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I Like to Draw Pictures of Random Molecules

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- Both oxalylchlorid and phosphortribromid arent evil at least to me. I handled nastier things before. (Say, gaseous phosgene)
- To make it even less atom economic (lol); but faster reaction and more complete in appel reaction, use hexabromoacetone or tribomoacetamide. This will occur at like 15C so no need reflux, more like needing an ice bath and it goes to completion in like 30 seconds, filter the phosphinoxid out as usual.
 
sekio said:
There are better variants of the Appel reaction... do they teach this concept of "atom economy" these days? Try for instance triphenylphosphine plus methyl iodide/methyl bromide.
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It is taught as something to strive for but in reality it's very much secondary to cost (and a number of other factors - toxicity, supply stability, etc.).

I wouldn't use tetrabromomethane personally, just suggesting it for those prioritizing the minimization of noxious vapours. I like to use triphenylphosphine and bromine, and have always found it to work very well.

The fact that all the reactants in an appel reaction are crystalline is actually bad for scaling as you tend to form huge amounts of TPPO sludge...
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Usually the mixture can be poured into pentane or another suitable hydrocarbon solvent, to crash out the triphenylphosphine oxide, and then filtered. Perhaps not ideal once past a certain scale.

"real men" would use mesyl/benzensulfonyl chloride (liquid) or tosyl chloride (solid) instead to form a group you can displace with e.g. dimethyl amine.
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Mesylate formation from alcohols is definitely more pleasant than installing a bromide, especially with mesyl anhydride (solid).
 
Volsam said:
JacksinPA, I very much appreciate your recent contributions with drawing out the correlations between opioid acting drugs and underlining the Tyrosine structure in them! It made me think...8)
The longer I look at molecules of different psychoactives, the more I see how they are all like keys with differing groves on them, but structural similarity is amazing! :D

:D
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I post here to keep my mind & my time useful. It's also to hopefully get people thinking about structure-activity relationships as well as choosing viable synthetic routes to get to new or existing molecules. Right now I'm back searching this thread to find my posts on converting tryptophan into DMT while avoiding the need for difficult or hazardous reagents.
 
DMT from tryptophan - summary

Here is a general recap of my recent posts over months on converting store-bought L-tryptophan into DMT without the use of any hazardous or difficult-to-obtain reagents.

The classic approach to methylating that amine is to use methyl iodide. As a thought, methyl bromide is a commercial (and highly toxic) insecticide/fumigant & might be more readily available in cylinders from commercial sources that might not ask too many questions.

A gas at room temperature, methyl bromide readily penetrates skin, cloth, and other protective materials such as rubber and leather. It is nonflammable and toxic at low concentrations. Methyl bromide is odorless and odor provides no warning of hazardous concentrations.

DMT-ex-TRP.jpg
 
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KrZ from the Hive successfully synthesized DMT from tryptophan years ago.

S/he decarboxylated tryptophan by refluxing it in turpentine, a high boiling solvent, and then reduced the resulting tryptamine with 2 molar equivalents of formaldehyde with sodium cyanoborohydride in methanol IIRC.
 
Dresden said:
KrZ from the Hive successfully synthesized DMT from tryptophan years ago.

S/he decarboxylated tryptophan by refluxing it in turpentine, a high boiling solvent, and then reduced the resulting tryptamine with 2 molar equivalents of formaldehyde with sodium cyanoborohydride in methanol IIRC.
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Turpentine is a good high-boiling solvent but there are obvious flammability & ventilation issues, as well as the difficulties involved with recovering the tryptamine. Partition with an aqueous weak acid like acetic might be less trouble than trying to distill the turpentine.

The hard part is that reducing agent which is not commonly available.

There are a number of reagents such as ethanolamines that are known to work in my demethylation scheme.
 
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Forget my suggestion of using CH3Br for the methylation. It is a banned substance (toxic + greenhouse gas), a gas & very toxic. No odor & it goes through rubber gloves. Much better option is CH3I, which is a liquid & can be made by a number of methods in the lab. Much less toxic as well.
 
Dresden said:
KrZ from the Hive successfully synthesized DMT from tryptophan years ago.

S/he decarboxylated tryptophan by refluxing it in turpentine, a high boiling solvent, and then reduced the resulting tryptamine with 2 molar equivalents of formaldehyde with sodium cyanoborohydride in methanol IIRC.
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According to references on Google, mineral oil (which is odorless) boils at 310 deg. C while turpentine (odor) boils in the range of 149-180 deg C. Since rate of reaction varies with temperature, my choice from a safety POV would be mineral oil. Heating mantle, Variac, temp probe, mag stirrer, reflux condenser.

As can be seen, turpentine does not come close to the melting point of L-tryptophan, but that might not be an absolute requirement.

Melting points:

L-tryptophan - 289 deg C.
Tryptamine - 113-116 deg C.
 
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JacksinPA said:
According to references on Google, mineral oil (which is odorless) boils at 310 deg. C while turpentine (odor) boils in the range of 149-180 deg C. Since rate of reaction varies with temperature, my choice from a safety POV would be mineral oil. Heating mantle, Variac, temp probe, mag stirrer, reflux condenser.
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I've never heard of someone using mineral oil as a solvent, and I certainly would not attempt to reflux it at over 300 C. If the reaction goes at the boiling point of turpentine there is no reason to try and raise the temperature higher. It will likely just lead to greater decomposition.
 
Thanks. My interest would be at or slightly about the m.p. of the Trp, not at the b.p. of mineral oil. Turpentine will not get up to the m.p. of Trp while mineral oil will. Despite the earlier report using turpentine, I'm skeptical that the reaction would go below the m.p.

New approaches begin with people trying things that others have not tried. I see nothing wrong with mineral oil & it does not have the odor & flammability of turpentine, which is a mixture of pinenes. Pinenes are one of the reason that soft wood forests make such intense fires. Weak bases such as tryptamine in this case can be extracted out of the oil using aqueous white acetic acid (vinegar). Upon evaporation the solid product would be tryptamine acetate.

So we've gotten half way through the proposed synthesis scheme using only products available at the local shopping mall. That sort of innocent simplicity makes it more interesting to me.
 
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I am simply reporting what KrZ used.
KrZ was no amateur and is legit AF.
An exhaustive methylation of tryptamine procedure can be found in TiHKAL by Shulgin.
 
Thanks. I will check that out. Still hard to believe that they used smelly turpenitine as the reaction medium. Would not be my first choice for the reasons I've already stated..
 
Mineral oil doesnt really dissolve anything, being mostly simple unbranched alkanes.
Also, decarboxylation seems to be somewhat accompanied by ketone (idk mechanism) catalytically, which i think is present in a small amount in turpentine (less than a percent) but enough to facilitate the reaction.
 
Turpentine heated in the presence of air will make ketones, alpha pinen+oxygen -> verbenone, limonene->carvone/piperitone, carene->carenone etc.
 
sekio,

This may be a stupid question, but does

Safrole + turpentine + O2 (g) --> PMK?
 
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