Transcript 13. Condensed azines. Quinoline. Isoquinoline. Acridine. Diazines

LECTURE № 13
THEME: Condensed azines.
Quinoline. Isoquinoline. Acridine.
Diazines. Purine.
associate. prof. Ye. B. Dmukhalska, assistant. I.I. Medvid
Plane
1. Receipt of quinoline and his derivatives. Synthesis of Skraupa and
synthesis of Debner—Miller. Physical and chemical properties of
quinoline.
2. Receipt of isoquinoline. Synthesis of Bischler-Napieralski. Physical
and chemical properties of isoquinoline.
3. Structure, nomenclature, methods of getting and physical and
chemical properties of acridine.
4. Methods of getting of sixmember heterocyclic connections with two
heteroatoms
5. Structure, nomenclature, physical and chemical properties of
pyridazine, pyrimidine, barbituric acid, pyrazine, purine, uric acid.
6. Structure, nomenclature and properties of azepines. Benzazepine,
diazepine. Benzodiazepine, Oxazepam. Radedrol (nitrazepam).
Seduxen (diazepam).
7. Classification of alkaloids.
1. Obtaining of quinoline and his derivatives. Synthesis of
Skraup and synthesis of Debner—Miller. Physical and
chemical properties of quinoline.
The impotent condensed of sixmembered heterocycles
connections are with one heteroatom is:
quinoline
isoquinoline
acridine
Quinoline, also known as 1-azanaphthalene, 1-benzazine, or
benzo[b]pyridine, is a heterocyclic aromatic organic compound. It
has the formula C9H7N and is a colourless hygroscopic liquid with a
strong odour. Aged samples, if exposed to light, become yellow and
later brown.
Quinoline is only slightly soluble in cold water but dissolves
readily in hot water and most organic solvents. Quinoline is
mainly used as a building block to other specialty chemicals.
Approximately 4 tonnes are produced annually according to a
report published in 2005. Its principal use is as a precursor to
8-hydroxyquinoline, which is a versatile chelating agent and
precursor to pesticides. Its 2- and 4-methyl derivatives are
precursors to cyanine dyes. Oxidation of quinonline affords
quinolinic acid (pyridine-2,3-dicarboxylic acid), a precursor to
the herbicide sold under the name "Assert".
The Skraup synthesis is a chemical reaction used to synthesize
quinolines. It is named after the Czech chemist Zdenko Hans
Skraup (1850-1910). In the archetypal Skraup, aniline is heated
with sulphuric acid, glycerol, and an oxidizing agent, like
nitrobenzene to yield quinoline. The Skraup synthesis place is
taken in three stages.
On the first stage glycerin is under the action of
сoncentrated H2S04 to dehydration with formation of
akrolein:
On the second stage appearing akrolein enters into the reaction of
condensation with an aniline:
-H2O
On the third stage of reaction of 1,2dihydroquinoline oxidizes nitrobenzol in to
quinoline:
Synthesis of Debner —Miller.
The reaction is opened in 1881. On the first stage there is krothonic
condensation of two molecules of aldehyde .
Further there is cooperation of krothonic aldehyde with aniline.
2-methyl-1,2-dihydroquinoline
2-methyl-quinoline
Chemical properties:
1. Reactions of heteroatom.
quinoline chloride
N-methylquinoline iodide
N-acethylquinoline chloride
2. Reactions of electrophilic and nukleophilic substitutions .
Reactions of electrophilic substitution in the molecula of
quinoline is entered in position of 5 and 8.
6- quinoline sulphatic acid
Reactions of nukleophilic substitution (is entered in position of 2) .
2- aminoquinoline
2- hydroxyquinoline
3. Reactions of reduction and oxidization.
quinolinic acid
Derivatives of quinoline
8-Hydroxyquinoline is an organic compound with the
formula C9H7NO. It is a derivative of the heterocycle
quinoline by placement of an OH group on carbon
number 8. This colorless compound is widely used
commercially, although under a variety of names. It is
usually prepared from quinoline-8-sulfonic acid and
from the Skraup synthesis from 2-aminophenol.
NaOH
-Na2SO3
8-Hydroxyquinoline is a monoprotic bidentate
chelating agent. Related ligands are the Schiff bases
derived from salicylaldehyde, such as salicylaldoxime
and salen. The roots of the invasive plant Centaurea
diffusa release 8-hydroxyquinoline, which has a
negative effect on plants that have not co-evolved
with it. The complexes as well as the heterocycle
itself exhibit antiseptic, disinfectant, and pesticide
properties. Its solution in alcohol are used as liquid
bandages. It once was of interest as an anti-cancer
drug.
O
[H]
CH 2=CH-C
NO 2
OH
NH 2
OH
OH
H2SO4
2-
+
OH
SO4
N
N
OH
H
quinozol
2
H
2. Receipt of isoquinoline. Synthesis of Bischler-Napieralski.
Physical and chemical properties of isoquinoline.
Isoquinoline, also known as
benzo[c]pyridine or 2-benzanine, is a
heterocyclic aromatic organic compound. It
is a structural isomer of quinoline.
Isoquinoline and quinoline are benzopyridines, which are
composed of a benzene ring fused to a pyridine ring. In a
broader sense, the term isoquinoline is used to make reference to
isoquinoline derivatives. 1-Benzylisoquinoline is the structural
backbone in naturally occurring alkaloids including papaverine
and morphine. The isoquinoline ring in these natural compound
derives from the aromatic amino acid tyrosine. Isoquinoline is a
colourless hygroscopic liquid at room temperature with a
penetrating, unpleasant odour. Impure samples can appear
