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.[2] 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.

Oxazole
Full structural formula
Skeletal formula with numbers
Ball-and-stick model
Space-filling model
Names
IUPAC name
1,3-oxazole
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.005.474
EC Number
  • 206-020-8
MeSH D010080
PubChem CID
UNII
CompTox Dashboard (EPA)
Properties
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)
Acidity (pKa) 0.8 (of conjugate acid) [1]
Supplementary data page
Structure and
properties
 Refractive index (n),
Dielectric constant (εr), etc.
Thermodynamic
data
 Phase behaviour
solid–liquid–gas
Spectral data
 UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Preparation

Classical oxazole synthetic methods in organic chemistry are

  • the Robinson–Gabriel synthesis by dehydration of 2-acylaminoketones
  • the Fischer oxazole synthesis from cyanohydrins and aldehydes
  • the Bredereck reaction with α-haloketones and formamide
  • the Van Leusen reaction with aldehydes and TosMIC

Other methods:

  • Oxazolines can also be obtained from cycloisomerization of certain propargyl amides. In one study[3] oxazoles were prepared via a one-pot synthesis consisting of the condensation of propargyl amine and benzoyl chloride to the amide, followed by a Sonogashira coupling of the terminal alkyne end with another equivalent of benzoylchloride, and concluding with p-toluenesulfonic acid catalyzed cycloisomerization:

Biosynthesis

In biomolecules, oxazoles result from the cyclization and oxidation of serine or threonine nonribosomal peptides:

Where X = H, CH
3 for serine and threonine respectively, B = base.
(1) Enzymatic cyclization. (2) Elimination. (3) [O] = enzymatic oxidation.

Oxazoles are not as abundant in biomolecules as the related thiazoles with oxygen replaced by a sulfur atom.

Reactions
  • Deprotonation of oxazoles at C2 is often accompanied by ring-opening to the isonitrile.
  • Electrophilic aromatic substitution takes place at C5 requiring activating groups.
  • Nucleophilic aromatic substitution takes place with leaving groups at C2.
  • Diels–Alder reactions with oxazole dienes can be followed by loss of oxygen to form pyridines.
  • The Cornforth rearrangement of 4-acyloxazoles is a thermal rearrangement reaction with the organic acyl residue and the C5 substituent changing positions.
  • 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:
In the balanced half-reaction three equivalents of water are consumed for each equivalent of oxazoline, generating 4 protons and 4 electrons (the latter derived from CeIV).
Use of an oxazole in the synthesis of a precursor to pyridoxine, which is converted to vitamin B6.[7]

See also
  • Isoxazole, an analog with the nitrogen atom in position 2.
  • Imidazole, an analog with the oxygen replaced by a nitrogen.
  • Thiazole, an analog with the oxygen replaced by a sulfur.
  • Benzoxazole, where the oxazole is fused to another aromatic ring.
  • Pyrrole, an analog without the oxygen atom.
  • Furan, an analog without the nitrogen atom.
  • Oxazoline, which has one double bond reduced.
  • Oxazolidine, which has both double bonds reduced.
  • Oxadiazoles with two nitrogens instead of one (e.g. furazan).
  • Oxazolone, an analog with a carbonyl group

References
  1. Zoltewicz, J. A. & Deady, L. W. Quaternization of heteroaromatic compounds. Quantitative aspects. Adv. Heterocycl. Chem. 22, 71-121 (1978).
  2. Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2
  3. A new consecutive three-component oxazole synthesis by an amidation–coupling–cycloisomerization (ACCI) sequence Eugen Merkul and Thomas J. J. Müller Chem. Commun., 2006, 4817 - 4819, doi:10.1039/b610839c
  4. Fully Automated Continuous Flow Synthesis of 4,5-Disubstituted Oxazoles Marcus Baumann, Ian R. Baxendale, Steven V. Ley, Christoper D. Smith, and Geoffrey K. Tranmer Org. Lett.; 2006; 8(23) pp 5231 - 5234; (Letter) doi:10.1021/ol061975c
  5. They react together in the first phase in a continuous flow reactor to the intermediate enol and then in the second phase in a phosphazene base (PS-BEMP) induced cyclization by solid-phase synthesis.
  6. "Ceric Ammonium Nitrate Promoted Oxidation of Oxazoles", David A. Evans, Pavel Nagorny, and Risheng Xu. Org. Lett.; 2006; 8(24) pp 5669 - 5671; (Letter) doi:10.1021/ol0624530
  7. Gérard Moine, Hans-Peter Hohmann, Roland Kurth, Joachim Paust, Wolfgang Hähnlein, Horst Pauling, Bernd–Jürgen Weimann, Bruno Kaesler (2011). "Vitamins, 6. B Vitamins". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.o27_o09.CS1 maint: uses authors parameter (link)