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J. Balog et al. / Tetrahedron Letters 52 (2011) 5264–5266
(1H,dd, J = 7.5, 6.9 Hz, H-7), 7.48–7.38 (2H, m, H-8, H-6), 7.89 (1H, d, J = 8.5 Hz,
These results indicate that the prepared compounds represent a
H-5); dC (75 MHz, CDCl3): 52.0 (C-20,C-60), 67.3 (C-30, C-50), 94.5 (C-4), 116.4 (C-
8a), 122.1 (C-5), 125.6 (C-7), 125.7 (C-8), 129.9 (C-6), 141.5 (C-4a), 152.8 (C-3),
161.2 (C-1). m/z (EI): 230.3 (M+H); Anal. calcd for C13H15N3O (229.27): C,
68.10; H, 6.59; N, 18.33. Found: C, 68.01; H, 6.70; N, 18.25. 4-methyl-1-
morpholinoisoquinoline-3-amine (6b): Yield: 55%; yellow crystals; mp: 143–
145 °C; mmax (KBr, cmꢀ1) 3365, 2957, 1633, 1564, 1114, 755; dH (300 MHz,
CDCl3): 2.30 (3H, s, H-4-CH3), 3.33 (4H, t, J = 9.1 Hz, H-20,H-60), 3.95 (4H, t,
J = 9.2 Hz, H-30, H-50), 4.26 (2H, s, NH2), 7.19 (1H, dd, J = 7.5, 7.8 Hz, H-7), 7.51
(1H, dd, J = 7.8, 7.5 Hz, H-6), 7.72 (1H, d, J = 8.5 Hz, H-8), 7.99 (1H, d, J = 8.4 Hz,
new valuable group of fluorescent isoquinoline derivatives. Com-
parison of the fluorescence spectra of the variously substituted
derivatives shows some significant changes as a consequence of
structural variations.
Acknowledgments
H-5); dC (75 MHz, CDCl3): 11.5 (Ca
), 52.2 (C-20,C-60), 67.4 (C-30,C-50), 99.5 (C-4),
The support of OTKA 77784, K75015, Nanotransport (CRC-HAS-
2009) and Hungarian GVOP-3.2.1.-2004-04-0210/3.0 projects are
gratefully acknowledged.
117.0 (C-8a), 121.6 (C-5), 122.3 (C-7), 126.1 (C-8), 129.8 (C-6), 139.8 (C-4a),
150.2 (C-3), 159.3 (C-1). m/z (EI): 244.3 (M+H); Anal. calcd for C14H17N3O
(243.30): C, 69.11; H, 7.04; N, 17.27. Found: C, 69.01; H, 7.15; N, 17.32. 4-
benzyl-1-morpholinoisoquinoline-3-amine (6c): Yield: 60%; pale brown
crystals; mp 82–84 °C; mmax (KBr, cmꢀ1): 3353, 2844, 1614, 1561, 1112, 762;
dH (300 MHz, CDCl3): 3.39 (4H, s, H-20,H-60), 3.97 (4H, s, H-30,H-50), 4.18 (4H, s,
H-4-CH2, NH2), 7.16-7.26 (6H, m, H-2,H-300,H-400,H-500,H-600, H-7), 7.48 (1H, dd,
J = 7.5, 7.2 Hz, H-6), 7.72 (1H, d, J = 8.5 Hz, H-8), 8.02 (1H, d, J = 8.3 Hz, H-5); dC
Supplementary data
Supplementary data (analytical data including 1H and 13C NMR
spectral assignments, UV and fluorescence spectra for the most
important compounds as well as absorption and fluorescence spec-
tra of selected compounds) associated with this article can be
(75 MHz, CDCl3+DMSO-d6): 31.7 (Ca
), 52.1 (C-20,C-60), 67.3 (C-30,C-50), 102.2
(C-4), 116.9 (C-8a), 121.7 (C-5), 122.3 (C-7), 126.2 (C-400), 126.5 (C-8), 128.3 (C-
300,C-500), 128.9 (C-200,C-600), 130.2 (C-6), 139.5 (C-100), 140.1 (C-4a), 150.9 (C-3),
160.0 (C-1). m/z (EI): 320.4 (M+H); Anal. calcd for C20H21N3O (319.40): C,
75.21; H, 6.63; N, 13.16. Found: C, 75.15; H, 6.42; N, 12.85.
