Sciencemadness Discussion Board

Opening a lactone - Easy?

Rich_Insane - 5-4-2012 at 12:46

Hey guys. So there is this reagent I need. The actual carboxylic acid is very, very expensive, but strangely the corresponding lactone is on the order of 5x cheaper. The cheapest I can find for HGA is $151/g from TCI America. The lactone is $51/g or $154 for 5 g. Even though I won't be spending out of pocket money (no, it will be paid for with taxpayer dollars), I want to get this stuff for the cheapest possible price and get as much as I can, as running out of important standards is a serious pain in the ass.

The acid I speak of is 2,5- dihydroxyphenylacetic acid (Homogentisic acid). So what I'm wondering is whether it would be possible to avoid buying the acid directly and simply buy the lactone (The gamma-lactone). Is it possible to open the lactone up easily? By easily, I mean without serious O Chem equipment. This will be done in a microbiology lab, so I'm limited to common acids/bases/salts and common glassware. Will base-hydrolysis work? The HGA will be dissolved in concentrated NaOH solution anyways. Will heating in such conditions be sufficient to open the lactone?

Bot0nist - 5-4-2012 at 16:09

"Heating a lactone with a base (sodium hydroxide) will hydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is a reversible reaction, with an equilibrium." ~ wiki

Is this useful?

mr.crow - 5-4-2012 at 17:13

If you dissolve it in NaOH to make the Na salt I can't see why the lactone won't work as a direct replacement (with refluxing). The ring is more stable, so maybe its harder to isolate the free acid compared to the lactone

Lambda-Eyde - 5-4-2012 at 17:44

I just checked with my local supplier, they carry the acid at 6400 NOK (~1000 USD) per gram, and that's not including 25% VAT! :o If one were to synthesize this, even in small quantities... ;)

[Edited on 6-4-2012 by Lambda-Eyde]

Rich_Insane - 5-4-2012 at 21:14
Quote:

"Heating a lactone with a base (sodium hydroxide) will hydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is a reversible reaction, with an equilibrium." ~ wiki Is this useful?



Yea, I saw that on Wikipedia, but I was afraid that the particular molecule I have might undergo some side reaction to strong base. We need this stuff exceptionally pure, as it will be used as a standard for identification of certain pigments, most of which are produced on the microgram level.


Quote:

If you dissolve it in NaOH to make the Na salt I can't see why the lactone won't work as a direct replacement (with refluxing). The ring is more stable, so maybe its harder to isolate the free acid compared to the lactone



Ah, this is good. The actual procedure involves first stirring the acid in a base (open the lactone) and then incubation of the result in acid. Even if we didn't pursue a dual purpose route, the lactone is so much cheaper.
Quote:

I just checked with my local supplier, they carry the acid at 6400 NOK (~1000 USD) per gram, and that's not including 25% VAT! :o If one were to synthesize this, even in small quantities... ;)



Yea, I really do want to synthesize it (because I do indeed enjoy chemical synthesis), but I'd have to confer with the Chemistry department. From a larger scale standpoint, it would be far, far more feasible to just synthesize it. At the moment, we only need anywhere from 100 mg- 250 mg for the standard. The mass production (2 milligrams of pigment/L!) of the product can be performed by bacteria (which produce the desired polymers naturally) which we grow in the lab.

bahamuth - 5-4-2012 at 23:29

Quote:
Addition of NaOH in the presence of Na2S03 allowed opening of the lactone ring without occurrence of the intense darkening and rapid oxidation of homogentisic acid which took place when the lactone was converted in the presence of air with alkali alone.


Chemical preparation of Homogentisic Acid

Reference details the complete synthesis from 1,4-dimethoxybenzene -> 2,5-dimethoxyacetophenone -> 2,5-dimethoxyphenylacetic acid to end product 2,5-dihydroxyphenylacetic acid (Homogentisic acid).

This looks like a fun synthesis and I would try it if I could get my hands on some hydroquinone.

Satan - 6-4-2012 at 06:31

Quote: Originally posted by Rich_Insane  
Is it possible to open the lactone up easily?

With sodium hydroxide; sodium sulfite
Wolkowitz; Dunn
Biochemical Preparations, 1955 , vol. 4, p. 6,11

Abbott; Smith
Journal of Biological Chemistry, 1949 , vol. 179, p. 365,367


in 90% yield
Bloomer, James L.; Damodaran, Kalyani M.
Synthesis, 1980 , # 2 p. 111

Nicodem - 6-4-2012 at 06:53

I always find it amusing when I see younger people having a lousier memory than myself, but sometimes this goes beyond the imaginable. Rich_Insane, you yourself provided these references for this exact lactone ring opening reaction in your previous thread on this same topic. The Synthesis paper that Satan also refers to, was then uploaded by me, but in that paper they used the same procedure as in that JBC paper.
And then people that know me personally say I have a terrible memory.
:(