PAPER
Reaction of Diaryl-1,2-diones with Homophthalic Anhydride
3743
3-[1,2-Bis(4-fluorophenyl)-2-oxoethyl]isobenzofuran-1(3H)-
one (6)
Mp 218–220 °C.
followed by ring closure to afford the maleic anhydride
(Scheme 4).
In conclusion, a direct and efficient method for the synthe-
sis of isobenzofuranone derivatives was described. It can
be adapted to the synthesis of substituted maleic anhy-
dride.10
IR (neat): 2956, 1767, 1683, 1597, 1507 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.95–7.81 (m, 6.23 H), 7.59–6.89
(m, 10.24 H), 6.30–6.28 (d, J = 7.5 Hz, 1 H), 6.21–6.18 (d, J = 8.7
Hz, 0.28 H), 4.79–4.76 (d, J = 7.5 Hz, 1 H), 4.65–4.63 (d, J = 8.7
Hz, 0.28 H).
13C NMR (125 MHz, CDCl3): d = 194.8, 194.7, 168.5, 168.4, 147.3,
147.0, 133.3, 131.6, 129.4, 125.7, 123.9, 116.4, 116.0, 115.9, 80.8,
80.7, 57.2, 57.0.
MS–FAB: m/z [M + 1]+ calcd for C22H14F2O3: 365.09; found:
365.66.
Melting points were recorded on a Büchi melting point apparatus
and are uncorrected. 1H NMR spectra were recorded at 300 MHz on
a Bruker Avance DPX-300 MHz NMR spectrometer; 13C NMR
were recorded at 125 MHz. Chemical shifts are reported relative to
TMS (1H) and CDCl3 (13C) as the internal standards. EI-HRMS
(5000 resolution) and FAB+-HRMS were carried out on a JEOL
JMS 600H mass spectrometer. IR spectra were recorded on a
Nicolet Impact 400D FT-IR spectrophotometer. Commercial grade
solvents were distilled prior to use.
3-[1,2-Bis(3-nitrophenyl)-2-oxoethyl]isobenzofuran-1(3H)-one
(7)
Mp 244–246 °C.
IR (neat): 2956, 1765, 1699, 1527, 1474 cm–1.
Isobenzofuran-1(3H)-ones 3–8; General Procedure
Homophthalic anhydride (1; 1 equiv) and the appropriate benzil 2
(1.5 equiv) were placed in a pear-shaped crucible. The reaction mix-
ture was heated at 145 °C for 6 h. The residue was purified by col-
umn chromatography [silica gel (60–120 mesh), EtOAc–hexane,
15:85]; this afforded the corresponding product. Recrystallisation
(CH2Cl2) yielded the products as white crystalline solids.
1H NMR (300 MHz, CDCl3): d = 8.46–8.13 (m, 6.24 H), 7.86–7.34
(m, 11.84 H), 6.35–6.28 (m, 1.56 H), 5.06- 5.04 (d, J = 7.8 Hz, 1 H),
4.88–4.85 (d, J = 8.7 Hz, 0.56 H).
13C NMR (125 MHz, CDCl3): d = 192.0, 191.4, 166.4, 166.3, 146.3,
145.1, 143.8, 134.0.
MS–FAB: m/z [M + 1]+ calcd for C22H14N2O7: 419.08; found:
419.39.
(S)-3-[(R)-2-Oxo-1,2-diphenylethyl]isobenzofuran-1(3H)-one
(3a)
Mp 147–149 °C.
IR (neat): 3037, 2926, 1716, 1708, 1458, 1265, 1184 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.81–7.89 (m, 4 H), 7.26–7.58 (m,
10 H), 6.26 (d, J = 9 Hz, 1 H), 4.72 (d, J = 9 Hz, 1 H).
3-[1,2-Bis(4-methoxyphenyl)-2-oxoethyl]isobenzofuran-1(3H)-
one (8)
Mp 208–210 °C.
IR (neat): 2858, 1769, 1681, 1573, 1175 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.69–7.65 (m, 6 H), 7.59–7.15 (m,
12 H), 6.39–6.27 (m, J = 8.9 Hz, 1 H), 6.20–6.18 (d, J = 7.8 Hz,
0.50 H), 4.69 (d, J = 7.8 Hz, 1 H), 4.63–4.60 (d, J = 8.9 Hz, 0.50 H),
3.83 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 197.4, 196.2, 169.5, 167.5, 145.3,
145.1, 133.4, 131.3, 131.6, 131.3, 130.8, 129.8, 128.7, 128.5, 127.9,
127.7, 125.2, 124.3, 122.1, 121.5, 82.4, 78.7, 55.8, 55.2.
