L ECTURE № 2

1. LECTURE №2 Theme: Inorganic drugs of Oxygen, Hydrogen, Magnesium, Manganese, Iodine, Sulphur and Nitrogen with redox properties Associate prof. Mosula L.M.

2. The plan • Inorganic drugs of Oxygen and Hydrogen: oxygen, hydrogen peroxide, hydroperitum, magnesium peroxide. • 2. Inorganic preparation of Manganese - potassium permanganate. • 3. Inorganic preparation of Magnesium - magnesium peroxide. • 4. Inorganic drugsof Nitrogen: nitrous oxide, sodium nitrite. • 5. Inorganic preparation of Iodine - iodine. • 6. Inorganic preparations of Sulphur: sulphur for external use, sodium thiosulphate.

3. Browse: British Pharmacopoeia 2009 SP IX British Pharmacopoeia Volume I & II Monographs: Medicinal and Pharmaceutical Substances Oxygen Oxygen Oxygenum* О2 General Notices (Ph Eur monograph 0417) 32.00 Oxygen should be kept in approved metal cylinders, the shoulders of which are painted white and the remainder black. The cylinder should carry a label stating 'Oxygen'. In addition, 'Oxygen' or the symbol 'O2' should be stencilled in paint on the shoulder of the cylinder. When Oxygen is intended for use in a room in which magnetic resonance imaging (MRI) is being performed, the cylinder and fittings should be made from suitable non-ferromagnetic materials and labelled accordingly. Ph Eur DEFINITION Content Minimum 99.5 per cent V/V of O2. This monograph applies to oxygen for medicinal use. 2H2 + O2

4. CHARACTERS Appearance Colourless, odourless gas. Solubility At 20 °C and at a pressure of 101 kPa, 1 volume dissolves in about 32 volumes of water. PRODUCTION Carbon dioxide Maximum 300 ppm V/V, determined using an infrared analyser (2.5.24). Carbon monoxide Maximum 5 ppm V/V, determined using an infrared analyser (2.5.25). Water (2.5.28) 2KClO3→2KCl + 3O2

5. Obtaining • Distillation of liquefied (condensed) air. Now oxygen to receive from air by its liquefaction. Air contains 21 % of oxygen О2 and 79 % of nitrogen N2. At distillation of liquefied (condensed) air, at first is distillate of nitrogen (-195,8 °С), and then - oxygen (-183 °С). • 2. Electrolysis of water. • Anode: 2Н2О – 4е  4Н+ + О2 • Cathode: 2Н2О + 2е 2ОН– + Н2 • 3. Laboratory methods (for obtaining no more quatitative O2): • а) Thermal decomposition of potassium chlorate: • 2KClO3 →2KCl + 3O2 • b) Thermal decomposition of mercury(II) oxide: • 2HgO → 2Hg + O2 • c) Interaction peroxides with CO2: • 2Na2O2 + 2CO2  2Na2CO3 + O2

6. IDENTIFICATION • First identification C. • Second identification A, B. • Place a glowing splinter of wood in the substance to be examined. The splinter bursts into flame. • B. Shake with alkaline pyrogallol solution R. The substance to be examined is absorbed and the solution becomes dark brown. • C. It complies with the limits of the assay. • Other reaction: • (SPU) Mix of nitrogen(II) oxide and oxygen and obtained brown colour of gas : • 2NO + O2 = 2NO2 • brown gas • (Difference from nitrogen (I) oxide).

7. TESTS Carbon dioxide(2.1.6) –inadmissible impurity. Maximum 300 ppm V/V, determined using a carbon dioxide detector tube. Or by means reaction: Ba(OH)2 + CO2 = BaCO3 + H2O opalescence is not be present Carbon monoxide(2.1.6) –inadmissible impurity. Maximum 5 ppm V/V, determined using a carbon monoxide detector tube. Or by means reaction: СО + 2[Ag(NH3)2]NO3 + 2H2O = 2Ag + (NH4)2CO3 + 2NH4NO3 brown colour is not be present Water vapour(2.1.6) Maximum 67 ppm V/V, determined using a water vapour detector tube. IMPURITIES Specified impurities A, B, C. A. carbon dioxide, B. carbon monoxide, C. water.

