* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 2, p. 389 - 396
[2] Patent: CN103951663, 2016, B,
2
[ 372-31-6 ]
[ 60-34-4 ]
[ 1481-02-3 ]
Yield
Reaction Conditions
Operation in experiment
85.8%
at 50℃; for 5 h;
0.1 ml of methyl hydrazine and 250 mL three-necked flask, add 10 mL of anhydrous ethanol, stirring heated to 50 C , dropwise 0. 1moL ethyl trifluoroacetoacetate, heating reflux 5 h, cooling crystallization , Vacuum filtration, drying, in a yellow solid; Yield: 85.8percent.
Reference：
[1] Patent: CN103951663, 2016, B, . Location in patent: Paragraph 0091; 0092; 0093
[2] Australian Journal of Chemistry, 2010, vol. 63, # 5, p. 785 - 791
With potassium tert-butylate; In sulfolane; at 20 - 130℃; for 3h;
EXAMPLE 1 2-(1-Methyl-3-trifluoromethylpyrazol-5-yloxy)-6-(but-2-enoyl-aminomethyl)-pyridine [0138] 1a) 2-(1-Methyl-3-trifluoromethylpyrazol-5-yloxy)-6-cyanopyridine [0139] 4.00 g (240 mmol) of 1-methyl-3-(trifluoromethyl)-2-pyrazol-2-one were introduced into 40 ml of sulfolane under a nitrogen atmosphere and at room temperature 2.70 g (24.0 mmol) of potassium tert-butoxide were added in portions to this initial charge. Then 2.56 g (18.5 mmol) of <strong>[33252-29-8]2-chloro-6-cyanopyridine</strong> were added and the solution was heated at 130 C. for 3 h, cooled to room temperatured and poured into ice-water. The precipitate was filtered off, washed repeatedly with water and then dried. [0140] Yield 4.26 g (86%); melting point 87 C.[0141] 1b) 2-(1-Methyl-3-trifluoromethylpyrazol-5-yloxy)-6-(aminomethyl)-pyridine [0142] 7.00 g (26.1 mmol) of 2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-6-cyanopyridine were dissolved in 150 ml of glacial acetic acid, admixed with 1.40 g of Pd(OH)2, 20% on charcoal, and hydrogenated under a hydrogen overpressure of 17 bar. After 2 h, the catalyst was removed by filtration and the filtrate was concentrated by evaporation. The residue was taken up in water, admixed with 20 ml of 2 N HCl and subjected to multiple extraction with ethyl acetate. The aqueous phase was subsequently adjusted to a pH of 10 using 2 N NaOH and then subjected to multiple extraction with ethyl acetate. The combined organic extracts were then dried using MgSO4, filtered and concentrated. [0143] Yield 2.58 g (34%); melting point: 44 C. [0144] 1c) 2-(1-Methyl-3-trifluoromethylpyrazol-5-yloxy)-6-(but-2-enoyl-aminomethyl)-pyridine [0145] 0.100 g (0.368 mmol) of 2-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)-6-(aminomethyl)-pyridine was introduced in 5 ml of methylene chloride together with 71.1 mg (0.55 mmol) of diisopropylethylamine, at room temperature 46.1 mg (0.44 mmol) of but-2-enoyl chloride were added and the mixture was stirred at room temperature for 3 h. The crude product was concentrated, subjected to extraction with 1 N HCl and ethyl acetate and then filtered over a silica gel bed. The filtrate was concentrated. The residue was crystalline. [0146] Yield 0.059 g (47%); melting point 75 C.
