5494
E. A. Bugnet et al. / Tetrahedron Letters 44 (2003) 5491–5494
3. Agency for Toxic Substances and Disease Registry
from 2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-dione (70.4
mg, 0.138 mmol) in acetic anhydride (2 cm3). The mixture
was stirred for 20 min at 0°C, before being allowed to
warm to room temperature and stirred overnight. After
17 h, water was added and the solution extracted with
CH2Cl2. The CH2Cl2 layer was washed once with 2 M
KOH solution, once with water, dried over MgSO4,
filtered and the volatiles removed under reduced pressure
to leave nitro-methoxy clip 2. Yield: 87 mg, 91.6%.
Found: C, 47.1; H, 4.6; N, 15.2. C27H28N8O14 requires:
C, 47.1; H, 4.1; N, 16.3%. Mass spectrum: ES m/z 1399
[2C27H28N8O14++Na], 711 [C27H28N8O14++Na]. IR (KBr
disk): w 1664 (CO), 1359, 1544 (NO2). 1H NMR l
(ATSDR); Toxicological Profile for Cresols (Draft); US
Public Health Service Department of Health and Human
Services, Atlanta, GA, 1990.
4. Watson, W. D. Tetrahedron Lett. 1976, 30, 2591.
5. Cremlyn, R. J. Agrochemicals: Preparation and Mode of
Action; John Wiley and Sons: Chichester, 1991; p. 221.
6. Matolcsy, M.; Nadasy, G.; Andriska, V. Pesticide Chem-
istry; Elsevier: Amsterdam, 1988; p. 487.
7. Olah, G. A.; Ohamnesian, L.; Arvanaghi, M. Synthesis
1986, 868.
8. (a) Lindsay Smith, J. R.; McKeer, L. C. Tetrahedron
Lett. 1983, 24, 3117; (b) Lindsay Smith, J. R.; McKeer,
L. C.; Taylor, J. M. J. Chem. Soc., Perkin Trans. 2 1987,
1533; (c) Lindsay Smith, J. R.; McKeer, L. C.; Taylor, J.
M. J. Chem. Soc., Perkin Trans. 2 1988, 385; (d) Lindsay
Smith, J. R.; McKeer, L. C.; Taylor, J. M. J. Chem. Soc.,
Perkin Trans. 2 1989, 1537.
9. (a) Silberrad, O. J. Chem. Soc. 1921, 119, 2029; (b)
Campbell, A.; Shields, D. J. Tetrahedron 1965, 21, 211;
(c) Bolton, R.; de la Mare, P. D. B. J. Chem. Soc. (B)
1967, 1044; (d) Delaude, L.; Laszlo, P. J. Org. Chem.
1990, 55, 5260; (e) Deb, S.; Das, K. R. J. Sci. Ind. Res.
1998, 57, 539.
2
(CDCl3): 1.50 (s, 6H, CH3), 3.74 (d, 4H, JHaHb 16.3 Hz,
Ha), 4.02 (s, 12H, OCH3), 4.50 (s, 2H, CH), 5.74 (d, 4H,
2JHaHb 16.3 Hz, Hb). 13C NMR l (CDCl3): 22.7 (CH3),
32.5 (C
139.3 (ArNO2, A
18. Bugnet, E. A.; Thornton-Pett, M.; Kee, T. P., unpub-
lished results.
6
(CH3)2), 46.3 (CH2), 64.4 (OCH3), 81.9 (CH),
rCH).
6
19. We find that molecular clips 1 and 2 do not lead to
polychlorination of the o-cresol, nor to chlorination of
the clip itself when the clip is not present in excess. When
clip 1 is exploited in excess, it does become mono-chlori-
nated once all o-cresol has been chlorinated.18 Dynamic
range issues effectively limit precise 500 MHz intensity
measurements to ratios but problems are not expected
below ratio values of 100 (Fisher, J., personal communi-
cation). All Rp/o ratio measurements were made using 500
MHz NMR spectroscopy with extended relaxation delay
times (>3 s) as reported in a previous study (Ref. 13).
20. 1:1 Association constants, Ka, (as supported by Job
10. (a) Breslow, R.; Kohn, H.; Siegel, B. Tetrahedron Lett.
1976, 20, 1645; (b) Bovonsombat, P.; McNelis, E. Synthe-
sis 1993, 237; (c) Hirano, M.; Yakabe, S.; Monobe, H.;
Clark, J. H.; Morimoto, T. J. Chem. Soc., Perkin Trans.
1 1997, 3081; (d) Smith, K.; Butters, M.; Paget, W. E.;
Goubet, D.; Fromentin, E.; Nay, B. Green Chem. 1999,
83.
11. Masilanani, D.; Rogie, M. M. J. Org. Chem. 1981, 46,
4486.
1
analyses) were determined by H NMR titrations at 500
12. (a) Watson, W. D. J. Org. Chem. 1985, 50, 2145; (b)
Watson, W. D. US Patent, 3,920,757, 1975; (c) Guy, A.;
Lemaire, M.; Guette, J.-P. Tetrahedron 1981, 38, 2339.
13. Bugnet, E. A.; Brough, A. R.; Greatrex, R.; Kee, T. P.
Tetrahedron 2002, 58, 8059.
MHz on a Bruker DRX500 instrument at 298 K in
freshly distilled CDCl3 solvent referenced to internal
TMS as 0 ppm. In each case concentrations of molecular
clip 1 and 2 were measured precisely between 5.5 and 7.7
mM and the concentration of the guest component varied
between 15-times and beyond the concentration of host
as required for compliance with standard double recipro-
cal Benesi–Hildebrand treatments.21 In each case, we
have monitored the change in host aromatic signals [for
molecular clip 1] and backbone proton environments for
molecular clip (2) upon increasing concentrations of guest
molecule.
14. Breslow, R.; Campbell, P. J. Am. Chem. Soc. 1969, 91,
3085.
15. (a) Jansen, R. J.; Rowan, A. E.; de Gelder, R.; Scheeren,
H. W.; Nolte, R. J. M. Chem. Commun. 1998, 121; (b)
Rowan, A. E.; Elemans, J. A. A.; Nolte, R. J. M. Acc.
Chem. Res. 1999, 32, 995; (c) Jansen, R. J.; de Gelder, R.;
Rowan, A. E.; Scheeren, H. W.; Nolte, R. J. M. J. Org.
Chem. 2001, 66, 2643.
21. Fielding, L. Tetrahedron 2000, 56, 6151.
16. Guy, A.; Lemaire, M.; Guette, J.-P. Tetrahedron 1982,
38, 2339.
22. Molecular mechanics and semi-empirical analyses were
performed at the MM+ and AM1 levels respectively
using the HyperChem 7.0 package (HyperCube Inc., 1115
NW 4th St., Gainsville, FL, USA).
17. In a 25 cm3 round-bottomed flask equipped with a mag-
netic stirrer, 0.55 cm3 of HNO3 50% aqueous solution
was added dropwise at 0°C to the methoxy-clip 1 derived