[Alcane2214]

Hi guys

As always, thank you for your quality answers 

I have a relatively ambarassing problem. I need to do an aldol condensation on an aromatic compound. My compound have aldehyde and ester fonctionnal groups and when i do the synthesis, i got almost no product. I have it on TLC and i mostly recover my starting material, even if i have 2 new spots for the reaction products.

I dissolve my thiamine (catalyst) on water/Methanol (1:2) and add NaOH at 0degree. I used to believe that i added NaOH to thiamine too fast, but i have done it slowly,drop by drop, with some time between each of them. There is no improvements.

does anybody have a suggestion on what am i doing wrong here?

Thank you

[chenbeier]

It is to less information, which compounds you talking about?

[Alcane2214]

Hi

I am trying to make the dimethyl 4,4'-(2-hydroxyacetyl)dibenzoate from his monomer, the 4-methylformylbenzoate

Even with the procedures i find in the internet, it is not working. I don't know what to do

Thank you

[hollytara]

Just to clarify - you are actually doing a benzoin condensation - connecting two benzaldehydes - not an aldol - where an enolate reacts with an aldehyde.

[Vidya]

Is this your starting material.
Please check the attached file

[rolnor]

Alkane, your naming of the compounds are confusing. Also I se some risc of hydrolysing the ester but this is maybe not a major problem.

[Alcane2214]

Hi everyone.

yes, my starting material is the methyl 4-formylbenzoate, as vidya said. I use the procedure here to do this reaction. I tried to add the NaOH slower and to heat a little more, but nothing to do. This procedure does not work for me and this is strange

Thiamine hydrochloride (1.80 g, 5.35 mmol) was dissolved in 5 mL of water and 15 mL of methanol, using an ice bath was added dropwise 5 mL of NaOH solution (2M) for a period of 10 minutes. To this solution add 4-formyl benzoate (14.9 g, 91 mmol). The mixture was heated to 60 °C for about 15 minutes and reflux conditions for 1 hour. The mixture was cooled to room temperature and the white solid is filtered. Yield: 12.3 g (82%).

Thanks

[Vidya]

Is this your starting material.
Please check the attached file

But this molecule has no alpha hydrogen.So I am wondering how can we can aldol product.There is some information which is not correct.

[Alcane2214]

Hi guys

Yeah. the aldehyde fonction should do the condensation. I was wrong, it IS a benzoin type condensation. This synthesis has been done many time, so there is probably something i do wrong.

Is this type of synthesis really sensitive about something? temperature of NaOH addition? NaOH addition rate? Both? Is there anything else i should pay attention?

Thank you, once again

[kriggy]

Maybe you are getting ester hydrolysis. I mean, 60°C with NaOH is no joke for methylesters.. My methylesters were hydrolyzed with hydroxide at room temperature and at elevated temperatures even with carbonate.

Also, maybe you are not using enough hydroxide? I think you are adding less then 1eq of hydroxide to the thiamine (by my calculation you are using 5.4 mmol of thiamine but only 0.01 mmol of hydroxide. I think in this case, you are not generating enough of the heterocyclic carbbene to catalyze your reaction.

OR you might be getting some imine formation bentween thiamine and your aldehyde.

My suggestions:
a) try your conditions but leave it for longer time
b) try more hydroxide
c) try different base like tBuOK or TEA

btw, if you are just reproducing a procedure from literature, take if with grain of salt.

[rolnor]

Kriggy, can you show how you get this amount of NaOH?

[hollytara]

You may want to go old school on this.  The hydroxide is supposed to neutralize the thiamine hydrochloride catalyst, releasing free thiamine.

But the original way of doing this benzoin condensation used sodium cyanide as the catalyst.  Thiamine is the less toxic alternative. 

My understanding of that reaction is that the conditions are water/alcohol mixed solvent (if you use methanol since you have amethyl ester any transesterification is moot), and about 0.1 - 0.2 equivalents NaCN (handle with care!).  No base needed.  The reaction was developed in the 1830's so you can surely find procedures. 

My other suggestion is to go milder on your base. Use sodium bicarbonate instead of the hydroxide. 

[kriggy]

Kriggy, can you show how you get this amount of NaOH?

Oh, never mind, I screwed up my units its obv 0.005 L * 2M = 0.01 mol = 10 mmol

Anyway, doesnt the reaction require slightly acidic conditions?

[hollytara]

There are some benzaldehydes that won't do a benzoin.  If it is too electron rich, it can't act as a base.  If too electron poor, it can't act as an acid.  The ester is an electron withdrawing group, so it could be too electron poor.