E. C. Constable, C. E. Housecroft et al.
FULL PAPER
1435 (m), 1362 (s), 1345 (m), 1329 (m), 1319 (w), 1292 (s), 1266
(w), 1220 (m), 1171 (s), 1131 (s), 1096 (m), 1067 (w), 1043 (m),
1004 (m), 963 (s), 947 (w), 876 (s), 827 (m), 812 (s), 766 (m), 732
(m), 682 (m), 638 (m), 623 (m) cm–1. MALDI-TOF MS: m/z = 634
[M + K]+. C32H48O8S (592.8): calcd. C 64.84, H 8.16; found C
64.98, H 8.26.
(1.0 g, 6.0 mmol). The reaction mixture was heated under reflux for
3 d, after which time all the solid material was removed by fil-
tration. The fitrate was collected and the solvent removed. After
the addition of water and CH2Cl2, the organic layer was collected,
dried with Na2SO4, and the solvent was removed; 6 was isolated
as a yellow oil and used in the next step without further purifica-
tion. 1H NMR (500 MHz, CDCl3): δ = 0.96 (t, J = 7.5 Hz, 6 H,
Me), 1.48 (m, 4 H, CH2Me), 1.75 (m, 4 H, OCH2CH2), 3.89 (s, 3
H, OMe), 3.97 (t, J = 6.5 Hz, 4 H, OCH2), 6.63 (t, J = 2.5 Hz, 1 H,
4-HAr), 7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.2 (Me), 19.6 (CH2Me), 31.5 (OCH2CH2), 52.4
(OMe), 67.8 (OCH2), 106.6 (CAr-4), 108.1 (CAr-2), 132.5 (CAr-1),
Compound 4: Compound 3 (1.00 g, 1.69 mmol) was dissolved in
THF (15 mL), and the solution was cooled to 0 °C. Freshly pre-
pared LDA (5.1 mmol in 10 mL THF) was added by syringe, and
the reaction mixture was stirred at 0 °C for 30 min, after which
time HCl (4 mL, 5% aqueous) was added. The product was ex-
tracted with ethyl acetate and then the solvent removed. Column
chromatography (SiO2; ethyl acetate/hexane, 1:2) yielded 4 as a
white solid (700 mg, 1.36 mmol, 80%). M.p. 49–52 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 6 H, Me), 1.25–1.32
[m, 16 H, (CH2)4Me], 1.42 (m, 4 H, OCH2CH2CH2), 1.76 (m, 4 H,
OCH2CH2), 3.90 (s, 3 H, OMe), 3.93 (t, J = 7.0 Hz, 4 H,
160.5 (CAr-3), 167.3 (C=O) ppm. IR (neat): ν = 2962 (m), 2878
˜
(m), 2852 (m), 1705 (s), 1597 (s), 1450 (m), 1358 (m), 1327 (m),
1304 (m), 1234 (m), 1165 (s), 1049 (m), 1003 (w), 949 (w), 910 (w),
849 (w), 764 (m), 741 (w), 679 (w), 617 (w) cm–1. EI-MS: m/z =
280 [M]+.
