310
Golob, Biberger, Walter, and von Angerer
6,11-Dihydro-11-[4-[4-(4,4,5,5,5-pentafluorpentylsulfonyl)butoxy]benzyl]-
6,11-Dihydro-3,8-dihydroxy-11-[4-[4-(pentylsulfonyl)butoxy]benzyl]-5H-
3,8-di-(tetrahydropyran-2-yl-oxy)-5H-benzo[a]carbazole (5e)
benzo[a]carbazole (6d)
1H-NMR (CDCl3) δ = 0.88–2.12 (m, 13H,
Prepared from 3 and 12b and purified by chromatography (Al2O3) with
CH2Cl2 /Petroleum ether (4 : 1) as eluent to give an orange resin (51%) that
was reacted without further characterization.
Colorless foam, yield 72%.–
CH3-(CH2)3-, -(CH2)2-CH2-OAr), 2.83–3.07 (m, 8H, Ar-(CH2)2-Ar, SO2-
(CH2-)2), 3.92–4.00 (m, 2H, -CH2-O-), 4.50 (s, br, 1H, Ar-OH), 4.76 (s, br,
1H, Ar-OH), 5.45 (s, 2H, -N-CH2-), 6.58 (dd, 3J = 8.4 Hz, 4J = 2.7 Hz, 1H,
Ar-H9), 6.68 (dd, 3J = 8.7 Hz, 4J = 2.5 Hz, 1H, Ar-H2), 6.82 (d, 4J = 2.5 Hz,
1H,Ar-H4), 6.84, 7.13 (AA′BB′, 3J = 8.7 Hz, Ar-H), 6.98 (d, 4J = 2.7 Hz, 1H,
Ar-H7), 7.00 (d, 3J = 8.7 Hz, 1H, Ar-H10), 7.10 (d, 3J = 8.4 Hz, 1H, Ar-H1).
General Procedure for the Cleavage of the Methoxy Groups
Under N2, a solution of the dimethoxybenzo[a]carbazole derivative
(0.54 mmol) in 10 ml of CH2Cl2 was added slowly to a stirred solution of
1.16 mmol of BBr3 in 10 ml of CH2Cl2 at –10 °C. After addition, the cooling
bath was removed and the mixture was stirred for 3 h at room temperature.
The ice-cold mixture was treated with small portions of a cold saturated
NaHCO3 solution (60 ml). After addition of ethyl acetate (50 ml), the mixture
was stirred for 15 min. The organic layer was removed and the aqueous phase
extracted with EtOAc. The combined organic layers were washed with
NaHCO3 solution and water, and dried (MgSO4). After removal of the
solvent, the crude product was purified by chromatography and recrystallized
if possible.
6,11-Dihydro-3,8-dihydroxy-11-[4-[4-(4,4,4,5,5-pentafluorpentylsulfonyl)-
butoxy]benzyl]-5H-benzo[a]carbazole (6e)