brownish, as is typical for nitrogen heterocycles. It crystallizes
platelets that have a low solubility in water but dissolve well in
ethanol, acetone, diethyl ether, carbon disulfide, and other
common organic solvents. It is also soluble in dilute acids as the
protonated derivative.
 In the Bischler-Napieralski reaction an β-phenylethylamine is acylated
and cyclodehydrated by a Lewis acid, such as phosphoryl chloride or
phosphorus pentoxide. The resulting 1-substituted-3,4-dihydroisoquinoline
can then be dehydrogenated using palladium. The following BischlerNapieralski reaction produces papaverine.
1-substituted-3,4dihydroisoquinoline
1-substituted isoquinoline
Chemical properties:
1. Reactions of electrophilic and nukleophilic substitutions .
Reactions of electrophilic substitution in the molecula of isoquinoline is
entered in position of 5 and 8. Reactions of nukleophilic substitutions tare
place in position of 1.
isoquinoline of chloride
N-methylisoquinoline of iodide
2. Reaction of reduction
1,2,3,4tetrahydroisoquinoline
3. Reaction of oxidization
3,4- pyridinedicarbonic acid
Methods of getting:
1. Condensation of diphenylamine with carbonic
acids :
diphenylamine
acridine
2. Cyclization N-fenilanthranilic acid on the reaction of
Drozdov—Mahidson—Hrihorovsky:
N-fenilanthranilic acid
anhidride chloride
N-fenilanthranilic
acid
acridone-9
acridole-9
9,10-dihydroacridine
9-chloracridine
acridine
1.
Reactions of heteroatom.
acridinium chloride
N-oxide of acridine
N-methylacridine iodide
2. Reactions of electrophilic and nukleophilic substitutions .
9-hydroxacridine,
acridole-9
9- oxoacridine,
acridone-9
3. Reactions of oxidization.
acridinic acid
4. Reactions of reduction.
9,10-dehydroacridine,
acridane
Derivatives of acridine
9- Aminoacridine is an antiseptic and disinfectant.
Acidylating flows on aminogroup:
9-N-acethylaminoacridine
9-aminoacridine chloride
arcihine
rivanol
medicinal preparations
COOH
O2N
Cl
OC2H5
COOH
H2N
O2N
NH
O
OH
O2N
OC2H5
POCl3
OC2H5
C
POCl3
-HCl
NH
NH2
OC2H5
N
N
O2N
Cl
O2N
OC2H5
OC2H5
NH3
-HCl
[H]
O2N
N
9-amino-2-ethoxy-6-nitroacridine
NH2
OC2H5
COOH
+
HC OH
N
H2N
CH3
NH2
OC2H5
H2N
N
.
COOH
HC OH
CH3
ethacridine lactate,
rivanol,
6,9 – diamimo-2-ethoxyacridine lactate
Sixmembered heterocycles connections are with two
heteroatoms
In addition to these three diazines, the
bicyclic tetraaza compound, purine,
is an important heterocyclic system.
These ring systems, particularly that of pyrimidine, occur commonly
in natural products. The pyrimidines, cytosine, thymine, and uracil
are especially important because they are components of nucleic
acids, as are the purine derivatives adenine and guanine.
The рurine nucleus also occurs in such
compounds as caffeine (coffee and tea) and
theobromine (cacao beans).
4. Methods of getting of sixmember heterocyclic connections with two
heteroatoms
CH
HC
C
H
C
H
NH 2 NH 2
O
O
N
- H 2O
N
maleinaldehide
pyridazine
O
O
H
C
CH
OC H
2
H N
5
+
2
C
OC H
2
C H ONa
2
5
2
C
Malene ephir
H
N
N
C
H
O
-C 2H 5O H
H N
O
N
2
HO
O
H
urea
O
5
барбітурова
barbituric acid
Cl
POCl 3
N
6H (Zn)
N
Cl
N
N
Cl
OH
pyrimidine
N
OH
These method use for obtaining pyridazine and his derivatives
NH2
CH2
H
O
C
to
C
- 2 H2O
+
CH2
O
NH2
glyoxal
NH2
NH2
N
N
- H2O
N
2,3- dihydropyrazine
pyrazine
O
+
N
O
H
ethylendiamine
N
N
C H
HO
N
N
- 2 H2O
N
N
H
purine
5. Structure, classification, nomenclature, physical
and chemical properties of pyridazine.
Pyridazine is a heteroaromatic organic compound
with the molecular formulaC4H4N2, sometimes
called 1,2-diazine. It contains a six-membered
ring with two adjacent nitrogen atoms. It is a
colorless liquid with a boiling point of 208 °C.
Pyridazine has no household use. It is mainly
used in research and industry as building block
for more complex compounds. The pyridazine
structure is found within a number of herbicides
such as credazine, pyridafol and pyridate. It is
also found within the structure of several
pharmaceutical drugs such as cefozopran,
cadralazine, minaprine, hydralazine, and
cilazapril.
Pyridazine
Other names
1,2-diazine, orthodiazine,
oizine
Properties
Molecular formula
C4H4N2
Molar mass
80.09 g mol−1
Appearance
colorless liquid
Density
1.107 g/cm3
Melting point
-8°C
Boiling point
208°C
+
N
N
I-
CH3
HCl (í àäë.)
CH3I
Nmethylpyridazine
iodide
+
N
N
N
CH3COOOH
+
N
Cl-
N
H
Pyridazine
chloride
N-oxide pyridazine
N _
O
thethramethyleldiamine
Derivatives of pyridazine
6. Structure, nomenclature, physical and chemical
properties of pyrimidine.
Three nucleobases found in nucleic acids (cytosine,
thymine, and uracil) are pyrimidine derivatives: In DNA
and RNA, these bases form hydrogen bonds with their
complementary purines. Thus the purines adenine (A)
and guanine (G) pair up with the pyrimidines thymine (T)
and cytosine (C), respectively.
Pyrimidine
Properties
Molecular formula
C4H4N2
Molar mass
80.088
Melting point
20–22 °C
Boiling point
123–124 °C
+
N
N
HCl
H
_
ê. HNO3
N
Cl
N
NH2
NH2
N
HO
pyrimidine chloride
N
ê. H2SO4
N
HO
N
N
4-amino-2-hydroxypyridine
Br2
N
N
NH2
Br
N NaNH2
N
N
NH2
N
NO2
2- aminopyridine
N
N
N
NH2
Derivatives of pyrimidine
Barbituric acid (2,4,6-trihydroxypyrimidine)
Keto-enole and lactam-lactim tautomery
7. Structure, nomenclature, physical and chemical properties of
barbituric acid.

