1

Heterocycles

2

Heterocyclic compoundsAromatic 5-membered Ring

Heterocycles. Pyrrole, Furan, and Thiophene.

• Huckel’ Rule 4n+2

N

HPyrrole

O

Furan

SThiophene

..

..

..

..

3

Hückel's rule estimates whether a planar ring molecule will have aromatic properties.

•Coplanar structure, with all the contributing atoms in the same plane•A delocalized conjugated π system, most commonly an arrangement of alternating single and double bonds•Contributing atoms arranged in one or more rings•A number of π delocalized electrons that is even,

but not a multiple of 4. That is, 4n + 2 number of π

electrons, where n=0, 1, 2, 3, and so on

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Pyrrole

Pyrrole is a heterocyclic aromatic organic compound, a five-

membered ring with the formula C4H4NH. It is a colourless volatile

liquid that darkens readily upon. s, exposure to air. Substituted

derivatives are also called pyrrole.

Pyrrole’s structure.N-atom electron configuration

7Nsp2 p

6

Chemical Properties. Ur ‘ev’s cycle.

6

OCH

CH

CH

CHS

CH

CH

CH

CH

NH

CH

CH

CH

CH

+ H2S

H2O

NH3

H2O

NH3

H2S

+

+

++ +

7

• No basic properties• Acidic Properties.

N-methylpyrrole

N

H

N

HC

HCN

H

HC

K

I

I

3

33 t+

-

1/2 2

• Pyrrole is acidoforbic: С4Н4NH +H+ → С4Н4NH2 + → Polymer

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•Aromatic Properties (SE )

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3

Pyridine sulphotrioxide Sulphopyridine

δ-

δ+ δ+

N

H

N

HN

H

+ BrFeBr

-HBrBr

+Br

Br

Br

Br

Br-HBr

..

N

H

N

H

+ C H N SO SO H + C H N5 5

.3 5 53

Bromination

Sulphonation

9

Pyrrole - Pyrroline - Pyrrolidine

Incresing of basity

9

•Hydrogenation

Proline ( Prо)- essential amino acid.

10

Salts of Proline

11

PeptidesGli-Pro-Аlа

• pI=6-7

11

N C HH

HNH

OC

OH

NH

HC H

OC

OHC H

OC

O

2

3

NC

O

N

H

C H

C H

OC

O

C HNH

O

C

3

23-

++2 H2O

H

-2H2O

Structure of porphine, the simplest porphyrin.

Structure of Heme B Heme A Heme A is synthesized from Heme B. In two sequential reactions a 17-hydroxyethylfarnesyl moiety (blue) is added at the 2-position and an aldehyde (purple) is added at the 8-position. Nomenclature is shown in green.The most common type is heme B; other important types include heme A and heme C. Heme Еcong=840 кJ/mol

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Metabolic Reactions of Triptophane

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N

H

C H

C HH COOHN

N

O

H

C H

C HH COOHN

H

N

H

C H

C HHN

HO

2

2

2

22

2

2

Enzime Enzime

-СО2

5-HydroxytriptophaneSerotonine(neiromediator)

N

H

,, N

H

CHCH

NH

COOH

Indole Tryptophane

Enzime

-СО2

Triptamine

N

H

C H

C HH COOHN

N

H

C H

C HHN

N

H

C H COOH

N

H

C H

N

H

2

2

2

2

2

2

3

-СО2

Enzime

ScatoleIndole

Enzime

1616

Thiophene

S SSO H+ H SO 32 4

α-Sulphotiophene

-Н2О

20 °C.

Thiophene is the heterocyclic compound with the formula C4H4S. Consisting of a flat five-membered ring, it is aromatic as indicated by its extensive substitution reactions.

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Pentose Furfurol 5-Nitrofurfurole

OON HC NR O

ON HC N NH C NH

O

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Furociline2

Furan is a heterocyclic organic compound,

consisting of a five-membered aromatic ring

with four carbon atoms and one oxygen. The

class of compounds containing such rings

are also referred to as furans.

Vitanim B7 (Biotin)

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4(Н)

S S+ 4(Н)

O O

S

N NH HC

O

HC CO O H

+

2( )4

ТГФ

Pd

Six-membered HeterocyclesPyridine

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Pyridine is a heterocyclic organic compound with the chemical

formula C5H5N. It is structurally related to benzene, with one CH

group replaced by a nitrogen atom.

Pyridine’s structure.N-atom electron configuration

7N

sp2 p

20pK = 5,2C5H5NH

NHO H

H ClNH

O H

Cl

+

+

+ -

+:+ -

+

Basic Properties

Pyridine was originally industrially produced by extraction from coal tar.

