Miscellaneous The Big & Dandy Psychedelics of the Future Thread

[fastandbulbous]

adding the phenyl grignard, then dehydrating the tertiary alcohol gives both possible alkenes, ie the 2-3 alkene and the 3-4 alkene

As tropane is symmetrical, the 2,3-alkene is identical to the 3,4-alkene (if it wasn't symmetrical than tropine would be optically active & it isn't)

Anybody have any ideas on these?

Only 5a & 5b have any possibilities. Alpha vinyl PEA's are pretty much untested territiry, but alpha vinyl tryptamine might just have unexpected activity as it's capable of positioning the double bond in the same manner as the double bond of the C ring of LSD.

Aromatic amines are generally known to be carcinogens & 2 would be unstable (besides epoxide rings are DNA alkylators and as such, well didgy)

 

[Oddeye]

It's fun, I would like to be able to understand but I have absolutely no idea what you are saying. I don't even understand what you are trying to think about, some new compounds that could be synthetizable?

 

[Psychedelics_r_best]

^Exactly, with good and desired effects.

 

[vecktor]

I don't see how. The 5-MeO is the same as it would be with 2C-B.

yes but the 5 position methoxy is not constrained so it is irrelevant because it can rotate to take up positions where the lone pair syn or anti to the 2 position ,
the 2 position is constrained and the lone pairs are directed towards the 4 position and away from the amino alkyl sidechain, this has already been shown to give little activity at 5ht2a, see nichols' dragonfly papers.

 

[bigmac74]

yes but the 5 position methoxy is not constrained so it is irrelevant because it can rotate to take up positions where the lone pair syn or anti to the 2 position ,
the 2 position is constrained and the lone pairs are directed towards the 4 position and away from the amino alkyl sidechain, this has already been shown to give little activity at 5ht2a, see nichols' dragonfly papers.

I guess that throws it out the window as a psychedelic then, but what about an analogue of MMDA?
Pihkal #134

 

[vecktor]

As tropane is symmetrical, the 2,3-alkene is identical to the 3,4-alkene (if it wasn't symmetrical than tropine would be optically active & it isn't)

to put it quite simply the two alkenes are not identical, and your scheme is fatally flawed.
the issue is that tropinone and therfore the intermediate tertiary alcohol is symetrical therefore the 2 and 4 positions have equal reactivity and each alkane has the same thermodynamic stability therfore each alkane is equally likely, unless a chiral auxillary is used, if the 2 and 4 positions were not idential then kinetic or thermodynamic control could be used to give some stereoselectivity but it cannot because they are the same.

the images are simplified to only show the important stereochemistry, there should be an methyl on the nitrogen and a fluoro on the phenyl, but it isn't relevant.

the 2,3 alkene is

the 3,4 alkene is

How can you overlay the two wthout inverting the nitrogen bridge, in effect pushing it through the cycloheptane ring?????

there is an additional problem in that the adding HBR to the alkene restores the chiral centre at position 3 meaning that the phenyl can go endo or exo....more isomers.

As a rule, a sensible chemical route should avoid inserting chirality just to eliminate it and then restore it at a later step,

 

[vecktor]

I guess that throws it out the window as a psychedelic then, but what about an analogue of MMDA?
Pihkal #134

that is a very intriguing molecule, a constrained 2C version of MMDA 3a .. make it and taste it is the only answer, I suspect it would be a dopamine and serotonin reuptake inhibitor maybe even a serotonin substrate releaser but it seems that anything at 2,5,6 reduces the activity of MD compounds as releasers. I couldn't find anything particularily similar in the literature. the unconstrianed 2c version appears to be a mild mood enhancer nothing more

 

[Oddeye]

That pretty cool, does the effect on RC vary a lot or still fits only the "old" categories of drugs and you are trying new mixture. Psychedelic / empathogens / entactogens / deliriant, etc, ;-P
Because I guess their can't be a million of different psychoactive effect.

 

[Xorkoth]

^^ What? Each "RC" has a different effect from each other one. For example, many are psychedelic, but each of the psychedelic ones is unique, and not like any of the traditional psychedelics except in certain ways.

 

[IGNVS]

heres another rc i just thought of lookin at the acid and dragonflies thread

beta etheyl n isopropyl n methyl tryptamine

actualy ... just the part where they layed the tryptamines over acid

 

[fastandbulbous]

to put it quite simply the two alkenes are not identical, and your scheme is fatally flawed.

