LECTURE LECTURE № № 55

Halogenderivatives of hydrocarbons, Halogenderivatives of hydrocarbons, which are used in the medical which are used in the medical

practice. Some alcohols, aldehydes practice. Some alcohols, aldehydes and ethers as drugsand ethers as drugs

associate prof. Mosula L. M.associate prof. Mosula L. M.

The PlanThe Plan

1. Halogenderivatives of Halogenderivatives of hydrocarbonshydrocarbons : Ethyl Chloride, Chloroform, Iodoform, Fluothane.

2. AlcoholAlcohol - Ethanol. 3. Ether – Anaesthetic ether. 4. Aldehyde - Formaldehyde.

Halogenderivatives of hydrocarbons as drugs

Ethyl Chloride Aethylii chloridum

C2H5Cl M.m. = 64,52 g/mol

Aethylium chloridumAethylium chloratumAethylis Chloridum*

Aether chloratus

H3C-CH2Cl (C2H5Cl) 64.52The chemical name: ethyl chloride, chloroethane.

It may be prepared by the action of hydrogen chloride on ethanol or on Industrial Methylated Spirit; in the later case it may

contain a small variable of methyl chloride.

ObtainingObtaining 1. Heating (110-1201. Heating (110-120) absolute ethyl alcohol with dry ) absolute ethyl alcohol with dry HCl (or concentrated HNO3) HCl (or concentrated HNO3)

in the presence of dehydrating means (CaCl2 anhydrous, ZnCl2 or conc. H2SO4):in the presence of dehydrating means (CaCl2 anhydrous, ZnCl2 or conc. H2SO4): C2H5OH + HCl C2H5Cl + H2OC2H5OH + HCl C2H5Cl + H2O 2. Hydrochlorination of ethylene2. Hydrochlorination of ethylene:: НН22СС==СНСН2 + HCl = H3C–CH2Cl2 + HCl = H3C–CH2Cl 3. Chlorination ethane3. Chlorination ethane:: C2H6 + Cl2 C2H6 + Cl2 C 2H5Cl + HCl C 2H5Cl + HCl CharacteristicsCharacteristics.. Gaseous at ambient temperature and pressure, but usually Gaseous at ambient temperature and pressure, but usually

compressed to a colorless, mobile, flammable and very volatile liquid; odour, compressed to a colorless, mobile, flammable and very volatile liquid; odour, ethereal. ethereal.

Slightly soluble in water, miscible with ethanol and with ether.Slightly soluble in water, miscible with ethanol and with ether.

IdentificationIdentification.. A.A. Burns with a luminous flame with the production of Burns with a luminous flame with the production of

hydrogen chloride.hydrogen chloride. C2H5Cl + 2O2 = CO2 + 2H2O + HClC2H5Cl + 2O2 = CO2 + 2H2O + HCl B.B. Vigorously shake 2 ml with 5M sodium hydroxide and Vigorously shake 2 ml with 5M sodium hydroxide and

warm on a water bath. Reserve a portion of the solution warm on a water bath. Reserve a portion of the solution for test C. To the resulting solution add 2 ml of iodinated for test C. To the resulting solution add 2 ml of iodinated potassium iodide solution and warm. potassium iodide solution and warm. Crystals of iodoform Crystals of iodoform are producedare produced ((iodoformiodoform test) test)....

or or C2H5Cl + NaC2H5Cl + NaОНОН C2H5 C2H5ОНОН + Na + NaClCl C2H5OH + 4I2 + 6C2H5OH + 4I2 + 6NaNaOH = OH = CHI3CHI3 + HCOO + HCOONaNa + 5 + 5NaNaII yellow yellow precipitate and precipitate and its its specific smellspecific smell

C.C. The solution reserved in test B yields The solution reserved in test B yields the reactions characteristic of the reactions characteristic of chlorideschlorides..

KKClCl + AgNO3 + AgNO3 AgClAgCl + KNO3 + KNO3 white precipitatewhite precipitate Cl– + Ag+ Cl– + Ag+ AgCl AgCl AgCl + 2NH4OH Ag(NH3)2Cl + 2H2OAgCl + 2NH4OH Ag(NH3)2Cl + 2H2O

TestsTests 1. Definition of temperature of boiling1. Definition of temperature of boiling. . 2. Density measurement2. Density measurement.. 3. Acidity3. Acidity. . 4. Ethanol4. Ethanol (an inadmissible impurity) which define (an inadmissible impurity) which define

bymeans of iodoform test (see above); bymeans of iodoform test (see above); there should there should not be a turbiditynot be a turbidity..

5. Organic impurity5. Organic impurity (an inadmissible impurity). At (an inadmissible impurity). At mixing of a preparation with concentrated sulphatic mixing of a preparation with concentrated sulphatic acid H2SO4 at cooling in the ice water, the received acid H2SO4 at cooling in the ice water, the received solution should be colourlesssolution should be colourless..

6. The rest at evaporation6. The rest at evaporation. .

StorageStorage.. The list of strong substances. Ethyl chloride The list of strong substances. Ethyl chloride should be stored at temperature not exceeding 15*C, in the should be stored at temperature not exceeding 15*C, in the cool place protected from light.cool place protected from light.

.. INDICATIONS FOR USE INDICATIONS FOR USE Anaesthetic, an inhalation Anaesthetic, an inhalation

narcoticnarcotic. For . For externalexternal use only use only Ethyl Ethyl ChlorideChloride is a vapocoolant (skin refrigerant) intended is a vapocoolant (skin refrigerant) intended

for topical application to control pain associated with for topical application to control pain associated with injections, minor surgical procedures (such as lancing boils, injections, minor surgical procedures (such as lancing boils, incisions, and drainage of small abscesses) and athletic incisions, and drainage of small abscesses) and athletic injuries. It is also intended for the treatment of restricted injuries. It is also intended for the treatment of restricted motion associated with myofascial pain caused by trigger motion associated with myofascial pain caused by trigger points. points.

Contents under pressure. Store in a cool place (controlled Contents under pressure. Store in a cool place (controlled room temperature). Do not store above 120°C. Do not store room temperature). Do not store above 120°C. Do not store on or near high frequency ultrasound equipment. on or near high frequency ultrasound equipment.

