Download 05 Halogen deriv. of hydrocarbons. Alcohols,ethers, esters

 LECTURE № 5
 Halogenderivatives of hydrocarbons,
which are used in the medical
practice. Some alcohols, aldehydes
and ethers as drugs
 associate prof. Mosula L. M.
The Plan
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1. Halogenderivatives of
hydrocarbons : Ethyl Chloride,
Chloroform, Iodoform, Fluothane.
2. Alcohol - 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 chloridum
Aethylium chloratum
Aethylis Chloridum*
Aether chloratus
H3C-CH2Cl
(C2H5Cl)
64.52
The 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.
 Obtaining
 1. Heating (110-120) absolute ethyl alcohol with dry HCl (or
concentrated HNO3) in the presence of dehydrating means (CaCl2
anhydrous, ZnCl2 or conc. H2SO4):
 C2H5OH + HCl C2H5Cl + H2O
 2. Hydrochlorination of ethylene:
 Н2С=СН2 + HCl = H3C–CH2Cl
 3. Chlorination ethane:
 C2H6 + Cl2  C 2H5Cl + HCl
 Characteristics. Gaseous at ambient temperature and pressure,
but usually compressed to a colorless, mobile, flammable and very
volatile liquid; odour, ethereal.
 Slightly soluble in water, miscible with ethanol and with ether.
 Identification.
 A. Burns with a luminous flame with the production of
hydrogen chloride.
 C2H5Cl + 2O2 = CO2 + 2H2O + HCl
 B. Vigorously shake 2 ml with 5M sodium hydroxide and
warm on a water bath. Reserve a portion of the solution
for test C. To the resulting solution add 2 ml of iodinated
potassium iodide solution and warm. Crystals of iodoform
are produced (iodoform test)..
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 C2H5Cl + NaОН  C2H5ОН + NaCl
 C2H5OH + 4I2 + 6NaOH = CHI3 + HCOONa + 5NaI
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yellow
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precipitate and its specific smell
 C. The solution reserved in test B yields
the reactions characteristic of chlorides.
 KCl + AgNO3 AgCl + KNO3
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white precipitate
 Cl– + Ag+  AgCl
 AgCl + 2NH4OH Ag(NH3)2Cl + 2H2O
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Tests
1. Definition of temperature of boiling.
2. Density measurement.
3. Acidity.
4. Ethanol (an inadmissible impurity) which define
bymeans of iodoform test (see above); there should
not be a turbidity.
 5. Organic impurity (an inadmissible impurity). At
mixing of a preparation with concentrated sulphatic
acid H2SO4 at cooling in the ice water, the received
solution should be colourless.
 6. The rest at evaporation.
 Storage. The list of strong substances. Ethyl chloride
should be stored at temperature not exceeding 15*C, in the
cool place protected from light.
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 INDICATIONS FOR USE Anaesthetic, an inhalation
narcotic. For external use only
 Ethyl Chloride is a vapocoolant (skin refrigerant) intended
for topical application to control pain associated with
injections, minor surgical procedures (such as lancing boils,
incisions, and drainage of small abscesses) and athletic
injuries. It is also intended for the treatment of restricted
motion associated with myofascial pain caused by trigger
points.
 Contents under pressure. Store in a cool place (controlled
room temperature). Do not store above 120°C. Do not store
on or near high frequency ultrasound equipment.
CHLOROFORM
 Chloroformium
M =119,38 g/mol
 Chloroform for narcosis
 Chloroformium pro narcosi
 Chloroformium
Anaesthesicum* CHCl3
 The chemical name:
Chloroform, trichloromethane.
Cl
H
C
Cl
Cl
 Obtaining
 1. Electrolysis solution of sodium chloride in the
presence of ethanol or acetone (a modern method).
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This method consists of such stages.
 a) Electrolysis solution of sodium chloride with
formation of alkali and chlorine and hydrogen gases:
 2NaCl + 2HOH
 K (–): Na +; H2O 2H2O + 2e → 2OH - + H2 ↑
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A (+): Cl–; H2O 2Cl- – 2e → Cl2
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b) Reaction disproportionation of chlorine in an
alkali solution:
 NaOH + Cl2 = NaCl + NaClO + H2O
