ORTHO-DOB: 2-bromo-4,5-dimethoxyamphetamine

[phenethyl_man]

Am I correct to assume this phenethylamine could be made from vanillin taking this 2-step route to the benzaldehyde:

Methylate vanillin with CH3I yielding veratraldehyde.
Brominate veratraldehyde with Br2 (this will attack the 2-position, correct?) to yield 2-bromo-4,5-dimethoxybenzaldehyde.

Can the nitrostyrene be formed through the traditional method using HOOAc or excess nitroethane as solvents, and ammonium acetate as the catalyst?

Here is all Shulgin has to say about the compound in PiHKAL:

The positional isomer of DOB with the bromine in the ortho-position is 4,5-dimethoxy-2-bromoamphetamine and is called, not surprisingly, ORTHO-DOB. It has been made by the condensation of 2-bromo-4,5-dimethoxybenzaldehyde with nitroethane to give 1-(2-bromo-4,5-dimethoxyphenyl)-2-nitropropene with a mp of 105-106 °C. Reduction to the amphetamine had to be conducted at a low temperature and using only an equimolar amount of lithium aluminum hydride, to minimize reductive removal of the bromo group. The hydrochloride salt of 2-bromo-4,5-dimethoxyamphetamine (ORTHO-DOB) had a mp of 214-215.5 °C, and the hydrobromide salt a melting point of 196-197 °C or of 210 °C. Both have been reported. The yield from the direct bromination of 3,4-DMA was apparently very bad. I do not think that the compound has ever gone into man.

My main concern is that he does not state a method for formation of the nitrostyrene.  I am also wondering if extra caution would need be taken to avoid removal of the bromo group if reduction of the nitro compound is achieved through the use of Al/Hg rather than LAH.

As a side note, has anyone actually tasted this compound yet?  Any information as to what an active dose is?  I find it hard to believe no one has, if in fact it is so easily formed using vanillin as a starting point.

However, I am concerned the compound will be inactive based on the inactivity of EMM (pihkal,#76); this doesn't seem to show much much merit for manipulation of the 2-position, despite this being merely a positional isomer of the extremely potent DOB.

Any thoughts?

[Rhodium]

Ortho-DOB is unfortunately inactive in rats:

Post 453757 (missing)

(Rhodium: "Nichols: First synthesis of DOB (1971)", Methods Discourse)

[phenethyl_man]

Well, that saves me a lot of wasted time and effort; thanks for the link.

On a similar note, I have been experimenting recently with many compounds arising from vanillin.  I have found that the amphetamine which corresponds to 5-bromovanillin (3-bromo-4-hydroxy-5-methoxyamphetamine) gave me what seemed to be a threshold effect around 15mg, and unmistakably, a weak amphetamine-like stimulation ~30mg.  I was hesitant to test any higher, and no psychedelic effects were noted; however, I think it's possible at higher levels.

Just thought I would contribute that info, since I have not heard of this compound ever being tasted by any human either.