Hey! Not sure if this is the right forum, but as i'm definitely a beginner, here it goes:
Can any one give me some hints on the practical procedure of the decarboxylation of phenylalanine to
phenylethylamin?
Any reply highly appreciated, there's so much theoretical general stuff to find but nothing practical ...
Thanks!!Esplosivo - 23-1-2005 at 12:55
First of, the reaction you mention is no decarboxylation. The addition of an ethyl group to the benzene ring is referred to as an alkylation, which is
usually carried out by Friedel-Crafts alkylation technique.
It basically involves anhydrous AlCl3 as a catalyst and chloroethane and refluxing. You may have some problems due to the oxidation of phenylamine and
also due to its decomposition at its boiling point. I would suggest working to your product by first obtaining ethylbenzene, nitrating this and then
reducing the nitro group ta an amine. This will produce the ortho- (2-) or para- (4-) methyl isomer though.
You could produce the meta- (3-) isomer by protecting the amine group. This can be done by reacting phenylamine with an acid chloride or an acid
anhydride producing the respective substituted amide. On this produt Friedel-Crafts alkylation could be carried out. Hope this helps.
[Edited on 23-1-2005 by Esplosivo]sparkgap - 23-1-2005 at 13:34
Uh, Esplosivo, you seem to be confused.
dr. nick was asking about the conversion from phenylalanine to phenylethylamine, or, as I prefer to call it, phenethyl amine (PEA).
That is a true blue decarboxylation:
Ph-CH2-CH(NH2)-COOH --> Ph-CH2-CH2-NH2
You most likely confused it with ethylaniline, from the synthesis you gave.
Matter of fact, something similar happens to both histidine and tryptophan, the first being converted to histamine; the second being converted to
tryptamine.
As to dr. nick's question, I am not at all aware of decaboxylation reactions for amino acids save enzyme-mediated ones. These, I am sure, were
the ones you found during your search.
Sorry for not of being much help.
sparky
(edit: misspelling)
[Edited on 23-1-2005 by sparkgap]JohnWW - 23-1-2005 at 14:09
Amphetamine or benzedrine (a powerful stimulant, C6H5-CH2CH(CH3)-NH2) , mescaline (an hallucinogen, 3,4,5-trimethoxy-1-phenylethyl(2-amine)),
serotonin, adrenalin, and noradrenalin, along with LSD and opiates (with much more complex structures) like morphine and codeine and heroin, are all
derivatives of phenylethyl-2-amine, C6H5-CH2-CH2-NH2, which Dr Nick wants to make from decarboxylation of the amino-acid phenylalanine. Am I correct
in assuming that Dr Nick wants to use the phenylethyl-2-amine produced to make one of the above derivatives?
In practice, however, while decarboxylations are exothermic because of the stability of CO2, special groups usually have to be present in the molecule
for it to occur sufficiently readily to be useful in synthesis; for example, beta-keto-acids which form a ketone and CO2. Aromatic carboxylic acids
decarboxylate when their salts are heated with Cu and quinoline and an alkali, although these are very "forcing" conditions.
In the Hunsdiecker reaction, the Ag salt of a carboxylic acid is heated with Br2 in CCl4, resulting in the -COOH being replaced by Br, along with CO2
and AgBr. But then you would have to find some way to reduce the Br to H; reaction with Zn and aqueous acid should do it, taking advantage of the
exothermicity of production of ZnBr2.
Ref: Decarboxylation
solo - 23-1-2005 at 15:11
Here is a procedure from the Rhodium files.......solo
Decarboxylation of phenylalanines to phenethylamines
by Ritter
[ Back to the Chemistry Archive ]
Procedure
Mix 10g phenylalanine isomer of your choice in 50ml cyclohexanol. Add about 0.1 to 0.3ml cyclohexanone. Amino acid will not dissolve in cyclohexanol
until it is pretty hot. Bring mix up to about 140°C. Rapid and somewhat violent decarboxy-lation will start. The soln will bubble like beer (CO2
release) and slowly turn a light yellow. An interesting crackling noise is produced as temp gets up to reflux point (161°C) that sounds like popcorn
popping. It is actually pretty startling when done on a larger scale! When CO2 emission comes to a halt after about half an hour cool mix and extract
w/ dilute HCl. Basify HCl extract to isolate the pretty pure phenethylamine as a light yellow fishy smelling liquid. Yield unfortunately is variable -
anywhere from 4-8g has been isolated from this rxn. I'm sure other high BP solvents will work fine, cyclohexanol happens to be what was at hand.