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c) Oxidation of ethanol or acetone* by means of sodium hypochlorite
NaClO to acetic aldehyde or acetone trichloride (*then use acetone
receive purer chloroform):
C2H5OH
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H3C
C
+
O
+1
NaClO
CH3
H3C
C
H
acetic aldehyde
+
3 NaClO
+
H3C
-1
NaCl
C
CCl3
+
H2O
+
3 NaOH
O
acetone trichloride
O
acetic aldehyde further is oxidised to trichloroacetaldehyde:
O
H3C C
H
O
+
3 NaClO
CCl3
C
+
H
trichloroacetaldehyde
 Thus, the total equation of oxidation of ethanol:
 C2H5OH + 4NaClO Cl3CCНO + 3NaOH + NaCl + H2O
3 NaOH
d) Decomposition acetone trichloride or trichloroacetaldehyde
by means of alkali with chloroform formation:
O
CCl3 C
H
O
+
NaOH
CHCl3 + H C
ONa
chloroform
sodium formiate
O
H3C
C
O
CCl3
+
NaOH
CHCl3 +
chloroform
H3C
C
ONa
sodium acetate
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2. Alkali action on chloral hydrate (receive purer chloroform):
OH
CCl3
C
H
OH
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O
+
NaOH
CHCl3
+
HC
ONa
+
H2O
4. Reduction tetrachlormethane by iron in the presence of water.
ССl4 + Fe + HOH → CHCl3 + FeOHCl
Chloroform clearing.
Chloroform for narcosis Chloroformium pro narcosi receive similarly
to chloroform with that distinction, that it subject to additional clearing by
fractional clearing at temperature 70 With, thus impurity remain in a
solution.
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.
IDENTIFICATION
A. 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
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a) Chlorides-ions: with solution of AgNO3:
Сl–+ Ag + → AgCl ↓
white
AgCl + 2NH4OH = [Ag (NH3) 2] Cl + 2H2O
b) Potassium formiate НСООК: with Feling reagent
Фелинга - formation of red precipitate Cu2O:
 НСООК + 2CuO + KOH = K2CO3 + Cu2O +Н2О
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red
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Reaction with phenols: the product of
condensation with resorcinol has red colouring, and with β-
naphthol – dark blue.
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TESTS
Distillation range
Not more than 5.0% v/v distils below 60° and the remainder distils at 60° to 62°, Appendix V C.
Weight per ml
1.474 to 1.479 g, Appendix V G.
Acidity or alkalinity
Shake 10 ml with 20 ml of freshly boiled and cooled water for 3 minutes and allow to separate. To 5 ml of the
aqueous layer add 0.1 ml of neutral litmus solution. 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 water .
Chloride
To 5 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 5 ml of water and 0.2 ml of
silver nitrate solution. The solution is clear, Appendix IV A.
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
zinc iodide and 0.1 ml of starch mucilage. No blue colour is produced.
Aldehyde
Shake 5 ml with 5 ml of water and 0.2 ml of alkaline potassium tetraiodomercurate solution in a glassstoppered flask and allow to stand in the dark for 15 minutes. Not more than a pale yellow colour is
produced.
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Ethanol
Carry out the following test for Chloroform that contains ethanol. Carry out the method for gas
chromatography, Appendix III B, injecting 0.1 µl of each of the following solutions. Solution (1)
contains 1.0% v/v of absolute ethanol and 1.0% v/v of propan-1-ol (internal standard) in water .
Solution (2) is the substance being examined. Solution (3) contains 1.0% v/v of the internal standard
in the substance being examined.
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
peak in the chromatogram obtained with solution (2) is less than 15% of the height of the ethanol
peak.
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).
Non-volatile matter
25 ml, when evaporated to dryness and dried at 105°, leaves not more than 1 mg of residue.
IMPURITIES
A. carbon tetrachloride,
B. dichloromethane,
C. bromochloromethane
 ASSAY. Pharmacopoeia quantitative definition
does not demand, but it is possible to use reaction
with spirit solution of alkali for the back acid-base
titration. To defined volume of investigated
substance add excess of standard solution of
alkali KOH:
 CHCl3 + 4KOH → НСООК + 3KCl + 2H2O

