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panziandi
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More importantly hector2000 should have questioned it rather than asking for more details on it!
Anyway before he asks...pyruvoyl chloride can be made from pyruvic acid and a,a-dichloromethyl methyl ether in moderate yield cf Organic Syntheses,
Coll. Vol. 7, p.467 (1990); Vol. 61, p.1 (1983).
Hector I do not think Sauron was ever implying that phenylglyoxalic acid could be converted to l-PAC ... though you could have fun trying that one out
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Sauron
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Quite right. I did not say that LPAC can be made from phenylglyovalic acid. Somone else posted that the Friedel Crafts acylation of benzene with
oxalyl chloride, followed by hydrolysis, would give L-PAC BUT he was wrong. That gives only phenylglycolic acid.
assym-dichlorodimethyl eyjer is a powerful reagent not too easy prepared. is there no more practical way tp pyruvyl chloride?
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panziandi
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Well conventional reagents such as PCl5 would add to the ketone I'd imagine forming gym-dihalides. Orgsyn mentions that "conventional reagents are
unsatisfactory" and that phosgene and oxalyl chloride both yield ether solutions with a low conversion. And that aa-dichloromethyl methyl ether was
the most satisfactory method for pyruvoyl and other alpha-ketoacoyl chlorides.
I am unsure if the Ph3P/CCl4 or benzotrichloride methods would work. And I shall leave you to speculate on the use of the infamous TCT 
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Sauron
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That Org.Syn. monohraph is >25 years old, a lot can happen in a quarter century of chemistry.
Remember the yield with DCMME is 45-60% which is OK but not thrilling.
An alternative prep is mentioned as useful: trimethylsilil pyruvate and oxalyl chloride
Häusler, J.; Schmidt, U. Chem. Ber. 1974, 107, 145–151.
But I have not yet obtained it, and it sounds expensive.
I may have overstated the difficulty of preparing 1,1-dichlorodimethyl ether. It is commercially available, and is prepared from methyl formate and
PCl5 in POCl3. So if PCl5 and POCl3 are available to you as they certainly are to hector2000, this is rather a piece of cake.
A review of Friedel Crafts actlations should establish whether or not pyruvyl chloride works in this reaction.
Another gambit:
Is there an acyl chloride of lactic acid?
And if so will it work in the F-C acylation of bemzeme, which would give DL-PAC (racemic pehylacetylcarbinol) directly?
Lactic acid is a fermetation product and ought to be cheaper than pyruvic acid. I do not remember ever hearing about lactyl chloride but that means
nothing. Nor do I recall anything about acyl chlorides of a-hydroxy carboxylic acids being impossible. Though polymerization may be problematic.
I will post the Org.Syn. prep of ptruvyl chloride bwlow.
Attachment: CV7P0467.pdf (159kB)
This file has been downloaded 1894 times
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Sauron
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And here is the prep of the reagent 1,1-dichloromethyl methyl ether
Assuming that lactyl chloride (acyl chloride of lactic acid) is a problem due to self condensattion as seems likely (cf. glycollic acid) then:
Lactic acid is 2-hydroxypropionic acid.
How about 2-chloropropionyl chloride? No oligomerization. Use this in the F-C acylation of benzene and then hydrolyze the product to racemic PAC.
Starting with cheap lactic acid, and at the end no reduction, just hydrolysis, looks better than F-C with pyruvyl chloride to me.
I would say, NCS for the a-chlorination of lactic acid then your choice of reagent for the acyl chloride:
SOCl2
TCT
benzoyl chloride
Whatever.
Attachment: CV5P0365.pdf (139kB)
This file has been downloaded 1921 times
[Edited on 29-4-2009 by Sauron]
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DJF90
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Sauron: How selective is the F-C reaction with 2-chloropropionic chloride? I imagine that acylation will definatately dominate, but what % if any
would you expect alkylation to occur? And you're right, it probably is a more attractive reaction compared with pyruvyl chloride... Lets hope our
friend Hector agrees.
