psyx7 (Stranger)
01-23-04 04:28
No 484108
       Darzen condensation for halobenzaldehydes     

Will the Darzen condensation work with halogenated benzaldehydes, or would the halogen interfere with the rxn?

ie. would 4-bromo-2,5-dimethoxybenzaldehyde + 2-ClPrOOMe give 4-br-2,5-dmp2p? Or is that just wishful thinking? crazy

Thanks in advance!
-psyx 		 
 
 
 
    Rhodium
(Chief Bee)
01-23-04 18:15
No 484207
       Green Light     

Mechanistically speaking, there would be no problems associated with using a substituted aryl halide as substrate. The reaction would be slower than that with p-dimethoxybenzene itself (due to the deactivating effect of the halide) but it would be fater than with benzene itself (due to the activating effects of the methoxy groups).

So - go ahead, and please report your results.
The Hive - Clandestine Chemists Without Borders 		 
 
 
 
    Nicodem
(Hive Bee)
01-23-04 21:05
No 484234
       The reaction would be slower than that with...     

The reaction would be slower than that with p-dimethoxybenzene itself (due to the deactivating effect of the halide) but it would be fater than with benzene itself (due to the activating effects of the methoxy groups).

Rhodium, I don’t agree with that. According to A guidebook to mechanism in organic chemistry. (Peter Sykes, 6th edition): “…the influence of electronic affects alone [on the reactivity of benzaldehides toward the nucleophiles] may be seen in the series of compounds ( p-X-C6H4-CHO ).
Relative rates: X= NO2 > H > MeO.”

Then it goes on explaining how electronwithdrawing groups on the bezaldehide increase the electrophilicity of the carbonyl group, while the electrondonating groups (R-O- etc.) reduce it. Therefore a halogen para to the aldehido group increase its reactivity toward nucleophiles while the methoxies reduce it.
As an example, here are the cianohydrine formation equilibrium constants (K) for the three above-mentioned benzaldehides:
p-NO2-C6H4-CHO     K=1420
C6H5-CHO            K=210
p-MeO-C6H4-CHO      K=32
Well, luckily the Darzen rxn is not as reversible as cianohydrine rxn.

Psyx, god luck with your synt.
“The real drug-problem is that we need more and better drugs.” – J. Ott 		 
 
 
 
    Rhodium
(Chief Bee)
01-23-04 21:52
No 484240
       Out of my mind. Back in a few minutes.     

You are fully correct Nicodem, I had a brain outage and imagined the wrong mechanism. Sorry for my misinformation.
The Hive - Clandestine Chemists Without Borders