excess
 Not reacted KOH titrate by standard solution of
НСl in the presence of methyl orange colouring
before transition from yellow to the pink.

T
 KOH + HCl → KCl + H2O
 rest
 Em (CHCl3) = M. m./4
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STORAGE
Chloroform should be kept in a well-closed container with a glass
stopper or other suitable closure and protected from light.
LABELLING
The label states whether it contains ethanol or amylene.
Action and use
General anaesthetic; antimicrobial preservative.
Preparations
Chloroform Spirit
Chloroform Water
Double-strength Chloroform Water

IODOFORM
 Iodoformium
 CHI3
 Formylum triiodatum
 Obtaining
 Obtaining methods iodoform are similar to methods of obtaining of
chloroform.
 1. Electrolysis solution of potassium iodide at the presence of
sodium carbonate and ethanol:
 2КI + 2HOH H2 + I2 + 2KOH
 K (–): K +; H2O 2H2O + 2e → 2OH - + H2 ↑

A (+): I–; H2O 2I - – 2e → I2
 4I2 + C2H5OH + 3Na2CO3  CHI3 + HCOONa + 5NaI + 3CO2 +
2H2O

yellow
 2. Interaction crystal iodine with ethanol in solution of sodium
carbonate (at 70C). Brown colouring quickly disappears and is
formated CHI3 in the form of 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
CHARACTERISTICS
Iodoform is a yellow crystalline powder (m.p. 116120ºC); odor characteristic;
Insoluble in water, practically insoluble in alcohol, ether,
chloroform.
 Identification
 1. Decomposition (oxidation) of a substance.
Heat in the test tube. The violet vapor of I2 is
produced:
 2CHI3 + 2O2 = 3I2 + CO + CO2 + H2O

violet vapor
 2. Saponification by means of alcoholic
solution of alkali. CHI3 dissolve in alcoholic
solution of alkali KOH, and then the received
solution acidify by HNO3; yellow colouring of I2 is
formed:
 CHI3 + 4KOH → 3KI + НСООК + 2Н2О
 6KI + 8HNO3 = 2I2 + 6KNO3 + 2NO + 2H2O

yellow
 Tests for cleanliness.
 1. Impurity of mineral acids, dyes (inadmissible impurity). At vigorous
stirring of a preparation with water and filtration the filtrate should be
colourless.
 2. The maintenance of impurity of chlorides, sulphates within
standards.
 ASSAY. Argentometry, Volhard method.
 Shot of substance dissolve in spirit, add excess of a standard solution
AgNO3, acidify by HNO3, heat up on a water heater within 30
minutes, protecting a reactionary mix from light. Excess of AgNO3
titrate by standard solution of ammonium thiocyanate NH4SCN in the
presence of the indicator (NH4) Fe (SO4) 2 before pink colouring.
 In parallel spend control experience.
 CHI3 + AgNO3 + H2O = AgI + 3HNO3 + CO

excess
yellow

T
 AgNO3 + NH4SCN = AgSCN + NH4NO3

T
white
 3NH4SCN + (NH4) Fe (SO4) 2 = Fe (SCN) 3 + 2 (NH4) 2SO4

Ind
pink colouring
 Еm = M.м.
 Storage
 In well corked containers, in banks of dark
colour, in the cool place protected from light
for the prevention of decomposition of a
preparation.
 Action and use. An external
antiseptic(ointment).
 FLUOTHANE (Halothane)
 F3C-CHClBr
 Phthorothanum
 Halothanum*

M. m. = 197,39 g/mol
 CH(Br)ClCF3
(2-Bromo-2-chloro-1,1,1-trifluoroethane)
 Halotane, a volatile halohenated hydrocarbon (b.p. 50*C),
is now taken as a standard inhalation anesthetic agent.

 Obtaining
 1. Bromination of 1,1,1-trifluoro-2-chloroethane at
465 C:
 F3C–CH2Cl + Br2 = F3C–CHClBr + HBr
 Properties
 Description. Transparent, colourless, a heavy, mobile liquid with
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
mix with air and with an aether (to 13 %). Contains 0,01 % мас.
The stabilizer тимола.

Solubility. Slightly soluble in water (0,345 %). Mixes up with
waterless spirit, ether, chloroform, oils (flying and nonvolatile),
trichloroethylene.
 Identification
 1. Measurement of physical constants:

Definition of temperature of boiling. The temperature of boiling
(distillation) is equal 49–51 C.

Measurement of relative density. The relative density at 20
With is equal 1,865–1,870/ml Having the big density, фторотан,
unlike chloroform and трихлорэтилена, at addition of the
concentrated sulphatic acid is in the bottom layer.

