drone's amphetamine synthesis contest

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Author Topic:   drone's amphetamine synthesis contest
drone 342
Member   posted 12-23-98 04:35 PM
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A while back, a character by the name Dr. Haney put together an informal contest for novel amphetamine syntheses. Its been a while, new information is out, and I think its time for another such contest to be held. I'm officially opening it up, with the same rules as the first one, the same prises, the same everything -- just a different judge. For a quick refresher, here's a link to the compiled list http://rhodium.lycaeum.org/chemistry/speedcon.txt . Alright. Let's see what you can do.

Labrat
Member   posted 12-24-98 09:38 AM
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Well, I'll start off with my own creation: making benz from phenylalanine.
Thus, phenylalanine is reduced with sodium borohydride/H2SO4 in THF to get the 2,3-aminoalcohol.

This aminoalcohol is reduced by HI/red P at reflux to amphetamine. The validity of this method has recently been proven by Assholium (thanks!). Lr/

drone 342
Member   posted 12-24-98 10:50 AM
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How 'bout this:
alanine is esterified with EtOH, an imine is formed with benzaldehyde, then the product is reacted with benzyl chloride to yield the benzylimine ethyl ester of alpha-methyl phenylalanine, which then is hydrolyzed to give alpha methyl phenylalanine, which is decarboxylated to yield benzadrine.

I knew you'd like that one.

drone 342
Member   posted 12-24-98 10:50 AM
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How 'bout a mitsunobu reaction of phenylisopropanol with methylamine?

drone 342
Member   posted 12-24-98 10:52 AM
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Just to get it out of the way, Red P/I reduction of phenylpropanolamine, ephedrine, or pseudoephedrine.

timeless
Member   posted 12-24-98 11:13 AM
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benzene + propionyl chloride -- AlCl3 -> Propiophenone (90%)
propiophenone + Br2 (in acetic acid) --> bromoketone (80%)

bromoketone + phtalimide (potassium carbonat) --> cathinone (70% - 85% i don't know)

cathinone + H -- Pd/C in glacial acetic acid --> amphetamine (80%)

Osmium
Member   posted 12-28-98 04:51 AM
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Here's my submission:
propiophenone + alkyl nitrite -------> oxime (I) in almost quantitative yield

(I) ---(H2;Pd/C;AcOH)----> amphetamine, yield about 80 for this step

Rhodium
Administrator   posted 12-30-98 07:28 AM
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I'd like to add what I posted in the Serious Chemistry Forum a while ago:
Alkylation of benzene with D-acetylalanyl chloride in the prescence of AlCl3, followed by Clemmensen reduction (Zn/Hg), which reduces the carbonyl and deprotects the nitrogen in one step to give enantiomerically pure D-amphetamine.

P2P is produced in quantitative yield when benzyl chloride is reacted with acetyl chloride in the prescence of a Pd catalyst (US Pat 5,146,001), and this is then reacted with NH4OAc/Mg to give amphetamine (JCS Perkin 1 265, 1995) in 75% overall yield.

P2P is reacted with

drone 342
Member   posted 12-30-98 03:37 PM
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Likewise, I'd also like to post a few goodies involving benzyl chloride.
Toluene is chlorinated to make benzyl chloride. Post 108053 (Jeremy McGrath: "Decarboxylation of 5 Hydroxytrptophan", Novel Discourse)

Benzyl chloride react with magnesium to form a grignard reagent, which is combined with CO2 to make phenylacetic acid.

Or, the same Grignard reagent can be reacted with acetic anhydride to make phenylacetone directly.

Or, the classic reaction of benzyl chloride with KCN to make benzyl cyanide, which is hydrolyzed to make phenylacetic acid.

Alternatively, the benzyl cyanide from the aforementioned reaction can be reacted with MeMgI to produce phenylacetone.

Phenylacetic acid is converted to phenylacetone in any number of ways, and subsequently is reductively aminated in any number of ways.

Alternatively, benzyl chloride can be reacted with acetic anhydride with a little electrolysis to make phenylacetone.

If you follow the link provided at the top of this message, as well as Post 108164 (CHEM GUY: "Let us try to find the one step alkene to amine", Novel Discourse)[/i], you'll find a bunch more ideas.

ChemHack
Member   posted 01-01-99 04:28 AM
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heh.
Vicks inhaler is extracted with....