8. Assay Determine the concentration of oxygen using a paramagnetic analyser. (Ph. Eur. method 2.5.27) Pass the gas to be examined through the instrument at a constant flow rate until a suitable reading is obtained. STORAGE As a compressed gas or liquid in appropriate containers, complying with the legal regulations. Taps and valves are not to be greased or oiled. Action and use Apply at the diseases, accompanied hypoxia(oxygen depletion). In particular, at poisonings of СО, HCN, Cl2, phosgene COCl2 and other gases use a mix with air, containing 40-60 % of oxygen. Use an oxygen cocktail (oxygen foam) forglaucoma treatment, and also for improvement of exchange processes. Widely use oxygen for so-called hyperbaric oxygenation - oxygen application under the raised pressure (1,2 - 2 atm), in surgery (operation in special pressure chamber), intensive therapy of heavy diseases, in reanimotologia. Thus saturation of tissues by oxygen, the brain is protected from hypoxia. Carbogenum – is the gas mix, containing 95 % О2 and 5–7% СО2, applied in anesthesiology for respiration stimulation.

9. Browse: British Pharmacopoeia 2009 SP IX British Pharmacopoeia Volume I & II Monographs: Medicinal and Pharmaceutical Substances Chlorinated Lime Chlorinated Lime General Notices Calcaria chlorata Calcii hypochloris crudus Calcium hypochlorosum Possible structure of Chlorinated Lime is: Chlorinated Lime is a mix of Ca(ClО)2 and CaCl2: Ca(ClО)2CaCl2 = Ca2O2Cl4 = 2CaOCl2 Elementary formula of Chlorinated Lime is: CaOCl2

10. DEFINITION Chlorinated Lime contains not less than 30.0% w/w of available chlorine, Cl. OBTAINING Heating (t  1000 C) Calcium natural minerals with the next saturation of chlorine (Cl2): CaCO3  CaО + CO2 CaО + H2O = Ca(OH)2 + Q Ca(OH)2 + Cl2 = CaOCl2 + H2O CHARACTERISTICS A dull white powder. Partly soluble in water and in ethanol (96%).

11. IDENTIFICATION A. (BrPh, SP IX). Interaction with mineral acids.Evolves chlorine copiously on the addition of 2M hydrochloric acid . CaOCl2 + HCl = CaCl2 + H2O + Cl2↑ B.(BrPh, SP IX).When shaken with water and filtered, the filtrate yieldsreaction C characteristic of calcium salts and reaction A characteristic of chlorides, Appendix VI. Calcium and Calcium Salts: A. (BrPh, SPU).Reaction with glyoxal-hydroxyanil alcoholic solution in the alkaline medium. To 0.2 ml of a neutral solution containing a quantity of the substance to be examined equivalent to about 0.2 mg of calcium (Ca2+) per millilitre or to 0.2 ml of the prescribed solution add 0.5 ml of a 2 g/l solution of glyoxal-hydroxyanil R in ethanol (96 per cent) R, 0.2 ml of dilute sodium hydroxide solution R and 0.2 ml of sodium carbonate solution R. Shake with 1 ml to 2 ml of chloroform R and add 1 ml to 2 ml of water R. The chloroform layer is coloured red.

12. B. (BrPh, SPU).Reaction with potassium ferrocyanide solution in the acetic-acid medium. Dissolve about 20 mg of the substance to be examined or the prescribed quantity in 5 ml of acetic acid R. Add 0.5 ml of potassium ferrocyanide solution R. The solution remains clear. Add about 50 mg of ammonium chloride R. A white, crystalline precipitate is formed. Ca2+ + К + 2NH4+ + [Fe(CN)6]4– →(NH4)2КCa[Fe(CN)6]↓. white, crystalline precipitate

13. 5. Nitrates and nitrites (an inadmissible impurity). To 1 ml of water cautiously add 1 ml fresh prepared solution of diphenylamine; there should not be a dark blue colouring: 6. Ammonia (an admissible impurity). At interaction of water of 10 ml about 0,2 ml of Несслера‘s reagent(an alkaline solution of potassium tetraiodomercurat [K2HgI4]), the formed yellow colouring should not be more intensive, than colouring of the standard (etalon), containing 10 ml of 0,0002 % (0,002 mg/ml) solution NH3):

