Generation of profluorescent isoindoline nitroxides using click chemistry

Article abstract of DOI:10.1021/jo200613r

Novel profluorescent nitroxides bearing a triazole linker between the coumarin fluorophore and an isoindoline nitroxide were prepared in good yields using the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction (CuAAC). Nitroxides containing 7-hydroxy and 7-diethylamino substitution on their coumarin rings displayed significant fluorescence suppression, and upon reaction with methyl radicals, normal fluorescence emission was returned. The fluorescence emission for the 7-hydroxycoumarin nitroxide and its diamagnetic analogue was found to be strongly influenced by pH with maximal fluorescence emission achieved in basic solution. Solvent polarity was also shown to affect fluorescence emission. The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic analogues makes these compounds ideal tools for monitoring processes involving free-radical species.

Full text of DOI:10.1021/jo200613r

The Generation of Profluorescent Isoindoline
Nitroxides using Click Chemistry
Jason C. Morris,†,‡ John C. McMurtrie,‡ Steven E. Bottle†,‡ and Kathryn E. Fairfull-Smith*,†,‡
‡
†ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Chemistry Discipline,
Faculty of Science and Technology, Queensland University of Technology, QLD, 4001, Australia.
SUPPORTING INFORMATION
Table of contents
1
Figure S1. 5-(1-Benzyl-1H-1,2,3-triazole-4-yl)-1,1,3,3,-tetramethylisoinsolin-2-yloxyl 5, H NMR
spectrum............................................................................................................................................. S3
Figure S2. 3-(4-(1,1,3,3-Tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-chromen-2-one
10, 1H NMR spectrum........................................................................................................................ S4
Figure S3. 7-Hydroxy-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 11, 1H NMR spectrum .............................................................................................. S5
Figure
S4.
6-Bromo-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 12, 1H NMR spectrum .............................................................................................. S6
Figure S5. 7-(Diethylamino)-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-
2H-chromen-2-one 13, 1H NMR spectrum........................................................................................ S7
Figure S6. 3-(4-(2-Methoxy-1,1,3,3-tetramethylisoindolin-5-yl)-1H-1,2,3-triazol-1-yl)-2H-chromen-
2-one 14, 1H NMR spectrum ............................................................................................................. S8
Figure S7. 7-Hydroxy-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 15, 1H NMR spectrum .................................................................................. S9
S1

Figure S8. 6-Bromo-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 16, 1H NMR spectrum ................................................................................ S10
Figure S9. 7-(Diethylamino)-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-
triazol-1-yl)-2H-chromen-2-one 17, 1H NMR spectrum ................................................................. S11
Figure
S10.
3-(4-(2-Methoxy-1,1,3,3-tetramethylisoindolin-5-yl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 14, 13C NMR spectrum........................................................................................... S12
Figure S11. 7-Hydroxy-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 15, 13C NMR spectrum............................................................................... S13
Figure S12. 6-Bromo-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 16, 13C NMR spectrum............................................................................... S14
Figure S13. 7-(Diethylamino)-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-
triazol-1-yl)-2H-chromen-2-one 17, 13C NMR spectrum ................................................................ S15
Figure S14. 5-(1-Benzyl-1H-1,2,3-triazole-4-yl)-1,1,3,3,-tetramethylisoinsolin-2-yloxyl 5, HPLC
chromatogram .................................................................................................................................. S16
Figure S15. 3-(4-(1,1,3,3-Tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-chromen-2-one
10, HPLC chromatogram................................................................................................................. S17
Figure S16. 7-Hydroxy-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 11, HPLC chromatogram........................................................................................ S18
Figure
S17.
6-Bromo-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 12, HPLC chromatogram........................................................................................ S19
Figure S18. 7-(Diethylamino)-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-
2H-chromen-2-one 13, HPLC chromatogram ................................................................................. S20
S2

5-(1-Benzyl-1H-1,2,3-triazole-4-yl)-1,1,3,3,-tetramethylisoinsolin-2-yloxyl 5, 1H NMR spectrum
(400 MHz, CDCl3)
S3

Figure S2. 3-(4-(1,1,3,3-Tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-chromen-2-one
10, 1H NMR spectrum (400 MHz, d6-DMSO)
S4

Figure S3. 7-Hydroxy-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 11, 1H NMR spectrum (400 MHz, d6-DMSO)
S5

Figure S4. 6-Bromo-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 12, 1H NMR spectrum (400 MHz, d6-DMSO)
S6

Figure S5. 7-(Diethylamino)-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-
2H-chromen-2-one 13, 1H NMR spectrum (400 MHz, d6-DMSO)
S7

Figure S6. 3-(4-(2-Methoxy-1,1,3,3-tetramethylisoindolin-5-yl)-1H-1,2,3-triazol-1-yl)-2H-chromen-
2-one 14, 1H NMR spectrum (400 MHz, d6-DMSO)
S8

Figure S7. 7-Hydroxy-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 15, 1H NMR spectrum (400 MHz, d6-DMSO)
S9

Figure S8. 6-Bromo-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 16, 1H NMR spectrum (400 MHz, d6-DMSO)
S10

Figure S9. 7-(Diethylamino)-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-
triazol-1-yl)-2H-chromen-2-one 17, 1H NMR spectrum (400 MHz, CDCl3)
S11

Figure S10. 3-(4-(2-Methoxy-1,1,3,3-tetramethylisoindolin-5-yl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 14, 13C NMR spectrum (100 MHz, d6-DMSO)
S12

Figure S11. 7-Hydroxy-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 15, 13C NMR spectrum (100 MHz, d6-DMSO)
S13

Figure S12. 6-Bromo-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-
yl)-2H-chromen-2-one 16, 13C NMR spectrum (100 MHz, d6-DMSO)
S14

Figure S13. 7-(Diethylamino)-3-(4-(2-methoxy-1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-
triazol-1-yl)-2H-chromen-2-one 17, 13C NMR spectrum (100 MHz, CDCl3)
S15

Figure S14. 5-(1-Benzyl-1H-1,2,3-triazole-4-yl)-1,1,3,3,-tetramethylisoinsolin-2-yloxyl 5, HPLC
chromatogram.
S16

Figure S15. 3-(4-(1,1,3,3-Tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-chromen-2-
one 10, HPLC chromatogram.
S17

Figure S16. 7-Hydroxy-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 11, HPLC chromatogram.
S18

Figure S17.
6-Bromo-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-2H-
chromen-2-one 12, HPLC chromatogram.
S19

Figure S18. 7-(Diethylamino)-3-(4-(1,1,3,3-tetramethylisoindolin-2-yloxyl)-1H-1,2,3-triazol-1-yl)-
2H-chromen-2-one 13, HPLC chromatogram.
NEt2
O
O
N
N
N
N
O
13
S20