Author Topic: Novel route to dialkyltryptamines  (Read 7754 times)

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Novel route to dialkyltryptamines
« on: June 02, 2004, 04:19:00 PM »
Conversions of Michael Adducts to Nitroolefins
Preparation of Carbonyl Compounds, 1,4-Diaminobutanes, Indoles, and Isoquinolines

Dieter Seebach, Volker Ehrig, Herbert F. Leitz und Rainer Henning

Chem. Ber. 108, 1946-1960 (1975)


Derivatives of 1,3- and 1,4-dicarbonyl-systems (3,5) are prepared from the Michael adducts of masked acyl anion equivalents or enolates, respectively, to nitroolefins (2,4) using Nef-type reactions. The same adducts (6,8) are reduced with lithium aluminium hydride in THF/dioxane to give amines (7,9) which are convenient precursors to indoles (cf. bufotenin, 10) or isoquinolines (cf. 4-dithianyl derivatives 15,17) if subjected to standard reactions such as the Bischler-Napieralski-, the Pictet-Spengler-, and oxidative indole-ring closures. An access to 1-dithianylisoquinolines (e.g. 25) is also described. All these transformations can be done on a preparative scale and in good to excellent yields. The effects of 1- and 4-dithianyl substituents on the n.m.r. spectral shifts of peri-hydrogens at C-5 and C-8 in di- and tetrahydroisoquinolines are discussed.

Could someone translate the experimental for the preparation of tryptamines from nitrostyrenes? (german)


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Translation of Chem. Ber., 1975, 108, 1946-1960
« Reply #1 on: June 03, 2004, 11:39:00 PM »
Grmph, this article is on Lego's harddisk for almost a year......
We need reference 3 as soon as possible, otherwise sleep will be hard to find!

Reduction of nitroalkanes 6 and 8 to the amines 7 or 9:
A suspension of 10-20 g LiAlH4 in 250-350 ml THF and 30-100 ml dioxane is heated to reflux. A solution of 50 mmol nitroalkane in 100-150 ml THF or dioxane is added dropwise and the solution is refluxed for further 5-8 h. After careful addition of water to the ice-cooled reaction mixture the formed precipitate is removed by filtration and refluxed for 2 h with ether. The pooled filtrates were dried over potassium carbonate and evaporated on a rotary evaporator. The mono- or dihydrochlorides, hydrogenoxalates or pikrates were synthesized in the usual manner, the m.p. or decomposition points are given in table 2 and data of the elemental analysis in table 3. The yields given in table 2 are isolated ammonium salts, based on used nitroalkane 6 or 8. [...]

2-(2,5-Dimethoxyphenyl)-N4,N4-dimethyl-1,4-butandiamine (7b):
A solution of 14.8 g (50 mmol) 3-(2,5-dimethoxyphenyl)-N,N-dimethyl-4-nitrobutyramid (6b)3 in 100 ml dioxane was added over a period of 30 min to a refluxing solution of 19 g LiAlH4, 350 ml THF and 50 ml dioxane. After 8 h of reflux the solution is hydrolysed with 75 ml while cooled with ice and worked-up as described above. 8.4 of a yellow oil are obtained which is dissovled in ether and a saturated solution of HCl in ether is added dropwise. Yield of dihydrochloride: 10.8 g (67%); m.p. 149-151 °C (EtOH/ether)

Bufotenine (10):
3.25 g (10 mmol) of 7b dihydrochlorid were heated to reflux with 48% HBr for 30 min in a inert gas atmosphere. The solution was diluted with 90 ml water and evaporated to dryness. The aqeuous solution of the residue was heated to reflux with activated carbon and evaporated. The residue is dried until no more weight is lost over P4O10 and NaOH in an evacuated descicator.
To the solution of the hydroquinone derivative (3.8 g) in 120 ml water a solution of 6.4 g K3Fe(CN)6 and 3.3 g NaHCO3 in 120 ml are added dropwise over a period of 10 min. After 30 min a very little amount of sodium dithionite is added. After removal of the precipitate by filtration the solution is extracted for 2 days with ether which is free of peroxides not sure if '2 d' really means 2 days or perhaps it is a typo and should read '2 x', whatever, extract with ether
The amorphous residue of the etheral solution consists of almost pure 10 (1.1 g, 54%), which could be purified by sublimation at 140 °C/10-4 Torr, m.p. 139 °C (lit. 15 143 °C).

3 D. Seebach, H. F. Leitz and V. Ehrig, Chem. Ber. 108, 1924 (1975) and literature cited therein


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Michael-type additions to nitroolefins
« Reply #2 on: June 15, 2004, 07:27:00 PM »
Here's the looong reference 3 requested by Lego:

Michael-type Addition of Lithium Enolates and Sulfur-substituted Organolithium Reagents to Nitroolefins
Dieter Seebach*, Herbert F. Leitz and Volker Ehrig
Chem. Ber.
, 108, 1924-1945 (1975)

The highly reactive lithium derivatives mentioned in the title (3-9) add smoothly to aliphatic (1a-c) and aliphatic nitroolefins (1d-s) between -70oC and -110oC. The structures of both reactants can be varied within a large scope. A discussion of the n.m.r. spectra of the products (10-22) is included.


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Bufotenine synthesis by ferricyanide cyclisation
« Reply #3 on: June 23, 2004, 10:12:00 PM »
Reference 5 from Angew. Chem., 1971, 83(14), 542-544.

Hydroxytryptamines. Part I. Bufotenine, 6-Hydroxybufotenine and Serotonin
John Harley-Mason and A. H. Jackson
J. Chem. Soc., 1954, , 1165-1171

Abstract: Convenient syntheses of bufotenine and serotonin involving the ferricyanide oxidation of 2-(2,5-dihydroxyphenyl)-4-dimethylamino- and -4-amino-butylamine, respectively, are described. A similiar synthesis gave 6-hydroxybufotenine, while attemps to isolated 6-hydroxyserotonin were unsuccessful.


2-(2,5-Dihydroxyphenyl)-4-dimethylaminobutylamine (III; R = H)
A solution of the amino cyanide (7 g) in ethanol (50 c.c.) saturated with ammonia was hydrogenated over Raney nickel at 100° and 100 atm. for 5 hr. The catalyst was filtered off, the solvent removed, and the residual oil distilled at 145-150°/2.5 mm, giving the diamine (III; R = Me) (5.8 g) as a pale oil. [...]

The dimethoxy-diamine (1.3 g) was refluxed with hydrobromic acid (d 1.49; 8 c.c.) for 45 min., and the resulting solution diluted with water and evaporated to dryness on the waterbath under reduced pressure of hydrogen. The residual dark brown solid was dissolved in water and boiled with charcoal, and the solution again evaporated under hydrogen. The last traces of water and hydrobromic acid were removed by storage in a vacuum desiccator over phosphoric oxide and sodium hydroxide, leaving the dihydroxy-diamine dihydrobromide as a light brown hygroscopic glass which did not crystallise.

Bufotenine (IV)
To a solution of the dihydroxy-diamine dihydrobromide (1.9 g) in water (60 c.c.), a solution of potassium ferricyanide (3.2 g) and sodium hydrogen carbonate (1.65 g) in water (60 c.c.) was added with stirring during 5 min. The mixtured darkened at first, but became paler after 20 min. A little sodium dithionite was added andd, after filtration from a small amount of flocculent precipitate, the light yellowish-brown solution was extracted continuously with peroxide-free ther for 2 days. Removal of the ether and drying of the residue in a vacuum over phosphoric oxide gave bufotenine (0.45 g; 45%) as a hard brown glass, purified by sublimation at 160°/10-4 mm. [...]