Mondal et al.
NMR (200 MHz, CDCl3) δ 1.42 (s, 3H), 1.56 (s, 3H), 1.66 (s,
3H), 1.68-1.79 (m, 2H), 2.01-2.17 (m, 2H), 4.12 (s, 3H), 5.03-
5.13 (m, 1H), 5.15 (s, 2H), 5.63 (d, J ) 10 Hz, 1H), 6.53 (s, 1H),
6.75 (d, J ) 10 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 17.5, 22.6,
25.6, 26.9, 41.4, 62.8, 68.7, 80.1, 104.5, 108.8, 114.3, 116.6, 123.6,
129.1, 131.9, 149.6, 155.1, 160.2, 168.6; IR (neat) 1755, 1643, 1609
cm-1; MS (m/z) 315, 232, 131, 103. Anal. Calcd for C19H22O4: C,
72.59; H, 7.05. Found: C, 72.41; H, 6.90.
10-Hydroxy-8-isopropyl-5a-methyl-5a,6,7,9-tetrahydro-3H-
2,5-dioxadicyclopenta[b,g]napthalen-1-one (10). Compound 7a
(500 mg, 1.66 mmol) was heated neat with stirring at 165-170 °C
for a period of 6 h. After cooling, the obtained residue on silica
gel column chromatographic purification using a mixture of 10%
ethyl acetate in petroleum ether furnished 10 (450 mg, 90%) as a
colorless waxy solid: 1H NMR (500 MHz, CDCl3) δ 1.39 (s, 3H),
1.50-1.59 (m, 1H), 1.67 (s, 3H), 1.73-1.83 (m, 2H), 1.87 (dd,
J ) 15, 5 Hz, 1H), 1.94 (d, J ) 5 Hz, 3H), 1.99-2.05 (m, 1H),
2.47 (dd, J ) 15, 5 Hz, 1H), 4.38 (s, 1H), 5.19 (s, 2H), 6.40 (s,
1H), 7.75 (s, 1H); 13C NMR (50 MHz, CDCl3) δ 20.0, 20.5, 22.4,
28.3, 29.2, 36.2, 40.0, 70.1, 76.4, 101.1, 102.1, 112.9, 123.2, 130.0,
145.2, 153.9, 163.8, 172.7; IR (Nujol) 3516, 3445, 1742, 1641,
1607 cm-1; MS (m/z) 301, 131, 103. Anal. Calcd for C18H20O4:
C, 71.98; H, 6.71. Found: C, 72.10; H, 6.66.
1,3-Dimethoxy-5-methylbenzene (13). A stirring mixture of 12
(5.00 g, 35.17 mmol), anhydrous K2CO3 (24.30 g, 175.87 mmol),
and methyl iodide (10.95 mL, 175.87 mmol) in acetone (100 mL)
was refluxed for 6 h. After cooling, the reaction mixture was filtered
through Celite. Removal of the solvent in vacuo followed by silica
gel column chromatographic purification of the residue using a
mixture of 2% ethyl acetate in petroleum ether afforded 13 (5.35
g, ∼100%) as a colorless oil: 1H NMR (200 MHz, CDCl3) δ 2.30
(s, 3H), 3.76 (s, 6H), 6.29 (d, J ) 2 Hz, 1H), 6.34 (d, J ) 2 Hz,
2H); 13C NMR (50 MHz, CDCl3) δ 21.6, 55.0, 97.4, 107.0, 140.0,
160.6; IR (neat) 2999, 2947, 2837, 1607, 1597 cm-1. Anal. Calcd
for C9H12O2: C, 71.03; H, 7.95. Found: C, 71.24; H, 7.88.
2-Bromo-1,5-dimethoxy-3-methylbenzene (14). To a solution
of 13 (5.00 g, 32.85 mmol) in CCl4 (60 mL) was added NBS (5.85
g, 32.85 mmol), and the reaction mixture was refluxed gently for
4 h. After cooling, the reaction mixture was filtered, and concentra-
tion of the filtrate in vacuo followed by silica gel column
chromatographic purification of the residue using a mixture of 5%
ethyl acetate in petroleum ether afforded 14 (7.51 g, 99%) as a
low-melting solid: 1H NMR (200 MHz, CDCl3) δ 2.38 (s, 3H),
3.78 (s, 3H), 3.85 (s, 3H), 6.34 (d, J ) 2 Hz, 1H), 6.42 (d, J ) 4
Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 23.5, 55.4, 56.2, 97.2,
105.1, 107.2, 139.8, 156.6, 159.3; IR (neat) 2939, 2839, 1612, 1591,
1574 cm-1; MS (m/z) 233, 231, 205, 203, 195, 181, 166, 122, 102.
