Author Topic: Phenylalanine to amphetamine or N-methylamphetamine  (Read 4476 times)

no1uno

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #20 on: October 24, 2009, 09:01:42 PM »
Just from interest, Java did you ever try the tosylate/mesylate on that primary alcohol? I seem to remember Donner, et al (IIRC) used that and Zn/I2 to get tyrosinol down to p-hydroxyamphetamine.
"...     "A little learning is a dang'rous thing;
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java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #21 on: October 24, 2009, 09:10:15 PM »
.....no i never did , i was told about it many times but thought it to be irrelevant to my goals at the time.....java


Not able to correct my error, stated on the reference by  DaLuka its TCA not TCCA....I stand corrected, thanks Goldmember, at least i know someone is reading my posts.....java

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« Last Edit: April 09, 2010, 07:01:10 AM by Enkidu »
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Goldmember

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #22 on: October 25, 2009, 01:30:41 AM »
Ive had trouble aquiring TCT(not tcca) in the past.
Shame as it has so many uses. Anyone got an easyish prep or dirivable source for this compound?

java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #23 on: October 25, 2009, 02:21:36 AM »
Synthesis

1,2,3-Triazines can be synthesized by thermal rearrangement of 2-azidocyclopropenes. 1,2,4-Triazines are prepared from condensation of 1,2-dicarbonyl compounds with amidrazones. A classical triazine synthesis is also the Bamberger triazine synthesis. Symmetrical 1,3,5-triazines are prepared by trimerization of cyanogen chloride or cyanimide. Benzoguanamine (with one phenyl and 2 amino substituents) is synthesised from benzonitrile and dicyandiamide in dimethoxyethane with potassium hydroxide.[6]

......source,

http://en.wikipedia.org/wiki/Triazine

also US patent 4329458
¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

Goldmember

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #24 on: October 25, 2009, 03:47:19 AM »
Rotflmfao!!!

"at least i know someone is reading my posts.....java"

Only a slight understatement I think. :P

iknowjt

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #25 on: October 26, 2009, 08:54:11 AM »
...there seems to be a misunderstanding about the synthesis of meth from phenylalanine.....it's not that there isn't  viable methods of the synthesis , it's the unobtainable regent's needed that makes the procedure difficult. the purpose of forums like this as many is to find methods with reagents available OTC to make the synthesis doable.


point well taken java.  It might be relevant to mention that in the original thread, the other had intended to do this with RP/I, but ironically, didn't have any RP around.

lugh

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #26 on: October 26, 2009, 04:28:12 PM »
An alternative route to cynogen chloride that doesn't involve hydrogen cyanide:
Chemistry is our Covalent Bond

no1uno

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #27 on: October 29, 2009, 11:15:40 PM »
.....no i never did , i was told about it many times but thought it to be irrelevant to my goals at the time.....java


Not able to correct my error, stated on the reference by  DaLuka its TCA not TCCA....I stand corrected, thanks Goldmember, at least i know someone is reading my posts.....java

Have a look at the suggested mechanism on this page - ie. the use of the mesyl chloride to form the primary alkyl mesylate, then displacement thereof by NaI (Finkelstein Rxn)... Methanesulfonyl Chloride is supposedly as far away as the 2-stage anhydrous/aqueous chlorination of DMSO, so it might be worth a wee look?
"...     "A little learning is a dang'rous thing;
    Drink deep, or taste not the Pierian spring:
    There shallow draughts intoxicate the brain,
    And drinking largely sobers us again.
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java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #28 on: November 04, 2009, 01:52:12 PM »
.....there may be a similar and easier ways, read and give your opinions......java

A Simple and Efficient Procedure for the Synthesis of Optically Active 4-Methoxy-?-Methylphenylethylamine from
Tyrosine'

Kohno, Harumichi, Iwakuma, Takeo and Yamada, Koichiro
Synthetic Communications 28:11, 1935 - 1945, 1998


Abstract:
Optically active 4-methoxy-a-methylphenylethylamin(e l ),a useful chiral building
block in medicinalchemistry. was synthesized from L- orDtyrosine by using a simple andefficient
prccedure via one-pot zinc reduction of the corresponding 0-tosylate (4) in the presence of H,O and
Nal in pure form.
¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

jon

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #29 on: November 13, 2009, 05:06:00 AM »
java used hypo/ i2 and it worked to reduce terminal iodoalkane.

in this exapmle;
Using (16.7 grams = 0.1 mole) of 1-phenyl-2-aminopropanediol and (140ml = 1.1 mole) of 58.4% Hydroiodic acid and (6.2 grams = 0.2 atomic wieght)red phosphorous, refluxed at 123-125*C for 24 hours yielded 85.4% 1-phenyl-2-amino-iodopropane with trace amounts of 1-phenyl-2-aminopropane and even smaller amounts of 1-pheny-2-aminopropanol-3.
And there are other examples in that patent that use much more red p and HI!

red p and hi and a lot of water floating around this hinders HI's reducing power hence no workey see the devilish details???
so oxy acids like h3po3 and so on increase hydride ion conc. increase reducing power and accelerate rxn rates.
i''m retarted and i know that.
« Last Edit: November 13, 2009, 05:09:23 AM by jon »

iknowjt

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #30 on: February 03, 2010, 10:16:31 AM »


red p and hi and a lot of water floating around this hinders HI's reducing power hence no workey see the devilish details???
so oxy acids like h3po3 and so on increase hydride ion conc. increase reducing power and accelerate rxn rates.
i''m retarted and i know that.


