Synthesis of Imidazoles and Oxazoles
COMMUNICATION
À
could be prepared in appreciable yield from two aldehydes,
a primary amine, an acid chloride, and HMDS as an ammo-
nia equivalent.
Keywords: aminonitriles · carbanions · C C coupling ·
heterocycles · umpolung
Experimental Section
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Imidazoles
(184.3 mg, 1.09 mmol; KHMDS=potassium hexamethyldisilazide) in dry
THF (1 mL) was added to stirred solution of aminonitrile
7 (representative procedure): A solution of KHMDS
a
1
(0.84 mmol) in dry THF (0.5 mL) at À788C under an argon atmosphere.
After the addition of a solution of the crude acylimine 3 (0.84 mmol) in
dry THF (0.5 mL), the mixture was stirred for 15–40 min at À788C
(monitored by TLC) and the reaction was quenched by the addition of a
saturated aqueous solution of NaHCO3 (10 mL). The reaction mixture
was extracted with ethyl acetate, the combined organic layers were
washed with brine, dried over MgSO4, and the solvent was removed in
vacuo. The resulting crude aminonitrile 5 was dissolved in dry toluene
(15 mL) and after addition of DBU (0.14 mL, 0.92 mmol), the mixture
was heated to reflux for 9–12 h under an argon atmosphere. After several
washings with brine, the organic layer was dried over MgSO4, and the
solvent was removed in vacuo to furnish the crude a-acylaminoimine 6.
This product was dissolved in dry dichloromethane (20 mL) and PCl5
(701 mg, 3.36 mmol) was added. The mixture was stirred for 1.5–4 h at
ambient temperature under an argon atmosphere until the starting mate-
rial was consumed (monitored by TLC). After careful addition of a satu-
rated aqueous solution of NaHCO3, and when the gas evolution had
ceased, the organic layer was washed several times with a saturated aque-
ous solution of NaHCO3, dried over MgSO4, and the solvent was re-
moved in vacuo. The crude imidazole 7 was purified by column chroma-
tography.
Oxazoles 9 (representative procedure): The crude a-acylaminoimine 6
was prepared as detailed above then 2n HCl (16 mL) was added to a so-
lution of the crude a-acylaminoimine 6 (0.42 mmol) in THF (16 mL).
After heating at reflux for 2 h, the mixture was partitioned between ethyl
acetate and a saturated aqueous solution of NaHCO3. The organic layer
was washed with a saturated aqueous solution of NaHCO3, dried over
MgSO4, and the solvent was removed in vacuo. The crude a-acylamino-
ketone 8 was cyclized in analogy to the procedure for the cyclization of
compounds 6, and the resulting oxazole 9 was purified by column chro-
matography.
¯
Crystal Data for 7i: Formula C29H24N2; triclinic; space group P1; a=
9.907(2), b=10.276(2), c=12.002(3) ꢃ; a=74.50(2), b=84.07(1), g=
67.97(2)8; V=1091.4(4) ꢃ3; z=2; 1=1.219 gcmÀ3; T=193 K; R=0.045;
Rw=0.1234. CCDC-705899 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
request/cif.
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Acknowledgements
[28] N. Meyer, F. Werner, T. Opatz, Synthesis 2005, 945–956.
This work was supported by the Deutsche Forschungsgemeinschaft. We
thank H. Kolshorn for the NMR spectroscopic measurements and Dr. D.
Schollmeyer for the crystallographic analysis of 7i.
Received: October 20, 2008
Published online: December 12, 2008
Chem. Eur. J. 2009, 15, 843 – 845
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
845