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           Synthesis of 2,5-Dimethoxy-4-methylamphetamine (STP, DOM)
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2,5-Dimethoxytoluene [1]
------------------------

1000ml of water was poured into a wide-mouthed 2000 ml flask, and magnetic 
stirring was initiated. In sequence, there was added 62 g toluhydroquinone,
160 ml 25% NaOH solution and finally 126 g of dimethyl sulfate. The flask was
covered with aluminum foil and stirred for a few days. The brown solution was
poured into 2500ml water, and the resulting solution was extracted with 3x100ml
of CH2Cl2 and the pooled extracts was stripped of solvent under vacuum.
The residue was distilled at about 70°C at 0.5 mmHg to give 49 grams (64%) of
2,5-dimethoxytoluene as a white liquid.


2,5-Dimethoxy-4-methylbenzaldehyde [2] 
--------------------------------------

40ml POCl3 and 45ml N-methylformanilide was stirred at room temp for 50 min
to give a nice orange solution of the Vilsmeyer complex. 15.2g (0.1 mole)
2,5-dimethoxytoluene was then added in one portion, and the reaction mixture
was heated to 70°C, during which time the reaction mixture became dark red.
The heat source was then removed, and the exothermic reaction, which evolved
large amounts of HCl gas, was allowed to go on until the mixture cooled down
and solidified. The flask was then heated on the steam bath for 2 hours, and
the warm reaction mixture poured into 2 liters of ice water, and was stirred
until all the ice had melted. The ice-cold solution was filtered, and the 
crude aldehyde was collected as a red solid. This was suspended in 50ml of 
boiling petroleum ether and was decanted. The procedure was repeated two more 
times with 50ml of petroleum ether each. This left a small amount of red goo 
on the bottom of the flask. The solution was allowed to crystallize in the 
fridge for an hour and was then filtered. The mother liquor was concentrated
to 25% of the original volume, again cooled in the fridge and filtered. The 
orange-brown precipitate was then recrystallized from 50 ml 80% aqueous MeOH 
to give 14.6g (88%) of 2,5-dimethoxy-4-methylbenzaldehyde as orange crystals. 


2,5-dimethoxy-4-methylphenyl-2-nitropropene 
-------------------------------------------

To 50 ml glacial acetic acid in a 100ml RB flask there was added 10.8 g of 
4-methyl-2,5-dimethoxybenzaldehyde, 7.5 g nitroethane, 4 g ammonium acetate 
and 2 ml of acetic anhydride. The solution was heated on a water bath for 3h, 
whereupon the solvent was removed under vacuum. The residue was mixed with 
100 ml H2O and extracted with 2x50ml CH2Cl2. The organic phase was washed with 
50ml 10% NaHSO3 followed by 50ml H2O. The pooled aqueous phases was extracted 
with 50 ml CH2Cl2, the organic phases dried over MgSO4, and the solvent was 
evaporated under vacuum. The residue was dissolved in 50ml IPA and was allowed 
to precipitate in the freezer to give 8.15 g of orange crystals (69%).                     


2,5-Dimethoxy-4-methylamphetamine [3]
-------------------------------------

In a two-necked round-bottomed flask, equipped with a reflux condenser and a
calcium chloride drying tube, a suspension of 9.5 g LAH in 750 mL well stirred
anhydrous Et2O was brought to a boil, and a THF solution of 9.5 g 2,5-dimethoxy-
4-methylphenyl-2-nitropropene was added dropwise through an addition funnel.
After the addition of the nitrostyrene was complete, the stirred suspension was
maintained at reflux for an additional 4 h with a water bath, then allowed to 
cool to room temperature and the stirring was continued overnight. The excess 
hydride was destroyed by the addition of 750 mL 8% H2SO4, cautiously, until the 
hydrogen evolution ceased, then at a speed that allowed the formed solids to 
disperse. The phases were separated, the aqueous phase washed once with Et2O, 
treated with 225 g potassium sodium tartrate, and finally made basic (pH >9) 
with 5% NaOH. This was extracted with 3x150 mL CH2Cl2, the extracts pooled, and 
the solvent removed under vacuum. The residue was 9.6 g of a clear oil which 
spontaneously formed crystals with a mp of 60.5-61°C from hexane. These solids 
were dissolved in 150 mL anhydrous Et2O, and saturated with anhydrous HCl gas.  
After standing at room temperature for 2 h, the crystalline 2,5-dimethoxy-
4-methylamphetamine hydrochloride (DOM) was removed by filtration, washed with 
Et2O, and air dried to constant weight. There was obtained 8.25g (84%) of 
glistening white crystals that had a mp of 190.5-191.5°C.


References:
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[1] Shulgin & Shulgin, Pihkal, p 511
[2] JMC 19, p 1400-1404 (1976)
[3] Shulgin & Shulgin, Pihkal, p 511

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