Sorry, couldn't resist!

drone 342
Member   posted 01-01-99 01:10 PM
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I mustin't forget my beloved halobenzene + acetone + strong base -> P2P synthesis!
Now if this only could be done without such rigrorous conditions...

-drone --342

Mother
Member   posted 01-01-99 03:09 PM
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Mother jist luvs all hur a vary inventive younguns!
Keep them brains a rockin' now, ya' heer?

All My Love,

Mother

Wizard X
Moderator   posted 01-05-99 07:49 PM
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As much as I would like to tell you what
A & B are I can not.
Here is mine : A + B ==(catalyst)==(reflux)===>> amphetamine 38% overall
The more substituted the aromatic ring the greater the yield.
Methylenedioxy substitute 63% overall
This reaction has none of the precurors stated in this thread.

ChemHack
Member   posted 01-05-99 11:40 PM
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Lemme guess:
A = P2P
B = Methylamine
catalyst = raney nickle/H2

heh

rev drone
Member   posted 01-06-99 11:31 AM
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Propiophenone + sulfur/morpholine catalyst ->
P-2-P.

Bam!

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-the good reverend drone

Beagle
Member   posted 01-06-99 01:55 PM
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Drone: Are you talking about the Wildgerodt (sp?) rxn, Kindler modification? Doesn't that take you to the phenylacetic acid?

psychokitty
Member   posted 01-06-99 04:12 PM
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Here's my little contribution although I don't have the references with me presently to back it up:
Phenylalanine is either refluxed with formic acid under a dean-stark trap or mildly reacted with acetyl-chloride or acetic-anhydride to form the formyl or acetyl amide, respectively. Then phenylalanine or any of the amides mentioned above are reduced with sodium borohydride and iodine in THF to form the aminoalcohol or its N-alkylated version. Yes, you read right! In an analogue to the reduction of phenylalanine using sodium borohydride/sulfuric acid formerly posted -- I think -- at the beginning of this thread, amides of phenylalanine are successfully reduced into their respective N-alkylated aminoalcohols in about 85-95%, if I remember correctly. But, yes, I know, I know. This is a a "novel amphetamine sythesis" contest, not one of presenting new and novel ways to synthesize methedrine and ethamphetamine. So I guess that in my submission, I'm limited to only using plain-'ol-phenylalanine as my experimental example, which is just fine. By the way, I hope I get some credit for selecting a synthesis which makes use of a precursor that clearly has great potential but up till now, has recieved little attention, and has been used even less in any real application. . . . Continuing on, reduction of the alcohol group located, I think, on the gamma carbon of the propyl side chain, could be achieved any number of ways. Admittedly, however, they are ways that are not very new or novel. But they are effective nonetheless.

Here are just a few: Pd/C; substitution of Cl for OH, to subsequently be reduced with NaBH4 or H2 and catalyst; Li in liquid NH3; possibly HI, but I doubt it; . . . oh, fuck it, etc., etc. After all, who am I kidding? It's not like I'm enlightening anyone here. You all know these proceedures as well as I do.

-Psychokitty-who-is-not-sad-anymore-because-his-submission-is-at-least-better-than-Drone's

psychokitty
Member   posted 01-06-99 04:27 PM
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Just kitting and poking fun, Drone. I'm not trying to be competetive in the least. And congratulations! Those are some pretty novel ways to get to amphetamine. You may very well be the one who wins his own contest! I've got a few more methods up my sleeve that might qualify me for the title position, but it might end up being a rehash of some of the other stuff I've already posted. Some pretty cool stuff I have yet to post, however, due to time constraints and distractions by my predominant interest in responding to various other posts.
By the way, what're the limitations to the submissions? Must every idea be based on a published source, or can anything within the stretch of the imagination qualify? That last question was rather broad, but I think you the point. Please respond ASAP, if you can. Thanks.

-- Psychokitty

rev drone
Member   posted 01-06-99 05:20 PM
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psychokitty,
Ideally, it should have some literature behind it, but all I ask is that the science behind it be *fairly* solid. Let your imagination go wild -- I want to see just how far people can take amphetamine chemistry.

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-the good reverend drone

ChemHack
Member   posted 01-06-99 07:48 PM
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psychokitty: Perhaps you could use Tyrosine instead of Phenylalanine in your above synth to yield 4-hydroxl-amphetamine.

