A strange, possible, amphetamine synthesis

[masterofpuppets]

I think that weter is the best solvent for this reaction - it is just too hard to get any significant amount of phenylalanine disolved in methanol.

Does anyone know how much current needs to pass through the solution for the conversion of a gram of phenylalanine (ie. how many coloumbs)?

Everyone repeat after me - "I am an individual, just like everybody else"

[WizardX]

After seening the trouble MasterofPuppets is having, I thought its time to put this too rest.

The Kolbe Electrolysis.

The process is the dimerization (joining together) of generated organic free radicals.

The basic mechanism is:
R-COONa ==solvent==>> R-COO(-) + Na(+)
R-COO(-) + e ==>> R. + CO2    R. represents the organic free radical
2R. ==>> R-R            R-R is the dimerization

Cross dimerization of two different organic free radical to make Meth is not easy and many by-products result due to many highly unstable 1st (primary) organic free radical combinations.

The perfect dimerization mechamism is:

C6H5-CH2-CH.-(NH2) + CH3. ==>> C6H5-CH2-CH-(NH2)-CH3

-CH.- is the primary organic free radical carbon atom.

From hereon PE. means C6H5-CH2-CH.-(NH2) the phenylethylamine radical.

A large excess of CH3. is need too force the chemical equilibium to the right and thus form more C6H5-CH2-CH-(NH2)-CH3 dimerization. Since CH3. & PE. are highly unstable 1st (primary) radicals, many combinations of products result through the rapid dimerization.

By-products are:

PE-PE that is C6H5-CH2-CH-(NH2)-(NH2)-CH-CH2-H5C6

H3C-CH3 Ethane

C6H5-CH2-CH-(NH2)-CO-O-CH3 Phenylalanine acetate

C6H5-CH2-CH-(NH2)-CH2-OH   Phenylalanine alcohol

C6H5-CH2-CH-(NH2)-CH2-O-CH3 Phenylalanine methyl ether

... and may more.

A varying degree of ethers, alcohols, olefins, parafins and acetates form.
The radicals are too unstable and unpredicable.

The methanol and acetic acid used as a solvent interacts with the radicals forming many combinations of products. The methanol is absolute methanol (ie dryed methanol), and sodium methoxide NaOCH3.

The sodium carboxylate salts can be first prepared:
C6H5-CH2-CH-(NH2)-COOH + NaOH ==>> C6H5-CH2-CH-(NH2)-COONa + H2O
The C6H5-CH2-CH-(NH2)-COONa must be anhydrous and in absolute methanol with anhydrous sodium acetate, 1:2 mole ratio.

The secondary organic free radicals generated are more stable than the primary radicals, but the CH3. radical is still highly unstable and dimerization with the C6H5-CH2-C.-(NH2)-(CH3) is STILL poor.

Now if secondary organic free radicals are generated by starting with:

C6H5-CH2-C-(NH2)-(CH3)-COO(-) + e ==>> C6H5-CH2-C.-(NH2)-(CH3)

C6H5-CH2-C.-(NH2)-(CH3) + CH3. ==>> C6H5-CH2-C-(NH2)-(CH3)-CH3 Phentermine


EXPERIMENTAL

Voltages 100-130 at approx 0.4 Amps (+ or - 10%) for 17 hours. Experiment 1.
Voltages 130-170 at approx 0.5 Amps (+ or - 10%) for 10 hours. Experiment 2.

Electrodes are two 2cm X 3cm, spaced 1cm apart, immersed completely in 100 mls of dimethylformamide solvent, in a 150 mls tall walled beaker. Externally ice water cooled and magnetically stirred.

Experiment 1: The anhydrous sodium carboxylate salts of Phenylalanine (0.1 mole) and acetic acid (0.2 mole) were used in a 1:2 ratio. Approx 19% yield.

Experiment 2: Anhydrous Phenylalanine (0.1 mole) and glacial acetic acid (0.2 mole) were used in a 1:2 ratio with 3 mls of triethylamine. Poor yield.

The use of a non-reacting, highly polar dimethylformamide solvent medium, helped diminished the by-products only slightly. The yield is less than 24%, between 19-24% with dimethylformamide.

The use of dimethylformamide solvent + diphenylacetic acid, (C6H5)2-CH2COOH, ONLY formed 24% of tetraphenylethane, (C6H5)2-CH2-CH2-(H5C6)2 Ref 2.

References:
(1) Vogel 5th Edition Pg 115, 484.
(2) The Kolbe Electrolysis in Dimethylformamide, JOC, Vol 25, Pg 136.

JOC means Journal of Organic Chemistry.

[jim]

Wizard X,

So this is from JOC?  Or did you perform this?  Either way, BRAVO!  I have been looking for something like this for a long time, but unable to find any reference to phenylalanine specifically. 

