono sodium derivative .

❖ It behaves as an unsaturated compound and as a strong reducing agent.

❖ Dehydro ascorbic acid on oxidation with sodium hypoiodite gives oxalic

Size of the lactone ring:

Synthesis of Ascorbic acid:

General methods of preparation of ascorbic acid:

Synthesis from glucose:

❖ The skin loses hair, it becomes dry and scaly.

STRUCTURAL ELUCIDATION OF PENICILLIN G

❖ It was therefore proposed on the foregoing evidence that penicillamine was

RCOCl+NH2CH2CH(OC2H5)2 RCONHCH2CH(OC2H5)2 RCONHCH2CHO

Mode of linking of penicillamine and penilloaldehyde It may explain the

❖ Chloramphenicol ————> product with UV spectrum similar to that of p-