Barbituric acid or malonylurea or 4hydroxyuracil is an organic compound based
on a pyrimidine heterocyclic skeleton. It is an
odorless powder soluble in hot water. Barbituric
acid is the parent compound of a large class of
barbiturates that have central nervous system
depressant properties, although barbituric acid
itself is not pharmacologically active.
The compound was discovered by the German chemist
Adolf von Baeyer on 4. December 1864—the feast of St
Barbara and therefore the name given to the
compound—by combining urea and malonic acid in a
condensation reaction. Malonic acid has since been
replaced by diethyl malonate.
Bases of pyrimidine (important derivatives )
These bases are present in nucleinic acids

Vitamin B1 (thiamine) contain pyrimidine and thyazole ring connect
through methyl group.
Physiological active form of vitamin B1 in living organisms is cocarboxilaza,
which take part in enzyme processes, in hydrocarbon exchange
Orotic acid is primary compound in biosynthesis of pyrimidine bases
Pyrazine
Other names
1,4-Diazabenzene, p-Diazine, 1,4Diazine, Paradiazine, Piazine, UN
1325
Properties
Molecular formula
C4H4N2
Molar mass
80.09 g/mol
Appearance
White crystals
Density
1.031 g/cm3
Melting point
52 °C
Boiling point
115 °C
Solubility in water
Soluble
The Gastaldi synthesis (1921) is another variation:
Chemical properties of pyrazine
N
N
N
H
N
H
pyperazine
(Na + CH3CH2OH)
NaNH2, NH3
N
N
H
N
2aminopyrazine
N
NH2
N
N
N
CH3COOOH
+
N
_
O
N- oxide pyrazine
Purine
Properties
Molecular formula C5H4N4
Molar mass
120.112
Melting point
214 °C
Synthesis of purine
Traube method: condnsation 4,5diaminopyrimidines with carbonic acids
The Traube purine synthesis (1900) is a classic
reaction (named after Wilhelm Traube) between an
amine substutited pyrimidine and formic acid
Chemical properties of purine.
For purine is characteristic of azole tautomery :
NH
Cl
NH
N
N
NH
Cl
Cl
NH
N
(1:1)
2
Cl
Cl
adenine
KOH
N
NH
Cl
Cl
N
OH
OH
OH
N
NH
N
NH
N
N
N
H
N
N
3
2
NH
(1:1)
3
H 2N
H
N
N
N
N
Cl
N
NH
H 2N
NH
N
guanine
H
HNO
O
O
N
HN
N
N
H
hypoxanthine
N
HN
O
N
H
N
H
xanthine
2
Purine is an amphoteric compound
Derivatives of purine
Main derivatives of purine are oxopurines:
Uric acid is colorless crystal compound, bad soluble in water, ethanol and
ether, soluble in dilute base solutions and glycerin. Uric acid is dibases acid.
Thauthomeric forms
O
HN
N
N
O
N
H
N
H
O
OH
H
N
HO
OH
N
H
N
uric acid
O
OH
N
HN
N
H
N
H
O
N
N
HO
N
H
N
xanthine
O
OH
N
HN
N
N
N
N
H
hypoxanthine
N
N
H