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Sauron
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Well, I always find acyl chloride preps interesting, esp. oddball ones. Regarding your question on F-C alkylation vs acylation as a competing
reaction, I don't know. Maybe a less reactive a-halo compound such as a-bromopropionyl chloride would solve this, if it is a problem.
As for hector, I am not really concerned. He is welcome to whatever he can learn if anything, it;s a free forum.
I have not availed myself of the extensive material on L-PAC solo has posted in Recent Hournal Articles of Interest,,,simply because I am not really
interested in L-PAC or any of its progeny (ephedrinem psuedoephedrine, phenylpropanolamine etc.)
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hector2000
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I found DICHLOROMETHYL METHYL ETHER here but reaction for making PYRUVOYL CHLORIDE is very difficult.(one step need -50c temp)
Sauron,
You want to say 2-chloropropionyl chloride+benzen in the FC Reaction and hydrolyze will produce PAC?
[Edited on 29-4-2009 by hector2000]
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Sauron
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2-chloropropionyl chloride
Me-CH(-Cl)-C(=O)-Cl
Pyruvoyl chloride
Me-C(=O)-C(=O)-Cl
Ig you use former you must reduce the carbonyl adjacent to rung to hydroxyl
If you use latter you must still do that but first you must hydrolyze -Cl ro -OH then oxidize to carbonyl.
A little more work than I first rghought
[Edited on 29-4-2009 by Sauron]
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solo
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.............sometimes leading the thirsty to water isn't enough.........solo
http://www.sciencemadness.org/talk/viewthread.php?tid=1936
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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panziandi
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Hector so you do not have the ability to distil under reduced pressure with ice-salt baths for condensers?
Indeed Sauron I believe lactoyl chloride would not exist. (Also yes 25years is a long time in chemistry )
1) the alcohol OH is more prone to chlorination that the acyl OH so you would likely form the chloro-acid before the acid-chloride
2) it would react with other molecules in a polymerisation to get a polyester
Indeed I expect you could chlorinate both alcohol and acid OH's obtaining 2-chloropropanoyl chloride which would be used in a FC. I'd expect the -COCl
to react most readily in an FC to give a monoacylated product.
Indeed lactic acid is cheaper than pyruvic acid. You can oxidise the lactic alcohol to a keto in order to go from lactic acid to pyruvic acid, i.e.
dichromate etc. Then isolate and chlorinate, likely best route:
Lactic acid is present as 85%, and readily condenses to a lactone, at this and higher concentrations, chlorination to get chloropropanoyl chloride
would be difficult since you have 15% water contamination that would react with the chlorinating agent (PCl5, SOCl2, TCT etc) then you have two
chlorinations to perform, which I think would be highly wasteful of reagents... thoughts?
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Sauron
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Propionic acid is far cgeaper still.
NCS or NBS or TCCA will halogenate the 2-position of propionic acid (the a-carbon) and that acid is then readily converted to the acyl chloride.
The only part of the prep of pyruvoyl chloride that calls for low temperatures is the vacuum fractionation, in which the forerunb of methyl formate
needs trapping. All that is required is a Deware comdenser with dry ice (solid CO2)-acetone slurry and a bath of same to chill the receiving flask.
Thhis is a routine lab procedure. Hector, get yourself cylinders of CO2 with dip tubes and Frigimat Jr dry ice snow makers attached, make your dry
ice on site same as I do. It is cheap.
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panziandi
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But I thought we were talking about 2-hydroxypropionic acid (aka lactic) and chlorinating the OH of that as opposed to chlorinating the alpha carbon
of propionic acid?
If hector is going via the FC acylation I can see a few possible routes to suitable acid chlorides:
1) CH3-CH2-COOH > CH3-CHCl-COOH > CH3-CHCl-COCl
2) CH3-CHOH-COOH > CH3-CHCl-COOH > CH3-CHCl-COCl
3) CH3-CHOH-COOH > CH3-C(=O)-COOH > CH3-C(=O)-COCl
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Sauron
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Propionic acid is chaper than lactic acid which is cheaper than pyruvic acid
With propionic acid it is easy to make the a-chloro acyl chloride
Lactic acid has zero advantage amd "2-chlorolactoyl chloride" is identical to 2-chloropropionyl chloride.
