Is it possible to make lactate esters (OMe, OEt), starting from L-lactic acid, by direct esterification, without forming oligomer by-products? I need low molecular lactate esters for enzymatic polymerization (using N435).
My suggestion is to buy these substances. You would spend much more time playing with esterification than the delivery time will be.
Thanks for your answer, I know these compounds are commercialy available for a low price. However I was wondering if it would be worth the efford trying to make the ester in the lab. If it takes a lot of time to make this compound, then indeed it would be more convenient to buy a small quantity for just a few experiments.
İ did direct esterification with Mandelic acid and methanol. İt is very similer to Lactic acid ethyt ester. Dissolve 5 mL lactic acid in 40-50 mL EtOH and then add 1 mL H2SO4, stir and reflux for 2-3 hours. stop te reakcion and cool to r.t., add Na2CO3 to neutralize the reaction micture. then filter the ester (if solid) or ectratc with any organic solvent.
Well if you do not wish to buy it (it is dam cheap, you shall consider it) then you have two possibilities:
(1) Acidic conditions; see e.g. Bioorg. Med. Chem. Lett. 2012 , 22, 482
(2) Basic conditions; see e.g.: JACS 1993, 115, 9774
For acidic conditions you shall follow e.g. this protocol:
(1A) Benzyl alcohol (1.2 equiv) and p-toluenesulfonic acid (0.1 equiv) were taken in benzene/toluene and refluxed for 0.5 h, then compounds lactic acid (1 equiv) was added, and continuously reflexed until the completion of the reaction (monitored by TLC: petroleum ether/ethyl acetate, 8:1; typically 4 h). The reaction mixture was washed with saturated NaHCO3solution, water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. Purification by flash column chromatography gave the desired ester as colorless oil. (Now, if you add sulphuric acid, it will work as well ).
(2A) About the same (benzene/toluene reflux) but you have to use alkyl halide and base that is sufficiently strong to deprotonate the acid, yet sufficiently mild to keep alcohol protonated or mostly protonated (e.g. 1,8-diazabicyclo[5.4.0]undec-7-ene).
I suggest you buy these esters. If you make it, you have to check not only the purity but also enantiopurity. The racemization can happen very easily.
Thank you all for your contributions. Enantiopurity indeed may also be subject of discussion, the aim is use L-lactate derrivates as model compounds, as they are also obtained by microbial fermentation. Aditionaly, I am also wondering if the enzyme will polymerize a certain enanatiomer, most reactions with CALB are stereoselective.
Perhaps you should use this procedure: thionyl chloride in a large excess of methanol for 6-12 hrs at reflux temperature. The main concepts behind this are: very low concentration and temperature to avoid oligomerization. Pelase see this procedure applied to aminoacids in J Méx Chem Soc 2001,45,4,152-158, its free link is http://www.redalyc.org/articulo.oa?id=47545404 Lucky with your reaction.
You can take a look and perhaps use a modified procedure based on:
Rehberg, C. E. Allyl lactate [Lactic acid, allyl ester]. Organic syntheses, Coll. Vol. 3, p. 46 (1955); Vol. 26, p. 4 (1946)
It can be found online.
In my own experience, I prepared allyl lactate by the reported procedure and using DCC; when using the Org. Syn. procedure, secondary compounds were also formed (GC control). Pure allyl lactate can be prepared using the DCC method (without racemization according chiral GC). I can send you the experimental procedure.
As it was suggested, for OMe and OEt lactate esters is easier to buy a small quantity of the substances.
UPDATE:
A short discussion about the question and the experimental procedure for the preparation of several alfa-hydroxyesters using DCC (a modified Steglich esterification) including lactic acid alkyl esters, is reported in the attached file (Revista de la Sociedad Química del Perú, 2017, 83(2), 143-159).
I agree with Michal, It is not worth the effort you would need to put on it. Otherwise if you really want to do that can you follow a normal esterification method
Certainly, the best way to do it is to perform a classical esterification method by Fisher using large excess of the alcohol. As you're interested in low MW esters, the alcohols are very easy to remove by evaporation and very cheap and accessible to use them as solvents. I think you will not have problems with oligomerization doing it this way...
Try acetic anhydride in excess to peracylate your lactate. Once achieved try the use of your alcohol source in order to obtain the thermodynamic esther. Hope this helps.
fist you need orthogonal protection of any OH within your molecule....once achieved this would be followed by activation of the C terminal group with EDC and displacement of the so formed active ester by the nuchleopilic Et-OH or Me-OH in presence of an organic base
Don't forget that you 90% lactic acid has significant amount of oligomer in it. Just heat it longer with your alcohol and acid-catalyst and you will break oligomers to your desired lactates as well. L-Methyl lactate you can buy as well.