Sciencemadness Discussion Board

Oxidation of aldehydes to carboxylic acids?

Refinery - 6-7-2020 at 12:08

I found no definite discussion on oxidation of aldehydes into carboxylic acids on the forum, although it being quite an interesting topic on it's own.

I found such methods as:

- Silver oxide
- Chromium (VI)
- Potassium permanganate
- Manganese dioxide (with CN catalyst)
- Hypochlorite
- Oxone (in DMF)
- Sodium perborate w/ acetic acid (peracid)
- Hydrogen peroxide
- Molecular oxygen with catalyst (radical-chain reaction by peroxy-acid)

+ A plethora of more exotic catalytic oxidations

Of these, some might be less viable in practice, but of most interest would probaly be the lower ones of the list.

Has anyone actual experience with aldehyde oxidations? Literature has vast amount of data, but large portion of it is more of theory and reaction schemes. I'm sorry for not being able to give any input myself, having no experience on this reaction, at least for now, but I was hoping for a little discussion with the less uninitiated.

karlos³ - 6-7-2020 at 12:23

I can vouch for the use of oxone in DMF.
That works quick and clean, even like an actual charm, and the acid can be precipitated aqueous afterwards(of course only if its insoluble in the water).
Very simple and good method, very cheap and easy.

Although I have to add, I only tried this on a single substrate so far, but on the other hand, I tried the oxidation of the same substance with KMnO4 in a biphasic system, and the yield was much, much lower and the product less clean, also, the whole process took longer and was dirtier.

Might have to add more to this topic in the future, I still have an assortment of a few aliphatic straight chain aldehydes in storage, that are a few years old already and I lack any useful application for them.
I think the carboxylic acids are more useful to me, so I plan to oxidise them at some point in the future, or more precisely, the parts which haven't already autooxidised to the respective acid.

Refinery - 6-7-2020 at 12:59

The procedure appears as following:
Quote:

General Procedure for Oxidation of Aldehyde to Carboxylic Acid: The aldehyde (1 equiv)
was dissolved in DMF (0.1 M). Oxone (1 equiv) was added in one portion and stirred at RT for 3 h. The reactions were monitored by TLC and GC analysis. 1N HCl was used to dissolve the salts and EtOAc was added to extract the products. The organic extract was washed with 1N HCl (3x) and brine, dried over Na2SO4, and the solvent was removed under reduced pressure to obtain the crude product. Products were purified by silica gel column
chromatography.


Considering that DMF is high BP (150C) specialty solvent and it would be needed in such quantity (0.1M, or 0.1mol of aldehyde per liter of dmf?), could it be substituted with something else? 1,3-dioxolane? 1,4-dioxane?

karlos³ - 6-7-2020 at 13:27

DMF is polar aprotic, you can only replace it with something having similar properties like it.
And no, DMSO is out of question for this reaction, as it is vulnerable to oxidation itself.
Maybe NMP or DMAc will work, with the former being quite available OTC?
Also, acetonitrile might work too.

I don't know, what speaks against simply purchasing the DMF, cheap as it is?
You know that modifying anything that important as the solvent here will likely result in a less favorable outcome if it even works at all?

JJay - 6-7-2020 at 18:20

Oxidizing an aldehyde to a carboxylic acid is one of the easiest functional group transformations. Generally, the thing to worry about is to avoid oxidizing other functional groups. Chrome VI will convert aldehydes to acids nicely in aqueous acidic conditions. Manganese oxidizers will do it too, and they're more environmentally friendly and less toxic, but they also tend to attack more functional groups, including some carbon chains.

As a side note, DMF doesn't look like it would be hard to make, but the easy, amateur-accessible route requires dimethylamine. Dimethylamine is also amateur-accessible, but none of the preparations are incredibly convenient.

DraconicAcid - 6-7-2020 at 18:41

Sodium chlorite in aqueous isopropanol (sodium dihydrogen phosphate and hydrogen peroxide are also needed) works well, too. I know there's a name for that oxidation, but I can't recall it.

JJay - 7-7-2020 at 04:56

Pinnick oxidation?

DraconicAcid - 7-7-2020 at 08:41

Yes, that one.

JJay - 7-7-2020 at 11:24

Are there any selective aldehyde oxidation reactions that work generally and don't oxidize primary and secondary alcohols? The only selective aldehyde oxidation reaction I can think of offhand is the Cannizzaro reaction, and it can't oxidize aldehydes with alpha hydrogens.

Refinery - 7-7-2020 at 11:51

Probably oxidation by molecular oxygen (air) using catalyst. The documents I've seen warrant high yields, simple catalysts and solvents and conditions that are easy to scale both ways.

They probably won't work generally, but the basic principle does. Oxidation energy of aldehydes is designated to be very low, compared to decarboxylation energy.

DraconicAcid - 7-7-2020 at 12:05

Quote: Originally posted by JJay  
Are there any selective aldehyde oxidation reactions that work generally and don't oxidize primary and secondary alcohols? The only selective aldehyde oxidation reaction I can think of offhand is the Cannizzaro reaction, and it can't oxidize aldehydes with alpha hydrogens.

The Pinnick oxidation won't affect secondary alcohols (unless I'm doing it wrong), since I've been using isopropanol as the solvent.

JJay - 7-7-2020 at 12:31

Quote: Originally posted by DraconicAcid  
Quote: Originally posted by JJay  
Are there any selective aldehyde oxidation reactions that work generally and don't oxidize primary and secondary alcohols? The only selective aldehyde oxidation reaction I can think of offhand is the Cannizzaro reaction, and it can't oxidize aldehydes with alpha hydrogens.

The Pinnick oxidation won't affect secondary alcohols (unless I'm doing it wrong), since I've been using isopropanol as the solvent.


I think that would work for scavenging chlorous ions before they could react with the double bond in, for example, cinnamaldehyde if oxidizing to cinnamic acid. Does the isopropanol effectively prevent side oxidations if oxidizing glucose to gluconic acid or if oxidizing mandelic aldehydes (such as this one: https://pubchem.ncbi.nlm.nih.gov/compound/3-Methoxy-4-hydrox...) to mandelic acids?

DraconicAcid - 7-7-2020 at 13:12

I don't know- I've been using hydrogen peroxide as the hypochlorite scavenger.

I generally use this method: http://www.sciencemadness.org/talk/viewthread.php?tid=12746#...

(I've been told that I'm doing it wrong, but I haven't heard any suggestions for fixing it.)

[Edited on 8-7-2020 by DraconicAcid]

JJay - 7-7-2020 at 18:57

Quote: Originally posted by DraconicAcid  
I don't know- I've been using hydrogen peroxide as the hypochlorite scavenger.


I can't remember the last time I wanted to oxidize an aldehyde to a carboxylic acid, but I'll definitely have to give Pinnick oxidation a try.