T. Gunnlaugsson et al. / Tetrahedron 60 (2004) 5799–5806
5805
NaHCO3 and brine. The organic layer was collected, dried
over MgSO4, filtered and evaporated to give a white solid.
7.03 (2H, d, N–H), 5.59 (2H, d, C H(CH3)NH), 3.22 (4H,
m), 2.77 (4H, q), 2.40 (8H, m), 1.67 (6H, d, J¼6.5 Hz,
CH(CH3)NH); 13C NMR (100 MHz, CD3CN): 169.8
(CvO), 137.7 (Ar-H), 133.4 (Ar-H), 130.9 (Ar-H), 128.3
(Ar-H), 128.0 (Ar-H), 126.1 (Ar-H), 125.5 (Ar-H), 124.7
(Ar-H), 123.1 (Ar-H), 122.3 (Ar-H), 71.6, 60.2, 56.0, 54.8,
43.5, 19.7 (CH(C H3); ES-MS: m/z 552.9 (Mþ); D1/8¼225
(1/dm3 mol21 cm21 10399) 281.6 (11750) 293.2 (6889.5);
n/cm21 (KBr) 3272 (N–H); 2499, 2554 (ar CvH); 1656
(CvO amide); 1607, 1528 (ar CvC); 1468 (C–N amide);
1357 (C–N crown ether); 1132 (C–O–C crown ether).
4.2.1. 2-Chloro-N-[(S)-1-naphthyl]ethylethanamide 3.
0.58 g, 86.9% yield. Mp 140 8C; calcd for C14H14NOCl: C
67.88; H, 5.70; N, 5.65. Found C 67.63, H 5.77, N 5.86; 1H
NMR (400 MHz, CD3CN): d 8.16 (1H, d, Ar-H, J¼8.5 Hz),
7.96 (1H, d, Ar-H, J¼7.5 Hz), 7.87 (1H, d, Ar-H,
J¼7.5 Hz), 7.59 (1H, m, Ar-H), 7.25 (1H, sb, Ar-H,), 5.83
(1H, m, J¼7.0 Hz), 4.04 (2H, s), 1.63 (3H, d, J¼7.0 Hz);
13C NMR (100 MHz, CD3CN): 164.8, 138.8, 133.4, 130.2,
128.31, 127.3, 125.0, 125.3, 125.0, 122.6, 122.1, 42.2, 20.1;
ES-MS: m/z 247.9 (Mþ); n/cm21 (KBr) 3295 (N–H), 1648
(CvO), 1541 (CvC), 780 (C–Cl).
(at OD¼0.1, 225 nm)
lmax/nm (CH3CN) 260.7
Acknowledgements
4.2.2. 2-Chloro-N-[(R)-1-naphthyl]ethylethanamide 4.
0.60 g, 87.3% yield. Mp 140 8C; calcd for C14H14NOCl:
C, 67.88;H, 5.70; N, 14.31. Found: C; 67.67;H, 5.81; N,
5.83; 1H NMR (400 MHz, CDCl3): d 8.11 (1H, d,
J¼8.5 Hz), 7.92 (1H, d, J¼8.6 Hz), 7.86 (1H, d,
J¼7.6 Hz), 7.56 (4H, m), 6.81 (1H, s, N–H), 4.15 (2H, q),
1.74 (3H, d, J¼7.0 Hz); 13C NMR (100 MHz, CDCl3):
164.4 (qC), 137.0 (qC), 133.5 (qC), 130.5 (qC), 128.5 (Ar-H),
128.2 (Ar-H), 126.2 (Ar-H), 125.5 (Ar-H), 124.8 (Ar-H),
122.6 (Ar-H), 122.1 (Ar-H), 44.8 (C H2), 42.2 (C H2), 20.4
(C H3); ES-MS: m/z 247.9 (Mþ); n/cm21 (KBr) 3290 (N–
H), 1652 (CvO), 1540 (CvC), 782 (C–Cl).
We would like to thank Trinity College Dublin (Krieble
Fund 2001-2002), and HEA (Higher Education Authority in
Irealnd) under the PRTLI 98 (Molecular Cell Biology
Programme) for financial support, Dr. John E. O’Brien for
running NMR spectra, Dr. Hazel Moncrieff and Professor
D. Clive Williams (Biochemistry TCD) for their valuable
discussion.
References and notes
4.3. General synthesis of the sensors 1 and 2
1. de Silva, A. P.; McCaughan, B.; McKinney, B. O. F.; Querol,
M. Dalton Trans. 2003, 1902. De Silva, A. P.; Fox, D. B.;
Huxley, A. J. M.; Moody, T. S. Coord. Chem. Rev. 2000, 205,
41. Lavigne, J. J.; Anslyn, E. V. Angew. Chem., Int. Ed. 2001,
40, 3119. de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.; Moody,
T. S. Coord. Chem. Rev. 2000, 205, 41. Fabbrizzi, L.;
Licchelli, M.; Rabaioli, G.; Taglietti, A. F. Coord. Chem. Rev.
