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Lecture №25
Alkaloids indol’s derivatives, purine
alkaloids and their salts; some
synthetic analogues according to
the biological action as substances
of the medical drugs and
components of the dosage forms.
Ass. Medvid I. I.
Indole - condensed system of pyrrole and
benzene cycles which have two share
atoms:
Indole is a structural basis of physostigmine,
strychnine, reserpine alkaloids.
Group reaction on indole derivatives –
Van-Urk’s reaction
In the base of reaction is the process of electrophyllic
substitution. Reagent p-dimethylaminobenzaldehyde.
Reaction conducts at the presence of conc. H2SO4 and
FeCl3 as oxidant.
Derivatives of indole which have free 2 and 3 positions
give this reaction. Reserpine gives this reaction by the
opening of ring C in the presence of acids, as a result
position 2 becomes free.
Product of reaction can exist in 2 forms. Color of the
reaction product depends on the chemical structure of
primer compounds conditions of the reaction. Van-Urk’s
reaction can be hold with another aldehyde. So, for
reserpine solution of vanillin in chloride acid is used.
Physostigmine salicylate
(Physostigmini salicylas)
Eserini salicylas
CH3
H3C
N
H
C
O
COOH
O
*
N
N
CH3
CH3
OH
Salicylate of ester of methylcarbaminic acid and eseroline or
5-methylcarbaminoiloxy-1,3,1’-trimethyl-2,3,2’,3’tetrahydropyrrole indole
Physostigmine– the
main alkaloid of
calabaric beans (Faba
calabarica) –
poisonous seeds of
West African plant
Physostigma
venenosus , Fabaceae
Physical properties
Physostigmine salicylate - brilliant colorless or
almost colourless prismatic crystals. Soluble in water,
easily soluble in alcohol, practically insoluble in ether.
Aqueous solutions are unstable. It melts at about 182 °C,
with decomposition Optic active compound. When heated
with water easy hydrolyze and therefore its solutions for
parenteral usage produce in aseptic introductions. On the
air and light product paints in the red color –
pharmacological inactive rubrezerine formed.
Pharmacological action cased by the methylurethane group.
Proserine - white crystalline powder with bitter taste. Very
easily soluble in water, easily soluble in alcohol and
chloroform, ether. Hygroscopic. Becomes pink on the
light.
Identification of Physostigmine salicylate
1.
2.
3.
4.
5.
6.
Melting point, the specific rotation.
Substance gives reaction to salicylates (2 reactions in
SPU).
Total Pharmacopeial reaction on alkaloids (with
Dragendorff's reagent)
After evaporation of the preparation with ammonium
forms blue residue (physostigmine base), which is
dissolved in ethanol with formation of a blue solution
which after the acidification by СН3СООН becomes red.
Drug solution in H2SO4 conc. gradually becomes yellow.
Erdman and Frede reagents with medication give reddishyellow color, with HNO3 conc. – yellow color.
7. When heated with alkalis (and gradually when heated with
water) physostigmine salycilate hydrolyzed and appears
character odor methylamine:
8. At the heating with 0,1 % ninhydrine solution in conc.
H2SO4 on the water bath at 60 0С during 10 min. And than
after cooling solution have green fluorescence. Proserine
gives blue fluorescence at this conditions.
9. At the gradually adding to the solution boric acid, 0,1 М
solution of nitrate acid and sodium nitrite, after 1 min. add
sodium hydroxide solution, violet color appears.
Assay
Physostigmine salicylate
1. Alkalimetriya, direct titration . The drug is dissolved in
2.
3.
a mixture of ethanol and chloroform and titrated by 0,1 М NаОН
to the pink color (indicator – phenolphthalein). Е = М.m.
Acidimetry in non-aqueous medium. The drug is dissolved in a
mixture of chloroform and conc. CH3COOH, titrated by 0,1 М
НClО4. For determination of the end-point use potentiometry.
Equivalent point is fixed by potentiometric method. Е = М.m./2.
