evil_lurker
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a-halogenation of carboxylic acids...
Recently I have managed to locate some references to the halogenation of carboxylic acids, specifically the a-chlorination of propionic acid.
Patent US2010685 describes the chemical reactions involved in the process.
According to the reaction theory, the phosphorus trichloride forms an intermediate product, chloropropionyl chloride, which subsequently reacts with
propionic acid and is recycled by more chlorine. So in essence it is this halogenated product which is the true catalyst, not the phosphorus
trichloride itself.
"A mixture consisting of 2960 grams of propionic acid (40.0 moles) and 110 grams (0.8 mole) of phosphorus trichloride was stirred and heated to about
91C and approximately 3266 grams (46 moles) of clorine at a rate of 0.7 gram chlorine per minute. Approximately 40.2 moles of hydrogen chloride was
liberated during the course of such treatment. The quanitities of acyl chlorides present in the reacted mixture was determined by hydrolizing an
aliquot portion of said mixture with water and titrating the hydrochloric acid so liberated with silver nitrate. The quantity of water theoretically
required to hydrolyze the acyl halides present was then added to the main body of the reaction mixture and the latter was fractionally distilled.
There was separated 3985 grams (36.8) moles of substantially pure alpha-chloro-propionic acid, the yield being 91.8 percent of theoretical, based on
the quantity of propionic acid used. No beta-chloro-propionic acid was obtained."
What shocked me was the amount of phosphorus actually needed to produce 1 mole of the a-chloropropionic acid... if the patent's calculations are
correct, it equals out to be about 0.05 mole of PCl3 per mole of halogenated acid!
But the real shocker was that no elemental phosphorus or phosphorus trihalides at all was needed for the reaction! If one were to substitute another
acyl halide in the reaction, such as benzoyl chloride, then that could be used as a promotor. By adding a small amount of orthophosphorous acid as a
complexing agent, the reaction would totally go towards the alpha product.
Also, it is possible to chlorinate propionic acid using TCCA, or so the reference says... look in the wanted reference section...
If anyone has any references to bromo derivitives please post them.... I'd be most appreciative.
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not_important
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This is quite old. The long time used procedure of carboxylic acid plus a little red phosphorus and add Br2/Cl2 to get the alpha=halo acid. Esters
and acid anhydrides work too. I've read early 20th century preparations where a little acetyl chloride would be added to a large amount of some
higher boiling acid, then chlorine or bromine added to the 1:1 or 2:1 ration mark, and the mixture worked up. The acetyl chloride got
alpha-substituted too, but there was so little of it that simple workup removed it.
If you add an acyl chloride to an acid, then add bromine you will find that you have nearly if not completely 100% alpha-bromo substitution with no
alpha chloro formed.
Check early Org Synth, and organic chemistry books from 1880 to about 1940.
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Organikum
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Yes, thats actually from the 19th century and I am again surprised what one can patent in the USA.
Rederences from the same time state that this method is pretty tricky and does not work well for everybody. A better starting material with less
problems would be lactic acid as used in the industrial processes for production of alpha-chloro-propionic acid.
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not_important
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| Quote: | | A better starting material with less problems would be lactic acid as used in the industrial processes for production of alpha-chloro-propionic acid.
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Thought that there was a problem with dehydration vs replacement with halogen when trying that with typical lab gear ???
If not, those 19th and early 20th century books often had instructions for setting up a fermentation of sugar to produce lactic acid/calcium lactate.
Umm mmm - 25 liters of sour milk smell.
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Rubin
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Surely you can just buy lactic acid. It's used in wine-making.
What is this industrial process for the production of alpha-chloro-propionic acid from lactic acid? Is it done using HCl acid? If so, does it use a
catalyst (ZnCl2?)
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not_important
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The lactic acid route has come up before
http://www.sciencemadness.org/talk/viewthread.php?tid=3961
Lactic acid from brew supplies is pricy, for me 25 gr costs as much as a kg at commerical bakery supply prices; they won't sell to me as I am not a
bakery, and as Justin Case says "I'd rather not leave footprints".
[Edited on 8-8-2006 by not_important]
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Vitus_Verdegast
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Helv. Chim. Acta 20 (1937) 1580
This reference describes the electrochemical chlorination of propionic acid in hydrochloric acid at the platina anode, yielding a mixture of
3-chloropropionic acid and (+,-)-2-chloropropionic acid.
I suspect the ratio alpha-beta will be along the lines of...
...patent DE579654 (1931):
(translation mine)
"Propionic acid is treated in presence of light at temperatures below its boiling point with a small amount of chlorine. When particularly
temperatures between 30 and 60 °C seemed suitable, the procedure also works succesfully below and above these temperatures. Instead of light
different chlorination catalysts can also be used. Besides a relatively small portion of alpha-chloropropionic acid the main product obtained is
beta-chloropropionic acid. A more or less large remainder of propionic acid remains unchanged."
