Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1982-12-29
1984-11-20
Shippen, Michael L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C07C 51363
Patent
active
044840039
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to an improved preparation process of .beta.-chloroalanine through a reaction of an aziridine-2-carboxylate with hydrogen chloride.
BACKGROUND ART
.beta.-Chloroalanine is an amino acid having physiological activity and is an extremely useful compound as a synthesis intermediate not only for cystein, a sulfur-containing amino acid, but also for certain pharmaceutically valuable compounds and the like. Due to lack of industrially advantageous preparation processes, .beta.-chloroalanine has not yet been utilized fully. Among known synthesis processes of .beta.-chloroalanine, there may be mentioned to esterify serine, followed by chlorination and hydrolysis (J. L. Wood, and L. van Middlesworth, J. Bio. Chem., Vol. 179, Page 529, 1949); and to chlorinate and decompose a cystein derivative in an organic solvent by reacting the derivative with chlorine (H. Baganz and G. Dransch, Chem. Ber. Vol. 93, Page 782, 1960). However, these processes are not suitable for their applications in an industrial scale because both processes require very costly starting materials.
On the other hand, it has also been known to prepare .beta.-chloroalanine by reacting sodium aziridine-2-carboxylate with hydrogen chloride (K. D. Gundermann, G. Holtmann, H. J. Rose, and H. Schulze, Chem. Ber., Vol. 93, Page 1632, 1960). The above process however requires extraordinarily excessive hydrogen chloride upon carrying out the reaction. Furthermore, in order to separate the resultant sodium chloride from a mixture of .beta.-chloroalanine hydrochloride and .alpha.-chloro-.beta.-alanine hydrochloride which is a by-product, it is necessary to add a large amount of ethanol to the reaction mixture to extract the intended product and by-product. It is also required to treat the thus-obtained extract of .beta.-chloroalanine hydrochloride and .alpha.-chloro-.beta.-alanine hydrochloride with ammonia, to add water to the thus-treated extract so as to crystallize .beta.-chloroalanine and then to isolate same. The above process is not fully considered to be an advantageous preparation process from the industrial standpoint because, despite of the adoption of complex steps, the yield of isolated .beta.-chloroalanine is as low as 10% and its isolation steps are extremely cumbersome.
DISCLOSURE OF THE INVENTION
An object of this invention is to provide a preparation process of .beta.-chloroalanine through a reaction of an aziridine-2-carboxylate with hydrogen chloride, which process facilitates the isolation of .beta.-chloroalanine in a crystalline form from the liquid reaction mixture.
Another object of this invention is to provide a preparation process of .beta.-chloroalanine through a reaction of an aziridine-2-carboxylate with hydrogen chloride, which process permits to convert .beta.-chloroalanine still remaining in the liquid reaction mixture after its isolation as crystalline .beta.-chloroalanine into an aziridine-2-carboxylate.
The present inventors have found that, upon synthetically preparing .beta.-chloroalanine and .alpha.-chloro-.beta.-alanine through the reaction between an aziridine-2-carboxylate and hydrogen chloride, the reaction can be successfully carried out with a stoichiometric or slightly excessive amount of hydrogen chloride instead of using hydrogen chloride in an extraordinarily excessive amount with respect to aziridine-2-carboxylic acid or its salt and .beta.-chloroalanine may be isolated by causing same to selectively and solely crystallize out from the reaction mixture.
It has also been found by the present inventors that .beta.-chloroalanine may also be prepared from a solution recovered after isolating crystallized .beta.-chloroalanine from the liquid reaction mixture, which solution still contains .beta.-chloroalanine and .alpha.-chloro-.beta.-alanine, by treating the solution with the hydroxide of an alkali metal or alkaline earth metal or ammonia under extremely mild conditions to obtain a solution containing an aziridine-2-carboxylate and then reacting the thus-obtained aziridi
REFERENCES:
Gundermann, Chem. Ber., 93, pp. 1632-1643, (1960).
Higuchi Chojiro
Katoh Toshio
Kawashima Nobuhiro
Kawashima Nobuyuki
Mita Ryuichi
Mitsui Toatsu Chemicals Incorporated
Shippen Michael L.
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