May 2016
Synthesis of Xanthenones
987
an Electrothermal model 9100 apparatus (Bibby Scientific
Limited, UK) and are uncorrected. IR spectra were recorded on a
Shimadzu 4300 spectrophotometer (Shimadzu Scientific Instru-
ments, Columbia, MD). The 1H-NMR and 13C-NMR spectra were
recorded in DMSO-d6 on Bruker DRX-400 AVANCE spectro-
meters (Bruker Optics Inc., Billerica, MA). Chemical shifts (d) are
reported in parts per million and are referenced to the NMR solvent.
Mass spectra of the products were obtained with an high performing
Agilent 5973 Mass Selective Detector (Palo Alto, CA). Elemental
analyses were carried out by a Carbon-Hydrogen-Nitrogen
(CHN)-Rapid Heraeus elemental analyzer (Wellesley, MA).
(d, 1H, J= 17.6 Hz, CH2), 3.72 (s, 3H, OCH3), 5.80 (s, 1H,
methine-H), 6.56–8.32 (m, 9H, Ar—H), 8.95 (s, 1H, OH).
12-(4-Chlorophenyl)-9,9-dimethyl-2-hydroxy-8,9,10,12-
tetrahydrobenzo-[a]xanthen-11-one (5a). White solid;
mp= 308–310ꢀC; IR (KBr): 3187 (OH), 1626 (C═O), 1231
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.87 (s, 3H,
CH3), 1.06 (s, 3H, CH3), 2.12 (d, 1H, J = 16.4Hz, CH2), 2.34
(d, 1H, J = 16.4 Hz, CH2), 2.56 (d, 1H, J = 17.6 Hz, CH2), 2.67
(d, 1H, J = 17.6Hz, CH2), 5.35 (s, 1H, methine-H), 6.97–7.79
(m, 9H, Ar—H), 9.95 (s, 1H, OH) ppm.
12-(4-Methylphenyl)-9,9-dimethyl-2-hydroxy-8,9,10,12-
tetrahydrobenzo-[a]xanthen-11-one (5b). White solid;
mp= 298–300ꢀC; IR (KBr): 3173 (OH), 1625 (C═O), 1228
General procedure for the synthesis of xanthenones (4, 5). To
a mixture of aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione
(1 mmol), and naphthol (1 mmol), guanidinium chloride (10 mol%)
was added and heated at 80ꢀC for the appropriate amount of time
as indicated in Table 1. The progress of the reaction was monitored
by TLC. After completion, the reaction mixture was cooled to RT,
and EtOH (5 mL) was added until white solid products precipitated.
The precipitate was filtered, washed with cold ethanol, and dried.
The obtained products 3 were found to be pure upon TLC examination.
9,9-Dimethyl-12-(2-hydroxyphenyl)-8,9,10,12-tetrahydrobenzo-[a]
xanthen-11-one (4a). White solid; mp = 221–227ꢀC; IR (KBr): 3199
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.88 (s, 3H,
CH3), 1.06 (s, 3H, CH3), 2.11 (d, 1H, J = 16.0Hz, CH2), 2.33
(d, 1H, J = 16.0 Hz, CH2), 2.55 (d, 1H, J = 17.6 Hz, CH2), 2.67
(d, 1H, J = 17.6Hz, CH2), 5.30 (s, 1H, methine-H), 6.90–7.76
(m, 9H, Ar—H), 9.91 (s, 1H, OH) ppm.
12-(4-Methoxyphenyl)-9,9-dimethyl-2-hydroxy-8,9,10,12-
tetrahydrobenzo-[a]xanthen-11-one (5c). White solid;
mp= 296–297ꢀC; IR (KBr): 3190 (OH), 1625 (C═O), 1232
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.88 (s, 3H,
CH3), 1.06 (s, 3H, CH3), 2.11 (d, 1H, J = 16.4Hz, CH2), 2.33
(d, 1H, J = 16.4 Hz, CH2), 2.55 (d, 1H, J = 17.2 Hz, CH2), 2.67
(d, 1H, J = 17.2 Hz, CH2), 3.64 (s, 3H, OCH3), 5.29 (s, 1H,
methine-H), 6.75–7.76 (m, 9H, Ar—H), 9.20 (s, 1H, OH) ppm.
