The above mentioned hydroquinone (2,6-dimethyl-hydroquinone) can bee made with reasonable yield (20-30%) through Elbs-persulfate oxydation of 2,6-Xylenol, I have the paper somewhere, IIRC it is
J. Chem. Soc. 2303 1948W. Baker, N. C. Brown found from this old thread
Post 122784
(dormouse: "Bromo-benzodifuranyl-isopropylamine -Lilienthal", Serious Chemistry).
I agree with what you said in this thread Rhodium:
Still, making 2,5-dimethoxy-4,6-methyl-amphetamine (6-Me-DOM) from 2,6-dimethyl-p-hydroquinone would be very interesting. The compound should be really active.
as, AFAIK the 6-methyl group push the side chain downward in a good conformation, contrary to the 2-methyl group which push it upward in a less good conformation (also 2-ethoxy tweetios are less potent too). I remember this from somewhere i dont remember, I think it was from some paper on ring-methylated MDA analogs, and I also think the 3-methyl didnt have such a strong steric effect (as it is located further from the side chain).
In conclusion AFAIK:
- 2-methyl-DOM (if it existed, but only the tweetio (methoxy replaced by ethoxy) can exist, it is called Florence in Pihkal and has not been bioassayed yet) should be less potent than DOM:
Quote from Pihkal,
2C-D entry:
(
http://www.erowid.org/library/books_online/pihkal/pihkal023.shtml)
In every compound to be found in the 2C-X family, there are two methoxy groups, one at the 2-position and one at the 5-position. There are thus three possible tweetio compounds, a 2-EtO-, a 5-EtO- and a 2,5-di-EtO-. Those that have been evaluated in man are included after each of the 2C-X's that has served as the prototype. In general, the 2-EtO- compounds have a shorter duration and a lower potency, the 5-EtO- compounds have a relatively unchanged potency and a longer time duration; the 2,5-di-EtO- homologues are very weak, if active at all.
The 2-EtO-homologue of 2C-D is 2-ethoxy-5-methoxy-4-methylphenethylamine, or 2CD-2ETO. The benzaldehyde (2-ethoxy-5-methoxy-4-tolualdehyde) had a melting point of 60.5-61 °C, the nitrostyrene intermediate a melting point of 110.5-111.5 °C, and the final hydrochloride a melting point of 207-208 °C. The hydrobromide salt had a melting point of 171-173 °C. At levels of 60 milligrams, there was the feeling of closeness between couples, without an appreciable state of intoxication. The duration was about 4 hours.
2CD-2ETO is the 2C, phenethylamine homologue of Florence (3C, amphetamine homologue)
- 3-methyl-DOM exist, it is
Ganesha
(
http://www.erowid.org/library/books_online/pihkal/pihkal085.shtml) in Pihkal.
Its potency is a bit lowered, but not too much vs DOM (DOM: 3-10mg vs Ganesha: 20-32mg), and is a bit more long lived (DOM: 14-20h vs Ganesha: 18-24h).
So, I conclude the 3-methyl change slightly the duration and require 2 or 3x the same dosage, which is still quite good IMHO.
- 6-methyl-DOM exist, it is Juno in Pihkal, but sadly it is untested:
Quote from Pihkal,
Ariadne entry
(
http://www.erowid.org/library/books_online/pihkal/pihkal008.shtml)
And, finally, JUNO (3,6-dimethoxy-2,4-dimethylamphetamine) has been made (from 2,5-dimethoxy-m-xylene, which was reacted with POCl3 and N-methylformanilide to the benzaldehyde, mp 53-54 °C, and to the nitrostyrene with nitroethane, mp 73-74 °C from cyclohexane, and to the final amine hydrochloride with LAH in THF). Rather amazingly, I have had JUNO on the shelf for almost 14 years and have not yet gotten around to tasting it.
Personally I think Juno will bee, by extrapolation of the work on side chain configuration of methylated MDA analogs:
-Slighty more potent or at least equal potency than DOM.
-Slighty more long lived (wild guess from Ganesha).
-Of course very interesting.
Also, I have in this ref: Journal of Organic Chemistry, 48(17), 2932-3, 1983
the preparation of the above mentioned quinone (2,6-dimethyl-quinone) from 2,6-xylenol, by bichromate oxydation, easily, in good yield and big scale.
The abstract of this paper is:
Jones oxidn. of alkylphenols was a simple effective method for the large scale (30-60 g) prepn. of p-quinones, which usually gave quinones of reasonably high purity without chromatog. purifn. Six quinones thus prepd. included I-III.
And they claim the reaction 2,6-dimethyl-phenol ---Na2Cr2O7, H2SO4---> 2,6-dimethyl-quinone in 84% yield.
(in general alkylated quinones are easier to prepare than non alkylated ones btw)
This quinone can be reduced to the hydroquinone easily by shaking with sodium dithionite aqueous solution. Trimethylphosphate or any other methylating agent can then alkyl both phenols. For DMS check this ref, it could be interesting: Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry (1997), 36B(11), 1044-1046.
The real problem is in the formylation, as i have found no refs for this except the one from Pihkal. Further research is needed, it must exist a preparation somewhere!
As a side note, an alternative attractive procedure someone has to try is to use the beautiful reactivity of the quinone to our advantage. With a bit of luck, the 2,6-dimethyl-quinone will react with allyl-oxalate in the presence of AgNO3/Persulfate, to yield the allyl quinone in one step! (see Post 471656
(Chimimanie: "Why i prefer p-Meo-phenol?", Novel Discourse) and Chem. lett. 1992 7 1299)
2,6-xylenol --Jones Oxydation--> 2,6-dimethyl-quinone --allyl-oxalate, AgNO3/persulfate--> the allyl-quinone --1.dithionite, 2.methylation--> 2,5-dimethoxy-4,6-dimethyl-allylbenzene --> to Juno
...will obviate the need to use POCl3 which is a watched chem.
Please someone find some formylation refs for the 2,5-dimethoxy-m-xylene! Rhodium: your refs seems interesting, I will check them, thx!