trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclop

[entheogenic-gnosis]

Summary
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT2A and 5-HT2B receptors. Therefore, at appropriate doses – although (−)-4 and (−)-5 may be useful as tools to probe 5-HT2 receptor function – one would need to be mindful that their selectivity for 5-HT2A receptors is somewhat less than for DOI itself.

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT[2] family ...

www.ncbi.nlm.nih.gov

-eg

 

[entheogenic-gnosis]

Anticipating the potential need for a substance to replace DOI as a research tool, we sought to identify a molecule that might have pharmacological properties which are identical, or at least very similar to those of 1a. We had previously characterized the cyclopropane analogue of a hallucinogenic amphetamine known as DOM (2) and had shown that 3 (DMCPA) had high potency both in vitro and in vivo [1–3]. We thus considered whether the cyclopropane analogues 4 and 5 might be useful research tools. Accordingly, this report details the synthesis of racemic trans-1-(2,5-dimethoxy-4-iodophenyl)-2-aminocyclopropane (4) and its bromo homolog 5, the resolution of 4 into its (−)-(1R,2S)-enantiomer, as well as the resolution of the cyclopropane carboxylic acid precursor and subsequent bromination to provide both enantiomers of 5

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT[2] family ...

www.ncbi.nlm.nih.gov

-eg

 

[entheogenic-gnosis]

I figured there would be more interest in this topic...

Technically, you could take the ethylamine side chain of these active phenethylamines, or the three carbon side chain of the psychedelic amphetamines, and replace it with a cyclopropylamine moiety producing a novel, and active psychedelic molecule.

The pharmacology of these cyclopropylamine homologues of the 2Cx/DOx compounds is unique as well:

Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT(2A) and 5-HT(2B) receptors.

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT(2) receptor family - PubMed

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT(2) family of receptors; and the more potent...

www.ncbi.nlm.nih.gov

Racemic 4 and 5 were compared in radioligand competition assays against radiolabeled antagonists defined at the human 5-HT2A and 5-HT2C receptors and compared with racemic 1a and 1b. The results are shown in Table 1. As can be seen, the cyclopropane analogues 4 and 5 showed affinities for the 5-HT2A receptor 5–6-fold greater than 1a and 1b. Affinities at the 5-HT2C receptor were about two-fold higher than for 1a and 1b.

At the 5-HT2C receptor 1a was the most potent, with an EC50 that was about three times lower than for 1b, 4, or 5. In functional assays, therefore, the cyclopropane analogues 4 and 5 compared to 1a or 1b appeared as potent and had a similar degree of maximal stimulation at each of the respective 5-HT2 receptors.

We then carried out a broader screen of 4 and 5 for affinities at a range of other 5-HT receptor isoforms (Table 3). Their affinities at other 5-HT receptors, however, were higher than for 1a. In particular, the introduction of the cyclopropane appears to increase significantly affinities at the 5-HT1A, 5HT1B, and 5-HT1D receptors. In that regard, although (−)-4 and (−)-5 have affinities at the 5-HT2A receptor somewhat higher than 1a, their selectivity over the 5-HT1A receptor is less than 100-fold. As shown in Table 1, both 4 and 5 are extremely potent ligands in vitro. Furthermore, as anticipated, it was the (−)-enantiomers that proved to have highest affinity. We included (+)-5 in Table 3 simply to illustrate the difference in affinity between the two enantiomers. We assume that the final compounds have the (−)-(1R,2S) and (+)-(1S,2R) absolute configurations based on our earlier work establishing the absolute configuration of 3 [2], and the fact that substitutions at the 4-position of the aromatic ring in chiral substituted amphetamines do not change the sign of optical rotation [4]. The biological data are consistent with those configuration assignments.

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT[2] family ...

www.ncbi.nlm.nih.gov

In conclusion, our strategy to replace the ethylamine side chain of 1a (or 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-1R,2S-configuration. However, at appropriate doses, although (−)-4 and (−)-5 may be useful as tools to probe 5-HT2 receptor function, one would also need to be mindful that their selectivity for 5-HT2A over 5-HT1A is only about 70-fold

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT[2] family ...

www.ncbi.nlm.nih.gov

The synthesis of these molecules is not very difficult either...

-eg

 

[benzyme]

there just isn't alot of interest of phenethylamine rc's on the nexus. this is mostly a tryptamine-centric board, unlike the nook and other boards of that ilk. this isn't hive, ca. 1999/synthetikal, ca. 2003 (thank god/satan). those sites were full of darwin award winners and general dbags. a handful of them made it out alive, and started up another nest.
I'd know, i'm an old original bee (hypo).

this is by far, the finest board. part of that reason is, we don't discuss synthesis. I am probably the root cause of that policy.

 

[entheogenic-gnosis]

there just isn't alot of interest of phenethylamine rc's on the nexus. this is mostly a tryptamine-centric board, unlike the nook and other boards of that ilk. this isn't hive, ca. 1999/synthetikal, ca. 2003 (thank god/satan). those sites were full of darwin award winners and general dbags. a handful of them made it out alive, and started up another nest.
I'd know, i'm an old original bee (hypo).

this is by far, the finest board. part of that reason is, we don't discuss synthesis. I am probably the root cause of that policy.

