2344
J. Huang et al.
PAPER
idue was purified by column chromatography (silica gel, CH2Cl2–
MeOH, 2:1); this gave a pale yellow oil.
References
(1) Recent examples: (a) Hage, R.; Iburg, J. E.; Kerschner, J.;
Koek, J. H.; Lempers, E. L. M.; Martens, R. J.; Racherla, U.
S.; Russell, S. W.; Swarthoff, T.; van Vliet, M. R. P.;
Warnaar, J. B.; van der Wolf, L.; Krijnen, B. Nature 1994,
369, 637. (b) Garcia-Bosch, I.; Company, A.; Fontrodona,
X.; Ribas, X.; Costas, M. Org. Lett. 2008, 10, 2095.
(c) Che, C. M.; Yu, W. Y.; Chan, P. M.; Cheng, W. C.; Peng,
S. M.; Lau, K. C.; Li, W. K. J. Am. Chem. Soc. 2000, 122,
11380. (d) Custer, P. D.; Garrison, J. C.; Tessier, C. A.;
Youngs, W. J. J. Am. Chem. Soc. 2005, 127, 5738.
(e) Graham, B.; Spiccia, L.; Skelton, B. W.; White, A. H.;
Hockless, D. C. R. Inorg. Chim. Acta 2005, 358, 3974.
(f) Company, A.; Gómez, L.; Güell, M.; Ribas, X.; Luis, J.
M.; Que, L. Jr.; Costas, M. J. Am. Chem. Soc. 2007, 129,
15766.
(2) (a) Anderson, C. J.; Welch, M. J. Chem. Rev. 1999, 99,
2219. (b) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer,
R. B. Chem. Rev. 1999, 99, 2293.
(3) For example, see: Choi, H.-J.; Bae, Y.-K.; Kang, S.-C.; Park,
Y. S.; Park, J. W.; Kim, W.-I.; Bell, T. W. Tetrahedron Lett.
2002, 43, 9385.
(4) (a) Graham, B.; Comba, P.; Hearn, M. T. W.; Spiccia, L.
J. Biol. Inorg. Chem. 2007, 12, 11. (b) Johnson, D. L.;
Martin, L. L. J. Am. Chem. Soc. 2005, 127, 2018.
(5) (a) Richman, J. E.; Atkins, T. J. J. Am. Chem. Soc. 1974, 96,
2268. (b) Hoye, R. C.; Richman, J. E.; Dantas, G. A.;
Lightbourne, M. F.; Shinneman, L. S. J. Org. Chem. 2001,
66, 2722. (c) Madison, S. A.; Batal, D. J. WO 9400439,
1994. (d) Schmidt, J. A. R.; Giesbrecht, G. R.; Cui, C.;
Arnold, J. Chem. Commun. 2003, 1025.
(6) Searle, G. H.; Geue, R. J. Aust. J. Chem. 1984, 37, 959.
(7) Stones, G.; Tripoli, R.; McDavid, C. L.; Roux-Duplâtre, K.;
Kennedy, A. R.; Sherrington, D. C.; Gibson, C. L. Org.
Biomol. Chem. 2008, 6, 374.
(8) (a) Flassbeck, C.; Wieghardt, K. Z. Anorg. Allg. Chem. 1992,
608, 60. (b) Romakh, V. B.; Therrien, B.; Labat, G.; Stoekli-
Evans, H.; Shul’pin, G. B.; Suss-Fink, G. Inorg. Chim. Acta
2006, 359, 3297. (c) Romakh, V. B.; Therrien, B.;
Karmazin-Brelot, L.; Labat, G.; Stoekli-Evans, H.; Shul’pin,
G. B.; Suss-Fink, G. Inorg. Chim. Acta 2006, 359, 1619.
(d) Bambirra, S.; Leusen, D. V.; Cornelis, G. J.; Tazelaar, A.
M.; Hessen, B. Organometallics 2007, 26, 1014.
(9) Different detosylation methods were tried: (a) Helps, I. M.;
Parker, D.; Chapman, J.; Ferguson, G. J. Chem. Soc., Chem.
Commun. 1988, 1094. (b) Hosseini, M. W.; Lehn, J. M. J.
Am. Chem. Soc. 1982, 104, 3525. (c) Martin, L. Y.; Sperati,
C. R.; Busch, D. H. J. Am. Chem. Soc. 1977, 99, 2968.
(d) Lazar, I.; Takacs, Z. Synth. Commun. 2001, 31, 141.
(10) Chak, B. C. M.; McAuley, A. Can. J. Chem. 2006, 84, 187.
(11) Parai, M. K.; Panda, G.; Srivastava, K.; Puri, S. K. Bioorg.