14. In water cleared impurity NH3 in 10 times more, than at water distilled is supposed. 7. Chlorides (an admissible impurity). At interaction with a solution of AgNO3 at presenceof HNO3,formed opalescence should not be more intensively opalescenceof a standart (reference) solution: 8. Sulphates (an admissible impurity). At interaction of water with a solution ofbarium chlorideBaCl2 at presenceof HCl, opalescence should not exceed opalescenceof a reference solution:

15. 9. Calcium (an admissible impurity). Opalescence,formed at interaction with a solution (NH4) 2C2O4 in the presence of solution NH3, should not be more intensively opalescence a standart (reference) solution: 10. Heavy metals (an admissible impurity). At interaction about sodium sulphideNa2S in the presence of acid aceticCH3COOH and the further comparison with the standard(etalon) supposes only light opalescence at the expense of sulphur, which is allocated from sulphide sodium. Microbic cleanliness.Water cleared should contain no more than 100 microorganisms in 1 ml.

16. Storage conditions (recommendations of the Pharmacopoeia of Japan are thus used): “water store in the closed bottless from materials, which do not change properties of water and protect it from foreign particles and microbic pollution”. Application Water cleared is water for preparation of medical drugs, except what should be sterile and depyrogenized.

17. British Pharmacopoeia 2009 SPU, add.1 Hydrogen Peroxide Solution (3 per cent) General Notices H2O2 Dilute Hydrogen Peroxide Solution (Ph Eur monograph 0395) Hydrogenii peroxidum 3 per centum Solutio Hydrogenii peroxydi diluta Hydrogeniun peroxydatum DEFINITION Content 2.5 per cent m/m to 3.5 per cent m/m of H2O2 (Mr 34.01). 1 volume of hydrogen peroxide solution (3 per cent) corresponds to about 10 times its volume of oxygen. A suitable stabiliser may be added. CHARACTERS Appearance Colourless, clear liquid. OBTAINING Interaction barium peroxide with acid(Tenar method, 1818): ВаО2 + H2SO4 ВаSO4 + Н2О2

18. Identification 1. Reaction withK2Cr2O7 in the acid medium in the presence of ether – formations of pechromic acids; ethereal layercolouring in dark blue colour: K2Cr2O7 + H2SO4 = K2SO4 + H2Cr2O7

19. 2. identification of stabilizer acetanilide AcetanilideН3ССОNНС6Н5contains in a molecule acetylated an aromatic amino group. That it to release, spend acid hydrolysis by heating of the dry rest with chloride acid: Then spend reaction of identification of an aromatic amino group: for this purpose use diazotization at interaction about sodium nitrite in the medium of chloride acid with the subsequent condensation of the received salt diazonium with an alkaline solution -naphtholwith formation of azo dye red colour.

21. Assay 1. Permanganstometry, direct titration(indicator-free a method). Defined volume of an investigated solution of a hydrogen peroxide dilute of water in a volumetric flask to defined volume, acidify a solution of sulphatic acid and titrate by means of standard solution of potassium permanganateKMnO4before light pink colouring (at the expense of a excess drop of titrant in an equivalence point):

22. 2. Iodometry, substitute titration (indirect titration(on the assistant)). To a solution of preparation H2O2add excess of a solution KI, acidify sulphatic acidH2SO4and allocated iodine I2titrateby means of a solution of sodium thiosulphateNa2S2O3in the presence of starch (before disappearanceof dark blue colouring):

23. 3. Stabilizer Na-benzoatedefine by means of method of direct acidimetrywith the help with chlorideacidHCl in the presence of an ether (the ether takes insoluble in water benzoic acid) with indicator use - mixes methyl orange and methylene dark blue; in a point of equivalence the water layer is painted in lilac (light violet) colour. С6Н5СООNa + HCl = C6H5COOH + NaCl

24. Storage. In banks with ground glass stoppers, in the cool place protected from light. The list of strong substances. Application.Antiseptic, disinfectant, hemostatic agent. If in the recipe concentration is not specified, release 3 % solution of Н2О2.Apply to rinsings and washings at diseases of mucous membranes (a stomatitis, quinsy), gynecologic diseases. Shows hemostatic action. Apply as depigmentation agent in cosmetology.

