Easy DOM (2,5-dimethoxy-4-methylamphetamine) from DMA theory.My dear fellow bees!
I have searched thoroughly on the search engine, but have not found anything that corresponds to my idea, so i truly hope it is a novel idea and not a sleazy knock off
.
Brief overviewDMA.HCl is bromomethylated, and the resulting DOMBr is subsequently isolated. DOMBr is then dehalogenated using rather simple and non toxic chemicals to DOM.
Paraformaldehyde, KBr, H2SO4
DMA.HCl ---------------------------> DOMBr
NaBH4, DMSO
DOMBr ----------------------------> DOM
Description of the ideaDOM has always been notoriously difficult to prepare because of the somewhat odd precursors required and the formylation step needed to make the benzaldehyde. After the discussion in the serious chemistry forum about the two new active compounds DOMCl and DOMOM (
Post 486635
(Rhodium: "Two new DOM analogs made and evaluated", Serious Chemistry)), the idea for the new DOM synthesis spawned.
The starting material is DMA.HCl In the article
here
(
https://www.thevespiary.org/rhodium/Rhodium/pdf/domcl-domom.pdf) they chloromethylate this in very high yields(70.8%). As debated earlier chloromethylation is not a very nice procedure, because of the complicated set up, noxious and toxic gasses involved. Bromomethylation ala Lego looks much nicer(see
Post 475109
(Lego: "Amphetamines/PEAs w/o benzaldehyde or nitroethane", Novel Discourse), as no gassing is required. I
suppose the same yields can be expected from the bromomethylation as the chloromethylation. After the isolation of the -most likely nasty/toxic- DOMCl the next step can commence.
As the whole DOM molecule is quite stable there are many ways of dehalogenate this. Many reducing agents will do the job
[1]. The most common being lithium aluminium hydride
[2]. Another powerful reagent, which reduces primary, secondary, tertiary, allylic, vinylic, aryl and neopentyl halides, is a complex formed from lithium trimethoxyaluminium hydride LiAlH(OMe)3 and CuI
[3]. A milder reducing agent is Sodium Borohydride, NaBH4, in a dipolar aprotic solvent such as Me2SO (DMSO), DMF or sulfolane
[4], which at room temperature or above reduces primary, secondary, and some tertiary
[5] halides in good yield without affecting other functional groups that would be reduced by LiAlH4.
There are also many other ways of dehalogenating alkylhalides, but many of these seem quite exotic compared to the ones i have mentioned. See
[6] for further reading.
For bees the route with borohydride in DMSO / DMF is probably the best way to go. The yields are supposed to be high, and the reaction conditions are mild. An obstacle
could be the large aromatic ring connected to the same carbon as the halogen, which could cause some sterical hinderance. However,
[4] and
[5] states that secondary and even some tertiary halogens are reduceable using this method. I would guess that it ought to work even though it might be a bit hindered with this in mind. I don't have the reference on the specific reaction conditions on this one, but perhaps a friendly bee can dig it up somewhere? After a successfull dehalogenation, we all know what wonderfull molecule awaits us
. So if it really is a feasible route i would think that the synthesis of DOM has become quite alot easier. But i suppose there is only one way of finding out if it works nicely
Anyone have some feedback on the idea?
Regards
Bandil
References[1]Reviews: Hudlický
Reductions in Organic Chemistry; Ellis Horwood: Chichester, 1984, pp 62-67, 181.
Pinder
Synthesis 1980, pp. 425-452.
For a list of reagents see Larock Comprehensive Organic Transformations; VCH New York, 1989, pp. 18-24.
[2]
Reviews: Pizey Synthetic Reagents, vol. 1; Wiley: New York, 1974, vol 1, 1974, pp. 101-294.
[3]Masamune; Rossy; Bates
J. Am. Chem. Soc. 1973, 95, 6452.
Masamune; Bates; Georghiou
J. Am. Chem. Soc.,
1974, 96, 3686.
[4]Bell; Vanerslice; Spehar
J. Org. Chem. 1969, 34, 3923.
Hutchins; Hoke; Keogh; Koharski
Tetrahedron Lett. 1969, 3495.
Vol'pin; Dvolaitzky; Levitin
Bull. Soc. Chim. Fr. 1970, 1526.
Hutchins; Kandasamy; Dux; Maryanoff; Rotstein; Goldsmith; Burgoyne; Cistone; Dalessandro; Puglis
J. Org. Chem. 1978, 43, 2259.
[5]Hutchins; Bertsch; Hoke
J. Org. Chem. 1971, 36, 1568.
[6]March
Advanced Organic Chemistry, Fourth ed. pp. 438-439.