Natural Science Forum / Chemistry / Organic Synthesis / May 2005

You may really have problem, formyl cloride wants to fall apart on its
own if you dont keep pressure on during the reaction and all the
efforts I have seen indicated it a lot more trouble than its worth.  I
suggest using an ethel ester transesterification at low pressure or
switching to acitalcloride.

I was making formate esters fairly recently and found two viable ways
(I'm sure there are many more...).  Either use formic acid and a
carbodiimide, or make a mixed anhydride of acetic/formic.  There's
procedures out there for both.  Good luck!

James.

dave wrote:

its

I

Yes, I would not recommend formyl chloride because of experimental
inconvenience. My first thought was to suggest a simple formate, like
ethyl or methyl formate, in the presence of a base, something like
NaOEt in ethanol. The problems is that we?ve got the thermodinamics
wrong for the displacement of the alcoxide. The pKa of Meldrums`s acid
must be about 10, while the pKa of an alcohol is about 16-19. In other
words, Meldrum`s acid anion is a better leaving-group than an alkoxide,
which makes us think of formyl chloride which is very inconvenient.

I would suggest an alcoximethylation by reaction with methyl or ethyl
orthoformate, perhaps in the presence of a mild Lewis acid like ZnCl2,
followed by hydrolisys to the aldehyde.

Best regards.

Gabriel Tojo

Prep for mixed anhydride: add slowly 96% HCO2H into equal volume of
Ac2O on cold water bath and let the mixture sit for 3 hours under
baloon (with N2 or Ar) at room temp. Use neat, in excess, without any
base - just add alcohol or amine with cooling. This works very well
even for some very unreactive substrates. No acetylated side-products;
just formyl esters are obtained.

The mix slowly generates carbon monoxide (due to decomposition) and
should not be heated or stored in closed vessels! Use only freshly-made
mix.

This mixed anhydride idea looks very good.

Best regards.

Gabriel Tojo

I just used this mixed anhydride mix 2 days ago -  formylating a very
unreactive aniline. It was all complete in 1 hour at room temp. (I had
to add some sodium acetate solid to it because I had aniline as
hydrochloride salt.) Workup was just evaporation on higvac and
DCM/water extraction. Quantitative yield.