OXIDATION
(PHARMACEUTICAL PROCESS
CHEMISTRY)
PRESENTED BY:
ANAM ILYAS
M.PHARM 1st YEAR
PHARMACEUTICAL CHEMISTRY
SPER(JAMIA HAMDARD)
CONTENT:
q Introduction
q Types of oxidative reactions
q Liquid phase oxidation with oxidizing agents
q Non-metallic Oxidizing agents such as:
1. Hydrogen peroxide
2. sodium hypochlorite
3. Oxygen gas
4. ozonolysis
5.
2
§
INTRODUCTION:
§ Oxidation is a process of addition of oxygen and removal of hydrogen or loss of an
electron during a reaction by a molecule, atom or ion.
§ Oxidation occurs when the oxidation state of a molecule, atom or ion is increased.
§ The opposite process is called reduction, reduction is a process of removal of oxygen and
addition of hydrogen.
§ Reduction occurs when there is a gain of electrons or the oxidation state of an atom,
molecule, or ion decreases.
§ Oxidation and reduction always occur in pair, Therefore whenever something is oxidised,
something is reduced.
§ Oxidation and reduction together are called "REDOX REACTION"
§
3
TYPES OF OXIDATIVE
REACTIONS:
§ In the organic chemical industry, oxidation constitutes one of the most powerful tools used in the
synthesis of chemical compounds.
§ The principle types of oxidative reactions may be as follows:
q DEHYROGENATION:
It is illustrated in the transformation of:
Ø a primary alcohol to an aldehyde:
C2H5OH + 1/2O2 CH3CHO + H2O
Ø Or a secondary alcohol to ketone:
CH3CHOH + 1/2O2 CH3COCH3 + H2O
4
q An atom of oxygen may be introduced into a molecule
Ø The oxidation of an aldehyde to an acid:
Ø
CH3CHO + ½ O2 CH3COOH
Ø Or of a hydrocarbon to an alcohol:
Ø
(C6H5)3CH + 1/2O2 (C6H5)3COH
q
q A combination of dehydrogenation and introduction of oxygen may occur, as in the preparation of
Aldehyde from hydrocarbon:
CH4 + O2 CH2O + H2O
Ø
Ø or the preparation of benzoic acid from benzyl alcohol:
C6H5CH2CH.OH + O2 C6H5COOH + H2O 5
q Dehydrogenation, oxygen introduction and destruction of carbon linkages may all occur in the same
process of oxidation.
Ø In the oxidation of naphthalene to phthalic anhydride:
C10H8 + 4.5O2 C8H4O3 + 2H2O + 2CO2
q Oxidation may be accomplished indirectly through the use of intermediate reaction.
q
C6H5.CH3 C6H5CCl3 C6H5COOH
NaoH
C6H6 CH5SO3H C6H5OH
6
q Olefin may be oxidized under mild conditions to hydroxyl derivatives and may be converted to aldehydes and
carboxylic acids of lower molecular weight when stronger oxidizers are employed thus, oleic acid can be
converted to dihydroxystearic acid with Alkaline potassium permanganate.
KMnO
CH3(CH2)7CH=CH(CH2)7COOH 4 CH3(CH2)7CHOH(CH2)7-COOH
q PEROXIDATION: occurs readily under certain condition. Thus some reaction occur directly with air when
catalyzed by uv radiation.
Air/UV
Isopropyl Radiation Isopropyl Benzene Peroxide
q Amino compounds may be oxidized to azobenzene, p-aminophenol, or nitrobenzene under moderate
conditions or the N-containing radical may be completely removed under drastic conditions.
Ø In this way quinone is derived from Aniline.
7
q SULFUR COMPOUNDS:
§ It may be oxidized by Acid permangnate, as in the preparation of sulfonate, trianals and tetranals from
(CH3)2C(S.C2H5)2
§ In which the sulphide sulphur is oxidized to sulfonic groups.
§ It should be noted that mercaptans behave differently towards oxidizing agents from the alcohol in that the
action of strong oxidizing agents increases the valence of the sulfur atom instead of removing hydrogen as
in case of alcohols. Thus,
Oxidation ,
CH3CH2OH CH3CHO + H2O
CH3CH2SH CH3CH2SO2OH
8
LIQUID PHASE OXIDATION
WITH OXIDIZING AGENTS:
§ Liquid-phase oxidation is discussed in terms of the free radical chain mechanism proposed
by BOLLAND and his co-workers.
§ It is a process in which air or oxygen gas is contacted with the liquid reagent.
§ In Liquid phase oxidation H2O2 is being used more frequently as an oxidizing agent in place of
traditional oxygen transfer agents.
§ This scheme was devised for certain oxidations in which hydroperoxide is the major product.