Salts of uric acid called urats. Urats is bad soluble
in water, except salts with litium (Li).
 In hydroxyform uric acid gives reactions of
nucleophilic substitutions.
Chemical properties
O
H
O
N
H
N
O
2NaOH
O
N
H
H
N
N
H
+
NaO
HO
N
N
H
disodium salt of uric acid
Cl
N
OH
N
_ +
ONa
_
OH
N
H
N
N
H
POCl3
N
N
Cl
Cl
N
NH
2,6,8-threechlorpurine
Reactions of oxidation
aloxane
urea
alantoine
Murexidne’s reaction is the qualitative
reaction on uric acid

By heating uric acid with nitrate acid and next
adding of ammonium observe purpur-violet color
purpure acid
(enole form)
murexide
Reactions of reduction
xanthine
 Hypoxantine
and xantine have the same
chemical properties as uric acid
N-methyl derivatives of hypoxantine and xantine widely used in
pharmacy
Aminopurines
aminoderivatives of purine –
adenine and guanine present in nucleinic
acids as purine’s bases.
 Maine
Phenothiazine

Phenothiazine (dibenzo-1,4-thiazine) – colorless crystal compound,
insoluble in water, diethyl ether, well soluble in hot ethanol.
Method of getting
Chemical properties
1. Alkylation and acylation
2. Oxidation
3. Reaction of electrophilic sybstitution go in location 3 and 7
with oxidation of sulphur
Derivatives of phenothiazine
Pteridine (pyrazino[2,3-d]pyrimidine)
Method of getting: condensation of 4,5diaminopyrimidins with 1,2-dicarbonile compounds
Pteridine is light yellow crystal compound, soluble in water, ethanol, less soluble in
diethyl ether and benzole. Pteridine is stable to oxidation, by acting of acids and
bases pteridine cycle decompose. Gives reaction of electrophilic substitution,
protonate on nitrogen atom in 1 location.
Derivatives of pteridine
 Folic
acid (vitamin Bc)
Aloxasine and isoaloxasine
 These
compounds include benzyl,
pyrazine and hydrate pyriidine cycles
Flavine is a primery compound of riboflavin:
11. Structure, nomenclature and properties of
azepines. Benzazepine.
Sevenmember heterocyclic ring compounds
have received much attention in the past few
years owing to its wide range of biological
activity.
Azepines are heterocycles
of seven atoms, with a
nitrogen replacing a carbon
at one position.
A well known azepine is
caprolactam
 Skeletal
formula of caprolactam.
Sevenmember heterocycles which
containing nitrogen
Benzazepine: bicyclic structure consisting of
fused benzene and azepine rings; many
compounds with this structure react with
biogenicamine receptors, and so are psychotropic
and neurotropic.
Examples of benzazepine include fenoldopam and
galantamine.
fenoldopam
galantamine
12. Structure, nomenclature and properties
of diazepine. Benzodiazepine.
Diazepine is a sevenmember
heterocyclic compound with two
nitrogen atoms (e.g., in ring
positions 1 and 2) and three
double bonds.
When diazepine combined with a benzene ring, these is
the basis of the benzodiazepine family . In these
compounds the nitrogen atoms are at the 1 and 4
positions as, for example, in clobazam (depending on
the position of the fused benzene ring, the nitrogen
atoms are also in positions number 1 and 4).
5-Phenyl-1,3-dihydro-2H-1,4benzodiazepin-2-on
forms the skeleton on many of
the most common benzodiazepine
pharmaceuticals, such as diazepam
(chloro-substituted).