7. A mixture of the appropriate isoquinoline-amine derivative (3 or 6, 1 mmol), p-
TsOH (0.1 mol) and triethyl orthoformate (5 ml) was heated under reflux for
16 h with stirring. Excess triethyl orthoformate was removed by vacuum
distillation, 8% aqueous NaHCO3 solution (20 ml) was added and the product
was extracted with CH2Cl2 (2 ꢂ 20 ml). The organic layer was dried over
anhydrous Na2SO4, filtered, and concentrated to yield the crude product as a
yellow solid (75–90%) which was recrystallized from i-PrOH.
8. To a solution of formimidate derivative (4 or 7, 1 mmol) in dry toluene (5 ml)
was added morpholine (2 mmol). The solution was heated at 100 °C for 1 h
with stirring. After evaporation of the solvent the residue was dissolved in
CH2Cl2 (20 ml) and the solution washed with H2O (20 ml). The aqueous phase
was extracted with CH2Cl2 (2 ꢂ 20 ml) and the collected organic phase dried
over anhydrous Na2SO4. The solution was filtered, evaporated, and the crude
product (80–90%) recrystallized from i-PrOH.
References and notes
1. Riedl, Zs.; Filák, L.; Egyed, O.; Hajós, G. Arkivoc 2009, vi, 158.
2. Filák, L.; Riedl, Z.; Egyed, O.; Czugler, M.; Hoang, C. N.; Schantl, J. G.; Hajós, G.
Tetrahedron 2008, 64, 1101.
3. Tímári, G.; Soós, T.; Hajós, G.; Messmer, A.; Nacsa, J.; Molnár, J. Bioorg. Med.
Chem. Lett. 1996, 23, 2831.
4. Zdrojewski, T.; Jonczyk, A. Tetrahedron 1995, 51, 12439.
5. (a) Isoquinoline 3-triflate (1) (150 mg, 0.54 mmol) was dissolved in morpholine
(1 ml) and the solution was heated at 130 °C for 6 h with stirring. After cooling,
CH2Cl2 (10 ml) was added and the mixture was washed with H2O (2 ꢂ 10 ml).
The organic layer was dried over anhydrous Na2SO4 and concentrated. The
residue was purified by flash column chromatography on silica gel to give
bright yellow crystals of 2, 86 mg (75%), mp 124–126 °C (Lit mp 126–
127.5 °C4); (b) A similar procedure was applied for the transformation of 3a–
9. The fluorescence quantum yield was determined relative to that of quinine
sulfate in 1 N H2SO4, for which a reference yield of Uf = 0.546 was taken.10
Fluorescence lifetimes were measured using time-correlated single-photon
counting as described previously.11
c
into 6a–c. Thus, a solution of 1-bromoisoquinoline-3-amine 3a (0.22 g,
10. Melhuish, W. H. J. Phys. Chem. 1961, 65, 229.
1 mmol) in morpholine (2 ml) was refluxed for 24 h. The reaction mixture was
evaporated, H2O (10 ml) was added and the precipitated solid was filtered.
Recrystallization from EtOH yielded 0.1 g (45%) of product 6a, mp 151–154 °C.
6. Analytical and spectral data of 6a–c: 1-morpholinoisoquinoline-3-amine (6a):
11. Megyesi, M.; Biczók, L.; Jablonkai, I. J. Phys. Chem. C. 2008, 112, 3410.
12. Wan, Y.; Niu, W.; Behof, W. J.; Wang, Y.; Boyle, P.; Gorman, C. B. Tetrahedron
2009, 65, 4293.
13. Locations of all absorption maxima in nm for the compounds listed in Table 1:
3d: 207, 234, 281, 291, 363; 2: 209, 243, 290, 366; 6a: 205, 239, 301, 371; 6c:
204, 240, 305, 377; 6b: 207, 239, 305, 377; 5b: 217, 264, 273, 318, 372; 5c: 214,
264, 273, 320, 370; 5f: 213, 262, 270, 314, 363; 8b: 212, 264, 272, 327, 370.
Yield: 45%; brownish yellow crystals; mp 151–154 °C; m
max (KBr, cmꢀ1): 3348,
2847, 1638, 1557, 1109, 858; dH (300 MHz, CDCl3): 3.38 (4H, tt, J = 9.2 Hz, H-20,
H-60), 3.94 (4H, tt, J = 9.2 Hz, H-30, H-50), 4.26 (2H, NH2), 6.36 (1H, s, H-4), 7.15