G. Y. Yang et al. / Bioorg. Med. Chem. 15 (2007) 7704–7710
7709
5.1.2. 1,4-Bis-chloromethoxy-butane (4b). A mixture of
1,4-butane-diol (2.00 g, 22.2 mmol) and powdered cal-
cium chloride (2.0 g) in dried benzene (40 mL) was trea-
ted with paraformaldehyde (1.33 g, 44.4 mmol). HCl gas
was obtained in situ from H2SO4 (6 mL) and NaCl
(13 g), and HCl gas was bubbled through the reaction
mixture over 10 h. The reaction mixture was filtered
and the filtrate was purified by distillation to give 4b
and the mixture was stirred at rt for 27 h. The obtained
precipitate was washed with acetone and ethyl acetate to
give 6d (1.06 g, 55%) as a white solid. m.p. 118–120 ꢁC;
1H NMR (200 MHz, D2O) d 1.54–1.68 (m, 4H,
CH2CH2), 3.57–3.74 (m, 4H, OCH2), 6.07 (s, 4H,
NCH2O), 8.06–8.14 (m, 2H, ArH), 8.49–8.53 (m, 2H,
ArH), 8.60–8.64 (m, 2H, ArH), 8.71 (s, 2H, N@CH),
8.94–8.97 (m, 2H, ArH); 13C (50 MHz, D2O) d 27.6,
73.0, 90.5, 129.5, 130.2, 144.6, 146.9, 149.1, 149.8;
API-ES: m/z 359.0 [M-2Cl].
1
as colorless liquid (1.10 g, 26%). H NMR (200 MHz,
CDCl3) d 1.68–1.74 (m, 4H, 2CH2), 3.68–3.74 (m, 4H,
2OCH2), 5.50 (s, 4H, 2OCH2Cl); 13C NMR (50 MHz,
CDCl3) d 25.5, 70.0, 83.2.
Acknowledgment
5.1.3. 1,2-Dimethoxy-ethylene-bis-N,N0-4-pyridiumaldoxime
dichloride (6a). A mixture of 4a (0.10 g, 0.63 mmol) and
4-pyridinealdoxime (0.23 g, 1.89 mmol) in anhydrous
acetonitrile (10 mL) was heated at 45 ꢁC for 20 h. The
resulting white precipitate was collected by filtration
and washed with acetonitrile followed by ethanol to give
6a (0.17 g, 74%).
This work was supported by the Korea Foundation for
International Cooperation of Science & Technology
(KICOS) through a grant provided by the Korean Min-
istry of Science & Technology (No. K20606000001-
06B0100-00111).
1
Mp 162–165 ꢁC; H NMR (200 MHz, D2O) d 3.94 (s,
References and notes
4H, OCH2), 5.91 (s, 4H, NCH2), 8.27 (d, J = 6.6 Hz,
4H, ArH), 8.40 (s, 2H, N@CH), 8.92 (d, J = 6.8 Hz,
4H, ArH); 13C (50 MHz, D2O) d 69.4, 88.1, 124.3,
142.6, 145.8, 150.0; API-ES: m/z 332.1 [M-2Cl].
1. Taylor, P. Anticholinergic agents. In Goodman s The
Pharmacological Basis of Therapeutics; Hardman, J. G.,
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2. Marrs, T. C. Pharmacol. Ther. 1993, 58, 51.
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5.2. 1,2-Dimethoxy-ethylene-bis-N,N0-3-pyridiumaldoxime
dichloride (6b)
A mixture of 4a (0.10 g, 0.63 mmol) and 3-pyr-
idinealdoxime (0.23 g, 1.89 mmol) in anhydrous acetoni-
trile (10 mL) was heated at 45 ꢁC for 20 h. The resulting
white precipitate was collected by filtration and washed
with acetonitrile followed by ethanol to give 6b (0.17 g,
74%). mp 155–157 ꢁC; 1H NMR (200 MHz, D2O) d 3.98
(s, 4H, OCH2), 5.99 (s, 4H, NCH2), 8.16–8.23 (m, 2H,
ArH), 8.40 (s, 2H, N@CH), 8.83 (d, J = 8.2 Hz, 2H,
ArH), 8.96 (d, J = 5.8 Hz, 2H, ArH), 9.21 (s, 2H,
ArH; 13C (50 MHz, D2O) d 69.5, 88.8, 127.9, 133.2,
140.1, 142.1, 143.8, 144.3; API-ES: m/z 332.1 [M-2Cl].
5.3. 1,2-Dimethyl-propylene-bis-N,N0-4-pyridiumaldoxime
dichloride (6c)
A solution of 4-pyridine aldoxime (1.31 g, 10.7 mmol) in
DMF (20 mL) was treated with 4b (1.00 g, 11.4 mmol)
and the mixture was stirred at rt for 27 h. The obtained
precipitate was washed with acetone and ethyl acetate to
give 6d (2.32 g, 95%) as a white solid. mp 128–130 ꢁC;
1H NMR (200 MHz, D2O) d 1.95–2.01 (m, 4H,
CH2CH2), 3.75–3.81 (m, 4H, OCH2), 5.88 (s, 4H,
NCH2O), 8.26–8.29 (m, 4H, ArH), 8.41 (s, 2H, N@CH),
8.90–8.94 (m, 4H, ArH); 13C (50 MHz, D2O) d 27.7,
67.1, 88.1, 124.3, 142.5, 145.8, 149.9.
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API-ES: m/z 387.2 [M-CNOH].
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5.4. 1,2-Dimethyl-propylene-bis-N,N0-2-pyridiumaldoxime
dichloride (6d)
A solution of 2-pyridine aldoxime (1.31 g, 10.7 mmol) in
DMF (20 mL) was treated with 4b (1.00 g, 11.4 mmol)
14. (a) Gabel, F.; Weik, M.; Masson, P.; Renault,
F.; Fournier, D.; Brochier, L.; Doctor, B. P.;