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porator to yield a brown solid that was crystallized from
ethyl acetate and hexane to yield 124.34 g (49%) of 4 as
white crystals: mp 68–69 ꢁC (lit. mp 71–72 ꢁC); IR: Ar–
O–R (1220, 1031). 1H NMR (CDCl3) d 2.30 (p, 4,
ArOCH2CH2CH2Br, J=6.0 Hz), 3.52 (t, 4, ArOCH2-
CH2CH2Br, J=7.5 Hz), 4.15 (t, 4, ArOCH2CH2CH2Br,
J=7.5 Hz).
color of the solution to bright pink. After 45 min, the
solution was poured into a separatory funnel containing
approximately 25 mL of ice and water. The layers were
separated and the organic phase was washed with 3 M
HCl (2Â20 mL), H2O (2Â20 mL), and brine (1Â50 mL).
The organic layer was dried (MgSO4), and the solution
was run through a short flash column of silica gel (100–
200 mesh), eluting with methylene chloride. The solvent
was then evaporated on the rotary evaporator, yielding
a light-yellow solid that was recrystallized from ethyl
acetate and hexane to yield 3.363 g (90%) of 7 as yellow
needles: mp 79–80 ꢁC. IR C¼O (1681). 1H NMR
(CDCl3) d 10.5 (s, 1, ArCOH), 6.7 (s, 1, ArH), 4.1 (t, 2,
ArOCH2, J=5.1 Hz), 4.05 (t, 2, ArOCH2, J=5.1 Hz),
3.0 (t, 2, ArOCH2CH2CH2, J=6.6 Hz), 2.7 (t, 2,
ArOCH2CH2CH2, J=6.5 Hz), 2.0 (m, 4, ArOCH2CH2).
Anal. (C13H14O3) C, H.
1,4-Bis-(3-bromopropoxy)-2,5-dibromobenzene (5).
A
2-L, three-neck round-bottom flask was equipped with
an addition funnel, condenser, N2 inlet, and magnetic
stir bar, and 50.76 g (0.144 mol) of 4, followed by 600
mL of methylene chloride and a catalytic amount of
iron filings were added. A mixture of 15.8 mL (2.14
equiv) of Br2 and 100 mL of methylene chloride was
placed in the addition funnel and was introduced to the
reaction vessel dropwise, with stirring, over 1 h. After
stirring for an additional 24 h, the mixture was poured
into a separatory funnel and washed with 5% Na2S2O3
(3 75 mL), saturated NaHCO3 (3Â75 mL), and brine
(3Â75 mL). The organic phase was dried (MgSO4), and
the solvent was removed on the rotary evaporator. The
resulting dark-brown oil solidified when dried under
high vacuum, and the solid was recrystallized from ethyl
acetate to yield 52.46 g (71%) of 5 as a white powder:
mp 115–117 ꢁC. IR Ar–O–R (1216, 1066), Ar–Br (1028).
1H NMR (CDCl3) d 7.4 (s, 2, ArH), 4.0 (t, 4,
ArOCH2CH2CH2Br), 3.6 (t, 4, ArOCH2CH2CH2Br),
2.3 (p, 4, ArOCH2CH2CH2Br). Anal. (C12H14O2Br4) C, H.
5-(2-Nitroethenyl)-2,3,4,7,8,9-hexahydrobenzo[1,2b:4,5b0]
dipyran (8a). The aldehyde 7 (6.51 g, 29.80 mmol) was
placed in a 100-mL, three-neck, round-bottom flask
equipped with a N2 inlet and a magnetic stir bar.
Ammonium acetate (3.19 g, 1.39 equiv) was added to
the flask, followed by 30.0 mL of nitromethane. The
mixture was stirred at 80 ꢁC for 4.5 h before the volatiles
were removed under vacuum. The residue was taken up
in methylene chloride and washed with 3 N HCl (3Â25
mL), H2O (2Â25 mL), and brine (1Â25 mL). The pro-
duct was dried (MgSO4), and the solvent was removed
on the rotary evaporator. The crude product was
recrystalized from methanol to yield 6.55 g (84%) of 8a
as orange needles: mp 139–140 ꢁC. IR Ar–O–R (1247),
R-NO2 (1515). 1H NMR (CDCl3) d 8.1 (d, 1,
ArCH¼CH, J=13.4 Hz), 8.0 (d, 1, ArCH¼CH, J=13.5
Hz), 6.6 (s, 1, ArH), 4.24 (t, 2, ArOCH2, J=5.2 Hz), 4.0
(t, 2, ArOCH2, J=5.1 Hz), 2.8 (t, 2, ArOCH2CH2CH2,
J=6.7 Hz), 2.7 (t, 2, ArOCH2CH2CH2, J=6.4 Hz), 2.0
(m, 4, ArOCH2CH2). Anal. (C14H15NO4) C, H, N.