13C NMR (125 MHz, CDCl3): d = 197.1, 169.6, 148.6, 135.8, 134.5,
133.2, 129.5, 129.2, 128.8, 128.7, 128.2, 126.8, 126.5, 125.8, 123.9,
123.5, 81.9, 59.1, 58.2.
MS–FAB: m/z [M + 1]+ calcd for C22H16O3: 329.11; found: 329.03.
3-[1,2-Bis(4-chlorophenyl)-2-oxoethyl]isobenzofuran-1(3H)-
one (4)
Mp 217–219 °C.
IR (neat): 2926, 1766, 1681, 1591, 1490 cm–1.
MS–FAB: m/z [M + 1]+ calcd for C24H20O5: 389.41; found: 389.53.
2-(4-Methyl-2,5-dioxo-2,5-dihydrofuran-3-yl)benzoic Acid (10)
Homophthalic anhydride (1; 50 mg, 0.31 mmol, 1 equiv) and ethyl
pyruvate (9; 54 mg, 0.47 mmol, 1.5 equiv) were placed in a pear-
shaped crucible. The reaction mixture was heated at 145 °C for 6 h.
Trituration of the reaction mixture with CH2Cl2 afforded the prod-
uct as a white crystalline solid.
1H NMR (300 MHz, CDCl3): d = 7.85–7.83 (m, 5.5 H), 7.82–7.14
(m, 11 H), 6.67 (d, J = 9 Hz, 0.97 H), 6.27 (d, J = 6 Hz, 0.38 H),
4.75 (d, J = 6 Hz, 1 H), 4.62 (d, J = 9 Hz, 0.38 H).
13C NMR (125 MHz, CDCl3): d = 194.6, 193.8, 168.2, 147.1, 146,
139.5, 139.3, 133.9, 133.6, 129.2, 128.6, 128.5, 128.1, 125.7, 124.9,
124.7, 122.3, 80.2, 79.5, 57.4, 29.8, 29.6.
Yield: 62 mg (87%); mp 196–198 °C.
IR (neat): 2659, 1847, 1780, 1689, 1595, 1571, 1473, 1278 cm–1.
1H NMR (300 MHz, CDCl3–DMSO): d = 8.19 (d, J = 7.5 Hz, 1 H),
7.56–7.67 (m, 2 H), 7.27 (d, J = 7.5 Hz, 1 H), 2.11 (s, 3 H).
13C NMR (125 MHz, CDCl3–DMSO): d = 167.5, 166.2, 164.0,
144.5, 137.8, 132.1, 131.4, 130.3, 129.6, 128.6.
MS–FAB: m/z [M + 1]+ calcd for C12H8O5: 233.04; found: 233.15
MS–FAB: m/z [M + 1]+ calcd for C22H14Cl2O3: 397.03; found:
397.26.
3-[1,2-Bis(4-bromophenyl)-2-oxoethyl]isobenzofuran-1(3H)-
one (5)
Mp 211–214 °C.
IR (neat): 2854, 1771, 1684, 1587, 1178 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.77–7.71 (m, 6.32 H), 7.56–7.11
(m, 12.64 H), 6.28 (d, J = 8.9 Hz, 1 H), 6.18 (d, J = 7.8 Hz, 0.58 H),
4.74 (d, J = 7.8 Hz, 1 H), 4.61 (d, J = 8.9 Hz, 0.58 H).
Acknowledgment
13C NMR (125 MHz, CDCl3): d = 193.4, 193.2, 167.6, 167.5, 145.3,
145.1, 132.4, 132.3, 131.6, 131.3, 129.8, 129.2, 128.7, 128.5, 127.9,
127.7, 124.9, 124.2, 124, 122.1, 121.5, 79.4, 78.7, 55.9, 55.7.
MS–FAB: m/z [M + 1]+ calcd for C22H14Br2O3: 484.93; found:
484.94.
V.N. acknowledges the Department of Science and Technology
(DST), New Delhi for the Raja Ramanna Fellowship. The authors
also thank the Council of Scientific and Industrial Research for fi-
nancial assistance. Thanks are due to Mr. B. Adarsh, Ms Athira. N.
Raj, and Ms S. Viji for spectral data.
Synthesis 2010, No. 21, 3741–3744 © Thieme Stuttgart · New York