Benzene → HCID 57134261, compound

Participants

Reaction Steps

By way of illustration, the first step of Scheme A is shown. Iminodiacetic acid, disodium salt monohydrate is reacted with thionyl chloride to give diethyliminodiacetate. This reaction is conducted in ethanol. Time and temperature are not deemed critical to the conduct of this reaction. Time varies from 20 hrs. to 72 hrs. depending on the particular temperature employed. The resulting product from the first step -- diethyliminodiacetate -- is then treated with chlorodiphenylmethane. Time and temperature are typically in the range of 24 hrs. to 72 hrs. and 70°-150° C. This reaction is typically carried out at a temperature of 70°-80° C for 72 hrs. to afford diethyl-N-benzhydryliminodiacetate. Treatment of diethyl-N-benzhydryliminoacetate with hydrazine hydrate affords 5-diphenylmethyl-3,7-diketo-1,2-dihydro-1,2,5-triazepine. This reaction is conveniently carried out in the presence of methanol. Typically this reaction is carried out at reflux and a reaction time of 20 hrs. Treatment of 5-diphenylmethyl-3,7-diketo-1,2-dihydro-1,2,5-triazepine with 6-methylpyridine-2-carboxaldehyde affords 1-diphenylmethyl-4-(6-methyl-2-pyridylmethyleneamino)-3,5-diketopiperazine. This reaction is carried out in the presence of a solvent, a preferred solvent being benzene or toluene. Time and temperature are not critical, with reflux temperature and reaction time of 4 hours being typical. Reduction of the ketone groups on the piperazine ring is effected by the treatment of 1-diphenylmethyl-4-(6-methyl-2-pyridylmethyleneamino)-3,5-diketopiperazine with a mixture of diborane in tetrahydrofuran and boron trifluoride in diethyl ether. This procedure affords 1-diphenylmethyl-4-(6-methyl-2-pyridylmethylamino)piperazine. 1-Diphenylmethyl-4-(6-methyl-2-pyridylmethylamino)piperazine is then treated with 0.1M iodine/MeOH to afford the dehydrogenated product -- 1-diphenylmethyl-4-(6-methyl-2-pyridylmethyleneamino)piperazine. Dehydrogenation of 1-diphenylmethyl-4-(6-methyl-2-pyridylmethylamino)piperazine can also be accomplished using palladium-on-carbon in the presence of methanol in place of 0.1M iodine/MeOH reagent.

Provenance & Evidence