I am currently attempting to generate an arrow pushing mechanism for the oxidation of glucose to gluconic acid using Fehling's solution. My original thought was to go the route of alcohol oxidation using acidified dichromate where the alcohol attacks in and loses the H using a E2 mechanism.

In the aldehyde oxidation, I would have a hydroxide ion attack prior to the H bond collapse leaving an extra electron on the Cu from the $\ce{C-\mathbf{O-Cu}}$ bond resulting in reduction of $\ce{Cu^2+ -> Cu+}$. Which would satisfy the observed empirical data. After an attempt I googled the mechanism finding very little real information.

A post on this very site suggested the mechanism proceeds via enolate formation followed by single electron transfer with $\ce{Cu^2+}$. Unfortunately, there is no elaboration on this or a source, I also can't find a source online which corroborates this mechanism. Does anyone have a good source for this?


The exact nature of the mechanism is unknown

Be aware that some organometallic chemists consider arrow-pushing mechanisms inadequate/inappropriate for a variety of reasons (including the depiction of single electron transfer). For example, the arrow-pushing mechanisms we draw with alkyllithiums are incomplete in that they do not account for the oligomeric nature of the reagent.[2]

The elements which are known:

  • The aldehyde or α-hydroxyketone must be enolizable. The enolate tautomerization of reducing sugars is discussed in McMurray[3]. This is common to the Benedict’s test mechanism as well.
  • The rate of enolization determines the rate of oxidation J. Am. Chem. Soc. 1970, 92, 537
  • Cu(II) has long been known to mediate oxidative coupling of enolates by a radical mechanism J. Am. Chem. Soc. 1971, 93, 4605. Mechanistic studies point to a metal-chelated single-electron-transfer process.5
  • The active species is the metastable [Cu(tartrate)2]6- ( Eur. J. Inorg. Chem. 2016, 1798).

Drawing one plausible mechanism

  1. Convince yourself that the Cu(II) complex is a d9 17-electon complex. That suggests you could plausibly draw an inner-sphere or outer-sphere mechanism.
  2. For the inner-sphere mechanism: coordinate the aldehyde, and generate the enolate (considering C-vs-O coordination and necessity of ligand-slip).
  3. Form the hydrate of the C-bound enolate, then homolyze the bond to form an organic radical and Cu(I).
  4. A second molecule of Cu(II) oxidizes the radical to the cation, which gets quenched the elimination of H from the hydrate to generate the enol form of the carboxylic acid.

For the basics of an outer-sphere single electron transfer see Mark Vander Wal’s Basics of Electron Transfer

[2]: Advanced Organic Chemistry: Part A: Structure and Mechanisms, Carey & Sundberg, p. 413. [3]: Organic Chemistry: With Biological Applications, McMurry, p. 758


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.