Maybe this would be interesting in this thread......
Post 514141 (https://www.thevespiary.org/talk/index.php?topic=7234.msg51414100#msg51414100)
(psyloxy: "3,4,5 precursors revisited", Chemistry Discourse)
4-Desmethylmescaline
A. Brossi and S. Teitel
Org. Prep. Proced. Int. 1(3), 171-172 (1969)
4-Desmethylmescaline, a potential metabolite of mescaline which occurs as a minor alkaloid in Lophophora williamsii and Trichocerus pachanoi1, has been prepared from syringaldehyde by a multistep procedure2. A more convenient route is the facile conversion of mescaline by selective demethylation with mineral acid to afford 4-desmethylmescaline in 64% over-all yield. This procedure is another example of the preferential cleavage of the middle methoxyl that has been demonstrated3,4 for various alkaloidal systems containing three neighboring methoxy groups.
Experimental
A solution of 8 g. (32.4 mmole) of mescaline hydrochloride in 100 mL of 20% hydrochloric acid is refluxed for 2 hrs. and evaporated at 40°C under reduced pressure. The residual oil is crystallized from 100 ml. of ethanol to give 2.4 g of 4-desmethylmescaline hydrochloride: mp 249-250°C. ?EtOHmax sh 230 nm (6500), 272 (1280); nmr (DMSO-d6, 60-Mc, tetramethylsilane) ? s 2.93 (2CH2), 3.76 (2CH3O), 6.53 (2 aromatics), 8.23 (OH and NH3); tlc (silica gel G, developed with 100:10:5 EtOAc-MeOH:NH4OH for 11 cm. and detected with Dragendorff's reagent), Rf 0.40; identical in m.m.p., uv, nmr and tlc to an authentic sample2. Mescaline hydrochloride (4 g.) is recovered by evaporation of the filtrate followed by crystallization from 100 ml. of acetonitrile. The overall yield of 4-desmethylmescaline hydrochloride is thus 64%.
References
[1] S. Agurell and J. Lundström, Chem. Commun., 1638 (1968)
[2] F. Benington, R. D. Morin, and L. C. Clarke, Jr., J. Amer, Chem. Soc., 76, 5555 (1954) Post 523232 (https://www.thevespiary.org/talk/index.php?topic=11812.msg52323200#msg52323200)
(Rhodium: "Synthesis of Escaline and Homosyringylamine", Novel Discourse)
[3] A. Brossi, J. Van Burik, and S. Teitel, Helv. Chim. Acta, 51, 1965 (1968)
[4] A. Brossi, J. O'Brien, and S. Teitel, Helv. Chim. Acta, in press.
Actually, I think isoproscaline sounds quite interesting.
Yeah moo, I agree, it sounds very interesting, I would however like to taste the sec-butoxy analog, I don't think it has yet been made so I'm working on it.
For instance:
[Escaline: DOSAGE: 40 - 60 mg. DURATION: 8 - 12 h.]
[isoproscaline: DOSAGE: 40 - 80 mg. DURATION: 10 - 16 h.]
[proscaline: DOSAGE: 30 - 60 mg. DURATION: 8 - 12 h.]
[secbutoxy analog would hence probably have the same dosage/duration as proscaline, but it would probably halt at this lenght as receptor won't tolerate further homologation, see for instance the drop in potency with buscaline compared to proscaline (possibly the branched para-[3-penthoxy] would also show some activity, but it's hard to predict).]
Anyways, to the point of the post, this paper might interest you, notice how bromine on para shows increasd activity in sheep just like higher alkyloxy homolgs do, I think this could bee the study that Shulgin comments on in the DESOXY entry in Pihkal*:
Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogs
David E. Nichols, Donald C. Dyer;
J. Med. Chem.; 1977; 20(2); 299-301.
(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_imgs/pdf.gif)
*: A mescaline analogue with a bromo atom in place of the 4-methoxyl group is an analogue of mescaline in exactly the same way that DOB (a very potent am-phetamine) is an analog of TMA-2 (the original trisubstituted amphetamine). This analogue, 3,5-dimethoxy-4-bromoamphetamine, has been found to be a most effective serotonin agonist, and it is a possibility that it could be a most potent phenethylamine. But, as of the present time, it has never been assayed in man.
That is inconsequential, as only phenols need to be deprotonated to their corresponding anions for alkylation to proceed, the only requirement is that they are present as their free base.
An alternative to the use of a protection group on the nitrogen is to use the Mitsunobu Reaction: Post 506741 (https://www.thevespiary.org/talk/index.php?topic=6574.msg50674100#msg50674100)
(Rhodium: "O-Methylation of Phenolic Phenethylamine", Chemistry Discourse)