THEME: Condensed azines. THEME: Condensed azines. Quinoline. Isoquinoline. Acridine.Quinoline. Isoquinoline. Acridine. Diazines.Diazines. Purine. Purine.

associate. prof. Ye. B. Dmukhalska, assistant. I.I. Medvid

LECTURE № 13

PlanePlane1. 1. Receipt of quinoline and his derivatives. Synthesis of Skraupa and Receipt of quinoline and his derivatives. Synthesis of Skraupa and

synthesis of Debner—Miller. Physical and chemical properties of synthesis of Debner—Miller. Physical and chemical properties of quinoline. quinoline.

2. Receipt of isoquinoline. Synthesis of Bischler-Napieralski. Physical 2. Receipt of isoquinoline. Synthesis of Bischler-Napieralski. Physical and chemical properties of isoquinoline.and chemical properties of isoquinoline.

3. Structure, nomenclature, methods of getting and physical and 3. Structure, nomenclature, methods of getting and physical and chemical properties of acridine. chemical properties of acridine.

4. Methods of getting of 4. Methods of getting of sixmember heterocyclic connections with two sixmember heterocyclic connections with two heteroatomsheteroatoms

5. 5. Structure, nomenclature, physical and chemical properties of Structure, nomenclature, physical and chemical properties of pyridazine, pyrimidinepyridazine, pyrimidine, , barbituric acidbarbituric acid, , pyrazinepyrazine,, purine purine, , uric acid.uric acid.

6. Structure, nomenclature and properties of azepines6. Structure, nomenclature and properties of azepines. . BenzazepineBenzazepine,, diazepine. Benzodiazepine, Oxazepam. Radedrol (nitrazepam). diazepine. Benzodiazepine, Oxazepam. Radedrol (nitrazepam). Seduxen (diazepam). Seduxen (diazepam).

7. Classification of alkaloids.7. Classification of alkaloids.

1. Obtaining of quinoline and his derivatives. Synthesis of 1. Obtaining of quinoline and his derivatives. Synthesis of Skraup and synthesis of Debner—Miller. Physical and Skraup and synthesis of Debner—Miller. Physical and

chemical properties of quinoline.chemical properties of quinoline.

The impotent condensed of The impotent condensed of sixmembered heterocycles sixmembered heterocycles connections are with one heteroatom is: 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 Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Quinoline is readily in hot water and most organic solvents. Quinoline is mainly used as a building block to other specialty chemicals. mainly used as a building block to other specialty chemicals. Approximately 4 tonnes are produced annually according to a Approximately 4 tonnes are produced annually according to a report published in 2005. Its principal use is as a precursor to report published in 2005. Its principal use is as a precursor to 8-hydroxyquinoline, which is a versatile chelating agent and 8-hydroxyquinoline, which is a versatile chelating agent and precursor to pesticides. Its 2- and 4-methyl derivatives are precursor to pesticides. Its 2- and 4-methyl derivatives are precursors to cyanine dyes. Oxidation of quinonline affords precursors to cyanine dyes. Oxidation of quinonline affords quinolinic acid (pyridine-2,3-dicarboxylic acid), a precursor to quinolinic acid (pyridine-2,3-dicarboxylic acid), a precursor to the herbicide sold under the name "Assert". the herbicide sold under the name "Assert".

The The Skraup synthesisSkraup synthesis is a chemical reaction used to synthesize is a chemical reaction used to synthesize quinolines. It is named after the Czech chemist Zdenko Hans quinolines. It is named after the Czech chemist Zdenko Hans Skraup (1850-1910). In the archetypal Skraup, aniline is heated Skraup (1850-1910). In the archetypal Skraup, aniline is heated with sulphuric acid, glycerol, and an oxidizing agent, like with sulphuric acid, glycerol, and an oxidizing agent, like nitrobenzene to yield quinoline. The nitrobenzene to yield quinoline. The Skraup synthesisSkraup synthesis place is place is taken in three stages. taken in three stages.

On the first stage glycerin is under the action of On the first stage glycerin is under the action of сoncentrated Hсoncentrated H22S0S044 to dehydration with formation of to dehydration with formation of akrolein:akrolein:

On the second stage appearing akrolein enters into the reaction of On the second stage appearing akrolein enters into the reaction of

condensation with an aniline:condensation with an aniline:

-H2O

On the third stage of reaction of 1,2-On the third stage of reaction of 1,2-dihydroquinoline oxidizes nitrobenzol in to dihydroquinoline oxidizes nitrobenzol in to quinoline:quinoline:

Synthesis of Debner —Miller.Synthesis of Debner —Miller. The reaction is opened in 1881. On the first stage there is krothonic The reaction is opened in 1881. On the first stage there is krothonic condensation of two molecules of aldehydecondensation of two molecules of aldehyde ..

Further there is cooperation of krothonic aldehyde with aniline.Further there is cooperation of krothonic aldehyde with aniline.

2-methyl-1,2-dihydroquinoline 2-methyl-quinoline

Chemical properties:Chemical properties:

1. Reactions of heteroatom.1. Reactions of heteroatom.

quinoline chloride

N-methylquinoline iodide

N-acethylquinoline chloride

2. Reactions of electrophilic and nukleophilic substitutions .2. Reactions of electrophilic and nukleophilic substitutions .