Labrat
Member   posted 01-07-99 10:56 AM
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Drone, you have no honour!
There's a better way to make P2P from propiophenone, at least it uses OTC chemicals in catalytic quantity:

propiophenone + H2SO4 + HgSO4 -> P2P
The P2P is reductive aminated to give ----, ofcourse.

quirks
Member   posted 01-07-99 11:26 AM
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hmmm... Is it just me or are people losing there grasp on practicality??
I would think the novel method of most benifit would be a tuned variation of one we already have. Say benzaldehyde from otc flavourings, which can be bought by the gallon, to grignard, still otc, to safrole/isosafrole then whichever from there.

Insanity Clause
Member   posted 01-07-99 08:48 PM
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Pseudoephedrine is reacted with SOCl2, and the product is then reduced with Pd/BaSO4 under hydrogen at STP. Yields are very good - I have dreamt of 75% return.

ChemHack
Member   posted 01-07-99 11:11 PM
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Clause: Lets here more!

bio
unregistered   posted 01-09-99 02:23 AM
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category: stuff in your kitchen(mostly)
bitter almond oil+sugar+yeast->phenylacetylcarbinal
PAC+ammonia+H2+catalyst->phenylpropylamine
PPA -> pure D-amp by ways covered ad-nausium

it is pure D because the first step is done steoreoselectively by the yeast(as most bio processes are)

refs for the first step, as nobody cares of the others prolly

Biotechnology and Bioengineering Vol 33, Pp 657-660(1989)
Biotechnology and Bioengineering Vol 34, Pp 933-941(1989)
USPatent 5,312,742
Biotechnology and Bioengineering Vol XXIX, Pp. 783-785(1987)
Biotechnology and Bioengineering Vol XX, Pp 493-498(1991)
CA 110:113139k
Advances in Biochemical Engineering Biotechnology, Vol 56, pp33-59 (1997)

this is done every day in huge quantities commercially. the eph you buy in the store is made this way(MeAmine instead of ammonia of course)

bio
unregistered   posted 01-09-99 02:27 AM
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clearly, phenylproplyamine was meant to be phenylpropanolamine. AKA the crap in diet pills.

Labrat
Member   posted 01-09-99 10:51 AM
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Reducing chloroephedrine with Pd/BaSO4 and H2 at STP? Hmm, that sounds like you repeated the procedure of Hermann Emde in the HCA 12:365('29). I'll translate this for y'all:
"A solution of 3 g anhydrous NaAc in 40 ml water is neutralised with acetic acid to pH~7. 2 G of Pd on BaSO4 and 7.2 g chloro-pseudoephedrine were added and shaking under H2 at room temperature. After 2-3 hrs the rxn is halted, although the theoretical quantity of H2 is not absorbed. Adding new catalyst doesn't start the rxn again. The solution is filtered and made alkaline with NaOH solution. The ---- is steam-distilled (yes, that's possible!): most of the product ends up in the first 200 ml destillate. The free base is separated and the hydrochloride is prepared in the usual fashion. Yield ~90%."

Sorry Insanity Clause, but I just read this article, I couldn't resist. Lr/

psychokitty
Member   posted 01-11-99 01:58 PM
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Okay, Drone. Here is the reference you require in order to qualify my method:
JOC 1993,58,3568-3571 "A Convenient Reduction of Amino Acids and Their Derivitives".

And for the subsequent reduction of the primary alcohol I offer some super-duper stratagies and their references:

JOC 1992, 57, 2143-2147 "Reductive Deoxygenation of Ketones and Secondary Alcohols by Organoaluminum Lewis Acids".

SYNTHETIC COMMUNICATIONS, 26(24),4647-4654(1996) "Deoxygenation of Acylferrocenes with Sodium Borohydride and Zinc Chloride".

And the very fucking best of the lot:

Synthesis 1987, pp.736-738 "Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum (III)Chloride"

All of these, by the way, seem like they can be effectively used to reduce both phenylpropanolamine and ephedrine to d-----.

