Lecture "Phenols and amines" on Pharmaceutical Chemistry is devoted by synthesis, physico-chemical properties and analysis of medicinal substances, which are derivatives of phenols and aromatic amines.Also is included examples of tests "KROK-2".

1. National University of Pharmacy
Medicinal Chemistry Department
Medicinal substances,
which are the derivatives of
phenols and aromatic amines
Lecture for 4th
year students of foreign faculty
Lecturer: associate professor Oksana Kamenetska,
PhD

2. Classification of medicinal substances
alicycic
carbocyclic heterocyclic
inorganic organic
cyclic
aromatic
medicinal substances
 phenols;
 aromatic amines;
 aromatic acids;
 aromatic oxy acids;
 aromatic amino acids;
 aromatic sulfo acids
acyclic
(aliphatic)

3. Phenol = aromatic compound that is poisonous
and toxic to tissues.
 Phenol = naturally occurring molecule
 Phenols include carbolic acid or triclosan.
1st used as antiseptic in surgery in 1867.
 Its more common use today is a disinfectant.
Phenols

4. An image of a computed electrostatic surface
of neutral phenol, showing neutral regions in
green, electronegative areas in orange-red,
and the electropositive phenolic proton in
blue.
Phenols are much more acidic than
aliphatic alcohols:
a benzene ring is generally considered
electron withdrawing (inductive effect) , the
benzene ring stabilizes the negative charge
of the phenoxide ion through resonance
Chemical properties of phenols

5. Chemical properties of phenols
• Reactions on the –ОН group:
• Acidic properties :
•able to form salts under the action of alkalis:
OH
+ NaOH
ONa
+ H2O
•Ethers and esters formation.

6. phenols can be oxidized by strong oxidants to give hydroquinones and quinones:
Reactions of reduction and oxidation
Chemical properties of phenols
• halogenation
• nitration
• sulphonation
• alkylation and acylation
• azocoupling
Reactions on an aromatic ring (SE reactions):

7. Medicinal substances
Phenol Resorcinol
Thymol
Antiseptics
Xeroformium
OH
OH
OH
CH3
OH
CH3 CH3
OBr
Br
Br
Bi
OH
O
Br
Br
Br Bi2
O3*
3% Bismuth Tribromophenate

8. Medicinal substances
Antiviral
Oxolin
OH
Cl
NO2
Nitrofungin Phenolphathalein
SO3
HOH
OH
CH3NHCH3 ,
Etamsylate - anticoagulant Levodopa- antiparkinsonic
OH
OH
COOH
NH2
O
O
O
O
H2
O* 2
OH
C
O
O
C
OH

9. Phenol
OH
+ CH2=CH-CH3
CH3
CH3
CH
H3C CH3
C
O2; t=1000
C
H3C CH3
C
O OH
H2SO4
OH
+ H3C CH3
C
O
H
Appearance: colourless or faintly pink or
faintly yellowish, crystals or crystalline
masses, deliquescent.
Solubility: soluble in water, very soluble in
ethanol (96 percent), in glycerol and in
methylene chloride.
3. Sulfonation of benzene.
Obtaining:
1. From coal tar.
2. Partial oxidation of cumene:

10. Identification
• Indophenol test (blue colour):
• Ferric (ІІІ) chloride test (violet colour):
OH OO NHO
OH
NO OH
NaOCl NH3
OH OFeCl2
+ FeCl3 + HCl
OH
Phenol

11. Phenol
OHIdentification
• Test with bromine water (white precipitate):
OH OH
Br
Br
Br+ 3Br2 + 3HBr
OH N
SO3
H
N
Cl
ONa
N N SO3Na
NaOH
+
+
• Azocoupling test: with diazonium salts forms azodye (red or orange colour):

12. ASSAY
• Bromatometry, back titration.
OH OH
Br
Br
Br+ 3Br2 + 3HBr
KBrO3 + 5KBr + 6HCl 3Br2 + 6KCl + 3H2O
s
322322
mV
100VTf)V(V
%
p
vf
main
OSNaOSNa
blank
⋅
⋅⋅⋅⋅−
=
Excess of bromine is determined by iodometry:
Indicator: starch (in the end point the colour dissapears).
Carry out the blank titration (without
examined substance)
S=1
Usage: antiseptic
2KI + Br2 I2 + 2KBr
I2 + 2Na2S2O3 2NaI + Na2S4O6
main titration blank titration
OH
1000
)phenol(Мs)KBrO(C
ml/g,T r3 ⋅⋅
=

