This article is a kind of supplement to PIHKAL, since its covers the syntheses of some fluoro- and nitro analogs of 2,4,5-Trimethoxyamphetamine (TMA-2, Pihkal #158) and 2-Methoxy-4,5-Methylenedioxyamphetamine (MMDA-2, Pihkal (#133).

2-Nitro-4,5-dimethoxyamphetamine (6-Nitro-3,4-DMA)

A solution of 3,4-Dimethoxyamphetamine (3,4-DMA) (1.95 g, 10 mmol) in 2N HNO₃ (10 mL) was added with stirring at 15°C to 30 mL conc. HNO₃ (70%, 1.42 g/mL) diluted with water (12 mL). The solution was stirred for 3 h at RT, then poured into ice-water. The precipitate was suspended in 0.1 M NaOH, the solution extracted with CH₂Cl₂, the extracts dried (Na₂SO₄) and the solvent evaporated. The residue was dissolved in toluene and dry HCl gas was bubbled through it to give 1.9 g (69%) of 6-Nitro-3,4-DMA·HCl.

2-Nitro-4,5-Methylenedioxyamphetamine (6-Nitro-MDA)

Prepared in a similar way as described above, using 3,4-Methylenedioxyamphetamine (MDA). Yield ca 80%.

5-Fluoro-2,4-Dimethoxybenzaldehyde

Phosphorus oxychloride (15.3 g, 0.1 mol) and N-methyl-formanilide (13.5 g, 0.1 mol) was stirred for 30 minutes at 25°C. Add slowly 2,4-dimethoxyfluorobenzene (15.6 g, 0.1 mol). After addition is complete, let react for 3 hours at 35°C, leave overnight and pour in ice-water. Filter precipitate and dry to give 17.7 g of the benzaldehyde (96% yield)

1-(5-fluoro-2,4-dimethoxyphenyl)-2-nitropropene

A mixture of 2-fluoro-4,5-dimethoxybenzaldehyde (4 g, 0.02 mol) and ammonium acetate (0.38 g, 5 mmol) in nitroethane (21 mL) was heated for 3 hrs at 80°C. Excess solvent was evaporated and the oily residue scratched with cold EtOH to precipitate the nitropropene (3.6 g, 69% yield)

5-Fluoro-2,4-Dimethoxyamphetamine (5-F-2,4-DMA)

To a suspension of LAH (0.8 g, 0.02 mol) in dry THF (10 mL) was added with stirring a solution of the above nitropropene (1 g, 4.1 mmol) in dry THF (15 mL). The resulting mixture was refluxed for 3 hrs. It was then cooled and excees LAH was decomposed by adding water. After filtration and washing the inorganic precipitate with Et₂O, combined extracts were evaporated and the oily residue redissolved in 0.1 N H₂SO₄. Wash with ether, basify and extract with CH₂Cl₂. Evaporate the solvent and convert the free base to its hydrochloride salt by bubbling dry HCl gas through an ethereal solution of the base to get 0.6 g (58% yield) of the isopropylamine.