I realize it's possible that you don't like what I've offered so far, so here's another submission:

P2P from a-methylstyrene via thallium (III)nitrate in methanol in less that ten minutes and in 81% yield. And yes, I'm going to elaborate on this proceedure sometime soon because Fester indicated in his book "Practical LSD Manufacture" that isosafrole could be used in this reaction to make MD-P2P. Well, according to the information in the three articles and one patent that will be posted in this thread, he's dead wrong. Isosafrole will only make the hydratropic aldehyde (sp?). Using safrole, according to some examples, might work. But to be sure to get MD-P2P, you need a-methyl-MD-styrene. Anyway, here are the references:

US Patent 32,452,047 "Oxidation Of Olefinic Compounds With Solutions Of Thallium Salts"

JACS, 95:11, 1973, pp.3635-3640 "Thallium in Organic Synthesis. XXXII. Oxidative Rearrangement of Olefins Using Thallium (III) Nitrate (TTN)"

Tetrahedron Letters, 1970, pp.5275-5280 "THALLIUM IN ORGANIC SYNTHESIS. XX. OXIDATIVE REARRANGEMENT OF OLEFINS WITH THALLIUM (III) NITRATE: A SIMPLE ONE-STEP SYNTHESIS OF ALDEHYDES AND KETONES"

Aust. J. Chem., 1975,28,pp.903-8 "Diterpene Chemistry. V. Thallium (III) Nitrate Oxidations of Exocyclic Olefins"

And if that's not enough for you, here's a method -- although very theoretical in that it may not be applicable to aminoacids -- that you might appreciate:

JACS, 92:10, 1970, pp.3232-3233 "A New and Convenient Method for the Reduction of an Aromatic Carboxyl to a Methyl Group"

Here's another possibly useful article:

JOC, vol. 44, no. 13, 1979 "Novel Conversion of Aromatic Ester Groups to Methyl. Catalytic Effect of Iodine in Reactions Involving Iodotrimethylsilane"

And yes, yes, yes, I understand that the authors use aromatic carboxylic acids and not benzylic carboxylic acids, meaning that this reaction may not be feasibile for use in reducing amino acids which have an aliphatic carboxylic acid side chain. But its still a neat method, don't you think?

And last but not least, a new method (another one which I'll elaborate more on later) that makes use of readily available cinnamaldehyde (which can easily be obtained from oil of cassia) to synthesize in 60% yield, in a proportion of 4:1, allylbenzene and propenylbenzene. The actual precursor used in the article is cinnamic alcohol (just one reduction away from cinnimaldehyde) and is reduced to the mixture of alkenyl benzenes through reaction at low temperature with dissolving zinc metal in ethyl ether saturated with anhydrous HCl.

Could cinnimaldehye be used as a substitute for cimmamic alcohol in this reaction? Probably. All other starting compounds used in this reaction had that vinnyllic-aldehyde quality to their structure. For those interested in learning more, I'm afraid that although I have the one page where this diagram was printed, I don't have the exact reference. I know I got the page from a review in ORGANIC REACTIONS. The title of the review is, I think, "Clemmensen Reduction of Ketones". It was in the later volumes, somewhere between 10 and 25. Finding it may seem like an impossible task but keep in mind that out of all the volumes, there has been printed only two Clemmensen Reduction reviews. The first one -- which is not the one your looking for -- appeared somewhere in the first 5 volumes (I think). Just go volume by volume after volume 10, browsing each volume's table of contents. I know it's a pain in the ass, but when you consider how scarce allylbenzene and propenylbenzene are, and how easy Cassia Oil is to obtain, making the effort to locate the article will eventually seem more and more like one big gratifying chore.

By the way, here's a reference to an article that details the Clemmensen Reduction just a little bit more:

JOC, 1991, 56, 4269-4273 "Zinc-Promoted Reactions. 1. Mechanism of the Clemmensen Reaction. Reduction of Benzophenone in Glacial Acetic Acid"

Hope I've been of help.

-- Psychokitty.

Wizard X
Moderator   posted 01-11-99 04:47 PM
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Reducing chloroephedrine with Pd/BaSO4 and H2 at STP. Works !
Reduction of chloroephedrine (bromo or iodo) with a mercury cathode electrode at 0.9-1.1 volts. Works ! This is a true electrochemical interaction at the electrode.

rev drone
Member   posted 01-12-99 11:58 AM
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Psychokitty,
Thanks for the ref's on the amino acids, but *I* didn't ask for them. Wow, you certainly outdid yourself here, I must say. Quite a collection.