[Edited on 23-1-2005 by solo]Esplosivo - 23-1-2005 at 21:29
Damn, sorry my bad. Thought it was phenylamine not phenylalanine. Sorry again.dr. nick - 24-1-2005 at 13:04
hey, cool!
thanks all!!
but i guess cyclohexanon can not be substituted with anything else, right?
that's why i love this part of chemistry, one never get's in danger because one never comes to a reaction, every time one problem is solved
another 2 turn up
that's what i would call "built in safety", arrr enima - 28-1-2005 at 10:08
the cyclohexanone can be replaced with any other ketone, it acts as a catalyst, acetone or methyl ethyl ketone can be used here.trilobite - 28-1-2005 at 12:51
The acetone or MEK might reside mostly in the vapour phase at that temperature.dr. nick - 1-6-2005 at 08:51
Hey all, thanks for the hints!
it's some time gone meanwhile, and after talking to some other interested people the procedure was changed in so far, that Paraffinum Liquidum
was used instead of Cyclohexanol and the whole thing was started in a micro test run:
2g of l-Phenylalanin, 10ml of Paraffin Oil and 0.5ml Cyclohexanon where heated in a test tube with a thermometer over an open flame in an "oil
bath" (some oil in a tin cup). Even at over 160 C the Phenylalanin did not resolve. The Liquid became pretty yellow, but the phenylalanine seemed
to be still on the bottom of the tube ...
Also there was nothing like crackling noises - everything was dead silent
Don't know what to think now - is that normal? Or is there something wrong with the Paraffin Oil? Hm ...
any hints anyone?
Thanks!dr. nick - 23-6-2005 at 10:12
now same was tried with cyclohexanol instead of paraffine oil, everything went like in the write upbut - the PA still didn't dissolve ...
No Clue, no end in sight. The work up is also still a riddle to swim ...
Maybe the reaction can not be scaled down like dr. nick did?
darn, it's all so confusing. Can Phenylalanine become old?
After the reaction just acidify with diluted HCL? How? Adding some drops of it? Adding watery solution with a ph of 7, 6,5 ... ? What's the sense
of this step? Salting out the wanted PEA.hcl? After that one can simply evaporate the water? What about the cyclohexanol - it is water soluble, not
very much, but still ... And then? Basifying? What for? To get the freebase again? How to get that freebase out of the lye water? With non polar
solvent?
arrr, swim's cracking ...
Help, please, if anyone can ...
Every hint very welcome, swim don't get it anymore ... *sob*
Also that smell of toluen and stuff makes swim sick. rather sniffing acetone than this all the time. toluen smell has something of
sugar-sweet-smelling-dog-shit ... bwaark
[Edited on 23-6-2005 by dr. nick]dr. nick - 24-6-2005 at 13:50
ooouh pleeease - does really noone have any idea?!?
please help a stupid newb before his weak blockhead
pops up at the wall ... err, if you get what i mean ...
Any hints on isolating or every others step in this procedure very welcome, also interested in the theorectics behind this! I'm sorry, no clue
what i could offer for a hint,
i maybe could dance around on the street on one leg one finger in every nose hole, chanting "bah-bah, white sheep" or what ever may please
my potential saviour ...
(argh, forgive me, going nuts, trying and trying. maybe it's also that f***ing toluene ... ) Where ever swim searchs there's no practical information to find (at least not practical for swim) and noone
seems to know anything on this. is this really that much off key/uncommon/dumb?Cloner - 4-7-2005 at 01:13
i think dissolving stuff is pretty necessary in any reaction. If molecules don't meet each other, they don't react and for this reason you
need the stuff somewhat soluble in the chosen liquid.
I don't know the reaction but it looks like you need only two things: a high boiling ketone and a high boiling solvent that dissolves both the
ketone and the phenylalanin. Perhaps other solvents will do a better job, like diglyme, DMSO, even glycerol?
Dissolving phenylalanin wil also be PH influenced. Would it help dissolving in a minimum amount of water and then adding to cyclohexanol?
