7-Dialkylamino-1-alkylquinolinium Salts
exposure. As light source, a 9 W low-pressure mercury lamp was
used, mounted in the center of a carousel, which provided
homogeneous exposure of all samples. The whole setup was placed
in an aluminum-coated housing in order to maximize the exposure
intensity. The effective dose was calculated by integration of the
spectral overlap of the mercury lamp with the absorption spectrum
of the sample, using the following equation:
7-Amino-1-methylquinolinium Iodide (8) To 7-fluoro-1-
methylquinolinium iodide (6) (500 mg, 1.73 mmol) were added 2
mL of 30% ammonia solution (20 equivalents) and 2 mL of 96%
ethanol. The solution was heated at 60 °C for 1 h, and subsequently
the solvent was evaporated. After recrystallization in 96% ethanol
a yellow crystalline solid was obtained Yield: 316 mg, 64%. Mp
) 118-123 °C. 1H and 1H COSY NMR (acetonitrile-d3) δ (ppm):
9.30 (1H, d, H2, J2,3 ) 5.7 Hz), 9.16 (1H, d, H4, J4,3 ) 8.4 Hz),
8.50 (1H, dd, H5, J5,8 ) 9.3 Hz, J5,6 ) 6.0 Hz), 8.13 (1H, dd, H8,
J8,6 ) 9.6 Hz, J8,4 ) 1.8 Hz), 8.02 (1H, dd, H3, J3,4 ) 8.4 Hz, J3,2
) 5.7 Hz), 7.85 (1H, m, H6), 4.58 (3H, s, CH3N+). The COSY
spectrum shows cross-peaks for δ (ppm): 7.85 (H6) and 8.50 (H5),
8.02 (H3) and 9.16 (H4) and 9.30 (H2).
General Procedure for the Synthesis of Substituted 7-Ami-
noquinolinium Iodides (9-25). To 7-fluoro-1-methylquinolinium
iodide (6) (1 g, 3.46 mmol) were added 96% ethanol (10 mL) and
amine (7.61 mmol, 2.2 equiv). The mixture was subsequently heated
to reflux and allowed to cool slowly to room temperature. The
crystalline products were collected by filtration and washed with
cold absolute ethanol (2 × 5 mL) to give spectroscopically pure
materials in a yield between 60 and 98%.
General Procedure for the Synthesis of Substituted 7-Sul-
fenylquinolinium Iodides (26-28). To 7-fluoro-1-methylquino-
linium iodide (6) (0.5 g, 1.76 mmol) were added 96% ethanol (5
mL), triethylamine (0.28 mL, 1.1 equiv), and the thio compound
(1.1 equiv). The mixture was subsequently heated to reflux and
left to cool slowly to room temperature. The crystalline products
were collected by filtration and washed with cold absolute ethanol
(2 × 5 mL) to give spectroscopically pure materials.
νend
(1 - T(ν))*I(ν)*∆ν
(2)
∑
νstart
where T(ν) and I(ν) are the transmission of the sample and the
intensity of the mercury lamp at wavenumber ν, respectively.
Thermal Stability Measurements. Pieces of PMMA film (2.5
× 5 cm) on microscope glass slides were placed in the oven. After
1 h, the samples were removed from the oven and cooled by placing
them on a copper plate. Subsequently, a UV-vis absorption
spectrum was measured for each sample. This heating, cooling,
and measurement procedure was then repeated.
Reaction Constant Determination. To a solution (2 mL) of
aqueous amine (0.1 M) in a quartz cell was added 1 mL of aqueous
6 (20, 10, or 5 µM) solution and the resulting solution thoroughly
mixed. The cell was then transferred to a spectrophotometer, and
the absorbance at the absorption maximum was measured as a
function of time. The room was thermostated at 23 °C.
1
Synthesis. TLC analysis was performed on silica gel, and H
and 13C NMR spectra were measured at 300 and 75 MHz. Chemical
shifts are given in ppm (δ) relative to tetramethylsilane (TMS) as
internal standard..
7-Dimethylamino-1-hexylquinolinium Tetrafluoroborate (18b).
7-Fluoroquinoline monooxalate (4a) (1 g, 4.2 mmol) was dissolved
in water (50 mL), and potassium carbonate (1.16 g, 8.4 mmol) was
added. The aqueous solution was extracted with dichloromethane
(4 × 50 mL). The combined organic layers were concentrated in
vacuo and redissolved in methanol (5 mL). 1-Bromohexane (1.38
g, 8.4 mmol) and sodium iodide (1.26 g, 8.4 mmol) were added,
and the mixture was refluxed overnight. After being cooled to room
temperature, the mixture was concentrated in vacuo and the residue
was redissolved in dichloromethane. The dichloromethane solution
was washed with water (3 × 50 mL). The dichloromethane layer
was concentrated in vacuo, and 20 mL of a 1 M dimethylamine
solution in ethanol was added. The mixture was subsequently
refluxed for 30 min. After being cooled to room temperature this
solution was added slowly to a saturated solution of sodium
tetrafluoroborate in water (50 mL) under vigorous stirring. 18b
The synthesis of 13b according to Scheme 1 is described in ref
19.
The synthesis of 1:3 mixtures of 5- and 7-fluoroquinoline (4 and
5) was performed according to ref 31. Starting with 25 mL of 3,
27 g of product was obtained.
7-Fluoro-1-methylquinolinium Iodide (6). To a solution of 5-
and 7-fluoroquinoline isomers 4 and 5 (13.5 g, 92 mmol) in
methanol (40 mL) was added methyl iodide (9.5 mL, 138 mmol).
The reaction mixture was refluxed overnight. After being cooled
to room temperature, the mixture was diluted with ether. The yellow
precipitate was filtered and washed with ether (2 × 50 mL).
