From the VERY interesting article:
Structure-Activity Relationships in Psychotomimetic PhenylalkylaminesF. A. B. Aldous, B. C. Barrass, K. Brewster, D. A. Buxton, D. M. Green, R. M. Pinder, P. Rich, M. Skeels, and K. J. TuttJ. Med. Chem., 1974, Vol. 17, pp. 1100-1111 (1974)
(
https://www.thevespiary.org/rhodium/Rhodium/pdf/sar.psychotomimetic.phenylalkylamines.pdf)
Abstract
A study has been made of the relationship between the structure of phenylalkylamines and potential correlates of their psychotomimetic activity. Optimum activity is associated with (a) an isopropylamine side chain, with a R-(-) configuration at the carbon atom a to the amino group, and (b) 2,5-dimethoxy substitution, together with an alkyl or halo group at position 4 that is probably limited in bulk to n-propyl or bromo. The activity of compounds in producing hyperthermia in rabbits provides good quantitative correlation with reported psychotomimetic activities in man.(You'll like this one if you don't already have it - includes some new active substituted 2-phenylcyclopropylamines like DMCPA in pihkal)
Also more importantly, this article shows us a bunch of stuff that would be inactive - so we don't waste time on them. For instance 1-phenyl-3-aminobutanes, and 2,5-dimethoxy-4-methylphenyl-[CH(Me)CH2NH2, C(Me2)CH2NH2, CH(Me)CH(Me)NH2, CH2CH(Me)NHMe, CH2CH(Me)NHEt]. Yes, they are ALL inactive.
Okay, back to the DOB bromination. Bandil, maybe you should pretend to try this...
4-Bromo-2,5-dimethoxyphenylisopropylamine HydrobromideTo a solution of 2,5-dimethoxyamphetamine (1.5 g) in glacial AcOH (7.5 ml) was added a 50% solution of HBr in glacial AcOH (1.25 g), and to this mixture at 0-5C was added a solution of Br2 (1.23 g) in glacial AcOH (10 ml). The reaction mixture was stirred for 3 hr at room temperature and concentrated
in vacuo, and the residue was recrystallized from EtOAc. mp 145-146C, Yield: 70%.
Or if you want DOC...
4-Chloro-2,5-dimethoxyphenylisopropylamine HydrochlorideDry HCl was passed into a solution of 2,5-dimethoxyamphetamine (2.64 g) in glacial AcOH (15 ml) until 0.4 g had been absorbed. To this stirred solution at 0-5C was added a solution of Cl2 (0.9 g) in glacial AcOH (15 ml), the whole mixture was stirred at room temperature for 5 hr. Concentration
in vacuo, and recrystallization from EtOAc gave impure product, which was purified by further recrystallization from 2-propanol-Et2O. mp 187-188C, recrystallized from Acetone/EtOH, Yield: 50%.
The DOC made from the above reaction and used in the evaluations was nearly identical in potency to DOB. Both being active in the 0.062 mg/kg range, with DOC being metabolized faster than DOB. So if you're worried about polychlorination effecting potency, don't, because the resulting compound is just as active.