Reactions ofReactions of electrophilielectrophilicc substitution in the molecula of substitution in the molecula of quinoline quinoline is entered in position of 5 and 8.is entered in position of 5 and 8.

6- quinoline sulphatic acid

Reactions of nukleophilic substitution (is entered in position of 2) .

2- hydroxyquinoline 2- aminoquinoline

3. Reactions of reduction and oxidization.3. Reactions of reduction and oxidization.

quinolinic acid

Derivatives of quinolineDerivatives of quinoline

8-Hydroxyquinoline8-Hydroxyquinoline is an organic compound with the is an organic compound with the formula Cformula C99HH77NO. It is a derivative of the heterocycle NO. It is a derivative of the heterocycle quinoline by placement of an OH group on carbon quinoline by placement of an OH group on carbon number 8. This colorless compound is widely used number 8. This colorless compound is widely used commercially, although under a variety of names. It is commercially, although under a variety of names. It is usually prepared from quinoline-8-sulfonic acid and usually prepared from quinoline-8-sulfonic acid and from the Skraup synthesis from 2-aminophenol.from the Skraup synthesis from 2-aminophenol.

-Na2SO3

NaOH

8-Hydroxyquinoline is a monoprotic bidentate 8-Hydroxyquinoline is a monoprotic bidentate chelating agent. Related ligands are the Schiff bases chelating agent. Related ligands are the Schiff bases derived from salicylaldehyde, such as salicylaldoxime derived from salicylaldehyde, such as salicylaldoxime and salen. The roots of the invasive plant and salen. The roots of the invasive plant Centaurea Centaurea diffusadiffusa release 8-hydroxyquinoline, which has a release 8-hydroxyquinoline, which has a negative effect on plants that have not co-evolved negative effect on plants that have not co-evolved with it. The complexes as well as the heterocycle with it. The complexes as well as the heterocycle itself exhibit antiseptic, disinfectant, and pesticide itself exhibit antiseptic, disinfectant, and pesticide properties. Its solution in alcohol are used as liquid properties. Its solution in alcohol are used as liquid bandages. It once was of interest as an anti-cancer bandages. It once was of interest as an anti-cancer drug.drug.

2. Receipt of isoquinoline. Synthesis of Bischler-Napieralsk2. Receipt of isoquinoline. Synthesis of Bischler-Napieralskii. .

Physical and chemical properties of isoquinoline.Physical and chemical properties of isoquinoline. Isoquinoline, also known as Isoquinoline, also known as

benzo[c]pyridine or 2-benzanine, benzo[c]pyridine or 2-benzanine, is a is a heterocyclic aromatic organic heterocyclic aromatic organic compound. It compound. It is a structural isomer of is a structural isomer of quinoline. Isoquinoline and quinoline are benzopyridines, which quinoline. Isoquinoline and quinoline are benzopyridines, which are composed of a benzene ring fused to a pyridine ring. In a are composed of a benzene ring fused to a pyridine ring. In a broader sense, the term isoquinoline is used to make reference broader sense, the term isoquinoline is used to make reference to isoquinoline derivatives. 1-Benzylisoquinoline is the to isoquinoline derivatives. 1-Benzylisoquinoline is the structural backbone in naturally occurring alkaloids including structural backbone in naturally occurring alkaloids including papaverine and morphine. The isoquinoline ring in these natural papaverine and morphine. The isoquinoline ring in these natural compound derives from the aromatic amino acid tyrosine. compound derives from the aromatic amino acid tyrosine. Isoquinoline is a colourless hygroscopic liquid at room Isoquinoline is a colourless hygroscopic liquid at room temperature with a penetrating, unpleasant odour. Impure temperature with a penetrating, unpleasant odour. Impure samples can appear brownish, as is typical for nitrogen samples can appear brownish, as is typical for nitrogen heterocycles. It crystallizes platelets that have a low solubility in heterocycles. It crystallizes platelets that have a low solubility in water but dissolve well in ethanol, acetone, diethyl ether, carbon water but dissolve well in ethanol, acetone, diethyl ether, carbon disulfide, and other common organic solvents. It is also soluble disulfide, and other common organic solvents. It is also soluble in dilute acids as the protonated derivative.in dilute acids as the protonated derivative.

In the Bischler-Napieralski reactionIn the Bischler-Napieralski reaction an an ββ-phenylethylamine is acylated -phenylethylamine is acylated and cyclodehydrated by a Lewis acid, such as phosphoryl chloride or and cyclodehydrated by a Lewis acid, such as phosphoryl chloride or phosphorus pentoxide. The resulting 1-substituted-3,4-dihydroisoquinoline phosphorus pentoxide. The resulting 1-substituted-3,4-dihydroisoquinoline can then be dehydrogenated using palladium. can then be dehydrogenated using palladium. The following Bischler-The following Bischler-Napieralski reaction produces papaverine.Napieralski reaction produces papaverine.

1-substituted-3,4-dihydroisoquinoline

1-substituted isoquinoline

Chemical properties:Chemical properties:

1. Reactions of electrophilic and nukleophilic substitutions .1. Reactions of electrophilic and nukleophilic substitutions .

