The Journal of Organic Chemistry
Note
equiv), and 30% KHCO3 (8.27 mmol, 2.76 mL, 8.66 equiv) were used.
Filtration afforded 3 (220 mg, 64%) as a white solid.
CDCl3) δ 21.5, 100.8, 126.40, 126.49, 128.5, 130.4, 131.5, 136.4,
154.7, 171.0; HRMS (ESI) calcd for C20H16N2O2Na [M+Na]+
339.1104. Found 339.1097; UV−vis, 10 μM dichloromethane solution,
λmax = 250 nm, ε = 16000 M−1 cm−1; Fluorescence, 10 μM
dichloromethane solution, λmax = 327 nm (irradiated at 275 nm).
5,5′-Di-(4-methylphenyl)-3,3′-bisisoxazole (8). Method A. Di-
chloroglyoxime (75.0 mg, 0.47 mmol, 1.0 equiv), 4-ethynyltoluene
(127 mg, 1.09 mmol, 2.30 equiv), and 30% KHCO3 (4.13 mmol, 1.38
mL, 8.60 equiv) were used. Filtration afforded 8 (130 mg, 86%) as a
light brown solid.
Method B. Dichloroglyoxime (150 mg, 0.95 mmol, 1.0 equiv), 1-
decyne (396 mg, 2.86 mmol, 3.0 equiv), and 30% KHCO3 (8.27
mmol, 2.76 mL, 8.66 equiv) were used. Flash chromatography (5%
EtOAc/petrol) afforded 3 (229 mg, 66%) as colorless crystals. Data for
3: mp 69−70 °C; 1H NMR (500 MHz, CDCl3) δ 0.87−0.85 (6H, t, J
= 5.5 Hz), 1.33−1.23 (16H, m), 1.38−1.32 (4H, m), 1.74−1.69 (4H,
m), 2.78 (4H, t, J = 6.5 Hz), 6.46 (2H, s); 13C NMR (125 MHz,
CDCl3) δ 14.0, 22.6, 26.6, 27.3, 28.9, 29.0, 29.1, 31.7, 99.0, 154.4,
174.8; HRMS (ESI) calcd for C22H36N2O2Na [M+Na]+ 383.2669.
Found 383.2670.
5,5′-Dicyclohexyl-3,3′-bisisoxazole (4). Method A. Dichloroglyox-
ime (75.0 mg, 0.47 mmol, 1.0 equiv), cyclohexylacetylene (119 mg,
1.09 mmol, 2.30 equiv), and 30% KHCO3 (4.13 mmol, 1.38 mL, 8.60
equiv) were used. Filtration afforded 4 (95 mg, 66%) as a yellow−
white solid.
Method B. Dichloroglyoxime (75.0 mg, 0.47 mmol, 1.0 equiv),
cyclohexylacetylene (119 mg, 1.09 mmol, 2.30 equiv), and 30%
KHCO3 (4.13 mmol, 1.38 mL, 8.60 equiv) were used. Flash
chromatography (5% EtOAc/petrol) afforded 4 (100 mg, 69%) and
the 4,5′-regioisomer (9.85 mg, 6.9%) as colorless crystals. Data for 4:
mp 152−153 °C; 1H NMR (500 MHz, CDCl3) δ 1.32−1.26 (2H, m),
1.37 (2H, tt, J = 3.0, 12.5 Hz), 1.57−1.43 (6H, m), 1.75−1.71 (2H,
m), 1.82 (4H, dt, J = 3.5, 13.0 Hz), 2.08 (4H, dd, J = 3.5, 13.5 Hz),
2.83 (2H, tt, J = 3.0, 10.5 Hz), 6.44 (2H, d, J = 0.5 Hz); 13C NMR
(125 MHz, CDCl3) δ 25.7, 25.8, 31.2, 36.4, 97.6, 154.5, 178.9; HRMS
(ESI) calcd for C18H25N2O2 [M+H]+ 301.1910. Found 301.1914.
5,5′-Diphenyl-3,3′-bisisoxazole (5). Method A. Dichloroglyoxime
(358 mg, 2.28 mmol, 1.0 equiv), phenylacetylene (699 mg, 6.85 mmol,
3.0 equiv), and 30% KHCO3 (19.7 mmol, 9.20 mL, 8.66 equiv) were
used. Filtration afforded 5 (610 mg, 93%) as a white solid.