Complexonometry, reverse titration. As a stable titrant aceticacidic solution of bismuth nitrate is used in the presence of
potassium iodide. Scheme of reaction:
Product of the interaction is filtrated and an excess of reagent is
titrated by 0,1 М sodium EDTA solution. Е = М.m.
STORAGE and USAGE of Physostigmine
salicylate
In an airtight containers of dark glass, protected from
light. Poison compound.
Cholinesterase inhibitor, myotic mean (atropine
antagonist). Used for the treatment of glaucoma as
0,25-1% eye drops. Introduce subcutaneous 0,1% 1,0 solution the neuromuscular diseases (Alzheimer's
disease). H. d. – 0,0005 g, H. d. d. – 0,001 g.
Synthetic substitute of
physostigmine
Proserine (Proserinum)
Neostigmine methylsulfate*
H3C
+
N
C
H3C
O
O
N
CH3
CH3
CH3
CH3SO4-
N-(m-dimethylcarbamoiloxiphenyl)-N,N,Ntrimethylammonium methylsulfate
Identification of proserine
Reaction to methylsulfate-ion. If after heating the
drug with HNO3 conc. add solution of BaCl2,
white precipitate falls (BaSO4).
2. With a solution of iodine preparation forms brown
sediment of periodide.
1.
3. At the heating of drug with alkali dissolution of
urethane
group
takes
place
(mdimethylaminophenol formed, which is detected
by the condensation with diazotative sulfanylic
acid – cherry-red color (azo-dyes)):
Assay
The modified K'yeldal method. The drug is boiled in a
K'yeldal flask with NaOH. Dimethylamine, which
evaporates, distilled with water vapor in the receiver
with a solution of boric acid. Metaborate and tetraborate
of dimethylamine formed, which are titrated by 0,1 М
solution of HCl (mixed indicator). Е = М.m.
STORAGE and USAGE of proserine
In an airtight containers of dark glass, protected from
light. Poison compound.
Substitute of physostigmine.
Anticholinesterase, antimyasthenic mean. Curare
antagonist drugs. Used for treatment of
myasthenia, paralysis, neuritis, atony of intestine
and urinary bladder, glaucoma, for stimulating
labor activity as 0,25-1% as eye drops.
Issue – tablets 0,015 g, amp. 0,05%-1,0.
H. d., internally – 0,015 g, H. d. d., internally –
0,05 g; H. d. subcutaneous – 0,002 g, H. d. d. s/c –
0,006 g.
Strychnine nitrate (Strychnini nitras)
1
2
6
A
3
4
5
O
Cycles АВ, BD, ED – derivatives
of indole.
18 Cycle А – aromatic and strychnine
17
E
can be nitrated and halogenated.
N
16
19
N19 – tertiary atom, has a base
15
7
F
D
B
character and gives salts with
8
14
20
acids.
N9
13
21
N9 – is in the lactam group, which
C
G
10
12
22
may be disclosed by the
11
23
O
interaction with alcohol solution
* HNO3
of KOH with formation of
carboxyl and secondary aminogroups.
Strychnine can
be found with
brucine in the
seeds of tropical
plant Strychnos
Nux Vomica
(emetic nut)
Reserpine (Reserpinum)
N
H3CO
N
H
OCH3
H3COOC
O
OCH3
C
OCH3
O
OCH3
11,17-dimethoxy-16-carbmethoxy-18(3’,4’,5’,trimethoxibenzoyloxy)-alloyohimban
Reserpine molecule contains indole (АВ),
dihydroquinolysidine (СD),
partially hydrogenated 3-carbolynic (АВС), hydrogenated
isoquinoline (ED) cycles.
6
9
10
8
A
11
12
B
13
5
7
1
C
2
N
H
3
4
N
21
D
14
Alloyohiban
20
19
15
E
Àë î é î õ³ì áàí
16
17
18
Reserpine
contains in the
roots of the
plant
Rauwolfia
serpentina
Benth
Physical properties
Strychnine nitrate - a colorless brilliant crystals with very
bitter taste. Difficultly soluble in water and alcohol, easily
soluble in boiling water, practically insoluble in ether.