Green foam, yield 64%.– 1H-NMR (CDCl3) δ = 1.26–2.38 (m, 8H,
-(CH2)2-C2F5, -SO2-CH2-(CH2)2-), 2.86–2.93 (m, 4H, Ar-(CH2)2-Ar), 3.03–
3.12 (m, 4H, SO2-(CH2-)2), 3.96–4.01 (m, 2H, -CH2-O-), 5.45 (s, 2H,
3
4
3
-N-CH2-), 6.58 (dd, J = 8.4 Hz, J = 2.7 Hz, 1H, Ar-H9), 6.68 (dd, J =
8.6 Hz, 4J = 2.4 Hz, 1H, Ar-H2), 6.82 (d, 4J = 2.4 Hz, 1H, Ar-H4), 6.83, 7.10
(AA′BB′, 3J = 8.7 Hz, Ar-H), 6.97 (d, 4J = 2.7 Hz, 1H, Ar-H7), 7.00 (d,3J =
8.7 Hz, 1H, Ar-H10), 7.13 (d, 3J = 8.4 Hz, 1H, Ar-H1).
6,11-Dihydro-3,8-dihydroxy-11-[10-(pentylthio)decyl]-5H-benzo[a]carb-
azole (6a)
Syntheses of New Side Chains: 1-Bromo-10-(4,4,5,5,5-pentafluoropentyl-
thio)decane (7b)
Colorless crystals, mp 115–116 °C (CH2Cl2/n-hexane 1 : 1), yield 63%.–
Anal. (C31H43NO2S).– 1H-NMR (CDCl3) δ = 0.87–0.93 (m, 3H, CH3-CH2-),
1.25–1.65 (m, 20H, -(CH2)7-, CH3(CH2)3-), 1.83–1.86 (m, 2H, -N-CH2-
CH2-), 2.51 (t, 3J = 7.4 Hz, 4H, S(CH2-)2), 2.84 (m, 4H, Ar-(CH2)2-Ar), 4.28
(t, 3J = 7.8 Hz, 2H, -N-CH2-), 4.63 (s, br, 1H, Ar-OH), 5.12 (s, br, 1H,
Ar-OH), 6.73–6.78 (m, 2H, Ar-H2+9), 6.83 (d, 4J = 2.5 Hz, 1H, Ar-H4), 6.92
(d, 4J = 2.3 Hz, 1H, Ar-H7), 7.17 (d, 3J = 8.5 Hz, 1H, Ar-H10), 7.38 (d, 3J =
8.1 Hz, 1H, Ar-H1).
A solution of 4,4,5,5,5-pentafluoropentyl thioacetate (14.6 mmol) in 30 ml
of dry MeOH was added dropwise under N2 to a solution of 78 mmol sodium
methylate in 60 ml of dry MeOH. After heating to 60–70 °C for 30 min the
excess of sodium methylate was destroyed by careful addition of water. The
mixture was acidified with 2N HCl and extracted four times with n-hexane.
The combined organic layers were washed with water, dried (MgSO4),
diluted with 80 ml of anhydrous DMF, and added under N2 slowly to a stirred
suspension of NaH (10.8 mmol) in 10 ml of anhydrous DMF. After the
addition stirring was continued for 30 min. The mixture was transferred to a
dropping funnel and the bottom DMF-layer was added dropwise to a solution
of 1,10-dibromodecane (36.1 mmol) in 25 ml of dry DMF. The mixture was
heated to 50–60 °C for 2 h. After cooling, water was added until a clear
solution was obtained. After the addition of 100 ml EtOAc and 150 ml of
water the organic layer was separated and the aqueous phase extracted three
times with EtOAc. The combined organic layers were washed with saline
and dried (MgSO4). After evaporation of the solvent the residue was chro-
matographed (SiO2/CH2Cl2-petroleum ether 1 : 5) to give the desired product
as the second of three fractions. Slightly yellow oil which crystallized at
17–20 °C, yield 41%.– 1H-NMR (CDCl3) δ = 1.21–2.51 (m, 20H, -(CH2)8-,
-(CH2)2-C2F5), 2.57–3.05 (m, 4H, S(CH2-)2), 3.57 (t, 3J = 7.0 Hz, 2H,
-CH2Br).
6,11-Dihydro-3,8-dihydroxy-11-[10-(pentylsulfonyl)decyl]-5H-benzo[a]-
carbazole (6b)
Beige powder, mp 129–130 °C (CHCl3), yield 70%.– 1H-NMR (DMSO-
d6) δ = 0.87 (t, 3J = 7.0 Hz, 3H, CH3-CH2-), 1.20–1.33 (m, 16H, -(CH2)8-,
CH3(CH2)2-), 1.58–1.65 (m, 6H, -SO2-CH2-CH2-, -N-CH2-CH2-), 2.72 (m,
4H, Ar-(CH2)2-Ar), 3.03 (t, 3J = 7.9 Hz, 4H, SO2(CH2-)2), 4.28 (t, 3J = 7.9
Hz, 2H, -N-CH2-), 6.60 (dd, 3J = 8.7 Hz, 4J = 2.2 Hz, 1H, Ar-H9), 6.70 (dd,
3J = 8.3Hz, 4J = 2.3 Hz, 1H, Ar-H2), 6.75 (d, 4J = 2.3 Hz, 1H, Ar-H4), 6.76
(d, 4J = 2.2 Hz, 1H, Ar-H7), 7.21 (d, 3J = 8.7 Hz, 1H, Ar-H10), 7.39 (d, 3J =
8.3 Hz, 1H, Ar-H1), 8.67 (s, 1H, Ar-OH), 9.47 (s, 1H, Ar-OH).– MS (70 eV)
m/z (%) = 526 (100) [M+], 390 (13) [M+-(SO2-C5H11)], 264 (55, [M+-
(CH2)9-SO2-C5H11].
