Sciencemadness Discussion Board

Amino alcohol via Akabori, trial run

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CycloKnight - 8-6-2006 at 11:40

Recently I’ve been experimenting with the Akabori reaction, just curious to see if the process for making amino alcohols can be improved upon. I thought it would be quite an interesting amateur science experiment.
So far its been an interesting challenge !

The Akabori refers to the reaction between an aldehyde & amino acid to yield the corresponding amino alcohol.


For this run, the following chemicals were used:
83 g l-alanine (considerable excess)
40g benzaldehyde
250ml xylene as solvent (convenient & OTC)

The conventional low yielding approach is to simply heat benzaldehyde & l-alanine at 150-160 C until CO2 evolution ceases.
The objective with this variation is two fold: to keep the l-alanine in excess at all times by slowly dripping the aldehyde into the reaction mix, the idea being that this will increase yields wrt to consumed benzaldhyde, & to keep water out of the reaction.
When water gets into the reaction, by-products are immediately formed and the reaction mix will turn red (tar) quite quickly. The boiling temp of xylene is 139 C, therefore if water drips back into the boiling solution, the results can send foam as far as the condenser & beyond.
Foaming is another issue with this particular trial run, higher dilution is required, higher than what was used in this trial run. By the end of the reaction, due to tar formation, foaming was getting a bit out of control.

The reaction was maintained at high reflux to help flush out generated moisture, this was maintained for 1 hour before the aldehyde addition. To assist with this task, a DIY Dean Stark trap was hastily thrown together, to collect generated water and help keep it out of the mix.

First, the l-alanine was finely powdered as much as possible.


Vegetable oil was used for the oil bath. Stir bar spinning.


General setup.






Moisture starting to collect in the trap.




For the first aldehyde addition, 26 ml of aldehyde was slowly dripped into the solution. Later (see below), an additional 14 ml was added; 40 ml benzaldehyde added in total.







Aldehyde addition is begun, 1 drop every 2 seconds.


Byproducts collecting, the red drops are water.






1 hour after the addition. The addition of the 26 ml aldehyde took 1 hour 15 min to complete.


The reaction was run until water stopped condensing, then the addition of the rest (14 ml) of the aldehyde was begun.




Benzoic acid forming in the aldehyde dropping funnel…


2 hours after the aldehyde addition was started.








Total collected condensate at the end of the reaction


Water accumulation ceased, so the reaction was stopped.
Reaction time = 4 hours.




The reaction mix was put in a freezer to cool, and precipitate impurities.
Once no more impurities (l-alanine mostly) were seen to fall out of solution, the mixture was carefully removed, 3* 50 ml cold toluene was used to rinse the unreacted l-alanine, the pooled toluene extracts were then shaken with 15% HCl until the acid remain acidic upon settling. Temperature before acid addition was 10 C, after addition the temperature had increased to 26 C. A little extra dH2O was added to help with the interphase mixing.
Tar has settled to the bottom, aqueous layer is in the middle, with toluene/xylene on top.


Tar dripped out.


Aqueous fraction extracted 5 times with 50 ml toluene. 10 minutes settling time between each extraction


Followed by 5 extractions with 50 ml dichloromethane


Followed by 5 extractions with 50 ml ethyl acetate.


Aqueous solution was then placed in a pyrex dish and placed on a small pot boiling water to maintain 100 C until the level of the solution had boiled down into a paste. The paste was kneaded with a spatula until the HCl odour had mostly disappeared.




Ethyl acetate has been found to work well as solvent for crystallising the final product (Eureka, finally a means of cleaning up the goop.).

Ethyl acetate washing up. Don’t do as shown – its unnecessary and more difficult, just place the paste in a suitable container and then mix in the ethyl acetate (approx 80 - 100 ml).


The ethyl acetate soaked paste is poured into a 250 ml RBF and heated until all dissolved, then set aside to slowly cool.


After 8 hours, no more crystals appear to be forming. The flask was then put in the freezer for a few more hours.
The crystal mass fills half the flask, not only lining the glass edge as shown in the picture.






Then as fate would have it, luck ran out. Although the acetone used for the washup had been dried with a couple hundred grams of anhydrous magnesium sulphate, the crystals still dissolved somewhat. This was only realised after the acetone extracts were placed in the same container as the previous run’s acetone extracts, so I can't work out the exact yield (Doh!).
It would appear that either: the PPA.HCl salt (phenylpropanolamine.HCl aka norephredine.HCl) is slightly soluble in acetone, or the acetone was wet. SWIM has no idea, yet.
Either way, the dried yield was found to be 10 grams (not including the amount still in the acetone).
Judging by previous runs, the actual yield is probably at least several grams higher.

In the workup it was obvious that some benzaldehyde has remained unreacted, indicating that a higher dilution should be used in future runs.
Any suggestions on how to improve this process further?

Additional note: the ethyl acetate used was distilled from "acetone free" nail polish remover, and was later found to still contain a little isopropyl alcohol.


[Edited on 10-6-2006 by CycloKnight]

Vitus_Verdegast - 10-6-2006 at 08:39

By Jove!! Is that the Daily Mail you're reading ?! :o:o:o




Just kidding.... Good work!
I'm afraid I haven't read up enough on this reaction to give any suggestions, only the reports of failure that were posted a couple of years ago by somebody named 'DRIVEN'.

I think Beilstein should be able to give you PPA solubility info or at least where to find it.

[Edited on 10-6-2006 by Vitus_Verdegast]

Akabori runs

CycloKnight - 10-6-2006 at 13:56

........only the reports of failure that were posted a couple of years ago by somebody named 'DRIVEN'.

Its easy to carry out a sucessful reaction, the workup however is quite tricky.

The general procedure for amine extraction cannot be used here. The general procedure being:
-extraction of final reaction mix using dilute HCl
-basification with 25% NaOH solution
-extraction with organic solvent
-washing organic extacts to remove dissolved NaOH
-drying & gasification with HCl to give the amine salt
-washing the salt in suitable solvent

The reason is mainly because this freebase dissolves quite well in water, prohibiting the organic freebase extracts from being washed prior to gasification, resulting in lots of NaCl formation (and other garbage) in the product. The dissolved NaOH also prohibits the use of vacuum distillation for distillation of the freebase directly, since the NaOH will destroy it at the temperatures required for the vac distillation.
If the freebase/organic solvent mixture is washed to remove the NaOH, the product ends up in the aqueous washes and is very difficult to remove.

Even if the aqueous washing step is skipped in the general procedure, the final crystallised product (and salt!) forms a suspension in the gassed toluene solution, and forms an orange soup-like mix that still requires further purification.
The coloured impurities remaining from that step do not dissolve well in toluene, but do in acetone (with some loss of product).
If one chooses to use the photo procedure posted earlier and skip the HCl gassing/freebase step, then the final brown paste cannot be purified using acetone alone. Acetone was used only to purify the ethyl acetate soaked crystals (BTW, this was because SWIM had run out of dried ethyl acetate)

The use of ethyl acetate for final crystalisation has given the best results seen so far, definitely a step in the right direction for OTC workup.

The more conventional procedure is listed in Chemical Abstracts, Volume 47, column 3347 uses N-methyl-d,l-alanine instead for the synthesis of d,l-ephedrine. In that procedure they use 50 grams of benzaldehyde & 20 grams of the amino acid, mixed together and heated (without solvent). 12 g product are claimed.
When that procedure is used with alanine there is little or no benzaldehyde recoverable from the mix, it is simply mostly converted to tar, PPA, water & CO2 during the reaction.

With the xylene method, about half of the benzaldedhye is recoverable from the solvent !!
Therefore, taking only the REACTED benzaldehyde into account, the reaction efficiency is increased somewhat.

On the other hand, recovering the aldehyde from the xylene mixture by vacuum distillation isn't exactly ideal so what SWIM is aiming to find is the optimal dilution & reaction time that ensures that all the aldehyde is reacted thus giving (in theory at least) the highest reaction efficiency, without the hassle of recycling unreacted aldehyde.
During the xylene run posted ealier, solution colour began to change from light brown to orange after ~20 ml aldehyde had been added. It also appeared that the last 10 ml (30-40 ml addition) aldehyde was simply getting converted to tar.
This could indicate a target dilution, as well as an aldehyde to amino acid ratio, to aim for in order to decrease aldehyde consumption wrt yields.


As for product purity, this is what is known so far:
1) The light cream coloured product does react in warm NaOH solution to yield a light oily layer floating on top, posessing a very distinctive ammonia freebase odour.
2) The melting point is quite high, but hasn't been measured yet. On a stainless steel spatula, it takes a candle flame about 8 seconds before any melting is noted, which certainly doesnt rule out the mp being near the documented value of 195 C.
3) posesses a strong saline-bitter taste
4) if the freebase is acidified with H2SO4 to form the sulfate, and fed into 75% sulfuric acid at 145 C in the presence of ZnCl2 catalyst, the steam distilled product contains the corresponding ketone. This was confirmed by the formation of the bisulfite addition product. This would appear to confirm that the main product is indeed phenylpropanolamine.

S.C. Wack - 10-6-2006 at 16:29

I feel that identification of this as PPA is premature. TLC? MP of the freebase?

Product composition.

CycloKnight - 10-6-2006 at 19:42

The freebase hasn't yet been isolated on its own in sufficient purity for a mp test. Any suggestion(s) on how to do it?
How about an accurate mp test for the salt?

I'm not quite sure what else aside from PPA could produce the ketone according to this process:
http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/p...



[Edited on 11-6-2006 by CycloKnight]

Ramiel - 10-6-2006 at 21:14

I hate to be off topic CycloKnight (it looks like there's a good chemist here), but that's 37 pictures there... omg bandwidth! Someone pays for that megabyte or so for each person who view this page. In this case, perhaps a picture is worth omitting for a few concise descriptions, eh?

Polverone - 11-6-2006 at 00:44

Actually, we're fine as long as we don't go over the 240 GB or thereabouts that we're allowed each month. Below the threshold, it's a fixed rate regardless of bandwidth used.