Reactions ofReactions of electrophilielectrophilicc substitution in the molecula of iso substitution in the molecula of isoquinoline quinoline is is entered in position of 5 and 8. Reactions of nukleophilic substitutions tare entered in position of 5 and 8. Reactions of nukleophilic substitutions tare place in position of 1.place in position of 1.

N-methylisoquinoline of iodide

isoquinoline of chloride

2. Reaction of reduction 2. Reaction of reduction

1,2,3,4- tetrahydroisoquinoline

3. Reaction of oxidization

3,4- pyridinedicarbonic acid

Methods of getting:Methods of getting:

1. Condensation of diphenylamine with 1. Condensation of diphenylamine with carboniccarbonic acids acids ::

2. Cyclization N-fenilanthranilic acid on the reaction of Drozdov2. Cyclization N-fenilanthranilic acid on the reaction of Drozdov—Mahidson—Hrihorovsky:—Mahidson—Hrihorovsky:

diphenylamine acridine

N-fenilanthranilic acid anhidride chlorideN-fenilanthranilicacid

acridone-9

acridole-9 9-chloracridine

9,10-dihydroacridine acridine

1.1. Reactions of heteroatom.Reactions of heteroatom.

2. Reactions of electrophilic and nukleophilic substitutions . 2. Reactions of electrophilic and nukleophilic substitutions .

acridinium chloride

N-oxide of acridine N-methylacridine iodide

9-hydroxacridine, 9- oxoacridine,acridole-9 acridone-9

3.3. Reactions of oxidization.Reactions of oxidization.

4. Reactions of reduction.4. Reactions of reduction.acridinic acid

9,10-dehydroacridine,acridane

Derivatives of acridineDerivatives 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 NH2

OC2H5 COOH

O2N NH

OC2H5

POCl3

-HClO2N NH

OC2H5

N

OC2H5

OH

O2N

POCl3

C

O

N

OC2H5

Cl

O2N

NH3

-HClN

OC2H5

NH2

O2N

[H]

9-amino-2-ethoxy-6-nitroacridine

N

OC2H5

NH2

NH2

CH

CH3

OH

COOH

N

OC2H5

NH2

NH2

CH

CH3

OH

COOH

+

.

ethacridine lactate, rivanol,6,9 – diamimo-2-ethoxyacridine lactate

Sixmembered heterocycles connections are with two Sixmembered heterocycles connections are with two heteroatomsheteroatoms

In addition to these three diazines, the In addition to these three diazines, the bicyclic tetraaza compound, purine, is bicyclic tetraaza compound, purine, is an important heterocyclic system. an important heterocyclic system.

These ring systems, particularly that of pyrimidine, occur commonly These ring systems, particularly that of pyrimidine, occur commonly in natural products. The pyrimidines, cytosine, thymine, and uracil in natural products. The pyrimidines, cytosine, thymine, and uracil are especially important because they are components of nucleic are especially important because they are components of nucleic acids, as are the purine derivatives adenine and guanine.acids, as are the purine derivatives adenine and guanine.

The рurine nucleus also occurs in such The рurine nucleus also occurs in such compounds as caffeine (coffee and tea) and compounds as caffeine (coffee and tea) and

theobromine (cacao beans).theobromine (cacao beans).

4. 4. Methods of getting of Methods of getting of sixmember heterocyclic connections with two heteroatoms

NN

CH

CO

O

CCH H

H

NH2

NH2

- H2O

pyridazine

C H2

C

C

O

O

O C2H

5

O C2H

5

C

NH2

NH2

O

C2H

5O N a

-C2H

5O H N

N

O HOH

O H

N

N

O

O O

H

H

H

H

+C

barbituric acidбарбітурова

maleinaldehidemaleinaldehide

ureaureaMalene ephirMalene ephir

POCl 3

N

N

Cl

Cl

ClN

N6H (Zn)

pyrimidine

These method use for obtaining pyridazine and his derivatives

N

N

NH2

NH2

C HO

OH- H2O

N

N NH

N+

2

NH2

CH2

CH2

NH2

C

C

O

O

H

H

- H2O - H2O

O

N

N

N

N+

to

2

2,3- dihydropyrazine2,3- dihydropyrazineethylendiamineethylendiamine glyoxglyoxalal

pyrazinepyrazine

purinepurine

5. 5. Structure, classification, nomenclature, physical Structure, classification, nomenclature, physical and chemical properties of pyridazine. 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 names1,2-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

NN

NN

+

H

Cl-

NN

CH3

CH3I

NN

O

CH3COOOH

HCl (í àäë .)+ I-

+_

PyridazinPyridazine e chloridechloride

N-N-methylpyridazinmethylpyridazine iodidee iodide

N-oxide pyridazineN-oxide pyridazine

thethramethyleldiaminethethramethyleldiamine

Derivatives of pyridazineDerivatives 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

NN

NOH

NH2

ê. HNO3

ê. H2SO4

N

N

NH2

Br2

N

N NaNH2

N

NH

ClN

NOH

NH2

NO2

N

N

NH2

Br

N

N

NH2

N

N

_

+HCl

4-amino-2-hydroxypyridine4-amino-2-hydroxypyridinepyrimidine chloridepyrimidine chloride

2- aminopyridine2- aminopyridine

Derivatives of pyrimidineDerivatives of pyrimidineBarbituric acid (2,4,6-trihydroxypyrimidine)Barbituric acid (2,4,6-trihydroxypyrimidine)

Keto-enole and lactam-lactim tautomery

7. 7. Structure, nomenclature, physical and chemical properties of Structure, nomenclature, physical and chemical properties of barbituric acid.barbituric acid.