CHLOROFORMCHLOROFORM

ChloroformiumChloroformium MM =119,38 g/mol =119,38 g/mol

Chloroform for narcosisChloroform for narcosis Chloroformium pro narcosiChloroformium pro narcosi Chloroformium Chloroformium

Anaesthesicum*Anaesthesicum* CHCl3CHCl3 The chemical name: The chemical name:

Chloroform, trichloromethane.Chloroform, trichloromethane.

C ClH

Cl

Cl

ObtainingObtaining 1. Electrolysis solution of sodium chloride in the 1. Electrolysis solution of sodium chloride in the

presence of ethanol or acetone (a modern method).presence of ethanol or acetone (a modern method). This method consists of such stages.This method consists of such stages. a) Electrolysis solution of sodium chloride a) Electrolysis solution of sodium chloride with with

formation of alkali and chlorine and hydrogen gases: formation of alkali and chlorine and hydrogen gases: 2NaCl + 2HOH 2NaCl + 2HOH K (–): Na +; K (–): Na +; H2OH2O 2H2O + 2e → 2OH - + H2 ↑ 2H2O + 2e → 2OH - + H2 ↑ A (+): A (+): Cl–Cl–; H2O 2Cl- – 2e → Cl2; H2O 2Cl- – 2e → Cl2 b)b) ReactionReaction disproportionationdisproportionation of chlorine in an of chlorine in an

alkali solution:alkali solution: NaOH + Cl2 = NaCl + NaClO + H2ONaOH + Cl2 = NaCl + NaClO + H2O

c) Oxidationc) Oxidation of ethanol or acetoneof ethanol or acetone* by means of * by means of sodium sodium hypochlorite hypochlorite NaClONaClO to acetic aldehyde or acetone trichloride (*then use to acetic aldehyde or acetone trichloride (*then use acetone receive purer chloroform):acetone receive purer chloroform):

acetic aldehyde further is oxidised to trichloroacetaldehyde:acetic aldehyde further is oxidised to trichloroacetaldehyde:

Thus, the total equation of oxidation of ethanol:Thus, the total equation of oxidation of ethanol: C2H5OH + 4NaClO Cl3CCC2H5OH + 4NaClO Cl3CCННO + 3NaOH + NaCl + H2OO + 3NaOH + NaCl + H2O

C2H5OH NaClO CH3 CO

HNaCl

CH3 C CH3

O

NaClO CH3 C CCl3

O

NaOH

++1

+ + H2O-1

+ 3 + 3

acetic aldehyde

acetone trichloride

CH3C

O

HCCl3 C

O

H+ 3 NaClO + 3 NaOH

trichloroacetaldehyde

CCl3 CO

HNaOH CHCl3 H C

O

ONa+ +

chloroformsodium formiate

CH3 C CCl3

O

NaOH CHCl3 CH3 CO

ONa+ +

chloroformsodium acetate

d) Decomposition acetone trichloride or trichloroacetaldehyde by means of alkali with chloroform formation:

2.2. Alkali action on chloral hydrateAlkali action on chloral hydrate (receive purer chloroform): (receive purer chloroform):

4. Reduction tetrachlormethane by iron in the presence of water4. Reduction tetrachlormethane by iron in the presence of water .. ССССl4 + Fe + HOH → CHCl3 + FeOHCll4 + Fe + HOH → CHCl3 + FeOHCl Chloroform clearing.Chloroform clearing.

Chloroform for narcosis Chloroform for narcosis Chloroformium pro narcosi Chloroformium pro narcosi receive similarly receive similarly to chloroform with that distinction, that it subject to additional clearing to chloroform with that distinction, that it subject to additional clearing by fractional clearing at temperature by fractional clearing at temperature 70 70 WithWith, thus impurity remain in a , thus impurity remain in a

solution.solution.

CCl3 C H

OH

OH

NaOH CHCl3 HCO

ONa+ + + H2O

DEFINITION

Chloroform is trichloromethane to which either 1.0 to 2.0% of ethanol or 50 mg per litre of amylene has been added.

CHARACTERISTICS

A colourless, volatile liquid.

Slightly soluble in water ; miscible with absolute ethanol ,

with ether , with fixed and volatile oils and with most organic solvents.

IDENTIFICATIONA. The infrared absorbtion spectrum.

B. Heat with alcoholic solution of alkali (potassium hydroxide). Obtained solution yields reactions characteristic of chlorides.

CHCl3 + 4KOH → 3KCl + НСООК + 2Н2О

a) a) Chlorides-ions: Chlorides-ions: with with solution of AgNO3:solution of AgNO3: ССl–l–+ Ag + → AgCl ↓+ Ag + → AgCl ↓ whitewhite AgCl + 2NH4OH = [Ag (NH3) 2] Cl + 2H2OAgCl + 2NH4OH = [Ag (NH3) 2] Cl + 2H2O b) Potassium formiateb) Potassium formiate НСООКНСООК: with : with FelingFeling reagent reagent

ФелингаФелинга - - formation formation of red precipitate of red precipitate Cu2O: Cu2O: НСООКНСООК + 2CuO + KOH = K2CO3 + + 2CuO + KOH = K2CO3 + Cu2OCu2O + +НН22ОО redred Reaction with phenolsReaction with phenols: the product of : the product of

condensation with condensation with resorcinolresorcinol has has redred colouring, and with colouring, and with ββ--

naphtholnaphthol – – dark bluedark blue..

TESTSTESTS Distillation range Distillation range Not more than 5.0% v/v distils below 60° and the remainder distils at 60° to 62°, Appendix V C. Not more than 5.0% v/v distils below 60° and the remainder distils at 60° to 62°, Appendix V C. Weight per ml Weight per ml 1.474 to 1.479 g, Appendix V G. 1.474 to 1.479 g, Appendix V G. Acidity or alkalinity Acidity or alkalinity Shake 10 ml with 20 ml of freshly boiled and cooled Shake 10 ml with 20 ml of freshly boiled and cooled water water for 3 minutes and allow to separate. To 5 ml of the for 3 minutes and allow to separate. To 5 ml of the

aqueous layer add 0.1 ml of neutral aqueous layer add 0.1 ml of neutral litmus solutionlitmus solution. The colour produced is the same as that produced on . The colour produced is the same as that produced on adding 0.1 ml of the neutral litmus solution to 5 ml of freshly boiled and cooled adding 0.1 ml of the neutral litmus solution to 5 ml of freshly boiled and cooled water water . .

