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IndoleAmine
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Sat Mar 26, 2005 4:47 pm |
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As said already, I'm really a dumbass when it comes to stereochemistry sometimes, but my impression was too that d,l-ala would be the best choice - unless we know which stereomer of ala to use in the akabori to arrive at the "correct" isomer, to produce the more active 4-MAR isomer with the cyanate route (I am somewhat a bit afraid about using CNBr..  ).
So I will probably first racemize my ala into racemic mixture once I get hold of some, then we know at least how to make racemic PPA (which is useful for sure).
Have a nice easter,
i_a |
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IndoleAmine
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Sat Mar 26, 2005 5:08 pm |
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assuming minimal isomerization of the alanine enantiomer being used in conjunction with the potassium cyanate route, one enantiomer of alanine will lead to the weakest of the four stereoisomers while the other will lead to the strongest.
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I think thats exactly what Bandil said a few posts earlier: either you'll get a mixture of the weakest and strongest diastereomers, or you will get a mixture of the almost equipotent two medium strong diastereomers.
In each case, you'll have a racemic mixture with approx. the same strength - but upon optical resolution with tartaric acid, one mixture would give crap and highly potent 4-MAR 50/50, while the other will give two almost equally potent stereomers 50/50.....
So maybe it would be the best to just not resolve any optical isomers at all, but rather enjoy it racemic "as is"....
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Astrum
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stereo chemistry
Sun Mar 27, 2005 5:49 am |
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It sounds ok to me,
And the chances are that if yo do use L-alanine anyway,
You will most likely end up with dl-Alanine in-situ , and then that will go to dl.PPA, even even that dl.PPA gets a few more d's than l's by again further isomerization,
So I would tend to think that L-alaine, is going to give DL-PPA, with probably a higer=her % of D-isomer,
If the akabori, is stated to yield only 15%, that is 15% of BzCHO used, not alanine,
Since alanine would be the liniting reacteant(cost wise)
then You would say that you get a 50% yield, based on Alanine used,
That is definately not so bad,
syn
( i can't help but think there is a way once we find, which isomers(s) of PPA are best, then we could probably easily get the isomerizing to that isomer without too much trouble, if need be at all) |
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indole
Sun Mar 27, 2005 3:24 pm |
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Even if you start with L-alanine, it will be changed to dl-alanine insitu,
Resulting in racemic PPA,
l-alanine will be fine,
posted at wd.
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Why has no one picked up the glaring error with regards to chirality of the alanine. In the reaction the aldehyde and amino acid condense to form an addition product before loosing CO2 to form PPA. This means that the chiral centre of the alanine has been inverted to give the opposite stereocentre. So to obtain the prized dextrorotary PPA we would need to use the freely available L-alanine.
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syn |
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IndoleAmine
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!!
Sun Mar 27, 2005 4:08 pm |
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I haven't understood yet where the saturated 1-5C LOWER fatty acid should come from if the ala is racemized in situ - the only reagents I see are benzaldehyde and an amino acid - and no "fatty acid" lower/shorter than alanine which is required....
did you mean in-situ formed benzoic (this is longer than 5 carbons)? Or do you think the evolving CO2 could accomplish what is necessary?
However, nice find - and the "priced dextrorotary PPA" is suitable for the potassium cyanate route I would assume, right? (Bandil, Astrum?)
Would be too kewl if the cheapest alternative would be the best here.... 
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CherrieBaby
chouchou
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Process for the production of serine derivatives, USP 450191
Sun Mar 27, 2005 5:36 pm |
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Process for the production of serine derivatives, USP 4501919.
Abstract: Serine derivatives are synthesized by the condensation of an alkali metal salt of a glycine derivative and a carbonyl compound in the presence of a phase transfer catalyst.