Barbituric acidBarbituric acid or or malonylureamalonylurea or or 4-4-hydroxyuracilhydroxyuracil is an organic compound based is an organic compound based on a pyrimidine heterocyclic skeleton. It is an on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in hot water. Barbituric odorless powder soluble in hot water. Barbituric acid is the parent compound of a large class of acid is the parent compound of a large class of barbiturates that have central nervous system barbiturates that have central nervous system depressant properties, although barbituric acid depressant properties, although barbituric acid itself is not pharmacologically active. itself is not pharmacologically active.

The compound was discovered by the German The compound was discovered by the German chemist Adolf von Baeyer on 4. December 1864chemist Adolf von Baeyer on 4. December 1864—the feast of St Barbara and therefore the name —the feast of St Barbara and therefore the name given to the compound—by combining urea and given to the compound—by combining urea and malonic acid in a condensation reaction. Malonic malonic acid in a condensation reaction. Malonic acid has since been replaced by diethyl acid has since been replaced by diethyl malonate.malonate.

Bases of pyrimidine (important derivativesBases of pyrimidine (important derivatives ) )

These bases are present in nucleinic acids

Vitamin BVitamin B11 (thiamine) (thiamine) contain pyrimidine and thyazole ring connect contain pyrimidine and thyazole ring connect through methyl group. through methyl group.

Physiological active form of vitaminPhysiological active form of vitamin B1 in living organisms is cocarboxilaza, which B1 in living organisms is cocarboxilaza, which take part in enzyme processes, in hydrocarbon exchangetake part in enzyme processes, in hydrocarbon exchange

Orotic acid is primary compound in biosynthesis of pyrimidine bases

Pyrazine

Other names1,4-Diazabenzene, p-Diazine, 1,4-

Diazine, 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 The Gastaldi synthesisGastaldi synthesis (1921) is another variation: (1921) is another variation:

Chemical properties of pyrazineChemical properties of pyrazine

N

N H

(Na + CH3CH2OH)NH

NH

N

N NaNH2, NH3

N

N

NH2

N

N CH3COOOHN

N

O_

+

pyperazinepyperazine

2-2-aminopyraziaminopyrazinene

N- oxide pyrazineN- oxide pyrazine

Purine

Properties

Molecular formula C5H4N4

Molar mass 120.112

Melting point 214 °C

Synthesis of purineSynthesis of purineTraube method: condnsation 4,5-Traube method: condnsation 4,5-

diaminopyrimidines with carbonic acidsdiaminopyrimidines with carbonic acids

The The Traube purine synthesisTraube purine synthesis (1900) is a classic (1900) is a classic reaction (named after Wilhelm Traube) between an reaction (named after Wilhelm Traube) between an

amine substutited pyrimidine and formic acidamine substutited pyrimidine and formic acid

Chemical properties of purine.Chemical properties of purine. FFor purinor purinee is characteristic is characteristic of of azoazolele tautomer tautomeryy : :

N H

N

N

N

Cl

Cl

Cl

N H 3H

N H

N

N

N

Cl

Cl

N H 2

N H

N

N

N

N H 2

K O H

N H

N

N

N

Cl

Cl

O H

N H 3

N H

N

N

N

NH 2

Cl

O H

H

N H

N

N

N

NH 2

O H

H

NH

N NH

N

O

H N O 2

NH

NH

NH

N

O

O

(1:1)

adenine

(1:1)

guanine

hypoxanthine xanthine

Purine is an amphoteric compoundPurine is an amphoteric compound

Derivatives of purineDerivatives of purine

Main derivatives of purine are oxopurines: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 formsThauthomeric forms

NH

NH

NH

NH

O

O

O

N

N NH

NO H

OH

O H

uric acid

NH

NH

NH

N

O

O

N

N NH

N

OH

O H

xanthine

N

N NH

N

O HNH

N NH

N

O

hypoxanthine

Salts of uric acid called urats. Urats is bad soluble Salts of uric acid called urats. Urats is bad soluble in water, except salts with litium (Li).in water, except salts with litium (Li).

In hydroxyform uric acid gives reactions of In hydroxyform uric acid gives reactions of nucleophilic substitutions.nucleophilic substitutions.

