SHORT PAPER
Preparation of Cycloquaterbenzoxazole and Cycloquaterbenzimidazole
725
150 °C (Lit.3 mp 155 °C). This product was used in the next step
without further purification.
and normal pressure; this procedure was accompanied by partial
sublimation.
UV (DMSO):
349 (4.82), 340 (4.87), 284 nm (4.66).
(log ) = 393 (3.99), 372s (4.24), 356s (4.78),
max
3-Amino-2-hydroxybenzamide (4)
Compound 3 (17.2 g, 94.5 mmol) was dissolved in EtOAc (350
mL), 10% Pd/C (1.7 g) was added and the nitro group was reduced
with H2 at normal pressure and r.t. The catalyst was filtered off,
washed with EtOAc and the filtrate was evaporated; yield: 14.5 g
(98%); mp 127–129 °C. The product was sufficiently pure for the
next step. An analytical sample was purified by chromatography
(silica gel, EtOAc) and recrystallized from toluene; colorless crys-
tals; mp 134–135 °C.
1H NMR (500 MHz, DMSO-d6, 120 °C): = 7.51 (t, 2 H, J = 8 Hz),
7.53 (t, 2 H, J = 8Hz), 7.79 (d, 2 H, J = 8 Hz), 7.96 (d, 2 H, J = 8
Hz), 8.23 (d, 2 H, J = 8 Hz), 8.40 (d, 2 H, J = 8 Hz). No signal of
NH protons could be detected.
EIMS: m/z (%) = 464 (M+, 3), 40 (100).
Anal. Calcd for C28H16N8 (464.5): C, 72.40; H, 3.47; N, 24.12.
Found: C, 72.51; H, 3.56; N, 24.05.
UV (propan-2-ol): max (log ) = 330 (3.55), 266 (3.44), 260 (3.53),
253 nm (3.59).
7,7 -Bibenzoxazolyl (12)
3,3 -Diaminobiphenyl-2,2 -diol (11;5 6.85 g, 32 mmol) and formic
acid (46 g, 1 mol) were refluxed for 3 h. The acid was distilled off
and the residue was heated at 180 °C for 2 h under N2. After cooling,
the product was washed with H2O and dried. Chromatographic pu-
rification (silica gel, EtOAc) and recrystallization from MeOH gave
2.77 g (37%) of pure 12; faint ochre crystals; mp 226–228 °C.
1H NMR (80 MHz, THF-d8): = 4.2 (br s, 2 H, NH2), 6.4–6.95 (m,
3 Harom), 7.15 (br s, 2 H, CONH2), 13.1 (br s, 1 H, OH).
EIMS: m/z (%) = 152 (M+, 69), 136 (65), 107 (100).
Anal. Calcd for C7H8N2O2 (152.2): C, 55.26; H, 5.30; N, 18.41.
Found: C, 55.56; H, 5.24; N, 18.11.
UV (propan-2-ol): max (log ) = 265 nm (4.27).
1H NMR (80 MHz, CDCl3): = 7.4–8.0 (m, 6 Harom), 8.2 (s, 2 H,
CH).
Cyclo-2,7 :2 ,7 :2 ,7 :2 ,7-quaterbenzoxazole (5)
Compound 4 (4 g, 26 mmol) was stirred with PPA (120 g) and heat-
ed at 220 °C under N2 for 24 h. After cooling, the mixture was
poured into about 1 kg of ice and neutralized with NH3 (25% in
H2O) to pH 6–7. After standing overnight, the precipitate was re-
moved by filtration, washed well with H2O and dried. The product
(3.22 g) was extracted using a jacketed Soxhlet extractor with pyri-
dine (250 mL) for 9 d, which separated from the solution as grey-
white powder; yield: 0.98 g (32%). Recrystallization from quinoline
and subsequent sublimation (490 °C, 5 10–3 hPa) gave pure 5; col-
orless microcrystals; mp 517–520 °C (no decomposition). The
melting point was achieved in sealed capillaries with an internal
pressure of 200 hPa of N2.
