Efficient aldehyde synthesis

[Horza2002]

A lot of my synthetic routes at the moment require me to oxidise alcohols to aldehydes. Until recently, I have been using the Swern oxidation; while this has been working perfectly well, its just too fiddley keep everything at -78^OC and anhydrous as well. I have since found the great hypervalent iodine oxidant 2-iodoxybenzoic acid (IBX); an older version the the Dess-Martin periodate.

 

http://pubs.acs.org/doi/abs/10.1021/ol026427n

 

This reagent is unfazed by air or moisture and is basically insoluble in almost all organic solvents. While this might sound pretty useless, as elevated temperatures, enough is soluble to make this reaction efficient. At the end of the reaction, simple filtration and removal of the solvent is required to give the desired aldehyde in close ot quantitive yields.

 

Anyway, just thought I'd share this!

[hypervalent_iodine]

Always good to see my screen-namesake put to good use. Although it should be said that I in fact use a different hyperiodine complex for a different reaction. Still, I love all hyperiodine complexes equally. They are amazing.

 

A good alternative to IBX that is markedly more soluble is safe IBX, or SIBX. Alternatively, DMSO is a good solvent, as can be oxane in water. DMP, a derivative of IBX, is also a fantastic substitute - unless you have amines or sulfides in your compound (it's pretty functional group tolerant otherwise). DMP is also used to cleave diols, whereas IBX cannot (in excess, IBX will just oxidise both of the hydroxys to carbonyls).

 

I could go on for pages, really.

[Horza2002]

IBX does seem to have a large range of application and its a lot cheaper than the Dess-Martin periodate. DMSO is an ok solvent I have discovered...apart from trying to get rid of it at the ened of a reaction. So far, my only way to do it has been to swamp is with water to make my compound crash out as the DMSO goes into the water. Alterntively I have removed it by vacuum distillation a few times...anyone got ideas of how to get rid of it more easilly?

[Dan_Ny]

I think it depends on the solubility of your aldehyde and its stability towards aqueous conditions (I am not sure about hydrate formation and when that occurs and if it is revesible etc.). In general, to get rid of DMSO is the following (if your product it is considerably more soluble in organic solvents (like ethyl acetate, DCM, diethylether or others)):

 

Take the reaction mixture after completion of the reaction. Add water (or Sodium Phosphate ph7 buffer). Extract a couple of times with a volatile organic solvent (DMC, or one of the above). Wash the organic layer with water two or three times (take 10 times as much water as the amount of DMSO you had in the reaction!!!). DMSO is more soluble in water than in organic solvents. It will be gone.

 

Evaporate organic solvents. Take a crude NMR, you know, column and then stock solution in benze, freezer. The usual procedure.

 

Best,

Dan

Edited March 9, 2011 by Dan_iel

[mississippichem]

Always good to see my screen-namesake put to good use. Although it should be said that I in fact use a different hyperiodine complex for a different reaction. Still, I love all hyperiodine complexes equally. They are amazing.

 

A good alternative to IBX that is markedly more soluble is safe IBX, or SIBX. Alternatively, DMSO is a good solvent, as can be oxane in water. DMP, a derivative of IBX, is also a fantastic substitute - unless you have amines or sulfides in your compound (it's pretty functional group tolerant otherwise). DMP is also used to cleave diols, whereas IBX cannot (in excess, IBX will just oxidise both of the hydroxys to carbonyls).

 

I could go on for pages, really.

 

It is noteworthy that my copy of March's Adnaved Organic Chemistry, an organic reactions reference book that I highly recommend; has almost an entire section devoted to hypervalent iodine reagents.

 

Hypervalent_iodine [the person], it seems you chose your username wisely!

[Horza2002]

Hypervalent iodine compounds are extremely useful...this was just a new reagent I hadn't come across before.

 

In the end, I just washed with water lots of times and then evapourated the residual DMSO. Seemed to work fine...no columns or anything!

[Dan_Ny]

Even though water is very often our worst enemy, it can have it's uses sometimes...

[Porphyring]

You can also use Pyridinium Chlorochromate, it contains chromium ions but it is very effective at oxidizing alcohols to their corresponding aldehydes and hardly ever over-oxidizes to the carboxylic acid.

[Horza2002]

While yes, pyridinium chlorochromate is good at going to the alcohol....its is absolutely horrible to work with. For starters, is is highly toxic..very small amount can cause some very serious sideaffects. Additionally, the reaction can at time be so exothermic that you run the risk of the reaction catching fire (obviously dependning on what solvent it is). We did have an incident with that not so long ago.

 

The byproduct of it is also absolutey horrible. It is a black tarry substance that doesn't dissolve very well in any solvent and also sticks very well to glassware. I have had the unfortunate experience of having to clean glass wear after a PDC reaction...that is the main reason I don't use it.

 

TPAP (tetrapropylammonium perruthenate) is now my new favourite one. It is far more soluble than IBX and you only need a catalytic amount if you use a sarcafisal oxidant, typically NMO (N-methylmorpholine N-oxide). The side products can then very easilly be removed by passing through a plug of silica gel (no more than 2cm high is required). It has the other advantage that it is very cheap. As you only need a catalytic amount of TPAP, and NMO is dirt cheap, it works out as a much cheaper reagent to use than IBX.

 

I've basically spent the week trying out the full range of alcohol-aldehyde oxidants...Overall, while IBX is useful, TPAP is the way forward for me I beleive.