14. RESORCINOL
OH
OH
Benzen-1,3-diol
CHARACTERS
A colourless or slightly pinkish-grey, crystalline powder or
crystals, turning red on exposure to light and air, very soluble
in water and in alcohol.
Obtaining: sulphonation of benzene:
сплав
H+
OH
OH
SO2OH
SO3H
SO3H ONa
ONa
H2SO4 H2SO4
NaOH
бензолсульфокислота
м-бензолдисульфокислота
резорцин

15. 1. Melting point 109°С…. 112°С.
2. All typical reactions of phenols: oxidation, substitution, nitration etc.
For example: ferric chloride test (blue colour):
OH
OH
FeCl3
OFeCl2
OFeCl2
H Cl-2
RESORCINOL
OH
OH
Identification

16. RESORCINOLUM OH
OH
Identification
OH
OH
ONa
NaO
CH Cl
Cl
ONa
NaO
C H
O OH
OH
CNaO O
ONa
ONa
NaOONa
OH
OH
OH
OH
OH
OH
CH
NaOH
CHCl3
NaOH
2
HCl
NaOH
3. With conc. NaOH and chloroform:
HCl

17. 4. Test with potassium phthalate – intense green fluorescence forms:
OHOH
H
OHOH
H
C
C
O
O
OK
OH
C
OOH OH
OH
COOK
C
OOH O
COOK
- 2H2O
t 0
- H2O
ОН
RESORCINOLUM OH
OH
Identification

18. ASSAY
• Bromatometry, back titration.
OHOH OHOH
Br
BrBr
5KBr + KBrO3 + 6HCl 3Br2 + 6KCl + 3H2O
+ 3Br2 + 3HBr
Br2 + 2KI I2 + 2KBr
I2 + 2Na2S2O3 2NaI + Na2S4O6
%w)-(100
OSNaKBrO
sp
vf213
mV
100100V)fVf(V
% 322
*
⋅⋅
⋅⋅⋅−
=
•
S=1
Indicator: starch (in the end point the colour dissapears).
Usage: antiseptic
RESORCINOLUM OH
OH
1000
)resorcinol(Мs)KBrO(C
ml/g,T r3 ⋅⋅
=

19. TEST of KROK 2
Qualitative reaction for phenol is the reaction with
bromine water. What compound is produced as
a result of the interaction of phenol with bromine
water and drops out as a white solid?
• A 2,4,6-tribromophenol
• B 2-bromophenol
• C 3-bromophenol
• D 4-bromophenol
• E 2,4-dibromophenol

20. TEST of KROK 2
An analyst of the National drug quality control
inspection carries out quantitative analysis of
“Resorcin" substance by method of
bromatometry (back titration). What indicator is
used by doing so?
• A Starch
• B Ammonium iron (III) sulfate
• C Potassium chromate
• D Phenolphtalein
• E Sodium eozinat

21. TEST of KROK 2
An analytical chemist determines the quantity of a
drug by the method of indirect bromatometry.
Which of the following titrated solutions is to be
used?
• A Sodium thiosulfate
• B Calcium bromate
• C Sodium edetate
• D Sodium nitrite
• E Silver nitrate

22. THYMOL
CH3
OH
CH3 CH3
5-methyl-2-(methylethyl)phenol
Obtaining
1. Found in thyme oil (Thymus Vulgaris).
2. Synthesis from m-cresol:
[H2], Ni
tº
CH3 C CH3
O
(CH3CO)2O
тимолизопропенил-м-крезол
м-крезол
OH
CH3
CHH3C CH3
OH
CH3
CH CH2H3C
CH3
OCOCH3OH
CH3
Appearance: colourless
crystals.
Solubility: very slightly soluble
in water, very soluble in
ethanol(96 per cent), freely
soluble in essential oils and in
fatty oils,sparingly soluble in
glycerol. It dissolves in dilute
solutions of alkali hydroxides.

