Y. Kajiwara et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
475
heated at 90 °C for 15 h. The mixture was poured into water
(400 mL) and was extracted with three portions of 200 mL of a
mixture of EtOAc/hexane (1/1). The combined organic layer
was washed three times with 10% aqueous solution of sodium
hydroxide (200 mL), twice with brine (200 mL), and dried over
magnesium sulfate. The solvent was removed to yield the crude
product by rotary evaporation. The obtained light yellow solid
was ground and washed with hexane (60 mL) for 30 min, then
filtered and dried under. Yield = 83%. 1H NMR (CDCl3,
400 MHz): ¤ 9.88 (s, 1H, -(C=O)-H), 7.83 (d, 2H, J = 8.7
Hz, Ar-H), 6.99 (d, 2H, J = 8.5 Hz, Ar-H), 4.05 (t, 2H, J =
6.4 Hz, Ar-OCH2-), 3.67 (t, 2H, J = 6.0 Hz, -CH2OH), 1.83
(m, 2H, Ar-OCH2CH2-), 1.66-1.37 (m, 7H, -CH2CH2CH2-
CH2-OH). HRMS (APCI) Calcd for C13H19O3 [M + H]+: m/z
223.1334. Found: m/z 223.1324.
4-(dimethylamino)pyridine (55 mg, 0.45 mmol) in CH2Cl2 (20
mL), followed by addition of acetyl chloride (0.96 mL, 14
mmol) dissolved in CH2Cl2 (2.0 mL) at 0 °C. After stirring at
room temperature for 18 h, the product was extracted with
CH2Cl2 (200 mL), and the organic layer was washed with
water, saturated sodium hydrogen carbonate, brine, dried over
anhydrous magnesium sulfate, and concentrated with a rotary
evaporator. The residue was purified by silica gel column
chromatography (hexane/EtOAc = 3/1 ¼ 2/1) to afford 14
1
(3.46 g, 84%) as a yellowish oil. H NMR (CDCl3, 400 MHz):
¤ 7.92 (m, 2H, Ar-H), 7.30-7.17 (m, 2H, Ar-H), 6.93-6.82
(m, 4H, Ar-H), 4.80-4.62 (m, 2H, -CH2-NO2), 4.13 (m, 1H,
>CHCH2-NO2), 4.07 (t, 2H, J = 6.6 Hz, -CH2OAc), 3.91 (t,
2H, J = 6.5 Hz, Ar-OCH2-), 3.87 (s, 3H, Ar-OCH3), 3.36 (m,
2H, Ar-(C=O)-CH2-), 2.04 (s, 3H, CH3COO-), 1.77 (m, 2H,
Ar-OCH2CH2-), 1.65 (m, 2H, -CH2CH2OAc), 1.53-1.36 (m,
4H, -CH2CH2CH2CH2OAc). HRMS (APCI) Calcd for
C25H32NO7 [M + H]+: m/z 458.2179. Found: m/z 458.2170.
Synthesis of Diacetyl Azadipyrromethene Ligand 15:
Ammonium acetate (42.1 g, 0.55 mol) was added to a solution
of 14 (3.20 g, 7.0 mmol) in ethanol (100 mL). The mixture was
refluxed for 24 h. The reaction solution was cooled to room
temperature, and the solvent was concentrated to 50 mL, and
filtered. The isolated solid was washed with a large amount of
ethanol for several times. The residue was dried under vacuum
Synthesis of (E)-1-[4-(6-Hydroxyhexyloxy)phenyl]-3-(4-
methoxyphenyl)-2-propenone (12):
A solution of 4-(6-
hydroxyhexyloxy)benzaldehyde (11) (8.89 g, 40 mmol) and 4¤-
methoxyacetophenone (6.01 g, 40 mmol) in absolute methanol
(40 mL) was prepared under nitrogen at room temperature.
Solid sodium hydroxide (0.160 g, 4.0 mmol) was added under
nitrogen flow and the mixture was refluxed for 5 h. After the
reaction was completed, the precipitate was filtered, washed
with ethanol and water, and dried under vaccum to afford a
1
slightly yellowish solid 12 (10.5 g, 74%). H NMR (CDCl3,
1
400 MHz): ¤ 8.03 (dt, 2H, J = 8.8, 2.5 Hz, Ar-H), 7.78 (d, 1H,
J = 15.5 Hz, Ar-CH=CH-(C=O)-), 7.59 (dt, 2H, J = 8.9, 2.3
Hz, Ar-H), 7.43 (d, 1H, J = 15.6 Hz, Ar-CH=CH-(C=O)-),
6.98 (dt, 2H, J = 8.8, 2.5 Hz, Ar-H), 6.92 (dt, 2H, J = 8.8,
2.5 Hz, Ar-H), 4.01 (t, 2H, J = 6.4 Hz, Ar-OCH2-), 3.89
(s, 3H, Ar-OCH3), 3.67 (m, 2H, -CH2OH), 1.83 (m, 2H, Ar-
OCH2CH2-), 1.62 (m, 2H, -CH2CH2-OH), 1.56-1.41 (m, 4H,
-CH2CH2CH2CH2-OH), 1.30 (t, 1H, J = 5.4 Hz, -CH2-OH).