2000, 205, 85. de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.;
McClenaghan, N. D.; Roiron, J. Coord. Chem. Rev. 1999, 186,
297.
1,4-Diaza-9-crown-3-ether (1 equiv.), Cs2CO3 (6 equiv.)
and KI (0.1 equiv.) were stirred in MeCN under inert
atmosphere. The appropriate chromophore (2.1 equiv.) in
MeCN was added via a pressure equalized dropping funnel.
The mixture was left to reflux at 80 8C overnight under inert
atmosphere. The reaction was filtered and the solvent
evaporated. The yellow residue was dissolved in CHCl3 and
washed with 10% K2CO3 (3£20 mL). The organic layer was
collected, dried over MgSO4, filtered and evaporated to give
a white solid. After purification by alumina chromatography
with DCM: 0!5% MeOH, the product was washed and
recrystallized from diethyl ether to yield a white solid.
2. Chemical Sensors and Biosensors for Medical and Biological
Applications. Spichiger-Keller, U. S., Ed.; Wiley-VCH:
Weinheim; Germany, 1998. Chemosensors of Ion and
Molecular Recognition. Desvergne, J. P., Czarnik, A. W.,
Eds.; Kluwer Academic: Dordrecht, Netherland, 1997.
3. de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E.
Chem. Rev. 1997, 97, 1515. Czarnik, A. W. Acc. Chem. Res.
1994, 27, 302. Fluorescent Chemosensors for Ion and
Molecular Recognition. Czarnik, A. W., Ed.; ACS Books:
Washington, 1993.
4.3.1. Compound 1 (S,S). 0.22 g, 32.7% yield. Mp 107 8C;
calcd for C34H40N4O3: C 73.88; H, 7.29; N, 10.14. Found C
73.39, H 7.14, N 9.66; 1H NMR (400 MHz, CD3CN): d 8.12
(2H, d, Ar-H, J¼8.5 Hz), 7.91 (2H, d, Ar-H, J¼7.5 Hz),
7.81 (2H, d, Ar-H, J¼8.0 Hz), 7.53 (8H, m, J¼8.0 Hz), 5.80
(2H, m, J¼7.0 Hz), 3.24 (4H, m), 3.05 (4H, s), 2.57 (8H, m),
1.68 (6H, d, J¼7.0 Hz); 13C NMR (100 MHz, CD3CN):
139.2 133.4, 130.5, 128.2, 127.2, 125.8, 125.3, 124.9, 122.8,
122.2, 71.7, 60.2, 56.3, 55.1, 43.7, 19.8; ES-MS: m/z 553.5
(Mþ), D1/8¼þ25 (at OD¼0.1, 225 nm); lmax/nm (CH3CN)
260.8 (1/dm3 mol21 cm21 10427) 281.6 (11801) 293.2
(6801.5); n/cm21 (KBr) 3287 (N–H); 2525, 2554 (ar
CvH); 1650 (CvO amide); 1602, 1511 (ar CvC); 1450
(C–N amide); 1357 (C–N crown ether); 1126 (C–O–C
crown ether).
4. Examples include: Gunnlaugsson, T.; Lee, C. T.; Parkesh, R.
Org. Lett. 2003, 5, 4065. Gunnlaugsson, T.; Lee, C. T.;
Parkesh, R. Org. Biomol. Chem. 2003, 1, 3265. He, H.;
Mortellaro, M. A.; Leiner, M. J. P.; Fraatz, R. J.; Tusa, J. K.
J. Am. Chem. Soc. 2003, 125, 1468. Tusa, J. K.; Leiner, M. J.
P. Ann. Biol. Clin-Paris 2003, 61, 183. Gunnlaugsson, T.;
Nieuwenhuyzen, M.; Richard, L.; Thoss, V. J. Chem. Soc.,
Perkin Trans. 2 2002, 141. de Silva, A. P.; Gunaratne, H. Q.
N.; Maguire, G. E. M. J. Chem. Soc., Chem. Commun. 1994,
1213. Bissell, R. A.; de Silva, A. P.; Gunaratne, H. Q. N.;
Lynch, P. L. M.; Maguire, G. E. M.; McCoy, C. P.;
Sandanayake, K. R. A. S. Top. Curr. Chem. 1993, 168, 223.
Huston, M. E.; Czarnik, A. W.; Engleman, C. J. Am. Chem.
4.3.2. Compound 2 (R,R). 0.18 g, 30.1% yield. Mp 107 8C.
Accurate mass: calcd for C34H40N4O3: found C34H41N4O3;
1H NMR (400 MHz, CDCl3): d 8.02 (2 ArH, d, J¼8.4 Hz),
7.67 (5 ArH, dd, J¼8.0 Hz), 7.53 (4H, d, Ar-H, J¼8 Hz),