Benzaldehyde → 1-Benzyl-1H-pyrazol-5-amine

Participants

Reaction Steps

A solution of hydrazine hydrate (14.55 mL, 300 mmol) and ethanol (75 mL) was cooled in an ice water bath and then 2-propenenitrile (15.3 g, 288 mmol) was added dropwise. After stirring at room temperature for 2 h, benzaldehyde (31.8 g, 300 mmol) was added dropwise and the reaction mixture was allowed to stir at room temperature for 2 d. The solvent was removed under reduced pressure. The crude oil was cooled in an ice/water bath followed by dropwise addition of a n-BuONa solution (Na 6.9 g, (300 mmol) in n-Butanol (300 mL)). The reaction mixture was heated at reflux for 1 h, and then cooled to room temperature. The contents were poured onto 300 mL of water and then extracted with Et2O (2×200 mL). The ether phase was extracted with 1N HCl (3×100 mL). The combined HCl extracts were combined and cooled in a ice/water bath, followed by addition of 6N NaOH until basic (pH>12). The mixture was extracted with Et2O (4×100 mL), washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified via silica gel chromatography (eluent: 0 to 50% EtOAc:Hex). The final product was collected as 6.96 g (14%). LCMS E-S (M+H)=174.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.39 (br. s., 2H), 5.23 (s, 2H), 5.59 (d, J=1.77 Hz, 1H), 7.17 (d, J=6.82 Hz, 2H), 7.28-7.37 (m, 4H)

Provenance & Evidence