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Lecture 12
Sixmember heterocyclic compounds with
one heteroatom. Pyrane. Pyridine.
The most important derivatives of pyridine.
Ass. Medvid I.I.,
ass. Burmas N.I.
Outline
1. Structure, classification, nomenclature, izomery, methods of
getting and chemical properties of pyridine.
2. Structure, nomenclature, methods of getting and chemical
properties of pycoline.
3. Structure, methods of getting and chemical properties of
hydroxypyridine and aminopyridine.
4. Pyridine carbonic acids: structure, classification,
nomenclature, izomery, methods of getting and chemical
properties.
5. Methods of receipt and property of heterocycles of group of
pyran.α- and γ-pyrones. Synthesis and chemical properties
of the condensed derivatives of pyrones (coumarin,
chromone). Flavonoids.
1. Structure, classification, nomenclature, izomery, methods
of getting and chemical properties of pyridine.
Heterocycles containing as a heteroatom atom of nitrogen,
behave to the most widespread representatives of this group of
connections (azynes):
pyridine
quinoline
isoquinoline
acridine
Pyridine, obtained commercially by distillation of coal tar, is
the nitrogen – containing heterocyclic analog of benzene. Like
benzene, pyridine is a flat, aromatic molecule with bond angles
of 120° and C-C bond lengths of 139 pm, intermediate
between typical single and double bonds. The five carbon
atoms and sp²- hybridized nitrogen atom each contribute one π
electron to the aromatic sextet. Unlike the situation in pyrrole,
the lone pair of electrons on the pyridine nitrogen atom
occupies an sp² orbital in the plane of the ring and is not
involved in bonding (Figure 1).
Figure 1
Electronic structure of pyridine, a six-π-electon, nitrogen –
containing analog of benzene. The electrostatic potential map shows
that the nitrogen is the most negative atom (red).
The sp²- hybridized nitrogen atom in pyridine, with 33% s character,
holds the lone-pair electrons more tightly than the sp³- hybridized
nitrogen in an alkylamine (25% s character).
Methods of getting:
1.
Heating to 400 °C of acetone with ammonia.
α-picoline
γ- picoline
2. At heating of akroleine with an ammonia turns out β-picoline:
β-picoline
3. Cooperation of acethylene with the strong acid:
pyridine
4. Condensation of acetaldehyde and formaldehyde with an
ammonia:
pyridine
Chemical properties of pyridine.
Characteristic for pyridine reactions can be divided into
three groups:
I. Reactions which followings with participation of
heteroatom.
II. Reactions of substituting for the hydrogen atoms of
pyridines ring.
III. Reactions of reduction and oxidization.
I. Reactions which followings with participation of heteroatom.
1. Cooperating with acids.
Due to the indivisible pair of electrons atom of nitrogen of
pyridine shows weak basic properties. At cooperating with strong
mineral and organic acids he forms soluble salt of pyridine.
pyridine bromide
2. Reaction with the oxide of sulphur (VI).
II. Reactions of substituting for the hydrogen atoms of
pyridines ring.
1. Reactions of electrophilic substitution (SE).
The reactions of nitration, sulphonation and halogenation pass
slowly drastic and with low exits. Thus an electrophilic reagent is
direct in position 3.
3-nithropyridine
3-pyridinesulphure acid
2. Reactions of nucleophilic substitution.
The substitution goes on positions 2,4,6, most easy of nucleophilic
reagent is entered in position of 2,6 (α-position ). The prime
example of reaction of this type is an amination of pyridine with
sodium of amide on Chychybabyne. The reaction flows to the
mechanism SN2:
σ- complex
2- aminopyridine
III. Reactions of reduction and oxidization.
1.
Reduction .
pyperedine
2. Oxidization .
nicotinic acid
By action of peroxiacids of pyridine oxidizes on the atom of
nitrogen with organized of N-oxide.
N-oxide of pyridine
N-oxide-4-nitropyridine
4-nitropyridine
4-aminopyridine
N-oxide-4-chloride pyridine
4-chloride pyridine
2. Structure, nomenclature, methods of getting and chemical
properties of pycoline.