OCH2CH2), 4.99 [s, 2 H, CH2O(ringA)], 6.41 (t, J = 2.3 Hz, 1 H, Compound 7: 18-Crown-6 (350 mg, 1.3 mmol), K2CO3 (2.00 g,
4-HB), 6.55 (d, J = 2.3 Hz, 2 H, 2-HB), 6.66 (t, J = 2.0 Hz, 1 H, 4-
14.5 mmol) and 1-bromohexane (2.3 mL, 16 mmol) were added to
HA), 7.13 (m, 1 H, 6-HA), 7.24 (m, 1 H, 2-HA) ppm. 13C NMR an acetone (50 mL) solution of methyl 3,5-dihydroxybenzoate
(125 MHz, CDCl3): 14.3 (Me), 22.9 (CH2), 26.3 (1.0 g, 6.0 mmol). The reaction procedure and workup were as for
δ
=
(OCH2CH2CH2), 29.5 (2CH2), 29.6 (CH2), 32.0 (CH2), 52.5 6. Compound 7 was isolated as a yellow oil and used in the next
1
(OMe), 68.3 (OCH2CH2), 70.5 [CH2O(ringA)], 101.1 (CB-4), 105.9 step without further purification. H NMR (500 MHz, CDCl3): δ
(CB-2), 107.5 (CA-4), 108.5 (CA-2), 109.6 (CA-6), 132.4 (CA-1), = 0.90 (m, 6 H, Me), 1.30 (m, 8 H, CH2CH2Me), 1.44 (m, 4 H,
138.8 (CB-1), 156.8 (CA-5), 160.2 (CA-3), 160.8 (CB-3), 166.9 (C=O) OCH2CH2CH2), 1.76 (m, 4 H, OCH2CH2), 3.89 (s, 3 H, OMe),
ppm. IR (neat): ν = 3361 (br.), 2954 (w), 2942 (m), 2921 (m), 2849
(m), 1694 (m), 1607 (m), 1592 (s), 1470 (m), 1447 (m), 1392 (w),
3.96 (t, J = 6.5 Hz, 4 H, OCH2), 6.62 (t, J = 2.5 Hz, 1 H, 4-HAr),
7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C NMR (125 MHz,
˜
1372 (w), 1334 (m), 1321 (m), 1256 (m), 1244 (m), 1156 (s), 1141 CDCl3): δ = 14.2 (Me), 22.8 [(CH2)2Me], 25.9 (OCH2CH2CH2),
(s), 1117 (w), 1050 (s), 1026 (w), 1013 (w), 1009 (w), 999 (w), 990
(w), 957 (w), 861 (m), 852 (m), 823 (m), 766 (s), 728 (w), 712 (w),
675 (s), 640 (m) cm–1. EI-MS: m/z = 514 [M]+. C31H46O6 (514.7):
calcd. C 72.34, H 9.01; found C 71.86, H 9.22.
29.3 (OCH2CH2), 31.7 [(CH2)2Me], 52.4 (OMe), 68.5 (OCH2),
106.7 (CAr-4), 107.8 (CAr-4), 132.0 (CAr-1), 160.3 (CAr-3), 167.2
(C=O) ppm. IR (neat): ν = 2932 (m), 2862 (m), 1921 (w), 1852 (w),
˜
1720 (s), 1597 (s), 1512 (m), 1443 (s), 1350 (m), 1327 (m), 1304 (m),
1234 (m), 1165 (s), 1080 (w), 1049 (m), 1026 (w), 980 (w), 918 (m),
848 (m), 771 (s), 752 (w), 687 (w), 656 (w), 625 (m) cm–1. EI-MS:
m/z = 336 [M]+.
Compound 5: 18-Crown-6 (20.6 mg, 0.78 mmol), K2CO3 (161 mg,
1.17 mmol) and benzyl bromide (100 mg, 0.58 mmol) were added
to a solution of 4 (200 mg, 0.39 mmol) in acetone (15 mL). The
reaction mixture was heated at reflux for 48 h, after which time
water was added. The organic layer was extracted with CH2Cl2,
dried with MgSO4, and the solvent was removed. Column
chromatography (SiO2; ethyl acetate/hexane, 1:3) yielded 5 as a
Compound 8: 18-Crown-6 (500 mg, 1.86 mmol), K2CO3 (3.0 g,
21.8 mmol) and 1-bromoheptane (3.6 mL, 23 mmol) were added to
an acetone (80 mL) solution of methyl 3,5-dihydroxybenzoate
(1.5 g, 9.0 mmol). The reaction procedure and workup were as for
white solid (200 mg, 0.33 mmol, 85%). M.p. 38 °C. 1H NMR 6, and 8 was isolated as a yellow oil and used in the next step
1