Reserpine - colorless, white or slightly yellow, small
crystals or crystalline powder with melting point 261265°С. Insoluble in water, soluble in chloroform, acetone,
pyridine and ether, darkening slowly on the exposure to
light. Optic active compound. At the heating with acids or
alkalis hydrolysis takes place (reserpinic acid, methanol,
trimethoxybenzoic acid form).
Identification of strychnine nitrate
1. Pharmacopeial reaction on alkaloids.
2. Solution of the drug in H2SO4 conc. + crystal of K2Cr2O7 –
formed the blue-violet strips which pass into the red and
lilac-green.
3. Vitali-Moren’s reaction. At the interaction with HNO3
conc. drug becomes yellow (as opposed to brucine, which
becomes blood-red) by nitration of benzene cycle А; after
the evaporation of reaction product the residue gives with
alcohol solution of КОН formed red-violet color.
4. Van-Urk’s reaction (on indole cycles). With 1% vanillin
in glycerol in the presence of H2SO4 dil. Pink-violet
color appears.
5. Reaction on nitrate ions NO3–-:
а) SPU. The interaction with nitrobenzene in the presence of sulfate
acid
Quantity of substance, listed in a separate article, add to the mixture of
0,1 ml of nitrobenzol R and 0,2 ml of sulfate acid R and after 5 min.
cooled in ice water. Continuing to cool slowly and while stirring
add 5 ml of water R, 5 ml of sodium hydroxide concentrated
solution R NaOH, 5 ml of acetone R, shake and put for standing; the
apper layer becomes dark purple.
b) SPU, N. Not discolors potassium permanganate
The solution of the substance, acidified by acid sulfate diluted R
H2SO4, not discolors solution of 1 g/l potassium permanganate R
(difference of nitrite ).
с) Not pharmacopeial reaction. Interaction with iron (ІІ) sulfate
FeSO4 in the medium of conc. H2SO4; brown ring is formed
(FeSO4NO) (on the clock glass ):
2 Strychnine•НNO3 + 6FeSO4 + 4H2SO4 = 2NO + 3Fe2(SO4)3 +
(Strychnine)2•Н2SO4 + 4H2O
NO + Fe2+ + SO42–  [Fe(NO)]SO4
d) Unpharmacopeial reaction. Interaction with
diphenylamine in acidic medium. (conc. H2SO4),
formed an bright blue organic dye:
2
NH
H2SO4
+ NO2
NH
NH
H2SO4
diphenylbenzidine
+
N
N
HSO4
H
Sulfimmonium salt of diphenylbenzidine (blue dye)
Identification of reserpine
1. Specific optical rotation (6 assymetric carbon
atoms).
2. UV-spectroscopy (chromophor groups – indole
and trimethoxybenzoatic acid – 2 maximum of
absorption on UV-spectrum).
3. Reactions of indole cycle. With chloric water –
purple, with KMnO4 – dark lilac, with vanillin in
the presence of HCl - pink, with Н2О2 – yellowlilac color.
4. Water solutions of reserpine in UV-light – blue
fluorescence.
5. Alcohol solution of the preparation + H2SO4 +
NaNO2 – green fluorescence.
6. With Frede reagent – red color, which goes to the
blue.
7. On ester groups:
а) alkali hydrolysis;
б) hydroxame sample.
8. Van-Urk’s
reaction.
With
pdimethylaminobenzaldehyde
+
H2SO4 +
СН3СООН – green coloring that goes into the
red. With vanillin in chloride acid – pink color.
Assay
Strychnine nitrate – Alkalimetry, direct titration.
Titration of the drug in alcohol-chloroform solution
of 0,1 М NaOH (phenolphthalein indicator).
Е = М.m.
Specific additive - brucine.
Reserpine – Acidimetry in non-aqueous medium.
Hatch is titrated in the medium of anhydrous
СН3СООН by 0,1 М solution HClO4 (indicator
crystal violet) to the appearance of green color. Е =
М.m.
