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

HRID 655115

Reaction equation

HRID 655115 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:4]=1[NH:10][NH2:11].[OH-].[Na+].C(O[CH:17]=[C:18]([C:21]#[N:22])[C:19]#[N:20])C>CCOC(C)=O>[NH2:22][C:21]1[N:10]([C:4]2[C:3]([Cl:2])=[CH:8][CH:7]=[CH:6][C:5]=2[Cl:9])[N:11]=[CH:17][C:18]=1[C:19]#[N:20]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 671522-(Ethoxymethylene)propanedinitrileHCID 2723909(2,6-Dichlorophenyl)hydrazine monohydrochloride

Product 1

HCID 121505555-amino-1-(2,6-dichlorophenyl)-1H-pyrazole-4-carbonitrileYield 94.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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.

Workup

  1. customThe organic layer separated
  2. washwashed with water (50 mL), brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customwas suspended in methanol (50 mL) under nitrogen at −5° C
  7. temperatureheated
  8. temperatureat reflux under nitrogen for 2 hours
  9. temperatureto cool
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-f221ea0dd0c545bc9b52b94aa1c4dbad
Source dataset
uspto-grants-2011_12
Patent number
US08071585B2

Linked notes

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