Vitus_Verdegast - 11-6-2006 at 11:18

My Beilstein access is gone for the moment, does anyone have any information whether this reaction can be performed succesfully on substituted benzaldehydes?

(I recon there should be no problems)

S.C. Wack - 11-6-2006 at 14:13

It has been done with piperonal and N-methyl alanine, no yield given in CA. IIRC all three of the CA abstracts that I am aware of on this (this is the only one with a substituted benzaldehyde and (N-methyl) alanine) are translations from Japanese, a patent and two J. Pharm. Soc. Japan articles.

Update

CycloKnight - 21-6-2006 at 23:25

The yield of PPA given in the previous reaction was no more than about 50% of the final crystallised product.

So far a few different variations on this reaction have been attempted.
As solvent, white spirits works quite well.
Reflux was maintained at 165 C while the aldehyde was slowly added. But the reaction time was still quite high, 4 hrs minimum.

Overall, its been found that the lower temperature variations appear to be producing a larger proportion of other amines, most notably benzyl amine.
The best approach to use for this reaction, is the conventional one (without solvent).
This yields a higher proportion of the desired amine, and is far less time consuming.

Until someone finds a way to minimise the unwanted amine by-products, this is how its done.

Conventional akabori run.

200 ml benzaldehyde
100g l-alanine

equipment required: distillation apparatus & oil bath, hotplate w/stirrer

Simply set up the equipment for distillation, generated by-products will distill out of the reaction as they form.
Finely ground alanine is first added, then the aldehyde.
It's essential to keep the stir bar spinning for the duration of this reaction.
Oil bath temperature is heated to 150-160 C and maintained at this temperature until the evolution of CO2 diminishes (>1.5 hrs).









Reaction time ~ 2 hrs.

Extract the final reaction mix with an equal volume of toluene.
Wash the unreacted alanine a few times with a small volume of toluene.
Combine the toluene extracts and set aside to cool, separate the toluene from any precipitate that settles.
Wash the combined toluene extracts with dilute HCl to remove the amine(s).
Wash the aqueous amine solution with DCM to clean it up as much as possible. This is quite tedious and prone to emulsion forming, especially with toluene.



Basify by slowly adding NaOH granules.

Top layer is mostly freebase ~80 ml.

The freebase is extracted with organic solvent and carefully washed with several ml of distilled water to remove most of the NaOH.
Solvent is evaporated. Residue double distilled under vacuum to yield 35 grams PPA freebase. Melting point ~50 C.
If a way can be found to efficiently extract the remaining PPA from the other distillation fractions, then any remaining PPA could be recovered.

Overall, this was far less work than the previous runs using solvent. Not too impractical for producing a little PPA if you happen have benzaldehyde lying around.

[Edited on 23-6-2006 by CycloKnight]

mr_orange - 24-6-2006 at 02:24

Wow, read science madness off and on, but this thread floored me.
A thousand thanks for sharing the results and pictures of your experiments.
P.S.---Some of the guys over at www.synthetikal.com have been discussing this, it'd be nice if you joined us.

Devilfish - 5-7-2006 at 10:21

SWIM tried this way as well some months ago but adding NaOH he shot the pH too high, not knowing that this will destroy the PPA. Yielded some beakers clotted with a really sticky mass. It took hours to get the labsware clean again...

but reading this writeup SWIM had the idea, that it could worth a try to substitute the workup with a steamdestillation of the FB...

[Edited on 5-7-2006 by daFlo]

Maja - 5-7-2006 at 11:06

From one forum, one guy told that benzaldehyde can be replaced with other aldehyde as piperonal to get MDPPA and then to treat it same way as PPA freebase to get P2P,but in this case we would get MDP2P. Maybe you have tried it and/or have refs / patents ? I WOULD be very grateful

CycloKnight - 8-7-2006 at 16:20

Quote:
Originally posted by Maja
From one forum, one guy told that benzaldehyde can be replaced with other aldehyde as piperonal to get MDPPA and then to treat it same way as PPA freebase to get P2P,but in this case we would get MDP2P. Maybe you have tried it and/or have refs / patents ? I WOULD be very grateful


No refs, have not tried the MD variation - but it sounds interesting. I'd imagine the yields would be quite low.
I wonder if the piperonyl could be fed to the Neff reaction with nitroethane to give the substituted PPA?
Can say that the P2P approach is much simpler, much easier workup. Basically with the P2P variation, the amine mixture is converted to the sulfate with a little sulfuric acid, and the whole mix fed to the high temp acid (with ZnCl2 catalyst or other catalyst) and the ketone steam distilled. Droplets of ketone began distilling almost immediately. Quite easy, really.
The PPA reacts, and all the other garbage just gets left in the pot.
What doesn't steam distill (other amines left unconverted) is simply discarded. From 360 ml alehyde & equivalent amount of l-alanine, yielded about 65 ml free amine(s). On the first acid hydrolysis run SWIM attempted, this then gave at least 35 ml of ketone AFTER being vac distilled. Basically, the whole mix was added at once, higher yields would probably be gained if an amine.sulfate/sulf. acid mixture was dripped in during the steam distillation.
That yield of ketone is higher than the amount of PPA that SWIM has ever managed to reclaim from a reaction of that scale.
Trying to isolate pure PPA from the mixture of amines is quite tedious and doesn't appear too efficient either. There may be azeotropes forming with the PPA too, still haven't been able to work that one out. Also, if there is are significant oily impurities in the PPA, it will not crystallise at room temperature and will require redistilling.
Quote:
Originally posted by DaFlo
SWIM tried this way as well some months ago but adding NaOH he shot the pH too high, not knowing that this will destroy the PPA. Yielded some beakers clotted with a really sticky mass. It took hours to get the labsware clean again...

but reading this writeup SWIM had the idea, that it could worth a try to substitute the workup with a steamdestillation of the FB...


Definitely be careful with the NaOH, SWIM was quite apprehensive about it at first. Maybe try using sodium carbonate instead of NaOH. Either way, the NaOH needs to be washed out at much as possible prior to the vac distillation to prevent the product degrading to tar at the high temperatures. Some will inevitably remain and destroy some of the product before it can vac distill. Never managed to do a run without at least a teaspoon full of dark red tar remaining, SWIM always wondered what that tar might have been if a stronger vacuum had been used...
The only problem I can see with the steam distillation variation is with reclaiming the product from the water. Maybe it would work if the the PPA laden water were acidified to form the salt and then the water boiled off using a short packed column to minimise losses?

Punk - 9-7-2006 at 20:32

Looks to be a lot of work how does the yeild compare to simply heating the 2?

Devilfish - 11-7-2006 at 06:00

why using a column, when boiling off the water? the PPA is HCl-salt at this moment and won´t form an azeotrope with the water. only the freebase should do so or am I wrong?

CycloKnight - 11-7-2006 at 21:24

Quote:
Originally posted by daFlo
why using a column, when boiling off the water? the PPA is HCl-salt at this moment and won´t form an azeotrope with the water. only the freebase should do so or am I wrong?


No azeotrope with the salt. You''ll have say 35 grams of product in a relatively lare quantity of water. As you boil it down, your product concentrates and much of your product will carry over with the steam.

Devilfish - 25-7-2006 at 08:29

erm... having a solution of ephedrine.HCl or meth.HCl in water and boiling the water away won´t lower the ammount of ephedrin/meth.HCl remaining.
Why should PPA do so???

CycloKnight - 10-8-2006 at 13:13

Sorry maybe I should have explained that better.
I was only referring to aerosol carry over. Using a short column (prefereably with packing) helps eliminate the carry over, thats all.

And yes ephedrine HCl and meth HCl will also carry over.
Losses aren't that high, but if youre boiling down a dilute solution of your product, its easy to lose 20% or more of your product.
I.e. if you were to take 5 grams of table salt and dissolve it in a gallon of water, then boil it down to dryness without a short column (or similar), you'd be very lucky if you were able to recover 4 grams. The yield would decrease with increased boiling rate.


[Edited on 11-8-2006 by CycloKnight]

added trials

Punk - 15-8-2006 at 11:10

L-alanine/benz-->norpseudoephedrine freebase

Basicly the 2 were heated directly, diluted with a huge access of water, filtered out any solids, made basic with sodium bicarbinate and chilled. An expected amount of white fluffy crystals settled to the bottom whare they were filtered and washed with cold water.

next step hydrolisis

Anyone have suggestions on obtaining the highest yeild from a norpseudoephedrine--> norephedrine via hydrochloric acid hydrolisis ?

Ive read that only 50% of the starting material can be tranformed. Could someone explain why?

Why is there a strong sulfer smell when boiling norpseudoephedrine hcl in hydrochloric acid?

Could certain molar ratios be used to control the problem of the norephedrine shifting back to norpseudoephedrine?

Is there a feasable way to seporate norpseudoephedrine from norephedrine?

:o

[Edited on 15-8-2006 by Punk]

IOC - 21-8-2006 at 20:51

Try alanine/benz, heat directly, when CO2 is done add equal amount of toulene then add equal amount of H2O and acidify to PH 4, seperate water phase and 3 x methylene chloride to clean.

Boil down H2O pahse to a brown paste then add dry acetone to leave clean white powder.

Havnt had time to qualify MP, next time though

IOC......out

Nicodem - 23-8-2006 at 02:20

And what exactly makes you believe that without removing alanine your crude product is not mostly - guess what? – an alanine salt!

You need to wash with NaOH or Na2CO3 solution to remove the left over alanine before you extract any potentially formed 1-phenyl-2-aminopropanol. Using only water to wash off the alanine would reduce the yield since alanine can act as an acid and will take considerable amounts of 1-phenyl-2-aminopropanol with it into the washes (1-phenyl-2-aminopropanol is even by itself slightly soluble in water, but when protonated is taken into the water phase completely).