23. Identification
Physico-chemical methods:
1. Melting point 48 С до 52 С.
2. Infrared spectroscopy.
Chemical methods:
3. Test with NaOH and chloroform: a violet colour develops.
4. Test with mixture of acids: anhydrous acetic acid, sulfuric acid of
nitric acid. A bluish-green colour develops
OH O
CH
OH
NaOH, CHCl3
to
2
OH O
N
OH
O
H2SO4, HNO3
+
-
2

24. Bromatometry.
OH
CH3
CHH3C CH3
+ 2Br2
CH3
BrBr
OH
CH CH3H3C
+ 2HBr
KBrO3 + 5KBr + 6HCl → 3Br2 + 6KCl + 3H2O
s
KBrO
m
100TfV
%
3 ⋅⋅⋅
=
ASSAY
Usage: antiseptic
Thymol extract from the thyme plant was used thousands of years ago by the ancient Egyptians as a
preparation to help preserve mummies. This extract of thyme has now been shown to wipe out fungi and
bacteria.
Clergyman and pharmacist Caspar Neumann discovered the crystalline thymol in 1719. It was synthesized
in its pure form some 134 years later by chemist M. Lallemand. These days thymol is used for a number of
purposes including control of parasites and prevention of mold growth.
1000
)thymol(Мs)KBrO(C
ml/g,T r3 ⋅⋅
=

25. Medicinal substances,
which are the derivatives of
aromatic amines

26. Aromatic amines
OH
N
H
CH3
O
The simplest one is - aniline:
NH2
Chemical properties of aromatic amines are caused by the presence of two
functional groups: aromatic amino group and benzene ring.
Medicinal substances
Paracetamol Lidocaine hydrochloride
OHBr
Br
NH2
CH2
NH
HCl*
Ambroxol hydrochloride
Br
Br
NH2
CH2 N
CH3
HCl*
Bromhexine hydrochloride
H Cl.
CH3CH3
NH C
O
CH2
N
C2H5
C2
H5

27. NSAID

28. NSAID

29. NSAID

30. Acetaminophen
(Paracetamol)
From a historical perspective,
acetaminophen (paracetamol) and the
related analgesic antipyretic drugs such as
acetanilide, antipyrine, and dipyrone
were introduced into the market about the
same time as aspirin and the other
salicylates (i.e., acetanilide, 1886;
phenacetin, 1887; and acetaminophen,
1893).
They were once the most widely used
analgesic antipyretics for relieving pain and
reducing fever because, unlike aspirin and
salicylates, they do not cause ulceration or
increase bleeding time.
OH
N
H
CH3
O

31. PARACETAMOL
OH
N
H
C
CH3
O
N-(4-Hydroxyphenyl)acetamide
Obtaining
Paracetamol is prepared from phenol:
OH OH
NO
NaNO2
H2SO4
H2S; NH3
NH2
OH
CH3COOH
-H2O
OH
NHCOCH3
Appearance: white or almost white,
crystalline powder.
Solubility: sparingly soluble in water, freely
soluble in alcohol, very slightly soluble in
methylene chloride
Paracetamol is part of the class of drugs known as "aniline
analgesics"; it is the only such drug still in use today. It is not
considered an NSAID because it does not exhibit significant anti-
inflammatory activity (it is a weak COX inhibitor). This is despite
the evidence that paracetamol and NSAIDs have some similar
pharmacological activity.
Demand for paracetamol in the United States was estimated at 30–35 thousand tonnes per year in 1997, equal to the
demand from the rest of the world

32. Physico chemical methods
• Melting point168°С…172°С.
• Ultraviolet spectroscopy: the absorption
maximum at 249 nm. The specific absorbance
at the maximum is 860 to 980
Identification
• Infrared absorption spectrophotometry. Comparison: paracetamol CRS.
ClAA 1sm
1%
⋅⋅=
Cl
A
⋅
=1sm
1%
A

33. Chemical methods:
4. Indophenol test after hydrolysis. A violet colour develops
which does not change to red.
NHCOCH3
OH
NH2
OH
NH
O
OH NH2
N
O
NH2
HCl, t C
- CH3COOH
0
K2Cr2O7
5. It gives the reaction of acetyl with lantanum nitrate (2.3.1).
The blue colour develops in presence of iodine:
NHCOCH3
OH
H2O
H+
CH3COOH +
NH2
OH
Identification