I see the psychedelic tryptamines and phenethylamines as equal. Both are related to neurotransmitters, both classes contain entheogens with long histories of human use, both classes are mainly targeting the 5HT2a/c receptor sites...

When I hear of an entirely new active series of compounds with close molecular relation to known psychedelics it piques my interest.

I'm more interested in research, I honestly believe these compounds have value.

I've never been a fan of the research chemical market, and I can understand why synthesis is not discussed, but how something like this could hold little interest to those in the study of psychedelics...This is a mystery to me.

-eg

 

[Mindlusion]

The synthesis of these molecules is not very difficult either...

-eg

Might look simple on paper to the uninitiated, but not to someone who has actually worked with these materials...
The difference between the chemist and the 'textbook chemist'

A lot of bee's killed themselves with LAH/THF, but diazomethane? There would be none left. First of all, it's a gas that needs to be generated, its more acutely toxic than HCN, and its more explosive than most azides. It's known to detonate when coming in contact with just scratches in glassware. Deaths have been reported in professional labs let alone a home setting.

Besides, there are far better (and safer) carbenes to use than diazomethane

I have an interest in these compounds, the various substiuted phenethylamines as well as tryptamines. More of a curiosity than anything, always something new to explore. But in terms of psychedelics, you don't need much. DMT or mescaline or psilocybin are all way more than enough for a single human being, even all humanity

 

[entheogenic-gnosis]

The synthesis of these molecules is not very difficult either...

-eg

Might look simple on paper to the uninitiated, but not to someone who has actually worked with these materials...
The difference between the chemist and the 'textbook chemist'

A lot of bee's killed themselves with LAH/THF, but diazomethane? There would be none left. First of all, it's a gas that needs to be generated, its more acutely toxic than HCN, and its more explosive than most azides. It's known to detonate when coming in contact with just scratches in glassware. Deaths have been reported in professional labs let alone a home setting.

Besides, what you posted isn't even the full scheme. and there are far better (and safer) carbenes to use than diazomethane

I have an interest in these compounds, the various substiuted phenethylamines as well as tryptamines. More of a curiosity than anything, always something new to explore. But in terms of psychedelics, you don't need much. DMT or mescaline or psilocybin are all way more than enough for a single human being, even all humanity

Uninitiated?

I suppose I should be somewhat insulted, but honestly I can not summon up the ego required for a discussion on the matter, though I can assure you, your assumptions regarding myself are inaccurate to say the least.

there's nothing really complicated about the synthesis of these molecules, any professional could fairly easily synthesize these compounds. The point of the statement was to illustrate that there should be no chemical barriers to research, the compounds are easily synthesized ( by professionals) and thus, provided everything else is in order, they should be easy to research. I guess the term "easy" is subjective, however to an educated and trained chemist, the synthesis should not present any major issues in terms of complexity...the chemicals used may present potential hazzards, and may be potentially dangerous, but dangerous and complicated are two separate things, and even very dangerous chemicals can be safely employed (by professionals)...

In the link below diazomethane is discussed.

That diazo group is looking for an excuse to revert back to nitrogen gas, which process comes with an inevitable no-substitutions side order of kaboom. The chemist’s job is to not give it that excuse. That means that you can’t heat the stuff up, you don’t make it very concentrated, and you don’t even expose it to sharp or rough surfaces, because that can be enough right there. They sell distillation glassware specifically for diazomethane preps, with weirdly glossy ground-glass joints.

http://blogs.sciencemag.org/pipeline/archives/2008/04/30/how_not_to_do_it_diazomethane

If an individual can not safely handle tetrahydrofuran or lithium aluminum hydride then they don't belong in the laboratory, and if any individual is willing to attempt such synthesis procedures, specially one using diazomethane, at home, then maybe that's natural selection hard at work when they become injured or killed...

I'm aware I did not post the entire work-up, I didn't see the need, this topic was not generating any interest, and the synthesis was really the least interesting aspect of this topic, regardless, if you open the link all the information is provided.

-eg

 

[SnozzleBerry]

Not long ago, someone made an admission of engaging in pretentious behaviors. Imo, they would do well to remember their former words...

 

[entheogenic-gnosis]

Not long ago, someone made an admission of engaging in pretentious behaviors. Imo, they would do well to remember their former words...

How does this relate to novel phenethylamines?

-eg

 

[Mindlusion]

I didn't mean to offend. I really do appreciate your interest in this stuff eg and your posts on them.

Part of the reason we don't discuss synthesis as benz outlined is due to general amount of darwin award winners that attempt these things, as seen on the hive. That's why I made the joke about the LAH/THF vs diazomethane. The hive had a select few of talented and responsible chemists. Mind you, the skilled and experienced are actually more likely to make absent minded mistakes, sometimes fatal ones.

