12-11-03 20:16
No 476202
Would (1S,2S)-2-amino-1phenyl-1,3-propanediol be a likely precursor to amphetamine after reduction?
To clarify the question,
1)During reduction would cyclization be problematic?
2)Would stereochemistry after reduction be any sort of problem?
Possible routes would be diol->dichloro->alkene (the route I think that would most likely lead to cyclization), straight catalytic over Pd/C, or the Chlorotrimethylsilane/NaI/Acetonitrile routes...
I am still unclear whether or not catalytic hydrogenation causes inverted stereochemistry, after reading about 10 contradictory posts where the point was never brought to conclusion. I don't believe it to be the case though.
Please flame at leisure, if you are bored, I realize I am quite the target for proposing this. Yes, it isn't a common chem, and it's final product would not be n-methyl, but if it was simply lying around, could it be utilized in a facile manner?
(Wizard Master)
12-12-03 03:10
No 476277
Would (1S,2S)-2-amino-1phenyl-1,3-propanediol be a likely precursor to amphetamine after reduction
YES ! RP/HI reduction to reduce the diols on the 1st carbon and 3rd carbon of the propane.
(Hive Bee)
12-12-03 14:08
No 476394
I appreciate the reply WizardX, that is what I wanted to know!
I do believe that the TMSC method is possible, and that may be applied first, but failing that, it looks like the RP/I will be flown.
BTW, you have supplied about half of the info that I have on permanent files on the subject, your body of knowledge is not only impressive, it is appreciated and stockpiled...
Danke!
Atropos
(Chief Bee)
12-17-03 08:48
No 477353
(Rated as: excellent)
An Efficient Synthesis of (S)-(+)-Amphetamine from (1S,2S)-2-Amino-1-Phenyl-1,3-Propanediol
Tetrahedron: Asymmetry, 4(7), 1619-1624 (1993) (../rhodium /amph.p
Abstract
Optically active (S)-(+)-amphetamine hydrochloride (5·HCl) was prepared from (1S,2S)-2-amino-1-phenyl-1,3-propanediol (1) via its 3-iodo intermediate (3). A phthaloyl group was used for protecting the amine function.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
12-18-03 08:10
No 477565
Thanks much Rhodium, that was an excellent post. Seems like PPh3 turns up more and more in my research... Very handy reagent...
It also seems as if you always turn up exactly what I am looking for. Either I need a better search strategy or a better library (and faster computer),
The only thing that troubles me is: "In order to realize the outlined strategy, selection of a proper amine protecting group was essential."
HOW essential... I assume it is either due to cyclization, or the amine group also lost without protection with this route.
i think chemists should spend more time outlining their failures, with %'s, by products and previous failed reactions. I think I have learned more about the molecules I have worked with from my failures than my triumphs...
I can probably answer my own question, but it's late, and I am wiped out. Tomorrow it is...
(Chief Bee)
12-19-03 15:27
No 477838
HOW essential... I assume it is either due to cyclization, or the amine group also lost without protection with this route.
The reason is di/polymerization and cyclization, a primary alkyl iodide is very keen on alkylating any nearby amine irreversibly.
i think chemists should spend more time outlining their failures, with %'s, by products and previous failed reactions.
Definitely, that was more common in earlier times, but with the incredibly large scientific information production of today, they feel that only successful reactions are worth the paper they are printed on.
There is however a commercial database of failed reactions available from http://www.isinet.com but it has an outrageous pricing...
The Hive - Clandestine Chemists Without Borders