tongqiancao - 15-6-2007 at 04:54
I want to attain "(E)-3-(4-(benzylthio)phenyl)acrylic acid"
using the reaction as my attachment shows.
It's just a substitution reaction. But I only get a untolerated yield 20% after column chromatography purifying.
Only finded I acetone can good solve the raw material "(E)-3-(4-mercaptophenyl)acrylic acid", but the product seem to not easy to solve in different
solvents. This make a little difficult to purify it with column chromatography. Because there are some byproducts.
Attachment: q.cdx (7kB)
This file has been downloaded 704 times
Nicodem - 16-6-2007 at 12:36
Use water as solvent with 2 eq. of NaOH as base. Additionally, due to the low solubility of BnCl in the aqueous phase, you will need either very
intense stirring conditions or a cosolvent or a phase transfer catalyst. Personally, I would opt for a cosolvent like acetonitrile or ethanol in a 1:1
ratio with water. Try first at room temperature and heat only if the reaction is to slow. This way you will avoid the formation of the numerous side
products that can arise from your current method (which is, by the way, totally inappropriate for this reaction). The added BnCl phase should slowly
dissolve as the sodium salt of the product should be soluble in the aqueous phase (unless oversaturated). Some side products might be insoluble in the
aqueous phase, but you can remove these and the excess BnCl by washing the reaction mixture with CH2Cl2. Then acidify. If a solid precipitates filter
and recrystallize. If an oily product precipitates extract and do the chromatography or try to induce crystallization by whichever means.
tongqiancao - 16-6-2007 at 19:38
A cosolvent like acetonitrile is being tried and seem to work. Ethanol have already failed.
Thank you very much. I think now the only problem is time.
I have used EtoAc and EtoEt as extractant but the results were not good.Maybe CH2Cl2 will effect.
At first I dare not to use water,because BnCl ->BnOH. Now I use excess BnCl.
Nicodem - 17-6-2007 at 02:32
The reaction of BnCl with water is extremely slow and is of no relevance here. H2O is way less nucleophilic than, for example, Et3N that you were
using as a base previously. Water is the only practical solution in the case of your reaction since you can form the dianion of your cinnamic acid
which is needed for the selective S-alkylation and prevention of side products formation (like the products from Michael addition,
O-alkylation, etc). The only minor inconvenience is the insolubility of BnCl in aqueous phases, hence the use of a cosolvent. Do not use more than
about 10% excess of BnCl or else you might get lower yields due to the benzyl p-benzylthiocinnamate formation. It is also advisable to use
inert atmosphere to prevent dithiol formation.