Picoline refers to three different methylpyridine isomers,
all with the chemical formula C6H7N and a molar mass
of 93.13 g mol−1. All three are colourless liquids at
room temperature and pressure and are miscible with
water and most organic solvents. alpha-picoline, betapicoline, and gamma-picoline. The three compounds are
structural isomers. The names of the three compounds
indicate which of the hydrogens on the benzene ring
portion of the molecule have been replaced. They are
obtained from coal tar or petroleum. Because the boiling
points of these three compounds are nearly the same, a
separation of a mixture of the three into its pure
components is impractical.
Picolines are useful as solvents and as raw materials for various chemical
products used in the industry of polymers, textiles, fuels, agrochemicals,
pharmaceuticals and colorants.
α- picoline
β-picoline
γ-picoline
At oxidization β-picoline nicotine acid appears:
nicotinic acid
α- picoline and γ-picoline opposite to β-picoline give reaction of
condensation with aldehyds and ketons, by acting of sodium
amide form metalorganic compounds.
3. Structure, methods of getting and chemical properties of
hydroxypyridine and aminopyridine.
Depending on position of hydroxylic group distinguish three isomers:
α- hydroxypyridine
β- hydroxypyridine
γ- hydroxypyridine
Hydroxypyridine are crystalline matters, well
dissolve in an ethanol, acetone, undersoluble in
diethyl ether and benzol.
The special feature of α- and σ-isomers is that they exist in two
tautomeric forms:
hydroxyform
oxoform
hydroxyform
oxoform
β- hydroxypyridine in water solutions exist in neutral and
bipolar forms in correlation 1:1.
neutral form
bipolar form
The alcylhalohenyde react with 2- and 4- hydroxypyridine
form gives of N-alcylpyridone, and 3- hydroxypyridine salts N-alkilpiridiniya:
pyridinole-2 N-methylpyridinole pyridinole-3
N-methyl-3hydroxpyridinole
iodid
To the derivatives of hydroxypyridine belong to pyridoxyne
( vitamine B6).
Aminopyridine.
Depending on position of aminogroup distinguish:
α-aminopyridine
β- aminopyridine γ- aminopyridine
Aminopiridiny is white crystalline matters, easily dissolved in
water, ethanol and other organic solvents.
3-aminopyridine- dichloride
2 and 4-aminopyridine react with halogenalkanes
by the cyclic atom of nitrogen and with acylation
agents by atom of nitrogen of aminogroup:
4-acethaminopyridine
4-amino-1-methylpyridine iodid
4. Pyridine carbonic acids: structure, classification,
nomenclature, izomery, methods of getting and chemical
properties.
Depending on position of carboxyl group a- in a molecule is
distinguish of α- ,β- ,y- pyridine carbonic acids:
picoline acid
nicotine acid
isonicotinic acid
Pyridine carbonic acids are white crystal of matters, dissoled
in the hot water. Nicotine acid and its amide (Nicotinamidum)
is known in medicine as a provitamin of vitamin PP.
Presences of acid and basic centrs of pyridinkarbonic
acids show amphoteric properties, so, thee acids can react
with acids and alkalis:
Derivatives of isonicotinic acid:

Synthesis of phthyvazide and isoniazide
Derivatives of isonicotinic acid:
isoniazide
phthyvazide
Pyperidine
Piperidine — colourless liquid substance with a strong
ammoniac smell.
N-acethylpyperidine
N-methylpyperidine
O
NH 3
O
COOH
C
NH 2
-HCl
C
SOCl 2
N
Cl
Nicotinamidum (vitamin РР)
- HCl, -SO 2
N
O
N
(C 2H
5)2
-HCl
C
NH
N(C 2H 5) 2
N
N,N-diethylamide
nicotinic acid
cordiamine
O
Cl
COOH
O
C
N
SOCl 2
C2H5OH
- HCl, -SO 2
- HCl
N
OC 2H 5
O
C
NHNH 2
NH2NH2
- C2H5OH
N
N
isoniazid
O
C
NHNH 2
O
C
H
O
NH-N
C
+
N
isoniazid
C
H
- H2O
CH3O
OH
vanillin
N
OCH3
OH
4-hydroxy-3-methoxybenzyl-iden-
hydrazid of isonicotinic acid
phthivazid
5. Methods of getting and propertiesof α,γ-pyrans and α,γpyrones. Synthesis and chemical properties of the condensed
derivatives of pyrones (coumarin, chromone). Flavonoids.
