Process for preparation of crystallized monohydrated sodium phenylpyruvate

The invention concerns a process for preparation of crystallized monohydrated sodium phenylpyruvate comprising: hot reacting benzaldehyde in an aqueous medium in the presence of a catalytic quantity of ethanolamine with the stoichiometric quantity of hydantoin, then treating the reactional medium hot at pH=14 through an excess of sodium hydroxide, acidifying to pH=9 with concentrated hydrochloric acid the so obtained solution and separating the formed precipitate.

This invention relates to a process for preparation of 2-oxo-3-phenyl 
sodium propionate crystallized with one molecule of water hereinafter 
designated as crystallized monohydrated sodium phenylpyruvate. This salt 
is a precious raw material for preparing phenylalanine. 
Crystallized monohydrated sodium phenylpyruvate is known. It has been 
obtained among others by R. HEMMERLE upon hydrolysis of 
ethyl-3-cyano-2-oxo-3-phenyl-propionate (Annales de Chimie et de Physique, 
1917, (9) 7, 226-276). There is also known to prepare it by hydrolyzing 
5-benzylidene hydantoin (B. A. IVIN et al.Zhur.org.Khim. 1977 13 (9), 
1970-80) from the condensation of benzaldehyde over hydantoin (H. L. 
WHEELER et al. Amer.Chem.J. 1911,45 369; W. J. BOYD, Biochem.J. 1935, 29, 
542-5; The DOW CHEMICAL Co., U.S. Pat. No. 2,861,079; DEGUSSA A. G., 
European Patent Application Nos. 0 037 479 and 0 037 480, French Patent 
Application No. 2,485,011). Analysis of such documents shows that to 
accede at the sodium phenyl pyruvate crystallized with one molecule of 
water from benzaldehyde and hydantoin in the presence of a catalyst such 
as ammonium acetate or the alkanol amines, it is necessary to achieve such 
synthesis in two steps, with isolation of the intermediary 5-benzylidene 
hydantoin. Industrially, this method is therefore little economic and 
other synthesis methods were tried such as carbonylation of benzyl 
halides(MONTEDISON S.p.A. U.S. Pat. No. 4,351,952; RHONE POULENC S.A. 
French Patent Application No. 2,297,200). 
However, the Applicant has surprisingly discovered that sodium pyruvate 
crystallized pure with one molecule of solvatation water having an 
excellent yield can be obtained in one step starting from benzaldehyde and 
hydantoin. 
The process according to this invention is the more surprising because it 
is rapid, little expensive and of easy implementation. 
The process according to this invention is characterized by heating with 
reflux for several hours an aqueous equimolecular suspension of 
benzaldehyde and hydantoin in the presence of a catalytic quantity of 
ethanolamine, continuing with the reflux for several tens of minutes at 
pH=14 after addition of an excess of sodium hydroxyde into the reactional 
medium, then acidifying the obtained solution cooled to the ambient 
temperature at pH=9, with concentrated hydrochloric acid, then squeezing 
and washing by impasting with iced water the so obtained crystallized 
product and finally, drying under vacuum at 60.degree. C. at constant 
weight. 
Advantageously, the process according to this invention is carried out by 
heating for four hours with reflux a suspension consisting of one mole of 
benzaldehyde, one mole of hydantoin and 0.1 mole of ethanolamine in 240 g 
of permuted water, then continuing the reflux for 30 minutes in the 
presence of 1000 cm.sup.3 of 5N sodium hydroxyde, by acidifying thereafter 
the obtained solution previously cooled to the ambient temperature at 
pH=9, with concentrated hydrochloric acid, squeezing and then washing by 
impasting with iced water the formed precipitate and finally, drying at 
constant weight under vacuum at 60.degree. C. Thus, there is obtained 
sodium phenylpyruvate crystallized pure with one molecule of solvatation 
water with excellent yield higher than 75% of the theoretical value. 
As previously mentioned, sodium phenylpyruvate crystallized with one 
molecule of water submitted to a reducing amination reaction leads to 
phenylalanine. (UNITIKA Ltd. Japanese Patent Application No. 
52(77)-48601). 
The following Example illustrates this invention without however any 
limitation thereof:

EXAMPLE 1 
There is heated for 4 hours with reflux under agitation and in an inert 
atmosphere: 
106 g (1 mole) of benzaldehyde, 
100 g (1 mole) of hydantoin, 
6.1 g (0.1 mole) of ethanolamine in 240 g of permuted water. 
During the reflux the reactional medium passes into solution, then again 
provides a suspension. 
Thereafter, there is introduced 1000 cm.sup.3 of 5N sodium hydroxyde ie. 5 
moles of sodium hydroxide, then the reflux is continued for 30 minutes. 
The obtained solution is then cooled to the ambient temperature, and 
thereafter it is brought to pH=9 through addition thereto of concentrated 
hydrochloric acid. The desired product crystallizes slowly; the 
precipitate is left to mature for 24 hours, then it is squeezed and 
thereafter it is washed by impasting with one volume of iced water. Thus, 
there is obtained after drying at constant weight at 60.degree. C. under 
vacuum a first quantity of 153.1 g (0.75 mole) of sodium phenylpyruvate 
crystallized with one molecule of water colourless and homogeneous upon 
thin layer chromatography. 
Through concentration of mother waters there is isolated a second quantity 
of 28.5 g (0.14 mole) of sodium phenylpyruvate crystallized with one 
molecule of water, colourless and homogeneous upon thin layer 
chromatography. 
The overall yield is determined to 99% of the theoretical value. 
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Microanalysis: 
C.sub.9 H.sub.7 NaO.sub.3, H.sub.2 O 
C % H % H.sub.2 O %.sup.+ 
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calculated 52.94 4.44 8.8 
found 52.8 4.4 9.3 
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.sup.+ as determined by Karl Fischer. 
It will be understood that this invention was only described in a purely 
explanatory and not at all limitative manner and that any useful 
modification thereof can be effected without however departing from its 
scope as defined in the appended claims.