34. Reactions on phenol hydroxyl:
6. With ferric (III) chloride; violet colour appears:
OH
NHCOCH3
+ FeCl3
NHCOCH3
OFeCl2
+ HCl
7. Azocoupling reaction: with diazonium salts:
Identification
OH
NHCOCH3
N
R
N
Cl
ONa
NHCOCH3
N N RNaOH
+
+

35. Reactions on aromatic amino group:
8. Azocoupling reaction: formation of azo dye after hydrolysis of
substance.
NHCOCH3
OH
H2O
H+
CH3COOH +
NH2
OH
9. Reaction with aromatic aldehydes: primary arylamines react when
heated with aromatic aldehydes forming azomethines (Schiff bases).
Identification
OH
NH2
C
O
H
R
N CH
OH
R
H Cl
H2 O
+ -
OH
NH2
N
OH
N
Cl
NaOH
NaNO2
H Cl
OH N N
NaO
ONa
KBr
+
2,5

36. 1. Cerimetry (after hydrolysis). Carry out a blank titration;
indicator – ferroin. s=1/2
ASSAY
NHCOCH3
OH
NH2
OH
NH2
OH
NH
O
Ce2(SO4)3
H2SO4
H2SO4 , t0
+ 2Ce(SO4)2 + +;
N
N
3
N
N
3
Ce
3+
3+
Fe Fe
2+
+ Ce4+
red blue
yellow
окраши
+
rate with 0.1 M cerium sulfate until a greenish-yellow colour is obtained:
%w)-(100p..
24.24 100100.)..(
%
)()(
⋅⋅
⋅⋅⋅⋅⋅−
=
Vm
VvfTftbVtmV
analysisfor
SOCeSOCe
1000
)(
/, 24 )( lparacetamoМsC
mlgT
rSOCe ⋅⋅
=

37. ASSAY
2. Nitritometry (s=1).
Usage: over-the-counter analgesic (pain reliever) and antipyretic (fever reducer).
1000
)(
/, 2
lparacetamoМsC
mlgT
rNaNO ⋅⋅
=
%w)-(100..
2
.
2
100100.)..(
%
⋅
⋅⋅⋅⋅−
=
analysisform
TftbVtmV NaNONaNO
NHCOCH3
OH
H2O
H+
CH3COOH +
NH2
OH OH
NH2
N
OH
N
Cl
NaNO2
H Cl
KBr
+
2,5

38. Acetaminophen and other analgesic
antipyretics have similar analgesic and
antipyretic efficacies to the conventional
NSAIDs such as aspirin, ibuprofen, or
diclofenac..
However, unlike the conventional NSAIDs,
they lack the antiplatelet effects of aspirin
or the GI side effects associated with
NSAIDs.
Acetaminophen also has little or no anti-
inflammatory properties.
Acetaminophen
(Paracetamol)

39. ACETAMINOPHEN
is frequently used by
itself OTC (Panadol, Tempra, Tylenol) or in
combination with:
codeine (Tylenol 3),
hydrocodone (Vicodin),
or oxycodone (Percocet)
for the treatment of mild to moderate pain
and to reduce fever. It is available in
several nonprescription forms and is also
marketed in combination with aspirin and
caffeine (Excedrin, Vanquish).
NSAID
Acetaminophen
(Paracetamol)

40. A 26-year-old pregnant woman (III trimester of
pregnancy) complains about body temperature
rise up to 39o
C. What febrifuge may be
recommended in this case?
A Paracetamol
B Aspirin
C Diclofenac
D Analgin
E Indometacin
TEST of KROK 2

41. TEST of KROK 2
Prior hydrolysis is necessary in case of quantitative
determination of the following drug by the
nitritometric titration:
• A Paracetamol
• B Anesthesin
• C Procaine hydrochloride
• D Sodium p-aminosalicylate
• E Dicaine
NHCOCH3
OH
H2O
H+
CH3COOH +
NH2
OH
OH
NH2
N
OH
N
Cl
NaNO2
H Cl
KBr
+
2,5

42. Local anesthetics
Local anesthesia involves numbing a specific part of the body to
prevent any feeling of pain during surgical procedures.
An anesthetic drug - which has numbing effects - is applied to a
certain part of the patient's body.

