Methyl Glycolate Synthesis

Nippon Shokubai has developed a gold-based catalyst that enables the methyl ester of glycolic acid to be made directly from ethylene glycol [597]  

---

As early as 1904, 1,2-Propanediol Dinitrate was proposed (Ref 3) as an additive to lower the freezing temp of NG, but its practical application on a large scale was hindered by lack of the raw material, propane-1,2-diol. It is only recently that the synthesis of glycol from ethylene led to the development of a method for producing methyl glycol from propylene via cnioro-hydrin. Even so, propylene-1,2-glycol is somewhat more expensive than glycols derived from ethylene (Ref 9)... 

The duPont Co in 1940 put in operation a unique plant at Belle, West Virginia, in which glycol was manufd by hydrogenation of methyl-glycolate, the raw materials (or which included its own high pressure synthesis products formaldehyde and methanol... 

The first synthesis reported was that of a Syntex-group80. They used the well known addition of the anion of methyl glycolate to a, (3-unsaturated esters87-90 for the construction of the oxacyclopentane-system. 

Methyl chloroformate has also been employed in the synthesis of rosejuran [615], in a general and facile method for determining the configuration of steroid-17-yl methyl glycolates at C-20 [T. Suzuki, H. Tada, J. Chem. Soc., Perkin Trans. 1 1998, 3831-3836], and in a novel method for the stereospedfic generation of natural C-17 stereochemistry [616]. 

Gold catalyses one-step synthesis of methyl glycolate, Chem. Eng. (New York), Sept. 2004, 111, 20. Propylene epoxidation with O2 and H2 over gold nanoparticles supported on mesostructural titanium silicates, M. Haruta, A. K. Sinha, S. Sedan, B. Chowdhury, M. Dat, and S. Tsubota Proc. 13 Int. Congr. Catalysis, Paris, July 2004, 01-031 33. 

An example of this is found in the synthesis of a crown containing a mefa-xylylene unit (see also Sect. 3.5) and a convergent methoxyl group. 4-Methyl-2,6-bishydroxymethyl-anisole was treated with pentaethylene glycol and sodium hydride in THF solution to afford the crown (mp 71—73°) shown in Eq. (3.52) in 59% yield. 

From a study of the fluoroacetates so far mentioned, it appears that any compound which can give rise to fluoroacetic acid (or the fluoroacetate ion), either by hydrolysis or by oxidation (or both), is toxic. The toxic grouping is thus F-CH2-CO, and any substitution in this radical destroys the toxicity as far as relatively simple compounds are concerned. We had reached this conclusion by May 1943.1 We subsequently showed that esters of / -fluoropropionic acid were non-toxic, whereas esters of y-fluorobutyric acid were shown by American workers to be toxic. In 19442 we reported the synthesis of ethyl 5-fluoro-pentanecarboxylate, F,[CH2]g C02Et (I). This is a stable, colourless liquid and we showed that it possessed very potent toxic properties of the fluoroacetate type. By subcutaneous injection of the propylene glycol solution into mice the l.d. 50 was 4 mg./kg. Methyl fluoroacetate (II) may be taken as a convenient standard (p. 115) and has a l.d. 50 of about 6 mg./kg. for saline solutions, and 15 mg./kg. for propylene glycol solution.3 Therefore ethyl 5-fluoropentanecarboxylate was about 7 times as toxic as methyl fluoroacetate (molecule for molecule).4... 

---