Chemical propertiesChemical properties

N

NN

N

O

O

O

H H

HH

N

NN

N

O

NaO

ONa

H

H

H2NaOH

+ _

+_

N

N NH

NOH

OH

OH

POCl3

NH

N

N

N

Cl

Cl

Cl

disodium salt of uric acid disodium salt of uric acid

2,6,8-threechlorpurine2,6,8-threechlorpurine

Reactions of oxidationReactions of oxidation

alantoinealantoinealoxanealoxane ureaurea

Murexidne’s reaction is the qualitative Murexidne’s reaction is the qualitative reaction on uric acidreaction on uric acid

By heating uric acid with nitrate acid and next By heating uric acid with nitrate acid and next adding of ammonium observe purpur-violet color adding of ammonium observe purpur-violet color

purpure purpure acid (enole acid (enole form)form)

murexidemurexide

Reactions of reductionReactions of reduction

xanthinexanthine

Hypoxantine and xantine have the same Hypoxantine and xantine have the same chemical properties as uric acidchemical properties as uric acid

N-methyl derivatives of hypoxantine and xantine widely used in pharmacy

AminopurinesAminopurines Maine aminoderivatives of purine – Maine aminoderivatives of purine –

adenine and guanine present in nucleinic adenine and guanine present in nucleinic acids as purine’s bases.acids as purine’s bases.

PhenothiazinePhenothiazine Phenothiazine (dibenzo-1,4-thiazine) – colorless crystal compound, Phenothiazine (dibenzo-1,4-thiazine) – colorless crystal compound,

insoluble in water, diethyl ether, well soluble in hot ethanol.insoluble in water, diethyl ether, well soluble in hot ethanol.

Method of getting

Chemical properties

1. Alkylation and acylation

2. Oxidation2. 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)Pteridine (pyrazino[2,3-d]pyrimidine)

Method of getting: condensation of 4,5-diaminopyrimidins with 1,2-dicarbonile compounds

Pteridine is light yellow crystal compound, soluble in water, ethanol, less soluble in 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 diethyl ether and benzole. Pteridine is stable to oxidation, by acting of acids and bases pteridine cycle decompose. Gives reaction of electrophilic substitution, bases pteridine cycle decompose. Gives reaction of electrophilic substitution, protonate on nitrogen atom in 1 location. protonate on nitrogen atom in 1 location.

Derivatives of pteridineDerivatives of pteridine Folic acid (vitamin Bc)Folic acid (vitamin Bc)

Aloxasine and isoaloxasineAloxasine and isoaloxasine These compounds include benzyl, These compounds include benzyl,

pyrazine and hydrate pyriidine cyclespyrazine and hydrate pyriidine cycles

Flavine is a primery compound of riboflavin:

11. Structure, nomenclature and properties of 11. Structure, nomenclature and properties of

azepines. Benzazepine. Sevenmember heterocyclic ring Sevenmember heterocyclic ring

compounds have received much attention in the compounds have received much attention in the past few years owing to its wide range of past few years owing to its wide range of biological activity. biological activity.

AzepinesAzepines are heterocycles are heterocycles of seven atoms, with a of seven atoms, with a nitrogen replacing a carbon nitrogen replacing a carbon at one position.at one position.

A well known azepine is A well known azepine is caprolactamcaprolactam

Skeletal formula of caprolactam. Skeletal formula of caprolactam.

Sevenmember heterocycles which containing nitrogen

BenzazepineBenzazepine: bicyclic structure consisting of : bicyclic structure consisting of fused benzene and azepine rings; many fused benzene and azepine rings; many compounds with this structure react with compounds with this structure react with

biogenicamine receptors, and so are psychotropic biogenicamine receptors, and so are psychotropic and neurotropic.and neurotropic.

Examples of benzazepine include fenoldopam and Examples of benzazepine include fenoldopam and galantamine. galantamine.

ffenoldopamenoldopam galantaminegalantamine

12.12. Structure, nomenclature and properties Structure, nomenclature and properties

of of diazepine. Benzodiazepine..

DiazepineDiazepine is a sevenmember is a sevenmember heterocyclic compound with two heterocyclic compound with two

nitrogen atoms (e.g., in ring nitrogen atoms (e.g., in ring positions 1 and 2) and positions 1 and 2) and three three double bonds. double bonds.

When diazepine combined with a benzene ring, these is When diazepine combined with a benzene ring, these is the basis of the benzodiazepine family . In these the basis of the benzodiazepine family . In these compounds the nitrogen atoms are at the 1 and 4 compounds the nitrogen atoms are at the 1 and 4 positions as, for example, in clobazam (depending on positions as, for example, in clobazam (depending on the position of the fused benzene ring, the nitrogen the position of the fused benzene ring, the nitrogen atoms are also in positions number 1 and 4).atoms are also in positions number 1 and 4).

5-Phenyl-1,3-dihydro-2H-1,4- 5-Phenyl-1,3-dihydro-2H-1,4- benzodiazepin-2-on benzodiazepin-2-on

forms the skeleton on many of forms the skeleton on many of the most common the most common

benzodiazepine benzodiazepine pharmaceuticals, such as diazepam pharmaceuticals, such as diazepam

(chloro-substituted).(chloro-substituted).

The The benzodiazepinesbenzodiazepines are a class of psychoactive drugs with are a class of psychoactive drugs with varying hypnotic, sedative, anxiolytic (anti-anxiety), anticonvulsant, varying hypnotic, sedative, anxiolytic (anti-anxiety), anticonvulsant, muscle relaxant and amnesic properties, which are mediated by muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. Benzodiazepines are slowing down the central nervous system. Benzodiazepines are useful in treating anxiety, insomnia, agitation, seizures, and muscle useful in treating anxiety, insomnia, agitation, seizures, and muscle spasms, as well as alcohol withdrawal. They can also be used spasms, as well as alcohol withdrawal. They can also be used before certain medical procedures such as endoscopies or dental before certain medical procedures such as endoscopies or dental work where tension and anxiety are present, and prior to some work where tension and anxiety are present, and prior to some unpleasant medical procedures in order to induce sedation and unpleasant medical procedures in order to induce sedation and amnesia for the procedure. Benzodiazepines are also used to treat amnesia for the procedure. Benzodiazepines are also used to treat the panic that can be caused by hallucinogen intoxication.the panic that can be caused by hallucinogen intoxication.