Measurement of an indicator of refraction. The refraction
indicator at 20 With is equal 1,3695–1,3705.
 2. IR-spectroscopy. IR-spectrum of drug should correspond to IRspectrum the standard sample of fluothane.
 3. Identification of Fluorine (after fusion with metal
sodium) by means of mix of zirconium nitrate and
alizarine red (alizarine S).
 Technique. 0,5 ml of a preparation heat up with 0,05 г the
fused metal sodium, cool, cautiously add 2 ml of water, a
solution filter and to a filtrate add 0,5 ml ice СН3СООН. 0,1
ml of this solution add to 0,2 ml of the mix consisting from
identical volume fresh prepare of a solution alizarine S
and 0,1 % solution of zirconium nitrate in chloride acid;
change of red colouring of a solution in light yellow owing
to formation of very steady complex compound Na2ZrF6 is
observed.
 High quality
 In a drug there should be no a chlorides-, bromides-ions,
and also free chlorine and bromine. As conserving agent
use thymol, which in a drug should be 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 drugs
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Various alcohols have been used as antiseptics and disinfectants.
Antibacterial potencies of primary alcohols increase with molecular weight
up to C8. Beyond this point, water solubility is less than the minimum
effective concentration, and the apparent potency decreases with
molecular weight. Branching decreases antibacterial potency; hence, the
isomeric alcohols follow the order primary > secondary > tertiary.
Noneseless, isopropylalcohol is used commercially instead of normal
propyl alcohol, because it is cheaper. Isopropyl alcohol is slightly more
active than ethyl alcohol against vegetative bacterial growth, but alcohola
are largely ineffective against spores.
Alcohol ( C2H5OH, ethanol, spiritus vini rectificatus, wine spirit) is a
clear, colorless, volatile liquid having a burning taste and characteristic
pleasant odour. It is flammable and miscible with water and most organic
solvents. The commercial product contains about 95% ethanol by volume
because this concentration forms an azeotrope that distills at 78.2*F.
Alcohol has been known for centuries as a fermentation product from
grain and other carbohydrate sources. It can also be prepared
synthetically by the sulphuric acid-catalyzed hydration of ethylene.
 ETHANOL
 C2H5OH
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ETHANOL (96 PER CENTUM)
Ethanolum (96 per centum)
Ethanolum anhydricum
ETHANOL, ANHYDROUS
Absolute Alcohol; Dehydrated Alcohol
М.м. = 46,07 г/моль
(Anhydrous Ethanol, Ph Eur monograph 1318)
C2H6O
46.07
64-17-5
Ph Eur
DEFINITION
Content
Not less than 99.5 per cent V/V of C2H6O (99.2 per cent m/m), at 20 °C, calculated
from the relative density using the alcoholimetric tables (5.5).
 Obtaining
 1. Fermentation of natural sugary substances (grape juice, a
potato, grain and other starchconteining raw materials).
 a) From glucose under the influence of enzymes zymases, containing
in yeast, at temperature 30-35C:
 C6H12O6  2C2H5OH + 2CO2

b) With starchconteining raw materials:
 2 (C6H10O5) n + nН2O
nС12H22O11


starch
maltose

Further under the influence of enzymes maltase maltose hydrolyzes
to glucose:

 nС12H22O11 + H2O 2
nC6H12O6

maltose
glucose
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Glucose under the influence of group of enzymes zymases
gives end-products of fermentation – ethanol С2H5OH and carbonic
gas СО2:
 2nC6H12O6 
4nС2H5OH + 4nCO2
аmylase,t 600 C
maltase
zymases, 30350
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2. Synthetic methods
a) Hydration ethylene under a high pressure:

Н2С=СН2 + НОН
Н 3С–СН2ОН
p
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Or
H2C CH2+

