3,5-Bis(trifluoromethyl)pyrazole

Chemical Properties

colorless to light yellow crystalline powder

Synthesis

Hexafluoroacetylacetone 1a (29.4 g, 20 mL, 141 mmol) and anhydrous ethanol (100 mL) were added to a 250 mL three-necked, round-bottomed flask fitted with a magnetic stirrer, a thermometer, an aqueous condenser tube and a constant-pressure dropping funnel. The reaction system was cooled to 5 °C in an ice-water bath. Hydrazine monohydrate (7.0 g, 6.8 mL, 140 mmol) was slowly added dropwise over a period of 20 min, controlling the reaction temperature to not exceed 8 °C. After the dropwise addition, the reaction mixture was heated to reflux for 8 hours. After completion of the reaction, it was cooled to room temperature and subsequently concentrated under reduced pressure on a rotary evaporator, controlling the temperature of the water bath not to exceed 40 °C, to give a yellow syrupy product. The product was dissolved in 98% concentrated sulfuric acid (10 mL) under cooling in an ice bath and vigorous stirring.After 15 min, the reaction mixture was carefully decanted into ice (300 g) to precipitate a light yellow solid, which was washed with ice water (50 mL) to afford 3,5-bis(trifluoromethyl)-1H-pyrazole 2 (25.13 g, 88% yield) as a colorless solid with a characteristic odor. The product characterization data were as follows: 1H NMR (DMSO-d6/CDCl3, 2:1): δ= 5.70 (brs, 1H, NH), 7.40 (s, 1H, H-4). 13C NMR: δ= 138.1 (q, 2JC-F = 39 Hz, C-3/C-5), 120.5 (q, 1JC-F = 267 Hz, CF3). 105.2 (s, C-4).19F NMR (DMSO-d6/CDCl3, 2:1): δ= -62.5 (s).IR (cm-1): 3160 (s), 1510, 1595 (s), 1150 (s).GC-MS (tR 6.78 min). Elemental Analysis (C5H2F6N2) Calculated: C, 29.43; N, 13.73. Measured: C, 29.44; N, 13.76. pKa 7.10 [Literature Value 25: 7.5]. Melting point 81°C [Literature Value 25: 83-84°C]. The purity of the sample was determined to be >98% by differential scanning calorimetry (DSC) (scan rate 2.58°C/min; melting point 85.2°C).

References

[1] Journal of Fluorine Chemistry, 2012, vol. 139, p. 53 - 57
[2] Journal of Fluorine Chemistry, 1991, vol. 51, # 2, p. 283 - 289
[3] Journal of Organic Chemistry, 2012, vol. 77, # 1, p. 47 - 56
[4] Helvetica Chimica Acta, 1995, vol. 78, # 4, p. 993 - 1000
[5] Journal of Fluorine Chemistry, 1993, vol. 65, # 1-2, p. 21 - 24