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-the good reverend drone

ChemHack
Member   posted 01-12-99 05:11 PM
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"Thus, phenylalanine is reduced with sodium borohydride/H2SO4 in THF to get the 2,3-aminoalcohol." - LabRat
"Then phenylalanine or any of the amides mentioned above are reduced with sodium borohydride and iodine in THF to form the aminoalcohol or its N-alkylated version." - PsychoKitty

And from my O.Chem textbook:
"Carboxylic acids are reduced by powerful hydride reagents like lithium aluminum hydride (but not NaBH4) to yield primary alcohols. The reaxtion is difficult, however, and often requires heating in tetrahydrofuran solvent to go to completion."

"Borane, BH3, is also used for converting carboxylic acids into primary alcohols. Reaction of an acid with borane occurs rapidly at room temperatue, and this procedure is ofte4n preferred to reduction with LiAlH4 because of its relative ease and safety."

The example of the borane rxn shows p-Nitrophenylacetic acid to 2-(p-Nitrophenyl)ethanol in 94% yield.

FOOL
Member   posted 01-15-99 11:26 AM
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Now if one could vote on a new way, for an old way. Hasn't anyone noticed something RC hinted. Oh well, somedays I feel I am reading a different board than everyone else.
But I do go for the applicable stuff.
Thanks,
Fool and the bomb.

rev drone
Member   posted 02-01-99 04:40 PM
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I'm wrapping this contest up on Friday, Feb 5th, so if you still want to participate, be sure to submit your brainchild ASAP.
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-the good reverend drone

psychokitty
Member   posted 02-01-99 04:50 PM
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You are my brainchild, Drone! You my son! YOUUUUUUUUUU!
--Psychokitty

Piglet
Member   posted 02-02-99 04:07 AM
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Benzene + Chloroacetone --> P2P + HCl
P2P + Ni(NO3)2 + Zn + NaOH (in alcohol) ---> Amphetamine + Na2[ZnO]2 + Ni + NaNO3
Step one is the infamous chloroacetone, used by super-skilled & stupid only.

Step 2 is a nice alternative to Hg/Al which LR pulled out for me. What a nice bloke...
The Zinc/Nickel couple. Get your reference books out now, people.

Piglet

PS How about £10 + Junkie = 10x5mg Dexadrine. In Manchester, the doctors are prescribing dexadrine to help them stay off the smack (?). Of course, they all sell them real cheap. Yum, dexadrine is my favorite (especially with a couple of Diazepam)

rev drone
Member   posted 02-12-99 01:44 PM
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Here are the structures of the reactions given. There are so many clever, good ones in here, its hard to pick and choose. Please, vote for your favorites, and if I made a mistake, please say so. The structures look best as a text file, so you may have to cut-and paste to see them properly.
LABRAT

scheme 1

//\ /\ COOH //\ /\ /\
// \/ \/ NaBH4,H2SO4 // \/ \/ OH
| | | | --------> | | | |
| | | N THF | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H CH3

//\ /\ /\ //\ /\ /
// \/ \/ OH HI/red P // \/ \/
| | | | --------> | | | |
| | | N | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H H

scheme 2

/ /
< O=<
\ \
>=O H2SO4 > (unspecified
___/ HgSO4 ___/ reductive amin.)
/ _ \ ---------> / _ \ -------> ampetamine, ----, etc.
< (_) > AlCl3 < (_) >
\___/ \___/

scheme 3

Cl
|
//\ /\ / //\ /\ /
// \/ \/ H2, Pd/BaSO4 // \/ \/
| | | | --------> | | | |
| | | N STP | | | N
\\ / / \ \\ / / \
\\/ H CH3 \\/ H CH3

DRONE 342

scheme 1

//\ /\ COOH //\ /\ COOEt
// \/ \/ EtOH // \/ \/
| | | | --------> | | | |
| | | N HCl | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H H

//\ /\ COOH //\ /\ /\
// \/ \/ benzaldehyde // \/ \/ OH
| | | | --------> | | | |
| | | N | | | N
\\ / / \ \\ / \\
\\/ H H \\/ Bz

//\ /\ COOEt //\ /\ COOEt
// \/ \/ MeI // \/ \/_CH3
| | | | --------> | | | |
| | | N Base | | | N
\\ / \\ \\ / \\
\\/ Bz \\/ Bz

//\ /\ COOEt //\ /\ COOH
// \/ \/_CH3 H3O+ // \/ \/_CH3
| | | | --------> | | | |
| | | N | | | N
\\ / \\ \\ / / \
\\/ Bz \\/ H H