(1) Patent image. Go to:
http://l2.espacenet.com/espacenet/viewer?PN=US4501919&CY=ep&LG=en&DB=EPD
then click the link to "Requested Patent"
(2) Patent text. Go to:
http://patft.uspto.gov/netahtml/search-adv.htm
and enter "pn/4501919" as your query. Click Search.
PS: Phenylpropanolamine is a serine derivative. Alanine is a glycine derivative (see patent abstact). |
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Astrum
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405.92 Points
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Sun Mar 27, 2005 5:42 pm |
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Yeah, I caught what Rumplestiltskin said. He might be right but I'm not sure right now, I'll look at it later. I did do that late one night after a full day at university, so I might have made a dumb mistake like he said.
He didn't back up his post with any substantial information, sources, or work so I'm not sure if he just assumed the dextro enantiomer* will give you trans(4S,5S)-4-MAR or not**.
*Only one of the dextro enantiomers are suitable to be used with potassium cyanate. The other dextro enantiomer is cis and wouldn't give you 4-MAR at all. trans(1R,2R)-1-phenylpropan-1-ol-2-amine being d-norephedrine (debatable, but would agree with rhodium's, bandil's, and Rumplestiltskin's posts).
**This is assuming "..prized dextrorotary PPA.." insinuates the end product will be the most potent stereoisomer of 4-MAR. His post wasn't exactly clear on that. |
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CherrieBaby
chouchou
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Sun Mar 27, 2005 6:07 pm |
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| I would expect the end product to have a racemic mixture due to racemization during the reaction in a similar way to how reactants of the corresponding C-alkylation of amino acids are generally racemized, see: https://www.synthetikal.com/synthforum/viewtopic.php?t=584 They had to use chiral PTC catalysts to get chiral products out of that. So I don't think it matters whether you use D-, L- or DL- alanine. |
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IndoleAmine
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Sun Mar 27, 2005 6:56 pm |
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Something I have found over at WD: Fishinabottle clarifies on the chirality issue and answers the question quite good I think:
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Norephedrine is the isomer of PPA which can be converted into 4-MAR by potassium or sodium cyanate (not the toxic cyanide). PPA is +/- norephedrine and +/- norpseudoephedrine. Norpseudoephedrine requires cyanogen bromide - nasty stuff this is.
Norephedrine yields trans-4-MAR, the most potent isomer.
Norpseudoephedrine yields cis-4-MAR.
Oh, yes - cyanogen bromide also works on norephedrine, the cyanate works not on norpseudoephedrine though.
Confusion completed?
Ok. 
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..
i_a |
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IndoleAmine
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Sun Mar 27, 2005 8:40 pm |
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IOC
(Stranger)
12-07-01 04:28
No 245275
Akabori run Bookmark
crap, at best 15% using 100 g BnZ, 40g l-alanine.
Heat to 140 seems best, extracted into H2o and evaperate, then clean up.
would decarboxylation of a methylamino over the amino maybe improve results?
How about a base and high bp solvent with C5H5N??
as suggested in tfse.
could some one please explain the reaction mechanics for the reaction:
,on heating BzH and DL-alanine directly; PhCH2NH2, PhCH(OH)CHPhNH2 (2 dl-compds.), AcH, and CO2 are formed.
Is this a condensation (no H2o) or a decarboxylation?
what conditions would be pref?
any ed imput would be great, cheers
jim
(Hive Bee)
12-07-01 05:53
No 245287
Re: Akabori run Bookmark
Give references.
Personnally I don't know of this reaction, and am wondering why you would even attempt it? Get phenylalanine and decarboxylate instead...
Aurelius
(Hive Bee)
12-07-01 10:15
No 245346
Re: Akabori run Bookmark
complicated rxn mechanism for just words. you'd have to look up the actual article. (btw- your yeild will go up if you calculate according to the converted benzaldehyde, and recover the rest for a second go)
IOC
(Stranger)
12-08-01 01:33
No 245572
Re: Akabori run Bookmark
An otc way to PPA, what I,ve dug up so far
Synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes.
