OXIDATION ,PROCESS CHEMISTRY ,MPHARM

OXIDATION ,TYPES OF OXIDATIVE REACTIONS , NON-METALLIC OXIDIZING AGNETS ,LIQUID PHASE OXIDATION, PHARAMACEUTICAL PROCESS CHEMISTRY, MPHARM

1. Presented by: Shubham Sharma Pharmaceutical Chemistry Roll no. : 20029 Presented to : Dr. Ranju Bansal Professor ,UIPS, Panjab University SEMINAR ON OXIDATION

2. CONTENTS INTRODUCTION TYPES OF OXIDATIVE REACTIONS NON-METALLIC OXIDIZING AGENTS LIQUID PHASE OXIDATION

3. TYPES OF OXIDATIVE REACTIONS

4. NON METALLIC OXIDIZING AGENTS Non - metals act as oxidizing agent because they tend to accept electrons i.e. reduction. The substance which itself gets reduced by causing oxidation of others is an oxidizing agent , e.g., nonmetals.

5. Hydrogen peroxide H 2 O 2 Pure form, it is a pale blue, clear liquid, sl i ght l y m o r e Hydr o gen vis c ous peroxide t h a n wat e r . i s t he 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.

6. P R ODUCTION Previously, hydrogen peroxide was prepared industrially by hydrolysis of ammonium persulfate, which was itself obtained by the electrolysis of a solution of ammonium bisulfate (NH 4 HSO 4 ) 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. 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.

7. The simplified overall equation for the process is simple. 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.

8. Hydrogen Peroxide is one of the most powerful oxidizers known stronger than chlorine, chlorine dioxide, and potassium permanganate. And through catalysis, H 2 O 2 can be converted into hydroxyl radicals (.OH) with reactivity second only to fluorine . While hydrogen peroxide will oxidize free cyanide, it is common to catalyze the reaction with a transition metal such as soluble copper, vanadium, tungsten or silver in concentrations of 5 to 50 mg/L. Peroxymonosulfuric acid (Caro’s acid; H 2 SO 5 ) is an equilibrium product formed from hydrogen peroxide and sulfuric acid. With Caro’s acid, the conversion of cyanide to cyanate is complete in a few minutes, according to the above equation :

9. Hydrogen peroxide in both acidic and basic medium acts as an oxidizing as well as the reducing agent. The following reactions will give a clear picture: Hydrogen peroxide can be used to quickly oxidize soluble ferrous iron to ferric (Fe +3 ), forming a rapidly settling ferric hydroxide floc. The resulting floc can be removed with filtering or a clarifier. This reaction is shown below:

10. Hydrogen peroxide reacts with hydrogen sulfide under acid, neutral and alkaline conditions. The reaction is accelerated by increasing temperature and/or the addition of catalysts such as iron. The stoichiometry is also affected by pH . Under acidic or neutral conditions the reaction with hydrogen peroxide produces sulfur and water: In alkaline solution (> pH8), the dominant reaction is: Mercaptans and dialkyl sulfides present in number of refinery products undergo oxidation under acidic conditions according to the equation given below :

11. DECHLORINATION BY H 2 O 2 Hydrogen peroxide reacts with free available chlorine in solutions with pH > 7. While there is no upper limit to the pH (e.g., H 2 O 2 can be used to dechlorinate effluent from caustic/chlorine odor scrubbers), as a practical matter, pH 8.5 is preferred in order to provide an instantaneous reaction. Formaldehyde Oxidation using H 2 O 2 H 2 O 2 will oxidize HCHO in either acidic or alkaline media. Acidic medium would be needed to mineralize HCHO to CO 2 . In akaline medium HCHO will be oxidized to formate .

12. THIOETHERS TO SULFOXIDES H ydrogen peroxide i s frequen t ly an oxid i zing a ge nt. Illus t rative is used as oxida t ion of thioethers to sulfoxides. Alkaline hydrogen peroxide is used for epoxidation of electron-deficient alkenes such as acrylic acid derivatives, and for the oxidation of alkylboranes to alcohols, the second step of hydroboration-oxidation. It is also the principal reagent in the Dakin oxidation process.

13. Hydrogen peroxide forming hydroperoxide many metals. is a weak or peroxide salts a c id, with cor r espo n ding pe r oxide s . For example, I t a l s o conve r ts met a l oxides in t o the upon treatment with hydrogen peroxide, chromic acid forms an unstable blue peroxide CrO(O 2 ) 2 . This kind of reaction is used industrially to produce peroxoanions. For example, reaction with borax leads to sodium perborate, a bleach used in laundry detergents:

14. USES Bleaching Detergents Production of organic compounds Disinfectant Cosmetic applications Use in alternative medicine Propellant Other uses-Glow sticks Horticulture Fish aeration

15. SODIUM HYPOCHLORITE 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·5H 2 O, a pale greenish-yellow solid which is not explosive and is stable if kept refrigerated

16. 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.

