Author Topic: Tryptamine from scratch (different approach)  (Read 709 times)

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Tryptamine from scratch (different approach)
« on: December 20, 2002, 11:25:00 AM »
EDIT: Sytnthesis of other pre-cursors needed for the preparation of 6-subst. tryptophans were erased. However, if you are still interested turn your attention to the original patent (see reference)


The preparation of racemic and optically pure tryptophans is described. (The D-enantiomers of the 6-substituted compounds possess a potent sweetening capability.) Novel intermediates are also disclosed.

Step 1

2- 2-Nitrophenyl! acrolein

A stirred mixture of 50 g. (0.365 mol) of 2-nitrotoluene, 56.0 g. (0.47 mol) of N,N-dimethylformamide dimethyl acetal and 200 ml. of dimethylformamide was heated under N.sub.2 for 32 hr., raising the pot temperature gradually from to while the methanol formed during the reaction was removed by continuous distillation through a Vigreux column. Complete conversion of the starting 2-nitrotoluene was verified by nmr.-spectroscopy. The dark red solution of the enamine (compound III) was added to a mixture of 58 g. (0.52 mol) of 40% aqueous dimethylamine, 120 g. (1.48 mol) of 37% aqueous formaldehyde, 90 g. of acetic acid and 300 ml. of methanol at over 1 hr. The mixture was stirred for 30 minutes at and then the methanol was removed in vacuo. 1.5 l of water was added over 1 hr. at and the suspension stirred at for 2 hr. The crystalline precipitate was collected, washed with water and and dried to afford 55.8 g (86%) of product as brown crystals, m.p. The analytical sample was prepared by recrystallization from ethanol, followed by evaporative distillation at mmHg: white crystals, m.p.

Step 2

1-Formyl-5-hydroxy-4- 2-nitrophenyl!-pyrrolidine-2,2-dicarboxylic acid diethylester

To a stirred, icebath-cooled mixture of 42.5 g. (0.24 mol) of acrolein of Step 1 and 50.4 g (0.25 mol) of diethyl formamidomalonate in 200 ml. of absolute ethanol was added, over 15 minutes, 4 ml. of a 1M solution of sodium ethoxide in ethanol. The mixture was stirred at for 1 hour as the Michael adduct crystallized out. After the suspension had been stored for 4 hours at, the product was collected by filtration washed with ethanol ( and dried to yield 82.4 g (90%) of off-white crystals, m.p. The analytical sample was prepared by recrystallization from ethanol: white crystals, m.p.

Step 3

2-Formamido-3-(3-indolyl)-2-carbethoxypropionic acid ethyl ester

50.0 g (0.13 mol) of the compound of Step 2 in 500 ml. of methanol and 1 ml of acetic acid was hydrogenated in a rocking autoclave at room temperature and 200 psi in the presence of 6 g. of Raney nickel. After the hydrogen uptake (3 equivalents) was complete the filtered reaction mixture was concentrated in vacuo to a volume of 140 ml. Toluene (600 ml.) was added and the remaining methanol was removed by azeotropic distillation. The mixture was heated at reflux for an additional 30 minutes and then allowed to cool to room temperature. The precipitate was collected, washed with toluene and dried to yield 42.3 (97%) of white crystals, m.p. (lit. m.p. The analytical sample was prepared by recrystallization from ethanol: m.p.


A mixture of 40 g (0.12 mol) of the compound of Step 3 and 24.0 g (0.60 mol) of sodium hydroxide in 240 ml. of water was heated at reflux for 18 hours. 48 ml of glacial acetic acid was added to the solution and heating was continued for an additional 8 hours. The suspension was allowed to stand at overnight and the white precipitate was collected, washed with icecold water and dried to yield 24.7 g (100%) of crude product. Recrystallization from 80% aqueous acetic acid afforded, after drying at mmHg, 21.2 g (86%) of white crystals, m.p. (dec.) (lit. m.p. which was identical with an authentic sample.


Patent US4073795

- Synthesis of tryptophans


Taken from Cyrax post # 369921:

Post 369921

(Cyrax: "Tryptamine from scratch", Tryptamine Chemistry)

20 grams of DL-tryptophan was dissolved in 150 ml cyclohexanol containing 1.5 ml of 2-cyclohexen-1-one, and the temp of the solution was held at 154°C for 1.5 hours. The tryptamine was isolated as the HCl salt, mp 256°C. Yield 92.3%.

[End Of File]

Since the synthesis is rather tedious, some good ol' drum and bass might cheer you up - Past this into winamp and enjoy:

Merry X-mass


"Turn on, Tune in and Drop Out"


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I've now cleaned up the mess in the above post
« Reply #1 on: December 21, 2002, 06:25:00 PM »
Enjoy!  ;)

"Turn on, Tune in and Drop Out"