45. Local anesthetics
All local anesthetics consist of 3 principal components, each contributing a distinct property:

46. Lidocaine (hydrochloridum)
2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide
hydrochloride monohydrate
Appearance: white or almost white, crystalline powder.
Solubility: very soluble in water, freely soluble in ethanol (96 per cent).
Obtaining: Lidocaine may be prepared in two steps by the reaction of 2,6-xylidine with chloroacetyl
chloride, followed by the reaction with diethylamine:
CH3H3C
NH2
ClCH2COCl
CH3COOH
CH3H3C
NHCOCH2Cl
(C2H5)2NH
C6H6, HCl
. HCl
CH3H3C
NHCOCH2 N(C2H5)2
H Cl.
CH3CH3
NH C
O
CH2
N
C2H5
C2
H5

47. Identification
Physico chemical methods:
1. Melting point 74°С to 79°С.
2. Infrared absorption
spectrophotometry.
Comparison: lidocaine hydrochloride
CRS.
Chemical methods:
3. Formation of aci-nitro form salt. A green colour develops:
NH
CH3
CH3
C
O
CH2 N
C2H5
C2
H5
NH2
CH3
CH3
NO2
CH2
N
C2
H5
C2H5
COOH
NH
CH3
CH3
N
O OK
HNO3, t C
o
KOH
(alcoholic solution)-
- +

48. 3. Reaction with picric acid. The obtained precipitate has melting point
about 230С.
5. Reaction of lidocaine base with Co2+
: a bluish-green precipitate is produced
NH
CH3
CH3
C
O
CH2
N
C2
H5
C2
H5
H Cl NaOH
NH
CH3CH3
C
O
CH2 N
C2H5
C2H5
H 2
ONaCl
.
CH3
CH3
NH C
O
CH2 N
C2H5
C2H5
CH3
CH3
N C
O
CH2
N
C2H5
C2H5
CH3
CH3
N C CH2
N
C2
H5
C2H5
O
Co
Co(NO3)2
++
2
Identification
NH
CH3CH3
C
O
CH2
N
C2H5
C2
H5
OH
NO2
NO2O2
N
NH
CH3
CH3
C
O
CH2 N
C2
H5
C2H5
OH
NO2
NO2O2
N
.
H Cl
H Cl.
+
-

49. Identification
6. It gives reaction (a) of chlorides.
7. It gives reactions on aromatic amino group: azocoupling and
formation of azomethines (after hydrolysis of substance).
ClCl--
+ AgNO+ AgNO33 →→ AgClAgCl↓↓ + NO+ NO33
--
AgClAgCl↓↓ + 2NH+ 2NH44OHOH →→ [Ag(NH[Ag(NH33))22]Cl + 2H]Cl + 2H22OO
dil. HNOdil. HNO33
NH
CH3
CH3
C
O
CH2
N
C2H5
C2H5
H Cl
H2 O
NH2
CH3CH3
NaNO2
H Cl
N
CH3CH3
N
Cl
.
OH
NaOH N
CH3
CH3
N
NaO
H
+
+

50. ASSAY
. Alkalimetry. Carry out the potentiometric titration.
HCl +NaOH →NaCl +H2O
NH
CH3CH3
C
O
CH2 N
C2H5
C2H5
H Cl NaOH
NH
CH3
CH3
C
O
CH2
N
C2H5
C2
H5
H 2ONaCl.
C2H5OH
++
+
S=1
%w)-(100p..
100100
%
⋅⋅
⋅⋅⋅⋅
=
Vm
fKV
analysisfor
NaOH
1000
)/()(
/,
hydrochllidМsNaOHC
mlgT r⋅⋅
=

51. ASSAY
2. Acidimetry (non-aqueous titration).
3. Nitritometry after hydrolysis.
Usage: local anesthetic and antiarrhythmic
NH
CH3
CH3
C
O
CH2
N
C2
H5
C2
H5
H Cl
H2
O
NH2
CH3
CH3
NaNO2
H Cl
N
CH3
CH3
N
Cl
. H
+
+
4. Argentometry.
1000
)/()(
/, 2 hlМsNaNOC
mlgT r⋅⋅
=
%w)-(100p..
100100
%
⋅⋅
⋅⋅⋅⋅
=
Vm
fKV
analysisfor
NaNO2