Storage, usage
Reserpine
Strychnine nitrate
In airtight containers, in a dark
In airtight containers.
place. Powder - poisonous
Poison compound.
substance.
Neuroleptic , treatment of
CNS stimulant, tonic
hypertension. Included in
mean.
tablets: Adelphane (0.1 mg of
Issue - amp. 0,1%-1,0.
reserpine,10 mg of
dihydralasine), Adelphan –
H. d. s/c – 0,002 g;
H. d. d. s/c – 0,005 g. esidrex (Triresid) (Adelfane +
10 mg of dichlorothiazide),
Adelphane – esidrex -К
(Triresid К)(0,6 g of КСl),
Crystepin, Neocrystepin.
Raunatine–the amount of
Rauwolfia alkaloids.
Alkaloids, purine derivatives
Purine –condensed system of pyrimidine and imidazol
If in the core of purine hydrogen atoms in the pyrimidine
nucleus replaced by hydroxyl groups, we will get xantine :
Caffeine is contained in coffee beans (Coffea
arabica), tea leaves (Thea sinensis), cola (Cola
acuminata)
Pharmacology
Caffeine stimulates the central nervous system first
at the higher levels, resulting in increased alertness and
wakefulness, faster and clearer flow of thought,
increased focus, and better general body coordination,
and later at the spinal cord level at higher doses. Once
inside the body, it has a complex chemistry, and acts
through several mechanisms as described below.
Metabolism and half-life
Theophylline first
was isolated from
tea leaves (Thea
sinensis)
Theobromine is extracted
from cocoa beans
(Theobroma cacao)
Three natural alkaloids, derivatives
xantine: caffeine, theophylline,
theobromine:
Extracted from semi-synthetic uric acid,
guanine and urea.
Very convenient is the method of extraction of caffeine
and theobromine from xantine, which can be extracted
from uric acid (waste poultry farms) and guanine (fish
flakes, waste of paper):
Synthesis of caffeine and theophyllin by method
Hmelevskiy - Abramova( firs was synthesed by Traube
in1900 year).
Caffeine Medications
• Caffeine (Соffеіnuт) ,
Caffeine monohydrate
(Соffеіnuт
monohydricum) (SPhU)
• Caffeine-sodium
benzoate (Coffeinumnatrii benzoas)
O
O
O
C
H3C
N
H3C
N
N
CH3
O
O
N
N
N
CH3
1,3,7-Trimethyl-3,7-dihydro- 1Hpurine-2,6-dione
1,3,7-trimethylxantine
CH3
*
N
CH3
N
ONa
Physical properties
Caffeine - White or almost
Caffeine-sodiume
white, crystalline powder or
benzoate – white powder,
silky crystals, sublimes readily. odorless, bitter taste.
Moderately soluble
Easily soluble in water,
slightly soluble in ethanol.
in water, freely soluble in
Contains 38-40% caffeine.
boiling water, slightly soluble
in ethanol and ether. Soluble in Extracted by the mixing and
evaporation to the dry state
the concentrated solutions of
of aqueous solutions
alkali benzoate or salicylates.
containing equimolar
Very weak base, forms
quantity of caffeine and
unstable salts with acids by
sodium benzoate.
nitrogen in position 9.
General Pharmacopeial reaction - a reaction
on xantines (Murexide reaction or reaction on
purine alkaloids):
Identification of caffeine
1.
2.
3.
4.
5.
6.
By the physico-chemical constants: melting point, IRspectroscopy.
With potassium iodide in iodine in the presence of HCl dil.brown precipitate formed(periodide С8Н10N4О2•J2•HJ), which
dissolves in NaOH dil. solution at the neutralization.
Murexide sample.
Unpharmacopoeial reaction - with 1% solution of tannin – white
precipitate dissolved in excess of reagent.
With HgCl2 – white crystalline sediment, which is a complex
compound with the following content C5H10N4O2· HgCl2.
With acetylacetone and dimethylaminobenzaldehyde. Solution of
the substance in a mixture of acetylacetone and dil. NaOH heated
in a water bath, cooled, than add solution of
dimethylaminobenzaldehyde and heat again, cool and add water appears an intense blue color:
Caffeine monohydrate gives all reactions on
caffeine after a preliminary drying at 100-105 ° C.
