Dimethyl Sulfate → 2-Methoxy-4-methylbenzonitrile

HRID 8919

Reaction equation

HRID 8919 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O.[OH-].[Li+].S(OC)(O[CH3:18])(=O)=O>C1COCC1.C(OCC)C>[CH3:18][O:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 168937Lithium hydroxide, monohydrateHCID 143886562-Hydroxy-4-methylbenzonitrile

Product 1

HCID 124953732-Methoxy-4-methylbenzonitrileYield 90%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-Hydroxy-4-methylbenzonitrile (0.46 g, 3.46 mmol) in THF (17 mL) was added lithium hydroxide monohydrate (0.292 g, 6.95 mmol) followed by dimethyl sulfate (0.50 mL, 5.28 mmol). The resultant mixture was heated to reflux for 2 hours then cooled to room temperature. The mixture was diluted with diethyl ether (50 mL), washed with saturated aqueous NaHCO3 (3×15 mL), dried (MgSO4) and concentrated. Purification of the crude material by column chromatography on silica gel (4:1 hexanes-EtOAc) provided 0.456 g (90%) of 2-methoxy-4-methylbenzonitrile as a white solid. 1H NMR (CDCl3) δ 2.41 (s, 3H), 3.91 (s, 3H), 6.77 (s, 1H), 6.81 (d, 1H, J=6Hz), 7.43 (d, 1H, J=6 Hz). ES-MS m/z 148 (M+H).

Workup

  1. temperatureto reflux for 2 hours
  2. washwashed with saturated aqueous NaHCO3 (3×15 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (4:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-db2fd0075fa6482e8c3b42e6ac372ca6
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Linked notes

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