52. Lidocaine, is a local or topical anesthetic.
Lidocaine has been in the market since 1948, and is available over the counter,
which means no doctor prescription is needed to buy it or use it.
Lidocaine is used for a variety of medical conditions, and is often one of the
drugs
included in first-aid kits in the form of a combination antibiotic/pain relieving
cream.
Sprays for treating sunburn, insect bites, or poison iv often include lidocaine as
the main ingredient.
Lidocaine gel is often used in dental procedures as a way of numbing the area
before applying an injection, or to reduce pain after the procedure is finished.
USAGE OF LIDOCAINE

53. Modern local anesthetics
NH
CH3CH3
C
O N
NH
CH3
CH3
C
O N
Ropivacain
Bupivacai
n
NH
CH3CH3
C
O N
Mepivacain

55. Toxicity of local anesthetics

56. 0n n
c
F
−
=
20 1000
D
a
[ ]
l c
α
×
=
×
value device method application formula
Refractive
index n
refractometer refactometry
purity
identification
assay
Angle of
rotation
Specific
optical
rotation
[ἀ]20
d
polarimeter for optical
active
substances
polarimerty purity
identification
assay
Melting point
Tmp
capillary
method
purity
Identification
for solid organic
compounds
Relative
density
ῤ
areometer
pyknometer
for liquid organic
compounds
purity
Identification

57. A= A1%
1cm*l*C
%1
1смА
A
c =
0
0
А
CA
C
⋅
=
value device method application formula
optical
absorbance
spectro
photometer
spectro-
photomerty
(UV, visible)
Identification
assay

58. Impurity
(admixture)
Main reagent Additional
reagent
observations reaction
Cl-
Silver nitrate
AgNO3
Nitric acid
HNO3
White ppt
opalescence
SO4
2-
Barium chloride
BaCl2
Acetic acid
CH3COOH
White ppt
opalescence
Ca2+
Ammonium oxalate
(NH4)2C2O4
Acetic acid
CH3COOH
White ppt
opalescence
K+
Sodium
tetraphenylborate
NaB(C6H5)4
White ppt
opalescence

59. Impurity
(admixture)
Main reagent Additional
reagent
observations reaction
NH4
+
(A) Potassium
tetraiodomercur
ate
- yellow
NH4
+
(B) Silver-manganese
paper
- grey
As (A) Mercury bromide
paper
yellow
As (B) Sodium
hypophosphorus
brown

60. 34. A chemist of an analytic laboratory has to
prepare turbidity standards according to the
requirements of Pharmacopoeia. What
substances are to be used as the
reference?
A Hexamethylenetetramine and hydrazine sulphate
B Calcium sulphate and glycerin
C Sodium chloride and calcium nitrate
D Potassium chloride and barium sulphate
TEST OF KROK-2

61. TEST OF KROK-2
24. An analytical chemist determines the
admixture of sulphates in the boric acid.
What is the main reagent to be added?
• A Barium chloride
• B Sodium sulphide
• C Potassium ferrocyanide
• D Silver nitrate
• E Ammonium oxalate

62. TEST OF KROK -2
Chemist of the technical control department determines
the sodium cation in the substance in accordance to
Pharmacopoeia with the solution of:
А potassium pyroantimonate
В potassium chloride
С potassium ferrocyanide
D potassium hydroxide
Е potassium nitrate
a) witha) with ppotassiumotassium pyroantimonatepyroantimonate solutionsolution::
Na+
+ K[Sb(OH)6] → Na[Sb(OH)6]↓ + K+

63. TEST OF KROK -2
For identification of medicinal substance containing
a carbonate-ion, in obedience to the requirements
of SPh of Ukraine, a pharmacist-analyst must use
solution:
A dilute acetic acid
B ammonium oxalate
C potassium iodide
D sodium hydroxide
E sodium chloride

64. • A pharmacy analyst identifies sodium
hydrocarbonate. What indicator can confirm
the presence of alkalescent medium reaction
in the sodium hydrocarbonate solution?
• A Phenolphtalein
• B Starch
• C Tropeolin 00
• D Ferroin
• E Naphtholbenzein
TEST OF KROK -2

65. TEST of KROK-2
• One of the reactions of calcium identification
in accordance to Pharmacopoeia is the
reaction with:
• А glyoxalhydroxyanile
• В hydroxiquinoline
• С hydroxileamine
• D alizarine
• Е sulphuric acid
•

