Synthesis, Reactions and Medicinal Uses of Pyridine

 

Synthesis, Reactions, and Medicinal Uses of Pyridine        



Pyridine is a six-membered heterocyclic compound that contains one Nitrogen as heteroatom.

Physical properties:

Colour: colourless
State: liquid
Melting point: -41.6 oC
Boiling point: 115.2 oC
Solubility: Soluble in water

Structure and Aromaticity:

Pyridine contains five carbon atoms and one nitrogen atom, all are sp2 hybridized. Pyridine is a planar molecule that contains unhybridised p orbitals perpendicular to the ring. these p orbitals sidewise overlap to form pi bonds. Pyridine contains a total of six delocalised pi electrons, following the Huckls rule hence pyridine is aromatic.  

Resonance structures:

Basicity Of Pyridine:



Pyridine is more basic than pyrrole and less basic than Aliphatic amine. In pyridine, lone pair of electrons on nitrogen is easily available for protonation and participate in acid-base reactions. whereas in pyrrole, lone pair of electrons on nitrogen atom gets involved in pyrrole aromaticiy and is not available for acid-base reactions. 
When compared with aliphatic amines, Pyridine nitrogen atom sp2 hybridised whereas aliphatic amine  sp3 hybridised. sp2 hybridised nitrogen atom more electronegative than sp3 hybridised aliphatic nitrogen. Hence sp2 hybridised nitrogen atom tightly held lone pair electrons and are not easily available for acid-base reaction in comparison with the  sp3 hybridised nitrogen atom, It is less electronegative and have loosely held lone pair of electrons and is easily available for acid-base reactions.

Synthesis of Pyridine:

1. Hantzsch Synthesis:  

Condensation of two moles of β-dicarbonyl compounds or β-keto esters with aldehyde and ammonia gives substituted pyridine.

2. From Acetylene: 

Two moles of Acetylene and Hydrogen cyanide passed through a red hot tube gives Pyridine.

3. Guareschi Synthesis: 

Condensation of Acetoaacetic esters and Cyanoacetamide gives Pyridine derivatives.

4. From 1,5-Dicarbonyl compounds: 

1,5-Dicarbonyl compounds react with ammonia to give 1,4-dihydropyridines which upon dehydrogenated to give pyridine.

Reactions:

Electrophilic addition at "N" atom:  

1. Protonation: 

Pyridine reacts with acids gives pyridinium salts.

2. N-Alkylation: 

Pyridine reacts with alkyl halides gives N-alkyl pyridinium salts.

Electrophilic substitution reactions: 

Electrophilic substitution reactions preferably take place at the 3rd position.  

1. Nitration: 

Pyridine upon nitration gives 3-nitropyridine.

2. Sulphonation: 

Pyridine sulphonation with concentrated sulfuric acid in Mercuric sulfate give pyridine-3-sulphonic acid.

3. Halogenation: 

Pyridine upon halogenation gives 3-halo pyridine.

Friedel Craft's reactions are not observed due to aluminium chloride forming complex with pyridine which is highly unreactive.

Nucleophilic substitution reactions: 

Nucleophilic substitution reactions in pyridine preferably take place at the 2nd position.

1. Chichibabin reaction: 

Pyridine reacts with Sodamide in liquid ammonia gives 2-amino pyridine.


2. Reaction with Alkyl Lithium:

 Pyridine reacts with alkyl lithium gives 2-pyridyl lithium.


3. Reaction with KOH: 

pyridine reacts with KOH gives 2-hydro pyridine.

Reduction:

1. Pyridine reacts with hydrogen and palladium as catalyst gives Piperidine.
2. Birch reduction: Pyridine reacts with sodium in liquid ammonia gives 1,4-dihydropyridine.

3. Pyridine reduced with Lithium aluminium hydrate gives 1,2-dihydropyridine.

Oxidation: 

Pyridine is oxidised with various oxidising agents and gives Pyridine-N-Oxide.

Pyridine as Acylating agent: Pyridine is used as a catalyst for Acyalating phenols, alcohols and amines by reacting with acid chlorides or anhydrides.


Medicinal uses:

Drugs containing Pyridine ring:

1. Isoniazid and Ethionamide:  These are used for the treatment of Tuberculosis(TB).

2. Sulfasalazine: Sulfasalazine is used to treat Rheumatoid arthritis.

3. Sulfapyridine: Sulfapyridine is an antibiotic used to treat skin infections.
4. Omeprazole and Lansoprazole: These are proton pump inhibitors used to treat the Peptic ulcer.

5. Vitamin B3: It is also known as Niacin an essential nutrient used to lower bad cholesterol (LDL) and increase good cholesterol (HDL).

6. Vitamine B6: Improve brain health and reduce symptoms of depression and also used to anaemia and peripheral neuropathy.

References (Latest editions):


Heterocyclic chemistry by Raj K. Bansal.
Heterocyclic chemistry by T.L. Gilchrist.
Organic chemistry by Morrison and Boyd.
A  textbook of organic chemistry - Arun Bahl. B.S. Bahl.









Comments

Post a Comment

Popular posts from this blog

Synthesis, Reactions, and Medicinal Uses of Pyrazole

Image
  Synthesis, Reactions, and Medicinal Uses of Pyrazole Pyrazole is a five-membered heterocyclic aromatic compound containing two adjacent nitrogen atoms at 1 and 2 positions.  Physical properties: Colour                :  colorless State                   :   solid Boiling point     : 186 - 188  o C Melting point    :    66 - 70  o C Solubility           :    soluble in hot water, soluble in organic solvents. Structure & Aromaticity: All atoms in the pyrrole ring are  sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the four hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma bonds lie in one pla...
Read more

Relative aromaticity and reactivity of Pyrrole, Furan, and Thiophene

Image
Relative aromaticity and reactivity of Pyrrole, Furan, and Thiophene Relative aromaticity of Pyrrole, Furan, and Thiophene: Aromatic compounds are cyclic hydrocarbon compounds contains alternate double and single bonds.pi electrons are delocalised inside the ring enhance the stability of the compound. Pyrrole, thiophene and furan are the heterocyclic aromatic compounds contain nitrogen, sulfur and oxygen as heteroatom respectively. the lone pair of electrons on heteroatom get involved and participate in aromaticity. In order to know the order of aromaticity in pyrrole, furan and thiophene we need to about electronegativity of nitrogen, sulfur and oxygen. Electronegativity is the tendency of an atom which drags the shared pair of electrons towards it. Electronegative values of nitrogen, oxygen and sulfur are given below. High electronegative means it tightly holds the electrons, especially lone pair of electrons present on an atom and hinders the delocalisation of pi electrons ...
Read more

Synthesis, Reactions and Medicinal Uses of Oxazole

Image
  Synthesis, Reactions, and Medicinal Uses of Oxazole    O xazole is a five-membered heterocyclic compound having one oxygen and one nitrogen atom as a heteroatoms at 1 and 3 positions respectively. Physical properties: Colour                :  clear to pale yellow State                   :   liquid Boiling point     :  69 to 70 o C Melting point    :    -84 o C Solubility              :   partially soluble in water, soluble in organic solvents Structure & Aromaticity: C, N and O atoms in the oxazole ring are  sp 2   hybridised, so the oxazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the three hydrogens forming C-C, C-N, C-H, and...
Read more

Synthesis, Reactions and Medicinal Uses of Pyrrole

Image
Synthesis, Reactions, and Medicinal Uses of Pyrrole                 P yrrole is a five-membered heterocyclic compound having one nitrogen atom as a heteroatom. Physical properties: Colour                :  colorless State                   :    liquid Boiling point     : 131 o C Melting point    :    -23 o C Solubility           :    Insoluble in water, soluble in organic solvents Structure & Aromaticity: All atoms in the pyrrole ring are sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the five hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma ...
Read more

Synthesis, Reactions, and Medicinal Uses of Imidazole

Image
  Synthesis, Reactions, and Medicinal Uses of Imidazole I midazole is a five-membered unsaturated heterocyclic compound having two nitrogen atoms as heteroatoms at 1 and 3 positions. Physical properties: Colour                : White or colourless State                   :  Solid Boiling point     : 256 o C Melting point    :   89 to 91 o C Solubility           :   Soluble in water, soluble in organic solvents Structure & Aromaticity: All atoms in the Imidazole ring are  sp 2   hybridised, so the imidazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the four hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma bonds lie in one plane. Imidazole also h...
Read more

Synthesis, Reactions and Medicinal Uses of Thiazole

Image
  Synthesis, Reactions, and Medicinal Uses of Thiazole  Thiazole is a five-membered heterocyclic compound having one Sulphur and one Nitrogen atom as heteroatoms at 1 and 3 positions respectively. Physical properties: Colour                :  Colourless or pale yellow State                   :   liquid Boiling point     :  116 - 118  o C Melting point    :   -33  o C Solubility               :  slightly soluble in water, soluble in organic solvents Structure & Aromaticity: C, N and S atoms in the thiazole ring are  sp 2   hybridised, so the thiazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with the "s" atomic orbital of the three hydrogens forming C-C, C-N...
Read more

Synthesis, Reactions, and Medicinal Uses of Isoquinoline

Image
  Synthesis, Reactions, and Medicinal Uses of Isoquinoline  Isoquinoline is a bicyclic hetero-aromatic compound having nitrogen at the second position as heteroatom. It is also called benzo[c]pyridine, the benzene is fused with the "c" side of pyridine. another name for isoquinoline is 2-azanaphthalene. Physical properties: Colour: colourless State: liquid Melting point: 26 - 28  o C Boiling point: 242  o C Solubility: Slightly soluble in water and soluble in organic liquids and dilute acids. Structure and Aromaticity: All atoms in Isoquinoline are  sp 2  hybridised and have a planar structure. Unhybridised p-orbitals sidewise overlap to form five pi bonds. Isoquinoline contains a total of ten delocalised pi electrons, following the huckles rule hence quinoline is an Aromatic. Resonance structures: Synthesis of Isoquinoline: 1. Bischler-Napieralski synthesis:  2-aryl ethanamines react with acyl chloride to give an amide, which upon treated with phospho...
Read more

Synthesis, Reactions, and Medicinal Uses of Furan

Image
Synthesis, Reactions, and Medicinal Uses of Furan Furan is a five-membered heterocyclic compound having one Oxygen atom as a heteroatom. Physical properties: Colour                :   colorless State                   :    liquid Boiling point     :    31.3  o C Melting point    :    -85.6  o C Solubility           :   soluble in organic solvents(ethanol, ether, and acetone, etc.,)                                        slightly soluble in water. Structure & Aromaticity: All atoms in the Furan ring are  sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbita...
Read more

Synthesis, Reactions and Medicinal Uses of Quinoline

Image
  Synthesis, Reactions, and Medicinal Uses of Quinoline          Quinoline is a bicyclic hetero-aromatic compound having nitrogen at the first position as heteroatom. Physical properties: Colour: colourless State: liquid Melting point: -15  o C Boiling point: 237  o C Solubility: Slightly soluble in water and soluble in organic liquids. Structure and Aromaticity: Quinoline is a fused ring system of pyridine and benzene. All atoms in quinoline are  sp 2  hybridised and have a planar structure. Unhybridised p-orbitals sidewise overlap to form five pi bonds. Quinoline contains a total of ten delocalised pi electrons, follows the huckles rule hence quinoline is an Aromatic. Resonance structures: Synthesis of Quinoline: 1. Friedlander Synthesis: O-amino benzaldehyde reacts with carbonyl compound with active methylene compound in presence of alcoholic NaOH give Quinoline. 2. Knorr quinoline Synthesis:  Condensation of aniline with ke...
Read more