Chloride Chloride To 5 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 5 ml of To 5 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 5 ml of water water and 0.2 ml of and 0.2 ml of

silver nitrate solutionsilver nitrate solution. The solution is . The solution is clearclear, Appendix IV A. , Appendix IV A. Free chlorine Free chlorine To 10 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 1 ml of a 5.0% w/v solution of To 10 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 1 ml of a 5.0% w/v solution of

zinc iodidezinc iodide and 0.1 ml of and 0.1 ml of starch mucilagestarch mucilage. No blue colour is produced. . No blue colour is produced. Aldehyde Aldehyde Shake 5 ml with 5 ml of Shake 5 ml with 5 ml of water water and 0.2 ml of and 0.2 ml of alkaline potassium tetraiodomercurate solutionalkaline potassium tetraiodomercurate solution in a glass- in a glass-

stoppered flask and allow to stand in the dark for 15 minutes. Not more than a pale yellow colour is stoppered flask and allow to stand in the dark for 15 minutes. Not more than a pale yellow colour is produced. produced.

Ethanol Ethanol Carry out the following test for Chloroform that contains ethanol. Carry out the method for Carry out the following test for Chloroform that contains ethanol. Carry out the method for gas gas

chromatographychromatography, Appendix III B, injecting 0.1 µl of each of the following solutions. Solution (1) , Appendix III B, injecting 0.1 µl of each of the following solutions. Solution (1) contains 1.0% v/v of contains 1.0% v/v of absolute ethanol absolute ethanol and 1.0% v/v of and 1.0% v/v of propan-1-ol propan-1-ol (internal standard) in (internal standard) in water water . . Solution (2) is the substance being examined. Solution (3) contains 1.0% v/v of the internal standard Solution (2) is the substance being examined. Solution (3) contains 1.0% v/v of the internal standard in the substance being examined. in the substance being examined.

The chromatographic procedure described under Related substances may be used. The chromatographic procedure described under Related substances may be used. The test is not valid unless the height of the trough separating the ethanol peak from the chloroform The test is not valid unless the height of the trough separating the ethanol peak from the chloroform

peak in the chromatogram obtained with solution (2) is less than 15% of the height of the ethanol peak in the chromatogram obtained with solution (2) is less than 15% of the height of the ethanol peak. peak.

Calculate the percentage content of ethanol from the areas of the peaks due to ethanol and the Calculate the percentage content of ethanol from the areas of the peaks due to ethanol and the

internal standard in the chromatograms obtained with solutions (1) and (3). internal standard in the chromatograms obtained with solutions (1) and (3). Non-volatile matter Non-volatile matter 25 ml, when evaporated to dryness and dried at 105°, leaves not more than 1 mg of residue. 25 ml, when evaporated to dryness and dried at 105°, leaves not more than 1 mg of residue. IMPURITIESIMPURITIES   A. carbon tetrachloride, A. carbon tetrachloride,   B. dichloromethane, B. dichloromethane,   C. bromochloromethane C. bromochloromethane

ASSAY. PharmacopoeiaASSAY. Pharmacopoeia quantitative definition quantitative definition does not demanddoes not demand, but it is possible to use reaction , but it is possible to use reaction with spirit solution of alkali for with spirit solution of alkali for the back acid-base the back acid-base titrationtitration. To defined volume of investigated . To defined volume of investigated substance add substance add excess of standard solution of excess of standard solution of alkali alkali KOH:KOH:

CHCl3 + CHCl3 + 44KOH → KOH → НСООКНСООК + 3KCl + 2H2O + 3KCl + 2H2O excessexcess Not reacted KOH titrate byNot reacted KOH titrate by standard solution of standard solution of

НСНСl in the presence of l in the presence of methyl orangemethyl orange colouring colouring before transition from before transition from yellowyellow to to the pinkthe pink..

TT KOH + HCl → KCl + H2OKOH + HCl → KCl + H2O restrest EmEm (CHCl3) = M. m./4(CHCl3) = M. m./4

STORAGESTORAGE Chloroform should be kept in a well-closed container with a glass Chloroform should be kept in a well-closed container with a glass

stopper or other suitable closure and protected from light. stopper or other suitable closure and protected from light. LABELLINGLABELLING The label states whether it contains ethanol or amylene. The label states whether it contains ethanol or amylene. Action and use Action and use General anaesthetic; antimicrobial preservative. General anaesthetic; antimicrobial preservative. Preparations Preparations Chloroform Spirit Chloroform Spirit Chloroform Water Chloroform Water Double-strength Chloroform WaterDouble-strength Chloroform Water

IODOFORM IODOFORM IodoformiumIodoformium

CHI3CHI3 Formylum triiodatumFormylum triiodatum ObtainingObtaining Obtaining methods iodoform are similar to methods of obtaining of Obtaining methods iodoform are similar to methods of obtaining of

chloroform.chloroform. 1. Electrolysis solution of potassium iodide 1. Electrolysis solution of potassium iodide at the presence of at the presence of

sodium carbonate and ethanol:sodium carbonate and ethanol: 22ККI + 2HOH I + 2HOH HH2 + 2 + I2I2 + 2KOH + 2KOH K (–): K +; K (–): K +; H2OH2O 2H2O + 2e → 2OH - + H2 ↑ 2H2O + 2e → 2OH - + H2 ↑ A (+): A (+): I–I–; H2O 2I - – 2e → I2; H2O 2I - – 2e → I2 4I2 + C2H5OH + 3Na2CO3 4I2 + C2H5OH + 3Na2CO3 CHI3CHI3 + HCOONa + 5NaI + 3CO2 + + HCOONa + 5NaI + 3CO2 +

2H2O2H2O yellowyellow 2. Interaction crystal iodine with ethanol in solution of sodium2. Interaction crystal iodine with ethanol in solution of sodium

carbonate carbonate (at (at 7070C)C). Brown colouring quickly disappears and is . Brown colouring quickly disappears and is formated formated CHI3 CHI3 in the form of in the form of yellow precipitate.yellow precipitate.