Identification of caffeine-sodium
benzoate
1. Caffeine identify by:
a) melting temperature (234-237 ° C) after extraction
by chloroform from alkaline solution;
b) Murexide sample;
c) reaction with 1% solution of tannin;
d) reaction with iodine solution;
2. Sodium benzoate identify by:
e) the reaction with solution of iron (III) chloride pink-yellow sediment;
f) the sodium cation paints the flame in yellow color.
Assay
Caffeine
1.
2.
3.
Acidimetry in non-aqueous
medium in a mixture of acetic 1.
acid anhydrous, acetic
anhydride and toluene, a direct
titration. Potentiometric
indication, the control
2.
experiment (Е=М.m).
Iodometry, reverse titration,
indicator - starch (Е=М.m/4).
Cerimetry, reverce titration,
with iodometric ending. An
excess of cerium is neutralized
by potassium iodide solution.
Sodium thiosulfate used as
titrant. (Е=М.m/4).
Caffeine-sodium
benzoate
Caffeine content is determined by
iodometric method (Е=М.m/4). ).
In the dry matter it should be
38,0 - 40,0 %.
Sodium is determined in the
presence of mixed indicator
(methyl orange solution and
methylene blue at a ratio of
1:1) and ether (for the
extraction of benzoic acid,
available in the titration)
(Е=М.m). Sodium benzoate in
the dry matter must be not less
than 58,0 % and not more than
62,0 %.
Cerimetric determination of caffeine
O
H 3C
O
N
O
N
N
CH3
+ 4 Ce(SO4)2 + 3 H2O
N
H 2N
C
N
H
CH3 +
O
CH3
O
H3C
N
+
+ 2 Ce2(SO4)3 + 2 H2SO4
O
N
O
CH3
2 Ce(SO4)2 + 2 KI  I2 + K2SO4 + Ce2(SO4)3
I2 + 2 Na2S2O3  2 NaI + Na2S4O6
Storage, Usage
Caffeine
In a dry, dark place.
Central nervous system stimulant,
cardiotonic mean, at the
angiospasms; enuresis in
children; stimulant of mental
and physical disability,
poisoning with drugs. Produced
as powder.
Caffeine monohydrate is part of
the tablets: Theophedrine,
Cytramone, Cytropak,
Askofene, Cofficyll,
Cophetamine, Benalgin,
Coldrex, Solpadein, Panadolекстра. Apply in doses by
0,05-0,1 g as CNS stimulant.
Caffeine-sodium
benzoate
In a dry, dark place.
Central nervous system
stimulant, cardiotonic
mean. Thanks to the
solubility in water used in
the form of injection
solutions. Issue - powder,
tablets 0,1 and 0,2 g, 0,075
g (for children); 10% і 20%
solutions in amp. by 1,02,0 ml. Included in the
tablets: Anaprylline,
Pentalgin.
• Theobromine
Theobrominum
(SPhU)
• Theophylline
monohydrate
Theophyllinum
monohydricum (SPhU)
O
O
HN
N
CH3
H3C
N
NH
* H 2O
O
N
CH3
N
O
N
N
CH3
1,3-Dimethyl-3,7- dihydro-1Н3,7-Dimethyl-3,7- dihydropurine-2,6-dione
1Н-purine-2,6-dione, or
monohydrate, or monohydrate
3,7- dimethylxantine
of 1,3- dimethylxantine
Properties
Theobromine
Theophylline
White crystalline powder, White crystalline powder.
with bitter taste. very
Sightly soluble in water,
slightly soluble in water, ethanol and chloroform;
easily soluble in hot water;
ethanol ,ether and
soluble in dil. Solutions of
chloroform; slightly
acids and alkalis.
soluble in hot water;
easily in dil. Solutions of
alkalis and acids.
Theobromine and theophylline - amphoteric
compounds with a predominance of acidic
properties (by moving the hydrogen atom at the
nitrogen atom in position 1 or 7).