Anal. Calcd for C9H11BrO2: C, 46.78; H, 4.80; Br, 34.58. Found:
C, 46.61; H, 4.92; Br, 34.69.
Methyl 2,4-Dimethoxy-6-methylbenzoate (15). To a stirring
solution of 14 (7.00 g, 30.30 mmol) in THF (60 mL) at -78 °C
was added n-BuLi (1.50 M, 24.24 mL, 36.36 mmol) dropwise. After
the mixture was stirred at -78 °C for 1 h, freshly distilled methyl
chloroformate (7.00 mL, 90.90 mmol) was added slowly. The
reaction mixture was allowed to reach room temperature, and the
reaction was quenched with a saturated solution of NH4Cl. THF
was removed in vacuo, ethyl acetate (150 mL) was added to the
reaction mixture, and the separated organic layer was washed with
water and brine and dried over Na2SO4. Removal of the solvent in
vacuo followed by silica gel column chromatographic purification
of the residue using a mixture of 10% ethyl acetate in petroleum
ether afforded 15 (6.10 g, 96%) as a colorless oil: 1H NMR (200
MHz, CDCl3) δ 2.28 (s, 3H), 3.79 (s, 3H), 3.80 (s, 3H), 3.88 (s,
3H), 6.31 (bs, 2H); 13C NMR (50 MHz, CDCl3) δ 19.4, 51.5, 54.8,
55.4, 95.7, 106.3, 116.0, 137.8, 157.9, 161.1, 168.3; IR (neat) 1728,
1607 cm-1; MS (m/z) 211, 193, 179, 122, 102. Anal. Calcd for
C11H14O4: C, 62.85; H, 6.71. Found: C, 62.93; H, 6.56.
0 °C was added a solution of 15 (5.50 g, 26.19 mmol) in DCM (40
mL) dropwise. The reaction mixture was allowed to reach room
temperature and stirred for a further 12 h. After removal of the
DCM in vacuo, the residue was cooled to 0 °C, and water was
added very slowly to decompose the formed complex. To this
reaction mixture was added ethyl acetate (150 mL), and the
separated organic layer was washed with water and brine and dried
over Na2SO4. Removal of the solvent under vacuo followed by silica
gel column chromatographic purification of the residue using a
mixture of 15% ethyl acetate in petroleum ether furnished 16 (4.67
g, 98%) as a colorless crystalline solid: mp 136-138 °C; 1H NMR
(200 MHz, DMSO-d6) δ 2.29 (s, 3H), 3.81 (s, 3H), 6.18 (bs, 2H),
10.01 (bs, 1H), 10.76 (bs, 1H); 13C NMR (50 MHz, DMSO-d6) δ
22.3, 51.9, 100.7, 107.5, 110.5, 141.1, 161.4, 161.5, 170.5; IR
(Nujol) 3371, 3306, 1651, 1643 cm-1. Anal. Calcd for C9H10O4:
C, 59.34; H, 5.53. Found: C, 59.23; H, 5.47.
Methyl 2,7-Dimethyl-5-hydroxy-2-(4-methylpent-3-enyl)-2H-
1-benzopyran-6-carboxylate (17a). To a stirring mixture of 16
(1.00 g, 5.49 mmol) and Ca(OH)2 (814 mg, 10.99 mmol) in
methanol (25 mL) at room temperature was added citral (4.75 mL,
27.47 mmol). After the mixture was stirred for 72 h at room
temperature, methanol was removed in vacuo, and the reaction
mixture was diluted with ethyl acetate (60 mL). The separated
organic layer was washed with 2 N HCl, water, and brine and dried
over Na2SO4. Removal of the solvent in vacuo followed by silica
gel column chromatographic purification of the residue using a
mixture of 2% ethyl acetate in petroleum ether gave 17a (1.25 g,
72%) as a colorless oil: 1H NMR (200 MHz, CDCl3) δ 1.39 (s,
3H), 1.56 (s, 3H), 1.57-1.70 (m, 2H), 1.66 (s, 3H), 2.00-2.20
(m, 2H), 2.45 (s, 3H), 3.91 (s, 3H), 5.09 (t, J ) 6 Hz, 1H), 5.47 (d,
J ) 10 Hz, 1H), 6.18 (s, 1H), 6.73 (d, J ) 10 Hz, 1H), 11.99 (s,
1H); 13C NMR (50 MHz, CDCl3) δ 17.6, 22.6, 24.4, 25.6, 27.0,
41.6, 51.7, 79.6, 104.9, 107.0, 111.6, 116.8, 123.9, 126.2, 131.7,
142.7, 157.8, 159.7, 172.4; IR (neat) 3017, 1726, 1659, 1651, 1645,
1620, 1614 cm-1; MS (m/z) 317, 303, 301, 289, 285, 269, 233,
102. Anal. Calcd for C19H24O4: C, 72.13; H, 7.65. Found: C, 72.02;
H, 7.83.