This might also explains why CycloKnight got such low yields in the first attempt (I mean the one described in the first post). He should have made the postreaction mixture basic. Then he would not have to extract the water phase 5 times and still get so little product (assuming the conversion was better than what it looks like).
The work up in his latest solventless attempt is more exemplary, though it would be worth to try another approach as well. Some of that alanine precipitated from toluene might have well contained some 1-phenyl-2-aminopropanol absorbed as its toluene insoluble salt with alanine. If instead of removing the precipitate, it would be dissolved by adding enough 20% NaOH to the toluene diluted postreaction mixture, the yields of the 1-phenyl-2-aminopropanol extracted in the toluene might be possibly improved and absolutely all alanine removed (of course, if this issue really is a major problem).
However, I do think you are all underestimating the acidic properties of amino acids. It is true that their solutions are only negligibly acidic due to their ambiphilicity, but they can and will behave as acids toward bases of strength comparative or grater to that of the alpha-carboxylic amine group. 1-phenyl-2-aminopropanol is only very slightly less basic than alanine (pKa's of conjugated acids: 9.44 [PPA] vs. 9.69 [alanine])!

[Edited on 23-8-2006 by Nicodem]

???

Punk - 24-8-2006 at 00:08

Please explain how alanine can " act as an acid" if conditions were made basic with sodium bicarb and all solids were filtered out beforehand?

Nicodem - 24-8-2006 at 02:06

Quote:
Originally posted by Punk
Please explain how alanine can " act as an acid" if conditions were made basic with sodium bicarb and all solids were filtered out beforehand?

I underlined the stage where you failed to see the point of the problem. Now, try again to carefully read what I wrote in my previous post and perhaps you will be able to answer your question by yourself.:P

2bob - 29-8-2006 at 16:46

Sorry to ask a dumb question, but did anybody think to add up the Hydrogen atoms?

It appears to me that C7H6O + C3H7N02 = C9H13NO + CO2, which would appear to be synomonous with PPA rather than anything you may actually want.

However, by performing a streckert degredation (dunno, how about CaOCl?) on Phenylalanine to get Phenylacetaldehyde (C8H8O) and then performing this same reaction, it may be possible to come up with what is sought, eg.C10H15NO + CO2?

IOC - 30-8-2006 at 03:12

yes but if 4-mar is the desired result then C10H15NO will not deliver the goods.

Yes you are absolutley right Nicodem an alanine salt is more than likely the end result of this extraction from the said reaction (almost rhymes :-)

Have any dudes had joy with steam extraction of the PPA freebase from the alanine, H2O and PPA Mix?

The result of ZnCl2 route is still not where every one wants to go so how can the synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes actually produce 12g of PPA from an minimal amout of starting material actually work?

I know there was a methyl group in the write up but what mods can be done to make this more reliable?

Has any dude seen.......

Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
Journal Russian Chemical Bulletin
Publisher Springer New York
ISSN 1066-5285 (Print) 1573-9171 (Online)
Subject Chemistry and Materials Science and Russian Library of Science
Issue Volume 18, Number 11 / November, 1969
Category Organic and Biological Chemistry
DOI 10.1007/BF00906512
Pages 2371-2375
Online Date Monday, January 03, 2005
Add to marked items
Add to saved items
Recommend this article


Organic and Biological Chemistry
Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
V. M. Belikov1, S. V. Vitt1, N. I. Kuznetsova1, M. G. Bezrukov1 and M. B. Saporovskaya1

(1) Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, USSR

Received: 29 July 1968

Conclusions 1. The Akabori reaction involves a stage in which an intermediate imine copper complex is formed from acetaldehyde and copper alaninate.
2. The intermediate complex has a higher CH acidity than the initial alanine copper complex.

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2536–2541, November, 1969.

no % result given but that acidity could be a key.............

IOC .........out :cool:

IOC - 30-8-2006 at 03:14

yes but if 4-mar is the desired result then C10H15NO will not deliver the goods.

Yes you are absolutley right Nicodem an alanine salt is more than likely the end result of this extraction from the said reaction (almost rhymes :-)

Have any dudes had joy with steam extraction of the PPA freebase from the alanine, H2O and PPA Mix?

The result of ZnCl2 route is still not where every one wants to go so how can the synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes actually produce 12g of PPA from an minimal amout of starting material actually work?

I know there was a methyl group in the write up but what mods can be done to make this more reliable?

Has any dude seen.......

Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
Journal Russian Chemical Bulletin
Publisher Springer New York
ISSN 1066-5285 (Print) 1573-9171 (Online)
Subject Chemistry and Materials Science and Russian Library of Science
Issue Volume 18, Number 11 / November, 1969
Category Organic and Biological Chemistry
DOI 10.1007/BF00906512
Pages 2371-2375
Online Date Monday, January 03, 2005
Add to marked items
Add to saved items
Recommend this article


Organic and Biological Chemistry
Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
V. M. Belikov1, S. V. Vitt1, N. I. Kuznetsova1, M. G. Bezrukov1 and M. B. Saporovskaya1

(1) Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, USSR

Received: 29 July 1968

Conclusions 1. The Akabori reaction involves a stage in which an intermediate imine copper complex is formed from acetaldehyde and copper alaninate.
2. The intermediate complex has a higher CH acidity than the initial alanine copper complex.

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2536–2541, November, 1969.

no % result given but that acidity could be a key.............

IOC .........out

IOC - 30-8-2006 at 03:16

yes but if 4-mar is the desired result then C10H15NO will not deliver the goods.

Yes you are absolutley right Nicodem an alanine salt is more than likely the end result of this extraction from the said reaction (almost rhymes :-)

Have any dudes had joy with steam extraction of the PPA freebase from the alanine, H2O and PPA Mix?

The result of ZnCl2 route is still not where every one wants to go so how can the synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes actually produce 12g of PPA from an minimal amout of starting material actually work?

I know there was a methyl group in the write up but what mods can be done to make this more reliable?

Has any dude seen.......

Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
Journal Russian Chemical Bulletin
Publisher Springer New York
ISSN 1066-5285 (Print) 1573-9171 (Online)
Subject Chemistry and Materials Science and Russian Library of Science
Issue Volume 18, Number 11 / November, 1969
Category Organic and Biological Chemistry
DOI 10.1007/BF00906512
Pages 2371-2375
Online Date Monday, January 03, 2005
Add to marked items
Add to saved items
Recommend this article


Organic and Biological Chemistry
Reaction of the copper complex of L-alanine with acetaldehyde and the mechanism of the akabori reaction
V. M. Belikov1, S. V. Vitt1, N. I. Kuznetsova1, M. G. Bezrukov1 and M. B. Saporovskaya1

(1) Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, USSR

Received: 29 July 1968

Conclusions 1. The Akabori reaction involves a stage in which an intermediate imine copper complex is formed from acetaldehyde and copper alaninate.
2. The intermediate complex has a higher CH acidity than the initial alanine copper complex.

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2536–2541, November, 1969.

no % result given but that acidity could be a key.............

IOC .........out
:cool:

Nicodem - 30-8-2006 at 03:17

2bob, I don't think I understood what you’re asking and saying, but in order to avoid similar questions I figured out it would be quite appropriate and very polite to the readers, to have the reaction scheme depicted somewhere in this thread (it should fit besides so many nice pictures). A reaction scheme including the mechanism proposal would be an even better idea to facilitate comprehension.
So here it is:


(some obvious steps like H2O eliminations/additions in the imine formation/hydrolysis, proton transfers, carboanion intermediates, resonance structures and similar are omitted for simplicity sake)


All in all, I think CycloKnight’s latest procedure is quite good even though the yield is only 21%. But then again, the reaction in itself is low yielding anyway so that yield is not bad at all. It is also worth mentioning that some of the benzaldehyde can be recycled as well as some alanine if one is ready to purify them.
My compliments to CycloKnight. ;)

Erratum:
Posted 4 posts above by myself, this sentence:
"Then he would not have to extract the water phase 5 times and still get so little product (assuming the conversion was better than what it looks like)."
originated from a misreading of the work up description in the CycloKnight’s first post and should be ignored. What I saw as an extraction was actually just a washing of the extract.

2bob - 31-8-2006 at 06:20

Nicotinamide,

I see, but, wouldn't the aldehyde with the CH2 be more effective? (by the look of the structure it would be in the right place). In fact I am about to try this out, by the look of it, a streckert reduction on L-Ph.alanine => Ph.acetylaldehyde then add l-alanine may yeild l-eph (according to the rather sparse refs). I personally would prefer l-ps.eph to P2P any day.

Nicodem - 31-8-2006 at 10:40

2bob, you are lucky that I'm bored and pissed enough or otherwise I would reply in a very different way. The lucky part is that I’m not bored and pissed because of you, so you don’t have to take anything personally.

I’m sorry to say this, but you simply don’t SEE.
If you would see, you would see that my nickname is not Nicotinamide and that there is no such member here.
If you would see, you would see that your question makes little or no sense in the context of what you say you can see in my post above.
If you would see, you would see that this is not an illegal drugs and precursors forum and that members here generally don’t use weird and incomprehensible abbreviations and insinuations.
There are many other things you don’t see, but since I’m in a good mood I will rather give you a link to follow if you ever really want to SEE: https://sciencemadness.org/talk/viewthread.php?tid=6534

I’ll make an exception and will (for the first and hopefully last time) do my best to decrypt your post and thus be able to answer your questions. First, I need to know what the hell all those abbreviations are. Correct me if I’m wrong but I would estimate this way:

Forgive me if I will have to make some other assumptions. My first such assumption is that “the aldehyde with the CH2” stands for 2-phenylethanal. Now, I don’t know what you mean by this “[being] more effective”. I would assume you don’t speak about reaction yields, since even assuming the reaction would work, it would give a totally different product that I tend to believe is of little interest to anybody I know.
So I figured out, that you actually believe 2-phenylethanal would mysteriously give L-ephedrine. This also shows you had no insight in the reaction scheme (yeah, I know, it is so complex even if you do try).
What you failed to see is that by using 2-phenylethanal and L-alanine you can utmost obtain 3-amino-1-phenylbutan-2-ol (again, assuming the reaction would work on 2-phenylethanal). Furthermore since the reaction is symmetric at the carbonyl addition point and the only chiral centre on L-alanine is necessarily racemized in the process (as seen from the reaction mechanism), you can only obtain the racemic mixture of enantiomers. Utmost you could get an excess of one diastereoisomere over the other.
Now, if 3-amino-1-phenylbutan-2-ol is your goal than go ahead and bleach your “L-Ph.alanine”, but if it is not take some more time and effort to SEE.