Pyrones or pyranones are the class of cyclic chemical
compounds. They contain an unsaturated six member ring
containing one oxygen atom and a ketone functional group. There
are two isomers denoted as 2-pyrone and 4-pyrone. The 2-pyrone
structure is found in nature as part of the coumarin ring system. 4Pyrone is found in some natural chemical compounds such as
meconic and helidonic acid.
α-pyran
γ-pyran
2-Pyrone (α-pyrone or pyran-2-one) is an unsaturated cyclic
chemical compound with the molecular formula C5H4O2. It is
isomeric with 4-pyrone .
α-pyrone or pyran-2
4-Pyrone (γ-pyrone or pyran-4-one) is an unsaturated cyclic
chemical compound with the molecular formula C5H4O2. It is
isomeric with 2-pyrone. 4-Pyrone forms the central core of several
natural chemical compounds including maltol and kojic acid and of
the important class of the Flavones.
γ-pyrone or pyran-4
Tautomeric forms
4-hydroxpyrylyu chloride
4-methoxpyrylyu iodide
Reactions of nucleophilic additions
of γ-pyrone with mineral acids
and alkylhalogenides
 Interaction
Coumarin is a chemical compound (benzo[b]pyrone-2); a toxin
found in many plants, notably in high concentration in the cacao
bean, vanilla grass, woodruff, mullein, and bison grass. It has a
sweet scent, readily recognised as the scent of newly-mown hay,
and has been used in perfumes since 1882. It has clinical medical
value as the precursor for several anticoagulants, notably warfarin,
and is used as a gain medium in some dye lasers. The biosynthesis
of coumarin in plants is via hydroxylation, glycolysis and
cyclization of cinnamic acid. Coumarin can be prepared in a
laboratory in a Perkin reaction between salicylaldehyde and acetic
anhydride.
Synthesis of coumarine
Chemical properties
disodium salt of coumarin acid
On the benzol ring of coumarin enters into the reactions of
electrophilic substitution to position 6.
6- coumarin sulphatic acid
Chromone (benzo[b]pyrone-4) is a
derivative of benzopyran with a substituted
keto group on the pyran ring. Derivatives
of chromone are collectively known as chromones.
Most, though not all, chromones are also
flavonoids.
Cromoglicate is used as an mast cell stabilizer in allergic rhinitis, asthma and allergic
conjunctivitis.
Khellin is a naturally occurring chromone extracted from the medicinal plant Amni visnaga
long used in Egypt and the Eastern Mediterranean countries for the treatment of respiratory
disorders. It however has many side effects making it unsuitable.
Roger Altounyan studied chromones and eventually found disodium cromoglycate. This
drug was found to inhibit antigen challenge as well as stress induced symptoms.
Comparatively free of side-effects, unfortunately the short half-life limited its value.
Nedocromil sodium was found to have a somewhat longer half-life.
O
Derivatives of chromone:
O
1/
1/
O
O
1
flavone
isoflavone
Flavones are mainly found in cereals and herbs. In the West, the
estimated daily intake of flavones is in the range 20-50 mg per day. In
recent years, scientific and public interest in flavones has grown
enormously due to their putative beneficial effects against
atherosclerosis, osteoporosis, diabetes mellitus and certain cancers.
Flavones intake in the form of dietary supplements and plant extracts
has been steadily increasing.
Isoflavone differs from flavone (2-phenyl-4H-1-benzopyr-4-one)
in location of the phenyl group. Isoflavones are produced via a
branch of the general phenylpropanoid pathway that produces
flavonoid compounds in higher plants. Soybeans are the most
common source of isoflavones in human food; the major
isoflavones in soybean are genistein and daidzein. The
phenylpropanoid pathway begins from the amino acid
phenylalanine, and an intermediate of the pathway, naringenin, is
sequentially converted in to the isoflavone genistein by two
legume-specific enzymes, isoflavone synthase, and a dehydratase.
Similarly, another intermediate naringenin chalcone is converted
to the isoflavone daidzein by sequential action of three legumespecific enzymes: chalcone reductase, type II chalcone isomerase,
and isoflavone synthase. Plants use isoflavones and their
derivatives as phytoalexin compounds to ward off disease-causing
pathogenic fungi and other microbes. In addition, soybean uses
isoflavones to stimulate soil-microbe rhizobium to form nitrogenfixing root nodules.
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