2
$\begingroup$

I recently studied carbohydrates. I was taught that fructose on oxidation with strong oxidizing agents like concentrated $\ce{HNO3}$ yields glycolic acid and tartaric acid along with trihydroxy glutaric acid. Though I am confused why glycolic acid is formed instead of oxalic acid (since the terminal $\ce{-OH}$ should also have been oxidized) I am also satisfied that oxidation of the keto group in fructose breaks it off into 2 carboxylic acids and yields a 2 carbon(glycolic) and a 4 carbon(tartaric) containing acid.

But I am very much unable to figure out the formation of trihydroxy glutaric acid by oxidizing fructose since its a 5 membered carboxylic acid and in no reaction I know did I ever come across such breakage of ketones in 6=5+1. Some sources even cited the formation of trihydroxy butyric acid along with oxalic acid where I couldn't understand why tartaric acid wasn't formed by oxidation of the terminal $\ce{-OH}$ group.

Hence it will be very helpful if anyone can provide an insight into how do these products form.

Thank you.

$\endgroup$
  • 1
    $\begingroup$ A reference to your sources would be useful. HNO3 would oxidize both C1 and C6 to form carboxylic acid groups. α-Ketoacids undergo oxidative decarboxylation. Hence, the trihydroxyglutaric acid. Be aware that not every molecule of fructose is oxidized in the same way. Some oxidation pathways presumably lead to glycolic acid. $\endgroup$ – user55119 Sep 14 at 20:02
  • $\begingroup$ Well here's a few links chem-brains.blogspot.com/2012/04/biomolecules-five-marks.html, image.slidesharecdn.com/…, to name a few. Well can you elucidate the oxidative decarboxylation of alpha ketoacids ? What I saw at most sites talked about formation of tartaric and glycolic acid and hence I would like to ask why the terminal C doesn't get oxidized in glycolic acid to form oxalic acid. $\endgroup$ – Sir Arthur7 Sep 16 at 17:25
  • $\begingroup$ Trihydroxyglutaric, tartaric & glycolic acids are some of the products isolated from nitric acid oxidation of fructose. books.google.com/…. Study the Krebs cycle for the oxidation of alpha-ketoacids. Oxalic acid may well be formed and oxidized to CO2. $\endgroup$ – user55119 Sep 16 at 19:58
  • $\begingroup$ Ok so there are many possible products, right? But can you post the mechanism for oxidative decarboxylation of alpha ketoacids? I can understand that the COO- group in a pyruvate (let's say) will cleave away giving out CO2, but that would leave behind an unstable carbanion(CH3CO-), is that formation favorable? Also it has to convert into a carboxylic acid(a required addition of OH+), does that occur by the attack of H2O? Anyways its hard for me to find convincing answers. Would be great if you could elaborate. Thank you. $\endgroup$ – Sir Arthur7 Sep 17 at 4:21
  • $\begingroup$ I'll post an answer. It is not an acyl anion but rather a cation. $\endgroup$ – user55119 Sep 17 at 18:56
2
$\begingroup$

Sir Arthur7: From your comments you appear to know how to liberate CO2 and a proton by pushing arrows as illustrated by the blue arrows in generic α-oxoacid 1. You are correct in discrediting acyl anion 5 for two reasons. First, it is unstabilized and secondly, its protonation would provide an aldehyde, not a carboxylic acid. So why not push the red arrows in 1 to generate an acyl cation equivalent? The downside is that you don't want hydride as a leaving group. The solution is to replace the acidic hydrogen of 1 with a species that likes electrons, e.g., a high oxidation state metal or a hypervalent, non-metallic atom. Certainly, the nitrogen of HNO3 fits the bill where M = NO2 in structure 2. In this instance, nitrogen is n = 5 in structure 2 and 4. Bear in mind that for the purpose of electronic bookkeeping, transformation of the acyl anion 5 to a acyl cation 2 is a 2-electron oxidation while species M undergoes a 2-electron reduction. ---continued---

enter image description here

Moriarity, et. al.,1 have effected this oxidative decarboxylation with the hypervalent iodine species, iodosobenzene 7. The path of the red arrows within the brackets provides a step-by-step version of their mechanism using α-oxoglutaric acid 6.2 Notice that mixed "anhydride" 8 is the operational equivalent of species 2. The authors propose the formation of cyclic intermediate 9 that collapses to 12 with loss of CO2 and a proton. [Note: Structure 10 is drawn for clarity. Collapse of 9 to succinic acid 12 is proposed as concerted.] The collapse of structure 8 might be thought to follow the course of the green arrows but because the reaction is conducted in anhydrous dioxane, it is unlikely that an acylium ion is formed directly because it is apt to form succinic anhydride. See examples studied in the chart below.

enter image description here

The Moriarity paper describes the iodosobenzene oxidation of mandelic acid to benzaldehyde and CO2. See if you can now write a mechanism for this reaction.

1) R. M. Moriarty, S. C. Gupta, H. Hu, D. R. Berenschot, and K. B. White, J. Am. Chem. Soc., 1981, 103, 686. https://pubs.acs.org/doi/10.1021/ja00393a040

2) α-Oxoacid is preferred over α-ketoacid. The term keto (C=O) overcounts carbons. Oxo = (=O).

$\endgroup$
  • $\begingroup$ Thank you so very much. I got my concepts cleared, got to learn new things. Well as you mentioned, in the conversion of mandelic acid to benzaldehyde how does the -OH group get oxidized to -c=0? Does it occur in the presence of iodosobenzene itself? I could figure out the rest of the mechanism. Thanks a lot again. $\endgroup$ – Sir Arthur7 Sep 18 at 6:13

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.