The HCl step is meant for getting the HCl salt of the product. It is an amine, which is not soluble at all in water by itself but when ionized to
ammonium form, it is very soluble. So the product enters the water phase and after one or more extraction steps you don't seem to need to boil it
out at all since simply basification will make it insoluble in water again. No nonpolar liquids, it will come out of the water by itself. You might
extract the water afterwards just to be sure you got it all though.
[Edited on 4-7-2005 by Cloner]dr. nick - 6-7-2005 at 07:29
Wow, Cloner - Thank you!!
I was about to get nuts with this!
Thanks!
(If swim will ever have any success with this he will post ist, even if he don't knows if anybody at all is interested in it ...)dr. nick - 10-7-2005 at 10:24
another try - another failure
- the phenylalanine (2g in 10ml of dh2o) is still insoluble, even when boiling it.
- on the other hand it is pretty good soluble in strongly basified water (dh2o with naoh)
Now what swim is wondering about is:
Couldn't one basify the phenylalanine first in naoh solution and then put it to the desired amount of NP, in this case cyclohexanol?
Shouldn't the phenylalanine go into the np then?
Or dose this only work with amines? maybe i got this wrong, but as there aren't much docs on this swim got to the most related (he thinks) -
meth!
He believes that he has l-phenylalanine.hcl. (it's a white, small-shardy powder). if he bases it in naoh solution it should become the free base,
he thinks, which can then go into the np ...
after that the reaction could be done as in the write up ...
is this completely wrong?
THANKS!dr. nick - 18-7-2005 at 01:22
sorry, question was already answered. *sigh*
[Edited on 18-7-2005 by dr. nick]dr. nick - 13-4-2006 at 12:17
oh, oops - sorry, thought i already wrote this, but anyway - here it goes:
In the end it worked - the only problem was, that the reaction times in the Rhodium-File did not fit for dr. nick - after around the double time (1
1/2h, as far as i remember)
everything was done. Some A/B, and so on and voila ...
The only thing since then is: what to do with that crap ??? :
anyway, thanks for all the help!!!Vitus_Verdegast - 14-4-2006 at 07:09
Your phenylalanine doesn't have to be completely dissolved. It is strong stirring that is absolutely necessary to drive this reaction forward. Even
when the aminoacid substrate is completely dissolved in the solvent, without strong stirring the decarboxylation will take forever and a day to
complete.
At least that is what my grandmother told me about her attempts to decarboxylate tryptophan on a +-10gram scale.
Possible uses for phenethylamine: excessive methylation will give a N,N,N-trimethyl-phenethylammonium salt, which could be an interesting
phase-transfer catalyst.
Or you can diazotise it in an attempt to obtain phenylethanol, which smells like roses and should be more desirable to the smell of fish.nitroglycol - 15-4-2006 at 14:33
Quote:
Originally posted by enima
the cyclohexanone can be replaced with any other ketone, it acts as a catalyst, acetone or methyl ethyl ketone can be used here.
There's a procedure from JCS 3993(1965) for decarboxylation of tryptophan that uses no ketones; in this procedure 10 g of TRP are dissolved in 500 mL
Ph20 and refluxed for an hour under nitrogen. I've never tried this procedure; I wonder if it would work for PHE-->PEA?dr. nick - 17-4-2006 at 10:59
hey - thanks-thanks-thanks a lot!!!
at least a use for this!!
amino alcohols are good, someone told me - don't know what for, but well ...
On the stirring: may really be right, swis used only 5g of it without stirring, and it already took almost the double time as it should - thought he
got low quality reagents, but it might also have been from lack of stirring!
Swis used Cyclohexanol as it took him a lot of time to get it
Oh, and last but not least because he did not need any apparatus, like stirrer, reflux and so on which he does not have available ...
Was going to try it again with paraffin and turpentine oil, but not yet ...
Thanks!!
ps.: diazotisation?? got to look that up, i feardr. nick - 9-9-2006 at 02:16
Hi there,
been away for a long time, now i thought it was time to take a look again at this thread - the possibilites of getting interesting things from amino
acids ar far too interesting to forget about it.
Since the repeated tries lead to success (and the2-pea is pretty useless itself)
i try to find out more about opiat-synthesis outgoing from amino acids or 2-pea,
but all i could find where contradictory sources that say opiates where from the thyrosin-type, others say it was from tryptamin type and, last but
not least, some dark murmurs on a corey-fuchs synthesis from phenylalanin to morphin with 10% results.
