[xiaojunzhang]

hi,
I want to synthesize a compound like 3-Thiophenemalonci acid monoethyl ester from 3-Thiophenemalonci acid .before I used 3-Thiophenemalonci acid in a ratio of 1:1 with SOCl2 in  isopropyl ether  and reflux in 2 hours,then added absolute alcohol in a ratio of 1:1 with stir for  1 hour in -30 celsius degree.I got nothing like 3-Thiophenemalonci acid monoethyl ester .could you tell me how I should  do to get 3-Thiophenemalonci acid monoethyl ester in high yield ?

thanks for any *delete me*

[xiaojunzhang]

sorry，it is in 30 Celsius degree after adding alcohol anhydrous.

[sjb]

How do you know you don't have monomethyl ester? Have you added an equivalent of base to mop up the HCl byproduct from the esterification? Are you following an established procedure? What sort of scale are you doing this on - could you for instance treat the malonic acid with diazomethane or similar then do a standard transesterification?

[Smrt guy]

I would say try another method of esterification, like DCC coupling or Mitsunobu conditions.  It will likely be difficult to control mono vs diesterification. 

[orgopete]

I'd be leery of that sustained heating to make a mono-acid acid chloride of a malonic acid. I am also skeptical of making a mono-acid acid chloride itself.

I agree with sjb to try an alkylation type of procedure to make a mono ester, diazomethane, DBU + methyl iodide, or something similar. This will certainly work to at least some extent. The other option is to make the diester through a Fischer esterification and selective hydrolysis. This should be the same as the alkylation.

If the formation of ester or saponification were completely non-selective, then you should have a maximal yield of 50% with your product in a 2:1 mixture with the diacid. If separation is problematic, I'd simply carry on to the next step and try separation there.

If there is some selectivity and you don't mind recycling, the actual yield can be improved by under reaction, separation and recycle.

[xiaojunzhang]

How do you know you don't have monomethyl ester? Have you added an equivalent of base to mop up the HCl byproduct from the esterification? Are you following an established procedure? What sort of scale are you doing this on - could you for instance treat the malonic acid with diazomethane or similar then do a standard transesterification?

I have checked by IR the compound which I have got before, IR spectrum showed that it seemed like 3-Thiophenemalonci acid diethyl ester.
1.According to Example 6 in the patent U.S.ser.No.3853849, I mix 3-Thiophenemalonci acid(9.3g)   with dry isopropyl ether (30ml) treated with thionyl chloride (3.65ml) and dropwise adddimethylformamide (0.2ml) ,then reflux in 2 hours on a 60-centigrade water bath.
2. After  evaporation and dissolution,absolute alcohol(3ml) was added at once and refluxed for afurther 1 hour.
3.through being washed by water and being extracted by methylene chloride,then being evaporation , the solid residue was crystallised from benzene to get a colorless solid.
4.then I checked it by IR.

Please check it and give me some advise!

thank you for any *delete me*

[orgopete]

Okay, so the product is the diester. That is reasonable. Given that the question was, "What formed?" I was fearful that heating a malonic acid could result in decarboxylation, especially if you are getting an unexpected product.

I read the US patent example. That is a reasonable reference as it appears to have been chemistry that was actually done. If you can, I suggest you repeat the patent procedure and make the the phenyl ester. I note they report a modest yield (22%). Also phenyl esters are generally not synthesized by Fischer esterification reactions, so you could easily get a diester using the same procedure that gave them the monophenyl ester. (I also note the patent used diethyl ether, which has a lower bp and less likely to decarboxylate the intermediate or product.)

[xiaojunzhang]

Ok,I will try it according to your advice.You are very kind,orgopete,thank you very much!