OK, now I feel much better. Have a nice day. ;)

2bob - 31-8-2006 at 23:22

What a lovely reply,

OK.

Here is the ‘PROPERLY’ expressed argument:

1. I take it that you don’t have an issue that Phenylacetylaldehyde is in fact the major ‘strecker oxidation’ product of phenylalanine?

http://www.dfal.de/EJahr2001.html#1.1.4.

http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2005/53/i26/...

The latter publication suggests that not only lipid based oxidants are effective in performing this ‘strecker oxidation’ but also ‘reducing sugars’.

2. In precisely the same manner that benzaldehyde is the ‘strecker oxidation’ product of toloune?

http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/b...

3. I also take it as fact, that if the ‘akabori’ reaction between an amino acid and an aldehyde (such as is produced by the ‘strecker oxidations’ outlined above) is that which is produced in this reaction, thereby validating the reaction, with the important qualification being that the reaction between benzaldehyde and l-alanine gives phenylpropanolamine and carbon dioxide?

4. Therefore, in order for the researchers to have actually synthesized l-ephedrine/l-pseudoephedrine using the ‘akabori reaction’, as suggested here:

http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/e...

Toward the end of the article is a paragraph which states:

‘According to Akabori and Momotani (269), a mixture of an aromatic aldehyde and an amino acid on heating yield alkamines. By means of this reaction, ephedrine and norephedrine were synthesized.’

They must have taken notice of the loss of the carbon atom (as CO2), and substituted an aldehyde with an additional carbon in order to make the reaction work (this is my hypothesis, ie. It is a theory, not a fact).

5. However, I see no reason why this would result in the side reaction you claim, otherwise the reaction detailed here would probably have resulted in an abject failure (although I suggest that yields may be improved by keeping the heat down).

http://www.erowid.org/archive/rhodium/chemistry/nor-pseudo-e...

6. I do however, not really expect that the chirality of the molecule would remain intact throughout, however, I see no reason why I shouldn’t see if it does, especially as I intend to check to see if it has by use of mandelic acid (prepared by hydrolysis of amygdalin with hydrochloric acid).

Finally, I apologise wholeheartedly for offending your delicate sensibilities by overuse of shorthand for chemical names, and I do sincerely state that I will endeavour not to reoffend. Additionally, I understand that you would appear to prefer that people didn’t attempt to ‘experiment’ with analogues of previously tried reactions, however, that is the major reason why I have an interest in this form of chemistry, therefore, I make no apologies for my experimentation.

Nicodem - 1-9-2006 at 01:46

Great, that is a consolation. After posting, I got a bad feeling I unjustly accused you of “not seeing” while it could have been the consequence of some disability. I was already afraid I would have to have bad conscience for maltreating a disabled person, but you demonstrated that you can do better. Thank you.

Now all you have to do is to learn some basic organic and experimental chemistry, learn to follow and read scientific references, see where you have it all wrong, and way you go!

Finally! A simple and fully OTC route to 3-amino-1-phenylbutan-2-ol!

IOC - 2-9-2006 at 00:09

My humble, humble apoligies nicoteen or what ever else your calling yourself these days in between alcoholic drinks and fags of cause as it appears that the edit function isnt an option that is available at the mo, other wise I'd of used it!!!!!!

That function might not be available to me because I also cant spell or have bad grammar or cause Ive got my theories a bit bung or maybe my I's arn't in a line.....

But I'm sure glad I wasnt that little brat that dobbed other kids in or felt a drunkin urge to correct other contributors about there input to what ever.......get a life bro

This from memory even if it is short is a thread that CycloKnight started and although you have some pretty drawings to contribute he is really the only person who has actually had the real experience to talk about

2bob had a valid point in between spelling mistakes, but i guess you'd rather focus on reposts and re filling your drink huh, nice one.......go pour another one

IOC

IPN - 2-9-2006 at 02:11

I think a nice picture of some structures should clear this confusion.

http://koti.mbnet.fi/otto2000/products.gif

There is the Akabori reaction product with benzaldehyde and L-alanine, phenylethanal and L-alanine and the product 2bob would like to get with the Akabori reaction, L-pseudoephedrine.
The difference is quite easily seen...

2bob - 14-9-2006 at 14:29

seen it, sorry nicodem, but you can at least see what I was hoping for? Thank you for the pictures IPN, I had not noted that, sorry once more.:(

2bob - 14-9-2006 at 14:42

now,

at the lower temps, what other amines were formed? Are they still the ephedrine derivatives? I do like it as a possible back road to P2P, although I know nothing, and must not be allowed to learn in peace, apparently?

kafka - 18-9-2006 at 19:35

any updates on this project?

Stirrer/Hotplate Question

Hilski - 27-9-2006 at 07:55

This may be a dumb question, but how important is it that the alanine/benzaldehyde be continuously stirred throught the reaction? I only ask this because I have a mag stirrer, and I have a hot plate, but I don't have a hot plate/stirrer combo.
If it is absolutely required for the sucess of this reaction, then I suppose I'll have to get one when I can afford it.

Thanks.

[Edited on 28-9-2006 by Hilski]

Maja - 28-9-2006 at 04:09

I have tried twice this reaction increasing time even 2x without stirring and yields were at least 2x lower than with stirring... You can try with low amount to see if it worth your materials and time ...

Hilski - 28-9-2006 at 12:39

Quote:
I have tried twice this reaction increasing time even 2x without stirring and yields were at least 2x lower than with stirring... You can try with low amount to see if it worth your materials and time ...


I may try to make one of these. I suppose it would be better than nothing.

http://www.erowid.org/archive/rhodium/chemistry/equipment/ov...

MARXYZ - 28-9-2006 at 13:56

It was my understanding that Akabori said the reaction resulted in pseudo and/or ephedrine when n-methyl alainine was used. When a primary amine (alanine) was used, the amine reacted with the aldehyde to form an imine, and did not increase the length of the carbon chain beyond the aldehyde. Perhapse this is why yields have been low. I would like to see results of n-methyl alanine with an aldehyde. I am also curious what would be the results of an aldehyde with the calcium salt of pyruvic acid. Also, could N-methyl alanine be synthesized the by reductive amination of the calcium salt of pyruvic acid with methylamine?

Nicodem - 29-9-2006 at 03:28

N-methylalanine with benzaldehyde gives a mixture of the ephedrines, alanine with benzaldehyde gives a mixture of the norephedrines, as simple as that. The chirality of the alanines is irrelevant. Check the original papers for other details. The reaction with alanine works just like CycloKnight described. The yields however vary a lot and you might not be able to reproduce his 21% yield in the first attempt. Stirring is important since the reaction mixture gets very viscous and will not mix well by itself. Also, lots of CO2 evolves which results in foaming, which I imagine, would carry the mixture on the top of the condenser if not tempered with efficient stirring.

MARXYZ - 29-9-2006 at 20:38

The problem is that the primary amine forms substantially the side reaction in which the nitrogen bonds directly with the carbonyl to form an imine, and not the norephedrine. The secondary amine does not take this detour, allowing the carbon to bond with the aldehyde. This is clearly stated in his named reaction.

jon - 2-10-2006 at 14:55

man in that mechanism there is the tautomerizm you were talking about and the main product of the reaction is bis-phenyl-2-aminoethan-1-ol. I'm not sure how that's formed but I this perhaps stoichiometry is the reason that the first reaction went off so well as the aldehyde was added slowly. then temperature could make the tautomer more stable in one position rather than the other. I know that tautomer is the reason the principal byproduct is formed in the case of alanine but not in the case of the secondary amine (because of enamine formation as opposed to a tautomeric imine)
In the original reference I noticed that pyridine was used in the reaction with alanine to get 17% and without it it's a crapshoot I think pyridine serves as a base and changes the equilibrium between the two tautomers .temperature (165 celcius in the first reaction) may do the same thing.
another thing the bis compund I'm talking about is that lower phase you see in the seperation it's hydrochloride is insoluble in water as you see in the photo the bottom layer of the three.
and as for extraction the way to do this is too make the aqueous
alkaline, saturate with salt and then add isopropanol. the isopropanol will seperate clean and take the amines with it leaving the salts in the aqueous the isopropanol is then evaporated. that's how ppa is worked up.
oh another thing you think the alanine in the absence of water will protonate the shiff's base of the ppa produced? and affect it's solubility in the organic solvent used to extract it with? that's what your'e actually extracting and that's why half of the benzaldehyde does'nt react any further it's associated with the end product as a shiff's base.
ok so after you extracted the amines into toulene and let's assume you have some amines that are associated with the amino acid sludge that's left over how would you get at them? treat with base, and then what? you'd have a mess of alanine salts seems like a pain in the arse.

[Edited on 3-10-2006 by jon]

[Edited on 3-10-2006 by jon]

ONDDOLE - 19-11-2006 at 08:00

Some help plz?

In regards to cycloknights 2nd PPA synth after washing the aqueous amine solution with some dilute HCl solution, swih picture shows pink solution in the flask...

Problem- swim has given it ago however upon wash(HCl 10%=volume) swims aqueous solution is yellow?

any ideas why? swim used xylene instead of toleune could this be the reason?

also washing with DCM could just abit of acetone be used instead?

jon - 27-11-2006 at 12:13

wash the aqueous phase with acetone? you can try it but I'll think you'll be dissapointed.
acetone is miscible with water.
I think it was mentioned that this reaction has a degree of irreproducibility sometimes you'll get varied yeilds and so a different product composition can be expected and hence the color of the HCl extract.

haribo - 29-11-2006 at 11:39

Just out of interest, do you end up with a raecemic mixture? I ask because the cyanate route to 4MAR (the one that's 1-pot and uses safe chemicals!) only works on trans isomers (I think). Of course, if you lose a carbon by using glycine then you don't have that problem.


EDIT by The Davster:
Keep it chemistry, not how well it smokes and its effects. That has been deleted.