6,11-Dihydro-3,8-dihydroxy-11-[10-(4,4,5,5,5-pentafluorpentylsulfonyl)-
1-Bromo-10-(4,4,5,5,5-pentafluoropentylsulfonyl)decane (8b)
decyl]-5H-benzo[a]carbazole (6c)
A solution of meta-chloroperbenzoic acid (10.6 mmol) in 85 ml CHCl3
was added within 30 min to a stirred solution of 10b (4.95 mmol) in 240 ml
CHCl3. After stirring for 2.5 h at room temperature, the solution was poured
into 240 ml of sat. NaHCO3 solution. After stirring for 10 min the organic
layer was separated, washed with water, and dried (MgSO4). After evapora-
tion of the solvent the product was purified by crystallization from
EtOH to afford colorless crystals, mp 85–86 °C, yield 68%.– Anal.
(C15H26BrF5O2S).– 1H-NMR (CDCl3) δ = 1.30–2.71 (m, 20H, -(CH2)8-,
Brownish amorphous solid, yield 70%.– 1H-NMR (CDCl3) δ = 1.22–1.46
(m, 12H, -(CH2)6-), 1.78–1.91 (m, 4H, -SO2-CH2-CH2-), 2.17–2.39 (m, 4H,
-N-CH2-CH2-, -CH2-C2F5), 2.77–2.93 (m, 4H, Ar-(CH2)2-Ar), 2.97–3.10
3
(m, 4H, SO2(CH2-)2), 4.31 (t, J = 7.7 Hz, 2H, -N-CH2-), 4.58 (s, br, 1H,
Ar-OH), 5.28 (s, br, 1H, Ar-OH), 6.72–6.78 (m, 2H, Ar-H2+9), 6.84 (d, 4J =
2.1 Hz, 1H, Ar-H4), 6.93 (d, 4J = 2.4 Hz, 1H, Ar-H7), 7.18 (d,3J = 8.7 Hz,
1H, Ar-H10), 7.39 (d, 3J = 8.4 Hz, 1H, Ar-H1).
3
-(CH2)2-C2F5), 3.12–3.60 (m, 4H, SO2(CH2-)2), 3.75 (t, J = 7.0 Hz, 2H,
-CH2Br).
General Procedure for the Cleavage of the Tetrahydropyranyl Ethers
Under N2, 10 ml of aqueous oxalic acid (8 %) was added dropwise to a
solution of the (tetrahydropyran-2-yl)phenyl ether in 15 ml MeOH and 15 ml
THF. Then, the mixture was heated at 60–70 °C for 3.5 h. After cooling, the
mixturewas neutralized withNaHCO3 solution, stirred for additional 15 min,
extracted several times wth EtOAc. The combined organic layers were
washed with water and dried (MgSO4). After evaporation of the solvent, the
crude product was purified by chromatography. The following compounds
were obtained by this method:
Methyl 4-[4-(4,4,5,5,5-Pentafluoropentylthio)butoxy]benzoate (9b)
From 4,4,5,5,5-pentafluoropentylthiol and an equimolar amount of methyl
4-(4-bromobutoxy)benzoate by a method similar to that described for the
synthesis of 7b. Yellow oil, yield 73%.– 1H-NMR (CDCl3) δ = 1.61–2.51
(m, 8H, -(CH2)2-C2F5, -CH2-(CH2)2-CH2-), 2.65–3.08 (m, 4H, S(CH2-)2),
4.16 (s, 3H, -OCH3), 4.31 (t, 3J = 6.0 Hz, 2H, -OCH2-), 7.11, 8.15 (AA′BB′,
3J = 9.0 Hz, 4H, Ar-H).
Arch. Pharm. Pharm. Med. Chem. 333, 305–311 (2000)