extracted with tert-butyl methyl ether (150 ml × 2). The extract was dried over magnesium sulfate, three
quarters of the solvent was distilled off, the residue was diluted with hexane (200 ml), the precipitate was
recrystallized from hexane (200 ml) in cold (-20°C), and compound 1d (12.0 g) in 47% yield was obtained as
coarse light brown crystals, mp 100-103°C. The substance was stable in the air for several weeks, but on contact
with ammonia or alkali rapidly dimerized to a dark red pyrazino[2,1-a:5,4-a']diisoquinoline derivative [18].
Partial dimerization also takes place on isolating compound 1d, which reduces its yield. The hydrochloride salt
1d. HCl was obtained by passing dry HCl through a solution of 1d base in toluene, yield 85%; mp 191-193°C
(2-propanol–ether). IR spectrum (nujol), cm-1: 1630, 1600, 1550, 1510, 1330, 1275 (νas C–O–C), 1245, 1220,
1150, 1060 (νs C–O–C), 1035, 995, 870, 860 (the NH group was not observed in the IR spectrum due to the
1
formation of hydrogen bonds). H NMR spectrum (CDCl3), , ppm, J (Hz): 1.56 (6H, s, Me); 3.00 (2H, s,
δ
4-CH2); 3.93 (3H, s, OMe); 3.98 (3H, s, OMe); 5.29 (2H, s, CH2Cl); 6.82 (1H, s, 5-H); 7.36 (1H, s, 8-H); 14.85
(1H, br. s, NH).
1-(6,7-Dimethoxy-3,3-tetramethylene-1,2,3,4-tetrahydroisoquinolylidene)acetic Acid Ethyl Ester
(4). A solution of veratrole (12.8 ml, 0.1 mol), cyclohexene oxide (10 ml, 0.1 mol), and ethyl cyanoacetate
(10.7 ml, 0.1 mol) in toluene (80 ml) was added dropwise during 0.5 h to conc. H2SO4 (50 ml) (20-60°C). The
reaction mixture was stirred for 2 h, poured into cold water (300 ml), the organic layer was separated, the
aqueous layer was extracted with toluene (40 ml), and then neutralized with ammonium carbonate to pH ~7. The
precipitate was separated, washed with water, dried, and crystallized from 2-propanol, to give compound 4
(3.03 g, 9%); mp 150-152°C. Compound 3a was obtained similarly but the oily substance formed after
alkalization was extracted with hot hexane (50 ml × 2). After distillation of the hexane the residue was
crystallized from a hexane–CH2Cl2, 5 : 1 mixture. Compound 3a (0.9 g, 3%) was obtained.
6,7-Dimethoxy-1-methylthio-3,3-tetramethylene-3,4-dihydroisoquinoline (3b) was obtained
analogously to compound 4 from veratrole (12.8 ml, 0.1 mol), cyclohexene oxide (10 ml, 0.1 mol), methyl
thiocyanate (6.9 ml, 0.1 mol) in toluene (70 ml) and conc. H2SO4 (50 ml). The reaction mixture was stirred for
6 h at 25°C. The neutralized aqueous layer was extracted with CH2Cl2 (2 × 40 ml), the extract washed with
water, and dried over MgSO4. After distillation of the solvent the residue was crystallized from methanol by
cooling to -15°C. Compound 3b (1.9 g, 6%) was obtained.
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