//\ /\ COOH //\ /\ /
// \/ \/_CH3 ketone cat. // \/ \/
| | | | --------> | | | |
| | | N heat | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H H

scheme 2

\ COOH \ COOEt
\/ EtOH \/
| --------> |
N N
/ \ HCl / \
H H H H

\ COOEt 1.Benzaldehyde //\ /\ COOEt
\/ 2.BzCl/Base // \/ \/_CH3
| --------> | | | |
N | | | N
/ \ \\ / \\
H H \\/ Bz

//\ /\ COOH //\ /\ /
// \/ \/_CH3 ketone cat. // \/ \/
| | | | --------> | | | |
| | | N heat | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H H

scheme 3 Mitsunobu RxN

OH NH2
/ /
---< ---<
\ \
> DEAD, Ph3P >
___/ ___/
/ _ \ ------------------> / _ \
< (_) > < (_) >
\___/ \___/

scheme 4
N
CH3 Cl \\\
\ \ \
> > >
___/ Cl2, hv ___/ KCN ___/
/ _ \ ---------> / _ \ -------> / _ \ ----> Phenylacetic acid ---> (numerous routes)
< (_) > < (_) > < (_) >
\___/ \___/ \___/

scheme 5

1)MeMgI
2)hydrolysis workup
benzyl cyanide ------> P-2-P
/
CH3 Cl O=<
\ \ \
> > > nitromethane
___/ Cl2, hv ___/ electrolysis ___/ Al(Hg)
/ _ \ ---------> / _ \ -------> / _ \ ----> methedrine
< (_) > < (_) > < (_) >
\___/ \___/ \___/

scheme 6

/ /
O=< MeHN-<
\ MeNH2, \
X > electrolytic >
___/ acetone, hv ___/ reduction ___/
/ _ \ ---------> / _ \ -------> / _ \
< (_) > strong Base< (_) > < (_) >
\___/ \___/ \___/

Timeless
/ / /
< Br-< H2N-<
\ \ \
>=O >=O >=O
___ EtCOCl ___/ NaOCl ___/ phthalimide ___/ H2, cat.
/ _ \ ---------> / _ \ -------> / _ \ -------> / _ \ ------> benzedrine
< (_) > AlCl3 < (_) > H2O < (_) > < (_) >
\___/ \___/ \___/ \___/

Osmium

/ /
< HO-N=<
\ \
>=O >
___ EtCOCl ___/ ___/
/ _ \ ---------> / _ \ -------> / _ \ -------> benzedrine
< (_) > AlCl3 < (_) > H2O < (_) >
\___/ \___/ \___/

Rhodium

scheme 1
/ / /
< Br-< H2N-<
\ \ \
>=O >=O >=O
___ EtCOCl ___/ NaOCl ___/ phthalimide ___/ Zn (Clemmenson redcition)
/ _ \ ---------> / _ \ -------> / _ \ -------> / _ \ ------> benzedrine
< (_) > AlCl3 < (_) > H2O < (_) > < (_) >
\___/ \___/ \___/ \___/

scheme 2
/ /
Cl O=< H2N-<
\ \ \
> > >
___/ CH3COCl ___/ NH4OAc, Mg ___/
/ _ \ ---------> / _ \ -------> / _ \
< (_) > < (_) > < (_) >
\___/ \___/ \___/

Wizard X

scheme 1

A + B ==(catalyst)==(reflux)===>> amphetamine 38% overall

scheme 2

Cl
|
//\ /\ / //\ /\ /
// \/ \/ electrolytic reduction // \/ \/
| | | | --------> | | | |
| | | N 0.9-1.1 V | | | N
\\ / / \ \\ / / \
\\/ H CH3 \\/ H CH3

psychokitty

scheme 1

//\ /\ COOH //\ /\ COOH
// \/ \/ AcCl // \/ \/
| | | | --------> | | | |
| | | N THF | | | N
\\ / / \ \\ / / \
\\/ H H \\/ H C=O
|
CH3

//\ /\ COOH //\ /\ /\
// \/ \/ NaBH4,H2SO // \/ \/ OH reduction
| | | | --------> | | | | ------> ethylamphetamine
| | | N THF | | | N
\\ / / \ \\ / / \ CH3
\\/ H C=O \\/ H \/
|
CH3

reduction = HI/P; Li/NH3; 1)SOCl2, 2) H2/Pd;