Benzodiazepines can cause a physical dependence and a Benzodiazepines can cause a physical dependence and a benzodiazepine addiction to develop and upon cessation of long benzodiazepine addiction to develop and upon cessation of long term use a benzodiazepine withdrawal syndrome can occur.term use a benzodiazepine withdrawal syndrome can occur.

13. Oxazepam. Radedrol (nitrazepam). Seduxen (diazepam).

N

NO

Cl

O H

Oxazepam7-clorine-3-hydroxy-5-phenil-1,3-dihydro-2H-1,4-benzodiazepin-2-on

Oxazepam (marketed in English speaking 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 has moderate amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties compared to other benzodiazepines.

Oxazepam is an intermediate acting benzodiazepine. Oxazepam acts as inhibitor on the central nervous system. The half-life of oxazepam is 4-15 hours. Oxazepam has been shown to suppress cortisol levels.

Nitrazepam is a nitrobenzodiazepine It is a 1,4 benzodiazepine, with the

chemical name 7-nitro-5-phenyl-1,3-

dihydro-2H-1,4- benzodiazepin-2-on. 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.

N

NO

O 2N

NitrazepamNitrazepam

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 (gamma-aminobutyric 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

DiazepamDiazepam first marketed as first marketed as ValiumValium by by Hoffmann-La Roche, is a benzodiazepine Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, derivative drug. It possesses anxiolytic,

anticonvulsant, hypnotic, sedative, skeletal anticonvulsant, hypnotic, sedative, skeletal muscle relaxant and amnestic properties. It is muscle relaxant and amnestic properties. It is commonly used for treating anxiety, insomnia, commonly used for treating anxiety, insomnia, seizures, muscle spasms, alcohol withdrawal seizures, muscle spasms, alcohol withdrawal

and benzodiazepine withdrawal. and benzodiazepine withdrawal.

N

NO

Cl

CH3

O

diazepam(4N-oxide 7-chlorine-1-methyl-5-phenil-1,3-dihydro-2Н- 1,4-benzodiazepin-2-оne )

Diazepam occurs as solid white or yellow Diazepam occurs as solid white or yellow crystals and has a melting point of 131.5 to 134.5 °C. crystals and has a melting point of 131.5 to 134.5 °C. It is odorless, and has a slightly bitter taste. The British It is odorless, and has a slightly bitter taste. The British Pharmacopoeia lists diazepam as being very slightly Pharmacopoeia lists diazepam as being very slightly soluble in water, soluble in alcohol and freely soluble soluble in water, soluble in alcohol and freely soluble in chloroform. The United States Pharmacopoeia lists in chloroform. The United States Pharmacopoeia lists diazepam as soluble 1:16 in ethyl alcohol, 1:2 in diazepam as soluble 1:16 in ethyl alcohol, 1:2 in chloroform, 1:39 in ether, and practically insoluble in chloroform, 1:39 in ether, and practically insoluble in water.water.

Qualitative reactions on benzodiazepinesQualitative reactions on benzodiazepines

1. 1. With concentrated acids (H2SO4, HCl, HClO4) With concentrated acids (H2SO4, HCl, HClO4) derivatives of benzodiazepines form color salts.derivatives of benzodiazepines form color salts.

2. Heterocyclic nitrogen atom gives positive reaction with 2. Heterocyclic nitrogen atom gives positive reaction with common alkaloids precipitate reagents. common alkaloids precipitate reagents.

3. Specific reaction on benzodiazepines derivatives is 3. Specific reaction on benzodiazepines derivatives is formation of green color after pyrolisis.formation of green color after pyrolisis.

4. Formation of azodays after primary hydrolysis:4. Formation of azodays after primary hydrolysis:

Nozepam

5. Belshteine probe use for determination of halogens.5. Belshteine probe use for determination of halogens.

6. Noozepam by heating with conc. H2SO4 hydrolyzed with 6. Noozepam by heating with conc. H2SO4 hydrolyzed with formation of formaldehyde, which forms violet color with formation of formaldehyde, which forms violet color with fuxinsulfite acid.fuxinsulfite acid.

Pyridine and piperidine group: piperine, coniine, trigonelline, arecoline, Pyridine and piperidine group: piperine, coniine, trigonelline, arecoline, arecaidine, guvacine, cytisine, lobeline, nicotine, anabasine, sparteine, arecaidine, guvacine, cytisine, lobeline, nicotine, anabasine, sparteine, pelletierine.pelletierine.

Pyrrolidine and pyrolisidine group: hygrine, cuscohygrine, platyphylline, Pyrrolidine and pyrolisidine group: hygrine, cuscohygrine, platyphylline, nicotine.nicotine.