The benzodiazepines are a class of psychoactive drugs with
varying hypnotic, sedative, anxiolytic (anti-anxiety), anticonvulsant,
muscle relaxant and amnesic properties, which are mediated by
slowing down the central nervous system. Benzodiazepines are
useful in treating anxiety, insomnia, agitation, seizures, and muscle
spasms, as well as alcohol withdrawal. They can also be used
before certain medical procedures such as endoscopies or dental
work where tension and anxiety are present, and prior to some
unpleasant medical procedures in order to induce sedation and
amnesia for the procedure. Benzodiazepines are also used to treat
the panic that can be caused by hallucinogen intoxication.
Benzodiazepines can cause a physical dependence and a
benzodiazepine addiction to develop and upon cessation of long
term use a benzodiazepine withdrawal syndrome can occur.
13. Oxazepam. Radedrol (nitrazepam). Seduxen
O
(diazepam).
N
Oxazepam (marketed in English speaking
N
countries under the following brand names
Alepam, Medopam, Murelax, Noripam,
Ox-Pam, Purata, Serax and Serepax), is a
drug which is a benzodiazepine derivative.
Oxazepam
Oxazepam has moderate amnesic,
anxiolytic, anticonvulsant, hypnotic,
7-clorine-3-hydroxysedative and skeletal muscle relaxant
5-phenil-1,3-dihydro2H-1,4-benzodiazepin-2-on properties compared to other
benzodiazepines.
OH
Cl

Oxazepam is an intermediate acting benzodiazepine.
Oxazepam acts as inhibitor on the central nervous system. The halflife of oxazepam is 4-15 hours. Oxazepam has been shown to
suppress cortisol levels.
H
O
N
O 2N
N
Nitrazepam is a nitrobenzodiazepine It
is a 1,4 benzodiazepine, with the
chemical name 7-nitro-5-phenyl-1,3dihydro-2H-1,4- benzodiazepin-2-on.
Nitrazepam
Nitrazepam is a type of benzodiazepine
drug and is marketed in English speaking
countries under the following brand names Alodorm, Arem, Insoma, Mogadon,
Nitrados, Nitrazadon, Ormodon, Paxadorm,
Remnos and Somnite.
It is a hypnotic drug with sedative and motor impairing
properties, anxiolytic, anticonvulsant and skeletal muscle relaxant
properties. It is long acting drug, has lipophilic and hepatometabolitic
properties via oxidative pathways. It acts on benzodiazepine receptors
in the brain which are associated with the GABA receptors (gammaaminobutyric acid). GABA is a major inhibitor neurotransmitter in the
brain, involved in inducing sleepiness, muscular relaxation and control
of anxiety and seizures, and slows down the central nervous system.
H 3C
O
N
N
Cl
O
diazepam
(4N-oxide 7-chlorine-1-methyl-
Diazepam first marketed as Valium by
Hoffmann-La Roche, is a benzodiazepine
derivative drug. It possesses anxiolytic,
anticonvulsant, hypnotic, sedative, skeletal
muscle relaxant and amnestic properties. It is
commonly used for treating anxiety, insomnia,
seizures, muscle spasms, alcohol withdrawal
and benzodiazepine withdrawal.
5-phenil-1,3-dihydro-2Н1,4-benzodiazepin-2-оne )
Diazepam occurs as solid white or yellow
crystals and has a melting point of 131.5 to 134.5 °C.
It is odorless, and has a slightly bitter taste. The British
Pharmacopoeia lists diazepam as being very slightly
soluble in water, soluble in alcohol and freely soluble
in chloroform. The United States Pharmacopoeia lists
diazepam as soluble 1:16 in ethyl alcohol, 1:2 in
chloroform, 1:39 in ether, and practically insoluble in
water.
Qualitative reactions on benzodiazepines
1. With concentrated acids (H2SO4, HCl, HClO4)
derivatives of benzodiazepines form color salts.
2. Heterocyclic nitrogen atom gives positive reaction with
common alkaloids precipitate reagents.
3. Specific reaction on benzodiazepines derivatives is
formation of green color after pyrolisis.
4. Formation of azodays after primary hydrolysis:
Nozepam
5. Belshteine probe use for determination of halogens.
6. Noozepam by heating with conc. H2SO4 hydrolyzed with
formation of formaldehyde, which forms violet color with
fuxinsulfite acid.

Pyridine and piperidine group: piperine, coniine, trigonelline, arecoline,
arecaidine, guvacine, cytisine, lobeline, nicotine, anabasine, sparteine,
pelletierine.
N
N
H

Pyrrolidine and pyrolisidine group: hygrine, cuscohygrine, platyphylline,
nicotine.
N
N
H

Tropane group: atropine, cocaine, ecgonine, scopolamine, catuabine.
N CH 3

Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine,
strychnine, brucine, veratrine, cevadine.
N

Isoquinoline group: opium alkaloids (papaverine, narcotine, narceine),
sanguinarine, hydrastine, berberine, emetine, berbamine, oxyacanthine.
N

Phenanthrene alkaloids: opium alkaloids (morphine, codeine,
thebaine)
Phenethylamine group: mescaline, ephedrine, dopamine

Indole group:

