Acetic Acid → 1-hydroxy-3-methylnaphthalene-2-carbonitrile

HRID 514138Notes

Reaction equation

HRID 514138 reaction equation
[C:1]1([CH2:7][C:8](=O)[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[C:14](=[O:18])[CH2:15][C:16]#[N:17])C.C(O)(=O)C.C([O-])(=O)C.[NH4+].C(N)(=O)C>C1C=CC=CC=1>[OH:18][C:14]1[C:6]2[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=2)[CH:7]=[C:8]([CH3:9])[C:15]=1[C:16]#[N:17]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 178AcetamideHCID 7678PhenylacetoneHCID 7764Ethyl cyanoacetateHCID 517165Ammonium Acetate

Product 1

HCID 2193751-hydroxy-3-methylnaphthalene-2-carbonitrileYield 40.5%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
160 °C

Procedure

Phenyl-2-propanone (24.93 g, 0.178 mol) was combined with ethylcyanoacetate (19.8 mL, 0.180 mol), acetic acid (8.0 mL, 0.14 mol), ammonium acetate (2.82 g, 0.0370 mol) and 80 mL of benzene in a round bottom flask equipped with a Dean-Stark trap and condenser cooled by a chiller. The reaction was heated to 160° C. for 4 h. The mixture was removed from heat and the trap drained so that the mixture could be concentrated by distilling off excess (˜50 mL) benzene. The solution contained crude (E)-ethyl 2-cyano-3-methyl-4-phenylbut-2-enoate. The concentrated mixture was removed from heat and heat adjusted to 240° C. Acetamide (50.9483 g, 0.862 mol) was added, and a Claisen head attached to distill any ethanol resulting while the mixture was heated at 240° C. for 60-90 minutes. The mixture was cooled to ˜100° C., and poured into room temperature water to quench the reaction. A clumpy orange solid was formed, removed by filtration and triturated with ice cold absolute EtOH. The solid was filtered off and the process repeated 4 times to harvest additional material. The resulting product was a pale yellow fine powder (13.20 g, 36% yield). 1H-NMR: (300 MHz, DMSO-d6): δ 11.28 (s, 1H); 8.24 (d, J=8.4 Hz, 1H); 7.80 (d, J=8.0 Hz, 1H); 7.62-7.58 (m, 1H); 7.52-7.48 (m, 1H); 7.34 (s, 1H); 2.47 (s, 3H).

Workup

  1. customequipped with a Dean-Stark trap and condenser
  2. temperaturecooled by a chiller
  3. customThe mixture was removed
  4. temperaturefrom heat
  5. concentrationcould be concentrated
  6. distillationby distilling off excess (˜50 mL) benzene
  7. customThe concentrated mixture was removed
  8. temperaturefrom heat
  9. temperatureheat
  10. customadjusted to 240° C
  11. distillationto distill any ethanol resulting while the mixture
  12. temperaturewas heated at 240° C. for 60-90 minutes
  13. temperatureThe mixture was cooled to ˜100° C.
  14. additionpoured into room temperature water
  15. customto quench
  16. customthe reaction
  17. customA clumpy orange solid was formed
  18. customremoved by filtration
  19. customtriturated with ice cold absolute EtOH
  20. filtrationThe solid was filtered off

Sources & evidence

ORD record
ord-51190aa37f0c4311887c3856a6e9f2e7
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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