The alanine is reduced via -COOH => -CH2-OH
Reaction between aromatic aldehydes and a-amino acids. I. New facts on the Akabori reaction. Takagi, Eiichi. J. Pharm. Soc. Japan (1951), 71 648-51. Journal written in Unavailable.
Abstract
The Akabori reaction (I) (C.A. 41, 3774g) on BzH and dl-MeCH(NHMe)CO2H (II) with and without pyridine and removal of the unreacted BzH by steam distn. gave dl-ephedrine and dl-y-ephedrine. Similarly, direct heating of piperonal and II gave 2 dl-1-(3,4-methylenedioxyphenyl)-2-methylamino-1-propanols. A new reaction (III), differing from I, takes place on heating BzH and DL-alanine directly; PhCH2NH2, PhCH(OH)CHPhNH2 (2 dl-compds.), AcH, and CO2 are formed. It is considered that the I-type reaction occurs when the N of the amino acid is secondary and the III-type reaction when it is primary.
Fester5 sites that direct heating of 20g N-methyl-alanine
with 50g Bnz at 150deg untill fizzing stops, produces
12g of a mixture 3g ephedrine and 9g pseudoephedrine isomers.
Reactant BRN 471223 benzaldehyde
1720250 DL-alanine
Product BRN 3196917 (1RS,2RS)-2-amino-1-phenyl-propan-1-ol
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Reaction Details
Reaction Classification Preparation
Temperature 140 #65533;C
Other conditions Erwaermen des Reaktionsprodukts mit wss.-aethanol. HCl
Ref. 1 2262852; Journal; Takagi et al.; YKKZAJ; Yakugaku Zasshi; 73; 1953; 1086; Chem.Abstr.; 1954; 12021;
As promised, here are some more refs on the interesting condensation reaction between aromatic aldehydes and glycine/alanine:
BER 25: 3445 (1892) + 52 :1734 ('19)
ANN. 284: 36 + 307: 84
JCS 1943 ('26) + 2600 ('22)
JACS 76: 1322 ('54)
J.PHARM.SOC.JAP. 67: 218 ('47)
Most of the articles are pretty old to say the least but they contain some interesting stuff on the reaction we're interested in here. I'm especially interested in the J.Pharm.Soc.Jap article, which describes the preparation of a methylenedioxy-substituted phenylserine. But the practical way to go is definitely as mentioned in a certain patent, that is using a two-phase solvent system. This prevents the benzylidene phenylserine from crystallising and makes sure that the reaction mixture can be stirred at all times.
After decarboxylation, these phenylserine derivates turn into amino alcohols, the perfect substrates for aminoxazolines. By substituting the benzaldehyde, a lot of phenylserine and amino alcohol derivates can be made and thus a lotta aminoxazolines!
So with some 10x experiments with 20g alanine + 50g BnZ
a massive 15% return sux, any suggestions besides learn how to make nitroethane?
java
(Hive Bee)
12-04-02 08:24
No 386214
Re: akabori: Bookmark
Did I read this correctly then one can then make ephedrine using this method.......well have you tried it and what are the conditions since I can't find the article ,,,anyone?
Akabori
Also known as Akabori-Momotani
Synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes.
[image]
Bibliography
Akabori S., Momotani K., J. Chem. Soc. Japan, 1943, 64, 608; C. A., 1947, 41, 3774
Dose K., Ber., 1957, 90, 1251.
Belikov V. M., Izv. AN SSSR. OHN, 1969, 2536.
This I was able to locate.
Rhodium
(Chief Bee)
12-04-02 08:53
No 386225
Akabori Bookmark
Yes, it's correect that you can make ephedrine very simply with the Akabori reaction between Benzaldehyde and N-methylalanine. Ordinary alanine would give phenylpropanolamine.
The only one of the above articles I could locate was J. Am. Chem. Soc. 76, 1322 (1954) (https://www.rhodium.ws/pdf/akabori.phcho.glycine.pdf).