Not really thinking of trying this in practise but still very interested to understand as swid is kind of a chronic pain patient and opiates and
analgetica are around all time.
can anyone give me a hint leading to the right path on this, regarding opiat precursor, amino acids and so on?
there's so much information out there i can not find a way through it ...
Thanks!
[Edited on 9-9-2006 by dr. nick]solo - 9-9-2006 at 03:13
Reference Information
Recent Progress in the Synthesis of Morphine Alkaloids Josef Zezulaa, Tomas Hudlicky Synlett 2005: 388-405
Abstract
Recent accomplishments in the field of total synthesis of morphine alkaloids are reviewed. Approaches to the skeleton of morphine are included as are
various efforts towards related medicinally important agents. The literature coverage begins after the publication of our last update in 2000 and
continues mid-way through 2004.
1 Introduction
2 Total Syntheses of Morphine
2.1 Taber
2.2 Trost
2.3 Ogasawara
3 Approaches to the Morphine Skeleton
3.1 Vollhardt
3.2 Ogasawara
3.3 Cheng
3.4 Passarella
3.5 Hudlicky
3.6 Hudlicky
4 Unnatural Analogs and Mimics
4.1 Rice
4.2 Grauert
4.3 Trost
4.4 Ohno
4.5 Schmidhammer
5 Conclusions and Outlook
Key words
morphine - total synthesis - alkaloids - approaches to morphine skeleton - morphine analogs and mimics
domo honto ni arigato gozaimashita, or so 2bob - 12-9-2006 at 06:30
try this, I have been meaning to get around to it, but UNI shit keeps getting in the way!!!dr. nick - 12-9-2006 at 09:16
we-hell, after reading the info i could find yet i'd love to take a closer look,
but do you maybe have any practical advice?
All i found yet was too theoretical for me ...2bob - 18-9-2006 at 00:43
sorry, I must have hit the post button too early (and for some reason I cannot submit after 'editing'). The procedure that I wished to avert to is
here:
this is a weird, electrochemical methylation/reduction of phenylalanine to methyl phenethylamine. I am unsure if this sucker works, but I intend to
try it during the xmas break from uni.dr. nick - 18-9-2006 at 03:17
very interesting indeed, even if i'd be more interested in simple Phenylisopropylamin - but in the end it doesn't matter, it's just for the
fascinating thing what all can be done from phenylalanine (or other amino acids).
The problem is i do not have any practical access to this kind of procedure -
can anyone provide some practical-how-to on experiments like this?
(Something like "Elektrolysis for Beginners" or even better "for Dummies"?
Or where to find something like that?
[Edited on 18-9-2006 by dr. nick]solo - 18-9-2006 at 09:11
Reference Information
Synthetic Organic Electrochemistry Albert J. Fry John Wiley & Sons, New York, 1989, 339 pp., $55.00
The reviewed book is a textbook of electrochemistry for organic synthetic chemists. It will interest beginners and please the advanced. In ten
chapters the author convinces the reader that electrochemistry has become an important and prospective tool of organic synthesis. The first three
chapters are devoted to an introduction of basic terms, electrochemical principles and techniques used in the study of electrochemical reactions
(cyclic voltam- metry, polarography, coulometry and preparative electrolysis). Of great value is the fourth chapter, dealing with methods that can
be used to influence organic electrode reactions (the effect of potential, electrode material, and surface interception of inter- mediates generated
on electrodes). Cathodic reduction of organic substrates (reductive cleavage of single bonds, reduction of multiple bonds and conjugated systems)
are the subject of Chapters 5, 6 and 7. Ox- idation processes, particularly the oxidation of carboxylic acids and aromatic compounds, are treated in
Chapter 8. Of special synthetic interest is the so-called indirect electrolysis which allows per- formance of electrochemical reactions at
potentials where the studied compound is elec- troinactive. Both the basic types of indirect electrolysis-electrocatalysis and redox re- actions
with electochemically generated reagents (mediators) are dealt with in Chapter 9. Experimental conditions for preparative electrolysis (power
sources, electrochemical cells, electrodes and their material, reference electrodes, solvents, and electrolytes ) are discussed in Chapter 10. From
an immense amount of material the author has selected many instructive, synthetically important and prospective reactions that can be performed on
electrodes. These are not only redox transformations of functional groups but also reactions of electrochemically generated intermediates leading
to new carbon skeletons. The concise, clear, and to-the-point content of the individual chapters-discussion of mechanism of electrode reactions and
comparison of their advantages over the classical ones, together with representative and recent references-make the book not only a textbook of
electroorganic synthesis, but also a useful handbook for synthetic chemists looking for applications of non-traditional procedures in organic
synthesis.
