Author Topic: A strange, possible, amphetamine synthesis  (Read 3640 times)

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CHEM_GUY

  • Guest
A strange, possible, amphetamine synthesis
« on: May 16, 2000, 10:45:00 AM »
Okay this synthesis involves the decarboxylation and methylation of phenylalanine in one step.  The basic equation is:

C6H5-CH2-CHNH3-COOH + CH3COONa --{electroysis @ Pt anode}--> C6H5-CH2-CHNH2-CH3 + H2 + CO2

The problem that I find with this is the solublity of phenylalanine...  What does phenylalanine, or it's salt dissolve in?  Where could I find that...

________
From "Synthetic Organic Electrochemistry", by Albert J. Fry, yr 1972
Library of Congress # QD273.F78, page 273

"8  OXIDATION PROCESS

...

8.1 CARBOXYLIC ACIDS

It has been known for conciderably more than a century that
electrochemical oxidation of salts of carboxylic acids results in
dimeric products [6]:

2 RCO2(-) --{O}--> 2 CO2 + RR

This reaction is known as the Kolbe reaction after the early
investator who, though not it's discoverer, studied it in sufficent
 detail to outline its scope.  Perhaps no other organic reaction has
been studied as intensively as has the Kolbe reactioon;  indeed,
investigation into its sublter aspects have continued right up to the
 present day.  While some mechanistics details still remain unclear,
the preparative methodology and mechanism are sufficently well
established that synthetic applications are straight forward.  ...

8.1.1 The Kolbe and Related Reactions

Mechanism

Weedon has discussed optimal experimental procedures for the Kolbe
reaction [1].  ... Apparently, a film of absorbed intermeditates
inhibits oxidation of the solvent and permits a potential to be
attained where the Kolbe reaction can then occur.  This feature is of
interest synthetically because it results in considerable experimental
 simplifications.  Since anodic potential control (to avoid oxidation
 of the solvent) is rendered unnecessary by this absorption process,
one may use constant-current, rather than controlled-potential,
electrolysis.  As Weedon has pointed out, the experimental apparatus
 for the Kolbe reaction can be quite simple, merely a beaker
containing both the solution and a pair of platinium electrodes
 connected to a source of direct current (see Chapter 9) [1]. 

...

Synthetic Scope and Limitations

Kolbe dimers are formed in 50-90% yeild when the intermeditate radical
 is either primary [1] or is substituted by electron-withdrawing groups
 [15], that is,

RC*H2 or RC*HX or RC*X2_____________(X = COO2R', CONR2', etc.) 

When the [alpha] position of the acid containsa substituent capable of
 stablizing a carbonium ion (X = alkyl, alkoxyl, halogen, aryl, etc.),
 yields of the Kolbe dimer are very low ( 0-10% ).  In such cases, the
 intitially formed radical is oxidized further to a carbonium ion:

RCO2(-) - e(-) --{ -CO2}--> R* --{ - e(-)}--> R(+) --> products

...  There are a few other other cases where the Kolbe yields are low.
  Aryl [16] and [alpha], [beta]-unsaturated acids [17] afford little or
 no dimer, for example.  The isolation of benzene from the oxidation of
 benzonic acid [16], ...

Other than these, there are really very few restrictions on the nature
 of the R group in a carboxylic acid (RCO2H) that is to be submitted to
 the Kolbe reaction.  ...

...

A valuble extension of the Kolbe reaction was first reported by Wurtz
 [23].  He found that oxidation of a mixture of two different
carboxylic acids results in a mixture of three possible coupling
products:

RCO2H  +  R'CO2H --{ -e(-)/ -CO2}--> RR + RR' + R'R'

The fact that the three are formed in more or less statistical ratio
 need not be a detterent, for the proper choice of the molecular size
 of R and R' the products can be made to differ substantially in
 physical properties, thus making separation easy, and use of a large
 excess of the cheaper acid increases the relative yield of the desired
 mixed product RR'.  ... 

