Process for preparing alpha-oxo-esters

An operationally simple and economical process for preparing alpha-oxoesters is provided by reacting an acetylenic compound of formula EQU R--C.tbd.C--OR' with an oxidizing mixture composed of osmium tetroxide and an alkaline or alkaline earth chlorate and recovering the osmium tetroxide at the end of the reaction.

This invention relates to a process for preparing alpha-oxoesters of 
formula I 
##STR1## 
in which R and R', the same or different, may be alkyl, aryl, arylalkyl or 
cycloalkyl groups, and in addition R may be hydrogen. 
Alpha-oxoesters according to the present invention may be converted very 
easily into the corresponding alpha-oxoacids by methods known to any 
expert of the art. 
Both alpha-oxoesters and alpha-oxoacids are useful synthesis intermediates 
particularly in the preparation of alpha-aminoesters or alpha-aminoacids, 
respectively by reductive amination or by reaction with hydroxylamine 
followed by catalytic hydrogenation. 
More recently, asymmetric syntheses have been developed for obtaining 
optically active alpha-aminoacids from alpha-ketoacids (see for example E. 
J. Corey et al., J. Am. Chem. Soc., 92, 2476 (1970); K. Morada et al., 
Bull. Chem. Soc. Jap., 43, 921-1970). 
In the process according to the present invention, alpha-oxoesters are 
prepared from acetylenic derivatives of general formula II: 
EQU R--C.uparw.C--OR' II 
in which R and R' have the same meanings as heretofore, by reaction with an 
oxidizing mixture composed of osmium tetroxide and an alkaline or alkaline 
earth chlorate. 
Relative to known methods for preparing the aforesaid alpha-oxoesters, the 
method according to the present invention has the advantage of being not 
only operationally more simple, but also more economical in that the 
osmium tetroxide may be recovered at the end of the reaction. 
Furthermore, the crude product obtained has in many cases a degree of 
purity sufficient to allow it to be used as such in the next process 
stage. 
In the process according to the present invention, the oxidizing agent for 
the acetylenic compound is osmium tetroxide, the chlorate serving to 
regenerate the osmium tetroxide in situ, so that this latter may be used 
in catalytic quantites. 
As stated, the osmium tetroxide may be recovered at the end of the 
reaction, either by entraining it in a stream of nitrogen and collecting 
it in a no longer volatile form in a trap containing the initial 
acetylenic compound of a subsequent batch, or by precipitating it with 
sulphidric acid in the form of osmium sulphide, which may be recycled as 
such, as the chlorate reoxidizes it to osmium tetroxide, or by any other 
methods known to any expert of the art. 
The initial acetylenic derivatives of type II may be notably prepared from 
aldehydes of formula RCH.sub.2 CHO in which R has the same meaning as 
heretofore, or from other commercial products following known procedures 
such as described for example in J. F. Arens, Adv Org. Chem., 2,121, 
(1960), or in L. Bradsma, H. J. T. Bos, J. F. Arens "Acetylenic Ethers and 
Thioethers" in "Chemistry of Acetylenes" H. C. Viehe, Ed., Marcel Dekker 
inc., New York, 1969, p. 750. 
The acetylenic compound oxidation reaction is carried out in water or a 
monophase or bi-phase mixture of water with an inert organic solvent 
(preferably ethyl ether) at a temperature of 0.degree.-100.degree. C. 
(generally at ambient temperature) and at a pressure such as to maintain 
the liquid phase in the system. 
In some cases it is advantageous to work at a controlled pH (5.5-7.5) which 
may be attained in various ways, for example by means of an automatic 
titrator.

The operational details will be more evident from the illustrative examples 
given hereinafter, which however in no way limit the invention. 
EXAMPLE 1 
Preparation of methyl pyruvate from 1-propinyl methylether 
12.7 g (0.181 moles) of 1-propinyl methylether are added at ambient 
temperature over a period of 20 minutes to an agitated mixture of 200 ml 
of water, 300 ml of ethylether, 36 g (0.294 moles) of potassium chlorate 
and 2 g (0.0079 moles) of osmium tetroxide while maintaining the pH at 6.8 
by means of an automatic titrator charged with 1 N KOH. 
After a further 4 hours of agitation under the same condition, the black 
colouration of the mixture disappears and the ether phase is separated 
from the aqueous phase, and this latter is extracted with ethylether in a 
liquid-liquid extractor. 
Sulphydric acid is dripped slowly for 10 min. at 0.degree. C. into the 
combined ether solutions made anhydrous (Na.sub.2 SO.sub.4), the formed 
precipitate is digested for a further 15 min. at 0.degree. C., and the 
osmium sulphide is then filtered, and may be re-used as such, as it is 
re-oxidized to osmium tetroxide by the chlorate. 
The ether solution is concentrated at 0.degree. C. in the rotating 
evaporator and the residue is distilled (Vigreux column) under a vacuum of 
15 mmHg collecting the fraction with a B.P. of 50.degree.-53.degree. C. 
(boiler 85.degree. C.). 
8.65 g (0.085 moles) of gas-chromatographically pure product are obtained. 
Yield: 46.8%. B.P. 134.degree. C.; ir (film): .nu.max 1725 cm.sup.-1 (CO 
of ester and ketone); NMR (C.sub.6 D.sub.6): delta 2.45 (3H, s, CH.sub.3 
CO); 3.75 (3H, s, COOCH.sub.3). 
EXAMPLE 2 
Preparation of methyl alpha-ketobutyrate from 1-butinyl methylether 
A mixture of 120 ml of water, 210 ml of ethyl ether, 16.7 g (0.136 moles) 
of potassium chlorate, 0.69 g (0.0027 moles of osmium tetroxide and 5.5 g 
(0.065 moles) of 1-butinyl methylether is agitated at ambient temperature 
for 16 hours. 
After processing as described in example 1, distilling the crude under a 
vacuum of 27 mmHg and collecting the fraction with a B.P. of 
72.degree.-74.degree. C. (boiler 100.degree.-105.degree. C.), 5.2 g (0.045 
moles of gas-chromatographically pure methyl alpha-ketobutyrate are 
obtained. Yield: 69%. Ir (film): .nu.max 1730 cm.sup.-1 (CO of ester and 
ketone); NMR (C.sub.6 D.sub.6): delta 0.90 (3H, t, J=6 Hz, CH.sub.3 C), 
2.57 (2H, q, J=6 Hz, CH.sub.2 CO), 3.53 (3H, s, COOCH.sub.3). 
EXAMPLE 3 
Preparation of methyl alpha-ketoisovaleriate from isopentinyl methylether. 
A mixture of 200 ml of water, 350 ml of ethyl ether, 40.2 g (0.328 moles) 
of potassium chlorate, 1.66 g (0.0065 moles) of osmium tetroxide and 14.6 
g (0.149 moles) of isopentinyl methylether is agitated at ambient 
temperature for 16 hours. 
After processing as described in example 1, distilling the crude under a 
vacuum of 23 mmHg and collecting the fraction with B.P. of 
64.degree.-68.degree. C., 15.5 g (0.119 moles) of gas-chromatographically 
pure methyl alpha-ketoisovaleriate are obtained. Yield: 79.9%. Ir (film): 
.nu.max 1730 cm.sup.-1 (CO of ester and ketone); NMR (C.sub.6 D.sub.6): 
delta 1.08 (6H, d, J=6 Hz, (CH.sub.3).sub.2 C), 3.15 (1H, m, J=6 Hz, CH), 
3.42 (3Hn s, COOCH.sub.3).