I doubt that the original reference has been retrieved as it is written in Japanese, and "IOC" is not likely to answer you either, as he hasn't been logged in since June.
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dormouse
(Member)
04-22-00 02:13
No 108531
phenylpropanolamine from benzaldehyde and alanine -drone 342 Bookmark
the Hive BB
Novel Discourse
phenylpropanolamine from benzaldehyde and alanine
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Author Topic: phenylpropanolamine from benzaldehyde and alanine
drone 342
Member posted 10-15-98 09:18 AM
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Reactant BRN 471223 benzaldehyde
1720250 DL-alanine
Product BRN 3196917 (1RS,2RS)-2-amino-1-phenyl-propan-1-ol
-------------------------
Reaction Details
Reaction Classification Preparation
Temperature 140 #65533;C
Other conditions Erwaermen des Reaktionsprodukts mit wss.-aethanol. HCl
Ref. 1 2262852; Journal; Takagi et al.; YKKZAJ; Yakugaku Zasshi; 73; 1953; 1086; Chem.Abstr.; 1954; 12021;
This informative post was brought to you by drone(tm) #342, who reminds you: euphoria -- its what's for dinner.
-drone #342
Rhenium
Member posted 10-15-98 10:20 AM
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Drone,
I have a similar paper here, it's in Japanese and was published around 1942. I can't read it, but the pictures suggest that they reflux the two and get the PPA and CO2 produced. They have a little picture of piperonal as well, but I can't figure out what they're trying to do with it.
Take care,
Rhenium
beagle boy
unregistered posted 10-15-98 10:50 AM
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Shwing! I like what I hear. But I only hear the basic outline. Can anyone (please) fill in the details. Like what solvent? How long a reaction time? Japanese writing looks cool, but thats about all I get out of it.
Labrat
Member posted 10-15-98 10:51 AM
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This is great and shit at the same time, great because it's one beautiful method of making PPA from simple reagents, shit because the article is in Japanese!
There are professional translators on the Net. How about paying one to translate the experimental section of the two Yakugaku Zasshi articles we have? If we share the costs, it won't be that expensive. Lr/
drone 342
Member posted 10-15-98 03:38 PM
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I have a friend who's a Japanese native. The problem is she knows nothing of chemistry. I sat down with her, and we went through the Yakugaku Zasshi article from a while back, but they really didn't say anything too intersting that I hadn't read elsewhere.
I could talk to her about translating the the two papers, but you'll have to send me the second one, Rhenium. Hope you have a scanner.
-drone #342
Cherrie Baby
Member posted 10-15-98 04:48 PM
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US patent 4501919 describes the reaction of glycine with p-nitrobenzaldehyde (in a two phases: H2O-DCM with MeBu3NCl as a PTC and concn. NaOH as a base, at 5-7#65533;C) to give b-hydroxy,p-nitro-tyrosine.
What would happen if alanine were used in place of glycine? The a-methyl analog?, which could be decarboxylated to p-nitro-norephedrine? Your guess is as good as mine. This looks like an interesting patent to explore as all the reagents are OTC.
It would work with other ring-substituents apart from nitro-, but I only discovered the Chem. Abstract tonite [CA:102, 204296] and I've not yet read the patent!
beagle boy
unregistered posted 10-15-98 08:48 PM
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Just checked that patent and saw that they were getting 70+% yield of the #65533;-hydroxy phenylalanine derivative from this easy procedure. And makes sense that alanine gives the alpha-methyl derivative, which should be more readily decarboxylated, no?
So if just refluxing these cpds. in say, xylene, will decarboxylate in good yields, this is one dandy scheme. Easy access to both ethanolamines and propanolamines for that comprehensive aminorex study.
Rhenium
Member posted 10-16-98 10:22 AM
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Drone : My friend with the scanner will be back in a couple of days. I will try sending it to you after that. This could be a very interesting procedure, hopefully the yields will be nice...