(One common application of this crossed Kolbe coupling is the oxidation
 of a carboxylic acid in the presense of a large excess of acetate ion,
 thus resulting in efficent conversion of the acid RCO2H to the alkane
 RCH3 in one step [10-12].  This reaction would be useful for the
introduction of a labeled methyl group.)

The crossed Kolbe coupling reaction has the dual advantage of being
 able to accommodate a wide variety of functional groups and of
 enabling quick assembly of molecular subunits whose coupling by other
 routes might be lengthy.  ..."

[1] B. C. L. Weedon, Advan. Org. Chem., 1, 1 (1960)

[6] H. Kolbe, Ann., 69, 257, (1849)

[10] W. J. Koehl, Jr., J. Org. Chem. 32, 614 (19670.

[11] W. A. Bonner and F. D. Mango, J. Org. Chem., 29, 430 (1964).

[12] H. Breederveld and E.C. Kooyman, Rec. Trav. Chim., 76, 297 (1957).

[13] G. W. Kenner, M.A. Murray, and C. M. B. Tylor, Tetraherdon, 1,
 259 (1957)

[15] L. Eberson, Acta Chem. Scand., 17, 1196 (1963);  L. Eberson and
 B. Sandberg, Acta Chem. Scand., 20, 739 (1966); but see L. Eberson
and S. Nilsson, Acta Chem. Scand., 22, 2453 (1968).

[16] F. Ficher and R. E. Myer, Helv. Chim. Acta, 17, 535 (1934); F.
Ficher and H. Stenzl, Helv. Chim. Acta, 22, 970 (1939).

[17] J. Petersen, Z. EleKtrochem., 18, 710 (1912); P. Karrer and M.
 Stoll, Helv. Chim. Acta, 14, 1189 (1931).

[23] A. Wurtz, Ann. Chim. et Phys., 44, 291 (1855);  A. Wurtz,
Jahresberichte, 575 (1855).

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

From "The Journal of Organic Chemistry", Vol. 29, yr 1964, page 430
Title "Kolbe Electrolyses of 3-Phenyl- and 3,3-Diphenylpropanonic
Acids"

"EXPERIMENTAL

...

...  The electrode unit consisted of two platinium foil electrodes
 (1.25 X 1.25 cm.) spaced approximately 2 mm. apart and joined to
 wires sealed into a tapered glass head (...) equipped with a gas exit
 tube.  The cell compartment (30 mL), fitted to recieve the electrode
unit, was equuipped with a water jacket for thermosating.  The
electrolysis appartus was energized by a 12-V Heathkit battery
eliminator. 

...

Electrolysis of 3-Phenylpropanonic Acid in Acetic Acid.-  A solution of
 3-phenylpropanonic acid (2.89 gr.) [0.01927 mol], and sodium acetate
 (1.43 g.) [0.0174 mol], in acetic acid (25 mL) [assume Glacial acetic
 acid- .425 mol @ 17 mol/L] was electrolyzed as above for 21 hr. (0.2
amp., 8 f./mol).  ...  The observed retention times showed that
n-propylbenzene and 2-phenylethyl acetate were present..."

============================================================


This post is for informational purposes only an is not intended to facilate illegal activity.

neville

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #1 on: May 18, 2000, 01:32:00 AM »
H20  10-50mg/ml
is your best bet


Osmium

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #2 on: May 18, 2000, 03:26:00 AM »
It should be much more soluble in acidic or basic solutions, like the ones used in that synthesis.


Nutmeg238

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #3 on: May 21, 2000, 08:53:00 AM »
I thought of this idea before.  I also found a book in the library that said that carboxylic acids that are branched at the alpha position produce little or no yield of hydrocarbon product (Kolbe reaction).  Also, the amino group might be a problem, ie. note the free radical intermediates.


CHEM_GUY

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #4 on: May 22, 2000, 01:02:00 PM »
I have read a couple articles that the alpha-amino carboxyl acids do produce Kolbe dimers, but not in perfect yields.  Even if the yield is low it still is easy...

