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turd
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What a strange choice of words, given that I never promised great yields or anything. But let's do the math:
The reference I posted gives 45% for mandelic-acid + MeLi --> PAC. Yes, a lousy yield.
Now via the mandelamide.
Orgsyn gives: mandelic-acid + NH3 (liquid!) --> mandelamide 62%, I'd say OK, but you'll probably find better.
The 1932 article: mandelamide + MeI + Mg --> PAC 70% (nice, but maybe a little bit optimistic - they took a fraction from 110°-140°C)
Gives 62% x 70% = 43%
So unless my calculations are off, you have 45% in one reaction vs. 43% in two reactions (meaning more solvent, more work, and so on). I
guess common sense has a clear answer to that one. A part from that I still don't see why MeLi from MeI would be more demanding than doing classic
Grignards. Or how someone who can handle liquid NH3 would have problems with MeLi.
PS: I really don't care what route hector2000 choses, I'm not here to win some strange popularity contest. How silly would that be?
PPS: I'm not an organiker so take everything with a grain of salt.
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turd
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Quote: Originally posted by DJF90  | | Hector: -10C is a simple temperature to achieve. Supposedly NaCl/crushed ice in a ratio of 1:3 (w/w I believe) will get you to -20C, but this is
slightly unrealistic. However -10C should be well in its ability. |
This is so strange... The guy can buy get oxalylchloride and whatnot, but no dry ice? Also I think he missed the part about the liquid ammonia, how is
he going to condense that? Maybe the suggestion of a secondary/tertiary amide isn't so dumb after all? But first and foremost I think the guy should
start thinking for himself.
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DJF90
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Hector may have access to dry ice, but if the reaction only needs to be cooled to -10C then I dont think there is a dry ice bath he could use for
that. Theoretically he could use a CaCl2.6H2O/ice bath to ~-40C, and this should be sufficient for condensing ammonia although it will not work as
well as a dry ice bath.
[Edited on 11-5-2009 by DJF90]
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turd
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| Quote: Originally posted by DJF90 | | Hector may have access to dry ice, but if the reaction only needs to be cooled to -10C then I dont think there is a dry ice bath he could use for
that. |
Why? It's just a matter of how deep you insert your flask in the cooling bath.
| Quote: | | Theoretically he could use a CaCl2.6H2O/ice bath to ~-40C, and this should be sufficient for condensing ammonia although it will not work as well as a
dry ice bath. |
Well sure, good luck with that.
But seriously, he should simply use a non-volatile amine together with a water scavenger like toluene, which will give higher yields and will need
much less work. Maybe even use an enantiomeric amine, then he could do the enantiomeric resolution at this step.
The best advice still is: just buy the silly thing.
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DJF90
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Just buying it isnt exactly going with the flow of amateur chemistry now is it...
I know that the CaCl2/ice bath isnt efficient, but its better than nothing and should do the job (I did imply it wouldn't be great...)
Toluene is NOT a "water scavenger"... It merely forms an azeotrope which is distilled off, removing the water from the reaction mixture. Hydrolysing
an amide takes pretty harsh conditions, and so if theres no conc. acid or conc. base around then I doubt very much that yields will suffer due to the
presence of just water.
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Sauron
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Bandying words with turd is not a productive pasttime. He's out to wreck this thread, not to enlighten anyone about anything.
Give his a wide berth and no replies t all. Send him to Coventry.
Sic gorgeamus a los subjectatus nunc.
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turd
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Of course not. But hector has made it quite clear that he needs 100g L-PAC to sell it to a "pharm-company". My opinion is that his best option would
be to act as a reseller, lest he hurts himself more. So I think this is the best advice we can give him. Still we can discuss the chemistry, although
IMHO it's quite boring to discuss chemistry that no one will perform.
| Quote: | | I know that the CaCl2/ice bath isnt efficient, but its better than nothing and should do the job (I did imply it wouldn't be great...)
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An honest question: would *you* do that? Can you imagine a situation where someone can acquire large amounts of anhydrous NH3 but no dry ice?
| Quote: | | Toluene is NOT a "water scavenger"... It merely forms an azeotrope which is distilled off, removing the water from the reaction mixture.
