Harmaline and Other Beta-carbolines

Dissolve 3.3 g 4,5, or 6 methoxy (or ethoxy, methyl, etc.)-tryptamine or its HCl salt in 350 ml 0.1 N HCl heat on steam bath two hours with 1.1 g glycoaldehyde (reaction over when aliquot no longer gives a precipitate with dinitrophenylhydrazine). Filter, concentrate by heating on water bath or evaporate in vacuum basify with 20% NaOH and extract with ether (best to do in an extractor for eighteen hours). Dry and evaporate in vacuum the extract to get about 5 g residue or oil which may precipitate on standing. Add 250 ml 90% phosphoric acid and heat on steam bath two hours. Evaporate in vacuum (or dilute with water, basify with 20% NaOH extract with ether in extractor and dry, evaporate in vacuum the 

To 24 ml acetic anhydride in 80 ml formic acid add 22 g 4,5 or 6 methoxy (or analog) tryptophan and reflux V2 hour. Concentrate to thick syrup on steam bath with vacuum and add slowly with stirring 180 ml water and let stand twelve hours at 0°. Filter, wash with 2% HCl and water to get about 18 g N-formyl-methoxy-tryptophan (1) (recrystallize-benzene-ethanol). 10 g (I), 119 g polyphosphoric acid, 

10 ml POCI3 mixed in 500 ml flask with vigorous stirring. Heat on 

011 bath at 125 for eighty minutes (HCl andCO evolution). Add ice, cool, filter and neutralize filtrate with concentrated NH OHto get about 5 g norharmaline or isomer. To get harmaline isomers, use 

4 g N-acetyl-methoxy-tryptophan, 14 g polyphosphoric acid and 3 ml POCI3 and proceed as above. 

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