This post is for informational purposes only an is not intended to facilitate illegal activity.

Nutmeg238

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #5 on: May 22, 2000, 06:39:00 PM »
Looks interesting CHEM_GUY.  Can you list any references where they talk about alpha amino acids?


CHEM_GUY

  • Guest
References...
« Reply #6 on: May 23, 2000, 09:52:00 AM »
I'll try but I don't think I ever notated them.  For now here's a good reference with a lot more information, hell it probably has the references for the the alpha-substituted compounds sited:

Topics in Current Chemistry, Vol 152, Electrochemistry IV, edited by E. Stekhon, Library of C # QD1 F58 V.152

This post is for informational purposes only an is not intended to facilitate illegal activity.

Promethium

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #7 on: May 31, 2000, 03:47:00 PM »
This looks very interesting ... I will check with the lokal library and report ASAP.
(Phukin' lurkin' around for two years ....)



Promethium, burnin' yar beard!

CHEM_GUY

  • Guest
More info on this synthesis...
« Reply #8 on: July 01, 2000, 10:36:00 AM »
Here's some more shit on this synthesis.  Have fun!


Phenylalanine Properties:

Phenylalanine, dl- CAS# 150-0-1
Phenylalanine, l- CAS#  63-91-2

From-

http://ntp-server.niehs.nih.gov/htdocs/CHEM_H&S/NTP_Chem6/


         Radian63-91-2.html
[for l-phenylalanine]
*SOLUBILITIES:
       WATER : 10-50 mg/mL @ 25 C (RAD)

        DMSO : <1 mg/mL @ 25 C (RAD)

 95% ETHANOL : <1 mg/mL @ 25 C (RAD)

    METHANOL : Very slightly soluble [031,295]

     ACETONE : <1 mg/mL @ 25 C (RAD)

     TOLUENE : Not available

 OTHER SOLVENTS:
  Ether: Very slightly soluble Post 043 (not existing)
  Alcohol: Very slightly soluble [043,295]
  Dilute mineral acids: Very slightly soluble Post 295 (not existing)

From- www.chemfinder.com

[for L-phenylalanine]

water solutblity: 1-5 g/100 mL at 25 C

@

http://esc.syrres.com/interkow/webprop.exe?CAS=63-91-2


[for L-Phenylalanine]

Water Solubility:
   Value : 2.69E+004 mg/L
   Temp  : 25 deg C
   Type  : EXP
   Ref   : YALKOWSKY,SH & DANNENFELSER,RM (1992)

End of Properties-
==================

From "Topics in Currnet Chemistry" Volume 152, Electrochemistry IV,
edited by E. Stekhan, LoC# QD1. F58 v.152

page 93
"The yield and selectivity of the Kolbe electrolysis is determined by
the reaction conditions and structure of the carboxylate.  ...
Experimental factors that influence the the outcome of the Kolbe
electrolysis are the current density, the temperature, the pH,
additives, the solvent, and the electrode material.

High current densities and high carboxylate concentrations favor the
 formation of dimers.  This is due to a high radical concentration at
the elctrode surface that promotes dimerization.  Furthemore, at high
current densities the so called critical potential of about 2.4
(vs NHE) is reached [28] above which the Kolbe dimerization proceeds
smoothly.  ...  There is, however, no need for potential control in
Kolbe electrolysis as the critical potential is already exceeded at 1
to 10 mA/cm^2.  This is much below the usually applied current density,
 which should be as high as possible, normally equal to or greater than
 250 mA/cm^2.  ...

...

A nuetral, or even better a weakly acidic medium seems to be
prefferable for the Kolbe reaction.  This is achieved by nuetralizing
 the carboxylic acid to an extent of 2 to 5%, in some cases up to 30%,
 by an alkali metal hydroxide or alkoxide.  ...  The endpoint of the
electrolysis is indicated by a change of the electrolyte to an alkaine
 pH.  ...