Right, got you. I was just thinking in terms of the piperidine ring without the ethylene bridge. I forgot that they are pretty firmly constrained (three legged stool effect on carbons attached to nitrogen). The scheme would work with the arecoline analogues as the ring isn't contrained (but I don;t know just how active they are). It also involves para fluoro-MPTP as an intermediate product, so possibly best left well alone.

 

[Smyth]

With regards to (2) and (3) posted by bigmac74, the first one seems reminiscent on a tranylcypromine ring structure, whereas the other one looks similar to some aminotetralins.

I guess since phenylpropanolamine is quite synthable, you could make (2) by dehydration with, say MnO2, followed by epoxidation with peroxyacid.

Then since (3) is related to aminotetralin, I think ive read that dehydration/aromatization can occur with quinoline or something, although i'd have to chech how exactly in order to be sure.

Tropene analogs are possible although they tend to display more activity as 5HT rather than DA RI's. There's definately some potential in this area though although not in the form of the answers that you suggested.

You can also make the above analog which pays homeage to the F&B hypothesis. I dont like my structure there though since the nitrogen is tied up in an aromatic ring. Let me suggest a structure related to anatoxin-a. Try searching for the structure of UB-165 to see where im going with this.

 

[fastandbulbous]

I guess since phenylpropanolamine is quite synthable, you could make (2) by dehydration with, say MnO2,

No you get the aziridine formed by dehydrating (nor)ephedrine type compounds, which are extremely toxic. The oxirane (epoxide) ring is highly reactive and that compound (2) would be highly unstable & reactive. Tranylcypromine is stable as it's an alicyclic (all carbon) ring as opposed to a heterocyclic ring

 

[Smyth]

Yeah, some of that stuff is diabolical, I only posted answers to humor myself. But I thought aziridines required nitrenes (c.f. carbenes) in order to make.

 

[hugo24]

No need to cry...

For the third year in a row:

PiPT (N-propyl,N-isopropyltryptamine). This one actually IS mentioned in TiHKAL - But only mentioned as a name in a list. Is it *that* impossible to synth?? geez.

*cries*

Just stumbled across this (my net connection has been cut,ouch-moved to a new place...).PIPT exists,I was up to 25mg with no clear effects noted,maybe something placebo/threshold.It would be the first one of the isopropyltryptamines with no activity at 25mg.But I bet it WILL have at higher levels...

 

[Morninggloryseed]

25mg orally? Well I wouldn't sweat it yet. It may have no auditory properties, and the full dose of DiPT and DPT are much higher than 25mg. Perhaps we need to approach 100mg to see much.

 

[bigmac74]

Aromatic amines are generally known to be carcinogens & 2 would be unstable (besides epoxide rings are DNA alkylators and as such, well didgy)

What do you mean by 'generally'? Is it just hit and miss whether they are carcinogenic or not or does N-substitution come in to play? Paracetamol is an aromatic amine that AFAIK is non-carcinogenic, along with many of the benzodiazepines.

 

[Dude I'm sooo high]

I want an RC that gives me the feel good effects of ecstasy, the visuals of LSD, the munchies of pot, the alertness of speed, the pain relief of opiates, and the erection of viagra. Is that too much to ask for? Sheesh Shulgin... get to work already!

 

[vecktor]

What do you mean by 'generally'? Is it just hit and miss whether they are carcinogenic or not or does N-substitution come in to play? Paracetamol is an aromatic amine that AFAIK is non-carcinogenic, along with many of the benzodiazepines.

it is rather hit and miss, sometimes it seems to be to do with whether they are metabolically oxidised, for example 2 naphthylamine causes bladder cancer whereas 1 naphthylamine doesn't. N substitution, the position of the amino group, the other sustituents and the pharmacodynamics all play a part.
just how hit and miss is illustrated by paracetamol versus phenacetin, they are both acetyl derviatives of aniline phenacetin has a 4 methoxy rather than a 4 hydroxy and is a known carcinogen wheras there is little evidence that paracetamol is carcinogenic. indeed phenacetin is metabolised into paracetamol in vivo.

 

[fastandbulbous]

It basically requires an aromatic amine to have a big pol;ar group attached somewhere to facilitate excretion; with paracetamol/phenacetin, the moethoxy group doesn't make it polar enough for the kidenys to get rid of it before it can do it's nasty little work, that's why para-aminobenzoic acid isn't dodgy but 4-methylanaline is. Of course there are some weird affairs like the aforementioned napthylamines