Bromine Bromobenzaldehyde

Bromobenzaldehyde from aluminum chloride catalyzed bromination of benzaldehyde, 40, 9 Bromobenzene, conversion to Grignard reagent, 41, 91... 

SYNTHESIS The starting material 3,5-dimethoxy-4-bromobenzoic acid (made from the commercially available resorcinol by the action of methyl sulfate) was a white crystalline solid from aqueous EtOH with a mp of248-250 °C. Reaction with thionyl chloride produced 3,5-dimethoxy-4-bromobenzoyl chloride which was used as the crude solid product, mp 124-128 °C. This was reduced with tri-O-(t)-butoxy lithium aluminumhydride to produce 3,5-dimethoxy-4-bromobenzaldehyde which was recrystallized from aqueous MeOH and had a mp of 112-114 °C. Anal. (C9H9BrO,) C,H. This aldehyde, with nitroethane and anhydrous ammonium acetate in acetic acid, was converted to the nitrostyrene l-(3,5-dimethoxy-4-bromophenyl)-2-nitropropene, with a mp of 121-121.5 °C. Anal. (CnHl2BrN04) C,H,N. This was reducedat low temperature withjustone equivalent of LAH, to minimize reductive removal of the bromine atom. The product 3,5-dimethoxy-4-bromoamphetamine hydrochloride (4-BR-3,5-DMA) was isolated in a 37% yield and had a mp of 221-222 °C. Anal. (C,, H17BrClN02) C,H,N. 

Side-chain bromination occurs under the influence of light (cf. Expt 6.28) and the extent of bromination is controlled by ensuring that the bromine (used in the theoretical amount) is added no faster than the rate at which it is consumed. The halogen in the benzylidene halide is reactive and hydrolysis occurs readily under mild conditions. In the example cited (p-bromobenzaldehyde, Expt 6.118) the use of a boiling aqueous suspension of calcium carbonate gives good results. 

Anthraquinone synthesis.1 The original anthraquinone synthesis (10, 75) from benzamides and benzaldehydes involving a tandem orf/io-lithiation can be improved by use of an ort/to-bromobenzaldehyde as the second component. In this version, the second lithiation involves halogen-metal exchange, which results in higher yields. In the example cited here, the yield was only 15% in the absence of the bromine substituent on the aldehyde. 

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