Given the molar ratios of the phenylalanine to the acetate ion, 1 to 2 respectively, the theorical yield would have been only 66%, which means that the actual yeild is just under 1/3 of the theory in this set up.  Therefore if one increases the acetate ions in relation to phenylalanine one can approach a theorical 100% yeild which translates into an actual yield of roughly 26%.

Although this is not a wonderful yield it still proves that it works! 

As an improvement I would increase the Amps/cm^2 used.

Maybe someone should try using methanol, or DMF/methanol, or even a DMSO variation....  

Thjanks a million Wizard X...  I will look up that JOC articel right now

[WizardX]

I used the JOC procedure with the diagram and info from Vogel. Remember, that generating MORE CH3. primary radicals would give higher yeilds in respect to the "collision law", BUT would also generate MORE BY-PRODUCTS.

[jim]

By-Products?  The decomposition products?

I don't know about that, however i think that pH control is a huge factor in this experiment as well, come to think of it.  The acetate and the phenylalanine ionize in different ways:  The phenylalanine is a  zwitteron afterall.

I am not sure what a good pH would be, or how to go about that however...

What do you think?

I do think that given that the catalysis takes place at the anodes surface that given a larger quantity of carboxylate ions at the anode's surface the yield of dimers should go up.  I think that since most people are not going to use pressure, the next best thing is a higher current density.

[perpeetuum]

And what kind of electrodec should be used
(surely Pt or Pd -not easy to obtain- but what about the 'second' electrode - katode??? ---thinking on carbon ...but lead (plumbum) maybe too ??)

[perpeetuum]

maybe little offtopic, but what about this

 At the first place I¨d like to say, that I am very comprehent that on the Hive there is several (nearly hundred ) of threads on pheny, but in no of these there is no complete steps .This thread is to be something such as racemate version of all those pheny threads

 I would like to ask the huge scientists on Hive, if is possible this "substitution":

 - according master KRZ and his catalytic hydrogenation (via Rylander) of l-phenylalanine into dextroamph. via Pt/C 5% catalyst, glacial acetic acid and anhydride Ethanol (as a solvent for reaction) in hydrogenator at 6 atmospheres (90 psi) - if is possible to make this reaction without using pressurized hydrogen vessel , but , as a substitude use some kind of hydrogen donor (i dont know what king exactly) is possibility to use some of these hydrogen donors - ammonium formate , cyclohexane , hydrazine (not much good) , formic acid , cyclohexadiene , phosphinic acid , sodium hypophosphite , LiAlH4 , NaBH4 or LiBH4 (i dont know which are basis or acidy) I suppose also that , if this way is possible , the best hydrogen donor should be formic acid ,
cause it reacts via this:   H(C=O)OH (catalyst)--> O=(C=O) + nascent hydrogen (H2)  (gives hydrogen and produces CO2).

 - the second "main" question I have to all math-profesors and math-scientist on Hive is this:
 is possible to provide the reaction (again) via KRZ (l-pheny to dextroamph.) with using stronger catalyst than Pt/C 5% - something for ex. as Pd/C 10 %
(maybe for the prize of little lowered 'ring reduction' - and lowered yield) ?
if yes, so there is my (very apprentice) idea to make reaction in MW oven (under reflux) on low irradiation (and maybe on modulated irradiation - but this thing is another big question) and as a hydrogen source use some kind of Gas Hydrogen generator (for example by Mr. Drone #342) and bubble the hydrogen through the
'reacting' solution (same as use KRZ) under very good stirring and under MW irradiation (as above). The temperature sholdnt rise above 45 - 50 C degrees ,
so the MW irradiation is to be very low (defrosting stage ? - it is about 30% and is modulated) and so there will be no evaporation of ethanol (solvent) or rather no evap. at all.
Is this pioneer idea possible ? How much time should the reaction take ? Or is the better way to use some kind of hydrogen donor (if some exist for this
type of reaction) ? Or this thread is bullshit (excuse for this word) and the only way is to use pressure vessel

thank you for your reply


Perpeetuum (goes forever and forever and forever and ....)

P.S: Please, don't blame me for all these words above, I'm just appretice in chemia.

[terbium]

catalytic hydrogenation (via Rylander) of l-phenylalanine into dextroamph

It is generally accepted that this doesn't work.

[perpeetuum]

In fist place, sorry to cros-post this article. I promise, I will never cros-post again !  
I understand, that this quazi-mw-bubling method won't work (or there will be no or very tiny yield).
But the pressure method of Mr. KRZ works. Or not ? (when not , will You give some reason why the Catalyst will not change the esterificated pheny- (uder pressure) into dextro , please.)

Perpeetuum

[terbium]

when not , will You give some reason why the Catalyst will not change the esterificated pheny- (uder pressure) into dextro ,

Don't know why, that is just the way things are. I do not know of any examples of catalytic hydrogenation being used to convert a carboxylic acid or its ester to a methyl.