Sedit (Stranger)
11-17-00 07:13
No 69775
      MDMA and the Indole Structure  Bookmark   

    This has been on my mind fo ra while now an i was just woundering if anyone besides me has noticed the simularitys between the ring structure of MDMA and the indole structure?
Replace the bottom oxygen of MDMA with N and the Top with C and you have the ring structure of the indole class. Has any one heard of th effects of such a drug? And so you thing that this could explain why MDMA blocks the reuptake of dopamine and serotonin while Meth only blocks dopamine(correct me if im wrong).If this proves to be the caseit could really help in the creation of new and exotic substances. Does any one have any Ideas On how to go about synthesising this sort of substance cuz if it hasnt been made yet i will devote all my time and effet into the creation and testing of such a substance. So whos with me on this one . IndolMeth


Life is short then ya Die so lets go party and all get High
 
 
 
 
    savestheday
(Hive Bee)
11-20-00 22:41
No 69954
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

wait, but the methylene dioxy ring isn't a benzene ring, right? correct me if im wrong though...
 
 
 
 
    Rhodium
(Chief Bee)
11-21-00 10:07
No 70072
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

The nitrogen-containing ring in indole is aromatic and thus flat. The methylenedioxy ring in MDMA is aliphatic, and does project somewhat out of the plane (envelope shape).


http://rhodium.lycaeum.org
 
 
 
 
    Sedit
(Stranger)
11-22-00 04:39
No 70238
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

   OHHHhhhhh....  Then what is it that makes one flat and the other aliphatic and would there be any way to make the indol structure aliphatic with out destroying activity. has any one tryed to replace the 2 O atoms in the ring with something else to see if it still retains activity?


Life is short then ya Die so lets go party and all get High
 
 
 
 
    Lilienthal
(Moderator)
11-22-00 11:28
No 70316
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Yes, this looks very interesting.
http://www.fortunecity.com/westwood/storey/116/ Lilienthal's Reference #305:
4-, 5-, 6-, and 7-isotryptamines from formylindoles, Helv. Chim. Acta 1616 1968, F. Troxler
 
 
 
 
    serodronin
(Hive Bee)
11-26-00 11:55
No 70951
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

how do you intend to change out the methylenedioxy ring?  might be possible if you started with something like eugenol and changed out the oxygens, then methylenated it.


I try to take my reactions on one at a time, but lately several reactions have attacked me at once.
 
 
 
 
    Bozakium
(Hive Bee)
10-11-01 22:30
No 223293
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

sedit: the aromatic ring if flat due to the double bonds between the p-orbitals of the  carbon atoms. The single-bonded aliphatic chain is "3-d" because the 4 single bonds on the carbon atom are at 120 degree angles to each other. The spatial relations of atoms in a covalently-bonded molecule are due to the shape of the s and p-orbitals and sp-orbital hybridization. It it tough to explain in words, but a molecular model kit or intro collecge organic chem text can illistrate it for you very easily.--Bz138
 
 
 
 
    foxy2
(Distinctive Doe)
10-12-01 09:49
No 223564
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

What would be interesting is to take 5-bromoindole and make 5-(2-aminopropyl)indole, a substituted amphetamine analog.  I wonder how one could go about this? 
Seems there would be polymerization and other issues because of the reactivity of the 3 position of the indole ring, right?

Do Your Part To Win The War
 
 
 
 
    slappy
(Hive Bee)
10-12-01 10:06
No 223567
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Actually Boz, that would be 109.5 between bonds on an sp3 hydridized carbon.

From all of the molecular modeling that I have seen, the methylenedioxy group (except the Hydrogens) pretty much stays within the plane.
 
 
 
 
    pantopon_rose
(Stranger)
10-12-01 11:52
No 223585
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Bozakium has explained very well for someone who can visualize the orbitals and their effects on the positions of atoms. I suggest you read into stereochemistry, sedit. That will give help explain the concept of these structures. Like it's been said, they aren't flat like we draw them on pieces of paper, they are three dimensional (and probably four dimensional, depending on whether you consider time a dimension and the fourth to be a spatial bumping time up to fifth).

How many times must the cannon balls fly, before they're forever banned?
 
 
 
 
    Rhodium
(Chief Bee, Ex Hive Addict)
10-12-01 12:30
No 223593
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Foxy: Yes that would be an interesting chemical adventure. The reactivity of the 3-position is a problem, but I believe it can be protected by bisulfite (or similar).
 
 
 
 
    wandering101
(Hive Bee)
10-12-01 13:05
No 223607
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

pantopon_rose, please explain what you mean by 4 dimensional, with time as a fifth.
I've done 10-d, and 26-d (OK, I still can't handle the 26 stuff even a little bit) views of reality in physics (time NOT seperated from the spatial dimensions) - it's just more complex calculus....
 
