Simple way from diazotized aniline to tryptamine and DMT

Lego · Sun Jul 10, 2005 5:40 pm

Thanks to Lilienthal for giving the references of these articles.
http://members.fortunecity.com/lilienthal_/referenc.htm

Synthesis of derivatives of indole, diindolylmethan and indolyl(tetrahydroindolyl)methane
Carl Heinz Brieskorn, Guenther Wittig
Arch. Pharm., 1978, 311, 954-960
http://rapidshare.de/files/2942970/Arch._Pharm.__1978__311__954-960.pdf.html

3-[2-(Dimethylamino)ethyl)]-2-indole carboxylicacid ethylester hydrochloride

To a mixture of 14.8 g (0.159 mol) aniline, 90 ml concentrated HCl and 140 g ice a solution of 11.2 g (0.162 mol) sodium nitrite in 60 ml H₂ O is added dropwise while maintaining a temperature of -5°C. After further 10 min of stirring sodium acetate is added until pH of 3-3,5 (approximately 130 g sodium acetate). This solution and 34.g (0.161 mol as raw product) 7 are simultaneously to a stirred mixture of 50 ml 3N NaOH and 100 g ice. During the reaction 3N NaOH is added until pH of ~6. The orange-red reaction mixture is stirred for further 3 h at room temperature. Then the reaction is alkalised with K₂ CO₃ (pH 9) and extracted with ether (deepred extract). After drying with K₂ CO₃ and evaporation of the solvent a deepred oil (48.3 g) is obtained. This raw phenylhydrazone is dissolved in 200 ml anhydrous ethanol and while cooling with ice dry HCl is introduced. After ~2h precipitation starts and left over night. After addition of 250 ml ice water the precipitate is removed by filtration. After washing with petroleum ether, ether and CHCl₃ 8.5 g(17.7%) of yellowish crystals are obtained. Melting point 254-257 (ethanol).

2-Acetyl-5-(dimethylamino)pentanoic acid ethylester (7)

To a sodium ethoxide solution made of 4.60 g (0.4 mol) Na and 125 ml ethanol 24.8 g (0.2) ethyl acetoacetate is added. The solution is refluxed and 16.0 g (0,2 mol) 3-chloro-N,N-dimethylpropylamine hydrochloride in 75 ml ethanol is added dropwise over a period of 30 min. After 3 h of reflux the solvent is evaporated in vacuo, the formed salt is solubilised with 70 ml icewater and extracted with ~500 ml ether, dried over Na₂ SO₄ . The organic phase is evaporated and the residue is distilled in vacuo, yield: 7.1 g( 33%) of a colourless oil. Boiling point₁₂ : 134-136 °C.
Yields are not differented if the free amine and less sodium ethoxide is used.

A new route to tryptamines
Cs.Szantay, L. Szabo, Gy. Kalaus
Synthesis, 1974, 354-356
http://rapidshare.de/files/2942984/Synthesis__1974___354-356.pdf.html

2-Ethoxycarbonyltryptamine hydrochloride

A solution of potassium hydroxide (6.4 g, 0.11 mol) in dry ethanol (70 ml) was added dropwise, with exclusion of moisture, to a stirred solution of diethyl 3-chloropropylmalonate (1) (23.7 g, 0.1 mol) in dry ethanol (70 ml). Stirring was continued for 2 h. Meanwhile, a solution of benzenediazonium chloride was prepared as follows. Aniline (9.3 g, 0.1 mol freshly distilled) was dissolved in water (100 ml) and conc. hydrochloride acid (27 ml).A solution of sodium nitrite (7.0 g, 0.11 mol) in water (15 ml) was added gradually while maintaining the temperature at 0-3°. After completion of the diazotization the pH of the solution was adjusted to 6 by the addition of 10% aqueous sodium carbonate (~77 ml), the temperature being kept below 0°C.

The alkaline solution of 1 was cooled to -5°C and the solution of the benzenediazonium chloride was added with stirring. The pH of the mixture was then adjusted to 7.4-7.5 by the addition of 10% aqueous sodium carbonate (~15 ml). The mixture was kept under nitrogen for 1 h at 0°C, acidified with acetic to pH 6, and left at room temperature overnight. The solution was then diluted with water, and the precipitated dark red oil was extracted with dichloromethane. The organic phase was washed with 2N sodium hydroxide, then with water (3x) and dried with magnesium sulfate. After evaporation of the solvent in vacuo, the dark red residue (24.0 g) was heated in boiling butanol (160 ml) containing 4 drops of water for 24 h under nitrogen. When the solution was cooled to 0°, the product crystallized: yield: 9.6 g. Concentration of the mother liquor to half of its volume afforded a further 0.4 of product: total yield: 10.0 g (37%); m.p. 238°C; after recrystallization from ethanol, m.p. 243-244°C

2-Carboxytryptamine
A solution of 2-ethoxycarbonyltryptamine hydrochloride (10.0 g, 0.037 mol) in 4N aqueous sodium hydroxide (100 ml) was refluxed for 2 h, then cooled to 0°, and acidified with acetic acid, yield: 7.6 g (99%); m.p. 244°C (form aqueous ethanol).

Tryptamine
A solution of 2-carboxytryptamine (5.0 g, 0.024 mol) in 15% sulfuric acid (100 ml) was refluxed for 4 h. The mixture was then allowed to cool and was basified to pH 9 with conc. aqueous sodium hydroxide. The precipiated crystals were separated (2.8 g). The mother liquor was extracted with chloroform and the extract evaporated to give a second crop of tryptamine (0.3 g); yield 3.1 g (80%); m.p. 118-120°C. Upon acidification of the mother liquor, 0.5 g of starting material was recovered.

This procedure also works with 4-methoxyaniline yielding 5-methoxytryptamine. Instead of malonic acid ethyl acetoacetate can bee used also.

So if a bee would combine these to methods one could get DMT, DET, DIPT, etc. from aniline with cheap chemicals.......