M. Harig, B. Neumann, H.-G. Stammler, D. Kuck
FULL PAPER
(14), 77 (14). C17H18O5 (302.33): calcd. C 67.54, H 6.00; found C
67.45, H 5.99.
1:1) ϭ 0.11] was obtained containing several condensation prod-
ucts, as indicated by mass spectrometry.[23]
Bis(3,4-dimethoxyphenyl)methane (12): Palladium on charcoal
(1.00 g, 10% Pd, oxidic form) was added to a solution of benzo-
2-[Bis(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxy-1H-indene-
1,3(2H)-dione (14): A solution of the indane-1,3-dione 8 (3.61 g,
phenone 11 (12.1 g, 40.0 mmol) in 400 mL of glacial acetic acid. 17.5 mmol) and para-toluenesulfonic acid monohydrate (380 mg,
The suspension was shaken in a Parr apparatus under hydrogen
(6.0 bar, 20 °C) for 3 d. The solution was then filtered through silica
gel (Kieselgel 60, л Յ 0.063 mm, Merck) and the filter washed
with dichloromethane. The combined solutions were concentrated
to dryness and the residue obtained was recrystallized from meth-
anol to give 12 as a colorless solid (9.39 g, 81%), m.p. 68Ϫ69 °C
2.00 mmol) in 100 mL of benzene (p.a.) was heated to reflux in a
flask equipped with a ThieleϪPape extractor containing molecular
˚
sieves (4 A). A solution of 13·H2O (6.45 g, 20.0 mmol) in 80 mL of
1,2-dichloroethane, formed by gentle warming, was added slowly.
At the beginning of the reaction, purple streaks formed in the yel-
low reaction solution but vanished immediately due to the stirring.
(69Ϫ71 °C[34b]), Rf (n-hexane/EtOAc, 1:1) ϭ 0.64. 1H NMR Towards the end of the addition, the reaction mixture turned red
(500.1 MHz, CDCl3): δ ϭ 3.83 (s, 6 H), 3.86 (s, 6 H), 3.88 (s, 2 H), brown. Heating was continued for 1 h and the mixture was then
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6.70 (d, JH,H ϭ 2.1 Hz, 2 H), 6.72 (dd, JH,H ϭ 8.0, JH,H
ϭ
allowed to cool. It was washed with water, dried with sodium sul-
fate and concentrated to dryness. The residue obtained was purified
3
2.1 Hz, 2 H), 6.80 (d, JH,H ϭ 8.0 Hz, 2 H) ppm. 13C NMR
(125.8 MHz, CDCl3): δ ϭ 41.0 (CH2), 55.8 (CH3), 55.9 (CH3), by column chromatography (EtOAc) and the product collected was
111.1 (CH), 112.1 (CH), 120.7 (CH), 133.9 (C), 147.3 (C), 148.9
recrystallized from methanol to furnish 14 (6.94 g, 81%) as a light
(C) ppm. IR (KBr): ν˜ ϭ 2968 cmϪ1, 2942, 2897, 2845, 1608, 1589, yellow solid, m.p. 107Ϫ108 °C, Rf (EtOAc) ϭ 0.81, Rf (n-hexane/
1
1513, 1466, 1449, 1417, 1334, 1295, 1242, 1201, 1188, 1154, 1135, EtOAc, 1:1) ϭ 0.27. H NMR (500.1 MHz, CDCl3): δ ϭ 3.75 (m,
1027, 852, 816, 800, 770, 640. MS (EI, 70 eV): m/z (%) ϭ 288 (100)
[M·ϩ], 287 (8), 273 (6), 257 (47), 242 (6), 241 (11), 213 (5), 199 (6),
166 (5), 151 (19), 144 (6), 128 (9), 115 (10), 107 (5).
