4-Chloropyrazole

Chemical Properties

White to light yellow crystalline powder

Uses

4-Chloropyrazole serves as a starting material for the synthesis of 4-chloro-3,5-dinitropyrazole via nitration with sulfonitric acid[6]. It acts as a ligand in the stepwise photosubstitution reaction to synthesize the ruthenium complex cis-[Ru(bpy)2(Clpz)(ClpzH)]2+[7].

Synthesis

General method: synthesis of 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole. To a 16 mL reaction vial containing 1-benzyl-3,5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stirrer, 0.7 mL of water and 0.3 mL of ethyl acetate were added sequentially. Subsequently, sodium chloride (123 mg, 2 mmol) was added and the reaction flask was placed in a room temperature water bath to control the exothermic nature of the reaction. Next, Oxone (322 mg, 0.52 mmol KHSO5) was added and the reaction vial was sealed. The reaction was carried out under continuous vigorous stirring until thin layer chromatography (TLC) analysis (1 h) showed complete consumption of the feedstock. The remaining oxidant was reduced by addition of solid sodium bisulfite until starch iodide paper tested negative. The reaction mixture was diluted with water (5 mL) and extracted with a 1:1 hexane/ether solvent mixture (3 x 5 mL). The organic phases were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by fast column chromatography (14×1 cm, eluent 9:1 hexane/ethyl acetate) to afford pure 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole as a light yellow oil (215 mg, 93% yield).

References

[1] Canadian Journal of Chemistry,  1991,  vol. 69,  # 3,  p. 432 - 439
[2] Journal of Heterocyclic Chemistry,  2014,  vol. 51,  # 6,  p. 1621 - 1627
[3] Tetrahedron Letters,  2017,  vol. 58,  # 43,  p. 4111 - 4114
[4] Advanced Synthesis and Catalysis,  2013,  vol. 355,  # 2-3,  p. 499 - 507
[5] Angewandte Chemie - International Edition,  2016,  vol. 55,  # 52,  p. 16132 - 16135
[6] Feng, X.-Q., Cao, D.-L., Cui, J.-L. (2016). Synthesis and Thermal Decomposition Mechanism of the Energetic Compound 3,5-Dinitro-4-nitroxypyrazole. Journal of Energetic Materials, 34(3), 288–296. https://doi.org/10.1080/07370652.2015.1064491
[7] Hirahara, M., Iwamoto, A., Teraoka, Y., Mizuno, Y., Umemura, Y., Uekita, T. (2024). Ruthenium Pyrazole Complexes: A Family of Highly Active Metallodrugs for Photoactivated Chemotherapy. Inorganic Chemistry, 63(4), 1988–1996. https://doi.org/10.1021/acs.inorgchem.3c03716