3. Interaction crystal iodine with acetone in solution of sodium carbonate (it is similar to chloroform):

3I2 + CH3СОCH3 + 2Na2CO3 CHI3 + 3CH3COONa + 3NaI + 2CO2 + H2O

CHARACTERISTICSIodoform is a yellow crystalline powder (m.p. 116-

120ºC); odor characteristic; Insoluble in water, practically insoluble in alcohol, ether,

chloroform.

IdentificationIdentification 1. Decomposition (oxidation) of a substance1. Decomposition (oxidation) of a substance. .

Heat in the test tube. The violet vapor of I2 is Heat in the test tube. The violet vapor of I2 is produced: produced:

2CHI3 + 2O2 = 32CHI3 + 2O2 = 3I2I2 + CO + CO + CO2 + CO2 + H2O + H2O violet vaporviolet vapor 2. Saponification by means of alcoholic 2. Saponification by means of alcoholic

solution of alkalisolution of alkali. . CHI3 CHI3 dissolve in alcoholicdissolve in alcoholic solution of alkalisolution of alkali KOH, and then the received KOH, and then the received solution acidify by HNO3; solution acidify by HNO3; yellow colouring of yellow colouring of I2 is I2 is formed:formed:

CHI3 + 4KOH → 3KI + CHI3 + 4KOH → 3KI + НСООКНСООК + 2 + 2НН22ОО 6KI + 8HNO3 = 26KI + 8HNO3 = 2I2I2 + 6KNO3 + 2NO + 2H2O + 6KNO3 + 2NO + 2H2O yellowyellow

Tests for cleanlinessTests for cleanliness.. 1. Impurity of mineral acids, dyes1. Impurity of mineral acids, dyes (inadmissible impurity). At (inadmissible impurity). At

vigorous stirring of a preparation with water and filtration the filtrate vigorous stirring of a preparation with water and filtration the filtrate should be colourlessshould be colourless..

2. The maintenance of impurity of chlorides, sulphates2. The maintenance of impurity of chlorides, sulphates within within standards.standards.

ASSAY. Argentometry, Volhard method.ASSAY. Argentometry, Volhard method. Shot of substance dissolve in Shot of substance dissolve in spiritspirit, add , add excess of a standard solution excess of a standard solution

AgNO3, acidify by HNO3, AgNO3, acidify by HNO3, heat upheat up on a water heater within on a water heater within 30 30 minutesminutes, , protecting a reactionary mix from lightprotecting a reactionary mix from light. Excess of AgNO3 . Excess of AgNO3 titrate bytitrate by standard solution of ammonium thiocyanate standard solution of ammonium thiocyanate NH4SCN in the NH4SCN in the presence of the indicator (NH4) Fe (SO4) 2 presence of the indicator (NH4) Fe (SO4) 2 before before pinkpink colouring colouring..

In parallel spend control experienceIn parallel spend control experience.. CHI3 + AgNO3 + H2O = AgICHI3 + AgNO3 + H2O = AgI + 3HNO3 + CO + 3HNO3 + CO excess yellow excess yellow T T AgNO3 + NH4SCN = AgSCNAgNO3 + NH4SCN = AgSCN + NH4NO3 + NH4NO3 T T white white 3NH4SCN + (NH4) Fe (SO4) 2 = Fe (SCN) 3 + 2 (NH4) 2SO43NH4SCN + (NH4) Fe (SO4) 2 = Fe (SCN) 3 + 2 (NH4) 2SO4 Ind pink colouringInd pink colouring ЕЕm = M.m = M.мм..

StorageStorage In well corked containers, in banks of dark In well corked containers, in banks of dark colour, in the cool place protected from light colour, in the cool place protected from light

for the prevention of decomposition of a for the prevention of decomposition of a preparation.preparation.

Action and use.Action and use. An external An external antisepticantiseptic(ointment).(ointment).

FLUOTHANEFLUOTHANE (Halothane) (Halothane) F3C-CHClBrF3C-CHClBr

PhthorothanumPhthorothanum Halothanum*Halothanum*

M. m. = 197,39 g/molM. m. = 197,39 g/mol CH(Br)ClCF3 (2-Bromo-2-chloro-1,1,1-trifluoroethane) CH(Br)ClCF3 (2-Bromo-2-chloro-1,1,1-trifluoroethane) Halotane, a volatile halohenated hydrocarbon (b.p. 50*C), Halotane, a volatile halohenated hydrocarbon (b.p. 50*C),

is now taken as a standard inhalation anesthetic agent.is now taken as a standard inhalation anesthetic agent. ObtainingObtaining 1. Bromination of 1,1,1-trifluoro-2-chloroethane at 1. Bromination of 1,1,1-trifluoro-2-chloroethane at

465 465 C:C: F3C–CH2Cl + Br2 = F3C–CHClBr + HBrF3C–CH2Cl + Br2 = F3C–CHClBr + HBr

PropertiesProperties Description. Transparent, colourless, a heavy, mobile liquid with Description. Transparent, colourless, a heavy, mobile liquid with

a smell reminding a smell of chloroform. Has sweet and burning a smell reminding a smell of chloroform. Has sweet and burning taste. Does not burn and does not ignite, does not blow up in a taste. Does not burn and does not ignite, does not blow up in a mix with air and with an aether (to 13 %). Contains 0,01 % mix with air and with an aether (to 13 %). Contains 0,01 % масмас. . The stabilizer The stabilizer тимолатимола. .

Solubility. Slightly soluble in water (0,345 %). Mixes up with Solubility. Slightly soluble in water (0,345 %). Mixes up with waterless spirit, ether, chloroform, oils (flying and nonvolatile), waterless spirit, ether, chloroform, oils (flying and nonvolatile), trichloroethylene.trichloroethylene.

IdentificationIdentification 1. Measurement of physical constants:1. Measurement of physical constants: Definition of temperature of boiling. The temperature of Definition of temperature of boiling. The temperature of

boiling (distillation) is equal 49–51 boiling (distillation) is equal 49–51 C.C. Measurement of relative density. The relative density at 20 Measurement of relative density. The relative density at 20

With is equal 1,865–1,870/ml Having the big density, With is equal 1,865–1,870/ml Having the big density, фторотанфторотан, , unlike chloroform and unlike chloroform and трихлорэтиленатрихлорэтилена, at addition of the , at addition of the concentrated sulphatic acid concentrated sulphatic acid is in the bottom layeris in the bottom layer. .