In aqueous solution an elevated pressure favors the Kolbe-coupling
against non-Kolbe products [37].  ...

Temperature has some effect on Kolbe electrolysis.  Higher temperatures
seem to support disproportionation against the coupling reaction and
intramolecular additions to double bonds against a competing inter-
molecular coupling (Chap. 6).  ...

Additives can strongly influence the Kolbe-reaction.  Foreign anions
should be definitively excluded, because they seem to disturb the
formation of the necessary carboxylate layer at the anode.  Their
negative effect increases with the charge of the anion.  ...

Foreign cations can increasingly lower the yield in the order of
Fe(+2), Co(+2) < Ca(+2) < Mn(+2) < Pb(+2) [22].  Alkali and alkaline
earth metal ions, alkylammonium ions and also zinc or nickel cations do
not effect the Kolbe reaction [40] and are therefore counter ions of
choice in preparative applications.  Methanol is the best sutied
solvent for Kolbe electrolysis [7, 43].  ...  The following
electrolytes with methanol as a solvent have been used:  MeOH-sodium
carboxylate [44], MeOH-MeONa [45, 46], MeOH-NaOH [47],
MeOH-Et3N-pyridine [48].  The yield of the Kolbe dimer decreases in
media that contains more than 4% water.

In aqueous solutions especially, the current yield is distinctly lower;
 furthermore, solublity problems can occur when the salt-deficit method
 is used.  In aqueous solution, alpha-amino- or alpha-phenyl subsituted
carboxylates lead mainly to decomposition products, whilst in dry
methanol or methanol-pyridine, coupling products were obtained with
alpha-phenyl- and alpha-acetylaminocarboxylates [49].

... 

As anode material, smooth platinum in the form of a foil or net seems
to be most univerisally applicable [32, 33].  ...

...

The nature of the cathode material is not critical in the Kolbe
reaction.  ...

...

In summary the following general experimental conditions should be
applied for a sucussful dimerization of carboxylic acids:  An undivided
beaker type cell can be used equipped with a smooth platinum anode and
a platinum, steel or nickel cathode in close ditance;  a current
density of 0.25 A/cm^2 or higher should be provided by regulated power
supply, a slightly acidic or nuetral electrolyte, prefferable methanol
as solvent and a cooling device to maintain temperatures between 10 to
45 C should be employed.  With this simple procedure and equipment
yields of coupling product as high as 90% can be obtained, provided
the intermediate radical is not easily further oxidized (see Chap. 7)."

Read my Disclaimer. 

http://chemguy.homestead.com/disclaimer.html


masterofpuppets

  • Guest
Re: References...
« Reply #9 on: December 15, 2000, 07:05:00 PM »
Hi guys,

So what is the verdict on this method??  I am kind of suprised that there hasn't been more interest in this as it would appear to be one of the easiest methods out there.

I just had some thoughts that might be of interest/use.

1. Using 99.9% pure silve would be almost as good as Pt would it not?  (just for all those people who don't have solid sheets of platnium hanging around the house)

2. Are there any other chems besides Sodium Acetate that could be used (ie. ones that are a bit easier to procure).  This would be useful info for our non-US friends.

Anyway thanks to Chem_guy for finding this method

Cheers


--------------------
Master of Puppets is pulling your strings.....

jim

  • Guest
Re: References...
« Reply #10 on: December 16, 2000, 05:14:00 PM »
You're welcome,...