HC

HO
HO
S
O
O
O
H3C CH2
O S OH
+HOH
H3C CH2
OH
+
H2SO4
O
ethylsulphate acid
b) From acetylene on Kucherov reaction with the
subsequent reduction acetic aldehyde to spirit:
CH
+
HOH
Hg2+
H+
OH
H2C CH
vinyl alcohol
tautomerism
O
H3C
C
H
acetic aldehyde
Acetic aldehyde drive away and restore hydrogen Н2 in the
presence of catalysts (N і, HgSO4) to alcohol:
O
Ni
H3C CH2 OH
H3C C
+ H2
H
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CHARACTERS
Appearance
Colourless, clear, volatile, flammable liquid, hygroscopic.
Solubility
Miscible with water and with methylene chloride.
It burns with a blue, smokeless flame.
bp: about 78 °C.
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IDENTIFICATION
First identification
A, B.
Second identification
A, C, D.
A. It complies with the test for relative density (see
Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Comparison
ethanol .
Ph. Eur. reference spectrum of anhydrous
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C. Mix 0.1 ml with 1 ml of a 10 g/l solution of potassium
permanganate R and 0.2 ml of dilute sulphuric acid R in a test-tube.
Cover immediately with a filter paper moistened with a freshly
prepared solution containing 0.1 g of sodium nitroprusside R and
0.5 g of piperazine hydrate R in 5 ml of water R. After a few minutes,
an intense blue colour appears on the paper and becomes paler
after 10-15 min.
5C2H5OH + 2KMnO4 + 3H2SO4 → 2MnSO4 + 5CH3CHO + K2SO4 +
8H2O
MnO4– + 8H+ + 5е Mn2+ + 4H2O
|5|2
C2H6O – 2е C2H4O + 2H+
|2|5
5C2H5OH + 2MnO4– + 6H+ 2Mn2+ + 5CH3CHO + 8H2O
D. To 0.5 ml add 5 ml of water R, 2 ml of dilute sodium hydroxide
solution R, then slowly add 2 ml of 0.05 M iodine. A yellow
precipitate is formed within 30 min.
 C2H5OH + 4I2 + 6NaOH  CHI3  + 5NaI + HCOONa + 5H2O
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yellow
 Formation ethylacetate. At heating of drug with CH3COOH and
concentrated sulphatic acid H2SO4 it is formed ethyl-atcetic ester
with a characteristic fruit smell (a smell of pears):
O
O
H3C CH2
OH
+
H2SO4
C
HO
CH3
conc.
H3C CH2
O
C
CH3
+
H2O
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TESTS
Appearance
It is clear (2.2.1) and colourless (2.2.2, Method II) when compared with water R. Dilute 1.0 ml
to 20 ml with water R. After standing for 5 min, the dilution remains clear (2.2.1) when
compared with water R.
Acidity or alkalinity
To 20 ml add 20 ml of carbon dioxide-free water R and 0.1 ml of phenolphthalein solution R.
The solution is colourless. Add 1.0 ml of 0.01 M sodium hydroxide. The solution is pink (30
ppm, expressed as acetic acid).
Relative density (2.2.5)
0.805 to 0.812.
Absorbance (2.2.25)
Maximum 0.40 at 240 nm, 0.30 between 250 nm and 260 nm and 0.10 between 270 nm and 340
nm.
Examine between 235 nm and 340 nm, in a 5 cm cell using water R as the compensation
liquid. The absorption curve is smooth.
 Residue on evaporation
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 Maximum 25 ppm m/V.
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 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.
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 IMPURITIES
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A. 1,1-diethoxyethane (acetal),
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B. acetaldehyde,
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C. Acetone
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ASSAY
1. Relative density (2.2.5)
0.805 to 0.812.
2. Iodometry. Ethanol oxidise by solution K2Cr2O7 in the medium of H2SO4
Excess of K2Cr2O7 establish by iodometry (the indicator – starch).
K2Cr2O7 + 3C2H5OH + 4H2SO4 → Cr2 (SO4)3 + 3CH3CHO + K2SO4 +
7H2O
excess
Cr2O72– + 14H+ + 6е 2Cr3+ + 7H2O
|6|3|1
C2H6O – 2е C2H4O + 2H+
|2|1|3
K2Cr2O7 + 6KI + 7H2SO4  Cr2 (SO4)3 + 3I2 + 4K2SO4 + 7H2O
excess
Cr2O72– + 14H+ + 6е  2Cr3+ + 7H2O | 6 | 3 | 1
2I– – 2е  I2
|2|1|3
T
I2 + 2Na2S2O3  NaI + Na2S4O6
2I– – 2е  I2
2S2O32– – 2е  S4O62–
Em(C2H5OH) = М.м./4
 3. In drugs recommend to define
concentration of alcohol on density or
behind boiling temperature.

 STORAGE
 Protected from light. In densely corked
containers, in a cool place.