[Edited on 30-11-2006 by The_Davster]

haribo - 2-12-2006 at 10:21

Sorry about that. Yes, I'm interested in knowing if anyone has tried this particular reaction replacing the alanine with glycine. The product has only 1 optical centre and therefore, should undergo cyclization to an oxaziline ring using the enviroment (and chemist) friendly cyanate route. Even if the yield is only 20%, if cyclization can be performed with 78% yield (or their abouts) you would still end up with 17% product. Not GREAT, I agree, but for the availability/cost of the precursors, it really would be cheap.

Nicodem - 2-12-2006 at 10:39

Given that the resulting compound would be 1-phenyl-2-aminoethanol, I doubt anybody would consider wasting time and resources with an Akabori reaction when the same compound is easily accessible from styrene in two simple and well documented steps both having yields above 70%.

haribo - 2-12-2006 at 14:42

That may be the case with unsubstituted varients, but it may be a useful route to substituted analogs. Forgive my ignorance, but what are these 2 'well documented' steps? I'm familiar with aldehyde->nitroalcohol->aminoalcohol but not this one. Forgive my ignorance...

jon - 10-12-2006 at 00:38

I'd like to suggest something in the workup of ppa. PPA is a solid at room temperature and the other amine in the workup (benzylamine) of the first reaction has a m.p. of -46 degress c.; the other nitrogeneous compund formed in abundance (bis-phenyl-1-amino-2-ethanol) is insol. in water as the hydrochloride, so it formed the third phase during the hcl extraction you saw in the photos.
So here's what you do,( I used this on ephedrine which has this property also) you evap. the Hcl extract. and clean it up with ethyl acetate (make sure the ethyl acetate is alcohol, and water free it will suck up water you know) then dissolve it into water a minimal amount of water, and add base (a weak base like NaCO3) then heat this, and extract into naptha (naptha has this property of dissolving aminoalcohols, ephedrines, at elevated temperatures and when it cools they come out of solution as a solid this works with amphetamines too). so you want to quiclky seperate the phases before you mixture cools, it also helps to filter the naptha hot before it cools.
this ought to do a really nice job of seperating your amino alcohol from benzylamine without having to fractionate it twice.
regarding acetone solubilty I've seen this parallel with the ephedrines too. the erythro isomers will dissolve in acetone too. you can probably skip the evaporation of the HCl and just nuetralize it then satuturate it with salt to drive the amino alcohol out.

[Edited on 10-12-2006 by jon]

[Edited on 10-12-2006 by jon]

[Edited on 10-12-2006 by jon]

[Edited on 10-12-2006 by jon]

[Edited on 10-12-2006 by jon]

jon - 12-12-2006 at 05:00

it appears I stand corrected 2-amino1,2diphenylethanol is soluble as it's hydrochloride just like any other amine salt. And it's freebase melts at 146 centigrate did'nt mean to mislead anyone.
it seams though that beta hydroxy amino alcohols can be decarboxylated via the shiff's base of cyclohexeneones not cyclohexanones! as the intermediatdiate is a condjugated diene of some sort as illustrated in Rhodium's and Wikipeadia, theronine is decarboxylated to amino-propanoic acid, theronine is a beta-hydroxy-aminoacid as illustrated in Rhodium's mirror. so you can see the utility in this towards serines and the betamethylserines, the aldol codenseation could be some what sterically hindered but this is a toss up because this is only the case in diaklyl substitued (alpha-acidic carbons) as you see in typical aldol condensations in this case the alpha carbon on which the dissassociable hydrogen is located is adjacent to both an imine and a carboxylic group ( the only way steric hindrence can interfere in this case is by ;limiting the abstractability of this proton which isn't likely to occur sandwhiched between two electron withdrawing moities)

New Years Possibilities

roamingnome - 1-1-2007 at 00:36

1) Tetrahedron Letters
Volume 44, Issue 12 , 17 March 2003, Pages 2565-2568

ScienceDirect - Tetrahedron Letters : Rapid cyclopeptide analysis by microwave enhanced Akabori reaction

As a bonus discussed in that issue, novel indole compounds discovered in corals. As if global warming wasn’t killing them fast enough


2) Highly diastereoselictive synthesis of 1,2-oxazolidines under thermodynamic control using focused microwave irradiation under solvent-free conditions
http://rsc.org/delivery/_ArticleLinking/DisplayArticleForFre...




3) Endocannabinoid Metabolomics: A Novel Liquid Chromatography–Mass Spectrometry Reagent for Fatty Acid Analysis
Abstract
We have synthesized 4,4-dimethoxyoxazoline derivatives of several fatty acids associated with the endocannabinoid metabolome using tris(hydroxymethyl)aminomethane in a 1-step reaction by microwave irradiation. The derivatization incorporates a nitrogen into the final product, which allows for improved detection by liquid chromatography–mass spectrometry in positive atmospheric pressure chemical ionization (APCI) mode. Palmitic and oleic acid derivatives show a 200-fold increase in sensitivity compared with the free acids when analyzed in negative-mode APCI. In addition to improving sensitivity, the oxazoline derivatization creates a similar ionization response for the fatty acids tested, which simplifies their quantitation. Fatty acid oxazoline derivatives can be detected using the same conditions optimized for the endocannabinoids, which allows for a simultaneous quantitation of the entire endocannabinoid metabolome.
Keywords: fatty acids, LC-MS, metabolome, oxazoline derivatives, microwave synthesis

4) Process for microwave chocolate flavor formulation, product produced thereby and uses thereof in augmenting or enhancing the flavor of foodstuffs, beverages and chewing gums
Document Type and Number: United States Patent 5041296 Link to this Page: http://www.freepatentsonline.com/5041296.html
Abstract: Described is a process for carrying out microwave production of a chocolate flavoring product, the product produced thereby and foodstuffs, beverages and chewing gums containing said product. The process comprises the steps of: (a) providing a composition of matter consisting essentially of precursors of a chocolate flavor (e.g., sugar, leucine and phenyl alanine) and a solvent capable of raising the dielectric constant of the reaction mass to be heated; (b) exposing the mixture of reaction precursors to microwave radiation for a period of time so that the resulting product is caused to have a chocolate flavor; (c) providing a foodstuff, chewing gum or beverage base; (d) admixing the chocolate flavor reaction product of (b) with the foodstuff, beverage or chewing gum base.



#4 touches on benzaldehyde a bit as well so I felt they all relate to amino alcohols and the Akabori reaction, and since a second look at this post mixed with mania in regards to microwave enhanced chemistry got me thinking about it.
Lets put it this way if I had benzaldehyde on me I would have mixed it with alanine in the microwave already….
Happy news years where ever you are….

roamingnome - 1-1-2007 at 17:54

acquired artifical flavor( benzaldehyde) in ethanol and water

dewatered 2X 65ml portions in dry MgSO4

poured this into a excess of l-alanine in silca gel

irradiated first portion. Some liquid boiling assumed to be ethanol.

going in cherry smell coming out no smell.

irradiated second portion to same affect.

assuming that nothing can be that simple desire at least an IR to analyze whats in there.

Fractal number of possible experiments now. Acidic or basic conditions. Alumina support or solvent, maybye its a two step reaction ..... ahhhhhhh

unfortunately im bogged down in the synthesis of Bz, its smells too good to be a "bad guy", why is an aromatic ring bad.

carbon atoms ... are bad.... do you have a licence and permit for those carbon atoms?

jon - 2-1-2007 at 11:02

can you describe the colour changes did it go through the same changes to burgandy? also was there vigorous bubbling? any other observations?

Hilski - 2-1-2007 at 17:36

The diastereoselectivity (is that even a word?) of this reaction is very appealing, as is the notion that when equimolar amounts of reagents are used, little or no post reaction workup is required. Whether or not all of these findings are applicable to reactions with amino acids as opposed to amino alcohols is yet to be determined I guess.
I will try this once I get some alanine.

[Edited on 3-1-2007 by Hilski]

roamingnome - 3-1-2007 at 07:57

As per your sound advice jon,

I used a thermometer to ensure the temperature of the the sandy mix acheived 160 degrees centigrade.

Very sharply at that temp a mildly choking cloud of white smoke began pouring out of the microwave
The white mass had turned yellow

Due to the uneven heating of the poorly crafted test some areas where very yellow to a brownish color in one area.

Since alanine can form crystals its to soon to say that i did see a shimmery crystal look to the silca gel that was not appearent with just the powered alanine silica mix before the test.

Finally i hope to use pure IPA to flush out the formed whatevers hopfully leaving behind most of the alanine for the next run.

Hilski - 3-1-2007 at 10:55

Quote:
poured this into a excess of l-alanine in silica gel

Just out of curiosity, why are you using silica gel? I see no need for it in this particular case, since there shouldn't be enough water in the reaction to make a difference. Or are you using it because of the alcohol still present from the almond flavoring you used?

become the molecule

roamingnome - 3-1-2007 at 11:54

jon mentioned this as well...

since it realases its water at the temps in question

doesnt it have catalytic properties, lewis acid zones?

i dont know, formulation chemistry is fun but challenging becuase 1 drop of an opposing solvent can change the whole system.

im referring to the phtocatalytic (400nm) oxidation of styrene in water. the reaserchers found small amounts of other solvents disruputed the said mechanism. intersting way to benzaldehye...


anyway please put your thinking caps on and help figure this out. Nicoderms pictures help for sure. It may not deleiver the yields in the end, but with the number of possible variables i bet something can work here.....

i mean the skys the limit..... ethylene glycol, xylene, driped in benzaldehyde, or excess benz.... summoning all synthetic method chemists

jon - 3-1-2007 at 12:46

I dont' think a lewis acid will serve you, in this case the reaction depends on proton abstraction which uses a base, the base is formed insitu that being the imine, but another abstract mentions the use of pyridine.
try using the extraction method cycloknight used with toulene, I'm not sure but i think alanine is soluble in alcohols.
extract everything into a non-polar like xylene or toulene, filter, and extract this into an acid. then work this up like cycloknight described.
and as for the use of an alcohol solvent in an aldol condensation the alcohol will add to the aldehyde to give an acetal, this will block the aldehyde's reactivity.
And if you study cycloknight's result's he says using excess alanine gave a lot of benzylamine i think having a molar deficiency of aldehyde and having a lot of water kicking around led to this result, but then also he dripped in the aldehyde too.
I like the idea of using a basic heterogeneous catalyst as both a support and a catalyst, some other microwave reactions use different clays like montmorillite and such as supports in lieu of a solvent, alumina is a basic support.

roamingnome - 3-1-2007 at 14:08

nice.... i will try alumina.

preventing tautomerism is a good idea no?

i saw that alanine is not soluble in ether or non polars

but how about ppa feebase solubitly in ether.... me no find on the net...just FDA recall infomarion....