Tropane group: atropine, cocaine, ecgonine, scopolamine, catuabine.Tropane group: atropine, cocaine, ecgonine, scopolamine, catuabine.

Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine, Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine, strychnine, brucine, veratrine, cevadine.strychnine, brucine, veratrine, cevadine.

Isoquinoline group: opium alkaloids (papaverine, narcotine, narceine), Isoquinoline group: opium alkaloids (papaverine, narcotine, narceine), sanguinarine, hydrastine, berberine, emetine, berbamine, oxyacanthine.sanguinarine, hydrastine, berberine, emetine, berbamine, oxyacanthine.

NN

H

3N CH

N

N

N N

H

Phenanthrene alkaloids: opium alkaloids (morphine, codeine, Phenanthrene alkaloids: opium alkaloids (morphine, codeine, thebaine)thebaine)

Phenethylamine group: mescaline, ephedrine, dopaminePhenethylamine group: mescaline, ephedrine, dopamine

Indole group: Indole group:

Tryptamines: serotonin, bufotenine, psilocybinTryptamines: serotonin, bufotenine, psilocybin Ergolines (the ergot alkaloids): ergine, ergotamine, lysergic acidErgolines (the ergot alkaloids): ergine, ergotamine, lysergic acid Beta-carbolines: harmine, harmaline, tetrahydroharmineBeta-carbolines: harmine, harmaline, tetrahydroharmine Yohimbans: reserpine, yohimbineYohimbans: reserpine, yohimbine Vinca alkaloids: vinblastine, vincristineVinca alkaloids: vinblastine, vincristine Kratom (Kratom (Mitragyna speciosaMitragyna speciosa) alkaloids: mitragynine, 7-) alkaloids: mitragynine, 7-

hydroxymitragyninehydroxymitragynine Tabernanthe ibogaTabernanthe iboga alkaloids: ibogaine, voacangine, coronaridine alkaloids: ibogaine, voacangine, coronaridine Strychnos nux-vomicaStrychnos nux-vomica alkaloids: strychnine, brucine alkaloids: strychnine, brucine

Purine group: Purine group:

Xanthines: caffeine, theobromine, theophyllineXanthines: caffeine, theobromine, theophylline

N

H

N

N

N

N

H

15. Alkaloids group of pyridine and piperine 15. Alkaloids group of pyridine and piperine (nicotine, anabasine, lobeline).(nicotine, anabasine, lobeline).

Systematic (IUPAC) name

3-3-[2’-(N-[2’-(N-methylpyrrolidimethylpyrrolidil)l)]pyridine]pyridine

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.

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.

CH3

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.

PharmacologyAnabasine 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.

β-(α’-pyperidile)pyridine

Systematic (IUPAC) nameSystematic (IUPAC) name

L-(-)-2benzoilmethyle-6-(2’-hydroxy-L-(-)-2benzoilmethyle-6-(2’-hydroxy-2’-phenylethyl)-1-methylpyperidine2’-phenylethyl)-1-methylpyperidine

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 longiflora. In its pure form it is a white amorphous powder which is freely soluble in water. Lobeline has been used as a smoking cessation aid, and may 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.

CH3

16. Alkaloids group of quinoline (quinine).16. Alkaloids group of quinoline (quinine).

QuinineSystematic (IUPAC) name (R)-(6-

methoxyquinolin-4-yl)- (8’-vinylquinuclidin-2’-yl)methanol

QuinineQuinine is a natural white crystalline alkaloid having is a natural white crystalline alkaloid having antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and anti-inflammatory properties and a bitter taste. It is a stereoisomer of anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine.quinidine.Quinine was the first effective treatment for malaria caused by Quinine was the first effective treatment for malaria caused by Plasmodium falciparumPlasmodium falciparum, appearing in therapeutics in the 17th century. , appearing in therapeutics in the 17th century. Since then, many effective antimalarials have been introduced, Since then, many effective antimalarials have been introduced, although quinine is still used to treat the disease in certain critical although quinine is still used to treat the disease in certain critical situations. Quinine is available with a prescription in the United situations. Quinine is available with a prescription in the United States. Quinine is also used to treat nocturnal leg cramps and States. Quinine is also used to treat nocturnal leg cramps and arthritis. arthritis.

Chemical structureChemical structureQuinine contains two major fused-ring systems: The aromatic quinoline and Quinine contains two major fused-ring systems: The aromatic quinoline and the bicyclic quinuclidinethe bicyclic quinuclidine ..

Qualitative reaction on quinineThaleyoquine test: emerald-green color

– with conc. H2SO4 – blue fluorescence;

– with sodium nitroprusside - yellow sediment.

PapaverineSystematic (IUPAC) name

1-(3’,4’-dimethoxybenzyl)-6,7-dimethoxyisoquinoline

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).

17. Alkaloids of group of quinoline and 17. Alkaloids of group of quinoline and phenanthreneisoquinoline phenanthreneisoquinoline (papaverine, morphine, codeine). (papaverine, morphine, codeine).

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.

3. With bromine water – yellow precipitate.

N

H3CO

H3CO

CH2

H3CO OCH3

HNO3

N

H3CO

H3CO

CH2

H3CO OCH3

NO2

O2N

N

H3CO

H3CO

CH2

H3CO OCH3

NO2

HNO3

жовте забарвлення оранжеве забарвлення

t 0C

Yellow 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.