Measurement of an indicator of refraction. The refraction Measurement of an indicator of refraction. The refraction indicator at 20 indicator at 20 With is equal 1,3695–1,3705.With is equal 1,3695–1,3705.

2. IR-spectroscopy. IR-spectrum of drug should correspond to 2. IR-spectroscopy. IR-spectrum of drug should correspond to IR-spectrum the standard sample of fluothane.IR-spectrum the standard sample of fluothane.

3. Identification of Fluorine (after fusion with metal 3. Identification of Fluorine (after fusion with metal sodium) by means of mix of zirconium nitrate and sodium) by means of mix of zirconium nitrate and alizarine red (alizarine S)alizarine red (alizarine S). .

TechniqueTechnique. 0,5 ml of a preparation heat up with 0,05 . 0,5 ml of a preparation heat up with 0,05 гг the the fused metal sodiumfused metal sodium, cool, cautiously add 2 ml , cool, cautiously add 2 ml of waterof water, a , a solution filter and to a filtrate add 0,5 ml solution filter and to a filtrate add 0,5 ml ice ice СНСН33СООНСООН. 0,1 . 0,1 ml of this solution add to 0,2 ml of the mix consisting from ml of this solution add to 0,2 ml of the mix consisting from identical volume fresh prepare identical volume fresh prepare of a solution of a solution alizarine Salizarine S and and 0,1 % 0,1 % solution of zirconium nitrate in chloride acidsolution of zirconium nitrate in chloride acid; change ; change of red colouringof red colouring of a solution in of a solution in light yellowlight yellow owing to owing to formation of very steady complex compound Na2ZrF6 is formation of very steady complex compound Na2ZrF6 is observed. observed.

High qualityHigh quality In a drug there should be no a chlorides-, bromides-ions, In a drug there should be no a chlorides-, bromides-ions,

and also free chlorine and bromine. As conserving agent and also free chlorine and bromine. As conserving agent use thymol, which in a drug should be use thymol, which in a drug should be 0,01 %0,01 %..

ASSAY of thymol (stabilizer) by means of colorimetry, on the basis of reaction with the titan (IV) oxide TiO2,

comparing intensity of colouring with a standard solution. Storage. The list of strong substances. In dense corkin bottles

(on 50 and 250 ml) from dark glass, in the dry, cool place protected from light (under the influence of light slowly decays).

Every 6 months the preparation is subject to repeated check.Application. Means for an inhalation narcosis

Alcohols and ethers as drugsAlcohols and ethers as drugs Various alcohols have been used as antiseptics and disinfectants. Various alcohols have been used as antiseptics and disinfectants.

Antibacterial potencies of primary alcohols increase with molecular weight Antibacterial potencies of primary alcohols increase with molecular weight up to C8. Beyond this point, water solubility is less than the minimum up to C8. Beyond this point, water solubility is less than the minimum effective concentration, and the apparent potency decreases with effective concentration, and the apparent potency decreases with molecular weight. Branching decreases antibacterial potency; hence, the molecular weight. Branching decreases antibacterial potency; hence, the isomeric alcohols follow the order primary > secondary > tertiary. isomeric alcohols follow the order primary > secondary > tertiary. Noneseless, isopropylalcohol is used commercially instead of normal Noneseless, isopropylalcohol is used commercially instead of normal propyl alcohol, because it is cheaper. Isopropyl alcohol is slightly more propyl alcohol, because it is cheaper. Isopropyl alcohol is slightly more active than ethyl alcohol against vegetative bacterial growth, but alcohola active than ethyl alcohol against vegetative bacterial growth, but alcohola are largely ineffective against spores.are largely ineffective against spores.

AlcoholAlcohol ( C2H5OH, ethanol, spiritus vini rectificatus, wine spirit) is a ( C2H5OH, ethanol, spiritus vini rectificatus, wine spirit) is a clear, colorless, volatile liquid having a burning taste and characteristic clear, colorless, volatile liquid having a burning taste and characteristic pleasant odour. It is flammable and miscible with water and most organic pleasant odour. It is flammable and miscible with water and most organic solvents. The commercial product contains about 95% ethanol by volume solvents. The commercial product contains about 95% ethanol by volume because this concentration forms an azeotrope that distills at 78.2*F. because this concentration forms an azeotrope that distills at 78.2*F. Alcohol has been known for centuries as a fermentation product from Alcohol has been known for centuries as a fermentation product from grain and other carbohydrate sources. It can also be prepared grain and other carbohydrate sources. It can also be prepared synthetically by the sulphuric acid-catalyzed hydration of ethylene.synthetically by the sulphuric acid-catalyzed hydration of ethylene.

ETHANOLETHANOL C2H5OHC2H5OH

ETHANOL (96 PER CENTUM)ETHANOL (96 PER CENTUM) Ethanolum (96 per centum) Ethanolum (96 per centum) Ethanolum anhydricumEthanolum anhydricum ETHANOL, ANHYDROUS ETHANOL, ANHYDROUS ММ..мм. = 46,07 . = 46,07 гг//мольмоль Absolute Alcohol; Dehydrated Alcohol Absolute Alcohol; Dehydrated Alcohol (Anhydrous Ethanol, Ph Eur monograph 1318)(Anhydrous Ethanol, Ph Eur monograph 1318) C2H6OC2H6O    46.07 46.07     64-17-564-17-5 Ph EurPh Eur DEFINITIONDEFINITION Content Content Not less than 99.5 per centNot less than 99.5 per cent V/V V/V of C2H6O (99.2 per cent of C2H6O (99.2 per cent m/m m/m), at 20 °C, calculated ), at 20 °C, calculated

from the relative density using the alcoholimetric tables (from the relative density using the alcoholimetric tables (5.55.5). ).