66. • In the medicinal preparations the calcium
cation can be determined with the help of
• А sodium nitrite
• В silver nitrate
• С potassium permanganate
• D ammonium oxalate
• Е sodium chloride
TEST of KROK-2
Ca2+
+ C2O4
2-
→↓CaC2O4

67. TEST of KROK-2
• According to the requirements of the
Ukrainian State Pharmacopoeia, a certain drug
is being measured by method of chelatometric
titration. What drug is it?
• A Calcium chloride
• B Potassium citrate
• C Potassium chloride
• D Sodium benzoate
• E Sodium thiosulfate

68. TEST of KROK-2
• Choose the reagent that is used during the
identification of iron (II) ions in accordance to
Pharmacopoeia.
• А lanthanum nitrate solution
• В ammonia
• С potassium ferricyanide solution
• D sodium hydroxide solution
• Е silver nitrate solution
•

69. TEST of KROK-2
• An analytical laboratory has to analyze ferrous
sulfate heptahydrate according to the State
Pharmacopoeia of Ukraine. A test portion of the
substance should be titrated with the following
solution:
• A Ammonium cerium sulfate
• B Silver nitrate
• C Ammonium thiocyanate
• D Sodium edetate
• E Potassium bromate

70. TEST of KROK-2
• A pharmacy analyst is measuring mercury dichloride
by method of indirect chelatometry. Excess of
titrated solution of sodium edetate can be titrated by
means of the following titrated solution:
• A Zinc sulfate
• B Sodium hydroxide
• C Sodium thiosulfate
• D Potassium bromate
• E Sodium methylate

71. 71
Test of «Krok-2»• In order to identify a polyatomic alcohol glycerol a pharmacy analyst
carries out dehydration reaction with potassium hydrogen sulphate. The
generated hereat product has a strong characteristic smell and gives grey
colour to the filter paper moistened with
alkaline potassium tetraiodomercurate solution.
What product is it?
A Diethyl ether
B Acrolein
C Acetic acid
D Ethanol
E Chloroform
CH2
OH
CH2
OH
KICHOH
KOH
C H
O
CH
K2HgI4
CH2
O
CH2
CH ++ 2+ OHg H
C OK
,2KHSO4
2
t
acrolein

72. 72
Test of «Krok-2»
• According to SPhU, formaldehyde can be identified when a
sample is reacted with chromotropic acid solution in the
presence of concentrated sulfuric acid. What colour is formed
by this reaction?
A Violet
B Yellow
C Blue
D Green
E Brown
OH
SO3H
SO3H
OH
C
HO3S
OH
HO3
S
OH
H H
HO3S
O
HO3S
OH
OH
SO3H
SO3H
OH
CH
OH
SO3Na
SO3Na
OH
H
O
C
H H
OH
NaO3S
NaO3S
OH
H
- H2O
[O]:
H2SO4
H2SO4
chromotropic acid
sodium salt

73. 73
Test of «Krok-2»
• A pharmaceutical analyst identifies the substance
of potassium acetate. What reagent confirms the
presence of potassium cation in the substance?
A Tartaric acid
B Sodium hydroxide
C Potassium permanganate
D Iron (III) chloride
E Zinc oxide
white pptwhite ppt
CH
CH
OH
OH
COOH
COOH
CH
CH
OH
OH
COOH
COO
K
+
H
+
K
+ +
CHCH33COOKCOOK

74. 74
Test of «Krok-2»
• An analytical laboratory is studying substance of
calcium lactate. In presence of ammonium chloride
calcium cation forms white crystalline precipitation
with the following reagent:
A Potassium permanganate
B Sodium chloride
C Potassium ferrocyanide
D Sodium tetraborate
E Sodium cobaltnitrite
C
H
OH
CCH3
O
O
2
Ca-
2+
. 5 H2O
CaCa2+2+
+ 2+ 2NHNH44ClCl ++ KK44[[FeFe((CNCN))66]] →→ ((NHNH44))22CaCa[[FeFe((CNCN))66]]↓↓ + 4+ 4KK++
+ 2+ 2ClCl--