Method B. Dichloroglyoxime (358 mg, 2.28 mmol, 1.0 equiv),
phenylacetylene (699 mg, 6.85 mmol, 3.0 equiv), and 30% KHCO3
(19.7 mmol, 9.20 mL, 8.66 equiv) were used. Flash chromatography
(5% EtOAc/petrol) afforded 5 (592 mg, 90%) as colorless crystals; mp
195−196 °C; lit.17 199 °C; 1H NMR (500 MHz, CDCl3) δ 7.09 (2H,
s), 7.53−7.47 (6H, m), 7.87−7.85 (4H, m); 13C NMR (125 MHz,
CDCl3) δ 97.8, 126.1, 129.2, 130.8, 155.1, 171.2, 155.1; HRMS (ESI)
calcd for C18H12N2O2Na [M+Na]+ 311.0791. Found 311.0796; UV−
vis, 10 μM dichloromethane solution, λmax = 272 nm, ε = 54000 M−1
cm−1.
Method B. Dichloroglyoxime (75.0 mg, 0.47 mmol, 1.0 equiv), 4-
ethynyltoluene (127 mg, 1.09 mmol, 2.30 equiv), and 30% KHCO3
(4.13 mmol, 1.38 mL, 8.60 equiv) were used. Flash chromatography
(10% EtOAc/petrol) afforded 8 (92 mg, 61%) as a colorless crystals;
mp 249−250 °C; lit.15 251−253 °C; H NMR (500 MHz, CDCl3) δ
1
2.42 (6H, s), 7.02 (2H, s), 7.30 (4H, dd, J = 0.5, 8.0 Hz), 7.74 (4H, dd,
J = 1.5, 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ 21.6, 97.2, 124.4,
126.0, 129.9, 141.1, 155.1, 171.3; HRMS (ESI) calcd for
C20H16N2O2Na [M+Na]+ 339.1104. Found 339.1129; UV−vis, 10
μM dichloromethane solution, λmax = 277 nm, ε = 50000 M−1 cm−1;
Fluorescence, 10 μM dichloromethane solution, λmax = 370 nm
(irradiated at 300 nm).
5,5′-Di-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxymethyl)-
3,3′-bisisoxazole (9). Method A. Not successful.
Method B. Dichloroglyoxime (50.0 mg, 0.31 mmol, 1.0 equiv),
propargyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside33 (283 mg, 0.73
mmol, 2.30 equiv), and 30% KHCO3 (2.75 mmol, 0.92 mL, 8.60
equiv) were used. Flash chromatography (50−70% EtOAc/petrol)
1
afforded 9 (174 mg, 64%) as an amorphous solid; H NMR (500
MHz, CDCl3) δ 1.99 (6H, s), 2.05 (6H, s), 2.11 (6H, s), 2.16 (6H, s),
4.02−4.07 (2H, m), 4.09 (2H, dd, J = 2.5, 12.5 Hz), 4.29 (2H, dd, J =
5.5, 12.5 Hz), 4.81 (4H, q, J = 14.0 Hz), 4.98 (2H, d, J 2.0 Hz), 5.28−
5.35 (6H, m), 6.85 (2H, s); 13C NMR (125 MHz, CDCl3) δ 20.7,
20.83, 20.88, 20.9, 60.1, 62.4, 68.8, 69.32, 69.36, 97.6, 102.4, 154.3,
168.7, 169.8, 169.9, 170.0, 170.7; HRMS (ESI) calcd for
C36H44N2O22Na [M+Na]+ 879.2278. Found 879.2269.
4,4′,5,5′-Tetramethoxycarbonyl-3,3′-bisisoxazole (10). Method
A. Dichloroglyoxime (75.0 mg, 0.47 mol, 1.0 equiv), dimethylacetylene
dicarboxylate (156 mg, 1.09 mmol, 2.30 equiv), and 30% KHCO3
(4.13 mmol, 1.38 mL, 8.60 equiv) were used. Filtration afforded 10
(119 mg, 77%) as a yellow−white solid.
Method B. Dichloroglyoxime (75.0 mg, 0.47 mol, 1.0 equiv),
dimethylacetylene dicarboxylate (156 mg, 1.09 mmol, 2.30 equiv), and
30% KHCO3 (4.13 mmol, 1.38 mL, 8.60 equiv) were used. Flash
chromatography (5% EtOAc/petrol) afforded 10 (141 mg, 91%) as
5,5′-Di-(4-fluorophenyl)-3,3′-bisisoxazole (6). Method A. Dichlor-
oglyoxime (115 mg, 0.73 mmol, 1.0 equiv), 1-ethynyl-4-fluorobenzene
(262 mg, 2.18 mmol, 3.0 equiv), and 30% KHCO3 (6.25 mmol, 2.08
mL, 8.60 equiv) were used. Filtration afforded 6 (190 mg, 80%) as a
yellow−white solid.
colorless crystals; mp 164−166 °C; lit.17 167−168; H NMR (500
1
MHz, CDCl3) δ 3.84 (6H, s), 4.05 (6H, s); 13C NMR (125 MHz,
CDCl3) δ 53.2, 53.8, 115.9, 152.1, 156.0, 159.6, 160.9; HRMS (ESI)
calcd for C14H12N2O10Na [M+Na]+ 391.0384. Found 391.0386.