Just as glycolloyl chloride cannot exist but chloroacetyl chloride does.
Pytuvoyl chloride is a lot costlier to make: cost of acid, cost of 1,1-dichlorodimethyl ether ( lots PCl5, POCl3)
With these facts it's time to try to determine from the lit. whether the F-C acylation with either the 2-chloropropionyl chloride, or pyruvyl chloride
has ever been done, and what results were. If this still looks good, then examine optical resolution of DL-PAC.
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hector2000
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Thanks Mr Sauron but,
You should accept that working with solid CO2 is difficult also working in -50c.
Here there is company that sale solid CO2 but far from my town and this is not easy to move it.
Only Chemical way for making PAC is reaction between pyruvyl chloride annd benzene?
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panziandi
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Hector: You only need the -50*C bath for preparing pyruvoyl chloride using the a,a-dichloromethyl methyl ether method.
So far Sauron has suggested using chloropropanoyl chloride in FC with benzene followed by hydrolysis of the -Cl to a -OH.
Or FC with pyruvoyl chloride with benzene followed by reduction of the C=O to a C-OH.
As yet we have no literature to support either FC acylation.
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hector2000
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Chloropropanoyl chloride in FC with benzene really will work?
Still i believe mandelic acid is very similar to PAC.really there is no way for shoot second OH group?
I know I2/P will shoot first OH group but no hope for second OH?
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panziandi
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I have to ask if you are familiar with (organic) chemistry at all?
Mandellic acid is EXACTLY that... a carboxylic acid! The "second OH" as you describe it is actually a "COOH" it has TOTALLY different chemistry to an
alcohol OH as the "first OH" is.
Besides Mandellic acid is far more expensive than a FC would cost.
Also Sauron I find that lactic acid is far cheaper an more available than propionic acid. Also if, as i expect, hector plans on a largish scale (God I
hope he doesn't scale a chemical method to a 350L reactor! ) .. lactic acid is
readily obtainable in high purity, high concentration (ca85%), in large quantity since it is so widely used in the food industry etc.
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hector2000
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Mr panziandi,
I know that but why we can shoot OH group in the Phenylacetic acid by Lead acetate but we cant do this work with mandelic acid?
lactic acid,mandelic acid and tartaric acid is very cheap here.
Lactic acid is 5$ per kilogram
Tartaric acid is 3$ per kilogram
Mandelic acid is 10$ per kilogram
Maybe you dont believe but we have lot of chemical shop here (like market)
[Edited on 29-4-2009 by hector2000]
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stateofhack
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Quote: Originally posted by hector2000  | Mr panziandi,
I know that but why we can shoot OH group in the Phenylacetic acid by Lead acetate but we cant do this work with mandelic acid?
lactic acid,mandelic acid and tartaric acid is very cheap here.
Lactic acid is 5$ per kilogram
Tartaric acid is 3$ per kilogram
Mandelic acid is 10$ per kilogram
Maybe you dont believe but we have lot of chemical shop here (like market)
[Edited on 29-4-2009 by hector2000] |
I think your have nearly no idea what your on about to start with. You seem to be going nowhere (just like this thread) and are waisting everyone
time.
Please take your "cooking" stuff elsewhere, i mean common, am i the only one who has realized what this tool is up too?
I am surprised this stuff has stayed for so long !
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panziandi
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No Sauron guessed earlier too, and I think most contributers have twigged too!
So hector: I think you should do the biotech route, I think a full prepub write-up on a 350L biotech synthesis would be a great addition to the board
to save this thread
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turd
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| Quote: Originally posted by hector2000 | | I know that but why we can shoot OH group in the Phenylacetic acid by Lead acetate but we cant do this work with mandelic acid?