"The reaction with chlorine is accelerated by sunlight, but can likewise very well be obtained in absence of sunlight by the addition of other
catalysts, e.g. iron salts. Thus for example in presence of 2.5 % water-free ferrous sulphate there is obtained after approximately 3 hours at
50-60°C 40% of chlorinated products in absence of direct sunlight, while in presence of sunlight under same conditions only about 2.25 hours reaction
time is necessary. In absence of a catalyst however the reaction duration is retarded greatly taking over the double the time necessary stated above."
"In 12.5 kg Propionic acid heated at 120°C are introduced 12 kg chlorine. After fractional distillation 11.35 kg beta-chloropropionic acid (62,2%
theoretical yield) and 5.15 kg of alpha-chloropropionic acid (28.1% theoretical yield) are obtained. The ratio alpha to beta amounts to 1: 2.21"
I realise the topic of this thread is the preparation of alpha-chloropropionic acid. However being unsuitable for the Darzen condensation -regarding
the preparation of phenylacetones from benzaldehydes- beta-chloropropionic acid is still interesting as it can be used as a valuable precursor for the
preparation of nitroethane.
EDIT:
A search on the preparation of alpha-chloropropionic acid (esters) from lactic acid (esters) only revealed papers that using either PCl5, SOCl2 or
COCl2/pyridine.
[Edited on 8-8-2006 by Vitus_Verdegast]
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evil_lurker
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Well this thread is about all such carboxylic derivitives, be they iodine, bromine or chlorine. And not just limited to propionic acid either.
Now this if OT, but how does one utilize the beta verion of chloropropionic acid for nitroethane production.
I was of the understanding that only the a-bromo derivitive could be used.
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Vitus_Verdegast
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I copied this directly from Rhodium's page, I did not realize it is a modification from an Org Syn method:
| Quote: |
Method 11: 3-chloropropionic acid sodium salt, and NaNO2
ClCH2CH2COONa + NaNO2 NO2CH2CH2COONa + NaCl
NO2CH2CH2COONa + H2O –heatNO2CH2CH3 + NaHCO3
Modification of Nitromethane synthesis from Organic Synthesis, Vol? Pg 401.
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http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/n...
Beilstein doesn't give any hits on this... 
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leu
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The proper citation to the Kolbe synthesis is Organic Syntheses, Coll. Vol. 1, p.401 (1941); Vol.
3, p.83 (1923).
The URL is:
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0401
expect a yield of about 20%
[Edited on 9-8-2006 by leu]
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jack-sparrow
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You can try R-CH2-COOH with N-bromosuccinimide in dichloromethane at reflux for 2 weeks. It works for the preparation of bromoacetic acid.
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Maja
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It's a typo ? 2 weeks ?
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sonogashira
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Carboxylic Acids can be a-Iodinated in good yields with I2 and a Cu(II) salt. See Chem. Lett. 1509 (1984) - Available for free via the website here:
http://www.journalarchive.jst.go.jp/english/jnlabstract_en.p...
Abstract:
Direct α-iodination of some carboxylic acids, namely, acetic acid, propionic acid, butyric acid, and valeric acid, using iodine-copper salt, gave
the corresponding α-iodo carboxylic acid in high yield. This new synthetic method afforded several advantage over classical α-iodo
carboxylic acid procedures.
[Edited on 19-8-2008 by sonogashira]
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Sauron
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TCCA works, NCS works, the halohydantoins work, preferably on the preformed acyl halide.
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Klute
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I take it no catalyst is required to halogenate the preformed acyl halide?
IIRC, the vogel preparation uses a little red phosphorus even after forming the acyl chloride with SOCl2... What's the use as the a-carbon is
already activated?
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Sauron
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The purpose of the red P or other "halogen carrier" catalyst in the HVZ reaction is to convert some of the acid to acid halide. So obviously, if the
substrate IS an acid halide, no catalyst is needed. You can find an example of this approach in Org.Syn. for the a-bromination of hexanoyl chloride
(caproyl chloride) on the way to making racemic norleucine out of it.
The relative unavailability of red P and of PCl3 propels me to eschew the formal HVZ. I do have and can get PBr3 though.
I am however saving that for a rainy day.
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Vogelzang
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Quote: Originally posted by Organikum  | Yes, thats actually from the 19th century and I am again surprised what one can patent in the USA.
Rederences from the same time state that this method is pretty tricky and does not work well for everybody. A better starting material with less
problems would be lactic acid as used in the industrial processes for production of alpha-chloro-propionic acid. |
I'd like to see the 19th century references that disclose the same process in the claims.
[Edited on 20-9-2009 by Vogelzang]
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Vogelzang
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How about amino acids as starting materials?
http://v3.espacenet.com/publicationDetails/originalDocument?...
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chemoleo
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That sounds like a very nice patent if it really works - quite amazing!
One would start with alanine (health store) to get the a-chloro propionic acid, seems HBr (instead of HCl) works even better!
Never Stop to Begin, and Never Begin to Stop...
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S.C. Wack
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Using amino acids is a very old and well-known route. Using nitrite instead of nitric. Mentioned here before, OS, etc.
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