Some Fluoro and Nitro Analogs of TMA-2 and MMDA-2
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OK, actually this is a supplement to PIHKAL, since its covers the synths for fluoro- and nitro analogs of 2,4,5-MeO-amphetamine TMA 2 (#158, 20-40 mg, 8-12 h) and 2-methoxy-4,5-methylenedioxyamphetamine MMDA-2 (#133, 25-50 mg, 8-12 h).
1-(2-Nitro-4,5-dimethoxyphenyl)-2-aminopropane
A solution of 1-(3,4-dimethoxyphenyl)-2-aminopropane (1.95 g, 10 mmol) in 2N HNO3 (10 ml) was added with stirring at 15°C to a concentrated solution of nitric acid (d 1.4, 30 ml) diluted with water (12 ml). Stir for 3 hrs at STP, then pour into ice-water. Precipitate was suspended in 0.1 M NaOH solution, free amine was extracted with CH2Cl2, solvent was dried and evaporated. Redissolve in PhMe and bubble HCL through it to get 1.9 g (69% yield) of the title cpd.
1-(2-nitro-4,5-methylenedioxyphenyl)isopropylamine
Prepared in a similar way as described above, by nitration of MDA in 80% yield.
2,4-dimethoxy-5-fluorobenzaldehyde
Phosphorus oxychloride (15.3 g, 0.1 mol) and N-methyl formanilide (13.5 g, 0.1 mol) was stirred for 30 mins at 25°C. Add slowly 2,4-dimethoxyfluorobenzene (15.6 g, 0.1 mol). After addition is complete, let react for 3 hrs at 35°C, leave overnight and pour in ice-water. Filter precipitate and dry to give 17.7 g fluorobenzaldehyde (96% yield)
1-(2-fluoro-4,5-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)
1-(2-fluoro-4,5-dimethoxyphenyl)-2-aminopropane
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 ethre, basify and extract with CH2Cl2. Evaporate solvent and convert free base to hydrochloride salt by bubbling HCL through an ethereal solution of the base to get 0.6 g (58% yield) of the isopropylamine.
Reference: Synthetic Communications 24(3), 417-426