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Gosh, you don't even seem to try to understand what you're doing. The reaction you're thinking about is a variation of the Dakin-West reaction.
http://en.wikipedia.org/wiki/Dakin-West_reaction
In the first paragraph it says: "Of special note, the amino-ketone product is always racemic.", therefore - given that this is also true for this
variation - you would get PAC, not L-PAC (do you even bother about which enantiomers you get?).
Then it proceeds to say that you need an alpha-amino group or an easily removable alpha-H+. I'm not good enough in organic chemistry to tell you if an
alpha-OH would substitute for the alpha-amino group, but I guess the acetyl group you will get will destabilze any carboanion, and therefore the PAA
mechanism will not run as smoothly. Just a guess though.
BTW, this is your chance of contributing to this board: just try it! This would actually be interesting! Also try the procedure with
n-methyl-imidazole, which was posted here some time ago. You have the chemistry shops. N-methyl-imidazole, mandelic acid and small amounts of acetic
anhydride are unsuspicious, so what is holding you back?
But why do I even bother, there's not going to come anything out of this... 
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hector2000
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| Quote: Originally posted by stateofhack |
I think your have nearly no idea what your on about to start with. You seem to be going nowhere (just like this thread) and are waisting everyone
time.
Please take your "cooking" stuff elsewhere, i mean common, am i the only one who has realized what this tool is up too?
I am surprised this stuff has stayed for so long ! |
Please dont accuse
Really i think you dont underestant my purpose
In the Tehran there is place (naser khosro)that sale lot of chemical componet(like market) this shops arent for me!
just i say we have(not me or my friend)my purpose was iranian.
I know if this reaction be possible DL-PAC will produce
In the below link you can see "making phenylacetone from phenylacetic acid by lead acetate"
http://www.erowid.org/archive/rhodium/chemistry/phenylaceton...
When i saw this i think may be this is possible for mandelic acid that convert to PAC
[Edited on 29-4-2009 by hector2000]
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panziandi
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@ Hector: as DJF90 said and as others have said: Your tagline states "Chemistry=Chem+ is+ Try" ... so you want to know if Mandelic acid will be
ocnverted to PAC with lead (IV) acetate? ... Well try it!
You don't have to try it on a large scale you stated that the l-PAC would be analysed with GC-MS so you could do a small scale reaction then analyse
the product as you stated you could ad find out if it worked, if it did and the yield is good you could scale it as suited.
Go try it out and post back results and this thread may have achieved something.
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Sauron
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Hector
1. You dismiss the FC with pyruboyl chloride because you say you cannot chill to -50 C. Your dry ice supplier too far away. I TOLD you buy tanks of
CO2 under pressure with dip tube and a Frigimat Jr dry ice snow maker and make your own solid CO2 snow on demand on site when you need it. This is
what I do, it costs very little.
2, There is NO requirement for such cooling in prep of 2-chloropropionyl chloride, so make this insteas. I do not care whether you make it from
propionic acid, or from lactic acid, as panziandi suggests, use whichever is cheaper in Iran on the scale you require.
3. Dry distillation of mandelic acid with lead acetate will not produce PAC but only phenylacetone, that benzylic hydroxyl will IMO never survive the
temperatures involved, and your pharm company buyer will not like product contaminated with Pb anyway.. Gorget it.
You CONSTANTLY want other people to do your thinking for you, while all you do is sit back and nitpick and dream up excuses for rehecting all
suggestions.
YOU ARE WASTING EVERYONE'S TIME HERE. STOP!
For those other who are interested here is a paper from Ber. (1974) describing the prep of pyruvoyl chloride by the reaction of trimethylsilyl
pyruvate and oxalyl chloride.
The TMS-pyruvate is (I think) prepared from trimethylsilyl chloride and sodium pyruvate. A proper translation by a German chemist is desired. (of the
small pertinent section only - the rest of the paper is immaterial.)
[Edited on 30-4-2009 by Sauron]
Attachment: Volume 107, Issue 1 (p 145-151).pdf (389kB)
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