02-25-02 19:58
No 273576
Not that I would ever claim this to be efficient anyway, but in the past, newbees have asked if it is possible to add a methylenedioxy ring to the benzene ring in methamphetamine, forming our beloved MDMA. It has often been stated, no. There is no such possibility, any way to graft such a ring onto the right place.
Perhaps there are indeed a few options at one's disposal for such a conversion, although they would not be high yielding. Although not practical at all, I do find such a subject very entertaing to think about.
Step one: Attach either a nitro group or a halide, specifically bromide or iodide, to the 4-position.
Either brominate methamphetamine, iodinate it, or nitrate it. Very simple idea.
Step Two: Make that EWG into a hydroxy.
Either reduce the nitro to an amine, and then diazotize with sodium nitrite to form the phenol, or react the bromide, or preferably iodide, with sodium hydroxide to form the phenol. I know aromatic chlorides do not like to come off, but I know bromides will with some good heat, and iodides even easier.
Step Three: Addition of a group ortho to our hydroxy.
Option one, a complete guess that I cannot bank on for certain: the Reimer-Tiemann reaction. Add an aldehyde ortho to the hydroxy, which is meta to the aliphatic chain. If this does not work, then I give you:
Add a carboxyl ortho to the hydroxy. Now we have a myriad of possibilities to transform this into a second hydroxy.
A)Preparation of the ammonium salt, followed by dehydration to the amide, Hoffmann rearrangement with Ca(OCl)2 to produce the aniline, and then another diazotization to get our catechol.
B)Reaction with calcium formate to reduce the acid to the aldehyde. This reaction may or may not work. Don't count on it.
C)The Hunsdieker Reaction.
Changes the carboxyl to a halide, preferably the iodide.
D)Any "standard" reduction method for reducing a carboxyl to an alcohol, followed by oxiation of the alcohol to the aldehyde.
Step Four: Transformation of the Meta Group into a Hydroxy.
If the group is an alcohol, oxidize it to an aldehyde.
If the group is a halide, react with sodium hydroxide.
If the group is an amine, diazotize with sodium hydroxide.
If the group is a carbaldehyde, use the Dakin reaction with H2O2 and NaOH to produce the catecholate salt.
Step Five: Building The MethyleneDioxy Bridge.
Methylenate with DCM and a phase transfer catalyst, or with diiodomethane. If you have gotten this far, congratulations! You have beaten the odds, and turned methamphetamine into ecstacy!
So, let me have it, why can't it work? I'm ready to hear it, I promise.
PrimoPyro
The Water Will Be Your Only Mirror
(Hive Bee)
02-25-02 20:05
No 273578
If cheese ever knows his chemistry like Pyro, cheese will throw in his 2 cents..... one day it will ALL make sense.
May The Source Bee With You...Always.
(Hive Bee)
02-25-02 20:29
No 273589
Pyro you da man. I knew there was some possibility. but would you have to worry about the MeNH2 group on the propenal chain being destroyed by any of those reactions. Atleast if it doesn't work we now know how to build a MD bridge from scratch.
Vl_
(Chief Bee)
02-25-02 22:32
No 273639
Even better, but still bad:
1) Protect the nitrogen (with something suitable)
2) Brominate the amide with dibromodioxane (very para-selective)
3) Switch the bromo for a hydroxy using 4M KOH/Cu/EtOAc
4) Monobrominate the 4-hydroxy in the 3-position with KBr/H2SO4/H2O2 (or Br2)
5) Switch the bromo for a hydroxy using 4M KOH/Cu/EtOAc
6) The N-protected 3,4-dihydroxymethamphetamine is methylenated with CHCl2/DMSO/NaI/PTC
7) The resulting N-protected MDMA molecule is deprotected and turned into the HCl salt
(Hive Bee)
02-26-02 01:21
No 273689
Rhodium
How come when I asked, you just said no?
VL_
(Hive Bee)
02-26-02 02:38
No 273716
Because this is not a synthetically viable route. By the time you got to MDMA, there wouldn't be anything left anyway!
(Stoni's sexual toy)
02-26-02 03:05
No 273730
Anyone planning to do a 7 step synth better knows their chemistry and only uses high-yielding reactions for those steps. One mistake and you end up with zero, nada, nothing. 70% yields in all the steps and you end up with 8% overall yield. Do the math, such reaction sequences are incredibly expensive and time consuming, and I can guarantee 100% failure rate when attempted by a newbee.
I'm not fat just horizontally disproportionate.
(Hive Prodigy)
02-26-02 04:33
No 273753
And that is precisely why the answer to this question has always been no, and it is precisely why this thread is for entertainment only. It is theoretically possible, but it is highly unreasonable due to practicality issues.
Yet another instance that proves real world situations are just as important as textbook theories and models.
By the way, bees: All information needed to outline such syntheses, exists, and was indeed found, on The Hive and Rhodium's website, in conjunction with Google for name reaction databases for additional inspiration. Isn't it amazing what you can think up when curiosity combines with a hyperactive mouse-clicker-finger?
PrimoPyro
The Water Will Be Your Only Mirror