SE

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NBr FeBr

N

BrHBr+ 2

3 +

δ+

δ+ δ+δ- δ-

β-Picoline

Nicotinamide (PP)- Niacin

Nicotinic acid (PP) Cordiamine

N

CH O

N

CO

OH

N H

NH

N

C

O

NH

N

C

O

N C H

C H2

2 5

5( )2

( )23

3

2

It is a colorless liquid with a distinctive, unpleasant fish-like odor. The pyridine ring occurs in many important compounds, including the vitamins nicotinamide and pyridoxal.

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Name(s) CAS# m.p. (°C) b.p. (°C)pKa of pyridinium ion

structure

2-Methylpyridine, α-picoline [109-06-8] -66.7 129.4 5.96

3-Methylpyridine, β-picoline [108-99-6] -18 141 5.63

4-Methylpyridine, γ-picoline [108-89-4] 3.6 145.4 5.98

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.Data

for the three compounds are summarized in the table.                                        

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N

H

NH

+ 6

Pyperidine

NCH

CH

NI I+ 3

:

3

δ-δ+

+-( )

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N

C H

H

O N

CH

H

HH

3

2

3

+ ++

+N

RN

R

HH

C

O

NHC H H COO H

C

O

NHC

OH

C H C OO HC

OH

++2

33

+ +

NAD NADН+

2

Azoles5-membered Heterocycles with two N-atoms

Pyridine’s N

Pyrrole’s N

Imidazole

Prototropic Tautomerism

HistamineHistidine

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Pyrazolone – 5

Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen; the term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS. The thiazole ring is notable as a component of the vitamin thiamine (B1).

Thiazole

Pyrazolone, a five-membered-ring lactam, is a derivative of pyrazole that has an additional keto (=O) group.

Oxazole

Pyrazole refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions, and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids, although they are rare in nature.

Pyrazole

Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base; its conjugate acid has a pKa of 0.8, compared to 7 for imidazole.

Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi.Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections. Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are Beta-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.

Azines.

Six-membered Heterocycles with Two Heteroatoms.

Hexazine (also known as hexaazabenzene) is a hypothetical

allotrope of nitrogen composed of 6 nitrogen atoms arranged in a

ring-like structure analogous to that of benzene. It would be the

final member of the azabenzene (azine) series, having all of the

methylidyne groups of the benzene molecule replaced with

nitrogen atoms. The two last members of this series, hexazine and

pentazine, have not been observed, although all other

members of the azine series have (such as pyridine,

pyrimidine, pyridazine, pyrazine, 1,3,5-triazine and tetrazine).

Pyridazine

Pyrazine

Pyridazine is a heteroaromatic organic compound with the molecular formula C4H4N2, sometimes called 1,2-diazine. It contains a six-membered ring with two adjacent nitrogen atoms.

Pyrazine is a heterocyclic aromatic organic compound. Pyrazine is less basic in nature than pyridine, pyridazine and pyrimidine.

рКВН =1,3

Pyrimidine

:

:

+ НCl

+ Н2O :

| H

–

+

Baisic Properties

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. It is isomeric with two other forms of diazine.

:

:

+ Br2

FeBr3

t°

:

: Br

+ НBr

Aromatic Properties (SE)

R

R+

НO

R, R’

Barbituric acid

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Barbiturates

C 2H5

C 2H5

C 2H5

C 2H5

+ NaOH

– Н2О

-+Cl

Thiamine. Vitamin B2

Uracil2,4-Dimethylpyrimidine

Lactim

:

..

Lactam: :

НН

Thymine (5 - methyluracil)

Citosine(4 – amino – 2 – hydroxypyrimidine)

: :

:

.. ..

Purines. A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their

tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature.

пуринT пл. = 216°С

Adenine

:

..

..

..

: ..

....

HNO2

-N2, -H2O

Hypoxanthine6- Hydroxypurine

10 ē

Guanine

HОNO

Xanthine2,6 -Dihydroxypurine

Guanine (G) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine. In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar.

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СН3

1,3,7 – TrimethylxantineCaffeine

Alkoloids-derivetives of Xanthine

In humans, caffeine acts as a central nervous system (CNS) stimulant, temporarily warding off drowsiness and restoring alertness. Caffeine is the world's most widely

consumed psychoactive substance, but, unlike many other psychoactive substances, is legal and unregulated in nearly all jurisdictions.

Caffeine (also spelled caffein) is a bitter, white crystalline xanthine alkaloid that is a psychoactive stimulant drug. Caffeine was isolated in 1820 by a German chemist, Friedlieb Ferdinand Runge, and in 1821 by French chemists working independently; viz., by Robiquet and by Pelletier and Caventou. It was Pelletier who coined the word "cafeine," whence "caffeine".

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он:

.. .. нн н

+ 2 NaOH NaOH

NaOH

2,6,8 - Trihydroxypurine

Uric Acid

1)[O] HNO3

2)NH3 изб. Murexide reaction

NH4

Ammonium purpurate

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