N
H
Tryptamines: serotonin, bufotenine, psilocybin

Ergolines (the ergot alkaloids): ergine, ergotamine, lysergic acid

Beta-carbolines: harmine, harmaline, tetrahydroharmine

Yohimbans: reserpine, yohimbine

Vinca alkaloids: vinblastine, vincristine

Kratom (Mitragyna speciosa) alkaloids: mitragynine, 7hydroxymitragynine

Tabernanthe iboga alkaloids: ibogaine, voacangine, coronaridine

Strychnos nux-vomica alkaloids: strychnine, brucine
Purine group:
N
N
H


N

N
Xanthines: caffeine, theobromine, theophylline
15. Alkaloids group of pyridine and piperine
(nicotine, anabasine, lobeline).
CH3
Systematic (IUPAC) name
Nicotine is an alkaloid found in the
nightshade family of plants (Solanaceae)
which constitutes approximately 0.6–3.0%
of dry weight of tobacco, with biosynthesis
taking place in the roots, and accumulating
in the leaves.
3-[2’-(N-methylpyrrolidil)]pyridine
It functions as an antiherbivore chemical with particular
specificity to insects; therefore nicotine was widely used as an
insecticide in the past, and currently nicotine analogs such as
imidacloprid continue to be widely used.
Anabasine is a pyridine alkaloid found in the Tree Tobacco
(Nicotiana glauca) plant, a close relative of the common
tobacco plant (Nicotiana tabacum). It is similar to nicotine. Its
principal (historical) industrial use is as an insecticide.
Anabasine is present in trace amounts in tobacco smoke, and
can be used as an indicator of a person's exposure to tobacco
smoke.
β-(α’-pyperidile)pyridine
Pharmacology
Anabasine is a nicotinic acetylcholine receptor
agonist. In high doses, it produces a depolarizing
block of nerve transmission, which can cause
symptoms similar to those of nicotine poisoning
and, ultimately, death by asystole. In larger
amounts it is thought to be teratogenic in swine.
Lobeline is a natural alkaloid found in
"Indian tobacco" (Lobelia inflata), "Devil's
tobacco" (Lobelia tupa), "cardinal flower"
(Lobelia cardinalis), "great lobelia"
(Lobelia siphilitica), and Hippobroma
CH3
longiflora. In its pure form it is a white
amorphous powder which is freely
Systematic (IUPAC) name
soluble in water. Lobeline has been used
L-(-)-2benzoilmethyle-6-(2’-hydroxy- as a smoking cessation aid, and may
2’-phenylethyl)-1-methylpyperidine have application in the treatment of other
drug addictions such as addiction to
amphetamines or cocaine.
Lobeline has multiple mechanisms of action, acting as
a VMAT2 ligand, which stimulates dopamine release to a
moderate extent when administered alone, but reduces the
dopamine release caused by methamphetamine.
16. Alkaloids group of quinoline (quinine).
Quinine
Systematic (IUPAC) name (R)-(6methoxyquinolin-4-yl)- (8’vinylquinuclidin-2’-yl)methanol
Quinine is a natural white crystalline alkaloid having
antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and
anti-inflammatory properties and a bitter taste. It is a stereoisomer of
quinidine.
Quinine was the first effective treatment for malaria caused by
Plasmodium falciparum, appearing in therapeutics in the 17th century.
Since then, many effective antimalarials have been introduced,
although quinine is still used to treat the disease in certain critical
situations. Quinine is available with a prescription in the United
States. Quinine is also used to treat nocturnal leg cramps and
arthritis.
Chemical structure
Quinine contains two major fused-ring systems: The aromatic quinoline and
the bicyclic quinuclidine .
Qualitative reaction on quinine
Thaleyoquine test: emerald-green color
– with conc. H2SO4 – blue fluorescence;
– with sodium nitroprusside - yellow sediment.
17. Alkaloids of group of quinoline and phenanthreneisoquinoline
(papaverine, morphine, codeine).
Papaverine is an opium alkaloid used
primarily in the treatment of visceral
spasm, vasospasm (especially those
involving the heart and the brain), and
occasionally in the treatment of erectile
dysfunction. While it is found in the
opium poppy, papaverine differs in both
structure and pharmacological action
from the other opium alkaloids
(opiates).
Papaverine
Systematic (IUPAC) name
1-(3’,4’-dimethoxybenzyl)6,7-dimethoxyisoquinoline
Qualitative reactions on papaverine
1. With conc. H2SO4 by heating – violet color after heating.
2. With conc. HNO3 – yellow color, that after heating becomes orange.
H3CO
H3CO
H3CO
N
N
