Methylation: Eschweiler-Clark

[Z_Hound]

In this reductive methylation method formic acid serves as a reductunt;
anyone else trying it with tryptamine?
See:
[1] Moore, M.L. Org. React., 1949, 5, 301
[2] J.C.S., 1342 (1950)
[3] J. Org. Chem., 50, 1110 (1985)
[4] J. Org. Chem., 51, 5169 (1986)
[5] Joseph Casanova and Praveena Devi, Synth. Comm., 23(2), 245-251 (1993)

Procedure below is taken from ref. [5]:
5 mmol of prime amine is dissolved in minimal amount of ether and placed in a 3-neck rbf equipped with a reflux condenser and a magnetic stirrer.
Solution is cooled to 0 C followed by addition of formaldehyde (38%, 9 mL) and formic acid ( 85%, 10 mL)
(Authors in [5] report that reaction is exotermic upon addition of formic acid,
in the case tryptamine it was not that obvious to me.)
After the addition the mix is heated at 80 C for 10 hrs
Cooled to RT
Ether was added (50 mL), mix was neutralized with 20% NaOH and stirred for 10 min.
Extracted with ether, -combined organic layers were dried over MgSO4. and the solvents removed.
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DO IT NOW!

Z_Hound


Any Possession is a Demonic Possession!

[Z_Hound]

Well, seems it is good with synthesis of betacarboline at least.

Still, the residue after evaporation, far from pure on TLC (I suspect mixture of dmt and carboline, and may be some 2- methyl);
 gave sweet 1-hr
mild trip with break through into Plato realms,
when bioassayed (vapor)
also, I believe, 2-Methyl substitute was present

How would I avoid formation of carbolines? I ll do low tempr, and reduce time.

Z_Hound

Any Possession is a Demonic Possession!

[Lilienthal]

Unfortunately it's impossible. beta-Carboline formation can't be avoided under acidic conditions.

[Z_Hound]

[PolytheneSam]

There's a lot of hits for beta-Carboline when UingTFSE.
http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[Z_Hound]

[foxy2]

Are tryptamines with a saturated indole ring double bond active?
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[cilliersb]

How about boiling your final product in Ethanolamine.

Might just do the trick??

[Lilienthal]

Foxy: As far as it is known they are inactive.
cilliersb: Ethanolamine - huh?! No way...

[PolytheneSam]

Note reference here

Post 276458

(PolytheneSam: "Benzothiophene analogs", Tryptamine Chemistry)
http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[obia]

i guess one way to use formic acid/ formaldehyde is to reduce the indol double bond first with cat h2. do the methylation, then oxidise with Mno2. the reduction of tryptophan to dihydrotryptophan is used in on of the lysergic acid synths.