Stimulants of the Future II

[Black]

for more info,we already have a thread dedicated to 4-methylamphetamine.

 

[dread]

I'd be much more interested in 3-methoxy-4-chloroamphetamine. Is there any studies on it? If the 3-methoxy-group would prevent the neurotoxicity or at least decrease it to a reasonable level, it might be an interesting substance... and one easily made from eugenol.

 

[vecktor]

I'd be much more interested in 3-methoxy-4-chloroamphetamine. Is there any studies on it? If the 3-methoxy-group would prevent the neurotoxicity or at least decrease it to a reasonable level, it might be an interesting substance... and one easily made from eugenol.

without discussing the synthesis in detail this is hardly easy from eugenol.

looks to me like a pretty worthless substance to explore.

 

[dread]

without discussing the synthesis in detail this is hardly easy from eugenol.

How so? Without discussing synthesis, the 4-hydroxyl in eugenol should be easily replaced with chlorine in a single step procedure. Then you just go the normal route, allylbenzene -> benzaldehyde -> amphetamine.

 

[ebola?]

do we have studies beyond anecdotes on 4-methyl-amp?

 

[vecktor]

How so? Without discussing synthesis, the 4-hydroxyl in eugenol should be easily replaced with chlorine in a single step procedure. Then you just go the normal route, allylbenzene -> benzaldehyde -> amphetamine.

ha ha ha

 

[dread]

ha ha ha

care to elaborate?

 

[nuke]

care to elaborate?

Phenols are not exactly congruous to alcohols in reactivity:

2. Elimination

There is good evidence that the synthesis of phenol from chlorobenzene does not proceed by the addition-elimination mechanism (SNAr) described above. For example, treatment of para-chlorotoluene with sodium hydroxide solution at temperatures above 350 ºC gave an equimolar mixture of meta- and para-cresols (hydroxytoluenes). Chloro and bromobenzene reacted with the very strong base sodium amide (NaNH2 at low temperature (-33 ºC in liquid ammonia) to give good yields of aniline (aminobenzene). However, ortho-chloroanisole gave exclusively meta-methoxyaniline under the same conditions. These reactions are described by the following equations.

...

The explanation for this curious repositioning of the substituent group lies in a different two-step mechanism we can refer to as an elimination-addition process. The intermediate in this mechanism is an unstable benzyne species, as displayed in the above illustration by clicking the "Show Mechanism" button. In contrast to the parallel overlap of p-orbitals in a stable alkyne triple bond, the p-orbitals of a benzyne are tilted ca.120º apart, so the reactivity of this incipient triple bond to addition reactions is greatly enhanced. In the absence of steric hindrance (top example) equal amounts of meta- and para-cresols are obtained. The steric bulk of the methoxy group and the ability of its ether oxygen to stabilize an adjacent anion result in a substantial bias in the addition of amide anion or ammonia.

http://www.cem.msu.edu/~reusch/VirtualText/benzrx2.htm

The reverse reaction usually doesn't happen.

See also: http://bio-che.mc.edu/valente/ch24.pdf

You also already have the three carbons for the amphetamine in eugenol, you can just oxidize the alkene and then make the amine if you want a secondary amine... You can do electrophilic addition across the alkene with Br or I and then make a primary amine in a somewhat reasonable yield.

But, anyway, I don't think you'd be make to make the p-Cl compound from eugenol.

 

[dread]

Ah, that's very enlightening. Thanks for the lesson.

 

[/navarone/]

I know this is another random structure but....looking at BZP and Phenmetrazine i thought of something in between:

2-phenyl-3-methylpiperazine ('piperphezine')

Basically i just swapped the oxygen in phenmetrazine with a nitrogen.

 

[nuke]

It's easy to make, F&B reported it as a reuptake inhibitor but not a releaser. The secondary amine (which is very basic and hydrophilic) has very different properties to the ether (which is very hydrophobic).

 

[holdout]

IUPAC: 1-(4-methylphenyl)-2-methylaminobutan-1-one

naming candidacy: Mebuphedrone

lol..... yea it's bad for you... but it will fly off the...... shelves? :S hehe

one thing i find funny is how changing the 4-methyl group to a hydroxy makes it cling clang around unable to cross the blood-brain barrier lol. molecules are funny! :D biochem is funny! :D laff a little! har har har!!!!

hmmm how come noone has even tried just plain 4-methylphenethylamine?

 

[fastandbulbous]

It's easy to make, F&B reported it as a reuptake inhibitor but not a releaser. The secondary amine (which is very basic and hydrophilic) has very different properties to the ether (which is very hydrophobic).

Are you not thinking of 2-methyl-3-phenylpiperidine? Can't remember posting anythiong about 2-methyl-3-phenylpiperazine

 

[/navarone/]

^^ Would yo be able to find some information on 2-methyl-3-phenylpyrrolidine (pretty similar to what you just mentioned) please?

PS: Hey, I remember from some time ago that you said you where given some Az-LAD that you where going to try and write a TR about it. What happend? I'm super-duper curious to hear how that went. Pleaseee let me know man!

 

[Rectify]

Stimulants of the Future

3-methylmethcathinone

 

[/navarone/]

Dudes! Check this shit out!

Prodilidine

I came across it while roaming on chemspider.

OK, OK, its an opioid analgesic but its metabolites (eg: ester hydrolysis and demethylation) cold definetly have a stim activity.

Trippy...

 

[dread]

I wonder if that one is likely to have MPTP like impurities as well if made poorly...?

 

[/navarone/]

I know this is another random structure but....looking at BZP and Phenmetrazine i thought of something in between:

2-phenyl-3-methylpiperazine ('piperphezine')

Basically i just swapped the oxygen in phenmetrazine with a nitrogen.

Found a Patent (Title: Antidepressive substituted phenylpiperazine compounds - Patent Number: 4912110).
Human trials have been made, with therapeutical antidepressant doses starting at about 100mg. Clearly shows stimulating properties with peripheral alpha-adrenergic stimulation at medium-high doses (but slightly sedating effects at low doses), increase in blood pressure but doesn't alter heart rate and doesn't cause insomnia nor affect regular sleep.

 

[TheAzo]

I wonder if that one is likely to have MPTP like impurities as well if made poorly...?

Which are you referrign to?

 

[/navarone/]

He's referring to Prodilidine which is very similar to MPPP. It has been found that a poor synthetic precedure is likely to give MPTP impurities (that metabolizes into MPP+, the real bad dude) which are known to selectively kill dopaminergic neurons giving rapid onset of irreversible parkinson symptoms.

It seems unlikely though that a possible byproduct metabolites such as phenyldimethylpyrrolium would behave like MPP+. Pyrrole behaves very differently from pyridine:

Wiki:
Pyrrole has very low basicity compared to conventional amines and some other aromatic compounds like pyridine. This decreased basicity is attributed to the delocalization of the lone pair of electrons of the nitrogen atom in the aromatic ring.

I could definetly be wrong though...