"review aldol chemistry gnome becuase blabbering"

[Edited on 4-1-2007 by roamingnome]

jon - 3-1-2007 at 14:37

Rhodium's website will give you a lot of data on PPA.
Tautomerism is going to happen in this reaction the only way you're not going to get tautomerism is if you use n-methylalanine which will give an enamine and the double bond will be fixed.
yes PPA is soluble in ether, I would'nt waste good ether on it's extraction.
Identification of 2-amino-1-phenyl-1-propanol
dl-Norephedrine dl-Norisoephedrine
Freebase mp 104-105°C mp 71°C
Hydrochloride mp 192°C mp 169°C
The product was a very viscous, colorless liquid which solidified on standing, mp 46-50°C. When dry hydrogen chloride was passed into an ether solution, a gelatinous precipitate resulted, which hardened on standing. This character of precipitate was attributed to the rather complex mixture of isomers, since an authentic sample of l-ephedrine yielded well formed crystals. A better product could be made from the base by treating it with concentrated hydrochloric acid to the end point of methyl red indicator, evaporating under reduced pressure, and recrystallizing from butanol-ether (50:50 v/v). The white crystals (mp 134-137°C) gave 18.87 and 18.89% chlorine by Fajan's method (theory 18.91%). The neutral equivalent of the free amine was 155 (theory 151). The material is therefore believed to be a mixture of dl-norephedrine and dl-norisoephedrine. These two compounds are diastereoisomers and the physical constants can be read in the table.

After four fractional crystallizations from absolute alcohol it was possible to obtain a hydrochloride mp 192°C. The melting point of a mixture of this compound and norephedrine hydrochloride was 192°C. Thus, it is possible to separate the components of the mixture by fractional crystallization but the yield is low. The method of Nagai and Kanao, which utilizes the greater solubility in ether of norisoephedrine to separate the isomers, was tried on the free base. After four crystallizations, the amino alcohol melted at 72-75°C. Since the original base mixture melted at 46-50°C, the difference in solubility is evidently not great.

The mixture of stereoisomers obtained in this synthesis was tested for physiological action by two manufacturers of pharmaceuticals who compared it with norephedrine hydrochloride and found it to have a similar effect on the blood pressure. The work of Jarowski and Hartung already has been mentioned.


just extract it into xylene, or toulene and work this up, as you see here you can use the ether as a recrystalization solvent.

about using alumina as a support does'nt this react with COOH to give a salt?
If it does this too would defeat the pupose of the reaction, as you might get a serine but it would not decarboxylate.
Something to look into I'd investigate a support that is either inert, or is basic but does'nt tie up the COOH end of the molecule.


[Edited on 3-1-2007 by jon]

Stop the press

roamingnome - 4-1-2007 at 13:00

check out this little wipper snapper


http://www.organic-chemistry.org/frames.htm?http://72.14.253...



http://www.scs.uiuc.edu/chem/gradprogram/chem435/fall05/Hoyt...


oh wait... im a morron.. ill admit it this time.. but i will post it anyway as a lesson in my own manic retardation.

can we squeeze this together a bit, little nip tuck?

Ephoton - 5-1-2007 at 05:08

I have an idea guys. its the temp that does it. under 160 its all benzyl but at the right temp it works. well the microwave doesnt go long enough and most of the reaction is done by 2 min. so heat the mix before putting it in the microwave. pritty obvious realy.

Ephoton - 5-1-2007 at 05:12

about that acetyl do you realy think ethanol will do this. I dont its in the patent as being a solvent for aldehydes in the reaction. possible if you did the origonal chocalate reaction with it pre heated it would get higher yeilds as well. another question does benzaldehyde azeotrope with ethanol as this would be a problem at these tempretures

roamingnome - 5-1-2007 at 10:07

Ephoton: i think your elduing to activation energy

the amine of alanine adding to the aldehyde should happen more easily, but the decarboxyation might require that extra energy.

******

Dry gasing of the solvent afforded a modest amount of white/cream colored globuls
The ratio of solvent to actaull product was too much though.

At the time it was rather dissapointing with the feeling that a lava lamp would have produced the same enjoyment, but reading that "When dry hydrogen chloride was passed into an ether solution, a gelatinous precipitate resulted, which hardened on standing" this is pretty much that.

Unfortunitaly the mechanism of this reaction is complex in that by products are going to form. There might be a reaction pathway to discover here, but i think l-pac is still me first love.....

jon - 9-1-2007 at 20:49

in the workup you did'nt give much detail as to how you worked it up and what you recovered.
if you simply gassed the extract from the reaction without partitioning it with dilute HCl it's concievable that what you have is a salt of the shiff's base of the end product.
As to acetal formation I stand corrected aldol condensations catylized by a strong base have used solvent systems like ethanol/water, a strong acid or base will split up an acetal (ketal or hemiketal) I don't know about this scenario though a strong base is'nt employed in the reaction, but it's worth a try (maybee a high boiling alcohol like ethylene glycol, propylene glycol, or even glycerin would work)
there are three amines that you will isolate from the reaction mixture (benzylamine, 1,2-diphenyl-2-amino-1-ethanol, and norephedrine) the former two are insoluble in water but norephedrine is soluble about 5 grams/100ml in water as a freebase.
this would allow for a novel extraction technique to be employed, the aqueous containing the norephedrine can be titurated and reduced in volume and worked up a number of ways.


Procedure Dispense 200 µL (210 mg, 2.0 mmol) of benzaldehyde directly into a clean, dry test tube (13 x 100 mm), and then add 1 mL 95% ethanol and a magnetic spin vane. Clamp the test tube to a ring stand, centered above a hot plate/stirrer and start stirring (the hot plate will not be used for heating!). Add 75 µL (59 mg, 1.0 mmol) acetone, 1 mL 3 M NaOH and stopper the test tube. Stir the reaction mixture at RT (∼20°C) for 30 minutes. Note the appearance of product as a yellow precipitate. Vacuum filter this precipitate and wash it thoroughly with 3 x 1 mL of cold water. Determine the weight and melting point of the crude sample, and then recrystallize it from ethyl acetate. Once your sample has air-dried (allow 15 minutes after recrystallization) obtain the weight and melting point of purified product and calculate the percent yield. Take an IR spectrum ofthe recrystallized sample.

product: 1,5-diphenyl-1,4-pentadien-3-one
[Edited on 10-1-2007 by jon]

[Edited on 10-1-2007 by jon]

roamingnome - 15-1-2007 at 21:21

http://www.chem.utoronto.ca/coursenotes/chm443/paper1.pdf


this article pretty much eludes that alanine forms the schiff base with aldehyde at room temperature in DMSO ..

the adding of the second benzaldehyde is where i begin having more questions about how it forms and how stable it is etc.
It seems like its the "committed"step of the reaction mechanism.

in the final step of the reaction a H2O molecule must add to break off the benzaldehyde and leave the desired amino alcohol


if tautomerism occurred is this bond flip dynamic back and forth, or since its a more substituted double bond and thus more thermodynamically favorable does it get locked.

my hope is that DMSO can form this "committed" step intermediate at near room temperature thus drastically preventing undesirable tautomerism.

i do know that isomerizing the terminal double bond of some olefins to the more substituted iso form takes considerable heat and catalysts

jon - 16-1-2007 at 18:07

no thermodynamicaly favorable just means it's a reversible equilibrium.
DMSO or any polar compound is going to raise the dielectric constant of the reactants, try it and report back it's all guesswork until you get empirical information, ie. try it.
maybe do some research using keywords "sovation effect" (the effect a solvent has on a reaction system) with respect to aldol type reactions.
that abstract stated in German to warm with ethanol maybe a high b.p. alcohol would do it? who knows.

oh snap

roamingnome - 30-1-2007 at 16:04

First of all im not posting these links just to be cool and think that im saving the whales with my link posting. Instead mechanistic insights are manifested. Precious yields need to be increased.


http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1954/76/i05/...

the classic I read to late… no one had even reported a failure of this with alanine? Yes it is sterically hindered, but the clue here is alkaline. Equal molar amount added based on added aldehyde


http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleFo...

gotta love the perkin people, thanks perkins people

again alkaline to …decarboxylate… ahhhhh


http://www.turpion.org/php/paper.phtml?journal_id=rc&pap...

who can tap into the Russian reviews, they seem like a wealth of info. If I had 2000 dollars for the membership Id hook it up, but alas…..

gleaning from google cash alone we see a 3 time molar excess of alkali to decarboxlate….

Salt is also known to aid decarboxylation as well. The lower the temp the better right


Then back to the glycine paper, the people add acid to hydrolyze the imine and recover half of the aldehyde.

Mechanistic gurus feel free to lash out at me… the worst I can do is try to bite off your kneecaps

1) 1 mole aldehyde added to one mole alanine in DMSO ( I did observe that alanine in DMSO when added benzaldehyde precipitated a fluffy gummy like solid that did not look like alanine. Since the previous post paper says it forms an imine readily I feel that step can occur quite nicely.

2) 1 mole KOH with 1 mole aldehyde in approx. 5 volumes alcohol is added.

( edited: because a carboanion not cation is the nucleophile which adds to the electrophillic aldehyde group to form a carbon-carbon bond)

3) salt or a bit more base can be added to facilitate decarboxylation. The alcohol may be evaporated as well. Monitoring CO2 release would be ideal. low temp is probably key

4) Finally it is made acidic which recovers aldehyde.