Identification of theobromine
1.
2.
3.
IR-spectrophotometry.
Dissolve the substance in ammonium solution at the heating.
After cooling add silver nitrate solution – solution must still be
colorless. After the boiling during few minutes white precipitate
formed.
Reaction on xantines (murexide sample). At the oxidation of
theobromine 3-methylalloxane and
methylurea formed.
Ammonium salt of dimethylpuepuric acid formed as a result of
murexide reaction:
4.
Unpharmacopoeial reactions
Reaction of the sodium salt of theobromine, obtained by the
interaction of alkali with an excess of preparation, with cobalt
(II)chloride solution – intense violet color appears, which quickly
disappears, grey-blue precipitate:
5.
The reaction of theobromine sodium salt with silver nitrate formed a dense gelatin mass (silver salt), which is thinning
by heating to 80° С and solidifies again at the cooling.
6. With HgCl2 – white crystalline precipitate.
Identification of theophylline
1.
2.
3.
Determination of the melting temperature alter the drying.
IR spectrophotometry.
Theophylline in the alkali medium decomposes to teophyllidine,
which can be identified by the reaction of azojoining with
diazonium salts, red color azo-dye formed.
4.
5.
Determination of the water by semimicromethod (К. Fisher)
(8-9,5 %).
Reaction on xantines (murexide sample). At the oxidation of
theophylline 1,3-dimethylalloxane and urea. Ammonium salt of
tetramethylpuepuric acid forme as a result of murexide reaction:
2.
The reaction of theobromine sodium salt obtained by the
interaction of alkali with an excess of drug, with a solution of
cobalt (II) chloride - formed white with pink tinge precipitate
of cobalt salt.
3.
With HgCl2 –white crystalline precipitate.
With alkali solution of sodium nitroprusside green color formed
dissappears at the adding an excess of acid.
4.
5.
The reaction of theobromine sodium salt with silver nirate formed a dense gelatin mass.
6.
Theophylline with 2,6-dichloroqiunonechloroimide in borate
buffer solution
(рН 8,5) gives intense blue
merocyanic dye:
Assay
Theophylline and Theobromine
Alkalimetry by the substituent (indirect alkalimetry).
Indicator – phenolphthalein (theobromine) or Bromothymol
blue (theophylline). Е = М.m.
Storage, usage
Theobromine
In airtight containers, place
protected from light.
Stimulates the activity of the
heart, somewhat expands
the coronary vessels and
bronchi, shows diuretic
effect. Issue - powder and
tablets by 0,25 g.
Included in tablets: Theminal
(with amidopyrine and
Phenobarbital),
Theodibaverine (with
papaverine and dibazole),
Theoephedrine.
Theophylline
In airtight containers, place
protected from light.
Non-selective phosphodiesterase
inhibitor (xanthine); treatment of
reversible airways obstruction.
Broncholitic, cardiotonic and
diuretic mean with moderate
influence on the stagnation
phenomena in the cardiac and
renal origin organs. Issue –
powder and tablets by 0,1 and 0,3
g; amp. 2%-5,0; candles by 0,2 g.
Teopek, Theotard, Neophylline,
Euphylline. Included in tablets:
Theoephedrine.
Pentoxifylline (Pentoxifyllinium)
Agapurine, Pentyline, Trental
A synthetic analogue of theobromine
O
O
H3C
C
C
H2
C
H2
C
H2
C
H2
O
N
N
N
CH3
N
CH3
3,7-dimethyl-1-(5’-oxohexyl)-3,7-dihydro-7Н-purine2,6-dion or 1-(5’-oxohexyl)-theobromine
Identification of pentoxifylline
Temperature of melting
IR-spectroscopy
TLC
Reaction on xantines
Formation of azo-dye (look theophylline)
Assay
pentoxifylline
Acidimetry in non-aqueous media in a mixture of
anhydrous acetic acid and acetic anhydride, direct
titration. Potentiometric indication. (Е=М.m).