Methyl 2,7-dimethyl-5-hydroxy-2-[(3E)-4,8-dimethyl-3,7-
nonadienyl]-2H-1-benzopyran-6-carboxylate (17b). Compound
17b was prepared similarly using 16 (1.00 g, 5.49 mmol), Ca(OH)2
(814 mg, 10.99 mmol), and farnesal (6.05 g, 27.47 mmol). 17b
1
(1.66 g, 79%): colorless oil; H NMR (200 MHz, CDCl3) δ 1.39
(s, 3H), 1.57 (s, 3H), 1.60 (s, 3H), 1.68 (s, 3H), 1.85-2.25 (m,
8H), 2.46 (s, 3H), 3.91 (s, 3H), 5.10 (t, J ) 6 Hz, 2H), 5.48 (d,
J ) 10 Hz, 1H), 6.19 (s, 1H), 6.74 (d, J ) 10 Hz, 1H), 11.99 (s,
1H); 13C NMR (50 MHz, CDCl3) δ 15.9, 17.6, 22.5, 24.3, 25.6,
26.6, 26.9, 39.6, 41.5, 51.6, 79.6, 104.8, 107.0, 111.6, 116.8, 123.7,
124.3, 126.1, 131.2, 135.3, 142.6, 157.8, 159.7, 172.3; IR (neat)
2968, 2926, 1653, 1618 cm-1; MS (m/z) 385, 383, 369, 365, 353,
348, 317, 233, 209, 201, 125, 102. Anal. Calcd for C24H32O4: C,
74.97; H, 8.39. Found: C, 75.11; H, 8.45.
2,7-Dimethyl-5-hydroxy-2-(4-methylpent-3-enyl)-2H-1-ben-
zopyran-6-carboxylic Acid (18a). To a stirring solution of 17a
(500 mg, 1.58 mmol) in methanol (15 mL) at 0 °C was added 3 N
KOH (5 mL) slowly. The reaction mixture was allowed to attain
room temperature, and after 72 h of stirring at room temperature,
methanol was removed in vacuo. The reaction mixture was acidified
with 2 N HCl at 0 °C and then extracted with ethyl acetate (50 mL
× 2). The combined organic layer was washed with water, brine
and dried over Na2SO4. Removal of the solvent in vacuo followed
by silica gel column chromatographic purification of the residue
using a mixture of 15% ethyl acetate in petroleum ether gave 18a
(392 mg, 82%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ
1.40 (s, 3H), 1.57 (s, 3H), 1.65-1.80 (m, 2H), 1.66 (s, 3H), 2.00-
2.15 (m, 2H), 2.53 (s, 3H), 5.09 (t, J ) 8 Hz, 1H), 5.48 (d, J ) 8
Hz, 1H), 6.23 (s, 1H), 6.73 (d, J ) 8 Hz, 1H), 11.71 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 17.6, 22.7, 24.4, 25.6, 27.1, 41.7, 80.0,
103.6, 107.1, 112.1, 116.7, 123.9, 126.3, 131.9, 144.4, 158.9, 160.6,
176.0; IR (Nujol) 3061, 2700-2500, 1651, 1643, 1632, 1620, 1614
Methyl 2,4-Dihydroxy-6-methylbenzoate (16). To a stirring
mixture of AlCl3 (20.95 g, 157.14 mmol) in DCM (100 mL) at
2074 J. Org. Chem., Vol. 72, No. 6, 2007