(500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H, Me), 1.25–1.36
[m, 16 H, (CH2)4Me], 1.44 (m, 4 H, OCH2CH2CH2), 1.77 (m, 4 H,
OCH2CH2), 3.91 (s, 3 H, OMe), 3.94 (t, J = 6.5 Hz, 4 H,
OCH2CH2), 4.99 [s, 2 H, (ringB)CH2O], 5.07 [s, 2 H, (ringC)-
CH2O], 6.41 (t, J = 2.0 Hz, 1 H, 4-HB), 6.55 (d, J = 2.0 Hz, 2 H,
of the synthesis without further purification. H NMR (500 MHz,
CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H, Me), 1.26–1.35 (m, 12 H,
CH2), 1.44 (m, 4 H, OCH2CH2CH2), 1.76 (m, 4 H, OCH2CH2),
3.89 (s, 3 H, OMe), 3.93 (t, J = 6.5 Hz, 4 H, OCH2), 6.63 (t, J =
2.5 Hz, 1 H, 4-HAr), 7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C
2-HB), 6.80 (t, J = 2.0 Hz, 1 H, 4-HA), 7.29 (m, 2 H, 2,6-HA), 7.31– NMR (125 MHz, CDCl3): δ = 14.3 (Me), 22.8 (CH2), 26.2
7.45 (m, 5 H, HC) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.3
(OCH2CH2CH2), 29.3 (CH2), 29.4 (OCH2CH2), 32.0 (CH2), 52.4
(Me), 22.8 (CH2), 26.2 (OCH2CH2CH2), 29.4 (2CH2), 29.5 (CH2), (OMe), 68.5 (OCH2), 106.7 (CAr-4), 107.8 (CAr-2), 132.0 (CAr-1),
32.0 (CH2), 52.4 (OMe), 68.2 (OCH2CH2), 70.4 [(ringB)- 160.3 (CAr-3), 167.2 (C=O) ppm. IR (neat): ν = 2924 (s), 2854 (m),
˜
CH2O+(ringC)CH2O], 101.0 (CB-4), 105.8 (CB-2), 107.4 (CA-4),
1720 (s), 1597 (s), 1450 (m), 1381 (w), 1350 (w), 1327 (w), 1304 (w),
1234 (m), 1165 (s), 1057 (w), 849 (w), 771 (w), 679 (w), 633 (w)
108.5 (CA-2,6), 108.6 (CA-2,6), 127.7 (CC-2,3), 128.3 (CC-4), 128.8
(CC-2,3), 132.2 (CA-1), 136.6 (CC-1), 138.7 (CB-1), 159.9 (CA-3), cm–1. EI-MS: m/z = 364 [M]+.
160.7 (CB-3), 166.9 (C=O) ppm. IR (neat): ν = 2950 (w), 2919 (m),
˜
Compound 9: 18-Crown-6 (6.26 g, 23.7 mmol), K2CO3 (40.9 g,
2855 (m), 1717 (m), 1597 (s), 1468 (m), 1455 (m), 1445 (m), 1431
(m), 1386 (m), 1378 (m), 1348 (s), 1299 (s), 1256 (m), 1231 (m),
1171 (s), 1154 (m), 1128 (w), 1056 (s), 1027 (s), 998 (w), 867 (w),
847 (m), 826 (m), 776 (w), 765 (m), 745 (w), 695 (m), 689 (w), 674
(w), 640 (w) cm–1. EI-MS: m/z = 604 [M]+. C38H52O6 (604.8): calcd.
C 75.46, H 8.67; found C 75.21, H 8.63.
296 mmol) and 1-bromododecane (70.9 mL, 296 mmol) were added
to an acetone (190 mL) solution of methyl 3,5-dihydroxybenzoate
(9.95 g, 59.2 mmol). The reaction mixture was heated at reflux for
39 h, after which it was cooled to room temperature. White needles
of 9 formed and were removed by filtration and washed with Et2O.
Ethyl acetate (100 mL), Et2O (200 mL) and water (300 mL) were
added to the filtrate, and the organic layer was collected and dried
Compound 6: 18-Crown-6 (350 mg, 1.3 mmol), K2CO3 (2.00 g,
14.5 mmol) and 1-bromobutane (2.0 mL, 19 mmol) were added to with Na2SO4. The solvent was then removed to yield 9 as a while
an acetone (50 mL) solution of methyl 3,5-dihydroxybenzoate solid. The combined products were recrystallized twice from acte-
2648
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Eur. J. Org. Chem. 2008, 2644–2651