§
9
Oxidation Of ANILINE Furnishes An Example
For Comparison Of A Number Of Oxidizing
Agent:
●
Oxidizing agent ●
product
●
Manganese dioxide in sulfuric acid ●
Quinone
●
Potassium dichromate in dil. H2SO4 at ●
Quinone
0-10oC, for 24 hour
●
Potassium permangnate: ●
Acid Aniline black
Alkaline Azobenzene + ammonia
Neutral Azobenzene + nitrobenzene
●
Alkaline hypochlorite ●
Nitrobenzene
●
Hypochlorous acid ●
P-aminophenol
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OXIDATION OF FURFURAL WITH
DIFFERENT OXIDIZING AGENT:
●
OXIDIZING AGENT ●
PRODUCT
● Sodium chlorate in neutral solution with V2O ●
Fumaric acid
catalyst
●
Sodium chlorate in dil. Acid with osmiumm ●
Mesotarttaric acid
tetraoxide(OsO4), catalyst
●
Hydrogen peroxide in presence of ferrous salts ●
5-Hydroxyfurfural
●
Bromine water at 100oC ●
Mucobromic acid
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NON- § Non-metals act as oxidizing agent because
they tend to accept electrons i.e. reduction.
METALLIC § The substance which itself gets reduced by
causing oxidation of others is an oxidizing
OXIDIZIN agent.
§ e.g., nonmetals.
G AGENTS
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HYDROGEN
PEROXIDE(H2O2)
§ Hydrogen peroxide H2O2 Pure form, it is a pale blue, clear liquid, slightly more viscous than
water.
§ It is the simplest peroxide (a compound with an oxygen–oxygen single bond).
§ It is used as an oxidizer, bleaching agent and antiseptic.
§ Concentrated hydrogen peroxide, or "high-test peroxide", is a reactive oxygen species and has
been used as a propellant in rocketry. Its chemistry is dominated by the nature of its unstable
peroxide bond.
§ It is unstable and slowly decomposes in the presence of light. Because of its instability, It is
typically stored with a stabilizer in a weakly acidic solution.
§ It is found in biological systems including the human body.
§ Enzymes that decompose hydrogen peroxide are classified as peroxidases.
13
STRUCTURE OF H2O2:
§ Hydrogen peroxide (H2O2) is a nonplanar
molecule as shown by Paul-Antoine
Giguère in 1950 using infrared
spectroscopy, with (twisted) C2
symmetry. Although the O−O bond is a
single bond
§ The molecular structures of gaseous and
crystalline H2O2 are significantly
different. This difference is attributed to
the effects of hydrogen bonding, which
is absent in the gaseous state.
14
PRODUCTION
§ Previously, hydrogen peroxide was prepared
industrially by hydrolysis of ammonium persulfate,
which was itself obtained by the electrolysis of a
solution of ammonium bisulfate (NH4HSO4) in
sulfuric acid.
§ Today, hydrogen peroxide is manufactured almost
exclusively by the anthraquinone process, which was
formalized in 1936 and patented in 1939.
§ It begins with the reduction of an anthraquinone (such
as 2-ethylanthraquinone or the 2-amyl derivative) to
the corresponding anthra hydroquinone, typically by
hydrogenation on a palladium catalyst. In the
presence of oxygen.
§ the anthrahydroquinone then undergoes autoxidation:
the labile hydrogen atoms of the hydroxy groups
transfer to the oxygen molecule, to give hydrogen
peroxide and regenerating the anthraquinone.
15
§ Most commercial processes achieve oxidation by bubbling compressed air through a solution of
the anthrahydroquinone, with the hydrogen peroxide then extracted from the solution and the anthraquinone
recycled back for successive cycles of hydrogenation and oxidation.
§ The simplified overall equation for the process is:
H2 + O2 H2O2
§ The economics of the process depend heavily on effective recycling of the extraction solvents, the
hydrogenation catalyst and the expensive quinone.
§ A process to produce hydrogen peroxide directly from the elements has been of interest for many years.
Direct synthesis is difficult to achieve, as the reaction of hydrogen with oxygen thermodynamically favours
production of water.
§ Systems for direct synthesis have been developed, most of which are based around finely dispersed metal
catalysts similar to those used for hydrogenation of organic substrates.None of these has yet reached a point
where they can be used for industrial-scale synthesis.
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DECOMPOSITION
§ Hydrogen peroxide is thermodynamically unstable and decomposes to form water and oxygen.
H2O2 H2 + O2
§ The rate of decomposition increases with rise in temperature, concentration and pH, with cool,
dilute, acidic solutions showing the best stability.
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ORGANIC REACTIONS:
§ Hydrogen peroxide is frequently used as an oxidizing agent.
Example is oxidation of thioethers to sulfoxides
Ph-S-CH3 + H2O2 Ph-S(O)-CH3 + H2O
§ Hydrogen peroxide is a weak acid, forming hydroperoxide or peroxide salts with many metals.
