J. Hellberg et al. / Tetrahedron 60 (2004) 8899–8912
8907
CH). 13C NMR (100 MHz, CDCl3) dZ11.7, 15.7, 111.6,
121.1, 124.8, 126.6, 129.8, 130.7, 137.3, 142.4. MS (EI) m/e
(%) 290 (MC, 100). Anal. Calcd for C20H18O2: C, 82.73; H,
6.25. Found: C, 82.44; H, 6.34.
Rf (hexane/CH2Cl2; 1:1)Z0.53. MpZ156 8C. 1H NMR
(400 MHz, CDCl3) dZ3.86 (s, 6H, CH3), 6.56 (s, 2H, CH),
7.21 (s, 2H, CH), 7.33 (m, 2H, CH), 7.64 (m, 2H, CH). 13C
NMR (100 MHz, CDCl3) dZ56.3, 100.9, 111.8, 125.1,
126.6, 130.7, 134.3, 141.7, 144.8. MS (EI) m/e (%) 294
(MC, 100). Anal. Calcd for C18H14O4: C, 73.45; H, 4.80.
Found: C, 73.43; H, 4.75.
4.1.11. Dioxin 11. 106 mg (2%) of white crystals was
achieved after chromatography.
1
Rf (CH2Cl2)Z0.3. MpZ127–129 8C. H NMR (400 MHz,
4.1.17. 2,3-Dihydrobenzo[1,4]dioxin-6,7-diol 25. 1,4-
Benzodioxane-6-carboxaldehyde (57.46 g, 0.35 mol) was
dissolved in CH2Cl2 (1200 mL) and MCPBA (45.30 g,
0.525 mol, 50% in H2O) was added to the solution, which
was gently refluxed at 45 8C for 17 h and a yellow
precipitate formed. The CH2Cl2 was evaporated and the
residue was dissolved in EtOAc, washed with a saturated
NaHCO3 solution, followed by brine and then dried over
MgSO4. The solvent was evaporated yielding 55.3 g (88%)
of formate as a red brown oil. This intermediate product was
dissolved in MeOH and was hydrolyzed at rt for 45 min with
a KOH solution (10% excess). The solution was neutralized
with 2 M HCl and the aqueous phase was extracted with
CH2Cl2, dried over MgSO4 and evaporated to dryness
yielding 39.7 g (85%) of 2,3-dihydrobenzo[1,4]dioxin-6-ol.
15 g of the crude product was submitted to chromatography
on a silica gel column (hexane/EtOAc; 80:20), affording
10 g pure material as a brown oil and 4.5 g of material with
some small impurities (overall yield of 73%).
CDCl3) dZ3.91 (s, 6H, CH3), 3.97 (s, 6H, CH3), 7.34 (m,
2H, CH), 7.36 (s, 2H, CH), 7.66 (m, 2H, CH). 13C NMR
(100 MHz, CDCl3) dZ61.8, 61.9, 112.4, 125.4, 126.8,
130.9, 132.4, 137.7, 141.0, 142.6. MS (EI) m/e (%) 354
(MC, 53). Anal. Calcd for C20H18O6: C, 67.78; H, 5.13.
Found: C, 67.47; H, 5.25.
4.1.12. Dioxin 12. Chromatography yielded 463 mg (9%) of
off-white crystals. This compound can also be recrystallized
from EtOH to give beige needles.
Rf (hexane/CH2Cl2; 1:1)Z0.54. MpZ159–162 8C. 1H
NMR (400 MHz, CDCl3) dZ2.30 (6H, s), 7.32–7.35 (4H,
m), 7.66 (2H, dd, JZ6.3, 3.3 Hz). 13C NMR (100 MHz,
CDCl3) dZ10.6, 109.3, 112.4, 125.1, 126.7, 130.3, 134.3,
140.9. MS (EI) m/e (%) 268 (MC, 100). Anal. Calcd for
C16H12O2S: C, 71.62; H, 4.51. Found: C, 71.42; H, 4.50.
4.1.13. Dioxin 19. Chromatography yielded 2.21 g (34%) of
white crystals.
1H NMR (400 MHz, CDCl3) dZ4.21 (m, 4H), 6.32 (dd, 1H,
JZ8.5, 2.7 Hz), 6.38 (d, 1H, JZ2.7 Hz), 6.72 (d, 1H, JZ
8.5 Hz). 13C NMR (125 MHz, CDCl3) dZ64.1, 64.6, 104.3,
108.3, 117.6, 137.6, 143.8, 150.0.