7 H), 3.77 (s, 6 H), 3.94 (s, 6 H), 4.94 (d, 3JH,H ϭ 2.0 Hz, 1 H), 6.68
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4
(d, JH,H ϭ 8.4 Hz, 2 H), 6.85 (dd, JH,H ϭ 8.3, JH,H ϭ 1.9 Hz, 2
H), 6.91 (d, JH,H ϭ 1.9 Hz, 2 H), 7.17 (s, 2 H) ppm. 1H NMR
4
(500.1 MHz, C6D6): δ ϭ 3.03 (s, 6 H), 3.31 (s, 6 H), 3.49 (s, 6 H),
Bis(3,4-dimethoxyphenyl)methanol Monohydrate (13·H2O): The
benzophenone 11 (24.2 g, 80.0 mmol) was suspended in methanol
(400 mL), which had been deacidified by passing it through basic
alumina. Pyridine (0.50 mL) and palladium on charcoal (1.40 g,
10% Pd, oxidic form) were then added and the mixture was shaken
under hydrogen in a Parr apparatus (6.0 bar, 20 °C) for 7 d. The
suspension was then filtered through silica gel (Kieselgel 60, л Յ
0.063 mm, Merck) and the filter washed with deacidified methanol
(see above). Removal of the solvent under reduced pressure gave a
residue which was recrystallized from toluene (technical grade) to
furnish the monohydrate of 13 (23.6 g, 92%) as a colorless solid,
m.p. 84Ϫ85 °C (95 °C[35a]), Rf (n-hexane/EtOAc, 1:1) ϭ 0.34. 1H
NMR (500.1 MHz, CDCl3): δ ϭ 1.94 (br. s, ca. 2 H, OH), 3.85 (s,
6 H), 3.87 (s, 6 H), 5.75 (s, 1 H), 6.82 (d, 3JH,H ϭ 8.2 Hz, 2 H), 6.88
(dd, JH,H ϭ 8.2, JH,H ϭ 1.8 Hz, 2 H), 6.92 (d, JH,H ϭ 1.8 Hz, 2
H) ppm. 13C NMR (125.8 MHz, CDCl3): δ ϭ 55.85 (CH3), 55.91
(CH3), 75.7 (CH), 109.7 (CH), 110.9 (CH), 118.9 (CH), 136.6 (C),
148.4 (C), 149.0 (C) ppm. IR (KBr): ν˜ ϭ 3560 cmϪ1, 3356, 3010,
2973, 2948, 2843, 1643, 1606, 1593, 1515, 1466, 1442, 1418, 1305,
1254, 1232, 1132, 1068, 1020, 870, 862, 813, 776, 767, 757, 645. MS
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3.73 (d, JH,H ϭ 2.3 Hz, 1 H), 5.45 (d, JH,H ϭ 2.0 Hz, 1 H), 6.57
3
4
(d, JH,H ϭ 8.2 Hz, 2 H), 7.01 (s, 2 H), 7.26 (d, JH,H ϭ 1.9 Hz, 2
H), 7.29 (dd, JH,H ϭ 8.2, JH,H ϭ 2.0 Hz, 2 H) ppm. 1H NMR
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(500.1 MHz, [D6]DMSO): δ ϭ 3.61 (s, 6 H), 3.66 (s, 6 H), 3.91 (s,
3
6 H), 4.12 (d, JH,H ϭ 2.7 Hz, 1 H), 4.79 (d, 3JH,H ϭ 2.6 Hz, 1 H),
3
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3
6.75 (dd, JH,H ϭ 8.3, JH,H ϭ 1.8 Hz, 2 H), 6.78 (d, JH,H
ϭ
8.5 Hz, 2 H), 6.90 (d, 4JH,H ϭ 1.7 Hz, 2 H), 7.30 (s, 2 H) ppm. 13
C
NMR (125.8 MHz, CDCl3): δ ϭ 49.3 (CH), 55.7 (4 CH3), 56.6 (2
CH3), 58.0 (CH), 103.0 (CH), 110.6 (CH), 112.2 (CH), 121.0 (CH),
134.0 (C), 137.7 (C), 147.4 (C), 148.3 (C), 155.8 (C), 198.8 (C) ppm.
13C NMR (125.8 MHz, C6D6): δ ϭ 50.0 (CH), 55.4 (4 CH3), 55.5
(2 CH3), 58.4 (CH), 103.3 (CH), 112.0 (CH), 114.0 (CH), 121.7
(CH), 135.1 (C), 138.1 (C), 148.9 (C), 149.9 (C), 156.1 (C), 198.7
(C) ppm. IR (KBr): ν˜ ϭ 3094 cmϪ1, 3002, 2952, 2911, 2837, 1728,
1690, 1582, 1518, 1463, 1445, 1416, 1318, 1263, 1238, 1227, 1202,
1177, 1141, 1114, 1039, 1026, 990, 858, 845, 767, 636. MS (EI,
70 eV): m/z (%) ϭ 492 (16) [M·ϩ], 287 (100), 257 (8), 241 (5), 206
(5), 181 (12), 165 (6), 151 (7), 149 (12), 136 (7). C28H28O8 (492.53):
calcd. C 68.28, H 5.73; found C 68.01, H 5.86.
