SHORT PAPER
Synthesis of 2,4-Disubstituted 2-Imidazolin-5-ones
27
Scheme 3
and compound 7 (50 mg, 0.19 mmol) in DMF (4 mL). The reaction
mixture was stirred at r.t. for 5 min, then aq sat. solution of NaHCO3
was added and the mixture was extracted with CH2Cl2. The organic
layer was washed with brine, and dried (Na2SO4). Purification by
flash chromatography on silica gel (EtOAc-hexane, 1:3) gave the
desired product (48 mg, 80%) as a yellow powder; mp 128–130 °C.
1H NMR (CDCl3, 200 MHz): d = 8.2 (d, J = 8 Hz, 2 H, ArH), 7.7
(m, 1 H, Hfuryl), 7.4 (d, J = 4 Hz, 1 Hfuryl), 7.2 (s, 1 H, =CH), 7.0 (d,
J = 8 Hz, 2 H, ArH), 6.7 (dd, J = 4, 1.7 Hz, 1 Hfuryl), 3.9 (s, 3 H,
OCH3), 3.5 (s, 3 H, NCH3).
In conclusion, the Liebeskind–Srogl coupling reaction
was performed with success in neutral conditions with 2-
methylthioimidazolin-5-one using tetrakis(triphenylphos-
phine)palladium as a catalyst, copper(I) thiophene-2-car-
boxylate as a mediation agent in a sealed tube, or under
microwave irradiation. It is noteworthy that the reaction
of compound 7 with organostannanes occurred at lower
temperature and in good yields. In addition it constitutes
another illustration of the use of thiomethyl group as a
leaving group in palladium coupling reactions, when the
heteroaromatic halide or corresponding O-triflate are not
available.
13C NMR (CDCl3, 50 MHz): d = 171.2, 161.8, 151.8, 146.1, 145.6,
137.4, 134.8, 128.7, 127.5, 116.2, 114.7, 112.9, 55.7, 28.9.
Anal. Calcd for C16H14N2O·0.5H2O: C, 65.97; H, 5.19; N, 9.62.
Found: C, 65.95; H, 5.12, N, 9.89.
The microwave reactor used was a multimods NORMATRON®
112 (reference 41500 from NORMALAB ANALYSIS S.A.).
References
4-{4-[(E)-(4-Methoxyphenyl)methylidene]-1-methyl-5-oxo-4,5-
dihydro-1H-imidazol-2-yl}benzonitrile (4c); Typical Procedure
Compound 7 (120 mg, 0.458 mmol), Pd(Ph3P)4 (26 mg, 0.022
mmol), CuTC (114 mg, 0.595 mmol), p-cyanophenylboronic acid
(90 mg, 0.504 mmol) were placed in a sealed tube and anhyd DMF
(3 mL) was added. This suspension was stirred and submitted to mi-
crowave irradiation (300 W) for 15 min. The solution was evaporat-
ed to dryness under reduced pressure and diluted with sat. aq
solution of NaHCO3. The aqueous solution was extracted with
CH2Cl2 (3 ×). The dried organic layer was evaporated in vacuo and
the resulting oil was purified by flash chromatography on silica gel
(EtOAc-hexane, 1:3) to afford the desired product 4c (101 mg,
70%) as an orange powder; mp 156–158 °C.
1H NMR (CDCl3, 200 MHz): d = 8.1 (d, J = 8.7 Hz, 2 H, ArH), 8.0
(d, J = 8.2 Hz, 2 H, ArH), 7.8 (d, J = 8.2 Hz, 2 H, ArH), 7.3 (s, 1 H,
=CH), 6.9 (d, J = 8.7 Hz, 2 H, ArH), 3.8 (s, 3 H, OCH3), 3.3 (s, 3 H,
NCH3).
13C NMR (CDCl3, 50 MHz): d = 171.5, 162.3, 159.4, 137.1, 135.2,
134.0, 132.9, 131.1, 129.5, 127.4, 118.4, 115.0, 114.8, 70.7, 55.8,
29.4.
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Anal. Calcd for C19H15N3O2: C, 71.91; H, 4.76; N, 13.24. Found: C,
71.63; H, 4.97, N, 12.79.
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Guillaumet, G. Org. Lett. 2003, 5, 803.
2-(2-Furyl)-5-[(E)-(4-methoxymethyl)methylidene]-3-methyl-
3,5-dihydro-4H-imidazol-4-one (8); Typical Procedure
2-(Tributylstannyl)furane (65.7 mL, 0.21 mmol) was added to a so-
lution of CuTC (79 mg, 0.41 mmol), Pd(Ph3P)4 (11 mg, 5 mol%)
Synthesis 2005, No. 1, 25–27 © Thieme Stuttgart · New York