Recrystallization from 96% ethanol gave pure 6 as yellow crystals.
1
Yield: 22 g, 80%. Mp ) 236.5-240 °C dec. H NMR (DMSO-
d6) δ (ppm): 9.54 (1H, d, H2, J2,3 ) 5.7 Hz), 9.32 (1H, d, H4, J4,3
) 5.7 Hz), 8.63 (1H, dd, H5, J5,6 ) 9.2 Hz, JH-F ) 6.1 Hz), 8.47
(1H, dd, H8, JH-F ) 10.8 Hz, J8,6 ) 2.1 Hz), 8.18 (1H, dd, H3, J3,4
) 8.24 Hz, J3,2 ) 5.86 Hz), 8.06 (1H, M, H6). 13C NMR (DMSO-
d6) δ (ppm): 164.9 (d, C7, JC-F ) 256 Hz), 150.6 (C4), 146.6
(C2), 139.7 (d, C9, JC-F ) 13.4 Hz), 133.5 (d, C5, JC-F ) 10.9
Hz), 126.4 (C10), 121.2 (C3), 120.1 (d, C8, JC-F ) 25.6 Hz), 105.0
(d, C6, JC-F ) 27.4 Hz), 45.5)N+CH3).
crystallized as yellow crystals. Yield: 1.0 g, 71%. Mp ) 144-
1
145 °C. H NMR (DMSO-d6) δ (ppm): 8.96 (1H, dd, H2, J2,3
)
6.0, J2,4 ) 1.2 Hz), 8.77 (1H, d, H4, J4,3 ) 7.5 Hz), 8.14 (1H, d,
H5, J5,6 ) 9.6 Hz), 7.61 (1H, dd, H6, J6,5 ) 9.3 Hz, J6,8 ) 2.4 Hz),
7.53 (1H, dd, H3, J3,4 ) 7.8 Hz, J3,2 ) 6.3 Hz), 6.85 (1H, d, H8,
J ) 2.1 Hz), 4.80 (2H, t, CH2N+, J ) 7.5 Hz), 3.27 (6H, s,
(CH3)2N), 1.85-2.00 (2H, t, â-CH2, J ) 7.2 Hz),1.2-1.42 (6H,
m, CH2), 0.86 (3H, t, CH3, J ) 6.9 Hz).
7-Fluoroquinoline Monooxalate (4a). To a solution of 5- and
7-fluoroquinoline isomers 4 and 5 (13.5 g, 92 mmol) in acetone
(100 mL) was added a solution of oxalic acid dihydrate (11.6 g,
92 mmol) in acetone (100 mL) under vigorous stirring. The mixture
was then concentrated in vacuo to a white solid, which was purified
by recrystallized from 96% ethanol to give pure 4a as white needles.
Yield: 13 g, 80%. Mp ) 152.5-156 °C dec. In DMSO, 4a
dissociates in 4 and oxalic acid as evidenced by the NMR spectra.
7-Dimethylamino-1-(2-hydroxyethyl)quinolinium Iodide (19).
7-Fluoroquinoline monooxalate (4a) (1 g, 4.2 mmol) was dissolved
in water (50 mL), and potassium carbonate (1.16 g, 8.4 mmol) was
added. The aqueous solution was extracted with dichloromethane
(4 × 50 mL). The combined organic layers were concentrated in
vacuo and redissolved in methanol (5 mL). Bromoethanol (1.05 g,
8.4 mmol) and sodium iodide (1.26 g, 8.4 mmol) were added, and
the mixture was refluxed overnight. The mixture was allowed to
cool to room temperature, and 20 mL of a 1 M dimethylamine
solution in ethanol was added. The mixture was subsequently
refluxed for 30 min. After being cooled to room temperature 19
crystallized as bright yellow crystals. Yield: 0.68 g, 47%. Mp )
250 °C dec. 1H NMR (DMSO-d6) δ (ppm): 8.87 (1H, dd, H2, J2,3
) 6.04, J2,4 ) 1.3 Hz), 8.79 (1H, d, H4, J4,3 ) 7.7 Hz), 8.15 (1H,
d, H5, J5,6 ) 9.5 Hz), 7.59 (1H, dd, H6, J6,5 ) 9.33 Hz, J6,8 ) 2.19
Hz), 7.53 (1H, dd, H3, J3,4 ) 7.69 Hz, J3,2 ) 6.04 Hz), 6.94 (1H,
1
1H and H COSY NMR (DMSO-d6) δ (ppm): 8.89 (1H, dd, H5,
J5,6 ) 4.3 Hz, J5,8 ) 1.8 Hz), 8.39 (1H, dd, H4, J4,3 ) 7.7 Hz, J4,2
) 0.8 Hz), 8.05 (1H, dd, H2, J2,3 ) 9.0 Hz, J2,4 ) 6.3 Hz), 7.72
(1H, dd, H8, JH-F ) 10.6 Hz, J8,6 ) 2.8 Hz), 7.48-7.54 (2H, M,
H3 and H6) The COSY spectrum shows cross-peaks for δ (ppm):
7.52 (H3) and 8.05 (H2) and 8.39 (H4), 7.54 (H6) and 8.89 (H5).
13C NMR (DMSO-d6) δ (ppm): 168.6 (CO oxalic acid), 163.0 (d,
C7, JC-F ) 246 Hz), 152.3 (C2), 149.2 (d, C9, JC-F ) 12.6 Hz),
136.8 (C4), 131.5 (d, C5, JC-F ) 9.5 Hz), 125.8 (C10), 121.6 (C3),
117.5 (d, C6, JC-F ) 25.2 Hz), 112.8 (d, C8, JC-F ) 20.5) Hz).
J. Org. Chem, Vol. 71, No. 7, 2006 2675