Med. Chem. Lett. 2008, 18, 776.
Yield: 1.2 g (83%).
1H NMR (400 MHz, CDCl3): d = 7.54 (d, J = 8.1 Hz, 2 H), 7.23 (d,
J = 8.1 Hz, 2 H), 2.91 (m, 4 H), 2.64 (m, 2 H), 2.54 (m, 4 H), 2.41
(m, 6 H), 2.33 (s, 3 H), 2.30 (s, 3 H).
ESI-MS: m/z = 327 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C15H27N4O2S: 327.1855;
found: 327.1870.
1,4,7-Trimethyl-10-tosyl-1,4,7,10-tetraazacyclododecane (21)
Compound 20 (5.70 g, 18.0 mmol) followed by a 37% aq formalde-
hyde soln (25.0 mL) were added to a 50-mL round-bottom flask.
The mixture was cooled with an ice bath and formic acid (25.0 mL)
was carefully added dropwise. After stirring for 0.5 h, the red-
brown soln was refluxed for 20 h. After the mixture had cooled to
r.t., 37% aq HCl (3 mL) was added and the volatiles were removed
by evaporation. The resulting brown oil was dissolved in H2O (5
mL), and aq NaOH (2 M; 35 mL) was added, whereupon a white
solid precipitated. (The pH of the mother liquor was 10.) The soln
was extracted with CHCl3 (4 × 10 mL). The combined organic lay-
ers were dried (Na2SO4) and the solvent was removed under re-
duced pressure. The residue was purified by chromatography (silica
gel, hexane–EtOAc, 1:1); this gave a pale yellow syrupy compound.
Yield: 4.50 g (68%).
1H NMR (400 MHz, CDCl3): d = 7.53 (d, J = 8.1 Hz, 2 H), 7.22 (d,
J = 8.0 Hz, 2 H), 2.92 (s, 4 H), 2.51–2.26 (m, 15 H), 2.13–2.11 (m,
9 H).
13C NMR (100 MHz, CDCl3): d = 143.5, 132.1, 129.5, 127.8, 57.1,
55.8, 55.7, 55.2, 52.5, 45.9, 45.7, 42.8, 21.4.
ESI-MS: m/z = 369 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C18H33N4O2S: 369.2324;
found: 369.2330.
1,4,7-Trimethyl-1,4,7,10-tetraazacyclododecane (22)
Concd aq H2SO4 (4 mL) was carefully added to compound 21 (1.0
g, 2.7 mmol) to yield a dark brown soln which was stirred for 24 h
at 120 °C under a N2 atmosphere. After cooling, the mixture was
poured onto crushed ice (5 g) and aq NaOH was added until the pH
of the mixture exceeded 10. The brown aqueous layer was extracted
with CHCl3 (4 × 25 mL). The combined organic layers were dried
(MgSO4) and evaporated; this gave a yellow oil.
Yield: 0.35 g (60%).
1H NMR (400 MHz, CDCl3): d = 2.43 (t, J = 4.8 Hz, 4 H), 2.10–1.92
(m, 12 H), 1.82 (s, 3 H), 1.79 (s, 6 H), 1.60 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 57.0, 56.7, 55.6, 54.8, 54.6, 45.6,
45.5, 42.6.
ESI-MS: m/z = 215 [M + H].
(12) Stetter, H.; Mayer, K. H. Chem. Ber. 1961, 94, 1410.
(13) (a) Lukyanenko, N. G.; Basok, S. S.; Filonova, L. K.
J. Chem. Soc., Perkin Trans. 1 1988, 3141. (b) Wilson,
J. M.; Giordani, F.; Farrugia, L. J.; Barrett, M. P.; Robins,
D. J.; Sutherland, A. Org. Biomol. Chem. 2007, 5, 3651.
(c) Suchý, M.; Hudson, R. H. E. Eur. J. Org. Chem. 2008,
4847.
(14) Compound 20 could be obtained by monotosylation of
commercially available 2; see: (a) Ohashi, M.; Konkol, M.;
Del Rosal, I.; Poteau, R.; Maron, L.; Okuda, J. J. Am. Chem.
Soc. 2008, 130, 6920. (b) Leivers, M.; Breslow, R. Bioorg.
Chem. 2001, 29, 345.
HRMS (ESI): m/z calcd for C11H27N4: 215.2236; found: 215.2230.
Acknowledgment
We acknowledge the support from the Hong Kong Polytechnic Uni-
versity and the Research Grants Council Central Allocation Fund
(CityU 2/06C).
Synthesis 2009, No. 14, 2341–2344 © Thieme Stuttgart · New York