levo...a very interesting find. I've looked up some leads and found this....
....the reviews mentioned point to the presence of one or more hydroxyl groups in the benzene ring as one of the most potent modifiers of the magnitude of the physiological effects of compounds possessing the basic /3-phenethylamine skeleton.
....as read, Physiologically Active Phenethylamines. I. Hydroxy- and Methoxy-a-methyl-Phenethylamines ( p-Phenylisopropylamines)
E. H. WOODRUFF AND THEODORE W. CONGER
Journal of the American Chemical Society Vol. 60, No. 2, 465,1938
...see Post 531663 (https://www.thevespiary.org/talk/index.php?topic=7530.msg53166300#msg53166300)
(java: "Propenylbenzenes Anyone?", Chemistry Discourse) for the full pdf. Also these are some readings for the OH addition and effects.......
https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitroalkene.reduction.review.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitroalkene.reduction.review.html)
Post 531710 (https://www.thevespiary.org/talk/index.php?topic=11621.msg53171000#msg53171000)
(Rhodium: "N-Hydroxy-Amphetamines from Amphetamines", Novel Discourse)
which may help to see the mechanism for adding the OH to an amine. I will keep this in mind, as I do my daily run through the chemistry archives on the web.
Would be interested in following your quest , so feel free to report it on this thread.....java
Note: edited by java
Here is the list of the NIDA monographs (online): http://www.drugabuse.gov/pdf/monographs/Monographindex.html (http://www.drugabuse.gov/pdf/monographs/Monographindex.html)
Which one is it, and on what page?
Upon reading the said study it shows it takes less than half of the dose as that of amph for the effect in the study....
....The N-hydroxy analog of AMPH (i.e., N-OH AMPH), a metabolite of AMPH, also produces AMPH-like effects and is about twice as potent as AMPH.
So I guess putting the OH of the amine will boost the effect to twice that of amph making almost as potent as methamphetamine......now which is easier to do starting with amph, seems like methylation would be easier.............as I see it, java
From http://www.drugabuse.gov/pdf/monographs/94.pdf (http://www.drugabuse.gov/pdf/monographs/94.pdf)
, page 50:
"The N-hydroxy analog of AMPH (i.e., N-OH AMPH), a metabolite of AMPH, also produces AMPH-like effects and is about twice as potent as AMPH (table 2)."
From Table 2:
dl-N-Hydroxyamphetamine 1.1 µmole/kg
dl-Amphetamine 2.6 µmole/kg
dl-Methamphetamine 1.5 µmole/kg
d-Methamphetamine 1.2 µmole/kg
This shows that both dl-N-Hydroxyamphetamine and d-Methamphetamine are about twice as potent as dl-Amphetamine. The d-isomer of the hydroxy analog may be more potent than d-Methamphetamine, but it is certainly of a shorter duration as N-hydroxy-amines are metabolized rather rapidly. I believe that nothing can be predicted about the potency of N-hydroxy-methamphetamine, as it is a tertiary amine, and they are in general of rather low potency, as can be seen with N,N-dimethylamphetamine and N,N-dimethylcathinone. However, as hydroxy groups are not methyl groups, nothing can be predicted with certainity.
Here's two sites I got from the king bee.....https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamine-1.pdf (https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamine-1.pdf)
also https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamine-2.pdf (https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamine-2.pdf)
It looks as if one must obtain d-amphetamine first.How?Know anyone with ADHD?OR Iguess you could synthesize d-amp.Then this is oxidized using(CPBA)n-chlorobenzoic acid giving the needed NITRO.Then the NITRO coumpound is reduced.Maybe reducing with Zn/NH4Cl???I'd say we just bypass the d/l and go straight to d-isomer.Let's all work on this together!!!
levo....you should read the entries on your thread as my first reply to your inquiry I posted Rhodium's articles Post 531806 (https://www.thevespiary.org/talk/index.php?topic=8791.msg53180600#msg53180600)
(java: "How to get to Hydroxylamphetamine.....", Stimulants) and had you read, this is what you missed.....
(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000531713-Hydroxylamphetamine.jpg)
(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000531713-method_of_synthesis.jpg)
and by the way the link you provided doesn't seem work .......java
Note...edited by java levo the articles you referenced are at Post 531710 (https://www.thevespiary.org/talk/index.php?topic=11621.msg53171000#msg53171000)
(Rhodium: "N-Hydroxy-Amphetamines from Amphetamines", Novel Discourse) as mentioned in my first post
See Post 531710 (https://www.thevespiary.org/talk/index.php?topic=11621.msg53171000#msg53171000)
(Rhodium: "N-Hydroxy-Amphetamines from Amphetamines", Novel Discourse) for the correct links.
N-Oxygenation of Amphetamine and Methamphetamine by the Human Flavin-Containing Monooxygenase (Form 3): Role in Bioactivation and Detoxication1
John R. Cashman2 , Yeng N. Xiong, Lifen Xu and Aaron Janowsky2
Pharmacology (1999) Vol. 288, Issue 3, 1251-1260
http://jpet.aspetjournals.org/cgi/content/full/288/3/1251 (http://jpet.aspetjournals.org/cgi/content/full/288/3/1251)
Abstract
(+)- And ()-amphetamine and methamphetamine were N-oxygenated by the cDNA expressed adult human flavin-containing monooxygenase form 3 (FMO3), their corresponding hydroxylamines. Two major polymorphic forms of human FMO3 were studied, and the results suggested preferential N-oxygenation by only one of the two enzymes. Chemically synthesized (±)-amphetamine hydroxylamine was also a substrate for the human FMO3 and it was converted to phenylpropanone oxime with a stereoselectivity ratio of trans/cis of 5:1. Human FMO3 also N-oxygenated methamphetamine to produce methamphetamine hydroxylamine. Methamphetamine hydroxylamine was also N-oxygenated by human FMO3, and the ultimate product observed was phenylpropanone. For amphetamine hydroxylamine, studies of the biochemical mechanism of product formation were consistent with the production of an N,N-dioxygenated intermediate that lead to phenylpropanone oxime. This was supported by the observation that -deutero (±)-amphetamine hydroxylamine gave an inverse kinetic isotope effect on product formation in the presence of human FMO3. For methamphetamine, the data were consistent with a mechanism of human FMO3-mediated N,N-dioxygenation but the immediate product, a nitrone, rapidly hydrolyzed to phenylpropanone. The pharmacological activity of amphetamine hydroxylamine, phenylpropanone oxime, and methamphetamine hydroxylamine were examined for effects at the human dopamine, serotonin, and norepinephrine transporters. Amphetamine hydroxylamine and methamphetamine hydroxylamine were apparent substrates for the human biogenic amine transporters but phenylpropanone oxime was not. Presumably, phenylpropanone oxime or nitrone formation from amphetamine and methamphetamine, respectively, represents a detoxication process. Because of the potential toxic nature of amphetamine hydroxylamine and methamphetamine hydroxylamine metabolites and the polymorphic nature of N-oxygenation, human FMO3-mediated metabolism of amphetamine or methamphetamine may have clinical consequences.