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Zubkov et al.
the sample into the ion source (ionizing voltage was 70 eV).
Thinꢀlayer chromatography was carried out on Silufol UVꢀ254
plates (visualization with iodine vapor).
Then the reaction mixture was cooled and poured into water
(100 mL). The precipitate was filtered off, washed successively
with cold (5×80 mL) and hot (1×100 mL) water and diethyl
ether (2×50 mL), dried at 100 °C to a constant weight, and
recrystallized from a PriOH—DMF mixture. Isoindoloquinoꢀ
linecarboxylic acids 9—14, 18, and 19 were prepared as colorꢀ
less crystals. Their physicochemical properties, elemental analyꢀ
sis data, and selected spectroscopic characteristics are given in
Table 4. The mass spectrometric data are listed in Table 11, and
the 1H NMR spectroscopic data for compounds 9, 10, and
11—14 are given in Tables 7 and 8.
4ꢀ(2´ꢀFuryl)ꢀ2ꢀmethylꢀ4ꢀNꢀ(mꢀmethylphenyl)ꢀ
(4a),
4ꢀ(2´ꢀfuryl)ꢀ2ꢀmethylꢀ4ꢀNꢀ(mꢀmethoxyphenyl)ꢀ (4b), and
4ꢀ(2´ꢀfuryl)ꢀ2ꢀmethylꢀ4ꢀNꢀ(mꢀchlorophenyl)aminobutꢀ1ꢀenes
(4c); 4ꢀ(2´ꢀfuryl)ꢀ4ꢀNꢀ(mꢀmethylphenyl)ꢀ (5a), 4ꢀ(2´ꢀfurylꢀ
phenyl)ꢀ4ꢀNꢀ(mꢀmethoxy)ꢀ (5b), and 4ꢀ(2´ꢀfuryl)ꢀ4ꢀNꢀ
(mꢀchlorophenyl)aminobutꢀ1ꢀenes (5c); 4ꢀ(2´ꢀfuryl)ꢀ2ꢀmethylꢀ4ꢀ
Nꢀ(αꢀnaphthyl)aminobutꢀ1ꢀene (16a) and 4ꢀ(2´ꢀfuryl)ꢀ4ꢀNꢀ
(αꢀnaphthyl)aminobutꢀ1ꢀene (16b) (general procedure). Schiff
base 6 or 2ꢀ(αꢀnaphthyliminomethyl)furan (0.30 mol) was added
dropwise at reflux to a stirred solution of allylmagnesium broꢀ
mide, which was prepared from allyl bromide (39 mL, 0.45 mol)
and magnesium turnings (22.0 g, 0.90 mol) in diethyl ether
(300 mL) (for amines 5), or to a solution of methallylmagnesium
chloride, which was prepared from methallyl chloride (41 mL,
0.45 mol) and magnesium turnings (22.0 g, 0.90 mol) in a 1 : 1
THF—diethyl ether mixture (300 mL) (for amines 4 and 16).
After the addition of the imine, the reaction mixture was stirred
at ~20 °C for 1 h, cooled, and poured into a saturated aqueous
NH4Cl solution (300 mL). Then the mixture was extracted with
diethyl ether (3×100 mL). The organic layer was dried over
magnesium sulfate and concentrated. The residue was distilled
under reduced pressure. Products 4a—c, 5a—c, and 16a,b were
obtained as colorless oils. Their physicochemical properties, elꢀ
emental analysis data, and spectroscopic characteristics are given
in Table 1. The 1H NMR spectroscopic data are listed in
Tables 2 and 3.