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Yeah, you know what I meant. Toluene + Dean Stark trap removes water, I don't know what the correct term is.
| Quote: | | Hydrolysing an amide takes pretty harsh conditions, and so if theres no conc. acid or conc. base around then I doubt very much that yields will suffer
due to the presence of just water. |
Well, they use a Dean Stark trap in the OrgSyn procedure Sandmeyer posted (http://www.orgsyn.org/orgsyn/prep.asp?prep=v81p0262). Maybe it is superfluous, but that makes my point even stronger: why make mandelamide with
liquid NH3, when you can make a secondary/tertiary amide with much less work and probably higher yields?
@Sauron: you're cute. But I think the members on this board are old enough to decide who they talk to.
[Edited on 12-5-2009 by turd]
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turd
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BTW, you are right, there is no need for a Dean Stark trap. Here are some examples (though I cannot assess if they are too sterically hindered).
Jpn. Kokai Tokkyo Koho, 05294911, 09 Nov 1993, Heisei (Patent written in Japanese 
)
Journal of Organic Chemistry, 52(22), 4978-84; 1987 (83% for the benzylamide)
Tetrahedron Letters, 26(7), 811-14; 1985
Journal of Molecular Catalysis A: Chemical, 276(1-2), 235-243; 2007 (DCC, 95%)
Tetrahedron: Asymmetry, 16(11), 1953-1958; 2005 (DCC, 94%)
Heterocycles, 22(4), 773-8; 1984 (39-79%)
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hector2000
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Turd,
Maybe reaction between MeLi and mandelic acid has better Yield but you should accept the price of MeLi is very expensive and sure this price isnt
important for 100gram LPac but if pharm company accept my sample then we should provide l-pac for pharma company continuesly and in this point the
price of final product will be important.
do you think reaction between Mei and Li make good yield MeLi?
2 Li + MeI → LiMe + LiI
Sauron(Thanks),
I did mandelamide reaction difficuly but i got mandelamide.
Now for reaction between mandelamide and MeMgI i should use mandelamide.Hcl ?
[Edited on 12-5-2009 by hector2000]
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Sauron
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Hector
Follow thw protocol in JACS
If it says mandelamine hcl, use that
Otherwise use free mandelamide
Did you resolve dl-mandelic acid, or did you buy d-mandelic acid (R)-(+)-mandelic acid?
MeLi gives crap yields with mandelic acid
MeMgI iodide gives good yields with mandelamide but protocol requires 4X excess.
This is not a problem if you make your own MeI and MeMgI.
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hector2000
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I buy (R)-(+)-mandelic acid for both reaction (MeLi reaction and Mandelamide reaction)
For purification of mandelamide i react it with HCL and dissolve it in water and separate water then react it (water+mandelamide.hcl) with Naoh
solution and separate it with DCM and evaporate solvent but when i add Naoh solution lot of gas produced(i think that was ammonia because i test this
gas with wet Ph paper and paper show Ph 14)this is normal?mandelamide didnt destroy?
I test result of reaction between 1,1dichloroacetone and benzene in FC by GC-MS and got interesting result.
GC-Ms show diffrent componet but really dont show this componet and we guess that is:
(PH)2-CH-C(=O)-CH3(~10-12%)(GS-Ms dont realize it and we guess it)
PH-CH(OH)-C(=O)-CH3(~30-36%)(GC-MS realize it)
Maybe i miskate but when i show result to my friend(chemist)he accept that probably this componet produced
[Edited on 12-5-2009 by hector2000]
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turd
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| Quote: | | Now for reaction between mandelamide and MeMgI i should use mandelamide.Hcl ? |
| Quote: | | If it says mandelamine hcl, use that Otherwise use free mandelamide |
| Quote: | | For purification of mandelamide i react it with HCL and dissolve it in water and separate water then react it (water+mandelamide.hcl)
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AmiDe guys, not amiNe.
hector: If you really made mandelamide, please post details of reaction, workup and analysis. I think this is quite interesting, since I have
D/L-mandelic acid and no use for it!
Yes, making MeLi is easy if you can work under intert gas, see the note Sandmeyer posted: | Quote: | | 4. The methyllithium must be prepared from methyl iodide because the presence of the iodide anion is essential. The submitters prepared methyl lithium
in the following manner. Methyliodide (425.7 g., 3.00 moles) was added with stirring to 48 g. (7.0 g. atoms) of lithium in 2.5 l. of ether under
nitrogen at a rate adequate to maintain gentle reflux of the ether. After 24 hours the solution of methyllithium was decanted into a storage vessel
filled with nitrogen. The concentration was estimated in the usual way by hydrolysis of an aliquot and titration with 0.1N hydrochloric acid.
