10.1002/ejoc.202000066
European Journal of Organic Chemistry
FULL PAPER
Consecutive three-component synthesis of 3,5-disubstituted
pyrazole 4h. A typical procedure. In a thick-walled 10 mL microwave
tube with a magnetic stir bar were placed Pd2(dba)3 (5 mg, 0.5 mol%),
CataCXium® Ptb (6 mg, 2 mol%), nBu4NCl (278 mg, 1.00 mmol), aryl
bromide 1q (205 mg, 1.00 mmol), methyl vinyl ketone (2b) (105 mg,
1.50 mmol), NaHCO3 (92 mg, 1.1 mmol), and DMF (3 mL). The reaction
mixture was overlaid with a nitrogen atmosphere and reacted in a
microwave reactor at 100 °C for 4 h. Then, tosylhydrazide (372 mg, 2.00
mmol) and 95% H2SO4 (103 mg, 1.00 mmol) were added and reacted in
the microwave reactor at 80 °C for 1.5 h. Then, NaOH (132 mg, 3.30
mmol) was added to the reaction mixture and heated in the microwave
reactor at 100 °C for 4 h. After cooling to room temp, ethyl acetate (10
mL) was added and extracted with brine (3 10 mL). The aqueous layer
was then extracted with ethyl acetate (3 10 mL). The combined organic
phases were dried (anhydrous magnesium sulfate) and the solvents were
removed under reduced pressure. The residue was adsorbed on Celite®
and purified by column chromatography on silica gel (n-hexane/ethyl
acetate) to give compound 4h (202 mg, 98%) as a beige solid, Mp 111-
112 °C, Rf (n-hexane/ethyl acetate 1:1) = 0.27. 1H NMR (600 MHz,
CDCl3) 8.48 (s, 1H), 7.48 – 7.38 (m, 2H), 6.93 (t, JH-H = 8.5 Hz, 1H),
6.24 (s, 1H), 3.89 (s, 3H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3)
162.8 (Cquat), 152.5 (d, JC-F = 245.1 Hz, Cquat), 147.4 (d, JC-F = 10.8 Hz,
Cquat), 142.8 (Cquat), 126.2 (d, JC-F = 7.1 Hz, Cquat), 121.6 (d, JC-F = 3.5 Hz,
CH), 113.7 (d, JC-F = 19.5 Hz, CH), 113.6 (d, JC-F = 2.2 Hz, CH), 101.9
(CH), 56.4 (CH3), 11.6 (CH3); 19F NMR (565 MHz, CDCl3): -135.7; EI-
MS (70 eV, m/z (%)): 207 (13), 206 ([M]+, 100), 192 ([M - CH2]+, 12), 191
Keywords: Acrolein • Catalysis • Heck reaction • Heterocycles •
Multicomponent reactions • Palladium
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tube with a magnetic stir bar were placed Pd2(dba)3 (5 mg, 0.5 mol%),
CataCXium® Ptb (6 mg, 2 mol%), nBu4NCl (278 mg, 1.00 mmol), aryl
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microwave reactor at 100 °C for 8 h. Then, tosylhydrazide (372 mg, 2.00
mmol) and 95% H2SO4 (103 mg, 1.00 mmol) were added and reacted in
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mL) was added and extracted with brine (3 10 mL). The aqueous layer
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phases were dried (anhydrous magnesium sulfate) and the solvents were
removed under reduced pressure. The residue was adsorbed on Celite®
and purified by column chromatography on silica gel (n-hexane/ethyl
acetate) to give compound 5c (162 mg, 60%) as a colorless solid, Mp
171-172 °C, Rf (n-hexane/ethyl acetate 3:1) = 0.13. 1H NMR (600 MHz,
CDCl3) 7.32 (d, JH-H = 8.4 Hz, 1H), 7.29 (d, JH-H = 8.6 Hz, 1H), 7.23 (d,
JH-H = 8.6 Hz, 1H), 7.11 (d, JH-H = 8.4 Hz, 1H), 2.23 (s, 2H); 13C NMR
(150 MHz, CDCl3) 141.1 (Cquat), 133.9 (Cquat), 132.8 (Cquat), 131.7
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([37Cl-M]+, 64), 302 ([35Cl-M]+, 100), 301 ([35Cl-M - H]+, 39), 268 (14), 267
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The authors gratefully thank the Fonds der Chemischen
Industrie.
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