PAPER
N-Demethylation of N-Methyl Alkaloids
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1H NMR (CDCl3): δ = 6.69 (d, J = 8.0 Hz, 1 H), 6.59 (d, J = 8.0 Hz,
1 H), 6.73 (dddd, J = 1.6, 1.6, 2.8, 9.6 Hz, 1 H), 5.28 (ddd, J = 2.8,
2.8, 9.6 Hz, 1 H), 4.88 (dd, J = 1.2, 6.4 Hz, 1 H), 4.22–4.17 (m, 1
H), 3.86 (s, 3 H), 3.67–3.63 (m, 1 H), 3.05–2.77 (m, 4 H), 2.62–2.57
(m, 1 H), 1.98–1.87 (m, 2 H), 1.80–1.50 (br, 2 H).
13C NMR (CDCl3): δ = 146.5, 142.0, 133.7, 131.1, 128.1, 127.4,
119.4, 112.9, 92.2, 66.4, 56.3, 51.7, 43.8, 41.2, 38.3, 36.5, 31.1.
References
(1) Fries, D. S. Opioid Analgesics, In Foye’s Principles of
Medicinal Chemistry; Lemke, T. L., Ed.; Lippincott William
and Wilkins: Philadelphia, 2002, 5th ed., 453–479.
(3) McCamley, K.; Ripper, J. A.; Singer, R. D.; Scammells, P.
J. J. Org. Chem. 2003, 68, 9847.
HRMS (ESI): m/z [M + H]+ calcd for C17H20NO3: 286.1438; found:
286.1449.
(4) Thavaneswaran, S.; Scammells, P. J. Bioorg. Med. Chem.
Lett. 2006, 16, 2868.
(5) (a) Dong, Z.; Scammells, P. J. J. Org. Chem. 2007, 72, 9881.
(b) Kok, G.; Ashton, T. D.; Scammells, P. J. Adv. Synth.
Catal. 2009, 351, 283.
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(7) Kok, G. B.; Scammells, P. J. Org. Biomol. Chem. 2011, 9,
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20, 4499.
N-Northebaine (6c) (Table 1, entry 18)
Purified via method A using a gradient of CHCl3–MeOH–NH4OH
(90:10:1–85:15:1); yield: 66 mg (81%); off-white solid; mp 146–
150 °C (Lit.32 mp 157–158 °C); [α]D24 –225 (c 0.82, 5% MeOH in
CHCl3) {Lit.33 [α]D23 –200 (c 0.1, 5% MeOH in CHCl3)}.
1H NMR (CDCl3): δ = 6.68 (d, J = 8.4 Hz, 1 H), 6.62 (d, J = 8.4 Hz,
1 H), 5.51 (d, J = 6.4 Hz, 1 H), 5.27 (s, 1 H), 5.03 (d, J = 6.4 Hz, 1
H), 3.92 (dd, J = 1.6, 6.0 Hz, 1 H), 3.86 (s, 3 H), 3.61 (s, 3 H), 3.25–
3.07 (m, 3 H), 2.94 (dd, J = 4.0, 13.6 Hz, 1 H), 2.40–2.20 (br, 1 H),
2.08 (ddd, J = 5.2, 12.8, 12.8 Hz, 1 H), 1.85–1.80 (m, 1 H).
13C NMR (CDCl3): δ = 152.4, 144.7, 142.7, 133.9, 133.3, 127.7,
119.1, 112.8, 110.0, 95.7, 89.1, 56.3, 54.8, 53.8, 46.6, 40.6, 38.4,
37.6.
(10) Grierson, D. Org. React. 1990, 39, 85.
(11) (a) Brand, J. C. D.; Snedden, W. Trans. Faraday Soc. 1957,
53, 894. (b) Peña, L. A.; Seidl, A. J.; Cohen, L. R.; Hoggard,
P. E. Transition Met. Chem. 2009, 34, 135, and references
cited therein.
HRMS (ESI): m/z [M + H]+ calcd for C18H20NO3: 298.1438; found:
(12) Traverso, O.; Scandola, F. Inorg. Chim. Acta 1970, 4, 493.
(13) See, for example: (a) Wilkinson, G.; Cotton, F. A. Prog.
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(14) Sato, M.; Yamada, T.; Nishimura, A. Chem. Lett. 1980, 925.
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158, 187.
298.1432.
N-Nororipavine Hydrochloride (7c) (Table 1, entry 24)
Purified via method B using a gradient of CHCl3–MeOH (24:1–
17:3); yield: 74 mg (81%); off-white solid; mp >200 °C (dec.);
[α]D24 –188 (c 1.0, 10% AcOH in H2O).