Rf (hexane/CH2Cl2; 1:1)Z0.43. MpZ233–234 8C. 1H
NMR (400 MHz, CDCl3) dZ3.24 (s, 4H, CH2), 6.82 (s,
2H, CH), 7.24 (s, 2H, CH), 7.33 (m, 2H, CH), 7.64 (m, 2H,
CH). 13C NMR (100 MHz, CDCl3) dZ29.5, 112.2, 116.5,
125.3, 126.4, 126.8, 130.7, 139.5, 141.4. MS (EI) m/e (%)
324 (MC, 100). Anal. Calcd for C18H12O2S2: C, 66.64; H,
3.74. Found: C, 66.45; H, 3.81.
To a solution of KH2PO4 (7.08 g, 52.0 mmol) in 450 mL
H2O, cooled on an ice-bath, NO(KSO3)2 (Fremy’s salt)
(50.00 g, 186.3 mmol) was added in portions under vigorous
stirring. 2,3-dihydrobenzo[1,4]dioxin-6-ol (14.18 g,
93.2 mmol) was dissolved in 20 mL MeOH and added
dropwise to the mixture during 25 min and was then left
stirring on the ice-bath for a further 1 h. The red precipitate
that formed was filtered, washed with H2O and dried in a
desiccator, yielding 2,3-dihydrobenzo[1,4]dioxin-6,7-dione
in 10.99 g (71%) yield as orange crystals.
4.1.14. Dioxin 20. Chromatography yielded 342 mg (8%) of
white crystals.
MpZ195–196 8C. 1H NMR (400 MHz, CDCl3) dZ2.31 (s,
1H), 3.21 (s, 1H), 7.27 (s, 1H), 7.32 (dd, 2H, JZ6.3,
3.3 Hz), 7.63 (dd, 2H, JZ6.3, 3.3 Hz). 13C NMR (100 MHz,
CDCl3) dZ12.0, 30.2, 111.9, 122.2, 125.1, 126.7, 127.0,
130.7, 137.5, 141.8. MS (EI) m/e (%) 352 (MC, 100), 337
(10), 324 (20). Anal. Calcd for C20H16O2S2: C, 68.15; H,
4.58. Found: C, 67.96; H, 4.65.
MpZ223–226 8C (lit. 232 8C31). 1H NMR (400 MHz,
CDCl3) dZ4.43 (s, 4H), 5.88 (s, 2H). 13C NMR
(100 MHz, CDCl3) dZ64.7, 108.6, 157.7, 179.2. MS (EI)
m/e (%) 168.2 (MCC2,20) 166.2 (MC, 10), 138.2 (100).
The 2,3-dihydrobenzo[1,4]dioxin-6,7-dione was suspended
in 200 mL H2O and reduced by addition of Na2S2O4. The
suspension was transferred to a separatory funnel and
extracted with Et2O. The organic phase was washed with
brine, dried over MgSO4 and the solvent was evaporated
yielding beige crystals of 25, 9.23 g (75%).
4.1.15. Dioxin 21. Chromatography yielded 231 mg (4%) of
off-white crystals.
1
Rf (hexane:CH2Cl2; 1:1)Z0.51. Mp O240 8C. H NMR
(400 MHz, CDCl3) dZ5.92 (s, 2H, CH2), 6.52 (s, 2H, CH),
7.20 (s, 2H, CH), 7.32 (m, 2H, CH), 7.63 (m, 2H, CH). 13C
NMR (100 MHz, CDCl3) dZ98.3, 101.5, 111.8, 126.7,
130.8, 135.6, 141.7, 143.0. MS (EI) m/e (%) 278 (MC, 100).
Anal. Calcd for C17H10O4: C, 73.37; H, 3.63. Found: C,
73.60; H, 3.76. Anal. Calcd for (21)AsF6: C, 43.70; H, 2.16.
Found: C, 43.47; H, 2.06.
MpZ173.5–174.4 8C. 1H NMR (400 MHz, DMSO-d6) dZ
4.07 (s, 4H), 6.24 (s, 2H) 8.46 (s, 2H, KOH). 13C NMR
(100MHz, DMSO-d6) dZ63.9, 104.2, 135.2, 139.2. MS
(EI) m/e (%) 168.2 (MC, 100).
4.1.16. Dioxin 22. Chromatography yielded 2.54 g (43%) of
white crystals.
4.1.18. 6,7-Dibromo-2,3-dihydrobenzo[1,4]dioxin 26. Br2
(25.83 g, 161.6 mmol) dissolved in 50 mL CH2Cl2 was