Aromatic chlorination using acetyl chloride & CAN

[demorol]

A Novel and Efficient Ceric Ammonium Nitrate Catalyzed Oxidative Nuclear Chlorination of Activated Aromaic Compounds by Acetyl Chloride

Abtract: A mild and efficient oxidative chlorination of activated aromatic compounds have been achieved in excellent yield using acetyl chloride in the presence of a catalytic amount of ceric ammonium nitrate (CAN) at room temperature. However, chlorination failed to occur with deactivated aromatic rings.

General procedure:

To a stirred mixture of the aromatic substrate (1.5 mmol) and freshly distilled acetyl chloride (1.52 mmol) in acetonitrile (10mL), was added ceric ammonium nitrate (0.15 mmol) in one portion under nitrogen at room temperature. The reaction mixture was allowed to stir for 7-8 h. After completition of the reaction, the reaction mixture was diluted with diethyl ether (25mL) and washed thoroughly with saturated NaHCO₃ (3 × 10mL), brine (3 × 10mL) and dried (Na₂SO₄). Volatiles were removed under reduced pressure and the residue obtained was purified with column chromatography over silica gel (2% ethyl acetate in light petroleum) to yield the pure chlorinated product.

Toluene -> 4-Chlorotoluene + 2-Chlorotoluene (70:30)*, 70%;

Anisole -> 4-Chloroanisole + 2-Chloroanisole (75:25)*, 85%;

p-Xylene -> 1-Chloro-2,5-dimethylbenzene, 86%;

1,3-Dimethoxybenzene -> 1-Chloro-2,4-dimethoxybenzene, 82%;

1,2-Methylenedioxybenzene -> 1-Chloro-3,4-methylenedioxybenzene, 80%;

N,N-Dimethylaniline -> 4-Chloro-N,N-dimethylaniline, 66%;

N,N-Diethylaniline -> 4-Chloro-N,N-diethylaniline, 62%;

Acetanilide -> 4-Chloroacetanilide, 86%:

Naphthalene -> 1-Chloronaphthalene, 84%;

1-Methoxynaphthalene -> 4-Chloro-1-methoxynaphthalene, 78%;

2-Methoxynaphthalene -> 4-Chloro-2-methoxynaphthalene, 74%.

* Ratio of the two regioisomers

Reference: Synlett 2003, No. 2, pp 221