75. 75
Test of «Krok-2»
• An analytical laboratory received calcium
gluconate for analysis. What method is used for its
quantification?
A Chelatometry
B Bromatometry
C Iodometry
D Mercurimetric determination
E Nitritometric determination
chelatometric method =
compexonometric method
C
H
COOC
H
C
H
OH OHOH
C
H
OH
CH2
OH
2
Ca
- 2+

76. 76
Test of «Krok-2»
• Calcium lactate can be quantitatively determined
by chelatometric method. According to the
Ukrainian State Pharmacopoeia, the following
substance should be used as indicator:
A Calconcarboxylic acid
B Diphenylcarbazone
C Naphtholbenzein
D Phenolphthalein
E Tropeolin 00
C
H
OH
CCH3
O
O
2
Ca-
2+
. 5 H2O

77. 77
Test of «Krok-2»
• According to the requirements of the Ukrainian
State Pharmacopoeia, a pharmacy analyst is
determining calcium gluconate quantity by method
of complexometric titration. What indicator is to
be used?
A Thymolphthalein
B Methyl red
C Crystal violet
D Calconcarboxylic acid
E Tropeoline 00
C
H
COOC
H
C
H
OH OHOH
C
H
OH
CH2
OH
2
Ca
- 2+

78. 78
Test of «Krok-2»
• According to the requirements of the Ukrainian
State Pharmacopoeia, the amount of calcium
gluconate can be determined by the chelatometric
method. What solution should be used as a
titrant?
A Sodium edetate
B Potassium permanganate
C Iodine monochloride
D Argentum nitrate
E Hydrochloric acid
C
H
COOC
H
C
H
OH OHOH
C
H
OH
CH2
OH
2
Ca
- 2+

79. 79
Test of «Krok-2»
• An analytical laboratory carries out quantitative
analysis of sodium citrate by method of ion-
exchanging chromatography on a cationite. What
titrated solution is to be used for the following
titration of generated citric acid?
A Iodine
B Sodium hydroxide
C Potassium iodate
D Hydrochloric acid
E Trilon B
CH2
C
CH2
OH
COONa
COONa
COONa . 2H2O
+ H 2OH+ NaOH
CH2
CH2
COONa
COONaO
COONa
H
CH2
CH2
O
COOH
COOH
COOH 33

80. 80
Test of «Krok-2»
• An analytical laboratory received substance of
citric acid for the analysis. According to the
requirements of the Ukrainian State
Pharmacopoeia, citric acid can be determined by
method of:
A Acidimetry
B Iodometry
C Alkalimetry
D Bromatometry
E Iodochlorometry
CH2
C
CH2
OH
COOH
COOH
COOH
+ H 2OH+ NaOH
CH2
CH2
COONa
COONaO
COONa
H
CH2
CH2
O
COOH
COOH
COOH 33

81. 81
Test of KROK-2
• In order to identify a drug an analytical chemist of the State
Inspectorate for Quality Control of Medicines carries out the
reaction with ninhydrin solution. Specify the drug to be
identified:
A Paracetamol
B Methionine
C Cortisone acetate
D Streptocide
E Ascorbic acid
O
O
O
+ H N H
H
+
O
O
HO H2O
N
O
O O
HO
NH3
O
ONH4
N
O
O
аммонийная соль дикетогидринденкетогидрина
(в енольной форме); сине-фиолетовое окрашива
+ NH3 + CO2R C
O
H
+
O
O
OH
tº. H2OO
O
O
CH COOH
NH2
+ R
O
O
O
+ H N H
H
+
O
O
HO H2O
O HO ONH4O
+ NH3 + CO2R C
O
H
+
O
O
OH
tº. H2OO
O
O
CH COOH
NH2
+ R
+ NH3 + CO2R C
O
H
+
O
O
OH
tº. H2OO
O
O
CH COOH
NH2
+ R + NH3 + CO2R C
O
H
+
O
O
OH
tº. H2OO
O
O
CH COOH
NH2
+ R
S CH2
CH2
C
H
O
CH3
blue-violet colour
ninhydrin
CH3 S CH2CH2 CH C
O
NH2
OH

82. 82
Test of KROK-2
 An analytical laboratory received a sample of alpha-
aminobutyric acid for analysis. What reagent should be
used by the analyst in order to identify this substance?
A Aniline
B Sodium nitrate
C Benzene
D Ninhydrin
E Calcium bromide
α-Aminobutyric acid