I always thought HI based reduction using elemntal red P where just a joke, I mean cmon!
heterogeneous reaction = any little physical detail can just ruin everything, so slow,
homogeneous = everything dissolves.  what any RP reaction wishes it was

Sedit

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #31 on: February 04, 2010, 06:26:43 AM »
You thought the reduction using Red phosphorus was a joke as in it didn't work? Im preeetty sure it works but the Red phosphorus is not what does the job, This is converted to H3PO2 IIRC which is homogeneous in the reaction. Most think the P is the catalyst but im pretty sure its the iodine that fills that role remaining unchanged at the end of the reaction where as Phosphorus is consumed.
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iknowjt

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #32 on: February 04, 2010, 08:42:27 AM »
you got a point sedit,
I guess I was thinking not so much of the reaction mechanism but the physical process required,
i.e. mix 4 things together, R, I2, P, H2O, yet the R needs to be Mixed with a capitol M, every step of the way,

either way for some reason, the RP is a very stubborn reactant.  it must be the consistensy of dust, it must be evenly blended, and something like 6 times excess of what actually reacts is needed to increase surface area.  There's the sure sign of non soluble, non miscible, reactants.
The H3PO3 crystals do not need to be milled up to fine powder for the reaction to occur.  I always thought it was because phosphorous acid is water soluble, and P is not, so having every molecule of one bump into every molecule of the other must be orchestrated by the chemist, almost 'artificially' you could say. 

jon

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #33 on: February 06, 2010, 10:14:25 PM »
certain acids hold red p into supension making it more reative h3po4 and caroboxylic accndis also good stit\rrring and you can get away with equimolar red p.


Just from interest, Java did you ever try the tosylate/mesylate on that primary alcohol? I seem to remember Donner, et al (IIRC) used that and Zn/I2 to get tyrosinol down to p-hydroxyamphetamine.
 
now that sounds intersting

java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #34 on: April 07, 2010, 04:44:55 PM »
Cyanuric Chloride. A Novel Laboratory Hydrochlorinating Reagent for Alcohols
STANLERY. SANDLER
J. Org. Chem.
1970,  Vol. 36, No. 11, 3967-3968


NOte:  ......so an easy reflux and distillation and the primary alcohol gets chlorinated.....and now for an easy reduction of the halogenated amine to the amphetamine is in order..........java
¡Prefiero morir de pie que vivir siempre arrodillado!.Emiliano ZapataIt is better to die on your feet than to live on your knees!.......

java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #35 on: April 08, 2010, 01:07:04 AM »
.....having said all that , i wonder if it would be better to methylate the alcohol then do the chlorination as i fear the cyanuric chloride will attach to the amine if it's not protected.....as in the study.


Cyanuric Chloride Derivatives. I. Aminochloro-s-triazines
Jack T. Thurston, James R. Dudley, Donald W. Kaiser, Ingenuin Hechenbleikner, Frederic C. Schaefer, Dagfrid Holm-Hansen
J. Am. Chem. Soc., 1951, 73 (7), pp 2981–2983
DOI: 10.1021/ja01151a001

Note: check out the free first page,

http://pubs.acs.org/doi/abs/10.1021/ja01151a001




......as for the elimination of the Cl , as one method the comment by Naft "There are also other metals you could use also, like zinc is excellent at replacing halogens with H.". catalytic hydrogenation using Pd/C and others , but feel free to make other methods as, the more we have the better for those with problems with access to reagents......java
« Last Edit: April 08, 2010, 01:16:12 AM by java »
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Naf1

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #36 on: April 08, 2010, 10:32:40 PM »
Excellent work Java! Here is an actual reference for that quote. As stated there are many more, but that was for the Zinc comment.

Reductive Dehalogenation of Arylhalides and Alkylhalides with Zinc in THF Saturated Aqueous Ammonium Chloride
Rahim Hekmatshoar,* Sodeh Sajadi and Majid M. Heravi
Journal of the Chinese Chemical Society, 2008, 55, 616-618
http://proj3.sinica.edu.tw/~chem/servxx6/files/paper_3077_1232001734.pdf

btw; Seems like a good candidate for Bz amine protection with benzoyl chloride? Simple hydrolysis to remove when done, easy enough to acquire. That last paper you quoted had an interesting comment that was only half there;
"We have discovered that the reactivity of the chlorine atoms in the last two series also varies greatly with the degree of substitution of the amino nitrogen atom. 2-Amino........"

They where obviously about to say something akin to ; 2-Amino<1-Amino<Amino , but would be interesting never the less.
« Last Edit: April 08, 2010, 10:35:07 PM by Naf1 »

Enkidu

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #37 on: April 09, 2010, 07:08:42 AM »
I split a couple of OT posts and merged them with the Short Questions thread..

java

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #38 on: April 09, 2010, 02:11:10 PM »
...with the vacancy of electrons it would probably be prudent to make the `hydrocloride  salt before attempting to halogenate the alcohol, or methylate and make the hydrochloride salt to eliminate any possible invasion of space by unwanted attachments......as i'm not sure that if just making the hydrocloride salt of the amine will exhaust the available sites for invasion ........java
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Enkidu

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Re: Phenylalanine to amphetamine or N-methylamphetamine
« Reply #39 on: April 09, 2010, 06:26:44 PM »
A novel method for reductive removal of tosyloxy and mesyloxy groups.
Yasuo Fujimoto and Takashi Tatsuno
Tetrahedron Letters Volume 17, Issue 37, September 1976, Pages 3325-3326 doi:10.1016/S0040-4039(00)93913-3

Chlorotrimethylsilane/Sodium Iodide/Zinc as a Simple and Convenient Reducing System; One-Pot Deoxygenation of Alcohols and Ethers
Morita, Tsuyoshi; Okamoto, Yoshiki; Sakurai, Hiroshi
Synthesis 1981 p.32 doi:10.1055/s-1981-29320