Anellated Hemicyanine Dyes
J. Phys. Chem. B, Vol. 107, No. 31, 2003 7901
2-Methoxymethylbenzaldehyde (11). 1,2-Bis(hydroxymethyl)-
benzene (Lancaster, U.K.) was reacted to give 2-methyl-
methoxybenzyl alcohol (1 equiv NaH in THF, then MeI, oil,
yield 50% ); subsequent oxidation (MnO2 in CHCl3) resulted
in 11 (oil, bp 52 °C at 0.012 mbar, yield 82%).25
otherwise) by a Hg high-pressure lamp (TQ 150, Heraeus-
Noblelight, Germany). After the evaporation of the solvent,
cyclization products 24-26 were isolated by flash chromatog-
raphy (EtOAc/heptane 1:1); crude 27 and 28 were obtained by
precipitation from CHCl3/MeOH and used for the final step
without further purification.
7-N,N-Dibutylaminophenanthryl-(1)-methyltriphenylphos-
phonium Bromide (12) and 8-N,N-Dibutyl-aminochrysenyl-
(1)-methyltriphenylphosphonium Bromide (13). Phosphonium
salt 4 (20 mmol) or 10 (20 mmol) with 20 mmol of sodium
methoxide were dissolved in dry methanol and stirred at 60 °C
for 3 h. Then, 20 mmol of aldehyde 11 in MeOH was added
dropwise, and the solution was allowed to reflux overnight. After
the evaporation of the solvent, the crude product was purified
by chromatography (silica gel; EtOAc/heptane 1:5); the obtained
alkenes E/Z-2-(3-N,N-dibutylaminostyryl)benzylmethyl ether
14a (yield 50%) or E/Z-2-(6-N,N-dibutylamino-1-naphthyl)-
vinylbenzylmethyl ether 15a (yield 61%) were cyclized as
described below (20 h, solvent CH2Cl2) to 7-N,N-dibutylamino-
1-methoxymethylphenanthrene 14 (yield 40%, oil) and 2-N,N-
dibutylamino-7-methoxymethylchrysene 15 (yield 50%, mp 215
°C), respectively. Ether 14 or 15 (10 mmol) was stirred with
20 mL of 62% HBr at 60 °C for 10 min. After neutralization
(KHCO3), the crude products were extracted with CHCl3 and
purified by chromatography (silica gel; EtOAc/heptane 1:5) to
yield 7-N,N-dibutylamino-1-bromomethylphenanthrene 16 (yield
53%, oil) and 2-N,N-dibutylamino-7-bromomethylchrysene 17
(yield 50%, mp 186 °C (dec)), respectively. Treating 16 and
17 with triphenylphosphine yielded phosphonium salts 12 (yield
81%, mp 213-214 °C) and 13 (yield 93%, mp 206 °C),
respectively.
7-N,N-Dibutylamino-2-azaphenanthrene (24): Yield
48%, 45 min of irradiation (quartz glass, -30 °C, 2-methyl-
tetrahydrofuran), yellow oil; FABMS m/z: 307.2 (M + 1,
C21H26N2 requires 306.2).
8-N,N-Dibutylamino-2-azachrysene (25): Yield 22%, 45
min of irradiation (quartz glass, 0 °C, cyclohexane), pale-yellow
solid, mp 213 °C (EtOAc); EIMS m/z: 356 (M+), 313 (M+
C3H7, C25H28N2 requires 356.2).
-
10-N,N-Dibutylamino-3-azapicene (26): Yield 25%, 40 h
of irradiation (cyclohexane), pale-yellow solid (EtOAc), still
containing minor impurities; FABMS m/z: 407.2 (M + 1,
C29H30N2 requires 406.2).
11-N,N-Dibutylaminobenzo[m]-3-azapicene (27): Yield
40% (crude product), 15 h of irradiation; EIMS m/z: 456 (M+),
413 (M+ - C3H7, C33H32N2 requires 456.3).
12-N,N-Dibutylaminonaphtho[5,6-m]-3-azapicene(28): Yield
46% (crude product), 15 h of irradiation; EIMS m/z: 506 (M+),
463 (M+ - C3H7, C37H34N2 requires 506.3).
ANNINES 3-7. A mixture of 2 mmol of 24-28 and 5.4 g
(40 mmol) of 1,4-butane sultone was stirred at 120 °C for
4 h.20 The resulting precipitate was collected, washed with ether,
purified by flash chromatography (silica gel, MeOH or CH2Cl2/
MeOH/H2O 50:20:4 and Sephadex LH 20 (Pharmacia), MeOH),
and recrystallized.
ANNINE-3: Yield 24%, yellow solid, mp > 300 °C (MeOH/
heptane); FABMS m/z: 443.2 (M + 1, C25H34N2O3S requires
442.2).
5-Formylisoquinoline (18) was obtained from 5-bromoiso-
quinoline26 by analogy to 4-formylisoquinoline27 (mp 116 °C,28
yield 55%).