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(EI, 70 eV): m/z (%) ϭ 304 (93) [M·ϩ], 302 (12), 288 (87), 287 (32), 2,2-Bis[bis(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxy-1H-indene-
273 (10), 263 (12), 257 (39), 241 (11), 167 (11), 165 (100), 151 (30), 1,3(2H)-dione (15): Besides single alkylation, the reaction of the
139 (91), 138 (39), 135 (17), 128 (10), 121 (10), 115 (11), 107 (10). indanedione 8 and the benzhydrol 13 gave rise to dialkylation to
Accurate mass by EI-MS (C17H20O5): calcd. 304.1311; found produce varying amounts of the bis(benzhydryl)indanedione 15.
304.1329. C17H20O5 (304.35): calcd. 67.09, 6.62; This compound was obtained by gravity column chromatography.
C
H
C17H20O5·H2O (322.36): calcd. C 63.34, H 6.88; found C 63.36,
H 7.08.
It was isolated as a yellow solid after recrystallization from meth-
anol, m.p. 128Ϫ129 °C, Rf (EtOAc) ϭ 0.63. 1H NMR (500.1 MHz,
CDCl3): δ ϭ 3.71 (s, 12 H), 3.75 (s, 12 H), 3.85 (s, 6 H), 4.63 (s, 2
Disproportionation of Bis(3,4-dimethoxyphenyl)methanol (13): A
solution of 3,3Ј,4,4Ј-tetramethoxybenzhydrol monohydrate,
13·H2O, (645 mg, 2.00 mmol) and para-toluenesulfonic acid
monohydrate (38.0 mg, 200 µmol) in 50 mL of toluene (p.a.) was
heated to reflux for 2 h. The water was removed by use of a
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H), 6.54 (d, JH,H ϭ 8.4 Hz, 4 H), 6.84 (dd, JH,H ϭ 8.3, JH,H
ϭ
1.9 Hz, 4 H, 6.89 (d, JH,H ϭ 1.8 Hz, 4 H), 6.91 (s, 2 H) ppm. 13C
NMR (125.8 MHz, CDCl3): δ ϭ 55.57 (4 CH3), 55.61 (4 CH3),
55.7 (CH), 56.4 (CH3), 67.3 (C), 102.0 (CH), 110.5 (4 CH), 113.0
(4 CH), 122.1 (4 CH), 132.5 (4 C), 138.1 (C), 147.2 (4 C), 148.0 (4
C), 155.6 (C), 203.4 (C) ppm. IR (KBr): ν˜ ϭ 2941 cmϪ1, 2838,
1728, 1688, 1578, 1514, 1459, 1314, 1264, 1144, 1114, 1028, 810,
768, 646. MS (EI, 70 eV): m/z (%) ϭ 778 (1) [M·ϩ], 492 (3), 491
(2), 490 (2), 287 (100), 257 (14), 241 (4), 151 (4). C45H46O12
(778.86): calcd. C 69.40, H 5.95; found C 69.33, H 6.14.
4
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ThieleϪPape extractor filled with molecular sieves (4 A). The reac-
tion mixture was allowed to cool to ambient temperature and then
washed twice with 25 mL of aqueous sodium hydroxide (2 ) and
once with 25 mL of water, then dried with sodium sulfate and con-
centrated to dryness. The residue was subjected to gravity column
chromatography (hexanes/EtOAc, 1:1). Besides diveratrylmethane
(12) (82.0 mg, 14%) and 3,3Ј,4,4Ј-tetramethoxybenzophenone (11)
all-cis-2-[Bis(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxyindane-
(160 mg, 26%), a third fraction [96.0 mg, Rf (n-hexane/EtOAc, 1,3-diol (16): A solution of the indane-1,3-dione 14 (4.93 g,
Eur. J. Org. Chem. 2004, 2381Ϫ2397