580
J. C. Daab and F. Bracher
Recrystallisation from ethanol=water gave 0.22 g (86%) 14 as a pale yellow powder. Mp 141–142ꢁC
(dec.); MS (70 eV): m=z (%) ¼ 253 (100, Mþ ), 236 (4), 224 (94), 209 (22); IR (KBr): ꢀꢀ ¼ 3414, 3403,
3347, 3337, 3274, 1609, 1593, 1511, 1476, 1435, 1362, 1293, 1246, 1178, 1044, 1017, 998, 840 cm ꢂ 1
;
1H NMR (CDCl3): ꢁ ¼ 8.36 (s, 1H, Pyr-CH), 7.34 (s, 1H, Pyr-CH), 7.22 (dt, J ¼ 2.8, 8.7Hz, 2H,
aromat. CH), 6.97 (dt, J ¼ 2.8, 8.7 Hz, 2H, aromat. CH), 4.56 (s, 2H, CH2O), 3.85 (s, 3H, OCH3), 3.80
(br. s, 1H, OH), 2.27 (s, 3H, CH3) ppm; 13C NMR (CDCl3): ꢁ ¼ 159.4 (quart. C), 150.0 (Pyr-CH),
145.1 (quart. C), 140.8 (quart. C), 137.0 (quart. C), 130.4 (2C, aromat. CH), 129.4 (quart. C), 128.7
(Pyr-CH), 114.0 (2C, aromat. CH), 88.2 (quart. C), 84.3 (quart. C), 55.4 (OCH3), 51.2 (CH2O), 19.9
(CH3) ppm.
3-[5-(4-Methoxyphenyl)-4-methyl-2-pyridyl]-propan-1-ol (15, C16H19NO2)
0.67g (2.6mmol) Alkynol 14 were dissolved in 50cm3 EtOH (60%), 0.20 g Pd=C (5%) were added,
and the mixture was shaken under H2. After filtration and evaporation the residue was purified by FCC
(CHCl3, then ethyl acetate, then ethyl acetate=MeOH 20:1) to give 0.58g (85%) 15 as a yellow oil. MS
(70 eV): m=z (%) ¼ 257 (2, Mþ ), 240 (4), 226 (10), 213 (100), 198 (16), 182 (3); IR (KBr): ꢀꢀ ¼ 1606,
1516, 1486, 1455, 1443, 1291, 1248, 1179, 1056, 1038, 1019, 834 cmꢂ 1; 1H NMR (CDCl3): ꢁ ¼ 8.29
(s, 1H, Pyr-CH), 7.22 (dt, J ¼ 5.0, 8.7 Hz, 2H, aromat. CH), 7.08 (s, 1H, Pyr-CH), 6.69 (dt, J ¼ 5.0,
8.7 Hz, 2H, aromat. CH), 4.32 (br. s, 1H, OH), 3.84 (s, 3H, OCH3), 3.74 (t, J ¼ 5.9 Hz, 2H, CH2O),
2.94 (t, J ¼ 7.0 Hz, 2H, Pyr-CH2), 2.25 (s, 3H, CH3), 2.01 (m, 2H, CH2) ppm; 13C NMR (CDCl3):
ꢁ ¼ 159.6 (quart. C), 159.1 (quart. C), 148.8 (Pyr-CH), 145.5 (quart. C), 135.0 (quart. C), 130.4 (2C,
aromat. CH), 130.0 (quart. C), 124.6 (Pyr-CH), 113.9 (2C, aromat. CH), 62.1 (CH2OH), 55.3 (OCH3),
34.7 (CH2), 32.0 (CH2), 19.9 (CH3) ppm.
6-(4-Methoxyphenyl)-7-methyl-1,2,3-trihydroindolizidinium Chloride (16, C16H18ClNO)
0.90g (3.5 mmol) of the pyridinepropanol 15 were dissolved in 100cm3 anhydrous CH2Cl2 and treated
with 1.09g (10.8 mmol) Et3N and 0.81g (7.1mmol) mesyl chloride and stirred at room temperature.
After completion of the reaction (tlc control) 100 cm3 brine was added to the mixture, followed by
NaOH solution to reach pH 12. The volatile organic solvents were removed by distillation. The
remaining aqueous layer was washed with ethyl acetate, saturated with NaCl and extracted with
CHCl3=CH2Cl2 (1:1). The organic extract was dried over CaCl2 and evaporated. The residue was
crystallised from i-PrOH to give 0.31 g (32%) 16 as white crystals. Mp 208–212ꢁC (dec.); MS (FAB,
NBA, pos.): m=z (%) ¼ 240 (100, Mþ ); IR (KBr): ꢀꢀ ¼ 3422, 3000, 1637, 1609, 1500, 1444, 1254,
1
1175, 1027, 853 cmꢂ 1; H NMR (CDCl3): ꢁ ¼ 9.14 (s, 1H, Pyr-CH), 7.85 (s, 1H, Pyr-CH), 7.41 (dt,
J ¼ 4.8, 8.7 Hz, 2H, aromat. CH), 7.01 (dt, J ¼ 4.8, 8.7 Hz, 2H, aromat. CH), 5.26 (t, J ¼ 7.5 Hz, 2H, N-
CH2), 3.86 (s, 3H, OCH3), 3.61 (t, J ¼ 7.7 Hz, 2H, Pyr-CH2), 2.59 (m, 2H, CH2), 2.53 (s, 3H, CH3)
ppm; 13C NMR (CDCl3): ꢁ ¼ 160.5 (quart. C), 156.3 (quart. Pyr-C), 155.1 (quart. Pyr-C), 140.6 (Pyr-
CH), 139.8 (quart. C), 130.7 (2C, aromat. CH), 125.5 (quart. C), 125.4 (Pyr-CH), 114.6 (2C, aromat.
CH), 59.1 (N-CH2), 55.5 (OCH3), 32.1 (Pyr-CH2), 22.0 (CH2), 21.5 (CH3) ppm.
6-(4-Hydroxyphenyl)-7-methyl-1,2,3-trihydroindolizidinium Chloride
(Ipalbidinium, 1, C15H16ClNO5)
0.28g (1.0mmol) 6-(4-Methoxyphenyl)-7-methyl-1,2,3-trihydroindolizidinium chloride 16 were dis-
solved in 10cm3 anhydrous CH2Cl2 and treated with 10cm3 (10.0 mmol) 1 M BBr3 solution in CH2Cl2.
The mixture was stirred at room temperature for 16 h then poured onto ice. The organic components,
obtained by extraction with CH2Cl2 were purified by FCC (ethyl acetate, then ethyl acetate:MeOH 5:1)
over Al2O3 followed by washing over an anion exchange resin (chloride), and finally recrystallisation
from i-PrOH to give 50 mg (19%) of the alkaloid 1 as a white solid. Mp>295ꢁC (dec.) (Ref. [3]: no