CH2

N+ N+

CH2

CH2

H H

H3CO

H3CO OCH3

OCH3

OCH3H3COOCH3OCH3

SO42-

Systematic (IUPAC) nameSystematic (IUPAC) name 3,6-dihydroxy-N-methyl- 4,5-3,6-dihydroxy-N-methyl- 4,5-epoxymorphinene-7epoxymorphinene-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.

ChemistryChemical 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 morphine1. 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

CodeineCodeineSystematic (IUPAC) nameSystematic (IUPAC) name

6-hydroxy-N-methyl-3-methoxy- 6-hydroxy-N-methyl-3-methoxy- 4,5-epoxymorphinen-74,5-epoxymorphinen-7

Codeine (INN) or methylmorphine 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 codeine1. 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 (Alkaloids group of purine (caffeine, theobromine, caffeine, theobromine, theophyllinetheophylline).).

1,3,7-1,3,7-trimethylxanthine, trimethylxanthine, trimethylxanthine,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

TheobromineSystematic (IUPAC) name 3,7-dimethyl-2,3,6,7-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:The mean theobromine concentrations in cocoa and carob products are:

ItemMean 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

TheophyllineSystematic (IUPAC) name 1,3-dimethyl-7H-purine-2,6-dione

SynthesisTheophylline can be prepared synthetically from Theophylline can be prepared synthetically from dimethylurea and ethyl 2-cyanoacetate.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, 19. Alkaloids group of tropane (atropine, scopolamine, cocaine).cocaine).

AtropineAtropine is a tropane alkaloid extracted from is a tropane alkaloid extracted from deadly nightshade (deadly nightshade (Atropa belladonnaAtropa belladonna), ), jimsonweed (jimsonweed (Datura stramoniumDatura stramonium), mandrake ), mandrake ((Mandragora officinarumMandragora officinarum) and other plants of the ) and other plants of the Solanaceae family. Solanaceae family.

Systematic (IUPAC) nameSystematic (IUPAC) name ( (8-8-methyl-8-azabicyclo[3.2.1]oct-methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-3-yl) 3-hydroxy-2-phenylpropanoate; tropinic phenylpropanoate; tropinic ester of tropic acidester of tropic acid

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:

ScopolamineScopolamineSystematic (IUPAC) nameSystematic (IUPAC) name

(-)-((-)-(SS)-3-hydroxy-2-phenyl-propionic acid )-3-hydroxy-2-phenyl-propionic acid (1(1RR,2,2RR,4,4SS,7,7SS,9,9SS)-)-9-methyl-3-oxa-9-methyl-3-oxa-9-aza-tricyclo[3.3.1.09-aza-tricyclo[3.3.1.02,42,4]non-7-yl ester]non-7-yl ester;;Scopinic ester of tropic acid Scopinic ester of tropic acid

ScopolamineScopolamine, known by the names , known by the names levo-duboisinelevo-duboisine and and hyoscinehyoscine, is a , is a tropane alkaloid drug with muscarinic tropane alkaloid drug with muscarinic antagonist effects. It is obtained from antagonist effects. It is obtained from plants of the Solanaceae family plants of the Solanaceae family (nightshades), such as (nightshades), such as DaturaDatura Stramonium. Stramonium.

It is among the secondary metabolites of these plants. It is among the secondary metabolites of these plants. Therefore, scopolamine is one of three main active components of Therefore, scopolamine is one of three main active components of belladonna and stramonium tinctures and powders used medicinally belladonna and stramonium tinctures and powders used medicinally along with atropine and hyoscyamine. Scopolamine has anticholinergic along with atropine and hyoscyamine. Scopolamine has anticholinergic properties and has legitimate medical applications in very small doses. properties and has legitimate medical applications in very small doses. An overdose can cause delirium, delusions, dangerous elevations of An overdose can cause delirium, delusions, dangerous elevations of body temperature, stupor and death.body temperature, stupor and death.

CocaineSystematic (IUPAC) name methyl (1R,2R,3S,5S)-3- (benzoyloxy)-8-methyl-8-azabicyclo[3.2.1] octane-2-carboxylate; methylester of benzoilechonine

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.

The coca plant, Erythroxylon coca.

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 iAlkaloids group of indole ndole (reserpine, strychnine).(reserpine, strychnine).

Systematic (IUPAC) nameSystematic (IUPAC) name 11,17-dimethoxy-16-11,17-dimethoxy-16-carbmethoxy-18-(3’,4’,5’-carbmethoxy-18-(3’,4’,5’-trimethoxybenzoyloxy)aloyohim-banetrimethoxybenzoyloxy)aloyohim-bane

NH

NH3CO

H3COOC

OCH3

O C

O

OCH3

OCH3

OCH3

Rauwolfia serpentina

Aloyohimbane

NH

NA C

D

E

12

34

56

789

10

1112

13

14

15

1617

18

19

20

21

B

Àëî é î õ³ì áàí

Strychnine

N

O

N

O

* HNO3

A B

C

D

E

F

G

12

34

5

6 7

8

9

1011

12

13

14

1516

17 18

19

20

21

2223

Strychnos Nux Vomica

Thank you for attention!