Knoevenhagel-Walter; another way

[Barium]

This has been published a few times but after using TFSE I havn´t found it mentioned here.

Some benzaldehydes are really tricky to condensate with nitromethane, nitroethane and particulary 1-nitropropane, the usual way. Shulgin´s favourite method using AcONH4 and AcOH on the steambath gives in many instances crappy yield or nothing. Equimolar amounts of the benzaldehyde and nitroalkane, 10% n-butylamine or cyclohexylamine in the dark for a week or two can work, but who can handle the waiting? I can´t.

This is a twitch that can work.

E.g., 100mmol of your favourite benzaldehyde and 100mmol n-butylamine (actually most aliphatic amines with 1-4 carbons work) is allowed to react in refluxing toluene. Water is removed with a Dean-Stark water trap. When 1,8ml water has been removed the toluene is distilled off. The resudual aldimine is combined with 1,1 equivalents nitroalkane in 50-100ml glacial acetic acid @ 90-100 deg C for 30-60min. When the aldimine has been consumed (TLC), the acetic acid and excess nitroalkane is removed in a rotovap and the residual oil is allowed to crystallise in MeOH @ 5 deg C.

This is just written from memory. I´ll come back with references and a few recipies.

[Barium]

This type of Knoevenhagel-Walter variation can be found in patent

Patent GB1449540

E.g.,
3-Bromo-4-hydroxy-beta-nitrostyrene

3-Bromo-4-hydroxybenzaldehyde (20,1g) and n-propylamine (7,6g) were refluxed in dry benzene (150ml) using a Dean-Stark water separator for 3 hours. The benzene phase was concentrated to get the crude aldimine as an oily product. The aldimine (24,2g), nitromethane (24ml) and glacial acetic acid (72ml) were refluxed for 45 minutes. The reaction mixture was diluted with cold water. The solid product was filtered off and crystallised from aqueous ethanol to obtain the title product; m.p. 132-34 deg C.

It seems to be a good method for hydroxybenzaldehydes. Admittedly there is no report of the yields here but I can imagine they aren´t too shabby.

[Rhodium]

It is also used to prepare the BDB (J) nitrostyrene precursor, as it cannot be made directly from piperonal/nitropropane:

Post 103792

(Rhodium: "3,4-Methylenedioxyphenyl-2-nitro-1-butene", Chemistry Discourse)