25. British Pharmacopoeia 2009 SPU, add. 1 Hydrogen Peroxide Solution (30 per cent) General Notices (Ph Eur monograph 0396) H2O2 Hydrogenii peroxidum 30 per centum Solutio Hydrogenii peroxydi concentrata Hydrogeniun peroxydatum Perhydrolum 34,01 DEFINITION Content 29.0 per cent m/m to 31.0 per cent m/m of H2O2 (Mr 34.01). 1 volume of hydrogen peroxyde solution (30 per cent) corresponds to about 110 times its volume of oxygen. A suitable stabiliser may be added. CHARACTERS IDENTIFICATION, TESTS and ASSAYthe same as for hydrogen peroxide solution (3%). Action and use Antiseptic; deodorant. When hydrogen peroxide is prescribed or demanded, Hydrogen Peroxide Solution (6 per cent) shall be dispensed or supplied. Ph Eur

26. Hydroperitum Hydroperitum H2NCONH2H2O2 The preparation represents a mix equimolar quantities of ureaH2NCONH2and a hydrogen peroxideН2О2 with addition of 0,08 % of a solution of citric acid as conserving agent. Contains 33-35 % Н2О2. Properties. A crystal powder of white colour, freely soluble in water, soluble in alcohol. Identification 1. Reaction on Н2О2.Formations of pechromic acidsafter interaction withK2Cr2O7 in the sulphate-acid medium in the presence of ether –ethereal layercolouring in dark blue colour: K2Cr2O7 + H2SO4 = K2SO4 + H2Cr2O7

27. 2. Biuret reaction to urea presence: at slow heating to temperature 150-160 °С urea decays with allocation of ammonia NH3 and formation of ureido formamide (biuret) H2NCONHCONH2: isocyanic acid ureido formamide (biuret) tautomerism: imide form

28. At interaction ureido formamide (biuret) (in the imide form) with ions of Copper (ІІ) in alkaline solutions the characteristic violet colouring, caused by formation chelate complex is observed: violet colouring Assay2. Iodometry, substitute titration (indirect titration(on the assistant)). – see Н2О2.

29. Storage. In the dense corked containers, in the dry place protected from light, at temperature not more then 20 °С. Application. An antiseptic (instead of a hydrogen peroxide). Tablets of hydroperitum on 0,15 g, which should contain not less than 0,48 g Н2О2. One tablet corresponds 15 ml 3 %-s' solution of Н2О2. Preparation action is based on allocation Н2О2 at dissolution of hydroperitum in water. At dissolution of one tablet in 200 ml of water receive 0,25 % a solution of hydrogen peroxide. Use for mouth and throat rinsing at stomatitises and angina.

30. BrPh 2007 SP X (Ph Eur monograph 1540) Magnesium peroxide Magnesii peroxydum MgO2MgO Magnesium peroxydatum Magnium peroxydatum The preparation contains not less than 25 % magnesium peroxide MgO2 and 75 % magnesium oxideMgO. Obtaining 1. Interaction magnesium chloride with alkali and hydrogen peroxide at temperature 7-8 °С: 2. Electrolysis 20% solution of magnesium chlorideMgCl2 – on the cathod formingMgO2.

31. Properties The description. Magnesium peroxide represents a white crystal powder without a smell. Solubility. It is practically insoluble in water, soluble in mineral acids and boiling acetic acid СН3СООН with allocation H2O2: MgO2 + 2HCl = MgCl2 + H2O2 Identification 1. Reaction onН2О2 (after dissolution in mineral acid). Formation perchromic acids at interactionwith potassium dichromateK2Cr2O7 in sulphate-acid mediumH2SO4 in the presence of an ether; occurrence of dark blue colouring of anethereal layer (chemism to see the hydrogen peroxide Н2О2) is observed.

32. 1. Reaction oncations of Mg2+(after dissolution in mineral acid). Assay Permanganatometry, direct titration(after dissolution in mineral acid). MgO2 + 2HCl = MgCl2 + H2O2 (chemism to see the hydrogen peroxide Н2О2); Еm=М.м./2.

