DOI: 10.1002/anie.201((will be filled in by the editorial staff))
Synthetic Methods
Supporting Information
General Experimental Procedures.
All reactions were carried out in 35 mL Schlenk tubes or in Carousel “reaction stations RR98030” Radley tubes, under a pure
and dry argon atmosphere. Methanol was distilled from magnesium/iodine and stored under argon atmosphere. Other solvents
were distilled and stored under argon atmosphere with classical technics. Tert-butylnitrite 90% (Acros), glacial acetic acid
99.5% (Carlo Erba), BF3.OEt2 (48% BF3 -Acros), CuI 99.5% (Aldrich), CuI metal basis 99.998% (Alfa Aesar), CuCl2 99%
(Acros), CuBr2 pure anhydrous 99% (Acros), Cu(acac)2 98% (Alfa Aesar), Cu(OTf)2 98% (Stream Chemicals), Cu(acetate)
99% (Stream Chemicals), Cu(acetate) anhydous 98% (Alfa Aesar), Cu(acetate)2 99.999% (Aldrich) and all other solid
materials were stored in the presence of P4O10 in a bench-top desiccator under vacuum at room temperature and weighed in the
air without further purification. Arylamines and nitrogene heterocycles were purchased from commercial sources. Column
chromatography was performed with SDS 60 A C.C silica gel (35-70 µm). Thin layer chromatography was carried out using
Merck silica gel 60 F254 plates. All products were characterized by NMR and GC/MS spectra. NMR spectra were recorded at
1
20°C on a Bruker AC 400 MHz or on a DRX-250 spectrometer working respectively at 400 MHz for H and at 100 MHz for
13C. Chemical shifts are reported in ppm/TMS for 1H and {1H}13C (δ 77.00 for CDCl3 signal). The first-order peak patterns are
indicated as s (singulet), d (doublet), t (triplet), q (quadruplet). Complex non-first-order signals are indicated as m (multiplet).
Gas chromatography – mass spectra GC-MS were recorded on a Shimadzu QP2012-SE instrument with a Zebron ZB-5ms
(20m x 0 ,18mm) capillary apolar column (stationary phase : 5% phenyl-arylene, 0.18µm). GC/MS method: Initial
temperature: 45°C; Initial time: 2 min; Ramp: 2°C/min until 50°C then 10 °C/min; Final temperature: 250°C; Final time: 10
min.
General procedure for synthesis of N-aryl heterocycles.
Protocol A (Table 2-3).
Standard procedure for the synthesis of arylazoles via in situ formation of arenediazonium salts intermediates: After standard
cycles of evacuation and back-filling with dry and pure argon, a Schlenk tube equipped with a magnetic stirring bar was
charged with aniline derivatives (1.5 mmol) under an atmosphere of dry argon. Methanol (3 ml) was added by syringe. The
solution was cooled at 0°C AcOH (0.2 equiv, 17µl) and t-BuONO (1.1 equiv, 176.6µl) were then added dropwise by syringe.
The resulting mixture was stirred at 0°C for 30 min, and was added to a mixture of pyrazole derivatives (1 mmol) and copper
acetate (20 mol%, 36,4 mg) in methanol (1.5 ml). The reaction mixture was stirred at 20°C for 18 h, filtered through a pad of
celite (5 g) and rinsed with ethyl acetate (20 ml). The resulting organic solution was washed with brine (3 x 10 ml). The
organic layer was dried over MgSO4, filtered, and concentrated (700 mbar, 40°C). The residue was further purified by flash
chromatography (SiO2, petroleum ether / ethyl acetate), yielding the corresponding arylazole.
Protocol B (Table 4).
Standard procedure for the synthesis of arylazoles via in situ formation of arenediazonium salts intermediates: After standard
cycles of evacuation and back-filling with dry and pure argon, a Schlenk tube equipped with a magnetic stirring bar was
charged with aniline derivatives (1.5 mmol) under an atmosphere of dry argon. Methanol (700 µl) was added by syringe. The
solution was cooled at 0°C and t-BuONO (1.1 equiv, 176.6µl) and AcOH (0.2 equiv, 17µl) were then added dropwise by
syringe. The resulting mixture was stirred at 0°C for 30 min and copper acetate (20 mol%, 36,4 mg) and Bu4NI (0.8 mmol)
were added in the medium. After 20 min at 90°C the nitrogen heterocycle (1 mmol) and Cs2CO3 (2 mmol, 2 equiv, 650 mg)
were added and the resulting reaction mixture was stirred at 120°C for 18 h. The resulting mixture was filtered through a pad
of celite (5 g) and rinsed with ethyl acetate (20 ml). The resulting organic solution was washed with brine (3 x 10 ml). The
organic layer was dried over MgSO4, filtered, and concentrated (700 mbar, 40°C). The residue was further purified by flash
chromatography (SiO2, dichloromethane / ethyl acetate), yielding the corresponding arylazole.
Toummini, Dounia
