[JeffG]

Hello.

After some trials I have problems with the condensation of 2-chlorobenzaldehyde with different alpha hydrogens under basic condition. I have tried with 2-fluorobenzaldehyde without any problems. I cant see what the difference should be. On the MSDS for 2-chlorobenzaldehyde it states that it is corrosive whereas for the 2-fluorobenzaldehyde nothing about that is said.

First why is there this difference? I mean they both contain a halogen in the ortho position. I have tried to make some differences in the amount of catalyst used, but this made no difference. I have tried to make the condensation with malonic acid and nitroethane. I found a reference on the internet where they used nitroethane and o-chlorobenzaldehyde in the production of an insectcide and tried to copy that way. But still no water was formed even after 14 hours reflux and nothing precipitated in the freezer as they did in the article. They used n-pentylamine, and absolut ethanol as the solvent in the article and I tried with n-butylamine and absolute ethanol. But I guess this should not give the difference. It also won´t work with malonic acid, which usually works with base.

Any suggestions why this is so strange?

Thanks in advance.

[sjb]

I suppose sterics may have a part to play, as the fluorine atom is probably only about the size of a hydrogen, but chlorine is much larger, for one

[OC pro]

What you observe is the so-called "ortho-effect". I would expect the 2-chlorobenzaldehyde to react a bit slower so maybe more drastic conditions are needed. I would use toluene and Dean-Stark apparatus. Oilbath temperature should be around 150°C. You can also add catalytic amounts of acid (e.g. camphorsulfonic acid) to activate the aldehyde. Then you will definitely observe conversion to the product.

[orgopete]

I am inclined to think it is not a problem with o-chlorobenzaldehyde per se.

I note these successful reactions:
http://pubs.acs.org/doi/abs/10.1021/ja01305a045
http://www3.interscience.wiley.com/journal/112723846/abstract?CRETRY=1&SRETRY=0 (pretty good yield reported here)

Since repetition of other lit reactions fail, I'd check on the starting material (or purchase a fresh bottle).

[JeffG]

Thank you for all these great replies.

[discodermolide]

Hello.

After some trials I have problems with the condensation of 2-chlorobenzaldehyde with different alpha hydrogens under basic condition. I have tried with 2-fluorobenzaldehyde without any problems. I cant see what the difference should be. On the MSDS for 2-chlorobenzaldehyde it states that it is corrosive whereas for the 2-fluorobenzaldehyde nothing about that is said.

First why is there this difference? I mean they both contain a halogen in the ortho position. I have tried to make some differences in the amount of catalyst used, but this made no difference. I have tried to make the condensation with malonic acid and nitroethane. I found a reference on the internet where they used nitroethane and o-chlorobenzaldehyde in the production of an insectcide and tried to copy that way. But still no water was formed even after 14 hours reflux and nothing precipitated in the freezer as they did in the article. They used n-pentylamine, and absolut ethanol as the solvent in the article and I tried with n-butylamine and absolute ethanol. But I guess this should not give the difference. It also won´t work with malonic acid, which usually works with base.

Any suggestions why this is so strange?

Thanks in advance.

This is a simple Knovenagel reaction, should work with ammonium acetate and a bit of acetic acid