Of course diazomethane can be handled safely, I've done it many times. But it's not the point I was trying to make. That is the least of your problems. Unless your lab is improvised, then you're a potential candidate for a darwin award.
I say uninitiated because theory, especially incomplete, only goes so far. Anyone can follow a diagram but actually doing it is a different story. Have you ever worked with cyclopropanes? They are not well-behaved molecules. They react and decompose with sunlight or during a work up. Not to mention they are chiral molecules, diazomethane would give you a mixture of enantiomers, which then requires resolution and determination of the correct enantiomer etc etc. It's a lot of work. The problems are not apparent unless you physically there doing the work and figuring this stuff out. No synthesis is exactly the same. Truly, Org chemistry is really more of an art than a science.

I react strongly to this because one too many times I've read posts on the hive or science-madness with users who read about actual work and think they understand and have mastered it off the bat, while totally oblivious to the reality of it. Then they go about spreading misinformation or something outright dangerous, without actually attempting it themselves.

I am not at all saying you are one of these people, again, I appreciate your posts. But yeah, that is where i'm coming from.

 

[entheogenic-gnosis]

I didn't mean to offend. I really do appreciate your interest in this stuff eg and your posts on them.

Part of the reason we don't discuss synthesis as benz outlined is due to general amount of darwin award winners that attempt these things, as seen on the hive. That's why I made the joke about the LAH/THF vs diazomethane. The hive had a select few of talented and responsible chemists. Mind you, the skilled and experienced are actually more likely to make absent minded mistakes, sometimes fatal ones.

Of course diazomethane can be handled safely, I've done it many times. But it's not the point I was trying to make. That is the least of your problems. Unless your lab is improvised, then you're a potential candidate for a darwin award.
I say uninitiated because theory, especially incomplete, only goes so far. Anyone can follow a diagram but actually doing it is a different story. Have you ever worked with cyclopropanes? They are not well-behaved molecules. They react and decompose with sunlight or during a work up. Not to mention they are chiral molecules, diazomethane would give you a mixture of enantiomers, which then requires resolution and determination of the correct enantiomer etc etc. It's a lot of work. The problems are not apparent unless you physically there doing the work and figuring this stuff out. No synthesis is exactly the same. Truly, Org chemistry is really more of an art than a science.

I react strongly to this because one too many times I've read posts on the hive or science-madness with users who read about actual work and think they understand and have mastered it off the bat, while totally oblivious to the reality of it. Then they go about spreading misinformation or something outright dangerous, without actually attempting it themselves.

I am not at all saying you are one of these people, again, I appreciate your posts. But yeah, that is where i'm coming from.

Understood. (but would you not feel a bit patronized or insulted as well? )

Regardless, unless it's related to research it's a waste of my time on the nexus, I'm not here to make friends, or to make a name for myself, I'm not looking for answers, and I'm not looking for anybody's respect, I simply want to research and discuss psychedelic compounds, everything else has its own time and place.

-eg

 

[entheogenic-gnosis]

I didn't mean to offend. I really do appreciate your interest in this stuff eg and your posts on them.

Part of the reason we don't discuss synthesis as benz outlined is due to general amount of darwin award winners that attempt these things, as seen on the hive. That's why I made the joke about the LAH/THF vs diazomethane. The hive had a select few of talented and responsible chemists. Mind you, the skilled and experienced are actually more likely to make absent minded mistakes, sometimes fatal ones.

Of course diazomethane can be handled safely, I've done it many times. But it's not the point I was trying to make. That is the least of your problems. Unless your lab is improvised, then you're a potential candidate for a darwin award.
I say uninitiated because theory, especially incomplete, only goes so far. Anyone can follow a diagram but actually doing it is a different story. Have you ever worked with cyclopropanes? They are not well-behaved molecules. They react and decompose with sunlight or during a work up. Not to mention they are chiral molecules, diazomethane would give you a mixture of enantiomers, which then requires resolution and determination of the correct enantiomer etc etc. It's a lot of work. The problems are not apparent unless you physically there doing the work and figuring this stuff out. No synthesis is exactly the same. Truly, Org chemistry is really more of an art than a science.

I react strongly to this because one too many times I've read posts on the hive or science-madness with users who read about actual work and think they understand and have mastered it off the bat, while totally oblivious to the reality of it. Then they go about spreading misinformation or something outright dangerous, without actually attempting it themselves.

I am not at all saying you are one of these people, again, I appreciate your posts. But yeah, that is where i'm coming from.

It's always a bad idea to make assumptions when you have no idea who you are speaking with...

-eg

 

[Mindlusion]

well, not too long ago we were attempting to explain some of the most basic principles of chemistry like resonance, and that did not go well. So forgive me for making 'assumptions'.

 

[SnozzleBerry]

Not long ago, someone made an admission of engaging in pretentious behaviors. Imo, they would do well to remember their former words...

How does this relate to novel phenethylamines?

-eg

This relates to your attitude and posts in this thread. Didn't think I'd have to spell it out for you...but there you go. Your posts above further demonstrate my point.