[Edited on 1-2-2007 by roamingnome]

[Edited on 1-2-2007 by roamingnome]

Reference Information

solo - 31-1-2007 at 03:12

Bipyrroles, furyl- and thienylpyrroles
S E Korostova (deceased), A I Mikhaleva, B A Trofimov
Russian Chemical Reviews 68 (6) 459 ± 482 (1999)

Contents
Introduction 459
II. Methods of synthesis 459
III. Reactivity 471
IV. Prospects for the use 479
V. Conclusion 479



Abstract
Data on the methods of preparation of bipyrroles and
furyl-, thienyl- and selenienylpyrroles are summarised and described
systematically. The reactivity and the prospects of application of
these compounds are discussed. Particular attention is paid to a new
convenient one-step method for the synthesis of hetaryl-substituted
pyrroles starting from alkyl hetaryl ketoximes and acetylene. The
bibliography includes 191 references.

Attachment: Bipyrroles, furyl- and thienylpyrroles.pdf (450kB)
This file has been downloaded 1732 times

carboanions

roamingnome - 1-2-2007 at 12:01

http://www.siue.edu/~tpatric/cban.pdf

dont be dumb like me, read about carboanions

favorite quote from, "imines are used because there is no competition for adol reactions"

time to brakeout those molecular models...

roamingnome - 3-2-2007 at 15:14

J. CHEM. SOC. PERKIN TRANS. 11 1986
“New Model for the Addition of Carbanions to Carbonyl Derivatives in the Absence of Chelation Control”

Our results suggest that the a-silyl carbanion behaves as a free carbanion, or more likely as a very loose ion-pair.. Phenylmethanide anions with bulky a-alkyl groups behave as loose ion-pairs. The phenyl(sily1)methanide anion, by analogy, would be expected to be loose-ion-paired, or approaching the free ions, as there is greater charge delocalisation in this ion, and HMPA is a powerful ionising solvent. Therefore, in our system, a relative insensitivity to counterion, M+, is not unexpected. It is also clear from the insensitivity to RO- in the carbanion- forming step that the a-silyl carbanion is essentially completely formed before addition to the carbonyl group takes place.

The Wittig reaction, in which the first step is reversible, is highly susceptible to salt effects. Wittig reactions are similarly highly solvent-dependent, being particularly sensitive to protic solvent. In the case of the Peterson reaction, protic solvents cannot be used, as they rapidly quench the a-silyl carbanion

frustrated by poor solubility and usually low yields of stilbenes, and are considered unreliable. Some other solvent systems are shown in Table 6
Dimethylsulphoxide coming in at 99%

The model that we are about to describe is most applicable to the initial stages of an addition where the approach angle is at least 109" and the deviation from planarity in the carbonyl compound is minimal. As the transition state becomes inter- mediate-like then the relative energies of possible intermediates assume a greater importance. Previous models for the addition of non-enolate carbanions to carbonyl compounds have concentrated on the anion attacking at 90" to the carbonyl framework. This approach leads directly to a comparison of the stabilities of diastereo- isomeric intermediates. The major problem with that model is that it completely fails to account for the so-called 'erythro- selectivity' of carbanion additions. The seminal work of Burgi and Dunitz l9 and Baldwin has forced a reappraisal of any model for nucleophilic attack at carbonyl groups. It has been shown convincingly that nucleophiles attack the carbonyl group approximately in the plane of the C-0 n-bond and with a Nu-C-0 angle of about 109". It is therefore misleading simply to analyse conformations of intermediates. The initial steric interactions should be analysed, as shown in Figure 1. We postulate that one interaction will be more important than the other two,

the first, major, steric influence will result from interaction amongst R', R, and H. This primary steric influence is a direct consequence of the carbanion attacking at an angle greater than 90". The most favoured orientation for attack will be that in which the primary steric influence is minimised. The steric outcome of the reaction is then determined by the relative extents of the secondary steric influences; the interaction of R2 and R3 with R. If we apply this to the reaction between PhCHSiMe, and PhCHO, two transition states can be drawn, one leading to cis- stilbene and the other to trans-stilbene, as shown in Scheme I. The primary steric influence is minimised by placing the anion hydrogen atom in the most hindered position, between the aldehyde phenyl group and hydrogen. The major secondary steric interactions are between (a) the benzaldehyde phenyl
--------------------------------------------------------------------------------
Bulky anions, such as PhCHC(CH,),, induced Cannizarro reactions with aldehydes (further evidence that the steric demands of the SiMe, group are not unduly large), and, with all anions, enolisable ketones underwent aldol condensations preferentially.

In summary, a general rule may be enunciated. Consider the irreversible addition of a carbanion &ML to a carbonyl compound S'L'C=O, where S, M, and L represent small, medium, and large groups, respectively. The stereochemical outcome of the reaction is determined by two steric influences, in the absence of chelation control. As a consequence of attack by the carbanion at 109" to the carbonyl compound the primary influence is such that the smallest carbanion ligand, S, is disposed between L' and S'. The most favoured disposition of the remaining ligands is with M and L1 and L and S'gauche.
Page 5



www.iupac.org/publications/pac/1979/pdf/5101x0139.pdf
until the red color of the carbanion had disappeared…..

http://www.arkat-usa.org/home.aspx?VIEW=MANUSCRIPT&MSID=...

Formation of carbanion on addition of a strong base to the THF solution of 2 can be followed by the appearance of an intense orange-red color

http://www3.interscience.wiley.com/cgi-bin/abstract/10403982...
since the original red color of the carbanion….

Polymer Volume 46, Issue 18 , 23 August 2005, Pages 6910-6922
The red color of the polymeric solution was attributed to a carbanion

For a more exhaustive paper
The Role of Carbonium Ions in Color Reception
http://www.jgp.org/cgi/reprint/48/5/753.pdf


I thought at the time this color was from like benzylamine or some other double bond system, but it was a truely magnificent red solution. I wonder…
This akabori reaction seems has every thing going for it here… hydroxide probably wont be best as base though…

jon - 9-2-2007 at 20:59

I'm a little confused you said you did a run in DMSO and got mostly benzylamine.
In another paper (chem beritche) I don't understand german fluently but they use a similar system (solvent with a high dielectric constant and aprotic) nitrobenzol zie germans called it and got guess what, benzylamine.
It's on rhodium's mirror I stumbled upon it at the university today too.
these other systems use ethers like thf with the lone pairs exposed due to steric factors to stabilize the carbanion ethers may be it high boiling ethers like glycol ethers and what not they are aprotic don't have very high dielectric constants but the lone pairs on the oxygen contribute to carbanion stabilization which is what we want in this reaction, If what you said about the DMSO route being a really good synth for benzylamine it appears solvents with high dielectric constants promote hydrolysis of the intermediate (as in the case of nitrobenzene solvent systems alluded to in the chem. beritche paper) did you do any quantitative analysis of the products?

roamingnome - 10-2-2007 at 11:47

ill try to be a breif as possible here

first, the comment about the benzylamine was a joke becuase who really wants that stuff.. hahha not funny

second i took just today some of the post reaction mixture thats has been sitting in a box

pH 9.63
UV/VIS absorbances at critical wavelengths
325nm- 4.23
335nm- 4.3
415nm 2.1
290nm 3.2

Benzylamine check at 260 nm only .77

so i might have some shiff base knocking around in equlibrium with some other forms....

i didnt though fully grasp carbanion addition so i went to decarboxylate prematurly and am considering the above tests as "observational recon missions" I am physically loosing sleep not having pure almond esseance to continue these expirments.

altering my research queries to Pyridoxal 5-Phosphate
i have found a wealth of quality information about this topic almost precisly! and am massing it in my little "octopus garden" of a thread under vitaminB6
its just a matter of time now
------------------------------------------------------------------

AKABORI fans and biotransformation fans
should love the up and coming possibility of the protien

8-amino-7oxopelargonate synthase

it binds alanine, forms a carbanion, adds a carbon-carbon bond, and it even decarboxylates it for you!! now thats a biotransformation.....
scientists are spawning it up right now in E-Coli

jon - 10-2-2007 at 16:53

when CO2 comes off then you have the carbanion i have the japanesse papers with the diagrams of the mechanism the shiff's base forms, then some electron juggling CO2 comes off and the carbanion is formed. i'll have to shoot you those papers you'll see, those chincks are smart.

comfort_develops - 13-4-2007 at 13:29

Somebody tried this reaction 2 times and really likes it.

But some questions:

Is it possible to do this reaction with Valine, instead of Alanine? Would the product be of intresst (if possible)?

Arent there any possible reactions with other aldehydes/amino Acids?

the north west passage

roamingnome - 14-4-2007 at 09:01

Well did you use some type of base to facilitate the adding of the aldehyde to C-H acid of alanine? Or is 20% yield your idea of a good time.

Valine’s C-H acid might form the anion easier, but its bulkier. The bioactivity is left for you to test

While simply doing the whole synth with benzaldehyde will probably be the best, since you can possiblity recover half of it back.
Functional group surfaces are becoming more common.
The google patent
American Chemical Society, Mar. 3, 1998, vol. 31, No. 22, p. 7618-7626.
Example 1

I searched around for threads that use Acrolein to learn that simply decomposing glycerin will form this noxious gas. Despite that, depositing this on a large glass surface with aldehyde groups sticking up might become surprisingly simple.

http://www.diss.fu-berlin.de/2005/271/Chapter2.pdf
or maybye not


Then alanine is poured on the surface to create Schiff base linkages.
Dehydrate
Then base, probably NaMethoxide creates a carbanion
Then benzaldehyde adds, possibly with stereo selectivity
The surface is then treating with dilute acid to severe the Schiff base linkages
The surface hopfully can be used a number of times.
We can decarboxylate later after reality catches up.

[Edited on 14-4-2007 by roamingnome]

jon - 14-4-2007 at 16:54

man you really go out to left field on this, did you ever do a tlc chromatogram of your dmso expiriment?