Application. External antiseptic and
irritating means.
 ANAESTHETIC ETHER
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Aether for narcosis
Aether anaestheticus
ANAESTHETIC
Aether medicinalis
M. m. = 74,12 g/mol
Aether medical
Aether pro narcosi
Aether aethylicus
Aether ethyl
 H5C2-O-C2H5
 The chemical name: diethyl ether, ethoxy ethane.
 C4H10O (CH3-CH2-O-CH2-CH3)
DEFINITION
 Diethyl ether.
 It may contain a suitable non-volatile
antioxidant at an appropriate concentration.
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CHARACTERS
Appearance
Clear, colourless liquid, volatile, very mobile.
Solubility
Soluble in 15 parts of water, miscible with ethanol (96
per cent) and with fatty oils.
It is highly flammable.
IDENTIFICATION
A. (BrPh, SPU, add. 1). Relative density 0.714 to
0.716.
B. (BrPh, SPU, add. 1). Distillation range 34.0 °C
and 35.0 °C.
 ASSAY not makes, according to
Pharmacopoeia.
 STORAGE
 Protected from light, in the dense corked
containers , protected from light, at a
temperature not less then 8 °C and not
more then 15 °C.
 Action and use
 General anaesthetic.

Browse: British Pharmacopoeia 2009
SPU, add. 1
 Formaldehyde Solution
 (Formaldehyde Solution (35 per cent), Ph Eur
monograph 0826)
 Formaldehydi solutio (35 per centum)
 FORMALDEHYDE SOLUTION (35 PER
CENT)
 Formalinum
 CH2O
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
30.03
DEFINITION
Content
34.5 per cent m/m to 38.0 per cent m/m of
formaldehyde (CH2O; Mr 30.03).
 It contains methanol as stabiliser.
 OBTAINING
 Methane oxidation:
2 CH4 + O2
2 CH3OH
O2
O
2H
C
 CHARACTERS

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Appearance
Clear, colourless liquid.
Solubility
Miscible with water and with ethanol (96 per cent).
It may be cloudy after storage.
H
+ 2 H2O
 IDENTIFICATION
A. (BrPh, SPU, add. 1). Reaction with chromotropic
acid sodium salt in the sulphuric-acid medium
 Dilute 1 ml of solution S (see Tests) to 10 ml with water R. To 0.05
ml of the solution add 1 ml of a 15 g/l solution of chromotropic acid
sodium salt R, 2 ml of water R and 8 ml of sulphuric acid R. A
violet-blue or violet-red colour develops within 5 min.
SO3H HO3S
SO3Na
HO
+
2
HO
SO3Na
HO
HC
O
H
H2SO4
кон ц.
HO
C
H2
HO
OH
SO3H HO3S
SO3H HO3S
C
H
HO
O
OH
SO3H HO3S
OH
[O]
H2O

B. (BrPh, SPU, add. 1). Reaction with phenylhydrazine hydrochloride and
potassium ferricyanide solution

To 0.1 ml of solution S add 10 ml of water R. Add 2 ml of a 10 g/l solution of phenylhydrazine
hydrochloride R, prepared immediately before use, 1 ml of potassium ferricyanide solution R and 5 ml of
hydrochloric acid R. An intense red colour is formed.
2
N
H
NH2 * HCl +
N
N
C
H2
CH2O
N
- H2O
N
H
N
H
C
H2
N
H
N
H
K3[Fe(CN)6]
N

C. (BrPh, SPU, add. 1). Reaction of “silver mirror”

Mix 0.5 ml with 2 ml of water R and 2 ml of silver nitrate solution R2 in a test-tube. Add dilute ammonia R2
until slightly alkaline. Heat on a water-bath. A grey precipitate or a silver mirror is formed.
 2AgNO3 + 2NH4OH = [Ag(NH3)2]NO3 + 2H2O
 НCНO + 2[Ag(NH3)2]NO3 + H2O = 2Ag + НCOONH4 + NH3 +
2NH4NO3

D. (BrPh, SPU, add. 1). It complies with the limits of the assay.
 ASSAY
 Iodometry in the alkaline medium, back
titration
 I20 + 2 NaOH = NaI-1 + NaI+1O + H2O
 NaI-1 + 1NaІ+1O + H2SO4 = 1I20 + Na2SO4 + H2O
 1I2 + 2Na2S2O3 = 2NaІ + Na2S4O6
 Em(HCHO) = M. m./2
 * Alkaline medium necessary because in the acid medium at
interaction iodine I2 with formaldehyde НСНО iodide acid НI is
formed, which is reducing agent and reaction has back direction.
 STORAGE
 Protected from light, at a temperature of 15 °C to 25 °C.
 Ph Eur
 Action and use
 When suitably diluted, used in the treatment of warts.
 Ph Eur
Thanks for attention!