Potassium Iodide → 1,4-Dihydroquinoline

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Reaction Steps

In Step A, a substituted benzaldehyde undergoes an aldol condensation with a substituted 2-nitroacetophenone in the presence of an inorganic base, such as NaOH, in a polar protic solvent such as a methanol/water mixture, to give the corresponding α,β-unsaturated ketone of formula (I). This product can then be reduced to the corresponding saturated aniline (II) by hydrogenation in the presence of a catalyst such as platinum (IV) oxide in a polar solvent such as methanol or tetrahydrofuran or a mixture of the above as described in Step B. The aniline (II) can be coupled with iodobenzene by heating at 160° C. in the presence of copper (0), potassium iodide and potassium carbonate in a polar solvent such as butyl ether as described in Step C. In Step D, the aniline of formula (IV) can be acylated by heating at reflux in the presence of an acyl chloride, such as methyl oxalyl chloride, in an apolar solvent such as toluene. The amide (IV) can cyclize by heating at reflux in a polar protic solvent, such as methanol, in the presence of an inorganic base such as potassium carbonate as described in Step E to afford the corresponding 1,4-dihydroquinoline.

Provenance & Evidence