Because of the low yields reported by people on the condensation of nitroethane and p-F-Benzaldehyde, I decided to try a few tweaks to boost the yields. Unfortunately it did not help , but i'll post this writeup anyway as failures can be just as helpful as success stories, such that fellow researches does not waste time on the same.
General theory:
p-F-benzaldehyde is condensed with nitroethane in the standard Henry reaction. SpicyBrown and others who has tried this using butylamine as the catalyst never reported more than 55% yield, which is somewhat on the low side, considering the price of this particular benzaldehyde. Aqueous methylamine seemed to perform even worse. In the henry reaction one mole of water is formed per mole of beta-nitropropene formed. In order to push the equilibrium as far as possible to the right, i decided to test how anhydrous conditions would perform by removing the water during the reaction as it is formed, using molecular sieves. As catalyst a 2M ethylamine in THF solution was used (no particular reason for this - it was simply available at the time). The whole reaction is run in IPA (3A sieves should be compatible with everything here, AFAIK...) One mole of water is formed per mole of benzaldehyde used (assuming quantitative yields of course). One mole of water equals 18 grams. 3A molecular sieves are able to bind 21% wt/wt of water per mass of sieves used. Thus 86 g's of 3A mol. sieves are required per mole of substrate. Assuming that a little water is present in the reactants 100 g's is probably better to use.
Experimental
Reagents used:
- 12,4 g (100 mmole, MW=124 g/ mole) p-fluoro-benzaldehyde
- 8,25 g (110 mmole, MW=75 g/mole) nitroethane
- 10 mL (20 mmole, MW=45 g/mole) 2M EtNH2 in THF
- 25 mL 99% IPA
- 10.5 g 3A mol. sieves
The Reaction:
The benzaldehyde was mixed with the nitroethane in a erlenmeyer flask, whereafter both of the measuring beakers where rinsed with 12.5 mL's IPA and poured into the reaction flask. 10 mL 2M EtNH2 in dry THF (smelly crap) was added using a glass pipette. Finally the molecular sieves where added in one portion. The solution was totally transparent and colourloess at this point. A magnet was dumped into the mixture, and the whole shebang was lowered into an oil bath at 60 degrees and stirred gently, to avoid destroying the sieves.
- At t+10 min: The reaction mixture had become canary yellow but still reeked of benzaldehyde.
- At t+30 min: The color was somewhat darker and the benzaldehyde smell was only faint.
- At t+60 min: The colour did not go any darker and the benzaldehyde smell was nearly gone.
- At t+120 min: No change from t+60
- At t+180 min: No change from t+60, 1,35 g's 85% formic acid added to neutralize the catalyst.
Flask removed from oil bath. - At t+181 min: Mixture filtered.
The flask was removed at t+180 mins, and the post reaction mix was suction filtered while still hot. The filtered sieves where rinsed with a minimal amount of IPA. The sieves where put in a brown jar for future regeneration.
The flask containing the product was placed in the freezer over night. In the morning the bottom of the flask was covered in pretty canary yellow needle like crystals. A few of the crystals where removed from the flask and saved in the freezer in case a later crystallization would prove difficult. Most of the solvent where stripped from the post reaction mixture on a waterbath under aspirator vacuum. A solid cake remained after refridgiating. This was recrystallized in boiling IPA and filtered yet again.
The yield was a mere 6.61 g of p-fluoro-nitropropene, which corresponds to a 38% molar yield.
Conclusion:
Seems that this particular molecule wants a long alkyl chain on the catalyst during the condensation. Even if the anhydrous conditions did help, it sure wasn't alot. Oh we'll it's not a complete waste as there has been previous discussions here on the-hive if more dry conditions for the Henry condensation will improve the yields. We'll this experiment has shown that if they do so, it is very miniscule.