12-(2-Chlorophenyl)-9,9-dimethyl-2-hydroxy-8,9,10,12-
tetrahydrobenzo-[a]xanthen-11-one (5d). White solid;
mp= 280–282ꢀC; IR (KBr): 3396 (OH), 1628 (C═O), 1228
1
(OH), 1625 (C═O), 1228 (C—O—C) cmÀ1; H-NMR (400 MHz,
DMSO-d6): 0.94 (s, 3H, CH3), 1.08 (s, 3H, CH3), 2.11 (d, 1H,
J= 16.4 Hz, CH2), 2.35 (d, 1H, J= 16.4 Hz, CH2), 2.58 (d, 1H,
J= 17.2 Hz, CH2), 2.72 (d, 1H, J= 17.2 Hz, CH2), 5.75 (s, 1H,
methine-H), 6.60–8.33 (m, 10H, Ar—H), 9.69 (s, 1H, OH) ppm.
9,9-Dimethyl-12-(4-bromophenyl)-8,9,10,12-tetrahydrobenzo-[a]
xanthen-11-one (4b). White solid; mp= 182–184ꢀC; IR (KBr):
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.90 (s, 3H,
1640 (C═O), 1221 (C—O—C) cmÀ1 1H-NMR (400 MHz,
;
CH3), 1.07 (s, 3H, CH3), 2.09 (d, 1H, J = 16.0Hz, CH2), 2.34
(d, 1H, J = 16.0 Hz, CH2), 2.57 (d, 1H, J = 17.2 Hz, CH2), 2.71
(d, 1H, J = 17.2Hz, CH2), 5.62 (s, 1H, methine-H), 7.01–7.77
(m, 9H, Ar—H), 9.92 (s, 1H, OH) ppm; 13C-NMR (100MHz,
DMSO-d6): 26.54, 29.42, 32.18, 33.29, 50.61, 106.02, 112.61,
114.03, 115.18, 117.47, 125.87, 127.56, 128.51, 129.60, 130.16,
130.64, 132.56, 133.34, 142.02, 148.31, 156.85, 157.02, 158.52,
164.75, 196.20 ppm; MS (EI): m/z 406 (M + 2)+, 404 (M)+, 369,
293, 237, 209, 181, 152; Anal. Calcd for C25H21ClO3: C, 74.16;
H, 5.19. Found: C, 74.20; H, 5.23.
DMSO-d6): 0.88 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.14 (d, 1H,
J = 16.0Hz, CH2), 2.35 (d, 1H, J = 16.0Hz, CH2), 2.59 (d, 1H,
J = 17.2Hz, CH2), 2.70 (d, 1H, J = 17.2 Hz, CH2), 5.58 (s, 1H,
methine-H), 7.24–8.02 (m, 10H, Ar—H).
9,9-Dimethyl-12-(4-chlorophenyl)-8,9,10,12-tetrahydrobenzo-[a]
xanthen-11-one (4c). White solid; mp= 185–187ꢀC; IR (KBr):
1640 (C═O), 1221 (C—O—C) cmÀ1 1H-NMR (400 MHz,
;
DMSO-d6): 0.88 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.14 (d, 1H,
J = 16.0Hz, CH2), 2.35 (d, 1H, J = 16.0Hz, CH2), 2.59 (d, 1H,
J = 17.6Hz, CH2), 2.70 (d, 1H, J = 17.6 Hz, CH2), 5.59 (s, 1H,
methine-H), 7.24–8.02 (m, 10H, Ar—H).
9,9-Dimethyl-12-(4-methoxyphenyl)-8,9,10,12-tetrahydrobenzo-[a]
xanthen-11-one (4d). White solid; mp= 200–201ꢀC; IR (KBr): 1645
(C═O), 1227 (C—O—C) cmÀ1; 1H-NMR (400 MHz, DMSO-d6):
0.90 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.10 (d, 1H, J = 16.0Hz,
CH2), 2.34 (d, 1H, J = 16.0 Hz, CH2), 2.58 (d, 1H, J = 17.2Hz,
CH2), 2.69 (d, 1H, J = 17.2 Hz, CH2), 3.63 (s, 3H, OCH3), 5.52 (s,
1H, methine-H), 6.73–8.05 (m, 10H, Ar—H).