17. OXIDATION OF METALS AND COMPLEXES Heterogeneous reactions of sodium hypochlorite and metals such as zinc proceed slowly to give the metal oxide or hydroxide . NaO Cl + Zn → ZnO + NaCl Homogeneous reactions with metal coordination complexes proceed somewhat faster. This has been exploited in the Jacobsen epoxidation . Other reactions If not properly stored in airtight containers, sodium hypochlorite reacts with carbon dioxide to form sodium carbonate . 2 NaOCl (aq) + CO2 (g) → Na 2 CO 3 (aq) + Cl 2 (g) Sodium hypochlorite reacts with most nitrogen compounds to form volatile chloramines, dichloramines, and nitrogen trichloride NH 3 + NaClO → NH 2 Cl + NaOH NH 2 Cl + NaClO → NHCl 2 + NaOH NHCl 2 + NaClO → NCl 3 + NaOH

18. PRODUCTION Chlorination of soda Potassium hypochlorite was first produced in 1789 by Claude Louis Berthollet in his laboratory on the Quai de Javel in Paris, France, 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 ( Eau de Labarraque ). Cl 2 (g) + 2 NaOH (aq) → NaCl (aq) + NaClO (aq) + H 2 O (aq)

19. ELECTROLYSIS OF BRINE Ne a r the end of t h e nin e t e e n th ce n t u r y , E . S . Smi t h 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 − → Cl 2 + 2 e − (at the anode) 2 H 2 O + 2 e − → H 2 + 2 HO − (at the cathode) From ozone and salt S od i u m h y pochlo r i t e c an b e e a s i ly p r oduc e d f o r r ese a r ch purposes by reacting ozone with salt. NaCl + O 3 → NaClO + O 2 Thi s r e a cti o n happe n s a t r o o m t empe r a tu r e and c an be helpful for oxidizing alcohols.

20. USES Bleaching Cleaning Disinfection Deodorizing Waste water treatment Endodontics Nerve agent neutralization Reduction of skin damage

21. 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 p e r i o d i c t a ble, 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 e l e m ent in the aft e r hyd r og e n a nd hel i u m . At un i vers e , st a n d a r d temperature and pressure, two atoms of the element bind to form dioxygen, a colorless and odorless diatomic gas with the formula O 2 . 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.

22. INDUSTRIAL PRODUCTION One hundred million tonnes of O 2 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 O 2 is left as a liquid. The other primary method of producing O 2 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% O 2.

23. Oxygen gas can also be produced through electrolysis of water into molecular oxygen and hydrogen. DC electricity must be used: if AC is used, the gases in each limb consist of hydrogen and oxygen in the explosive ratio 2:1. A simil a r electrocatalytic and oxoacids. method O 2 evoluti o n i s t h e fr om ox i d e s

24. Chemical catalysts can be used as well, such as in chemical oxygen generators or oxygen candles that are used as part of the life-support equipment on submarines, and are still part of standard equipment on commercial airliners in case of depr essur i z a t i on emergencies . Another air separation method is forcing air to dissolve through ceramic membranes based on zirconium dioxide by either high pressure or an electric current, to produce nearly pure O 2 gas.

25. APPLICATIONS of iron Smelting o r e into s t e el cons u m e s 55% of commercially produced oxygen. [ In this process, O 2 is injected thr o ugh a hig h - p re s su r e la n c e in t o m ol t en i ron, which removes sulfur impurities and excess carbon as the respective oxides, SO 2 and CO 2 . The reactions are exothermic, so the temperature increases to 1,700 °C.

26. Another 25% of commercially produced oxygen is used by the chemical industry. Ethylene is reacted with O 2 to create ethylene oxide, which, in turn, is converted into ethylene glycol; the primary feeder material used to m a n uf a ctu r e a host o f product s , including antifreeze and polyester polymers (the precursors of many plastics and fabrics). 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. Oxygen is used in oxyacetylene welding burning acetylene with O 2 to produce a very hot flame. In this process, metal up to 60 cm (24 in) thick is first heated with a small oxy-acetylene flame and then quickly cut by a large stream of O 2 .

27. O Z ONO L Y SIS Ozonolysis was invented by Christian Friedrich Schönbein in 1840.Ozonolysis refers to the organic chemical reaction where ozone is employed to cleave the unsaturated bonds of alkenes, alkynes, and azo compounds (compounds with the functional diazenyl functional group). Oxidation of alkenes with the help of ozone can give alcohols, aldehydes, ketones, or carboxylic acids. Alkynes undergo ozonolysis to give diketones . If water is present in the reaction, the diketone undergoes hydrolysis to yield two carboxylic acids. For azo compounds, the ozonolysis yields nitrosamines.

28. Electrophillic addition of ozone to the carbon carbon bond forms the molozonide intermediate.

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30. 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.

31. An example is the ozonolysis of eugenol converting the terminal alkene to an aldehyde .

32. 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.

33. 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.

34. 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, EPDM or viton.

35. OZONOLYSIS IN INDUSTRY Ozonolysis has been used frequently in major drug synthes i s such as (+)- artemisinin , indolizidine 251F and D,L - camptothecin , as well as i n fine ch e mi c al sy n thesis such as L - isoxazolylalanine and pros t a g landin endoperoxides ThalesNano has developed the IceCube reactor to overcome these disadvantages. When combined with the ozone module, ozonolysis can be performed in a safe and highly controlled manner.

36. O z onol y s i s ha s a nu m be r of ad v a n t a g es over conventional oxidation methods, including : Quicker reactions with improved yields Cleaner reactions and less side products Does not require addition of water

37. 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 sulfuric acid at O- lOoC , for 24 hr ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quinone Potassium permanganate: Acid ........................................ . . . . . . . . . . . .Aniline black Alkaline ................................... . .... Azobenzene + ammonia Neutral. ................................ . . . Azobenzene +nitrobenzene Alkaline hypochlorite ................................. . . . .... Nitrobenzene Hypochlorous acid ........................................ . . ..... p-Aminophenol Another substance exihibiting a variety of action toward oxidizing agent is furfural. LIQUID PHASE OXIDATION WITH OXIDIZING COMPOUNDS

38. Mesotartaric acid

39. REFERENCE GROGGINS, P.H. (1983) UNIT PROCESSES IN ORGANIC SYNTHESIS , PUBLISHED BY MCGRAW. HILL KOGAKUSHA, LTD. ; 5 TH EDITION ; CHAPTER NO. 9 (OXIDATION) ; PP 486-549.