Acetic Anhydride → 2,5-Dimethoxy-4-methylbenzonitrile

HRID 76854

Reaction equation

HRID 76854 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][CH3:13])=[CH:7][C:4]=1[CH:5]=O.Cl.[NH2:15]O.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][CH3:13])=[CH:7][C:4]=1[C:5]#[N:15]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 6020192,5-Dimethoxy-4-methylbenzaldehyde

Product 1

HCID 5957382,5-Dimethoxy-4-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
105 °C

Procedure

By analogy to steps outlined in J. Med. Chem. 1976, 19(12), 1400-1404. 2,5-dimethoxy-4-methylbenzaldehyde (14.8 g, 82.2 mmol) is dissolved in pyridine (300 mL) and to it, is added hydroxylamine hydrochloride (6.8 g, 98.6 mmol). The suspension is heated at 105° C. for 2 h. Acetic anhydride (15.5 mL, 164 mmol) is then added to the reaction and stirring is continued for another 2 h. The solution is evaporated to dryness and partitioned between EtOAc and saturated aqueous NaHCO3. The organic fraction is dried (Na2SO4) and evaporated to give a yellow solid which is taken up in hexanes and filtered to give 2,5-dimethoxy-4-methylbenzonitrile as a white solid. (cas #51267-09-5) MS (ESI) m/z 178.2 (M+H).

Workup

  1. customThe solution is evaporated to dryness
  2. custompartitioned between EtOAc and saturated aqueous NaHCO3
  3. dry with materialThe organic fraction is dried (Na2SO4)
  4. customevaporated
  5. customto give a yellow solid which
  6. filtrationfiltered

Sources & evidence

ORD record
ord-6b79e8d9a3d04e9ca9404c812e6c9891
Source dataset
uspto-grants-2014_09
Patent number
US08835646B2

Linked notes

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