2,3,4,7,8,9-Hexahydrobenzo [1,2b:4,5b] dipyran (6).20
The tetrabromo compound, 5, (30.45 g, 60.00 mmol)
was added to a 1-L, three-neck, round-bottom flask
equipped with a N2 inlet, and a magnetic stir bar.
Approximately 450 mL of anhydrous tetrahydrofuran
(THF) was then added, and the mixture was cooled to
ꢀ100 ꢁC. Next, 27.0 mL (4.5 equiv) of 10 M n-butyl-
lithium in hexanes was added slowly so the solution did
not warm above ꢀ80 ꢁC. After holding the reaction
mixture at ꢀ100 ꢁC for 45 min, the solution was warmed
to ꢀ78 ꢁC, and stirred for an additional 4.5 h before
being quenched with 75 mL of H2O. The THF was
removed on the rotary evaporator, and the remaining
liquid was taken up in ether, placed in a separatory
funnel, and washed with H2O (3Â50 mL). The organic
phase was dried (MgSO4), and the ether was removed to
yield a light-yellow solid that was recrystallized from
ethyl acetate to give 7.63 g (67%) of 6 as white needles:
mp 104–106 ꢁC (lit. mp 105–106 ꢁC). IR Ar–O–R (1235).
1H NMR (CDCl3) d 6.4 (s, 2, ArH), 4.1 (t, 4, ArOCH2),
2.7 (t, 4, ArOCH2CH2CH2), 1.9 (p, 4, ArOCH2CH2).
Anal. (C12H14O2) C, H.
5-(2-Nitro-1-propenyl)-2,3,4,7,8,9-hexahydrobenzo [1,2b:
4,5b0]dipyran (8b). The aldehyde 7 (10.16 g, 46.50
mmol) was placed in a 100-mL, three-neck, round-bot-
tom flask equipped with a magnetic stir bar and a N2
inlet. Ammonium acetate (3.9 g, 1.08 equiv) was then
added, followed by 40 mL of nitroethane. The mixture
was stirred at 80 ꢁC for 4.5 h before the nitroethane was
removed on the rotary evaporator. The remaining resi-
due was taken up in methylene chloride, placed in a
separatory funnel, washed with 3 N HCl (2Â25 mL),
H2O (2Â25 mL), brine (1Â25 mL), and dried (MgSO4).
After solvent removal under vacuum, the resulting
orange solid was recrystallized from methanol to yield
10.68 g (83%) of 8b as yellow crystals: mp 91–92 ꢁC. IR
Ar–O–R (1235), R-NO2 (1524). 1H NMR (CDCl3) d 7.8
(s, 1, ArCH¼C), 6.5 (s, 1, ArH), 4.1 (m, 4,
ArOCH2CH2CH2), 2.7 (t, 2, ArOCH2, J=6.5 Hz), 2.5
(t, 2, ArOCH2, J=6.5), 2.1 (s, 3, ArCH¼CCH3), 1.9 (m,
4, ArOCH2CH2). Anal. (C15H17NO4) C, H, N.
5-Formyl-2,3,4,7,8,9-hexahydrobenzo[1,2b:4,5b0]dipyran
(7). A 3.277 g (17.2 mmol) sample of 6 was placed in a
250-mL, three-neck, round-bottom flask equipped with
a N2 inlet and a magnetic stir bar. Approximately 100
mL of methylene chloride was added, and the solution
was cooled on an ice bath. Tin(IV) chloride (3.00 mL,
1.5 equiv) was introduced to the stirred solution via
syringe, whereupon the solution turned reddish-brown.
Approximately 15 min later, 2.34 mL (1.5 equiv) of
dichloromethyl methyl ether was added, changing the
5-(2-Aminoethyl)-2,3,4,7,8,9-hexahydrobenzo [1,2b:4,5b0]
dipyran hydrochloride (9aꢂHCl). A double tipped nee-
dle was used to transfer 250 mL of anhydrous THF to a
500 mL, three-neck, round-bottom flask equipped with