EIMS: m/z (%) = 236 (M+, 100).
Anal. Calcd for C14H8N2O2 (236.2): C, 71.18; H, 3.41; N, 11.86.
Found; C, 71.12; H, 3.56; N, 11.78.
7,7 :2 ,2 :7 ,7 -Quaterbenzoxazole (13)
A solution of 12 (1 g, 4.25 mmol) in aerated MeOH (1.3 L) was ir-
radiated with light of a 30 W low pressure Hg lamp (Orginal Hanau,
NN 30/89, = 254 nm, which was used as the immersion lamp) for
2 d. Product 13 separated during irradiation, which was filtered off,
washed and dried; yield: 180 mg (18%); colorless crystals; mp 358–
362 °C.
UV (CHCl3): max (log ) = 346 (4.51), 328 (4.75), 315 (4.73), 302
(4.76), 276 nm (4.58).
1H NMR (500 MHz, CDCl3, 50 °C): = 7.57 (t, J = 8 Hz, 4 H), 8.00
(d, J = 8 Hz, 4 H), 8.54 (d, J = 8 Hz, 4 H)
UV (CHCl3): max (log ) = 347 (4.29), 330 (4.49), 320 nm (4.47).
1H NMR (500 MHz, C2D2Cl4, 120 °C): = 7.6–8.1 (m, 12 Harom),
8.2 (s, 2 H, CH).
EIMS: m/z (%) = 468 (M+, 100), 234 (25).
EIMS: m/z (%) = 470 (M+, 52), 236 (100).
Anal. Calcd for C28H12N4O4 (468.4): C, 71.79; H, 2.58; N, 11.96.
Found: C, 71.59; H, 2.68; N, 11.90.
Anal. Calcd for C28H14N4O4 (470.4): C, 71.49; H, 3.00; N, 11.91.
Found: C, 71.39; H, 2.93; N, 11.93.
Cyclo-2,4 :2 ,7 :2 ,4 :2 ,7-quaterbenzimidazole (8)
To a solution of 2-amino-3-nitrobenzoic acid (6;4 9.1 g, 50 mmol)
in 5% aq NH3 (300 mL) was added 10% Pd/C (1 g) and the reduc-
tion with H2 was carried out at r.t. and normal pressure. The catalyst
was filtered off and the solution was evaporated to dryness. The re-
sulting ammonium salt of 2,3-diaminobenzoic acid (7; 8.28 g, 98%
yield) was used for the cyclization without further purification.
Compound 7 (4 g, 24 mmol) was stirred with PPA (125 g) and heat-
ed at 220 °C under N2 for 20 h. After cooling, the product was
poured into about 1 kg of ice and neutralized with NH3 (25% in
H2O) to pH 7–8. The very fine precipitate was filtered off, washed
well with H2O and dried; yield: 2.8 g. This was extracted using a
jacketed Soxhlet extractor with pyridine (250 mL) for 12 d. Product
8 separated from the solvent as green-gray microcrystals; yield: 396
mg (15%). It was purified by sublimation at 630 °C and 6 10–3 hPa
to give a yellow-green product. This substance slowly became dark
between 700 °C and 750 °C without melting when heated under N2
Acknowledgments
I wish to thank Mr. Reinhard Machinek of the Institute of Organic
Chemistry at the University of Göttingen for recording the 500
MHz NMR spectra.
References
(1) Grellmann, K. H.; Tauer, E. Tetrahedron Lett. 1974, 375.
(2) Wu, M. T.; Lyle, R. E. J. Heterocycl. Chem. 1971, 8, 989.
(3) Meldrum, A. N.; Hirve, N. W. J. Indian Chem. Soc. 1928, 5,
95.
(4) Denny, W. A.; Rewcastle, G. W.; Baguley, B. C. J. Med.
Chem. 1990, 33, 814.
(5) Diels, O.; Biebergeil, A. Ber. Dtsch. Chem. Ges. 1902, 35,
302.
Synthesis 2002, No. 6, 723–725 ISSN 0039-7881 © Thieme Stuttgart · New York