 
 
 
    pantopon_rose
(Stranger)
10-12-01 23:24
No 223776
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

I've just barely started calculus and don't have even the slightest clue how to do 10-d I group muchless the 26-d supersymmetry boson math. In other words, I have no idea how one would narrow the 10 spacetime dimensions down to at least even six, muchless four. I have just been reading too much supertstring mumbojumbo before I know how to do the math for it is all. Sorry if I got you excited or something; like thought you had someone who could discuss physics on that level with you. Maybe in about four years when I graduate?wink Any good books to recommend? (Sorry for changing the subject of the thread ya'll, it really was not my intent.)

How many times must the cannon balls fly, before they're forever banned?
 
 
 
 
    megamole
(Hive Bee)
10-14-01 07:00
No 224292
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Another interesting compound, heretofore undiscussed but along the same tangent, would be [2-(2,3-Dihydro-1H-indol-5-yl)-1-methyl-ethyl]-methyl-amine -- the indoline analog of MDMA. Aliphatic, but with the lone pair in the 4-position; this one should be relatively simple to make as well (it could be easily made from the corresponding indole by reduction with BH3*THF complex.)

"Give me ten minutes with your inner child, and I'll give you back an inner adult."
 
 
 
 
    foxy2
(Distinctive Doe)
10-14-01 14:23
No 224381
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Hmmm, Is that IUPAC naming???
wink wink

Do Your Part To Win The War
 
 
 
 
    Rhodium
(Synaptic Cleft Mountaineer)
10-14-01 16:55
No 224400
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Probably. It is MDMA with the methylenedioxy -O-CH2-O- substituted with -CH2-CH2-NH- instead. But I doubt it would be active, I know of no active compounds with an amine function on the benzene ring.
 
 
 
 
    Lilienthal
(Moderator)
10-16-01 02:32
No 224989
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

>>> it could be easily made from the corresponding indole by reduction with BH3*THF complex.

This doesn't work, but NaBH4 / AcOH could be used for that reaction.
 
 
 
 
    megamole
(Hive Bee)
10-16-01 20:14
No 225333
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   


I know of no active compounds with an amine function on the benzene ring.




benzodiazepines?
paracetamol?
fentanyls?


 
 
 
 
    Rhodium
(Synaptic Cleft Mountaineer)
10-16-01 20:40
No 225342
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

Okay, let's rephrase: "I know of no entheogens/entactogens with an amine or amide function on an aromatic ring". The 4-amino and 4-acetamido derivatives of 2,5-DMA is for example fully inactive.
 
 
 
 
    megamole
(Hive Bee)
10-17-01 11:06
No 225724
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   

>>it could be easily made from the corresponding indole by reduction with BH3*THF complex.

>This doesn't work, but NaBH4 / AcOH could be used for that reaction.

J.Org.Chem. (1984) 49(26), 5124-5131.
J.Org.Chem. (1985) 50(12), 2066-2073.

Admittedly, the reagent of choice for reducing the 2,3-double bond is NaCNBH3, but BH3*THF does indeed work, for the record. Other common reagents used to reduce the 2,3-double bond include zinc borohydride and tetrabutylammonium borohydride.
 
 
 
 
    megamole
(Hive Bee)
10-18-01 23:56
No 226407
      Re: MDMA and THE INDOLE STRUCTURE  Bookmark   


Okay, let's rephrase: "I know of no entheogens/entactogens with an amine or amide function on an aromatic ring". The 4-amino and 4-acetamido derivatives of 2,5-DMA is for example fully inactive.




"Entheogenic" is such a subjective term! And surely you would agree that there are many non-entheogenic biologically active compounds worthy of interest. Perhaps you may find the following articles interesting:

European Journal of Medicinal Chemistry (1996) 31 133-142.
European Journal of Medicinal Chemistry (1999) 34 137-151.
Journal of Medicinal Chemistry (1963) 6 519-524.
Journal of Medicinal Chemistry (1978) 21 1 56-63.
Journal of Medicinal Chemistry (1980) 23 2 154-162.
Journal of Medicinal Chemistry (1986) 29 8 1406-1412.

Each of the them is a study of biologically-active 4-amino phenethylamines. Of particular interest to this discussion is the article from '86, in which the indole homolog of MDA is studied, which turns out to be, among other things, a potent MAO inhibitor at serotoergic, norandegenergic, and dopaminergic receptor terminals.

Also worth reading is the JMC article from '63, in which 4-dimethylaminoamphetamine was found to be a more potent anorexigenic compound than phenmetrazine (albeit somewhat weaker than amphetamine itself.)