HNO3
H3CO
N
HNO3
H3CO
0
CH2
t C
CH2
H3CO
O2N
NO2
H3CO
OCH3
H3CO
OCH3
жовте забарвлення
Yellow
3. With bromine water – yellow precipitate.
CH2
NO2
H3CO
OCH3
оранжеве забарвлення
Orange
4. With Erdman reagent (H2SO4 conc.+HNO3 conc.) – red color.
5. With Phrede reagent ((NH4)2MoO4+H2SO4 conc.) – violet color after heating.
6. With Mandelin reagent (NH4VO3+H2SO4 conc.) – blue-green color becomes
blue.
7. With Marci reagent (HCOH+H2SO4 conc.) – at first forms red color,
then yellow and at the end orange. By adding bromine water and
ammonium appears violet precipitate, which dissolves in alcohols.
H3CO
OCH3
C
H2
H3CO
H3CO
OCH3
OCH3
C
H2
OCH3
N+
N+
H
H
C
H2
OCH3 SO4
2-
Systematic (IUPAC) name
3,6-dihydroxy-N-methyl- 4,5epoxymorphinene-7
Morphine is a highly potent opiate analgesic
drug, is the principal active agent in opium, and
is considered to be the prototypical opioid.
Morphine was in 1803 the first alkaloid isolated
from a plant source. Like other opioids, e.g.
oxycodone, hydromorphone, and
diacetylmorphine (heroin), morphine acts
directly on the central nervous system (CNS)
to relieve pain, particularly at the synapses of
the nucleus accumbens. Morphine has a high
potential for addiction; tolerance and both
physical and psychological dependence
develop rapidly.
Chemistry
Chemical structure of morphine in correct 3D configuration. The
benzylisoquinoline backbone is shown in blue. Morphine is a benzylisoquinoline
alkaloid with two additional ring closures. Most of the licit morphine produced is used
to make codeine by methylation. It is also a precursor for many drugs including
heroin (diacetylmorphine), hydromorphone, and oxymorphone. Replacement of the
N-methyl group of morphine with an N-phenylethyl group results in a product that is
18 times more powerful than morphine in its opiate agonist potency.
Morphinene
Qualitative reactions on morphine
1. With Marci reagent – purpur color quickly becomes blue-violet
(distinctive reaction between morphine and codeine).
2. With ammonium – white crystal precipitate dissolves in NaOH.
3. With Phrede reagent – at first forms violet color, that changes to blue
and by standing – to green.
4. With FeCl3 – blue color.
6. Oxidation reaction with K3[Fe(CN)6] and FeCl3 – blue color:
7. With Mandelin reagent – violet color.
8. With Erdmane reagent – intense red color:
9. With conc. HNO3 – red-orange complex compound:
10. With diazonium salts – azoday (red color).
Obtaining derivatives of morphine
Codeine
Systematic (IUPAC) name
6-hydroxy-N-methyl-3-methoxyCodeine (INN) or methylmorphine
4,5-epoxymorphinen-7
is an opiate used for its analgesic, antitussive
and antidiarrheal properties. It is by far the
most widely used opiate in the world and
probably the most commonly used drug
overall according to numerous reports over
the years by organizations such as the World
Health Organization and its League of Nations
predecessor agency and others.
Qualitative reactions on codeine
1. With Marci reagent – blue-violet color.
2. Formation of apomorphine. After heating with
conc. H2SO4 and FeCl3 appears blue color that
becomes red after adding 1 drop of dilute HNO3.
3. With conc. HNO3 – red color becomes yellow.
4. With AgNO3 – orange precipitate Ag3PO4.
5. With Erdman reagent (H2SO4 conc.+HNO3
conc.) -blue color after heating.
6. With Phrede reagent ((NH4)2MoO4+H2SO4
conc.) - green color becomes blue.
7. With Mandelin reagent (NH4VO3+H2SO4 conc.)
- green color becomes blue.
8. With sodium nithropruside– yellow sediment.
Alkaloids group of purine (caffeine, theobromine,
theophylline).
1,3,7trimethylxanthine,
trimethylxanthine,
Caffeine is a bitter, white crystalline xanthine alkaloid
that acts as a psychoactive stimulant drug and a mild
diuretic. Caffeine was discovered by a German
chemist, Friedrich Ferdinand Runge, in 1819. He
coined the term "kaffein", a chemical compound in
coffee, which in English became caffeine.
Caffeine present in sugh plants:Coffea
arabica, Thea sinensis and Cola acuminata
Thea sinensis
Theobroma cacao
Common reaction on caffeine, theobromine
and theophylline – Murexyde reaction
Theobromine
Systematic (IUPAC) name 3,7-dimethyl2,3,6,7-tetrahydro-1H-purine-2,6-dione
Specific reactions on theobromine
– theobromine reacts with NaOH and CoCl2, appears evanescent
violet color and separates gray-blue precipitate of cobalt salt.