Take care,
Rhenium
Cherrie Baby
Member posted 10-16-98 05:56 PM
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beagle boy
In one of my references that quotes this they said that it was an Aldol condensation between the aldehyde and the amine forming an imine - which was subsequently hydroysised back to an amine, after condensation with a further 1 mol of glycine. So it looks like a different reaction mechanism to the one Drone's talking about - theres only a slight possibility that it might work with alanine. [I don't think so - I'm almost sorry I posted it - but it looked good to me when I first saw it.
[no don't ask me I never thought that amines underwent Aldol condensations either!]
beagle boy
unregistered posted 10-16-98 10:12 PM
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Cherrie:
I believe the patent you gave claims alanine could be used. Checkitout: http://www.patents.ibm.com/cgi-bin/viewpat.cmd/US04501919__
Wierd amine aldol condensation, different from what I was thinking. The question about decarboxylation remains, but I think these serine derivatives should decarboxylate quite a bit easier than tryptophan.
One downside to the above condesation is that the benzaldehyde would have to be in twofold XS. The extra benzaldehyde is claimed to be recovered for recycling after the reaction, but I'm not so keen about letting precious aldehydes stir around in aq. NaOH and then trying to recover them. Maybe the other route will turn out better.
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#65533; Infopop Corporation (formerly Madrona Park, Inc.), 1998 - 1999.
Wouter
(Stranger)
01-28-03 17:40
No 402127
Full text journal of the akabori-momotani reaction Bookmark
Has any one the Full text journal of the akabori-momotani reaction?
Akabori S., Momotani K., J.Chem.Soc.Japan, (1943), 64, 608; C.A., (1947), 41, 3774
Is it possible to copy it and send it to me (wouter@chemist.com). Please??
java
(Hive Bee)
01-28-03 18:24
No 402132
Re : Akabori..... Bookmark
This is all that is currently available....Akabori
Also known as Akabori-Momotani
Synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes.
Bibliography
Akabori S., Momotani K., J. Chem. Soc. Japan, 1943, 64, 608; C. A., 1947, 41, 3774
Dose K., Ber., 1957, 90, 1251.
Belikov V. M., Izv. AN SSSR. OHN, 1969, 2536.
although not available there is this at Rhodium's place......................https://www.rhodium.ws/pdf/akabori.phcho.glycine.pdf.
this ofcourse combined with Rhegis's post Post 367468 (Regis: "The most interesting CTH reaction ever documented?", Novel Discourse)
makes for a nice package for the synthesis for amphetamines.........java
Rhodium
(Chief Bee)
01-29-03 01:00
No 402201
Lots of threads on Akabori Bookmark
Post 122768 (dormouse: "Condensations of benzaldehyde and alanine", Serious Chemistry)
Post 245275 (IOC: "Akabori run", Novel Discourse)
Post 278820 (ChemicalSolution: "alanine and Akabori???", Chemistry Discourse)
Post 300434 (not existing)
Post 329052 (Aurelius: "Akabori-Momotani reaction", Chemistry Discourse)
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Hope this helps!?
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IndoleAmine
Dreamreader Deluxe
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nzbee
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121.78 Points
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Tue Mar 29, 2005 2:11 am |
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| So has anyone sucessfully completed this reaction?? Would be keen to see a write up of a this if it was sucessful. |
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DrugPhreak
Working Bee
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4261.30 Points
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Tue Mar 29, 2005 3:30 am |
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| Shouldn't a solvent be used? All the patents I've read that use similar compounds, which give a good yield etc do so. The posts that state the yield was low just mixed the two together and maybe they didn't heat it high enough also. Details are non-existent. |
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Astrum
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Tue Mar 29, 2005 6:50 am |
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Yes it has been successfully completed.
Yes a solvent should be used. |
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2174
. If not then it can easily be isomerized so it's no big deal.