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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: aranel on January 10, 2011, 08:27:06 AM

Title: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: aranel on January 10, 2011, 08:27:06 AM
i have a compound which is base labile, and i need a way to oxidize the primary alcohol up to a carboxylic acid under neutral or acidic conditions. among the chromium based oxidizing agents, i tried PDC in DMF, which did not really work, plus i find the workup afterwards nasty. 

any ideas?  ???
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: nox on January 10, 2011, 11:10:01 PM
1. TEMPO based oxidations (Here's a very nice prep from OrgSyn http://www.orgsyn.org/orgsyn/orgsyn/prepcontent.asp?print=1&showprint=1&prep=v81p0195). TEMPO is pretty pricey though.

2. Heyns Oxidation using platinum black and oxygen. However you need to run this reaction in at least neural (pH 7) if not very slightly basic (pH 8 ) conditions to get reasonable rates and yields. Bicarb is commonly used as a base -- how sensitive is your substrate?

3. Oxidation to the aldehyde with Dess-Martin Periodinane, then Pinnick Oxidation to the acid. This is more roundabout, but probably the mildest out of the 3.
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: aranel on January 11, 2011, 09:14:31 AM
ah cool!

i thought tempo oxidized only up to an aldehyde. - i'll see how generous my boss feels himself, and go for this one. looks like 1 g is around 45€.

as for Heyns, i'd rather try it if nothing else works. just to be on the safer side.

Although it adds up one more step to oxidize first to an aldehyde, then to an acid, i know my compound is fine with Dess-Martin and Swern oxidations. So i could go for either one - i like Swern better eventhough it's stinky :) then the Pinnick. never tried that one before.

i'll see how it'll turn out. thanks a lot!! 
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: Fleaker on January 12, 2011, 04:01:03 PM
Permanganate?


First thing I'd reach for is the good ol' ceric ammonium nitrate :-)
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditio
Post by: g-bones on January 13, 2011, 04:18:30 AM
1. TEMPO based oxidations (Here's a very nice prep from OrgSyn http://www.orgsyn.org/orgsyn/orgsyn/prepcontent.asp?print=1&showprint=1&prep=v81p0195). TEMPO is pretty pricey though.

2. Heyns Oxidation using platinum black and oxygen. However you need to run this reaction in at least neural (pH 7) if not very slightly basic (pH 8 ) conditions to get reasonable rates and yields. Bicarb is commonly used as a base -- how sensitive is your substrate?

3. Oxidation to the aldehyde with Dess-Martin Periodinane, then Pinnick Oxidation to the acid. This is more roundabout, but probably the mildest out of the 3.

I agree with oxidation to the aldehyde then Pinnick oxidation.  common place in our group, never seems to let us down :-P
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: samir on January 25, 2011, 11:19:58 PM
Simplest would be to use warm/ hot potassium permanganate.
Fast reaction / no messy residues / solid MnO2 as a bye product.
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: nox on January 26, 2011, 10:49:00 PM
KMnO4 is good on simple substrates, but you should never try it on anything even moderately complex (or of significant value to you). Plus the problem with KMnO4 is if you have a 1,2-diol (glycol) in your molecule, more often than not it will lead to glycol cleavage.
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: movies on January 28, 2011, 12:00:12 PM
How about Jones' reagent? (CrO3, H2SO4, acetone) 

Conditions are pretty harsh, but it's a really easy reaction to perform!
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: aranel on January 31, 2011, 10:47:27 AM
i have tried pdc - pyridinium dichromate - which did not really work. that's why i didn't want to go for another chromium based reagent.

i've ordered tempo. will try that one first.  8)
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: movies on February 01, 2011, 01:01:16 PM
I believe Jones' reagent is quite a bit more reactive than either PCC or PDC, both of which are buffered.  PDC tends to give the aldehyde, not the carboxylic acid, as I recall.

Anyway, I am a big fan of the TEMPO oxidation methods as well, so good luck!
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: stewie griffin on February 03, 2011, 10:45:37 AM
A modified Ley oxidation: TPAP, NMO, and water will give the acid.
Normal TPAP/NMO with molecular sieves gives the aldehyde, but you add water and you can get the acid.
Title: Re: primary alcohol oxidation to a carboxylic acid under neutral/acidic conditions?
Post by: movies on February 03, 2011, 11:50:58 AM
Hehe – I was talking to a buddy of mine from the Ley group and he reminded me of the TPAP oxidation (for something unrelated) and I thought I would add it to the list of suggestions here.  Stewie beat me to it though!