(Hive Addict)
03-31-03 10:23
No 422671
(Rated as: excellent)

Classic method, one to add to your paper collection... wink

A Kubo e.a. A facile synthesis of 1,2,3,4-tetrahydroisoquinolines through cyclization of O,N-acetals. Synthesis (1987) 824-827

2,4,5-trimethoxy-3-methyl-beta-nitrostyrene - Ammonium acetate (850 mg, 11 mmol) is added to a stirred solution of 2,4,5-trimethoxy-3-methylbenzaldehyde (10.5 g, 50 mmol) in nitromethane (100 mL) at room temperature. The mixture is heated at reflux for 3 h, then poured into H2O (200 mL) and extracted with benzene (3 x 200 mL). The combined extracts are dried (Na2SO4) and evaporated under reduced pressure and the remaining yellow solid is recrystallized from MeOH to afford prisms of the nitrostyrene. Yield: 8.61 g (68%). mp: 121-123C (Lit9: 121-123C)

2,4,5-trimethoxy-3-methyl-phenylethylamine - LAH (3.0 g, 79 mmol) is added to a stirred solution of the nitrostyrene (7.59 g, 30 mmol) in dry THF (150 mL). The mixture is stirred at room temperature for 4 h, excess reagent is decomposed with H2O, and the mixture is filtered. The filtrate is evaporated under reduced pressure to give a pale yellow oil which is distilled in vacuo to give the PEA. Yield: 4.40 g (65%). bp: 142-144C/2 Torr.

[9] K Matsuo e.a. Chem Pharm Bull 30 (1982) 4170

Additional note: if interested, make sure to substitute the NH4OAc-catalyzed formation of the nitrostyrene by Ba's aqueous MeNH2 method. Much easier and shorter reaction time.

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