[Edited on 15-4-2007 by jon]

gambler - 17-4-2007 at 19:30

Look i have read the whole thread and still have a few questions (maybe foolish) that is irrelevant.

Firstly,

How is the DIY deakin stark trap created. Please point me in the direction of appropriate refrences if you wish.

Secondly, this procedure seems simple enough, is there any other notes that people who have performed this can give me....

Thirdly, I would greatly like some refrences in regards to the Akabori reaction.. However, there is an appropriate forum for this.

Thanks in advance]

gambler - 17-4-2007 at 20:26

Finally,

With benzaldehyde ever difficult to acquire, for the amateur is it best to

- Order bitter almond oil from ebay
- Cinammon conversion
- Toulene oxidisation
- Do what roamingone suggested and just buy essence..

However, am still confused by what roamingone wrote as to if he ever arrived at P2P or not..

Thanks

roamingnome - 18-4-2007 at 09:16

jon: the ball was hit deep into left field its going going.. bounces fowl off the pole…

it mainly is just theoretical banter, but double bonds can bind to silicon and forming an aldehyde surface would surly be cool, if it could be done with ease…
http://hamers.chem.wisc.edu/papers/pdf/hamers_jjap.pdf

this link which wasn’t working this morning explains it real nice. also sorry but "real life" has prevented all real chemistry for now, drat....

Gambler:
I hope no one minds me saying that as far as benzylaldehyde, hilski and predecessors have shown that oxidation of toluene is a most viable option. Soon juice will be run into a cell, OTC stuff is well a gamble…
Further more, in this thread I can not tell I lie, I have interest in the amino alcohol for certain cyclic urea studies…. But I have ZERO if 2% interest in p2p for any reason…. Using styrene is interesting for some reason, but not in this thread dude…

Astrum, fromthe hive supposly used a base in this reaction, but the sucker ran off to university before posting results...

gambler - 23-4-2007 at 20:30

So how is a DIY deakin-stark trap constructed?

And is this necessary for reaction to complete?

tupence_hapeny - 24-4-2007 at 00:42

look at the reaction procedures for producing phenylserine, the structure of which is here:

http://www.anaspec.com/products/product.asp?id=26317

(Disregard the fmoc/boc protecting group).

This is essentially what you want to make, is it not? Albeit with a methyl group where the carbonyl group is at the end?

Anyhow, phenylserine is produced by reacting glycine with benzaldehyde, in the presence of NaOH - which is essentially the same mechanism as that which you are asking about - the condensation of an aromatic aldehyde with an amino acid (aka the Akabori reaction)?

As fuck all information exists (in English at least) as regards the reaction between alanine and benzaldehyde, the reaction of a simple amino acid with benzaldehyde may offer some insight.

http://pubs.acs.org/cgi-bin/abstract.cgi/joceah/1973/38/i17/...

http://studentsupport.syr.edu/upload/Tracey-Ann%20Samuels%20...

I am not certain that this reaction is able to be directly translated to the reaction between alanine and benzaldehyde, however and given the structural similarity, it might very well work.;)

tup

[Edited on 24-4-2007 by tupence_hapeny]

Attachment: Process for the Production of B-Phenylserine (US Patent 4605759-1).pdf (321kB)
This file has been downloaded 1136 times

its just alanine

roamingnome - 24-4-2007 at 09:42

Enantioselective alkylation of alanine-derived imines using quaternary ammonium catalysts
Lygo, Barry; Crosby, John; Peterson, Justine, A.
Tetrahedron Letters 40(49): 8671-8674, 1999
Abstract
Application of N-anthracenylmethyl dihydrocinchonidinium bromide as a catalyst for the enantioselective alkylation of a series of alanine-derived imines is reported. Using solid K2CO3/KOH as the stochiometric base such alkylations can be achieved with enantiomeric excesses up to 87% allowing rapid access to alpha,alpha-dialkyl-alpha-amino acid esters.


i just read all the references ive been collecting because it was all i could do at the time....
the fancy catalyst probably isnt required or could be replaced with something simple like tryptophan aminoacid.

at this point though, were just running in circles its time to get the beakers wet....

removing water from this reaction to drive it to completion etc, might be acheived with things like MgSO4

jon - 24-4-2007 at 13:37

does'nt bitter almond oil contain triglycerides as well, meaning you would have to purify it to get uselful benzaldehyde.
regarding the foreign articles the chem beritche article on reaction of amino acids with bennzaldehde here:

http://www.erowid.org/archive/rhodium/pdf/akabori-1957.pdf

can be translated with OCR software Claro scan2text I found is useful for converting to text form which can then be pasted into babelfish to translate but the trial versions only let you do one page so my strategy is to download adobe distiller from limewire of some such p2p software sharing program, and convert the pdf into seperate single page PDF's and the translate each page one at a time.

tupence_hapeny - 15-5-2007 at 04:44

Jon,

If I can post the sucker it will be here in separate pages very soon.

tup

jon - 17-5-2007 at 14:05

yes it's got a lot of useful information in it, you can go to downloads.com (c-net) and get claro "scan2text"

jimmyboy - 3-12-2007 at 20:37

I was searching high and low for n-methylalanine references but nothing -- I did find this one patent - but not too sure this is the correct compound needed

http://www.freepatentsonline.com/5587506.html

more info on it would be welcomed or even a better route...

I also found this -- much easier route

http://www.sciencemadness.org/talk/viewthread.php?action=att...

[Edited on 4-12-2007 by jimmyboy]

solo - 4-12-2007 at 08:37

Refrence Information



Catalytic Decarboxylation of alpha-Amino-Acids
KLAUS DOSE
Nature vol.179, 734 - 735, 1957

.
Abstract
NON-enzymatic decarboxylation of alpha-amino-acids was tried many years ago by heating them above 200° C., often dissolved or dispersed in an inert solvent too. As the reactions are always exotherm, heating is only required to reach the rather high energies of activation. The way in which Nature lowers these energies by enzymatic reactions has been frequently discussed. The formation of a Schiff's base between an alpha-amino-acid and pyridoxal-phosphate as the proved prosthetic group of most of the decarboxylases is postulated by many authors, and the easiness of their decarboxylation may be understood with the help of the electronic theory of valence.


----------------------------------------------------------------------------------

THE DECARBOXYLATION OF AMINO ACIDS, PROTEINS,
AND PEPTIDES BY N-BROMOSUCCINIMIDE
EMMETT W. CHAPPELLE AND J. MURRAY LUCK


http://www.4shared.com/file/31147254/a39727cc/THE_DECARBOXYL...



[Edited on 4-12-2007 by solo]

Attachment: Catalytic Decarboxylation of alpha-Amino-Acids.pdf (457kB)
This file has been downloaded 1196 times

jon - 13-12-2007 at 14:19

the reaction don't go that way first the benzaldehyde condenses on the alanine decarboxylation takes place and then another mole of benzaldehyde adds to the decarboylated carbanion look it up yourself it's those japanesse articles with diagrams.

roamingnome - 22-12-2007 at 07:54

there a clearly two mechanistic pathways

jon eludes to the one that decarboxlation happens leaving room for a simultaneous alkalation

alternitivly, you can form a carbanion by abstacting the H from the C-H acid with strong base. The russians suggest the KOH/DMSO system is strong enough

jon - 22-12-2007 at 18:20

nope it won't work you need 2-bromopropionic acid, that's in org. synthesis you can look it up online.
you can bromonate it just like you can brominate a ketone because of tautomerism. it is done in ether. you would get a diamine using what you proposed.
I've given the serine route a thought but after some research I concluded it may or may not be possble because of the steric factors involved with alanine the carbon bearing the alpha hydrogen is substituted in alanine in the case of glycine it is not.

[Edited on 23-12-2007 by jon]

manimal - 15-1-2008 at 17:44

How about decarboxylating the phenylserine derivative by heating in sulfuric acid to 200C, or would that destroy the amino alcohol?

Geko127 - 18-1-2008 at 00:26

Could this reaction be sucsesfully done without haveing proper glassware ?

And couldent boiling chips be used instead of having to use a Mag/hotplat stirrer ?, Thats how they did it way back before Hoplate/stirrer's come around !

And is a dean stark trap essiential for water removal ?, Or could something getto be created ?
:(

roamingnome - 18-1-2008 at 18:50

The more I come back to this thread the more CycloKnight is awesome.

For right now you may just want to keep saving money on your car insurance and save up for the dean stark trap :P

Or you can help solve my problems for me

Just ten minutes ago, literally, my hands are black with graphite…
I was performing small test tube reactions to conserve stock

Powdered alanine, benzlaldehyde bisulfite adduct, graphite, and Microwave chemistry.

Very interesting stuff. Sure I didn’t add decraboxylating solvent catalysts like
N-methylpyrrolidone. But after adding K2CO3 base with a small bit of water to make a poultice, the post reaction methanol extraction has some translucent brown organics it it. Whereas without the base the methanol extraction was disappointingly clear. A few days ago without the graphite its even less good and smells like an old fart….

the point is im having fun and theres alot of ground to cover
Seriously Geko do you even have 50mls of benzlaldehyde to waste with a getto dean stark trap.






In other news ive found 4 anhydrous methods for deprotecting a bisulfite adduct. Only two are handy but notice the iron in both methods here.


http://www.ics-ir.org/jics/vol3/n1/articles/jicsv3n1r9.pdf
Deprotection Method of Aryl Aldehyde Bisulfite Adducts with Recoverable
[BPy]FeCl4 as a New Ionic Liquid Catalyst

http://www.ingentaconnect.com/content/ben/loc/2006/00000003/...
Selective Deprotection of Bisulfite Addition Products by FeCl3•6H2O and Fe(NO3)3•9H2O Supported on Silica Gel Under Solvent-Free Conditions

Geko127 - 27-1-2008 at 17:37

That still dident answer gekos question .

Couldent boiling chips Or a fishtank bubbler be used instead of a hot plate stirrer.:D

swip2 - 12-2-2008 at 05:46

And why cant the reaction sludge be based directly :(

Ephoton - 12-2-2008 at 05:57

tar.gz I belive.
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