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The Hive => Chemistry Discourse => Topic started by: tropine on December 11, 2003, 06:48:00 PM

Title: b-ketoglutamate from citric acid and conc H2SO4
Post by: tropine on December 11, 2003, 06:48:00 PM
There are copious amounts of citric acid and concentrated sulfuric acid avail, but not fuming sulfuric acid.  Being that making fuming slufuric acid is a very nasty process, I happened to note that the method described here for  ketoglutaric acid

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0010 (http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0010)

  says that:

""3. Discussion
Acetonedicarboxylic acid can be prepared from citric acid by the action of concentrated2 or fuming sulfuric acid""

So anyone have any comments on why conc H2SO4 can also work? Also, in the Findlay's "Cocenrning 2-carbomethoxytropinone" it states that the dimethyl-b-ketoglutamate is formed in this reaction, yet Org Syn link says that the free acid is formed, which is it? Thanx!
Title: Corrections & Clarifications
Post by: Rhodium on December 11, 2003, 08:41:00 PM
Acetonedicarboxylic acid = Beta-ketoglutaric acid (not "b-ketoglutamate")

H2SO4 = Sulfuric Acid (not "slufuric acid")

Also, in the Findlay's "Cocenrning 2-carbomethoxytropinone" it states that the dimethyl-b-ketoglutamate is formed in this reaction, yet Org Syn link says that the free acid is formed, which is it?

Taken from

Post 436988 (https://www.thevespiary.org/talk/index.php?topic=12539.msg43698800#msg43698800)

(Rhodium: "Findlay's 2-carbomethoxytropinone synthesis", Serious Chemistry)

Dimethyl beta-ketoglutarate

Powdered, anhydrous citric acid (192 g., 1.00 mole), m.p. 153°, was added in 32-g. portions to fuming sulfuric acid (383 g., 202 ml., 21%) with stirring, the first two cautiously at 0° and the other four at 15-20° during 1.5 hrs. The mixture was stirred 1 hr. at 25°, 3 at 35°, and 17 at 25°. To the stirred, yellow mixture absolute methanol (500 ml.) was added dropwise at -5 to 0° (3 hrs.). The mixture was kept 13-20 hrs. at 25° and added to a stirred mixture of sodium bicarbonate (700 g.), ice (500 g.), and water (200 g.). The precipitated salts were immediately filtered off and washed with 50% aqueous methanol (150 ml.). The slightly alkaline yellow filtrates were extracted with ether (7x400 ml.), the extracts dried (Na2SO4), and the solvent removed on the water bath and then in vacuo. The residual oil, which contained some water, was distilled in vacuo [...]

Do you notice any procedural steps in Findlay's procedure which is not present in the procedure in Organic Syntheses?

Title: acetonedicarboxylic acid from citric acid + H2SO4
Post by: Vitus_Verdegast on December 11, 2003, 11:42:00 PM
Pechmann, Ber. 17, 2542-43 (1884)

(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000476177-file_lcvu.gif)


Experimental part

Anhydrous citric acid is heated with concentrated sulfuric acid on a waterbath until besides the evolution of carbon monoxide a sudden vigorous evolution of carbon dioxide is noted. The reaction mixture is cooled and mixed with water, after which the mixture solidifies to a mass of colorless needles of acetonedicarboxylic acid. The larger quantity of acetonedicarboxylic acid can be extracted from the mother liquor with ether. Its composition was determined by the analysis of the recrystallised compound (from ethyl acetate).

The characteristics of the new compound do confirm the identity of acetonedicarboxylic acid. As a derivative of acetone it reacts with phenylhydrazine.
On heating it decomposes at a temperature somewhat below its melting point into carbon dioxyde and acetone and corresponds in this behavior completely to the monocarboxylic acid of acetone, acetoacetic acid. The melting point, which could not be determined for the aforementioned reason sharply, lies in the neighbourhood of 130°. When acetonedicarboxylic acid is heated with acids or alkalis, or in an aqueous solution, it undergoes the same decomposition. With ferric chloride it gives a violet color which is characteristic for acetoacetic acid.

Title: Acetonedicarboxylic acid
Post by: roger2003 on December 12, 2003, 12:03:00 AM
Pechmann found 1884 small amounts of this acid by heating conc. H2SO4 with dried citric acid and said nothing about the yield.

Findlay pp are producing this acid with Oleum at about
-10° C

Title: True...
Post by: Vitus_Verdegast on December 12, 2003, 12:22:00 AM
..but considering the cheapness and worldwide OTC availability of citric acid and sulfuric acid, even if the yield is really low, this still is a good alternative IMHO.

Maybe it would be a good idea to perform the procedure according to Findlay with conc. sulfuric acid to see what the yield is?

Title: exactly what I was thinking!
Post by: tropine on December 12, 2003, 02:13:00 AM
If infact, conc sulphuric can be used in Findlay's synth for the cyclic b-ketoglutarate product, this would be a tremendously powerful tool in 2-carbomethoxytropine chemistry.  I don't see why it couldn't be used, since at the point where the methanol is added to the oleum/citric acid mixture, the oleum is most likely all converted to conc sulphuric acid by that time.
Title: Pechmann
Post by: roger2003 on December 12, 2003, 11:34:00 AM
Pechmann takes dried citric acid and Findlay pp the monohydrate.

And I dont know what Pechmann 1884 means with conc. H2SO4, but I think it`s not the same like today.

Title: Citric Acid + Slufuric Acid :-)
Post by: politoxicomania on December 16, 2003, 11:18:00 PM
Sulfuric Acid.....

SWIM used this method and observed a yield of 87%
The product is stored at 0°C for weeks.
Title: Did you use conc H2SO4 right out of the bottle?
Post by: tropine on December 17, 2003, 05:26:00 PM
so did SWIM use standard conc H2SO4 right out of the bottle (not fumming?)
Title: Sulfuric Acid from the bottle.......
Post by: politoxicomania on December 17, 2003, 08:53:00 PM
Yes i did. 
The main problem in this reaction is the water in the citric acid and the temperature at which u work.
Use small flasks with dry-ice cooling. Make the citric acid waterfree by drying it in vacuu over sulfuric acid or P2O5 several days. Oleum isnt needed if the citric acid is waterfree. Keep the reaction as cold as u can.
good luck