Nꢀ(mꢀMethylphenyl)ꢀ (7a), Nꢀ(mꢀmethoxyphenyl)ꢀ (7b) and
Nꢀ(mꢀchlorophenyl)ꢀ2ꢀmethallylꢀ6ꢀcarboxyꢀ4ꢀoxoꢀ3ꢀazaꢀ
10ꢀoxatricyclo[5.2.1.01,5]decꢀ8ꢀenes (7c); Nꢀ(mꢀmethylpheꢀ
nyl)ꢀ (8a), Nꢀ(mꢀmethoxyphenyl)ꢀ (8b), and Nꢀ(mꢀchlorophenyl)ꢀ
2ꢀallylꢀ6ꢀcarboxyꢀ4ꢀoxoꢀ3ꢀazaꢀ10ꢀoxatricyclo[5.2.1.01,5]decꢀ8ꢀ
enes (8c); Nꢀ(αꢀnaphthyl)ꢀ2ꢀmethallylꢀ (17a) and Nꢀ(αꢀnaphꢀ
thyl)ꢀ2ꢀallylꢀ6ꢀcarboxyꢀ4ꢀoxoꢀ3ꢀazaꢀ10ꢀoxatricyꢀ
clo[5.2.1.01,5]decꢀ8ꢀenes (17b) (general procedure). The correꢀ
sponding amine 4, 5, or 16 (0.1 mol) was dissolved in benzene
(100 mL). Then an equimolar amount of maleic anhydride (9.8 g,
0.1 mol) was added. The reaction mixture was stirred at ~20 °C
for 2—7 days. The crystalline product that formed was filtered off,
washed with benzene (2×100 mL) and diethyl ether (2×80 mL),
and dried at 100 °C. Products 7, 8, and 17 were obtained as
white powders. Their physicochemical properties, elemental
analysis data, and selected spectroscopic characteristics are given
in Table 4. The 1H NMR spectroscopic data are listed in Tables 5
and 6, and the mass spectrometric data are given in Table 11.
2ꢀ and 4ꢀMethylꢀ (9a, 10a), 2ꢀ and 4ꢀmethylmethoxyꢀ
(9b, 10b), and 2ꢀ and 4ꢀmethylchloroꢀ5,5ꢀdimethylꢀ5,6,6a,11ꢀ
tetrahydroꢀ11ꢀoxoꢀ10ꢀcarboxyisoindolo[2,1ꢀa]quinolines
(9c, 10c); 2ꢀ and 4ꢀmethylꢀ (11a—14a), 2ꢀ and 4ꢀmethylmethoxyꢀ
(11b—14b), and 2ꢀ and 4ꢀmethylchloroꢀ5ꢀmethylꢀ5,6,6a,11ꢀ
tetrahydroꢀ11ꢀoxoꢀ10ꢀcarboxyisoindolo[2,1ꢀa]quinolines
(11c—14c); 7,8,8a,13ꢀtetrahydroꢀ7,7ꢀdimethylꢀ13ꢀoxobenꢀ
zo[h]isoindolo[2,1ꢀa]quinolineꢀ12ꢀcarboxylic acid (18);
7,8,8a,13ꢀtetrahydroꢀ7ꢀmethylꢀ13ꢀoxobenzo[h]isoindoꢀ
lo[2,1ꢀa]quinolineꢀ12ꢀcarboxylic acids (19a, 19b) (general proꢀ
cedure). A mixture of thoroughly ground adduct 7, 8, or 17
(0.01 mol) and H3PO4 (50 mL) was stirred at 120—130 °C (for 7
or 17b) or 145—155 °C (for 8 or 17a) for 1—2 h (TLC control).