[Ir(ppy)2(5,5′-diphenyl-3,3′-bisisoxazole)]BF4 (11). A solution of
silver tetrafluoroborate (18.2 mg, 93 μmol) and [Ir(ppy)2Cl]2 (50 mg,
47 μmol) in acetonitrile (10 mL) was stirred in the dark for 3 h. The
solution was filtered and the filtrate evaporated to dryness under
reduced pressure. The yellow solid residue was added to 5,5′-diphenyl-
3,3′-bisisoxazole (27 mg, 94 μmol) in 2-ethoxyethanol (3 mL) and the
mixture was heated at reflux under an inert atmosphere overnight. The
mixture was cooled to room temperature and water (5 mL) was added.
The precipitate was collected by filtration and washed with ether (10
mL) then pentane (10 mL) to give 11 as a brown solid (43 mg, 53%).
A sample for analysis was prepared by recrystallization from
dichloromethane/pentane. Single crystals suitable for X-ray analysis
were grown by evaporation of a dichloromethane/pentane solvent
Method B. Dichloroglyoxime (115 mg, 0.73 mmol, 1.0 equiv), 1-
ethynyl-4-fluorobenzene (262 mg, 2.18 mmol, 3.0 equiv), and 30%
KHCO3 (6.25 mmol, 2.08 mL, 8.60 equiv) were used. Flash
chromatography (10% EtOAc/petrol) afforded 6 (158 mg, 69%)
and the 4,5′-regioisomer (5 mg, 2.0%) as yellow crystals. Data for 6:
1
mp 257−259 °C; H NMR (500 MHz, CDCl3) δ 7.03 (2H, s); 7.21
(4H, t, J = 8.5 Hz), 7.85 (4H, dd, J = 5.5, 8.5 Hz); 13C NMR (125
MHz, CDCl3) δ 97.6, 116.4, 116.6, 123.4, 128.3, 155.1, 163.2, 165.2,
170.2; HRMS (ESI) calcd for C18H10F2N2NaO2 [M+Na]+ 347.0603.
Found 347.0611; UV−vis, 10 μM dichloromethane solution, λmax
=
271 nm, ε = 46000 M−1 cm−1.
5,5′-Di-(2-methylphenyl)-3,3′-bisisoxazole (7). Method A. Di-
chloroglyoxime (100 mg, 0.64 mmol, 1.0 equiv), 2-ethynyl toluene
(317 mg, 1.91 mmol, 3.0 equiv), and 30% KHCO3 (5.51 mmol, 1.84
mL, 8.60 equiv) were used. Filtration afforded 7 (153 mg, 76%) as a
yellow−white solid.
1
solution. H NMR (CDCl3, 500 MHz) δ 6.30 (2H, dd, J = 7.6, 1.0
Hz), 6.92 (2H, td, J = 7.5, 1.3 Hz), 7.06 (2H, td, J = 7.6, 1.2 Hz), 7.13
(2H, ddd, J = 7.3, 5.9, 1.4 Hz), 7.43−7.47 (6H, m), 7.67 (2H, dd, J =
7.9, 1.2 Hz), 7.79 (4H, dd, J = 8.0, 1.7 Hz), 7.82−7.85 (4H, m), 7.94
(2H, dd, J = 8.7, 1.3 Hz), 8.28 (2H, s); 13C NMR (CDCl3, 126 MHz)
δ 101.7, 119.7, 123.4, 123.7, 124.5, 125.4, 126.8, 129.4, 130.3, 132.0,
132.2, 138.6, 142.6, 144.2, 150.2, 156.5, 167.9, 174.6; HRMS (ESI)
calcd for C40H28N4O2Ir [M]+ 789.1842. Found 789.1844. Calcd for
Method B. Dichloroglyoxime (100 mg, 0.64 mmol, 1.0 equiv), 2-
ethynyl toluene (317 mg, 1.91 mmol, 3.0 equiv), and 30% KHCO3
(5.51 mmol, 1.84 mL, 8.60 equiv) were used. Flash chromatography
(5% EtOAc/petrol) afforded 7 (190 mg, 94%) and the 4,5′-
regioisomer (7.4 mg, 4%) as colorless crystals. Data for 7: mp 121−
1
123 °C; H NMR (500 MHz, CDCl3) δ 2.58 (6H, s), 7.02 (2H, s),
7.33−7.41 (6H, m), 7.79−7.81 (2H, m); 13C NMR (125 MHz,
E
dx.doi.org/10.1021/jo4008755 | J. Org. Chem. XXXX, XXX, XXX−XXX