12-(2-Hydroxy-3-methoxyphenyl)-9,9-dimethyl-2-hydroxy-
8,9,10,12-tetrahydrobenzo-[a]xanthen-11-one (5e). White
solid; mp= 269–270ꢀC; IR (KBr): 3406 (OH), 1633 (C═O), 1228
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.91 (s, 3H,
CH3), 1.07 (s, 3H, CH3), 2.10 (d, 1H, J = 16.0Hz, CH2), 2.34
(d, 1H, J = 16.0 Hz, CH2), 2.53 (d, 1H, J = 17.2 Hz, CH2), 2.68
(d, 1H, J = 17.2Hz, CH2), 5.57 (s, 1H, methine-H), 6.57–7.72
(m, 8H, Ar—H), 8.72 (s, 1H, OH), 9.79 (s, 1H, OH) ppm;P
13C-NMR (100MHz, DMSO-d6): 26.64, 28.88, 29.45, 32.10,
32.32, 50.60, 55.92, 106.21, 109.74, 113.32, 114.06, 116.67,
117.33, 119.37, 121.96, 125.84, 128.78, 130.38, 132.02, 133.52,
143.16, 148.12, 156.55, 158.42, 165.14, 197.11ppm; MS (EI):
m/z 416 (M)+, 312, 293, 257, 237, 241, 209, 181, 160, 152, 131;
Anal. Calcd for C26H24O5: C, 75.00; H, 5.77. Found: C, 75.08;
H, 5.71.
9,9-Dimethyl-12-(4-methylphenyl)-8,9,10,12-tetrahydrobenzo-[a]
xanthen-11-one (4e). White solid; mp= 175–177ꢀC; IR (KBr):
1645 (C═O), 1231 (C—O—C) cmÀ1 1H-NMR (400 MHz,
;
DMSO-d6): 0.89 (s, 3H, CH3), 1.07 (s, 3H, CH3), 2.11 (d, 1H,
J = 16.0Hz, CH2), 2.14 (s, 3H, CH3), 2.34 (d, 1H, J = 16.0Hz,
CH2), 2.58 (d, 1H, J = 17.6 Hz, CH2), 2.70 (d, 1H, J = 17.6Hz,
CH2), 5.53 (s, 1H, methine-H), 6.97–8.05 (m, 10H, Ar—H).
9,9-Dimethyl-12-(2-hydroxy-3-methoxyphenyl)-8,9,10,12-
12-(5-Bromo-2-hydroxyphenyl)-9,9-dimethyl-2-hydroxy-
8,9,10,12-tetrahydrobenzo-[a]xanthen-11-one (5f). White
solid; mp= 308–310ꢀC; IR (KBr): 3381 (OH), 1625 (C═O), 1222
tetrahydrobenzo-[a]xanthen-11-one
(4f).
White solid;
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.94 (s, 3H,
mp = 213–215ꢀC; IR (KBr): 3276 (OH), 1622 (C═O), 1238
1
(C—O—C) cmÀ1; H-NMR (400 MHz, DMSO-d6): 0.94 (s, 3H,
CH3), 1.07 (s, 3H, CH3), 2.11 (d, 1H, J = 16.0Hz, CH2), 2.34
(d, 1H, J = 16.0 Hz, CH2), 2.56 (d, 1H, J = 17.2 Hz, CH2), 2.69
(d, 1H, J = 17.2Hz, CH2), 5.47 (s, 1H, methine-H), 6.66–7.73
CH3), 1.08 (s, 3H, CH3), 2.11 (d, 1H, J= 16.0 Hz, CH2), 2.35
(d, 1H, J= 16.0 Hz, CH2), 2.58 (d, 1H, J= 17.6 Hz, CH2), 2.72
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet