Synthesis, Reactions and Medicinal Uses of Oxazole


 

Synthesis, Reactions, and Medicinal Uses of Oxazole  

 Oxazole 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 70oC
Melting point    :    -84oC
Solubility           :   partially soluble in water, soluble in organic solvents

Structure & Aromaticity:

C, N and O atoms in the oxazole ring are sp2 hybridised, so the oxazole contains a planar ring structure. the sp2 hybrid orbitals overlap with each other and with "s" atomic orbital of the three hydrogens forming C-C, C-N, C-H, and C-O sigma bonds. all these sigma bonds lie in one plane.
Oxazole also has unhybridized p orbitals and these are perpendicular to the plane of the ring. each p orbital on carbon atom contains one electron and the p orbitals on nitrogen and oxygen contain lone pair of electrons(two electrons). the p orbitals overlap to form delocalized pi molecular orbital. Oxazole shows aromaticity because the resulting pi molecular orbital (which contain 6 electrons) satisfies the Huckel's rule (n=1 in 4n+2).

Resonance structures:

Synthesis:

1. Robinson-Gabriel synthesis:
It is the most method for synthesis of oxazoles. It involves an Î±-acylamino ketone which undergoes cyclisation and dehydration in the presence of phosphorus pentoxide or strong mineral acid. This method is especially applicable for synthesis 2,5-diaryl oxazoles. 
Mechanism:


2. From Isocyanides: Reaction of α-metallated isocyanides with acid chlorides or anhydrides yields substituted oxazoles.
3. From α-hydroxy carbonyl compounds:  Î±-hydroxy carbonyl compounds condensed with amide or amide derivatives gives substituted oxazoles.

Electrophilic substitution reactions:

Oxazole less reactive for electrophilic substitution reactions because of highly electronegative oxygen present in the ring, it makes deactivates the ring and not available for electrophilic substitution reactions. However, if ring activated by electron-donating groups electrophilic substitution reactions are possible at 5th position. 

1. Halogenation: 


2. Nitration: Nitration and Sulphonation reactions are more difficult on oxazole ring.


3. Sulphonation:

Other important reactions:

Protonation: Oxazole acts as a base, accepts proton and forms oxazolium salt.


Reduction: Oxazole forms oxazolidines, when reduced with sodium metal in ethanol.
              Oxazole ring is cleaved when reduced with Lithium aluminium hydride.

Oxidation: Oxazole ring is not stable towards oxidising agents, the ring is opened.

N-alkylation: Oxazole reacts with alkyl halides to form quaternary ammonium salts.

Diels-Alder reaction: Oxazole acts diene, undergoes cycloaddition reaction at 2,5- positions.

Synthesis of furan: Cycloaddition of oxazole with alkyne derivative gives furan derivative.
Synthesis of pyridine: (Kondrat'eva pyridine synthesis)
Cycloaddition of oxazole with alkene derivative gives pyridine derivative.


Medicinal uses:

Drugs containing an Oxazole ring:

1. Oxaprozin: Used to treat pain, inflammation and rheumatoid disease.

2. Bengazoles: Bengazoles are antifungal agents used to treat fungal infections.

3. Benoxaprofen, Flunoxaprofen: These are analgesic, antipyretic and anti-inflammatory agents used to treat pain due to rheumatoid arthritis and osteoarthritis.

4. Ditazole: It is a non-steroidal anti-inflammatory agent, also have analgesic and antipyretic properties.

5. Aleglitazar: Used in the treatment of diabetes and cardiovascular diseases.

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 plane. Pyrazole also has unhybridized  p  orbitals and these are perpendicular to the plane of the ring. each  p  orbital on carbon atom contains one electron and the  p  orbital on nitrogen contains lone pair of electrons(two electrons). the  p  orbital overlap to f
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 within th
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 bonds lie in one plane. Pyrrole also has unhybridized p orbitals and these are perpendicular to the plane of the ring. each p orbital on carbon atom contains one electron and the p orbital on nitrogen contains lone pair of electrons(two electrons). the p orbital overlap to form
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 has unhybridized  p  orbitals and these are perpendicular to the plane of the ring. each  p  orbital on carbon atom contains one electron and the  p  orbital on nitrogen contains lone pair of electrons(two electrons). the  p  orbital overla
Read more

Synthesis, Reactions and Medicinal Uses of Pyridine

Image
  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  o C Boiling point: 115.2  o C Solubility: Soluble in water Structure and Aromaticity: Pyridine contains five carbon atoms and one nitrogen atom, all are  sp 2  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 aromatic
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, C-H, and C-S sigma bonds. all these sigma bonds lie in one plane. Thiazole also has unhybridized  p  orbitals and these are perpendicular to the plane of the ring. each  p  orbital on carbon atom contains one electron and the  p  orbitals on nitrogen and sulphur contain l
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 phosphorus pentoxide or 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 orbitals overlap with each other and with "s" atomic orbital of the five hydrogens forming C-C, C-O, C-H sigma bonds. all these sigma bonds lie in one plane. Furan also has unhybridised  p  orbitals and these are perpendicular to the plane of the ring. each  p  orbital on carbon atom contains one electron and the  p  orbital on Oxygen contains lone pair of electrons(two electrons). the 
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 ketoester gives anilide intermediate, which further cyclizati
Read more