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Q. Luo et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 65–69
200 mL of EtOAc and washed with water (2× 50 mL), the
water phase was extracted with 150 mL of EtOAc. The com-
bined organic phase was washed with 10% aqueous HCl, water,
and saturated aqueous NaCl, dried over anhydrous MgSO4 and
then filtered and concentrated under reduced pressure to yield
N,Nꢀ-bis(2-oxo-2-ethoxyethyl)isophthalamide (A) (2.0 g, 99%
yield) as a colorless oil which slowly solidified. The com-
δ = 7.80 (d, J = 8.0 Hz, 2H), 7.43 (t, J = 7.8 Hz, 1H), 6.31 (s,
2H), 4.22 (q, J = 7.1 Hz, 4H), 1.47 (t, J = 7.1 Hz, 6H). 13C NMR
(75 MHz, CDCl3): δ = 160.1, 150.9, 132.1, 130.9, 127.3, 120.0,
100.9, 68.3, 14.6. MS (EI-MS): m/z (%) = 380.1 (56), 378.1 (57)
[M+], 296.1 (98), 294.0 (100), 268.0 (44), 266.0 (46). Elemental
analysis for C16H15BrN2O4: found C 50.99, H 4.21, N 7.14, Br
20.51; calcd. C 50.68, H 3.99, N 7.39, Br 21.07.
1
pound could be used in the next step without purification. H
NMR (300 MHz, CDCl3): δ = 8.20 (t, J = 1.6 Hz, 1H), 7.92 (dd,
J = 1.8, 7.8 Hz, 2H), 7.46 (t, J = 7.7 Hz, 1H), 7.09 (t, J = 5.1 Hz,
2H), 4.26 (q, J = 7.1 Hz, 4H), 4.23 (d, J = 5.2 Hz, 4H), 1.32 (t,
J = 7.1 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ = 170.2, 166.7,
133.9, 130.5, 129.0, 125.4, 61.8, 41.9, and 14.2. A mixture of
B (338 mg, 1 mmol) and P2O5 (2.8 g, 20 mmol) in 40 mL of dry
ClCH2CH2Cl was stirred for 14 h at 90 ◦C. The reaction mix-
ture was cooled to room temperature, diluted with 30 mL of
Et2O, and then carefully neutralized with 10% cold KOH aque-
ous solution (ca. 35 mL) followed by extraction with EtOAc
(three portions of 50 mL). The combined organic phase was
washed with water and saturated aqueous NaCl, dried over anhy-
drous MgSO4 and then filtered and concentrated to dryness. The
crude product was purified by column chromatography (silica,
hexanes:EtOAc 1:1 as eluent) to afford 39 mg of 5a as a pale
white solid. Yield 13%. 1H NMR (300 MHz, CDCl3): δ = 8.42 (t,
J = 1.5 Hz, 1H), 7.92 (dd, J = 1.8, 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz,
1H), 6.22 (s, 2H), 4.19 (q, J = 7.0 Hz, 4H), 1.45 (t, J = 7.1 Hz,
126.1, 122.1, 101.1, 68.2, 14.6.
2.2.3. Bis(oxazole) 5c
To a stirred mixture of isophthaloyl dichloride (4a) (1.01 g,
5.0 mmol, 1.0 equiv.) in 12 mL of dry pyridine was added in
portions ␣-aminoacetophenone hydrochloride (1.88 g, 11 mmol,
2.2 equiv.). The reaction was refluxed for 30 min. Then the
mixture was allowed to cool and diluted with water. The pre-
cipitate was filtered and dissolved in hot ethyl acetate. The
organic solution was concentrated to a smaller volume and
diethyl ether was added. White to beige product commences
to crystallize out. Filtration afforded the crude product (0.99 g,
2.47 mmol, 49%), which was used without further purification.
