[kriggy]

Hi guys I´ve encountered some problems with my synthesis (the previous atempt described here http://www.chemicalforums.com/index.php?topic=73460.0)

the procedure is:
1 g of the cyclic compound (L1) was dissolved in 70 ml of MeOH and 0,11 g of bromoacetic acid (0,2 eq) in 5 ml of MeOH was slowly added dropwise into the refluxing solution of L1. After the addition was complete, the mixture was refluxed overnight.
The solution was then evaporated to dryness and dissolved in ~5 ml of distiled water and purified on strong anex. The unreacted L1 was elued by water and then by 5%NH₃. After washing the column with water until neutral pH, the product was elued by HCl (1/2 HCl/water).
After evaporation of HCl the product was obtained and characterized by MS and NMR to yield the desired compound.
MS: 310 (m+H⁺), 322 (m+Na+)

1HNMR in CDCl₃

After making Mn complex of this compound, all of it somehow ended on the wall of my fume hood (please dont ask, its embarassing  )
So I did the synthesis again, following the same protocol but got the freaking mixture of compounds..
MS2:

he peaks here are very veird: L1 has MW 251 but its not here, 310 is the desired compound, 561 is L1+the desired compound forming some kind of dimer i guess . When we analyze this peak 561 we got some crazyness too:

1HNMR in DMSO

We are unable to figure out, what caused this mess. Its most likely some mistake in my lab-work. We thought it might be some impurities in anex from previous chromatography, however the previous chromatography done was the 1st reaction (ie. the possible impurities are unreacted ligand or the reacted from previous reaction so this shouldnt make this mess.)
Im running out of time to do this (its not that big of a deal if I cant make this work, but failing so close to the end is frustrating)
Any help apreciated.
thank you very much, I hope I gave enough information for you to thow back any ideas. HPLC will be done on monday

[zsinger]

HPLC would be my recommendation.  Report back to us .

[orgopete]

I suggest just running the reaction again. The step I'd be concerned with is the evaporation to remove HCl. Check the purity of your product after elution. Heating with HCl may result in an elimination, see NMR.

[kriggy]

Can you be more specific about the NMR? My interpretation skills are pretty weak, the only thing I can see there is that there are most likely 3 or more compounds just by the amount of peaks in aromatic region and by elimination you mean like decarboxylation?

[orgopete]

I wasn't trying to be very precise. I simply looked at the spectrum of your product and of the (decomposed?) product. It has several peaks shifted to lower chemical shift. I thought this indicated decomposition. I then worked backwards. What if decomposition had occurred, at what step might this happen? Give up on the mixture. Just run the reaction again. It won't matter if I am right or not, this won't give you the product unless you run the reaction again. Just run it again.

Of the steps in the reaction, I just thought if isolation resulted in an excess of acid and then heating to remove the water could be the key step. I'd be careful in that step. I'm not sure if the procedure was the same. How did you monitor the amount of acid present in the eluent? It wasn't noted in the procedure in the first post. I'm only guessing as to what could have happened.

[kriggy]

Well the product was basicaly elued by HCl mixed with water 1:2 so there was huge excess of acid for sure.

[orgopete]

That is what I was guessing. So this part of the reaction could have differed. I would spot your eluent on a TLC plate and watch for the end of dark spots on plates with a fluorescer and then stop.

[kriggy]

I tried to do that but I couldnt spot my product because the HCl is fluorescent and covers the fluorescence of the product.

[orgopete]

Can anyone help here? I agree that you want to avoid collecting excess acid and eluent.

(I used to use an ISCO detector, so I just watched the UV absorption.)

[kriggy]

ok quick update if you are intersted:
a) HPLC not done yet
b) it seems I managed to get a crystal suited for X-rax from the remnants of the 1st reaction (the one which ended on the wall) which is pretty good. For further bio assay it will require to get the pure compound but I most likely wont do it because I want to switch to organics for masters and that means doing something totaly different.

I told my advisor about the decomposition by heating with HCl and he somehow agreed that it most likely might be it. Its surprising on the other hand, because HCl is normaly used for aminocarboxylic compounds and its volatile - compared to other acids like H₂SO₄ so thank you orgopete for this suggestion.

[AlphaScent]

What is strong anex??

[kriggy]

It is this one
http://www.sigmaaldrich.com/catalog/product/sial/217417?lang=en&region=CZ