HRMS (APCI) Calcd for C22H27O4 [M + H]+: m/z 355.1909.
Found: m/z 355.1899.
to afford 15 (1.42 g, 49%) as a brown solid. H NMR (CDCl3,
400 MHz): ¤ 8.03 (m, 4H, Ar-H), 7.88 (m, 4H, Ar-H), 7.05-
6.94 (m, 10H, Ar-H), 4.09-4.04 (m, 8H, -CH2OAc, Ar-
OCH2-), 3.90 (s, 6H, Ar-OCH3), 2.04 (s, 6H, CH3COO-), 1.85
(m, 4H, Ar-OCH2CH2-), 1.70 (m, 4H, -CH2CH2OAc), 1.55-
1.48 (m, 8H, -CH2CH2CH2CH2OAc). HRMS (APCI) Calcd for
C50H56N3O8 [M + H]+: m/z 826.4067. Found: m/z 826.4061.
Synthesis of Monoacetyl Azadipyrromethene Ligand 16:
Lithium hydroxide monohydrate (0.315 g, 7.5 mmol) was
added to a solution of 15 (1.24 g, 1.5 mmol) in 10/1 (v/v)
THF/distilled deionized water (330 mL) under stirring. The
solution was stirred at room temperature for 1.5 h. The reaction
was quenched with 50 mL of saturated aqueous solution of
NH4Cl. THF was evaporated and the product was extracted
with CH2Cl2 (150 mL © 6), dried with anhydrous magnesium
sulfate, and then the solution was filtered and concentrated in
vacuo. The resulting residue was purified by silica gel col-
umn chromatography (hexane/EtOAc = 9/1 ¼ 7/3 ¼ 5/5) to
Synthesis of 1-[4-(6-Hydroxyhexyloxy)phenyl]-3-(4-meth-
oxyphenyl)-4-nitrobutan-1-one (13):
To a solution of
12 (3.94 g, 11.1 mmol) and potassium hydroxide (0.500 g,
8.9 mmol) in methanol (300 mL) was added nitromethane
(11.9 mL, 222 mmol). The mixture was then heated under
reflux for 24 h. The solution was cooled and the solvent was
evaporated under vacuum. The product was extracted with
EtOAc/water, and then the organic layer was washed with
water, dried over anhydrous magnesium sulfate, and evaporated
in vacuo. The residue product was purified by silica gel column
chromatography (hexane/EtOAc = 1/2) to give 13 (3.80 g,
1
afford 16 (0.178 g, 15%) as a metallic brown solid. H NMR
(CDCl3, 400 MHz): ¤ 8.02 (m, 4H, Ar-H), 7.88 (m, 4H, Ar-H),
7.04 (m, 6H, Ar-H), 6.95 (m, 4H, Ar-H), 4.09-4.04 (m, 6H,
-CH2OAc, Ar-OCH2-), 3.91 (s, 6H, Ar-OCH3), 3.65 (t, 2H,
J = 6.7 Hz, -CH2OH), 2.06 (s, 3H, CH3COO-), 1.85 (m, 4H,
Ar-OCH2CH2-), 1.71-1.46 (m, 12H, Ar-OCH2CH2CH2CH2-
CH2CH2-). HRMS (ESI) Calcd for C48H54N3O7 [M + H]+:
m/z 784.3962. Found: m/z 784.3949.
Synthesis of Aza-BODIPY Dye 17: Dry triethylamine
(0.59 mL, 4.2 mmol) was added to a solution of 16 (0.33 g,
0.42 mmol) in CH2Cl2 (150 mL), followed by addition of
BF3¢OEt2 (1.04 mL, 8.4 mmol). After the reaction mixture was
stirred at 50 °C for 1 h, the solution was washed with water. The
organic layer was separated, dried over anhydrous magnesium
sulfate, and then concentrated by rotary evaporation. The
residue was purified by silica gel column chromatography
1
82%). H NMR (CDCl3, 400 MHz): ¤ 7.89 (dt, 2H, J = 9.1,
2.5 Hz, Ar-H), 7.17 (dt, 2H, J = 8.6, 2.6 Hz, Ar-H), 6.92 (dt,
2H, J = 9.1, 2.5 Hz, Ar-H), 6.83 (dt, 2H, J = 8.6, 2.6 Hz, Ar-
H), 4.82-4.60 (m, 2H, -CH2-NO2), 4.14 (m, 1H, >CHCH2-
NO2), 3.91 (t, 2H, J = 6.5 Hz, Ar-OCH2-), 3.86 (s, 3H, Ar-
OCH3), 3.65 (t, 2H, J = 6.6 Hz, -CH2OH), 3.35 (m, 2H, Ar-
(C=O)-CH2-), 1.77 (m, 2H, Ar-OCH2CH2-), 1.59 (m, 2H,
-CH2CH2OH), 1.51-1.38 (m, 5H, -CH2CH2CH2CH2OH).
HRMS (APCI) Calcd for C23H30NO6 [M + H]+: m/z
416.2073. Found: m/z 416.2063.
Synthesis of 6-{4-[3-(4-Methoxyphenyl)-4-nitrobutanoyl]-
phenoxy}hexyl Acetate (14): Dry triethylamine (1.88 mL, 14
mmol) was added to a solution of 13 (3.74 g, 9.0 mmol) and