Theophylline in these conditions forms cobalt salt - white
sediment with pink tinge:
– with HgCl3 - white crystal precipitate;
– sodium salt of theobromine reacts with AgNO3 –
forms gelatins mass (silver salt):
A chocolate bar and melted chocolate.
Chocolate is made from the cacao bean, which is a
natural source of theobromine.
The mean theobromine concentrations in cocoa and carob products are:
Item
Mean theobromine
content (mg/g)
Cocoa
20.3
Cocoa cereals
0.695
Chocolate
bakery
products
1.47
Chocolate
toppings
1.95
Cocoa beverages
2.66
Chocolate ice
creams
0.621
Chocolate milks
0.226
Carob products
0-0.504
Theophylline
Systematic (IUPAC) name 1,3dimethyl-7H-purine-2,6-dione
Synthesis
Theophylline can be prepared synthetically from
dimethylurea and ethyl 2-cyanoacetate.
Specific reactions on theophylline
– theophylline forms with CoCl2 salt - white sediment with pink tinge (look at the
previous slide);
– with alkali solution of sodium nitropruside – green color dissolved in excess of acid;
– with HgCl3 - white crystal precipitate;
– sodium salt of theophylline reacts with AgNO3 – forms gelatins mass (silver salt):
19. Alkaloids group of tropane (atropine, scopolamine,
cocaine).
Atropine is a tropane alkaloid extracted from
Systematic (IUPAC) name (8methyl-8-azabicyclo[3.2.1]oct3-yl) 3-hydroxy-2phenylpropanoate; tropinic
ester of tropic acid
deadly nightshade (Atropa belladonna),
jimsonweed (Datura stramonium), mandrake
(Mandragora officinarum) and other plants of the
Solanaceae family.
Atropine
Derivatives of tropane
Tropine
Scopine
Echonine
Common reaction on tropane alkaloids – rection of
Vitaly-Moren
In a porcelain cup to atropine add conc. HNO3
and heat to dry state – forms yellow polinitrocompound, dissolve this compound in
acetone, addo, 0,5M alcohol solution of KOH. Appears violet color disappears by
standing.
Qualitative reactions on atropine
– with picric acid – yellow precipitate;
– with Marci reagent – yellow color;
– formation of benzaldehyde:
Scopolamine
Systematic (IUPAC) name
(-)-(S)-3-hydroxy-2-phenyl-propionic acid
(1R,2R,4S,7S,9S)9-methyl-3-oxa9-aza-tricyclo[3.3.1.02,4]non-7-yl ester;
Scopinic ester of tropic acid
Scopolamine, known by the names
levo-duboisine and hyoscine, is a
tropane alkaloid drug with muscarinic
antagonist effects. It is obtained from
plants of the Solanaceae family
(nightshades), such as Datura
Stramonium.
It is among the secondary metabolites of these plants.
Therefore, scopolamine is one of three main active components of
belladonna and stramonium tinctures and powders used medicinally
along with atropine and hyoscyamine. Scopolamine has anticholinergic
properties and has legitimate medical applications in very small doses.
An overdose can cause delirium, delusions, dangerous elevations of
body temperature, stupor and death.
Cocaine
Systematic (IUPAC) name
methyl (1R,2R,3S,5S)-3(benzoyloxy)-8-methyl-8azabicyclo[3.2.1] octane-2carboxylate; methylester of
benzoilechonine
The coca plant,
Erythroxylon coca.
Cocaine (benzoylmethyl ecgonine) is a
crystalline tropane alkaloid that is obtained from
the leaves of the coca plant. The name comes
from "coca" in addition to the alkaloid suffix -ine,
forming cocaine. It is both a stimulant of the
central nervous system and an appetite
suppressant.
Specifically, it is a dopamine reuptake
inhibitor, a norepinephrine reuptake inhibitor
and a serotonin reuptake inhibitor. Its
possession, cultivation, and distribution are
illegal for non-medicinal and non-government
sanctioned purposes in virtually all parts of the
world. Although its free commercialization is
illegal and has been severely penalized in
virtually all countries.
Qualitative reactions on cocaine
– with KMnO4 – violet crystal precipitate:
– heating with conc. H2SO4 (specific smell of
methylbenzoate, by standing forms crystals of benzoic acid)
Alkaloids group of indole (reserpine, strychnine).
Systematic (IUPAC) name 11,17-dimethoxy-16carbmethoxy-18-(3’,4’,5’trimethoxybenzoyloxy)aloyohim-bane
N
H3CO
N
H
OCH3
H3COOC
O C
OCH3
OCH3
O
OCH3
Rauwolfia
serpentina
Aloyohimbane
6
9
10
8
A
11
12
B
13
5
7
1
C
2
N
H
3
4
N
21
D
14
20
19
15
E
Àë î é î õ³ì áàí
16
17
18
17
Strychnine
1
2
4
N
16
6
A
3
18
E
B
15
7
14
N 9
10
O
F
D
8
5
19
20
13
C
21
G
12
11
* HNO3
O
22
23
Strychnos Nux
Vomica
Thank you for attention!