§ It also converts metal oxides into the corresponding peroxides.
For example: upon treatment with hydrogen peroxide, chromic acid forms an unstable blue peroxide
CrO(O2)2.
§ This kind of reaction is used industrially to produce peroxoanions. For example, reaction with
borax leads to sodium perborate, a bleach used in detergent industry.
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SODIUM HYPOCHLORITE
(NaOCl)
§ Sodium hypochlorite is a chemical compound with the formula NaOCl or NaClO, comprising
a sodium cation (Na+) and a hypochlorite anion(OCl−or ClO−).
§ It may also be viewed as the sodium salt of hypochlorous acid.
§ The anhydrous compound is unstable and may decompose explosively.
§ It can be crystallized as a pentahydrate
§ NaOCl·5H2O, a pale greenish-yellow solid which is not explosive and is stable if kept
refrigerated.
§ Sodium hypochlorite is most often encountered as a pale greenish-yellow dilute solution
commonly known as liquid bleach or simply bleach, a household chemical widely used
(since the 18th century) as a disinfectant or a bleaching agent.
§
19
§ The compound in solution is unstable and easily decomposes, liberating chlorine, which
is the active principle of such products. Indeed, sodium hypochlorite is the oldest and
still most important chlorine-based bleach.
§ While sodium hypochlorite is non-toxic, its corrosive properties, common availability,
and reaction products make it a significant risk.
§ In particular, mixing liquid bleach with other cleaning products, such as acids or
ammonia, may produce toxic fumes.
§
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OXIDATION OF ORGANIC
COMPOUNDS
§ Oxidation of starch by sodium hypochlorite, that adds carbonyl and carboxyl groups, is
relevant to the production of modified starch products.
§ In the presence of a phase-transfer catalyst, alcohols are oxidized to the corresponding
carbonyl compound (aldehyde or ketone).
§ Sodium hypochlorite can also oxidize organic sulfides to sulfoxides or sulfones, disulfides
or thiols to sulfonylchlorides or bromides, imines to oxaziridines.
§ It can also de-aromatize phenols.
21
OXIDATION OF METALS AND
COMPLEXES
§ Oxidation of metals and complexes Heterogeneous reactions of sodium hypochlorite and
metals such as zinc proceed slowly to give the metal oxide or hydroxide.
NaClO + Zn ZnO + NaCl
§ Homogeneous reactions with metal coordination complexes proceed somewhat faster. This has
been exploited in the Jacobsen epoxidation.
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OTHER REACTIONS
§ If not properly stored in airtight containers, sodium hypochlorite reacts with carbon dioxide to
form sodium carbonate
§
2 NaOCl (aq) + CO2 (g) Na2CO3 (aq) + Cl2 (g)
§ Sodium hypochlorite reacts with most nitrogen compounds to form volatile chloramines,
dichloramines, and nitrogen trichloride
NH3 + NaClO NH2Cl + NaOH
NH2Cl + NaClO NHCl2 + NaOH
NHCl2 + NaClO NCl3 + NaOH 23
PRODUCTION
q CHLORINATION OF SODA : Potassium hypochlorite was first produced in 1789 by Claude Louis Berthollet by
passing chlorine gas through a solution of potash lye. The resulting liquid, known as "Eau de Javel" ("Javel
water"), was a weak solution of potassium hypochlorite. Antoine Labarraque replaced potash lye by the cheaper
soda lye, thus obtaining sodium hypochlorite.
Cl2 (g) + 2 NaOH (aq) NaCl (aq) + NaClO (aq) + H2O (aq)
q ELECTROLYSIS OF BRINE: Near the end of the nineteenth century, E. S. Smith patented the chloralkali process: a
method of producing sodium hypochlorite involving the electrolysis of brine to produce sodium hydroxide and
chlorine gas, which then mixed to form sodium hypochlorite. The key reactions are:
2 Cl_ Cl2 + 2 e− (at the anode)
2 H2O + 2 e− H2 + 2 HO− (at the cathode)
q FROM OZONE AND SALT : Sodium hypochlorite can be easily produced for research purposes by reacting ozone
with salt.
NaCl + O3 NaClO + O2
This reaction happens at room temperature and can be helpful for oxidizing alcohols. 24
q
OXYGEN GAS
§ Oxygen is the chemical element with the symbol O and atomic number 8.
§ It is a member of the chalcogen group on the periodic table, a highly reactive nonmetal, and an
oxidizing agent that readily forms oxides with most elements as well as with other
compounds.
§ By mass, oxygen is the third-most abundant element in the universe, after hydrogen and
helium.
§ At standard temperature and pressure, two atoms of the element bind to form dioxygen, a
colourless and odourless diatomic gas with the formula O2.