33. 2. Iodometry, substitute titration (see Н2О2). Storage. In dense corked containers, protecting from action of a moisture and carbon dioxide gas CO2. Application.Antiseptic and adsorbtionagent. Magnesium peroxide apply oral on 0,25-0,5 g 3-4 times a day as an antiseptic at intestinally-gastric diseases (dispepsia, fermentation in a stomach, a diarrhoeia).

34. British Pharmacopoeia 2009 SPU, add. 1 Potassium permanganate General Notices (Ph Eur monograph 0121) Kalii permanganas KMnO4 Kalium hypermanganicum 158.0 DEFINITION Content 99.0 per cent to 100.5 per cent. In nature Manganese meets in the form of a mineral pyrolusiteMnO2. Obtaining 1. Fusion of pyrolusiteMnO2 with alkali in the presence of oxidizers. At blowing off hot air it is formed manganateK2MnO4 (green colour), which under the influence of a strong oxidizer is oxidised to permanganateKMnO4 according to schemes:

35. Properties The description.Dark-violet or red-violet crystals or a small crystal powder with metal shine. At grinding with some organic substances and various reducers (the sulphur, the activated coal) can occur to explosion. At heating to temperature 240 °С decays (intramolecular ORR): 2KMnO4 К2MnO4 + MnO2 + 5O2 Solubility.Soluble in water, freely soluble in boiling water, ethanol and acetone.

36. Identification 1. Reaction of decolouration of a solution of a preparation at action a hydrogen peroxide in the acid medium: the test solutionof potassium permanganateKMnO4 acidify diluted sulphatic acid H2SO4 and add a solution a hydrogen peroxide H2O2; solution decolouration (formation of Mn2+ ions ) is observed:

37. 2. Reactions for ions of Potassium(K+) after heating of test solution with 90 % ethanol (until decolouration of solution): Filtrate (on the foilter paper is precipitate of MnO2, in the filtrate is ions of Potassium) and do reactions for ions ofK+. a) SPU: reaction with tartrate acidН2С4Н4О6; it is formed white crystal precipitate of potassium hydrogentartrate:

38. b) SPU: reaction with sodium cobaltinitrite Na3[Co(NO2)6] in the medium of СН3СООН;the yellow precipitate is formed:

39. c) SPU, N: Salts of Potassium paints a colourless flame in violet colour(at examining through dark blue glass - purple-red): К+ + h*К+ К+ + h1 Assay 1. Iodometry, substitute titration(see Н2О2).

40. Storage. In the banks from orange glass with plastic stoppers, in the place protected from light. Application. An antiseptic. Apply to washing of wounds (0,1-0,5 % solutions), for throat and mouth rinsing (0,01-0,1 % solutions); for greasing of burns and ulcers (2-5 % solutions) (the skin is dried and bubbles are not formed); for syringings and washings in gynecologic and urological practice (0,02-0,1 % solutions). At poisonings alkaloids, cyanides and phosphorus wash out a stomach 0,02-0,1 %-s' solutions of a preparation. Antimicrobic action is possible explain allocation of atomic Oxygen at preparation dissolution in water: KMnO4 + H2O = 2KOH + 2MnO2 + 3O

41. British Pharmacopoeia 2009 SPU, add. 1 Sulphur for External Use General Notices (Ph Eur monograph 0953) Sulfur ad usum externum S 32.07 DEFINITION Content 99.0 per cent to 101.0 per cent.

42. Obtaining 1. Milling of sulfurs cleared (Sulfur depuratum) at colloidal mills before obtaining of an amorphous powder of citreous colour. Sulphur cleared receive from sulfuric colour, which clear of impurity of sulphides Arsenic, and also from acids sulphatic and sulphitic. With that end in view sulfuric colour process an ammonia solution. Thus impurity of acids and Arsene's compounds pass in corresponding soluble salts (thioarsenites and arsenites or thioarsenates and arsenates ):

43. CHARACTERS Appearance Yellow powder. Solubility Practically insoluble in water, soluble in carbon disulphide, slightly soluble in vegetable oils. mp: about 120 °C. The size of most of the particles is not greater than 20 µm and that of almost all the particles is not greater than 40 µm. IDENTIFICATION A. (BrPh, SPU, add. 1).Burning of sulphur. Heated in the presence of air, it burns with a blue flame, emitting sulphur dioxide which changes the colour of moistened blue litmus paper R to red. S + O2 SO2 SO2 + Н2О  Н2SO3 2Н+ + SO32– B. (BrPh, SPU, add. 1).Reaction for sulphate ions after oxidation by means of bromine water.Heat 0.1 g with 0.5 ml of bromine water R until decolourised. Add 5 ml of water R and filter. The solution gives reaction (a) of sulphates(2.3.1). S + 3Br2 + 4H2O 6HBr + H2SO4 bromine water decolourised solution SO42– + Ва2+ ВаSO4 white precipitate

