Benzoic Acid → 2-(1H-pyrazol-1-yl)benzonitrile

HRID 916883Notes

Reaction equation

HRID 916883 reaction equation
F[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[OH-].[K+].C1OCCOCCOCCOCCOCCOC1.[C:30]([C:37]1[NH:38]C=CN=1)([C:32]1NC=C[N:36]=1)=O.C(O)(=O)C1C=CC=CC=1.C(NCC1C=CC=CC=1)C1C=CC2OCOC=2C=1>O1CCCC1>[N:38]1([C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[CH:37]=[CH:30][CH:32]=[N:36]1

Participants

8

Reactant 6

HCID 243Benzoic AcidHCID 14797Potassium HydroxideHCID 2855718-Crown-6HCID 678552-FluorobenzonitrileHCID 7697924720-73-4HCID 5250894Bis-(1H-imidazol-2-YL)-methanone

Product 1

HCID 71645582-(1H-pyrazol-1-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 20 mmol of 2-fluorobezonitrile and 40 mmol of pyrrazole is mixed together in dimethylformaide with 1 equivalent of potassium hydroxide and a catalytic amount of 18-crown-6. The mixture is stirred at room temperature overnight, quenched with water and ethyl acetate and extracted with ethyl acetate. The organic extract is washed repeatedly with 1 N NaOH solution. The organic layer is then diluted with ether and washed with 1N HCl solution, dried and concentrated. 1H NMR (CDCl3) 6.55 (t, J=2 Hz, 1H), 7.42 (M, 1H), 7.65–7.82 m, 4H), 8.15 (d, J=1 Hz, 1H). 2-Pyrazol-1-yl-benzoic acid. Compound 178. A solution of compound 177 in conc HCl is refluxed overnight, cooled and concentrated. The product is precipitated by addition of 1 N NaOH until pH of 5–6, filtered and dried. 1H (CDCl3) 6.52 (t, J=3 Hz, 1H), 7.40 (d, J=8 Hz, 1H), 7.50 (t, J=8 Hz, 1H) 7.62 (t, J=8 hz, 1H), 7.81 (m, 2H), 8.12 (d, J=8 Hz, 1H). N-Benzo[1,3]dioxol-5-ylmethyl-N-benzyl-2-pyrazol-1-yl-benzamide, Compound 179. 1.1 equiv of carbonyl diimidazole is added to a solution of benzoic acid 178 (200 mg) in tetrahydrofuran (5 mL); the reaction is stirred at room temperature for 3 h. After this time N-piperonyl-N-benzylamine (0.25 g) is added in one portion. After 30 min, the reaction is filtered, diluted with ether and washed with water. The organic layer is dried (Na2SO4) and purified over column chromatography to provide the desired product (390 mg). The proton NMR displays a typically doubled pattern. 1H (CDCl3) 3.83 and 4.32 (two doublets, J=16 Hz, 1H), 3.91 (two doublets, J=8 Hz, 1H), 4.18 two doublets (J=6 Hz, 1H), 5.0 and 5.1 (two doublets, J=14 Hz, 1H), 5.93 and 5.98 (s and doublet, J=2 Hz, 2H, OCH2O), 6.35–6.40 (m, 2H), 6.51 (d, J=4 Hz, 0.5H), 6.4 (m, 1.5H), 7.0–7.88 m, 15H). LC-MS 412.3

Workup

  1. customquenched with water and ethyl acetate
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washis washed repeatedly with 1 N NaOH solution
  5. additionThe organic layer is then diluted with ether
  6. washwashed with 1N HCl solution
  7. customdried
  8. concentrationconcentrated
  9. temperatureA solution of compound 177 in conc HCl is refluxed overnight
  10. temperaturecooled
  11. concentrationconcentrated
  12. customThe product is precipitated by addition of 1 N NaOH until pH of 5–6
  13. filtrationfiltered
  14. customdried
  15. stirringthe reaction is stirred at room temperature for 3 h
  16. waitAfter 30 min
  17. filtrationthe reaction is filtered
  18. additiondiluted with ether
  19. washwashed with water
  20. dry with materialThe organic layer is dried (Na2SO4)
  21. custompurified over column chromatography

Sources & evidence

ORD record
ord-004a139b7eb44e42924aee969398f767
Source dataset
uspto-grants-2007_09
Patent number
US07271270B2

Reaction notes

Loading…