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Of course you can not just react mandelic acid with MeLi. You will have to fetch literature references for good ideas. (First two aliquots of LiH? The
organic experts will be able to help you out.)
But really, you will never be able to compete against the pros in eastern asia, so buy the stuff, sell it for a profit and enjoy your free time!
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hector2000
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| Quote: Originally posted by turd |
AmiDe guys, not amiNe.
hector: If you really made mandelamide, please post details of reaction, workup and analysis. I think this is quite interesting, since I have
D/L-mandelic acid and no use for it!
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I didnt analyse it but when i add Naoh solution ammonia gas produce.maybe mandelamide.hcl will not produce and my method for purification is wrong.
Before i think HCL will made salt of mandelamide like amin because it has NH2 but i mistake sorry.
[Edited on 12-5-2009 by hector2000]
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DJF90
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Reacting the mandelic acid with two equivalents of MeLi will do the trick. Alternatively to save an equivalent you could use another base to
deprotonate the acid.
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turd
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I think you forgot the benzylic OH - that one has to be deprotonated too if you don't want to lose another equivalent of MeLi. I wonder if it will be
the cause of cyclisation - once I tried to make an amide of ethylenediamine and all I got was a silly imidazole. 
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hector2000
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I find out When reaction time between 1,1dichloroacetone and benzene in FC increase then yield of (PH)2-CH-C(=O)-CH3
Working with MeLi is not simple and that is very expensive and isnt easy to make
I see before that L-PAC is unstable componet and sensitive to high temp.this is true?
What temp?
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Cyrex
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I wonder how Amination of L-pac make L-ephedtine not D-ephedrine?!
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Sauron
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KINDLY STAY ON TOPIC!
Learn some stereochemistry and the answer will pop out.
Your question is a good one. HOWEVER, this thread is not about ephedrine, nor is it a proper venue for a discourse on stereochemical notation, nor
mechanism of reductive amination. Those are what it takes to answer your question fully, and if you want to start a thread about those with L-PAC
-> ephedrine as an example in point, I'm sure it will be an instructive one,
But not here!
[Edited on 14-5-2009 by Sauron]
[Edited on 14-5-2009 by Sauron]
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hector2000
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| Quote: Originally posted by Sauron | I stated far upthread that the racemic PAC will have to be resolved to an ee at least as good as what the biotech processes give c.ee 90%.
Hector has three choice
Traditional - fract cryst. of a derivative made with a chiral compounm e,g, tartaric acid
Chiral chromatography on a prep scale
Enzymatic resolution if such a method exists for this substrate.
The second method is probably unapproachable.
The first is laborious.
The third may be best if it exists.
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which type of tartaric acid?L(+)tartaric acid?D(-)tartaric acid?
d-tartaric acid?what is d-tartaric acid?(L(+)tartaric acid?)
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Sauron
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Hector, tartaric acid is simply an example.
It may or may not be effective for the resolution of racemic (dl-) PAC.
Why are you messing with such resolution when you have means of producing L-PAC now?
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hector2000
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I made little L-pac from mandelamide method but after calculate the price i find out that this methos isnt economic for our.
We decide to produce L-pac from 1,1 dichloro acetone because is very chepaer than mandelamide method and just in one step.
Now i am working on resolution of racemic PAC
Maybe you say we shoud separate DL-mandelic acid but i should say phenylethyllamine is very expensive here.
1,1 dichloro acetone has cheaper price
[Edited on 17-5-2009 by hector2000]
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Sauron
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OK hector, do what you want.
You will find the resolution of PAC tedious and expensive I think. Anyway search in the literature for best resolving agent and method for PAC.
Good luck. I think you will need it.
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hector2000
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Thanks Sauron
anybody has idea for resolution racemic DL-PAC?
[Edited on 17-5-2009 by hector2000]
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turd
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Yeah, oxidize it to PhCOCOCH3 and stereoselectively reduce it. And I'm only half joking. Suddenly propiophenone becomes interesting again, eh?
But totally seriously: If you enter PhCHOHCOCH3 as product molecule in SciFinder or Beilstein/Crossfire you will find quite a lot of papers on racemic
resolution of PAC. You will also find tons of different syntheses for your target molecule and this could have spared us the whole thread.
PS: When do we get the experimental details for mandelamide and its physical characteristics (mp), since you suggest that you made L-PAC via
the mandelamide?
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Cyrex
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interesting method
[Edited on 17-5-2009 by Cyrex]
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