DOM writeup

[Prometheuz]

psyloxy> Great suggestion! It does indeed sound like pure R-DOM would be closer to what is searched for... Not that the racemic version is bad at all   ... Unfortunately SWIM doesn't have the neccesary skill/equipment for seperation of the isomers - yet. Most of the procedures seem to be quite hard - unless you have access to some sort of stereoselective chromatography gear.

[hest]

Fractional rextalisation with l-tartaric acid (the natural form) or, even better, the benzyl ester of the r form is not that hard. Usual you won’t lose more than 5-10% (of the right isomer). Biggest drawback is that you want to work in the 3-10g scale.

For the more speculative part. I look's like it's the r-isomer who make all the fun it's 2 times as strong as the racemate. In pikhal under DOB ½mg s-isomer have no effect and 1mg only might have an effect. My guess is that whatever the s-isomer is doing (dopamine system?) it's not very strong and might not bee worth the trouble to sweep out

[psyloxy]

To successfully resolve R/S isomeres of DOM with tartaric acid the specific solubilities of both salts in a given solvent need to be known, right ? Is that data available ?

--psyloxy--

[hest]

Triel and error works just fine.
You rextalise all kind of stuff every day without knowing this. I have done it with TMA-2 with ethanole as the solvent. Works fine (but the difference was not that big, 2*power and not so much long term amphetamine effect)

[Rhodium]

I made a Beilstein Crossfire search for DOM, and retrieved the references about optical resolution or enantioselective synthesis of R-DOM. They can be seen below. You'll also get the full Beilstein outputs, which contains a whole lot of more references to pharmacology and racemic syntheses.

The green text above each citation is my own summaries.

Beilstein Crossfire - DOM (racemat)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/articles/beilstein/dom/dom.html)

Beilstein Crossfire - DOM (R-isomer)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/articles/beilstein/dom/r-dom.html)

Beilstein Crossfire - DOM (S-isomer)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/articles/beilstein/dom/s-dom.html)


As the title below implies, the article contains a SAR study of nearly 40 different psychedelic amphetamines and PEA's, as well as some comparisons between their optical isomers. It contains a lot of synthetic procedures, as well as pharmacological and physical data not seen before here at the Hive. I'm surprised that this hasn't been posted before.

Structure-activity relations in psychotomimetic phenylalkylamines
F. A. B. Aldous, B. C. Barrass, K. Brewster, D. A. Buxton, D. M. Green, R. M. Pinder, P. Rich, M. Skeels, K. J. Tutt

J. Med. Chem. 17(10), 1100-1111 (1974)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/sar.psychotomimetic.phenylalkylamines.pdf)


Very good article, where DOM is synthesized step by step from 2,5-dimethoxytoluene, and resolved using o-nitrotartanilic acid. It also contains a synthesis of 4-Methyl-2,5-Dimethoxyphenyl-2-propanone, as well as of the 4-COOH and 4-CH₂OH analogs of DOM.

Stereochemical aspects and metabolite formation in the in vivo metabolism of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane
S. B. Matin, P. S. Callery, J. S. Zweig, A. O'Brien, R. Rapoport, N. Castagnoli, Jr.

J. Med. Chem. 17(, 877-882 (1974)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/dom.synthesis.resolution.pdf)


This article contains preparation of the Tartanilic Acids used for resolving DOM in the previous article.

Substituted tartranilic acids. A new series of resolving acids
Thomas A. Montzka, Terry L. Pindell, John D. Matiskella

J. Org. Chem. 33(10), 3993-3995 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/tartanilic.resolving.acids.pdf)

(07-07-04): DOM is synthesized step by step from deuterated 2,5-dimethoxytoluene (prepared from p-dimethoxybenzene), and O-demethylated DOM analogs prepared.

In vitro O-demethylation of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane
Jonathan S. Zweig, Neal Castagnoli, Jr.

J. Med. Chem. 20, 414-421 (1977)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/dom.deuterio-synth.pdf)


Synthesis of N-Hydroxy-DOM from DOM, as well as optical resolution of the product.

Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding n-hydroxy metabolites with cytochrome P-450
N. Peter McGraw, N. Castagnoli, Jr.

J. Med. Chem. 24(3), 299-304 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/n-hydroxy-dom.isomers.pdf)


Catalytic reductive amination of substituted phenyl-2-propanones with either (+)- or (-)-alpha-phenethylamine, which by in situ hydrogenolysis forms the corresponding enantiomerically pure amphetamine. Among lots of others, DOM is one of the produced amphetamines.

Asymmetric synthesis of psychotomimetic phenylisopropylamines
David E. Nichols, Charles F. Barfknecht, David B. Rusterholz, Frederick Benington, Richard D. Morin

J. Med. Chem. 16(5), 480-483 (1973)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/nichols/nichols-asymmetric-amphetamines.pdf)


This patent (by Dave Nichols) describes essentially the same thing as the above article.

Patent US4000197