[Edited on 18-9-2006 by solo]dr. nick - 18-9-2006 at 12:29
thank you!
**
eek - just found out it's 199$ now ...
[Edited on 18-9-2006 by dr. nick]solo - 18-9-2006 at 19:58
The Handbook of Solid State Electrochemistry is a one-stop resource treating the two main areas of solid state electrochemistry: electrochemical
properties of solids such as oxides, halides, and cation conductors; and electrochemical kinetics and mechanisms of reactions occurring on solid
electrolytes, including gas-phase electrocatalysis. The fundamentals are presented, including structural and defect chemistry, diffusion and transport
in solids, conductivity and electrochemical reaction,
This book reveals electrochemistry as an integral part of modern physical chemistry, in particular as a branch of surface chemistry. It is written
without excessive mathematical complexity, and with an emphasis on the mechanisms of electrochemical reactions and how they may be explored using
modern techniques. Written primarily for mid to advanced level undergraduates and postgraduates of chemistry, the book is also intended for
electrochemists working in any of the vast range of industries exploiting electrochemical technology.
Electrochemical Activation of Catalysis: Promotion, Electrochemical Promotion, and Metal-Support Interactions
This book describes the phenomenology, theory and potential applications of the phenomenon of electrochemical promotion, where electrochemically
induced ion spillover activates and controls heterogeneous catalysis. The origin of electrochemical promotion is discussed in light of a plethora of
surface spectroscopic and electrochemical techniques. Electrochemical and classical promotion are compared, their common rules are identified and
promotional kinetics are rigorously modeled and compared with experiment.
The book is an up-to-date introduction to the fundamentals of the initial stages of Electrocrystallization, which are dominated by nucleation and
growth of the first clusters of the new phase. It offers a readable exposition of the topic, in simple terms, providing a detailed theoretical
description of the phenomena involved. The most relevant aspects of the experimental studies of electrochemical nucleation and growth are considered,
as well, including some important methods for acquiring and analyzing experimental results. Having specific properties quite different from those of
bulk materials, these small, nano-clusters have always attracted considerable attention, and many sophisticated methods have been developed for
cluster studies. In spite of this, information on small clusters can still be obtained by simple experiments, and the book shows that
Electrocrystallization is unique in this respect. In this special case the phase change may be controlled experimentally by controlling the voltage
and current, two simple and easily measurable electrical quantities. Certainly, this is what makes electrochemical systems an attractive object of
study both from a scientific and from a practical point of view.
Btw, before i forget - thank you very much for all those eBooks!
I guess i will have to get the mentioned "Synthetic Organic Electrochemistry" from somewhere - maybe anyone has it ... ?
I'm still completely confused even on the commencements of this technologie - what solvent to use, what tension, which kind of electrodes in a case
like electrolysis of Amino acids or Phenetylamines (or any other), and so on and so on - and that book sounded like it would serve my needs ...
I mean, just dissolving phenylalanine/2-phenethylamine in some water or what it needs to dissolve it, adding a batteriepole on each side of the vessel
with some stamping as electrodes ... i don't think that would work. Or ... ? Nicodem - 22-9-2006 at 10:17
The radical formed by the phenylalanine anodic oxidation is way too unlikely to couple with anything due to the adjacent amino group. There are too
many options for the rearrangement of the radical (H abstraction from either the -NH2 or the neighboring benzylic positions, leading to much more
stable radicals and oxidation products). In short, the anodic oxidation of phenylalaninates with acetates would result in phenylalanine oxidation to
crap. However, the phthalimido protection of the amino group would actually stabilize the radical, perhaps allowing the coupling with the Me°
radicals originating from the anodic oxidation of the acetate anions. Nevertheless, the chances of success are almost negligible.solo - 22-9-2006 at 12:01
Principles of Electrochemistry Jiri Koryta, Jiri Dvorak, Ladislav Kavan
Book Description:
This comprehensive book describes modern electrochemistry, from fundamental principles to the methods that can be used to study electrode and
electrochemical processes, and finally, at the wide-ranging applications in sensors, industry, corrosion, and bioelectrochemistry. The breadth of
coverage ensures that this volume will be valuable not only to undergraduate and graduate students, but also to research workers
Ok, as far as i got it, Electrolysis of Phenylalanine will lead nowhere -
how about 2-PEA? I believe to remember very vaguely there was a thread
on Electrolysis of 2-PEA somewhere sometime, but can't find it anymore ...
