Oxazole is a five-membered heterocyclic aromatic compound containing one oxygen atom and one nitrogen atom. It has a planar cyclic structure and follows Hückel's rule for aromaticity. Oxazole can be synthesized through the Robinson–Gabriel synthesis involving an intramolecular cyclization of a 2-acylamino-ketone. It can also be synthesized through the reaction of acid amides with α-haloketones or α-hydroxyketones. The Van Leusen reaction involving a ketone and TosMIC leads to the formation of an oxazole through a 5-endo-dig cyclization. Oxazole undergoes electrophilic aromatic substitution at C5 with activating

1. Five membered heterocyclic compound
containing two hetero-atom - OXAZOLE
Represented by – Vishal Singh Solanki
Ideal Institute of Pharmacy, MH

2. OXAZOLE

3. INTRODUCTION OF OXAZOLE
●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
●Aromaticity-Oxazoles follow huckle rule
(4n+2πe) because it have 6πe
●Show SP2 hybridization and cyclic planer
structure.

4. PHYSICAL PROPERTIES OF OXAZOLE
● It is a liquid
●Chemical formula - C3H3NO
●Molar mass - 69.06 g/mol
●Density - 1.050 g/cm3
●Boiling point - 69 to 70 °C (156 to 158 °F; 342 to 343 K)
●Pyridine like odour
●Miscible with water and some other organic solvents.
●Weakly basic (But slightly more than iso- oxazole)

5. SYNTHESIS OF OXAZOLE
1. Robinson–Gabriel synthesis - The Robinson–Gabriel synthesis is an organic
reaction in which a 2-acylamino-ketone reacts intramolecularly followed by a
dehydration to give an oxazole. A cyclodehydrating agent is needed to catalyze the
reaction

6. CONTI...
Mechanism
Protonation of the keto moiety (1) is followed by cyclization
(2) and dehydration
(3) the oxazole ring is less basic that the starting 2-acylamidoketone and so may be readily
neutralized
(4) Labeling studies have determined that the amide oxygen is the most Lewis basic and
therefore is the one included in the oxazole.

7. 2. REACTION B/W ACID AMIDE & α-
HALOKETONES/ α-HYDROXY
●REACTION B/W ACID AMIDE & α-HYDROXYKETONES TO GET
TRI-SUBSTITUTED OXAZOLE

8. CONTI...
Eg.

9. 3. Van Leusen reaction
The Van Leusen reaction is the reaction of a ketone with TosMIC leading
to the formation of a nitrile.When aldehydes are employed, the Van
Leusen reaction is particularly useful to form oxazoles and imidazoles.

10. MECHANISM
●The reaction mechanism consists of the initial deprotonation of TosMIC, which is facile
thanks to the electron-withdrawing effect of both sulfone and isocyanide groups.
●Attack onto the carbonyl is followed by 5-endo-dig cyclisation into a 5-membered ring.
●If the substrate is an aldehyde, then elimination of the excellent tosyl leaving group can
occur readily. Upon quenching, the resulting molecule is an oxazole.
●If an aldimine is used, formed from the condensation of an aldehyde with an amine, then
imidazoles can be generated through the same process.

11. MECHANISM

12. CHEMICAL PROPERTIES OF OXAZOLE
1.Deprotonation of oxazoles at C2 is often accompanied by ring-opening to the isonitrile.
2.Electrophilic aromatic substitution takes place at C5 requiring activating groups.
3.Nucleophilic aromatic substitution takes place with leaving groups at C2.
4.Diels–Alder reactions with oxazole dienes can be followed by loss of oxygen to form
pyridines.
5.The Cornforth rearrangement of 4-acyloxazoles is a thermal rearrangement reaction with
the organic acyl residue and the C5 substituent changing positions.
6.Various oxidation reactions. One study[6] reports on the oxidation of 4,5-diphenyloxazole
with 3 equivalents of CAN to the corresponding imide and benzoic acid

13. Deprotonation of oxazoles at C2

14. Electrophilic aromatic substitution

15. Diels–Alder reactions with oxazole

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