Compound 18. 1H NMR (DMSOꢀd6), δ: 1.41 and 1.44 (both
s, 3 H each, 2 Me(7)); 1.63 (dd, 1 H, Hax(8), J8 eq = 13.3 Hz,
,8
ax
J8
= 11.5 Hz); 2.58 (dd, 1 H, Heq(8), J8
= 13.3 Hz,
,8
ax eq
,8a
ax
J8 ,8a = 3.5 Hz); 5.32 (dd, 1 H, H(8a), J8
= 11.5 Hz, J8
=
,8a
,8a
eq
3.5 Hz); 7.51 (m, 2 H, H(5), H(6)); 7.7a0x (d, 2 H, H(1), eHq (4),
J1,2 = J3,4 = 8.7 Hz); 7.89 (t, 1 H, H(10), J9,10 = J10,11 = 7.7 Hz);
7.90 (br.d, 2 H, H(2), H(3), J1,2 = J3,4 = 8.7 Hz); 8.04 (br.d,
1 H, H(9), J9,10 = 7.7 Hz); 8.12 (br.d, 1 H, H(11), J10,11
=
7.7 Hz); 9.88 (br.s, 1 H, COOH). Major isomer 19amaj. 1H NMR
(DMSOꢀd6), δ: 1.36 (d, 3 H, Me(7), JMe(7),7 = 6.9 Hz); 1.45 (dt,
1 H, Hax(8), J8
= J8 ax = 13.2 Hz, J8 ,8a = 10.9 Hz); 2.88
,8
,7
ax
(ddd, 1 H, Heq(8)e,qJ8 ax = 13.2 Hz, J8 ax= 4.0 Hz, J8
=
=
=
,8
eq
,8a
,7
eq ax
6.6 Hz); 3.35 (m, 1axH, Hax(7), J8
eq= 13.2 Hz, J8
,7
,7
ax
6.6 Hz, JMe(7),7 = 6.9 Hz); 5.25 (dda,x 1 H, H(8a), J8eq
ax
,8a
ax
10.9 Hz, J8 ,8a = 4.0 Hz); 7.50—7.53 (m, 2 H, H(5), H(6)); 7.64
eq
(d, 2 H, H(1), H(4), J1,2 = J3,4 = 8.5 Hz); 7.89 (t, 1 H, H(10),
J9,10 = J10,11 = 7.5 Hz); 7.90 (br.d, 2 H, H(2), H(3), J1,2 = J3,4
8.5 Hz); 8.02 (d, 1 H, H(9), J9,10 = 7.5 Hz); 8.12 (d, 1 H, H(11),
J10,11 = 7.5 Hz); 9.75 (br.s, 1 H, COOH). Minor isomer 19bmin
1H NMR (DMSOꢀd6), δ: 1.03 (d, 3 H, Me(7), JMe(7),7 = 6.1 Hz);
3.35 (m, 1 H, Heq(7)); 5.29 (dd, 1 H, H(8a), J8 = 9.7 Hz,
=
.
,8a
ax
J8
= 4.2 Hz). The signals for other protons of the minor
,8a
eq
isomer 19b overlap with the signals for analogous protons of the
major isomer 19amaj
.
Nꢀ(mꢀMethylphenyl)ꢀ (15a), Nꢀ(mꢀmethoxyphenyl)ꢀ (15b),
and Nꢀ(mꢀchlorophenyl)ꢀ3ꢀallylꢀ7ꢀcarboxyisoindolinꢀ1ꢀones (15c)
(general procedure). A mixture of thoroughly ground adduct 8
(0.01 mol) and H3PO4 (50 mL) was stirred at 65 °C for 1 h (TLC
control). Then the reaction mixture was cooled and poured into
water (100 mL). The precipitate was filtered off, washed with
cold water (5×80 mL), dried at 100 °C to a constant weight, and
recrystallized from a PriOH—DMF mixture. Carboxyisoinꢀ
dolinones 15a—c were obtained as colorless crystals. Their physiꢀ
cochemical properties, elemental analysis data, and selected
spectroscopic characteristics are given in Table 4. The mass
spectrometric data are listed in Table 11, and the 1H NMR
spectroscopic data are given in Tables 9 and 10.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 04ꢀ03ꢀ
32433).
References
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1. J. Epsztajn, A. Józ´wiak, P. Koluda, I. Sadokierska, and I. D.
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3. Y. Abe, A. Ohsawa, and H. Igeta, Heterocycles, 1982, 19, 49.