Was it just a dream? A dream of a dream? hm ...
don't get me wrong, i don't have a special interest in the substances that may be suspected - it' just the only thing i ever heard of - i'd give
almost an arm or so for any results
btw.: thanks again, the book seems to be what i need.
[Edited on 22-9-2006 by dr. nick]not_important - 22-9-2006 at 22:59
Nicodem, whose name I seemed to be determined to mispell, is right. You need to switch from the electron-releasing NH2 to something
elctron-withdrawing to have much luck. I may be misremembering, but I believe that plain phenylacetic acid can be coupled with itself to give 1,4
phenyl-butane and cross couplings can be done on it too.
PEA is a simple amine, don't think much interesting will happen with it.dr. nick - 23-9-2006 at 01:01
Ah, i see.
Seems i got to get into Theory more first - hope i will find something interesting do do with it. Meanwhile i found something worthwhile (i hope) with
Pepsinolysis, but that got nothing to do with neither Phenylalanindecarbxoylation nor with Elektrolysis. If it has any results i could open a new
thread, maybe.
Thanks!Nicodem - 23-9-2006 at 03:35
Quote:
Originally posted by dr. nick
Ok, as far as i got it, Electrolysis of Phenylalanine will lead nowhere -
I did not say that it is impossible to obtain the wanted product by such electrolytic means. I said that phenylalanine should be protected by the
phthalimido group first and then perhaps there would be some chance of success. (A very little chance in my opinion, but
nevertheless more than zero.)
Quote:
how about 2-PEA? I believe to remember very vaguely there was a thread
on Electrolysis of 2-PEA somewhere sometime, but can't find it anymore ...
What about beta-phenylethylamine (I assume you mean this by "2-PEA")? This compound has no carboxylic groups so it can not be anodicaly oxidized to
the appropriate radical that can only form by the decarboxylation of the originally formed unstable -COO° radical:
So I don't know how beta-phenylethylamine fits into the context of this reaction?
Quote:
Originally posted by not_important
I may be misremembering, but I believe that plain phenylacetic acid can be coupled with itself to give 1,4 phenyl-butane and cross couplings can be
done on it too.
You probably meant 1,2-diphenylethane, since that would be the product of the anodic oxidation of the phenylacetate anions. I think such product would
form easily given that the intermediate benzylic radicals are very stabile. That is also one of the concerns on why N-phthalimido-phenylalanine salts
would not work well in the anodic oxidation. The formed radical could well rearrange to form the more stabile benzylic radical thus yielding
2,3-diphenyl-1,4-diaminobutane (with 2-phenyl-1-aminopropane in the presence of acetates) after the phthalimido deprotection. (But one could easily
answer this by checking the tables of radicals stability.)dr. nick - 23-9-2006 at 03:46
here probably my cluelessness will show up highly visible, but:
Did i get it right?
Elektrolysis is only of value with compounds that are able to be decarboxylated?
Or is this just the case with Phenylalanine in want of a special product?
Uff, turns out to be even more complicated than i expected it to be
ps.: yes beta-phenethylamin was meant by 2-pea, sorry if that was a completely daft idea. thought i read about it, but i probably mixed up something
...Nicodem - 23-9-2006 at 04:04
Quote:
Originally posted by dr. nick
Did i get it right?
Elektrolysis is only of value with compounds that are able to be decarboxylated?
Aren't we talking about anodic coupling of the carboxylate anions? Several posts above, 2bob posted a link to a pretty unfounded idea of a mixed
couplings of the radicals formed by the anodic oxidation of acetate and phenylalaninate salts mixture.
So all my replies were done in this context and you probably misunderstood with some other topic. Perhaps with the thread title reaction, the thermal
decarboxylation of phenylalanine to beta-phenylethylamine?