1H NMR (300 MHz, DMSO-d6): δ = 9.02 (t, 2H, J = 5.5 Hz),
8.48–8.42 (m, 1H), 8.12–8.00 (m, 6H), 7.74–7.52 (m, 7H), 4.83
(d, 4H, J = 5.5 Hz); 13C NMR (75.5 MHz, DMSO-d6): δ = 195.1,
166.0, 135.0, 134.1, 133.5, 129.9, 128.8, 128.5, 127.8, 126.4,
46.4; MS (PI-EIMS): m/z (%) = 400.2 (14) [M+], 295.2 (11)
[M+ − PhCO], 266.1 (84) [M+ − PhCOCH2NH], 105.1 (100)
[PhCO+], 77.1 (25) [Ph+]. A mixture of N,Nꢀ-bis-(2-oxo-2-
phenyl-ethyl)isophthalamide (1.03 g, 2.57 mmol, 1.0 equiv.) in
40 mL phosphorus oxychloride was refluxed for 16 h. Most of
the phosphorus oxychloride was distilled in vacuum into a cold
trap from the reaction mixture, and the residue was slowly added
to water contained in a 250 mL beaker. The solid was filtered,
washed with water and dried (crude product). Recrystalliza-
tion from pyridine afforded 0.49 g (1.34 mmol, 52%) of 5c as
a white to beige solid. mp 177 ◦C; 1H NMR (300 MHz, CDCl3):
δ = 8.85–8.79 (m, 1H), 8.21 (dd, 2H, J = 7.8, 1.6 Hz), 7.81–7.74
(m, 4H), 7.61 (t, 1H, J = 7.8 Hz), 7.55–7.43 (m, 6H), 7.41–7.33
(m, 2H); 13C NMR (75.5 MHz, CDCl3): δ = 160.4, 151.8, 129.5,
129.0, 128.7, 128.2, 128.0, 127.8, 124.4, 123.8, 123.5; IR (KBr):
3110, 3060, 1600, 1580, 1565, 1530, 1480, 1470, 1445, 1420,
1135, 1075, 1060, 1030, 965, 950, 940, 910, 860, 825, 800, 760,
710, 680 cm−1; MS (PI-EIMS): m/z (%) = 364.2 (100) [M+];
C24H16N2O2 (364.40): calcd. C 79.11, H 4.43, N 7.69; found C
78.42, H 3.77, N 7.49.
2.2.2. Bis(oxazole) 5b
2-Bromoisophthaloyldichloride 4b [7b](1.73 g, 6 mmol)and
ethyl glycinate hydrochloride (2.51 g, 18 mmol) were suspended
in 40 mL of dry CH2Cl2, and Et3N (8.4 mL, 60 mmol) was
added dropwise at 0 ◦C. After being stirred for 30 h with gradual
warming to room temperature, the resultant mixture was con-
centrated, diluted with 70 mL of H2O, and then extracted with
CH2Cl2 (four portions of 150 mL each). The combined organic
phase was washed with 10% aqueous HCl, water, and saturated
aqueous NaCl, dried over anhydrous MgSO4 and then filtered
and concentrated under reduced pressure to yield 2-bromo-
N,Nꢀ-bis(2-oxo-2-ethoxyethyl)isophthalamide (B) (2.10 g, 84%
yield) as a white solid. The compound could be used in the next
step without purification. mp 191–192 ◦C; 1H NMR (300 MHz,
CDCl3): δ = 7.54 (dd, J = 7.1, 8.0 Hz, 2H), 7.42 (dd, J = 6.9,
8.2 Hz, 1H), 6.48 (t, J = 4.8 Hz, 2H), 4.27 (q, J = 7.1 Hz, 4H),
4.25 (d, J = 5.0 Hz, 4H), 1.32 (t, J = 7.1 Hz, 6H). A mixture of B
(1.66 g, 4 mmol) and P2O5 (7.5 g, 52.8 mmol) in 80 mL of dry
ClCH2CH2Cl was heated for30 min at60 ◦C, andthen stirredfor
14 h at 90 ◦C. The reaction mixture was cooled to room tempera-
ture, diluted with 50 mL of Et2O, and then carefully neutralized
with 10% cold NaOH (ca. 55 mL) followed by extraction with
EtOAc (3× 150 mL each). The combined organic phase was
washed with water and saturated aqueous NaCl, dried over anhy-
drous MgSO4 and then filtered and concentrated. The crude
product was purified by column chromatography (silica, hex-
anes:EtOAc 1:1 as eluent) to afford 5b (880 mg, 58% yield) as a
light yellow solid. mp 56–57 ◦C; 1H NMR (300 MHz, CDCl3):
2.2.4. Bis(oxazole) 5d
To a stirred mixture of 2-bromo-1,3-benzenedicarbonyl
dichloride (4b) (1.50 g, 5.32 mmol, 1.0 equiv.) in 15 mL of
dry pyridine was added in portions ␣-aminoacetophenone
hydrochloride (2.00 g, 11.71 mmol, 2.2 equiv.). The reaction
was refluxed for 15 min—the mixture got red, then yellow.
The reaction was allowed to cool and diluted with water.
The resulting precipitate was filtered, washed with diethyl
ether and dried. This crude product was stirred in 20 mL of
ethyl acetate. Filtration of the cold (0 ◦C) mixture afforded
the product as beige solid (1.76 g, 3.67 mmol, 69%). 1H NMR
(300 MHz, DMSO-d6): δ = 8.87 (t, 2H, J = 5.6 Hz), 8.10–8.01
(m, 4H), 7.74–7.65 (m, 2H), 7.63–7.44 (m, 7H), 4.78 (d, 4H,