Synthesis of dihydroindoloisoquinolines
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002 2119
Scheme 3
(250 MHz) in CDCl3 with Me4Si as the internal standard. IR
spectra were recorded on a URꢀ20 instrument (in pellets with
KBr). Mass spectra were obtained with an MKhꢀ1303 specꢀ
trometer (ionizing voltage 70 eV). Fluorescence spectra were
measured on a Shimadzu RFꢀ540 spectrofluorometer. Ethanol
was used as a solvent; its purity was checked by UV absorption
and fluorescence spectra. The concentration of solutions of the
compounds studied in EtOH was ∼10–6 mol L–1
.
12ꢀArylideneꢀ5,6ꢀdihydroindolo[2,1ꢀa]isoquinolinium triꢀ
fluoroacetates 2a—f (general procedure). Trifluoroacetic acid
(10 mL) and an aromatic aldehyde (4.6 mmol) were successively
added to a stirred, iceꢀcooled solution of 5,6ꢀdihydroindoloꢀ
isoquinoline 1 (4.6 mmol) in 25 mL of THF. The reaction
mixture was kept at ∼20 °C for 6 h. The solvents were removed in
vacuo, and the residue was recrystallized from EtOH and puriꢀ
fied by chromatography on SiO2. The characteristics of trifluoroꢀ
acetates 2a—f are given in Tables 1 and 2.
Reduction of indolo[2,1ꢀa]isoquinoline
4
in
a
NaBH4—CF3COOH system. Sodium borohydride (0.46 g,
12 mmol) was added in 0.1ꢀg portions over 20 min to a vigorꢀ
ously stirred iceꢀcooled mixture of indoloisoquinoline 4 (0.65 g,
2.9 mmol) in 15 mL of anhydrous THF and 5.8 mL of TFA. The
reaction mixture was stirred at ∼20 °C for 6 h. The solvent and
the excess of TFA were removed in vacuo. The residue was
treated with a saturated aqueous solution of NaHCO3. The prodꢀ
uct was extracted with CHCl3 (4×10 mL), and the extract was
dried over anhydrous Na2SO4. The chloroform was removed,
and the oily residue was purified by column chromatography on
SiO2 to give 5,6ꢀdihydroindoloisoquinoline 1 (0.13 g, 20%).
Product 1 is identical in spectroscopic characteristics with an
authentic sample.9
Hydrogenation of 12ꢀbenzylideneindoloisoquinolinium triꢀ
fluoroacetate 2a over Re2S7. The reaction was carried out acꢀ
cording to the known procedure.9 Rhenium heptasulfide (0.05 g),
salt 2a (0.5 g, 1.2 mmol), and benzene (10 mL) were placed in a
reaction vessel. Hydrogenation was performed at 250 °C and a
hydrogen pressure of 140 atm for 2 h. Purification and separaꢀ
tion of the catalyzate on SiO2 gave nonsubstituted 5,6ꢀdihydroꢀ
indoloisoquinoline 1 (0.25 g, 96%). Product 1 is identical in
characteristics with an authentic sample.9
Reduction of 12ꢀarylideneindoloisoquinolinium trifluoroꢀ
acetates 3a—c and their 5,6ꢀdihydro analogs 2a—c in a
NaBH4—CF3COOH system. The synthesis of 12ꢀbenzylindoꢀ
lo[2,1ꢀa]isoquinolines 5a—c and 12ꢀbenzylꢀ5,6ꢀdihydroindoꢀ
lo[2,1ꢀa]isoquinolines 6a—c (general procedure). Trifluoroacetic
acid (1 mL, 1.54 g, 13.5 mmol) was added dropwise to a stirred,
iceꢀcooled suspension of an indoloisoquinolinium salt (3a—c or
2a—c) (0.5 mmol) and NaBH4 (0.073 g, 1.92 mmol) in 5 mL of
anhydrous THF. The reaction mixture was stirred at ∼20 °C for
6 h. The solvent and the excess of TFA were removed in
vacuo. The residue was neutralized with a saturated solution of
NaHCO3, and the product was extracted with CHCl3 (5×10 mL).
The combined extracts were dried over anhydrous Na2SO4. The
solvent was removed, and the residue was crystallized from EtOH
or purified by column chromatography on SiO2 in ether—hexꢀ
ane (1 : 1). 12ꢀBenzylindoloisoquinolines 5a—c or 6a—c were
isolated as slightly colored crystals. Side hydrogenolysis of comꢀ
pounds 3a—c gave indoloisoquinolines 1 and 4 in 0.5—1% and
3—5% yields, respectively; the yield of indoloisoquinoline 4 from
compounds 2a—c was ∼5%.
3, 5, 6: R = H (a), OМe (b), NO2 (c)
indolizine fragments, which in turn reduces πꢀconjugaꢀ
tion in the molecule. When the trifluoroacetate anion in
salt 3c is replaced by an acetate or trichloroacetate
one, the fluorescence bands experience a significant
shift (λmax = 377 and 446 nm, respectively) attribꢀ
uted to the degree of dissociation of these salts in soꢀ
lution.
The spectra of 5,6ꢀdihydro compounds 2 and 6 show
fluorescence maxima in the shorterꢀwavelength range
(λmax = 368—388 nm) compared to aromatic analogs 3
and 5 and mainly have a diffuse vibrational structure.
Apparently, both effects are due to the presence of a
—CH2—CH2— bridge, which breaks one of the πꢀconjuꢀ
gation chains. In addition, molecules 2 and 6 become less
planar in the excited state in ethanol, as evidenced by a
diffuse character of their fluorescence spectra.
Experimental
Compounds were isolated and purified by crystallization and
column chromatography on Lꢀ60 silica gel (40/100). The purity
of the products was checked by TLC on Silufol UVꢀ254 plates in
heptane—ether (1 : 1); spots were visualized with iodine vapor.
1H NMR spectra were recorded on a Bruker WPꢀ250 instrument
Soldatenkov