Insanity Clause

scheme 1

/ /
MeHN< MeHN-<
\ \
>-OH >-Cl
___/ SOCl2 ___/ H2, Pd/BaSO4
/ _ \ ---------> / _ \ -------> ----, 75%
< (_) > AlCl3 < (_) >
\___/ \___/

scheme 2

//\ /\\ / //\ /\ /
// \/ \\/ Th(NO2)3 // \/ \/
| | | --------> | | | | | 81%
| | | MeOH | | | | O
\\ / \\ /
\\/ \\/

scheme 3

O HO
| | \
<---< <---< ---< ===<
\\ \\ \\ \
> Reduction > > >
___/ ___/ Zn,HCl ___/ ___/ (subsequent
/ _ \ ------------------> / _ \ -------> / _ \ + / _ \ reactions
< (_) > < (_) > < (_) > < (_) > to ----)
\___/ \___/ \___/ \___/

bio
/ /
O O=< H2N-<
\\ \ \
> >-OH >-OH
___/ sugar, yeast ___/ NH3,H2,Pd ___/
/ _ \ ---------> / _ \ -------> / _ \ (pure d-----)
< (_) > < (_) > < (_) >
\___/ \___/ \___/

Piglet
/ /
O=< HN-<
\ \
> Ni(NO3)2 >
___ ClCH2COCH3 ___/ Zn ___/
/ _ \ ---------> / _ \ -------> / _ \
< (_) > < (_) > EtOH < (_) >
\___/ \___/ \___/

------------------
-the good reverend drone

Osmium
Member   posted 02-12-99 02:31 PM
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Who wins?

Labrat
Member   posted 02-13-99 10:35 AM
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Drone, the propiophenone -> P2P transformation is not quite right yet. It should be:
propiophenone, catalytic HgSO4/H2SO4 in 70% MeOH at reflux gives phenyl-1,2-propandione. Catalytic hydrogenation with PtO2 in MeOH gives the diol and this is refluxed in 20% H2SO4 to obtain P2P.

I guess you're very busy, so that's why you prolly missed the thread dedicated to just this topic. Lr/

Mobius
Member   posted 02-16-99 03:05 AM
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C6H5CH(OH)CH(NH2)CH2OH (Comercialy Available: 500 g - 150$) + PCl5... Well, I think you can figure the rest...
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Rhodium
Administrator   posted 02-17-99 06:27 PM
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If someone could email this to me as a textfile, I could put it on my page.

Scooby Doo
Member   posted 02-18-99 08:08 AM
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Balls of steel/Stupidity + Acetophenone + diazomethane = P2P
Scooby

dito
Member   posted 03-02-99 01:50 AM
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!!!!!!This is just a hypothetical rxn for getting the P2P from cinnamaldehyde!!!!!!!
!!!!!!!!!!!!!!!!!!!!!!!But go ahead and flame me, I can take the heat!!!!!!!!!!!!!!!!!!!!!!!!!!
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I thought if you reduce the double bond on the chain you would get phenylpropanal this can then be rearranged with H2SO4/-16?C to give P2P
in 60% yield. (See Rhodiums great page for more information on the H2SO4 route with phenylpropanal.)
It's the first step that is the problem, how should you go about reducing the double bond just pump H2 through some cinnamaldehyde in acetic acid, or how? If this works we should have an pretty OTC route to get to the final "(nazi "rocket" fuel)". I have no ref's what so ever on this though. But It could work.
LIVE HAPPY!

dito

Piglet
Member   posted 03-02-99 02:40 AM
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Dito: I'm sure I read some easy reduction, but forget where. Does exist, though. That's the important thing!

Osmium
Member   posted 03-02-99 05:21 AM
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dito: this one produces the wrong phenylpropanal isomer. Doesn't work.

Piglet
Member   posted 03-02-99 06:55 AM
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O: Wrong isomer? I don't understand?

Rhodium
Administrator   posted 03-03-99 08:53 PM
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We want phenyl-isopropanal, dito's synth would yield phenyl-n-propanal.

dito
Member   posted 03-05-99 07:35 AM
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I am sorry to hear that this wouldn't work. Sorry that I gave you some hope Piglet
This phenylpropanal can't be used for anything usefull then?

LIVE HAPPY!

dito