Author Topic: Indole Grignards  (Read 1746 times)

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Rhodium

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DMT by alkylation of Indole Grignards
« Reply #20 on: September 26, 2003, 03:56:00 PM »
Preparation of DMT by alkylation of Indole Grignard reagent, referenced in 

Post 270360

(Lilienthal: "Re: Indole Grignards", Tryptamine Chemistry)


A New Route to Tryptamine Derivatives
C. R. Ganellin and H. F. Ridley

Chemistry and Industry 1388-89 (1964)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/dmt.indole.grignard.html)

Rhodium

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Propynylindole and 3-Indolylacetone
« Reply #21 on: January 15, 2004, 06:17:00 AM »
3-Prop-2'-ynylindole
W. R. N. Williamson
J. Chem. Soc. 2834 (1962)

Brown, Henbest, and Jones1 reported their failure to prepare 3-prop-2'-ynylindole by treating 3-indolylmagnesium bromide with prop-2-ynyl bromide, "chiefly because the Grignard reagent reacted first with the active acetylenic hydrogen atom to regenerate indole". They do not report the solvent used, but it was presumably diethyl ether. According to Majima and Kotake2 anisole is a superior solvent for the preparation and subsequent reaction with carbonyl compounds of indolyl Grignard reagents. This apparently cannot be attributed to the higher boiling point of anisole, since in this solvent ethylmagnesium iodide evolves ethane on treatment with indole in the cold, while in ether no gas is evolved at room temperature and heat is required. When we used anisole in the preparation of 3-indolylmagnesium iodide from ethylmagnesium iodide, with subsequent reaction with prop-2-ynyl bromide, a 39.5% yield of 3-prop-2'-ynylindole was obtained. The compound, which was a pale yellow oil slowly becoming darker, was characterised by conversion into 3-indolylacetone2 by heating it with acidic mercuric sulphate.

Experimental

3-Prop-2'-ynylindole

Ethylmagnesium iodide [from magnesium (4.8 g.) and ethyl iodide (32 g.)] in dry anisole (20 ml.) was cooled in ice, and indole (15.6 g.) in anisole (20 ml.) was added dropwise. After being stirred (0.5 h) at 20°C it was treated at 0°C with prop-2-ynyl bromide (20 ml) in anisole (10 ml) during 15-20 min, stirring continued at 0°C for 11 h, and the mixture then stored at 20°C overnight. It was cooled to 0°C and treated with ether (100 ml), water (200 ml), acetic acid (12 ml), and more water (100 ml), and then extracted with ether (5x25 ml.). The extract was washed with sodium bicarbonate solution and water and dried (MgSO4 and charcoal), the solvents were removed under reduced pressure, and the 3-prop-2'-ynylindole (8.17 g) was distilled as a pale yellow oil, bp 143-145°C/2mmHg, which solidified when cooled below 20°C.

3-Indolylacetone

2N Sulphuric acid (10 ml) was treated with mercuric sulphate (0.05 g)3, stirred and heated on a steam-bath, and the propynylindole (1.5 g) in ethanol (10 ml) added. Stirring and heating was maintained for 2 hr. Pouring the solution into water and treatment with sodium hydrogen carbonate produced a brown gum (1.42 g.), mp 95°C (softening at 75°C). Crystallisation from benzene (charcoal) gave the ketone as brownish rhombs (0.28 g), mp 112-115°C. The mp of a mixture with authentic 3-indolylacetone was 112-115°C.

References
[1] Brown, Henbest, and Jones, J. Chem. Soc. 3172 (1952)
[2] Majima and Kotake, Chem. Ber. 55B, 3859-3865 (1922); cf. Kharasch and Reinmuth, "Grignard Reactions of Nonmetallic Substances", 1954, Prentice-Hall, Inc., New York, p. 81.
[3] Thomas, Campbell, and Hennion, J. Amer. Chem. Soc. 60, 718 (1938)


Rhodium

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Scaleable Route to Chiral alpha-Methyltryptamines
« Reply #22 on: May 13, 2004, 01:57:00 AM »
Process Development of a Scaleable Route to [chiral alpha-methyltryptamines]
Hiroshi Harada, Akihito Fujii, Osamu Odai, and Shiro Kato
Organic Process Research & Development 8, 238-245 (2004)





Several different routes are discussed in the article, weighing pros and cons, not just the nifty one in the picture. Note the NaBH4 reduction of a beta-keto-tryptamine, a topic recently discussed.


Rhodium

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3-Indolylacetaldehyde and 3-Indolylacetone
« Reply #23 on: June 05, 2004, 03:18:00 AM »
This is reference #1 from the article in

Post 482491

(Rhodium: "Propynylindole and 3-Indolylacetone", Tryptamine Chemistry)


3-Indolylacetaldehyde and 3-Indolylacetone
J. B. Brown, H. B. Henbest, and E. R. H. Jones

J. Chem. Soc. 3172-3175 (1952)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/3-indolylacetone.pdf)

Abstract
3-Indolylacetaldehyde (I), the aldehyde corresponding with heteroauxin, which has been claimed to have been detected in some plant sources, has been prepared for the first time, and has been fully characterized. The related 3-indolylacetone (VI) has also been prepared.


Offline sophie7

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Re: Indole Grignards
« Reply #24 on: January 29, 2017, 03:55:41 PM »
Is 4 benzyloxy indole useless?
The creating to make start from 2benzyloxy 6 nitrotoluene condensated with tpm(piperidine+triethyl ortho formate),j.org.chem . or tris nn dimethylamino methane 1.5 eq with heat 110C and under vacum  aspirator ,for 4Hours yield  B piperidine o nitrostyrine
The crude nitrostyryne disolved in minimal amt asceton and 6,2 eq of 20% soln Ticl3 and twice the vol of that  Ticl3 of 4M ammacetatete buffer
Mix  for at least 10minutes and extracted several times with diethyl ether, this also can be do for another ,chloro and another benzyloxy ,methoxy,cyano from voresponding o-nitrotoluene if had any chance or maybe some better than its describe, (more friendly) i think this not too friendly using any nn tris chemcal.  But why not , , around 62 % yield


« Last Edit: January 29, 2017, 04:36:45 PM by sophie7 »
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Offline Tsathoggua

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Re: Indole Grignards
« Reply #25 on: February 05, 2017, 04:46:59 AM »
If the corresponding n,n-dimethyltryptamine were the intended target, it could serve as a precursor for psilocin, methinks, via catalytic removal of the benzyl group to give psilocin, and subsequent esterification would be a good idea, due to the instability of 4-OH tryptamines.
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Offline Beard

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Re: Indole Grignards
« Reply #26 on: February 15, 2017, 06:14:27 PM »
If the corresponding n,n-dimethyltryptamine were the intended target, it could serve as a precursor for psilocin, methinks, via catalytic removal of the benzyl group to give psilocin, and subsequent esterification would be a good idea, due to the instability of 4-OH tryptamines.


David E. Nichols does exactly ALL of that starting with 4-benzoyloxy-indole (and goes directly from 4-benzoyloxy-DMT -> 4-Acetoxy-DMT) here: https://www.erowid.org/archive/rhodium/pdf/nichols/nichols-psilocin.pdf
« Last Edit: February 15, 2017, 06:19:19 PM by Beard »