§ Diatomic oxygen gas constitutes 20.8% of the Earth's atmosphere. As compounds including
oxides, the element makes up almost half of the Earth's crust.
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§ Dioxygen is used in cellular respiration and many major classes of organic molecules in living
organisms contain oxygen, such as proteins, nucleic acids, carbohydrates, and fats, as do the
major constituent inorganic compounds of animal shells, teeth, and bone.
§ Most of the mass of living organisms is oxygen as a component of water, the major constituent
of lifeforms.
§ Oxygen is continuously replenished in Earth's atmosphere by photosynthesis, which uses the
energy of sunlight to produce oxygen from water and carbon dioxide.
§ Oxygen is too chemically reactive to remain a free element in air without being continuously
replenished by the photosynthetic action of living organisms.
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INDUSTRIAL PRODUCTION
§ One hundred million tonnes of O2 are extracted from air for industrial uses annually by two
primary methods.
§ The most common method is fractional distillation of liquefied air, with N 2 distilling as a
vapor while O2 is left as a liquid.
§ The other primary method of producing O2 is passing a stream of clean, dry air through one
bed of a pair of identical zeolite molecular sieves, which absorbs the nitrogen and delivers a
gas stream that is 90% to 93% O2.
§ Oxygen gas can also be produced through electrolysis of water into molecular oxygen and
hydrogen.
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APPLICATIONS
§ Smelting of iron ore into steel consumes 55% of commercially produced oxygen.[In this
process, O2 is injected through a high-pressure lance into molten iron, which removes
sulphur impurities and excess carbon as the respective oxides, SO 2 and CO2. The reactions
are exothermic, so the temperature increases to 1,700°C.
§ Another 25% of commercially produced oxygen is used by the chemical industry. Ethylene is
reacted with O2 to create ethylene oxide, which, in turn, is converted into ethylene glycol.
§ Most of the remaining 20% of commercially produced oxygen is used in medical applications,
metal cutting and welding, as an oxidizer in rocket fuel, and in water treatment.
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OZONOLYSIS
§ Ozonolysis is a widely used reaction in organic synthesis. The reaction was invented by
Christian Friedrich Schoenbein in 1840.
§ Alkenes and alkynes are the most common substrates for the ozonolysis reaction.
§ Ozonolysis was an important diagnostic tool for the determination of the position of
unsaturation in unknown molecules before the invention and development of spectroscopic
techniques for identification and characterization of organic molecules.
§ The reaction was used for structure elucidation work because it provided chemists with
smaller and more readily identifiable carbonyl compounds.
29
OZONOLYSIS OF ALKENES:
§ The ozonolysis reaction involves bubbling ozone into a solution of olefin in an organic
solvent.
§ The reaction is rapid and produces an intermediate called ozonide.
§ The ozonide is unstable, and hence not isolated, but can be further reacted with various
reagents to give aldehydes, ketones, carboxylic acids, alcohols etc.
§ When the ozonide is treated with mild reducing agents like phosphines and thio compounds
(typically dimethyl sulfide or thiourea is used) aldehydes and ketones are produced.
§ Ozonides can be treated with strong reducing agents like sodium borohydride to produce
alcohols.
§ Ozonides when treated with oxidizing agents such as oxygen or hydrogen peroxide, they
produce carboxylic acids as the products.
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OZONOLYSIS OF ALKYNES
§ Alkynes also undergo ozonolysis but very slowly compared to alkenes.
§ Unlike alkenes, ozonides from alkynes do not need either an oxidizing agent or reducing agent
to provide end products.
§ Ozonides from alkynes upon treatment with water provide carboxylic acids are products.
§ Internal alkynes produce two different carboxylic acids while terminal alkynes produce
carboxylic acid with one less carbon; the terminal carbon is converted to carbon dioxide.
31
OZONOLYSIS OF ALKANES
§ Alkanes get oxidized when treated with ozone. The products formed are alcohols,
aldehydes/ketones or carboxylic acids. The rate of oxidative cleavage of alkanes is highest for
tertiary C-H bond, followed secondary and primary.
§
OZONOLYSIS OF ELASTOMERS
§ Ozone cracking is a form of stress corrosion cracking where active chemical species attack products
of a susceptible material. Ozone cracking was once commonly seen in the sidewalls of tires but is
now rare owing to the use of antiozonants. Other means of prevention include replacing
susceptible rubbers with resistant elastomers such as polychloroprene.
32
REFERENCES:
§ https://www.sciencedirect.com/science/article/pii/S0009250954800029
§ https://www.thoughtco.com/definition-of-oxidation-in-chemistry-605456
§ https://www.slideshare.net/ShikhaPopali1/oxidation-pharmaceutical-process-chemistry
§ https://www.slideshare.net/mounikaperli/oxidizing-agentsampozonolysis
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THANK
YOU...
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