Advice please- Darzen condensation faux-pa

[SpicyBrown]

SWIM made an absent minded mistake in a dream which is still in process.  SWIM is dreaming about the conversion of 4-fluorobenzaldehyde to the corresponding phenylacetone using the darzen condensation, primarily based on the procedures posted by Barium. Here's the dilema, any quick replies of advice would bee greatly appreciated.

SWIM dissolved the proper amount of freshly cut sodium metal in anhydrous methanol to prepare a solution of sodium methoxide. Meanwhile, a mixture of methanol, the benzaldehyde, and methyl 2-chloropropionate were stirred in a 3 neck RBF fitted w/addition funnel and thermometer. SWIM's stupid error was using 0.864ml of benzaldehyde instead of the proper 8.64ml. A very absent-minded mistake.  So, SWIM charged the addition funnel w/the methoxide solution, and began adding slowly, maintaining the temp under 15C.  After about half the methoxide solution had added, the reaction mixture became white (it was previously clear), as if a suspension or colloid had formed.  After the methoxide solution was fully added, the ice bath was removed and SWIM let it warm up to room temp.

Then SWIM realized the absent minded mistake, panicked and added the remaining 7.78ml 4-fluorobenzaldehyde in hopes the reaction may still work.

SWIM's concern is that, without the more reactive benzaldehyde around, the anion from the reaction between the methoxide and haloester may react with more haloester (the haloester was supposed to be present in roughly 0.5molar excess to the benzaldehyde) forming a byproduct and essentially making the later addition of the benzaldehyde pointless.  The remaining benzaldehyde was added about 30 minutes or so after the methoxide solution was added, which took about 20 minutes itself, so about 50 minutes afterthe very beginning of the reaction.

Do any bees think the reaction may still work, are SIWM's concerns about the haloester anion reaction with other haloester unfounded?

Thanks, your urgent response appreciated!!
-SpicyBrown

[Barium]

I´m sorry but I have no idea really. Perform the workup and see what has happened. Most of the unreacted benzaldehyde can be recovered by extraction after the alkaline hydrolysis has been performed.

[Vaaguh]

I dont think you need to worry about sidereactions, also the fact that the suspension became white is pretty normal as the solubility in methanol (salts!) decreases during the addition.

[Barium]

Any side reaction products between the haloester anion and haloester will follow through the work up - alkaline hydrolysis and acid decarboxylation. If the reaction mixture if made slightly alkaline after the decarboxylation the byproducts, which will be acids, can be trapped as salts in the aqueous enviroment while the ketone is removed by extraction.

[SpicyBrown]

Thank you both for your advice, SWIM will continue onto the hydrolysis and see what happens.

Barium, that makes sense about the byproducts remaining in the alkaline aqueous layer at the end, but why won't they be decarboxylated along with the glycidic acid? Is the glycidic acid just more prone to hydrolysis, with the carboxylic acids resulting from haloester byproducts requiring more vigorous conditions for decarboxylation?

-SpicyBrown

[SpicyBrown]

Well, things seem to have gone well. The rxn mixture was poured into a solution of NaOH and stirred for several hours. It is worth mentioning that at this point the smell was distinctly different than the starting material, which has a very strongly detectable smell.  The alkaline post-hydrolysis solution was diluted until all solids went into solution, and washed with toluene, the toluene was finally extracted with some water. The toluene was rather yellow. The combined aqueous phases were acidifed with HCl until pH of about 5 was reached. The solution began to bubble a bit. SWIM took this to be a good sign- the decarboxylation must be taking place. The solution was heated to 55-60 degrees celsius, and gas evolution continued for about 45 minutes. 

After the solution returned to room temp, solid sodium carbonate was added until a pH of about 9 was reached, some brine was added, and the solution was extracted multiple times with CH₂Cl₂.  The combined organic phases are now drying over Na₂SO₄, in a day or two when SWIM has time to distill he will let everybody know if it still worked out.

-SpicyBrown

[SpicyBrown]

Well, the yield was horribly low. Around 18% of a clear yellow oil, 2.25g from 10g of starting material. Ahh well, these things happen...

... repeatedly, it seems. It will be tried again, with no foolish mistakes. Whether or not the accidental delay in addition of starting aldehyde was the culprit SWIM doesn't know. Time permitting, SWIM may go and check for stuff in the various washes, but doesn't expect to find anything.

-SpicyBrown

[SpicyBrown]

After the general failure described above, SWIM set the ~2g or so of "ketone" aside, thinking eventually another attempt would be made and then the measly 2g's could be combined w/the results from a hopefully-more successful synth.

Anyways, that never happened, and a stoppered flask w/the 2g sat around for about a month. The residue was never distilled for purity. After a month or so SWIM was cleaning some stuff up and picked up the flask.. And was surprised (and a bit dismayed) to see a small mass of white, long needle-like crystals formed out of the yellowish liquid. The crystals did appear to be water soluble.

Any idea what these could be?? They came through an acid/base with CH₂Cl₂.

-SpicyBrown

[psygn]

SWIP encountered a similar unidentified product when attempting to convert 2,5-dimethoxyphenyl-2-nitropropene to the ketone w/Fe-HCl... the unidentified substance formed was a SOLID THAT CRYSTALLIZED. It did form a bisulfite addition product, and had a ketonic aroma. Reduction of this compound w/both Al-Hg and CTH gave no yield of amine