44. ASSAY (BrPh, SPU, add. 1). Alkalimetry after burning of test substance. Carry out the oxygen-flask method (2.5.10) , using 60.0 mg in a 1000 ml combustion flask. Absorb the combustion products in a mixture of 5 ml of dilute hydrogen peroxide solution R and 10 ml of water R. Heat to boiling, boil gently for 2 min and cool. Using 0.2 ml of phenolphthalein solution R as indicator, titrate with 0.1 M sodium hydroxide until the colour changes from colourless to red. Carry out a blank titration under the same conditions. 1 ml of 0.1 M sodium hydroxide is equivalent to 1.603 mg of S. S + O2  SO2 SO2 + Н2О2  Н2SO4 Н2SO4 + 2NaOH = Na2SO4 + 2H2O S Н2SO4  2NaOH 1 mol 1 mol 2 mol 2 equivalent 2 equivalent Еm(S) = А.m./2 STORAGE Protected from light. Action and use Keratolytic. Ph Eur

45. British Pharmacopoeia 2009 SPU, add. 1 Sodium Thiosulphate General Notices (Ph Eur monograph 0414) Natrii thiosulfas Natrium hyposulfurosum Natrium thiosulfuricum Na2S2O3  5H2O Chemical name: Sodium thiosulphate pentahydrate 248.2 DEFINITION Content 99.0 per cent to 101.0 per cent of Na2S2O3,5H2O.

46. OBTAINING 1. Boiling of sulphur with sodium sulphite solution Mix of S and Na2SO3 boiling until, then at additional of СаCl2 from solution any more precipitated CaSO3: Sodium sulphate to clear and to dry in the air. 2. Interaction of sodium sulphide with sulphur(IV) oxide: 2Na2S + 3SO2 = 2Na2S2O3 + S CHARACTERS Appearance Transparent, colourless crystals, efflorescent in dry air. Solubility Very soluble in water, practically insoluble in ethanol 96 per cent. It dissolves in its water of crystallisation at about 49 °C.

47. Identification 1. Reactions to ions Na+(see sodium fluoride): a) Interaction with potassium pyroantimonate; the white precipitate is formed; b) Reaction with methoxyphenylacetate acids reagent; the white precipitate is formed; c) With a zinc-uranyl-acetate solution; the yellow precipitate is formed; d) Colouring of a colourless flame in yellow colour. 2. Reactions on thiosulphate-anionsS2O32–. a) Interaction with a solution of silver nitrateAgNO3:at first is formed white precipitateAg2S2O3, which quickly turns yellow (S). At standing, under the influence of a moisture of air the precipitateblackensas a result of allocation of silver sulphide Ag2S:

48. b) Interaction with chloride acid HCl;the yellow precipitate of sulphur S is formed and allocation of gas SO2, having a smell of burned sulphur: Assay Iodometry, direct titrationby standard solution of iodineI2 n the presence of starch before occurrence of dark blue colouring:

49. Storage. In a cool place, in well corked utensils from dark glass, because light promotes its decomposition. Solutions of sodium thiosulphate at standing grow turbid from allocated sulphur. This process is accelerated in the presence of СО2 air. Therefore the utensils with solutions of sodium thiosulphate is supplied calcium chloride tube, which absorbs air carbonic acid. Application. Anti-inflammatory, desensitizing, detoxic agents. For scabies treatment use a liquid.

50. British Pharmacopoeia 2009 SP X Nitrous Oxide General Notices (Ph Eur monograph 0416) Nitrogenium oxydulatum “Laughing” gas Oxydum Nitrosum N2O Structural formula: • Nitrogen(I)oxidehas opened in 1776 year Priestley at interaction of iron with nitrate acid. • Obtaining • Thermal decomposition of ammoniumnitrate :