Reaction #742297

Reaction equation

2-(Ethoxymethylene)malononitrile

(2,6-Dichlorophenyl)hydrazine hydrochloride

NaOH

→

product

Yield 94.5%

5-amino-1-(2,6-dichlorophenyl)-1H-pyrazole-4-carbonitrile

Yield 94.5%

Solvents

EtOAc

Conditions

Workup

1. 1
   OtherThe organic layer separated
2. 2
   Washwashed with water (50 mL), brine (50 mL)
3. 3
   Dryingdried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   Otherwas suspended in methanol (50 mL) under nitrogen at −5° C
7. 7
   Temperatureheated
8. 8
   Temperatureat reflux under nitrogen for 2 hours
9. 9
   Temperatureto cool
10. 10
    Otherevaporated to dryness

Procedure

(2,6-Dichlorophenyl)hydrazine hydrochloride (5 g, 23.42 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (40 mL). The organic layer separated and washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated. The resultant oil was suspended in methanol (50 mL) under nitrogen at −5° C. 2-(Ethoxymethylene)malononitrile (2.86 g, 23.42 mmol) added portion-wise over 5 mins and the mixture stiffed at 0° C. for 30 mins. The reaction mixture was allowed to warm to room temperature and then heated at reflux under nitrogen for 2 hours. The reaction mixture was allowed to cool and evaporated to dryness to afford the product (5.60 g, 94%) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.47 (2H, s), 7.43-7.47 (1H, m), 7.51-7.53 (2H, m), 7.73 (1H, s); m/z (ES+) (M+H)+=253; HPLC tR=1.62 min. Alternatively the product was obtained by concentrating the reaction mixture to half volume and allowing the product to crystallise.

Source