With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 100℃; for 36h;
1. Preparation of 3-fluoro-5-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)nitrobenzene Under an atmosphere of nitrogen, 30.00 g (189 mmol) of <strong>[2265-94-3]3,5-difluoronitrobenzene</strong> were initially charged in 150 ml of N,N-dimethylformamide, and 28.67 g (207 mmol) of K2CO3 and 31.32 g (189 mmol) of 1-methyl-3-(trifluoromethyl)pyrazol-5-one were added at room temperature (RT). The mixture was heated at 85 C. for 33 h and at 100 C. for a further 3 h and then cooled to RT, and water was added to the reaction solution. The mixture was extracted three times with ethyl acetate. The combined phases were washed with water and then dried over MgSO4, filtered and concentrated. Column chromatography of the crude product gave 9.00 g of 3-fluoro-5-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)nitrobenzene in the form of an orange-red oil. 1H-NMR: delta[CDCl3] 3.84 ppm (s, 3H), 6.07 (s, 1H), 7.20 (dt, 1H), 7.80 (m, 2H)
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 20℃; for 1h;
Stage #2: 2,4-dihydro-2-methyl-5-trifluoromethyl-3H-pyrazol-3-one at 50 - 90℃; for 10h;
45.7%
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.333333h;
Stage #2: 2,4-dihydro-2-methyl-5-trifluoromethyl-3H-pyrazol-3-one at 80 - 90℃; for 5h;
1.2 (2) Preparation of 1-methyl-3-trifluoromethyl-5-chloro-4-pyrazolealdehyde intermediate:
To a 250 mL three-necked flask, 0.35 mol of DMF was added. At 0 ° C, 0.83 mol POCl was slowly added dropwiseAfter stirring for 20 min, 0.10 mol of 1-methyl-3-trifluoromethyl-5-pyrazolone was slowly added and the temperature was raised to 80 to 90° C reaction 5h, slowly cooled into 200 mL of ice water, standing 2 h, filtration, washing, drying, in yellow solid Yield: 45.7%.
2.2.2. FTIR spectroscopy
General procedure: The CT interaction between the donor (FP) and each acceptorwas examinedby IR spectroscopy using a Tracer-100 Shimadzu Fourier TransformInfrared (FTIR) Spectrophotometer. For this purpose, 1 mmol of FPdonorwas dissolved in 15 mL of methanol andmixed with 15 mL methanolicsolution containing 1 mmol of the acceptor (PA, CLA, TFQ, DDQ, orTCNQ). Color changes were observed upon mixing, as pictured in Fig. 2.After stirring the resultant five mixtures for 15-20 min at room temperature,solid, colored precipitates were harvested by slow evaporation.These colored precipitates were isolated, filtered, thoroughly washedwith methanol, and dried in a vacuum using CaCl2 (anhydrous). The PAformed a yellow-colored powder, CLA formed a reddish-brown-coloredpowder, TFQ formed an orange-colored powder, DDQ formed a reddishbrown-colored powder, and TCNQ formed a green-colored powder. TheFTIR spectra of the synthesized CTCs were collected and plotted in transmissionmodeover the 4000 to 400 cm-1 range at room temperature.
2.2.2. FTIR spectroscopy
General procedure: The CT interaction between the donor (FP) and each acceptorwas examinedby IR spectroscopy using a Tracer-100 Shimadzu Fourier TransformInfrared (FTIR) Spectrophotometer. For this purpose, 1 mmol of FPdonorwas dissolved in 15 mL of methanol andmixed with 15 mL methanolicsolution containing 1 mmol of the acceptor (PA, CLA, TFQ, DDQ, orTCNQ). Color changes were observed upon mixing, as pictured in Fig. 2.After stirring the resultant five mixtures for 15-20 min at room temperature,solid, colored precipitates were harvested by slow evaporation.These colored precipitates were isolated, filtered, thoroughly washedwith methanol, and dried in a vacuum using CaCl2 (anhydrous). The PAformed a yellow-colored powder, CLA formed a reddish-brown-coloredpowder, TFQ formed an orange-colored powder, DDQ formed a reddishbrown-colored powder, and TCNQ formed a green-colored powder. TheFTIR spectra of the synthesized CTCs were collected and plotted in transmissionmodeover the 4000 to 400 cm-1 range at room temperature.
2.2.2. FTIR spectroscopy
General procedure: The CT interaction between the donor (FP) and each acceptorwas examinedby IR spectroscopy using a Tracer-100 Shimadzu Fourier TransformInfrared (FTIR) Spectrophotometer. For this purpose, 1 mmol of FPdonorwas dissolved in 15 mL of methanol andmixed with 15 mL methanolicsolution containing 1 mmol of the acceptor (PA, CLA, TFQ, DDQ, orTCNQ). Color changes were observed upon mixing, as pictured in Fig. 2.After stirring the resultant five mixtures for 15-20 min at room temperature,solid, colored precipitates were harvested by slow evaporation.These colored precipitates were isolated, filtered, thoroughly washedwith methanol, and dried in a vacuum using CaCl2 (anhydrous). The PAformed a yellow-colored powder, CLA formed a reddish-brown-coloredpowder, TFQ formed an orange-colored powder, DDQ formed a reddishbrown-colored powder, and TCNQ formed a green-colored powder. TheFTIR spectra of the synthesized CTCs were collected and plotted in transmissionmodeover the 4000 to 400 cm-1 range at room temperature.
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