WizardX

  • Guest
Mixture of products.
« Reply #11 on: December 18, 2000, 05:28:00 PM »
I've posted this before on the Old Hive BB. The synthesis gives a mixture of products and CH3COONa MUST BE in large excess to minimize this.

masterofpuppets

  • Guest
Re: References...
« Reply #12 on: December 20, 2000, 04:48:00 PM »
Well SWIM tried out this synth but ran into problems with the current required.  For some reason there seemed to be a large amount of resistance in the solution (after putting in almost 18 V there were like 0.07 milliamps being produced).  This struck SWIM as being a bit strange, as usually there is too much amperage when the current is run through the solution in the festerlytic method.  Hmmmm....out of curiousity the solution was changed several times involving alcohol, water, and then finally some sulphuric acid.  It would not appear that there was anything wrong with any of the connects as when the electrodes touched each other in the solution it sent the amps soaring.  Does anyone have any ideas about what was happening?  Personally I would have thought that acetic acid (plus the sodium acetate and phenylalanine) would have been fairly good conductors (there is certainly no problems with inadequate current in the festerlytic method).  Any clues??

The idea about the Ag came from the festerlytic method - it can be substituted for the Pd or Pt in that reaction so I thought that its similar properties to these metals may have helped out in this instance.


--------------------
Master of Puppets is pulling your strings.....

jim

  • Guest
Re: References...
« Reply #13 on: December 23, 2000, 02:40:00 PM »
I say add more sodium acetate and decrease the electrode distance to several millimeters.

This should solve the problem.

WizardX

  • Guest
Re: References...
« Reply #14 on: December 26, 2000, 04:39:00 AM »
Acetic acid and phenylalanine are poor ionic conductors in electrolyte solutions. Sodium acetate is good. Just lookup their acid constants and solution ionization constants.

The high resistance can be minimized by large surface area electrodes.

masterofpuppets

  • Guest
Re: References...
« Reply #15 on: December 28, 2000, 08:32:00 PM »
Hi,

In regards to SWIM's earlier problems.  The acetic acid was essentially saturated with sodium acetate (ie. it wouldn't absorb any more of the stuff) and even when there was a tiny space between electrodes the current was very small.

Is there anything that can be done to reduce the resistance of the solution?

Also although it is suggested that platnium is used for the electrodes (and one or two people have stated that silver couldn't be used) I don't really understand why this is so.  Could someone please explain why silver, palladium etc can't be substituted for the platnium - although my chem experience is pretty inadequate I can't find any references that would suggest that these other metals wouldn't work (although not quiet as well).

Finally does anyone have any ideas about how many amp seconds have to pass through the solution per gram of phenylanaline for maximum yeilds??

Thanks again for all your help


--------------------
Master of Puppets is pulling your strings.....

PolytheneSam

  • Guest
Re: References...
« Reply #16 on: January 08, 2001, 06:14:00 PM »
Try putting in some water to reduce the resistance.  I noticed also that glacial acetic acid doesn't react too quickly with NaHCO3 and found that some water had to be added to get it going (indicated by faster effervesence).  The acetic acid probably needs water to be ionized. The same thing might be true with the sodium acetate, ie. it needs some water to ionize in solution.  I think you need the ionization to get an electrolytic cell to work.

Lilienthal

  • Guest
Re: References...
« Reply #17 on: January 09, 2001, 02:49:00 AM »
Maybe the power supply has a current regulation (or a short circuit detector) which was triggered by a too high current through your solution.

foxy2

  • Guest
Re: References...
« Reply #18 on: January 10, 2001, 01:36:00 AM »
"In summary the following general experimental conditions should be
applied for a sucussful dimerization of carboxylic acids: An undivided
beaker type cell can be used equipped with a smooth platinum anode and
a platinum, steel or nickel cathode in close ditance; a current
density of 0.25 A/cm^2 or higher should be provided by regulated power
supply, a slightly acidic or nuetral electrolyte, prefferable methanol
as solvent and a cooling device to maintain temperatures between 10 to
45 C should be employed. With this simple procedure and equipment
yields of coupling product as high as 90% can be obtained, provided
the intermediate radical is not easily further oxidized (see Chap. 7)."



:)


Happy New Year

thissuks

  • Guest
Re: A strange, possible, amphetamine synthesis
« Reply #19 on: February 24, 2001, 05:49:00 AM »

http://www.ticalc.org/archives/files/fileinfo/107/10751.html



solubilities


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