ANNINE-4: Yield 35%, yellow solid, mp > 300 °C (MeOH);
FABMS m/z: 493.5 (M + 1, C29H36N2O3S requires 492.2).
ANNINE-5: Yield 40%, red-orange solid, mp > 300 °C
(MeOH); FABMS m/z: 543.3 (M + 1, C33H38N2O3S requires
542.3).
ANNINE-6: Yield 21%, red-orange solid, mp > 300 °C
(MeOH); FABMS m/z: 593.4 (M + 1, C37H40N2O3S requires
592.3).
E/Z-3-(3-N,N-Dibutylaminostyryl)pyridine (19). Phospho-
nium salt 4 (3.5 mmol) was dissolved in dry MeOH; 190 mg
(3.5 mmol) of NaOMe was added, and the mixture was allowed
to reflux for 3 h. Then 3.5 mmol of 3-formylpyridine (Fluka)
dissolved in MeOH was added, and the solution was refluxed
overnight. The E/Z mixture was isolated by flash chromatog-
raphy (silica gel, EtOAc/heptane 1:1). Yield 28%, yellow oil;
EIMS m/z: 308 (M+), 265 (M+ - C3H7, C21H28N2 requires
308.2).
E/Z-3-(6-N,N-Dibutylamino-1-naphthyl)vinylpyridine (20).
The same procedure as that described for 19 was used but with
phosphonium salt 10. Yield 85%, yellow oil; EIMS m/z: 358
(M+), 315 (M+ - C3H7, C25H30N2 requires 358.2).
ANNINE-7: Yield 10%, red solid, mp > 300 °C (MeOH);
FABMS m/z: 643.5 (M + 1, C41H42N2O3S requires 642.3).
References and Notes
(1) Cohen, L. B.; Salzberg, B. M. ReV. Physiol. Biochem. Pharmacol.
1978, 83, 35.
(2) Gupta, R. K.; Salzberg, B. M.; Grinvald, A.; Cohen, L. B.; Kamino,
K.; Lesher, S.; Boyle, M. B.; Waggoner, A. S.; Wang, C. H. J. Membr.
Biol. 1981, 58, 123.
(3) Bullen, A.; Saggau, P. In Modern Techniques in Neuroscience
Research; Johansson, H., Ed.; Springer: Berlin, 1999; p 89.
(4) Loew, L. M.; Simpson, L. L. Biophys. J. 1981, 34, 353.
(5) Grinvald, A.; Hildesheim, R.; Farber, I. C.; Anglister, L. Biophys.
J. 1982, 39, 301.
(6) Grinvald, A.; Fine, A.; Farber, I. C.; Hildesheim, R. Biophys. J.
1983, 42, 195.
(7) Fluhler, E.; Burnham, V. G.; Loew, L. M. Biochemistry 1985, 24,
5749.
(8) Fromherz, P. J. Phys. Chem. 1995, 99, 7188.
(9) Loew, L. M.; Bonneville, G. W.; Surow, J. Biochemistry 1978,
17, 4065.
(10) Fromherz, P.; Lambacher, A. Biochim. Biophys. Acta 1991, 1068, 149.
(11) Fromherz, P.; Mu¨ller, C. O. Biochim. Biophys. Acta 1993, 1150, 111.
(12) Fromherz, P.; Schenk, O. Biochim. Biophys. Acta 1994, 1191, 299.
(13) Fromherz, P.; Dambacher, K. H.; Ephardt, H.; Lambacher; A.;
Mu¨ller, C. O.; Neigl, R.; Schaden, H.; Schenk, O.; Vetter, T. Ber. Bunsen-
Ges. Phys. Chem. 1991, 95, 1333.
E-5-(6-N,N-Dibutylamino-1-naphthyl)vinylisoquinoline (21).
The same procedure as that described for 19 was used but with
phosphonium salt 10 and aldehyde 18. Yield 73%, yellow solid,
mp 128-130 °C (EtOAc); EIMS m/z: 408 (M+), 365 (M+
C3H7, C29H28N2 requires 408.3).
-
E/Z-5-(7-N,N-Dibutylamino-1-phenanthryl)vinylisoquino-
line (22). The same procedure as that described for 19 was used
but with phosphonium salt 12 and aldehyde 18. Yield 82%,
yellow solid, EIMS m/z: 458 (M+), 415 (M+ - C3H7, C33H34N2
requires 458.3).
E/Z-5-(8-N,N-Dibutylamino-1-chrysenyl)vinylisoquino-
line (23). The same procedure as that described for 19 was
used but with phosphonium salt 13 and aldehyde 18. Yield
80%, yellow solid; FABMS m/z: 509.3 (M + 1, C37H36N2
requires 508.3).
Cyclization of Alkenes 19-23.29 A 5 × 10-3 M solution
of the corresponding E- or E/Z-alkene was irradiated (45 min-
40 h, duran glass, room temperature, and CH2Cl2 unless stated
(14) Ephardt, H.; Fromherz, P. J. Phys. Chem. 1989, 93, 7717.
(15) Ephardt, H.; Fromherz, P. J. Phys. Chem. 1991, 95, 6729.