ObtainingObtaining 1. Fermentation of natural sugary substances 1. Fermentation of natural sugary substances (grape juice, a (grape juice, a

potato, grain and other starchconteining raw materials). potato, grain and other starchconteining raw materials). a) From a) From glucose glucose under the influence of enzymes under the influence of enzymes zymaseszymases, containing , containing

in in yeastyeast, at temperature , at temperature 30-3530-35CC:: C6H12O6 C6H12O6 2C2H5OH + 2CO2 2C2H5OH + 2CO2 b) Withb) With starchconteining raw materialsstarchconteining raw materials: : 2 (C6H10O5) n + n2 (C6H10O5) n + nНН2O n2O nСС12H22O1112H22O11 starch maltose starch maltose Further under the influence of enzymes Further under the influence of enzymes maltasemaltase maltose hydrolyzes maltose hydrolyzes

to to glucoseglucose:: nnСС12H22O11 + H2O 2 nC6H12O612H22O11 + H2O 2 nC6H12O6 maltose glucosemaltose glucose Glucose under the influence of group of enzymesGlucose under the influence of group of enzymes zymaseszymases

gives end-products of fermentation – gives end-products of fermentation – ethanolethanol СС2H5OH and 2H5OH and carbonic carbonic gasgas СОСО2:2:

2nC6H12O6 4n2nC6H12O6 4nСС2H5OH + 4nCO22H5OH + 4nCO2

Ctаmylase 060,

maltase

03530,zymases

2. Synthetic methods2. Synthetic methods a) Hydration ethylene under a high pressure: a) Hydration ethylene under a high pressure: Н2С=СН2 + НОН Н2С=СН2 + НОН Н 3С–СН2ОНН 3С–СН2ОН

OrOr

b) From acetylene on Kucherov reaction with the b) From acetylene on Kucherov reaction with the subsequent reduction acetic aldehyde to spirit:subsequent reduction acetic aldehyde to spirit:

Acetic aldehyde drive away and restore hydrogen Acetic aldehyde drive away and restore hydrogen НН2 in the 2 in the presence of catalysts (N presence of catalysts (N іі, HgSO4) to alcohol: , HgSO4) to alcohol:

p

CH2 CH2

OS

OOH

OHCH3 CH2 O S OH

O

O

CH3 CH2 OH H2SO4+ +HOH +

ethylsulphate acid

CH CH HOH CH2 CH OH CH3 CO

H+ Hg2+

H+vinyl alcohol

tautomerism

acetic aldehyde

CH3 CO

HCH3 CH2

OH+Ni

H2

CHARACTERSCHARACTERS Appearance Appearance Colourless, clear, volatile, flammable liquid, hygroscopic. Colourless, clear, volatile, flammable liquid, hygroscopic. Solubility Solubility Miscible with water and with methylene chloride. Miscible with water and with methylene chloride. It burns with a blue, smokeless flame. It burns with a blue, smokeless flame. bp: about 78 °C. bp: about 78 °C.

IDENTIFICATIONIDENTIFICATION First identificationFirst identification  A, B.A, B. Second identificationSecond identification  A, C, D.A, C, D.   A. It complies with the test for relative density (see A. It complies with the test for relative density (see

Tests). Tests).   B. Infrared absorption spectrophotometry B. Infrared absorption spectrophotometry (2.2.24)(2.2.24). . ComparisonComparison  Ph. Eur. reference spectrum of anhydrous Ph. Eur. reference spectrum of anhydrous

ethanol .ethanol .

  C. Mix 0.1 ml with 1 ml of a 10 g/l solution of C. Mix 0.1 ml with 1 ml of a 10 g/l solution of potassium potassium permanganate Rpermanganate R and 0.2 ml of and 0.2 ml of dilute sulphuric acid Rdilute sulphuric acid R in a test-tube. in a test-tube. Cover immediately with a filter paper moistened with a freshly Cover immediately with a filter paper moistened with a freshly prepared solution containing 0.1 g of prepared solution containing 0.1 g of sodium nitroprusside Rsodium nitroprusside R and and 0.5 g of 0.5 g of piperazine hydrate Rpiperazine hydrate R in 5 ml of in 5 ml of water Rwater R. After a few minutes, . After a few minutes, an intense blue colour appears on the paper and becomes paler an intense blue colour appears on the paper and becomes paler after 10-15 min. after 10-15 min.

5C2H5OH + 2KMnO4 + 3H2SO4 → 2MnSO4 + 5CH3CHO + K2SO4 + 5C2H5OH + 2KMnO4 + 3H2SO4 → 2MnSO4 + 5CH3CHO + K2SO4 + 8H2O8H2O

MnO4– + 8H+ + 5MnO4– + 8H+ + 5ее Mn2+ + 4H2O | 5 | 2 Mn2+ + 4H2O | 5 | 2 C2H6O – 2C2H6O – 2ее C2H4O + 2H+ | 2 | 5 C2H4O + 2H+ | 2 | 5 5C2H5OH + 2MnO4– + 6H+ 2Mn2+ + 5CH3CHO + 8H2O 5C2H5OH + 2MnO4– + 6H+ 2Mn2+ + 5CH3CHO + 8H2O

  D. To 0.5 ml add 5 ml of D. To 0.5 ml add 5 ml of water Rwater R, 2 ml of , 2 ml of dilute sodium hydroxide dilute sodium hydroxide

solution Rsolution R, then slowly add 2 ml of , then slowly add 2 ml of 0.05 M iodine0.05 M iodine. A yellow . A yellow precipitate is formed within 30 min. precipitate is formed within 30 min.

C2H5OH + 4I2 + 6NaOH C2H5OH + 4I2 + 6NaOH CHI3 CHI3 + 5NaI + HCOONa + 5H2O + 5NaI + HCOONa + 5H2O yellowyellow Formation ethylacetate. At heating of drug with CH3COOH and Formation ethylacetate. At heating of drug with CH3COOH and

concentrated sulphatic acidconcentrated sulphatic acid H2SO4 it is formed H2SO4 it is formed ethyl-atcetic esterethyl-atcetic ester with a characteristic with a characteristic fruit smellfruit smell (a smell (a smell of pearsof pears):):

CH3 CH2 OH CO

OHCH3

H2SO4CH3 CH2

O C CH3

O

+ + H2Oconc.

TESTSTESTS Appearance Appearance It is clear It is clear (2.2.1)(2.2.1) and colourless and colourless (2.2.2, Method II)(2.2.2, Method II) when compared with when compared with water Rwater R. Dilute 1.0 ml . Dilute 1.0 ml

to 20 ml with to 20 ml with water Rwater R. After standing for 5 min, the dilution remains clear . After standing for 5 min, the dilution remains clear (2.2.1)(2.2.1) when when compared with compared with water Rwater R. .