Usage of pentoxifylline
Has a vasodilator effect, improves tissue oxygen
supply, decreases thrombosis aggregation and
reduces blood viscosity. Apply at the peripheral
circulatory disorders, atherosclerotic disorders,
ischemic condition after heart attack, in
ophthalmology, at the hearing disorders. Issue –
tablets of 0,1 g, ampoules of 2%-5,0. Adopt
inside by 0,2 g 3 times daily after meals. In the
acute disorders of peripheral or cerebral
circulation injected 0,1 g intravenous in 250-500
ml of NaCl or 5% glucose solution.
Synthetic analogues of theophylline
Theophylline-ethylenediamine (Theophyllinum et
ethylenediaminum) (SPhU),
Euphylline (Euphyllinum), Aminophilline
O
H3C
N
NH
H2C
NH2
H 2C
NH2
*
O
N
N
CH3 Theophylline with 1,2-ethylenediamine
White, sometimes with yellowish crystalline powder with slight
ammonia odor. On the air absorbs carbon dioxide, thus
decreasing its solubility. Soluble in water, aqueous solutions
have an alkaline reaction.
Identification of euphylline
1. Theophylline is identified after the
separation by HCl of ethylenediamine
according to SPhU:
а) By the melting temperature of theophylline
(269 - 274°С) after HCl acidification to рН 4-5;
b) IR-spectroscopy;
c) Reaction of azojoining (look theophylline);
d) murexide sample.
2. Ethylenediamine can be confirmed by the following
reactions:
а) determination of the melting temperature of the product
of reaction with benzoyl in alkali medium
(dibenzoylethylenediamine) (SPhU):
H2C
NH2
H2C
NH2
+
2
C
Cl
O
C
- 2 HCl
O
N
H
C C N
H2 H2 H
C
O
b) with a solution of copper (II) sulfate a bright purple
color forms :
H2C
NH2
2
H2C
+ CuSO4
H2C
NH2
NH2
Cu
SO4
H2C
NH2
2
c) with 2,4-dinitrochlorobenzene –yellow precipitate
Assay
Euphylline
1. Ethylenediamine can be determined by acidimetry,
indicator –methyl orange. Е = М.m./2.
H2C
NH2
H2C
NH2
+ 2HCl
H2C
NH2
* 2 HCl
H2C
NH2
Ethylenediamine in euphylline should be 13,5—15 % in
the dry matter.
2. Theophylline can be determined by alkalimetry by
substituent 1 after drying in a drying cabinet at 25-130
°С to the disappearance of amine odor.
The content of waterless theophylline in euphylline
should be 84- 87,4 %.
Storage, usage of euphylline
Given the ability to absorb carbon dioxide, stored in a
well corked filled to the end container, protected
from the effects of light and moisture.
Antispasmodic, bronchodilatin, diuretic mean. At the
bronchial asthma and bronchospasm, hypertension,
cardiac asthma, to improve blood circulation to the
brain, decreasing the intraperitoneal pressure and
brain edema in ischemic stroke.
Used oral by 0,15g after food, i/v (2,4%
solutions by 5,0) and i/m (24 % solution by 1 ml).
Diprophylline (Diprophyllinum)
O
OH
H 3C
O
N
N
N
CH3
7-(2',3'-Dioxipropyl)theophylline
N
C
H2
C
H
CH2OH
Less toxic than
theophylline. Used for
treatment of coronary
spasm, cardiac and
bronchial asthma,
hypertension. Issue –
tablets by 0,2 g; amp.
10%-5,0; candles by 0,5
g.
Xantinole nicotinate (Xantinoli
nicotinas) Complamine, Theonicol
O
OH
H3C
O
N
N
N
N
C
H2
C
H
C
H2
N
COOH
CH3
*
CH2CH2OH
N
CH3
7-[2’-oxi-3’-(N'-methyl-β- Used to improve peripheral
oxiethylamino)-propyl]- and cerebral circulation
theophylline nicotinate Issue – tablets by 0,15 g; amp.
15%-2,0 і 10,0.
Thank you for
attention!