Oxazoline

Source: Wikipedia, the free encyclopedia.
Oxazoline
Names
Preferred IUPAC name
4,5-Dihydro-1,3-oxazole
Other names
Δ2-oxazoline
Identifiers
3D model (
JSmol
)
ChemSpider
ECHA InfoCard
 100.007.274 Edit this at Wikidata
UNII
  • InChI=1S/C3H5NO/c1-2-5-3-4-1/h3H,1-2H2 checkY
    Key: IMSODMZESSGVBE-UHFFFAOYSA-N checkY
  • N\1=C\OCC/1
Properties
C3H5NO
Molar mass 71.079 g·mol−1
Density 1.075unit?[1]
Boiling point 98 °C (208 °F; 371 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Oxazoline is a five-membered

heterocyclic organic compound with the formula C3H5NO. It is the parent of a family of compounds called oxazolines (emphasis on plural), which contain non-hydrogenic substituents on carbon and/or nitrogen. Oxazolines are the unsaturated analogues of oxazolidines, and they are isomeric with isoxazolines
, where the N and O are directly bonded. Two isomers of oxazoline are known, depending on the location of the double bond.

Oxazoline itself has no applications however oxazolines have been widely investigated for potential applications. These applications include use as

asymmetric catalysis, as protecting groups for carboxylic acids and increasingly as monomers for the production of polymers
.

Isomers

2‑oxazoline, 3‑oxazoline, and 4‑oxazoline (from left to right)
 Three
azirines.[4] These three forms do not readily interconvert and hence are not tautomers
.

A fourth isomer exists in which the O and N atoms are adjacent, this is known as isoxazoline.

Synthesis

The synthesis of 2-oxazoline rings is well established and in general proceeds via the cyclisation of a 2-

amino alcohol (typically obtained by the reduction of an amino acid) with a suitable functional group.[5][6][7] The overall mechanism is usually subject to Baldwin's rules
.

From carboxylic acids

The usual route to oxazolines entails reaction of acyl chlorides with 2-amino alcohols. Thionyl chloride is commonly used to generate the acid chloride in situ, care being taken to maintain anhydrous conditions, as oxazolines can be ring-opened by chloride if the imine becomes protonated.[8] The reaction is typically performed at room temperature. If reagents milder than SOCl2 are required, oxalyl chloride can be used.[9] Aminomethyl propanol is a popular precursor amino alcohol.[10][11]

Modification of the

Montreal protocol
.

From aldehydes

The cyclisation of an amino alcohol and an

aliphatic aldehydes however electron rich aromatic R groups, such as phenols, are unsuitable as they preferentially undergo rapid electrophilic aromatic halogenation
with the oxidising agent.

From nitriles

The use of catalytic amounts of

nitriles was first described by Witte and Seeliger,[15][16] and further developed by Bolm et al.[17] The reaction requires high temperatures to succeed and is typically performed in refluxing chlorobenzene under anhydrous conditions. A precise reaction mechanism has never been proposed, although it is likely similar to the Pinner reaction; preceding via an intermediate amidine.[18][19] Limited research has been done into identifying alternative solvents or catalysts for the reaction.[20][21]

Applications

Ligands

Main article: Bisoxazoline ligand

Ligands containing a chiral 2-oxazoline ring are used in

asymmetric catalysis due to their facile synthesis, wide range of forms and effectiveness for many types of catalytic transformation.[22][23]

2-Substituted oxazolines possess a moderately

amino acids; which are both optically pure and inexpensive. As the stereocentre in such oxazolines is adjacent to the coordinating N-atom, it can influence the selectivity of processes occurring at the metal centre. The ring is thermally stable[24] and resistant to nucleophiles, bases, radicals, and weak acids[25] as well as being fairly resistant to hydrolysis and oxidation;[5]
thus it can be expected to remain stable in a wide range of reaction conditions.

Major classes of oxazoline based ligand include:

Notable specialist oxazoline ligands include:

Polymers

Some 2-oxazolines, such as

peptides; they have numerous potential applications[27] and have received particular attention for their biomedical uses.[28][29]

Analysis of fatty acids

The dimethyloxazoline (DMOX) derivatives of fatty acids are amenable to analysis by gas chromatography.

See also

Structural analogues

Other pages

  • Aminorex a drug bearing an oxazoline ring

References

  1. ^
    doi:10.1021/ja01276a036
    .
  2. doi:10.1021/ja00218a038
    .
  3. doi:10.1016/S0040-4039(00)86403-5
    .
  4. PMID 11667224
    .
  5. ^
    S2CID 95217957
    .
  6. doi:10.1021/cr60273a003
    .
  7. doi:10.1016/S0040-4020(01)86953-2
    .
  8. doi:10.1002/1099-0690(200006)2000:12<2257::AID-EJOC2257>3.0.CO;2-2
    .
  9. doi:10.1021/jo980296f
    .
  10. doi:10.15227/orgsyn.071.0107
    .
  11. S2CID 235855642
    .
  12. doi:10.1016/0040-4020(93)80021-K
    .
  13. doi:10.1055/s-2006-950198
    .
  14. doi:10.1016/j.tet.2006.11.077
    .
  15. doi:10.1002/anie.197202871
    .
  16. doi:10.1002/jlac.197419740615
    .
  17. doi:10.1002/cber.19911240532
    .
  18. PMID 12691592
    .
  19. doi:10.3987/S-1981-01-0361 (inactive 2024-03-07).{{cite journal}}: CS1 maint: DOI inactive as of March 2024 (link
    )
  20. S2CID 95389965
    .
  21. PMID 24201227
    . See the Supplementary Information for details
  22. PMID 15352789
    .
  23. PMID 19378971
    .
  24. doi:10.1039/B417389A
    .
  25. ^ Greene, T. W. (1991). Protective groups in organic synthesis, 2nd ed. New York: Wiley. pp. 265–266 & 433–436.
  26. doi:10.1002/pola.10090
    .
  27. PMID 19768817
    .
  28. PMID 17904246
    .
  29. PMID 22811405
    .
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