Acidity or alkalinity Acidity or alkalinity To 20 ml add 20 ml of To 20 ml add 20 ml of carbon dioxide-free water Rcarbon dioxide-free water R and 0.1 ml of and 0.1 ml of phenolphthalein solution Rphenolphthalein solution R. .

The solution is colourless. Add 1.0 ml of The solution is colourless. Add 1.0 ml of 0.01 M sodium hydroxide0.01 M sodium hydroxide. The solution is pink (30 . The solution is pink (30 ppm, expressed as acetic acid). ppm, expressed as acetic acid).

Relative density Relative density (2.2.5)(2.2.5) 0.805 to 0.812. 0.805 to 0.812. Absorbance Absorbance (2.2.25)(2.2.25) Maximum 0.40 at 240 nm, 0.30 between 250 nm and 260 nm and 0.10 between 270 nm and Maximum 0.40 at 240 nm, 0.30 between 250 nm and 260 nm and 0.10 between 270 nm and

340 nm. 340 nm. Examine between 235 nm and 340 nm, in a 5 cm cell using Examine between 235 nm and 340 nm, in a 5 cm cell using water Rwater R as the compensation as the compensation

liquid. The absorption curve is smooth.liquid. The absorption curve is smooth.

Residue on evaporation Residue on evaporation Maximum 25 ppmMaximum 25 ppm m/V m/V. . Evaporate 100 ml to dryness on a water-bath and dry at 100-105 Evaporate 100 ml to dryness on a water-bath and dry at 100-105

°C for 1 h. The residue weighs a maximum of 2.5 mg. °C for 1 h. The residue weighs a maximum of 2.5 mg. IMPURITIESIMPURITIES    A. 1,1-diethoxyethane (acetal), A. 1,1-diethoxyethane (acetal),    B. acetaldehyde, B. acetaldehyde,    C. AcetoneC. Acetone

ASSAYASSAY 1. Relative density 1. Relative density (2.2.5)(2.2.5) 0.805 to 0.812. 0.805 to 0.812. 2. Iodometry. 2. Iodometry. Ethanol oxidise byEthanol oxidise by solution solution K2Cr2O7 in K2Cr2O7 in the medium of H2SO4 the medium of H2SO4

Excess of K2Cr2O7 establish by iodometry (the indicator – Excess of K2Cr2O7 establish by iodometry (the indicator – starchstarch).). K2Cr2O7 + 3K2Cr2O7 + 3C2H5OHC2H5OH + 4H2SO4 → Cr2 (SO4)3 + 3CH3CHO + K2SO4 + + 4H2SO4 → Cr2 (SO4)3 + 3CH3CHO + K2SO4 +

7H2O7H2O excessexcess Cr2O72– + 14H+ + 6Cr2O72– + 14H+ + 6ее 2Cr3+ + 7H2O | 6 | 3 | 1 2Cr3+ + 7H2O | 6 | 3 | 1 C2H6O – 2C2H6O – 2ее C2H4O + 2H+ | 2 | 1 | 3 C2H4O + 2H+ | 2 | 1 | 3 K2Cr2O7 + 6KI + 7H2SO4 K2Cr2O7 + 6KI + 7H2SO4 Cr2 (SO4)3 + 3 Cr2 (SO4)3 + 3I2 I2 + 4K2SO4 + 7H2O+ 4K2SO4 + 7H2O excessexcess Cr2O72– + 14H+ + 6Cr2O72– + 14H+ + 6ее 2Cr3+ + 7H2O | 6 | 3 | 1 2Cr3+ + 7H2O | 6 | 3 | 1 2I– – 22I– – 2ее I2 | 2 | 1 | 3 I2 | 2 | 1 | 3 TT I2I2 + 2 + 2Na2S2O3Na2S2O3 NaI + Na2S4O6 NaI + Na2S4O6 2I– – 22I– – 2ее I2 I2 2S2O32– – 22S2O32– – 2ее S4O62– S4O62– Em(C2H5OH) = Em(C2H5OH) = ММ..мм./4./4

3. In drugs 3. In drugs recommend to define recommend to define concentration of alcohol on concentration of alcohol on densitydensity oror behind boiling temperaturebehind boiling temperature..

STORAGESTORAGE Protected from light. In densely corked Protected from light. In densely corked

containers, in a cool place.containers, in a cool place. Application. External antiseptic and Application. External antiseptic and

irritating means.irritating means.

ANAESTHETICANAESTHETIC ETHERETHER Aether for narcosisAether for narcosis Aether anaestheticusAether anaestheticus ANAESTHETIC ANAESTHETIC Aether medicinalis Aether medicinalis

M. m. = 74,12 g/mol M. m. = 74,12 g/mol Aether medicalAether medical Aether pro narcosiAether pro narcosi Aether aethylicusAether aethylicus Aether ethylAether ethyl

HH55CC22-O-C-O-C22HH55 The chemical nameThe chemical name: diethyl ether, ethoxy ethane.: diethyl ether, ethoxy ethane. C4H10O (CH3-CH2-O-CH2-CH3) C4H10O (CH3-CH2-O-CH2-CH3) DEFINITIONDEFINITION Diethyl ether.Diethyl ether. It may It may contain a suitable non-volatile contain a suitable non-volatile

antioxidant at an appropriate concentrationantioxidant at an appropriate concentration..

CHARACTERSCHARACTERS AppearanceAppearance Clear, colourless liquid, volatile, very mobile.Clear, colourless liquid, volatile, very mobile. SolubilitySolubility Soluble in 15 parts of water, miscible with ethanol (96 Soluble in 15 parts of water, miscible with ethanol (96

per cent) and with fatty oils.per cent) and with fatty oils. It is highly flammable.It is highly flammable. IDENTIFICATIONIDENTIFICATION A.A. (BrPh, SPU, add. 1).(BrPh, SPU, add. 1). Relative densityRelative density 0.714 to 0.714 to

0.716.0.716. B. (BrPh, SPU, add. 1).B. (BrPh, SPU, add. 1). Distillation rangeDistillation range 34.0 °C 34.0 °C

and 35.0 °C.and 35.0 °C.

ASSAY not makes, according to ASSAY not makes, according to Pharmacopoeia.Pharmacopoeia.

STORAGESTORAGE Protected from light, in the dense corked Protected from light, in the dense corked

containers , protected from light, at a containers , protected from light, at a temperature not less then 8 °C and not temperature not less then 8 °C and not more then 15 °C. more then 15 °C.