Obviously, electrolytic reactions involve way more than just this single one. Besides oxidations and radical reactions like this one, there are also
many cathodic reductions that can be done. The organic electrochemistry is full of useful reactions, it is just that the field is little researched
and not really popular. Its best years were at the beginning of the 20th century. Consequently, all those books that Solo posted are useless since
they don't talk about preparative organic electrochemistry but only about the physical chemistry behind the phenomenon of electrochemistry (not really
interesting to an organic chemists unless you like mathematics).dr. nick - 23-9-2006 at 04:50
oh, oops ...
my fault, but nevertheless somehow enlightening to me, too!
no, the thermal decarbox of of phenetylamine is already done,
i'm just fascinated what else can be done with amino acids and
electro chemistry looked especially interesting as it might be less
complicated from viewpoint of needed equipment. But now as i read
more it also seems to be even more complicated in planing than
standard reactions ....
Thanks!not_important - 23-9-2006 at 05:26
Quote:
Originally posted by Nicodem
Quote:
Originally posted by not_important
I may be misremembering, but I believe that plain phenylacetic acid can be coupled with itself to give 1,4 phenyl-butane and cross couplings can be
done on it too.
You probably meant 1,2-diphenylethane, since that would be the product of the anodic oxidation of the phenylacetate anions
Yes I did mean that. I plead the presence of a rather presistent distraction that resulted in elongating chains. But the basic idea was right,
alpha-amino acids generally fall down in the Kolbe reaction.
The stability of the benzylic radical isn't critical, ordinary alphatic carboxylic acids work OK in the reaction. The easy of oxidation to and
stability of the benzylic carbenium ion is important foe the amount and nature of side products. Alphatics tend to grab a H or OH, forming the monomer
hydrocarbon (vs dimer when another R. radical reacts) or alcohol, although other stuff is formed to. Phenylacetic gives noticable amounts of the
benzyl alcohol ester of phenylactetic acid and if the solvent contains an alcohol more of the mixed benzyl ether.Nicodem - 23-9-2006 at 06:33
Well, I finally took some time to (superficially) read the abstracts provided in that old Rhodium's page. What it says useful in regard of this
particular transformation on phenylalanine is:
1.) the reaction does not work with alpha-amino acids (so it does not work on phenylalanine);
2.) the N-acyl protection on alpha-amino acids leads to the formation of N-methoxymethylamides (so a normal acyl protection on phenylalanine would not
work);
3.) the coupling of 3-phenylpropanoic acid works (so the concerns I had about the rearrangement of the intermediate radical to form a more stable
benzylic one is obsolete);
4.) if the radical is too stabile it will get oxidized further on to the carbocation before the coupling can occur (I don't know how powerful the
alpha-phthalimido group is in stabilizing the radical);
5.) there are no reports on the use of the phthalimido protected alpha-amino acids (so there still are some chances that it might work on phthalimido
protected phenylalanine).
Obviously, we already figured out about the point (1), and since I suspected about (2), I recommended the phthalimido protection instead of the
standard N-acetyl. The radical stabilization trough rearrangement is now also out of my concern due to (3). About (4) we could still check the
literature (but this won't be me since I'm not that interested). So (5) remains the only consolation to those that want to try such a reaction.
Quote:
Originally posted by dr. nick
electro chemistry looked especially interesting as it might be less complicated from viewpoint of needed equipment. But now as i read more it also
seems to be even more complicated in planing than standard reactions ....
I don't see what is so difficult about such a reaction. In its practical aspect it is way simpler than most organic reactions and requires only the
substrate, sodium acetate, acetic acid and methanol for the solvent. The only practical problem is in obtaining a platinum electrode.dr. nick - 23-9-2006 at 08:43
Quote:
I don't see what is so difficult about such a reaction. In its practical aspect it is way simpler than most organic reactions and requires only the
substrate, sodium acetate, acetic acid and methanol for the solvent. The only practical problem is in obtaining a platinum electrode.
arr ... the whole discussion goes way above my head
Lost the thread somewhere and found myself lost in the wood, so to say ("Isn't it good to be lost in the wood? ..." Well, maybe, sometimes).
If it isn't too much work would you be so kind to describe the practical breadbord to me? And the Result? Either with Phenylalanine, Alanine (both L-)
or 2-PEA?
I'd even buy an Platinum Electrode, just to find out if it got at least something right.