1H NMR (D2O): δ = 6.78 (d, J = 8.0 Hz, 1 H), 6.74 (d, J = 8.0 Hz, 1
H), 5.90 (d, J = 6.4 Hz, 1 H), 5.50 (s, 1 H), 5.25 (d, J = 6.4 Hz, 1 H),
4.61 (d, J = 6.0 Hz, 1 H), 3.64 (s, 3 H), 3.46–3.22 (m, 4 H), 2.31
(ddd, J = 6.0, 13.3, 13.3 Hz, 1 H), 2.08–2.01 (m, 1 H).
13C NMR (D2O–CF3CO2D): δ = 153.0, 142.8, 138.6, 132.0, 124.4,
124.2, 120.8, 117.3, 117.0, 96.1, 87.7, 55.1, 53.2, 44.6, 37.0, 33.5,
33.1.
HRMS (ESI): m/z [M + H]+ calcd for C17H18NO3: 284.1281; found:
284.1287.
(19) See, for example: (a) Gorton, J. E.; Lentzner, H. L.; Watta,
W. E. Tetrahedron 1971, 27, 4353. (b) Rapic, V.;
Tabakovic, I.; Skundric, B.; Lacan, M. Croat. Chem. Acta
1978, 51, 333. (c) Nagy, A. G.; Toma, S. J. Organomet.
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J. Organomet. Chem. 1984, 277, 113. (e) Britton, W. E.;
Kashyap, R.; El-Hashash, M.; El-Kady, M.; Herberhhold,
M. Organometallics 1986, 5, 1029. (f) Fujjta, E.; Gordon,
B.; Hillman, M.; Nagy, H. J. Organomet. Chem. 1981, 218,
105. (g) Hillman, M.; Gordon, B.; Weiss, A. J.; Guzikowska,
A. P. J. Organomet. Chem. 1978, 155, 77. (h) El-Hashash,
M. A.; El-Najdy, S.; Saleh, R. Indian J. Chem., Sect. A:
Inorg., Phys., Theor. Anal. Chem. 1983, 22, 605. (i) Silva,
M. E. N. P. R. A.; Pombeiro, A. J. L.; da Silva, J. J. R. F.;
Herrmann, R.; Deus, N.; Castilho, T. J.; Silva, M. F. C. G.
J. Organomet. Chem. 1991, 421, 75. (j) Silva, M. E. N. P. R.
A.; Pombeiro, A. J. L.; da Silva, J. J. R. F.; Herrmann, R.;
Deus, N.; Bozak, R. E. J. Organomet. Chem. 1994, 480, 81.
(k) Asahara, M.; Natsume, S.; Kurihara, H.; Yamaguchi, T.;
Erabi, T.; Wada, M. J. Organomet. Chem. 2000, 601, 246.
(20) (a) Bashkin, J. K.; Kinlen, P. J. Inorg. Chem. 1990, 29, 4507.
(b) Zhong, Z.-H.; Matsumura-Inoue, T.; Ichimura, A. Anal.
Sci. 1992, 8, 877. (c) Blom, N. F.; Neuse, E. W. Transition
Met. Chem. 1987, 12, 301.
N-Northevinone (8c) (Table 1, entry 30)
Purified via method A using a gradient of CHCl3–MeOH–NH4OH
(98:2:1 to 95:5:1); yield: 46 mg (56%); off-white solid; mp 67–
24
23
69 °C; [α]D –234 (c 1.25, CHCl3) {Lit.34 [α]D –240 (c 0.1,
CHCl3)}.
1H NMR (CDCl3): δ = 6.65 (d, J = 7.8 Hz, 1 H), 6.55 (d, J = 7.8 Hz,
1 H), 5.93 (d, J = 8.8 Hz, 1 H), 5.56 (d, J = 8.8 Hz, 1 H), 4.56 (s, 1
H), 3.82 (s, 3 H), 3.61 (s, 3 H), 3.54–3.47 (m, 1 H), 3.18–2.70 (m, 6
H), 2.16 (s, 3 H), 1.90–1.70 (m, 3 H), 1.42 (dd, J = 6.4, 12.0 Hz, 1
H).
13C NMR (CDCl3): δ = 208.7, 147.9, 141.7, 135.7, 133.8, 128.0,
126.1, 119.2, 113.4, 95.6, 80.9, 56.4, 53.4, 52.7, 50.5, 40.1, 42.2,
37.2, 34.3, 33.0, 30.5, 29.4.
HRMS (ESI): m/z [M + H]+ calcd for C22H26NO4: 368.1856; found:
368.1872.
Acknowledgment
The authors thank the ARC Centre for Free Radical Chemistry and
Biotechnology for financial support.
Supporting Information for this article is available online at
(21) Castagnola, M.; Floris, B.; Illuminati, G.; Ortaggi, G.
J. Organomet. Chem. 1973, 60, C17.
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