Action and useAction and use GeneralGeneral anaesthetic.anaesthetic.

Browse: Browse: British Pharmacopoeia 2009 British Pharmacopoeia 2009 SPU, add. 1 SPU, add. 1

Formaldehyde SolutionFormaldehyde Solution (Formaldehyde Solution (35 per cent), Ph Eur (Formaldehyde Solution (35 per cent), Ph Eur

monograph 0826)monograph 0826) Formaldehydi solutio (35 per centum) Formaldehydi solutio (35 per centum) FORMALDEHYDE SOLUTION (35 PER FORMALDEHYDE SOLUTION (35 PER

CENT)CENT) FormalinumFormalinum

CHCH22OO 30.0330.03 DEFINITIONDEFINITION ContentContent 34.5 34.5 per cent per cent m/m m/m to 38.0 per centto 38.0 per cent m/m m/m of of

formaldehyde (CH2O; formaldehyde (CH2O; Mr Mr 30.03).30.03). It contains It contains methanol as stabilisermethanol as stabiliser..

OBTAININGOBTAINING Methane oxidationMethane oxidation::

CHARACTERSCHARACTERS AppearanceAppearance Clear, colourless liquid.Clear, colourless liquid. SolubilitySolubility Miscible with water and with ethanol (96 per cent).Miscible with water and with ethanol (96 per cent). It may be cloudy after storage.It may be cloudy after storage.

H CO

H22 CH4 + O2 2 CH3OH

O2+ 2 H2O

IDENTIFICATIONIDENTIFICATIONA.A. (BrPh, SPU, add. 1). (BrPh, SPU, add. 1). Reaction with chromotropic Reaction with chromotropic

acid sodium salt in the sulphuric-acid mediumacid sodium salt in the sulphuric-acid medium Dilute 1 ml of solution S (see Tests) to 10 ml with Dilute 1 ml of solution S (see Tests) to 10 ml with water Rwater R. To 0.05 . To 0.05

ml of the solution add 1 ml of a 15 g/l solution of ml of the solution add 1 ml of a 15 g/l solution of chromotropic acid chromotropic acid sodium salt Rsodium salt R, 2 ml of , 2 ml of water R water R and 8 ml of and 8 ml of sulphuric acid Rsulphuric acid R. A . A violet-blue or violet-red colourviolet-blue or violet-red colour develops develops within 5 min. within 5 min.

OH

OH

SO3Na

SO3Na

CHO

H

H2SO4CH2

OH

OH

SO3H

SO3H

OH

OH

HO3S

HO3S

CH

OH

OH

SO3H

SO3H

OH

O

HO3S

HO3S

2 + конц.[O]

H2O

B.B. (BrPh, SPU, add. 1). (BrPh, SPU, add. 1). Reaction with phenylhydrazine hydrochloride and Reaction with phenylhydrazine hydrochloride and potassium ferricyanide solutionpotassium ferricyanide solution

To 0.1 ml of solution S add 10 ml of To 0.1 ml of solution S add 10 ml of water Rwater R. Add 2 ml of a 10 g/l solution of . Add 2 ml of a 10 g/l solution of phenylhydrazine phenylhydrazine hydrochloride Rhydrochloride R, prepared immediately before use, 1 ml of , prepared immediately before use, 1 ml of potassium ferricyanide solution R potassium ferricyanide solution R and 5 ml of and 5 ml of hydrochloric acid Rhydrochloric acid R. An . An intense red colourintense red colour is formed is formed..

C.C. (BrPh, SPU, add. 1). (BrPh, SPU, add. 1). Reaction of “silver mirror”Reaction of “silver mirror” Mix 0.5 ml with 2 ml of Mix 0.5 ml with 2 ml of water R water R and 2 ml of and 2 ml of silver nitrate solution R2 silver nitrate solution R2 in a test-tube. Add in a test-tube. Add dilute ammonia dilute ammonia

R2 R2 until slightly alkaline. Heat on a water-bath. A until slightly alkaline. Heat on a water-bath. A grey precipitate or a grey precipitate or a silver mirror is formed.silver mirror is formed.

2AgNO3 + 2NH4OH = [Ag(NH3)2]NO3 + 2H2O2AgNO3 + 2NH4OH = [Ag(NH3)2]NO3 + 2H2O НCНO + 2[Ag(NH3)2]NO3 + H2O = НCНO + 2[Ag(NH3)2]NO3 + H2O = 2Ag2Ag + НCOONH4 + NH3 + НCOONH4 + NH3 + +

2NH4NO32NH4NO3

D.D. (BrPh, SPU, add. 1). (BrPh, SPU, add. 1). It complies with the It complies with the limits of the assay.limits of the assay.

NH

NH2 HCl CH2O NH

NH

CH2

NH

NH

K3[Fe(CN)6]

N N CH2

N N

*2 +- H2O

ASSAYASSAY Iodometry in the alkaline mediumIodometry in the alkaline medium, , back back

titrationtitration II220 + 2 NaOH = NaI-1 + NaI+1O + H2O0 + 2 NaOH = NaI-1 + NaI+1O + H2O

NaI-1 + 1NaІ+1O + H2SO4 = 1I20 + Na2SO4 + H2ONaI-1 + 1NaІ+1O + H2SO4 = 1I20 + Na2SO4 + H2O 11I2 + I2 + 22Na2S2O3 = 2NaІ + Na2S4O6Na2S2O3 = 2NaІ + Na2S4O6

EEm(HCHO) = M. m(HCHO) = M. mm./2./2 * * Alkaline medium necessary because in the acid medium at Alkaline medium necessary because in the acid medium at

interaction iodineinteraction iodine I2 I2 with formaldehyde with formaldehyde НСНО НСНО iodide acidiodide acid НI НI is is formedformed, , which is reducing agent and reaction has back directionwhich is reducing agent and reaction has back direction..

STORAGESTORAGE Protected from light, at a temperature of 15 °C to 25 °C.Protected from light, at a temperature of 15 °C to 25 °C. Ph EurPh Eur

Action and useAction and use When suitably diluted, used in the treatment of warts.When suitably diluted, used in the treatment of warts. Ph EurPh Eur

Thanks for attention!