Degussa methionine process

The Degussa methionine process exemplifies, how many industrial procedures gain attraction through the elegance of how they are conducted. In summary, methionine is formed from equimolar portions of acrolein, methanethiol, hydrogen cyanide and water. The yields of all the reaction steps exceed 90% (Fig. 4.14 and Fig. 4.15). 

Degussa AG uses immobilised acylase to produce a variety of L-amino adds, for example L-methionine (80,000 tonnes per annum). The prindples of the process are the same as those of the Tanabe-process, described above. Degussa uses a new type of reactor, an enzyme membrane reactor, on a pilot plant scale to produce L-methionine, L-phenylalanine and L-valine in an amount of 200 tonnes per annum. 

The acylase-catalyzed resolution of N-acetyl-D,L-amino acids to obtain enantiomerically pure i-amino acids (see Chapter 7, Section 7.2.1) has been scaled up to the multi-hundred ton level. For the immobilized-enzyme reactor (Takeda, 1969) as well as the enzyme membrane reactor technology (Degussa, 1980) the acylase process was the first to be scaled up to industrial levels. Commercially acylase has broad substrate specificity and sufficient stability during both storage and operation. The process is fully developed and allowed major market penetration for its products, mainly pharmaceutical-grade L-methionine and L-valine. 

The hydrolysis of an IV-acylated amino acid by an enzyme provides a resolution method to amino acids. Because the starting materials are readily available in the racemic series by the Schotten-Baumann reaction, the method can be cost effective (Scheme 2.21).68-71 The L-amino acid product can be separated by crystallization, whereas the D-amino acid, which is still /V-acylated, can be recycled by being resubjected to the Schotten-Baumann conditions used for the next batch. Tanabe has developed a process with an immobilized enzyme,72 73 whereas Degussa uses the method in a membrane reactor.69 74 The process is used to make L-methionine. 

An example of an acylase to perform a resolution is provided by the Degussa process to L-methionine (1). The racemic acetylmethionine (2) is prepared by a chemical synthesis. The acylase hydrolyses only the L-isomer (Fig. 2). The D-isomer is racemized by base and put back into the process stream (48). 

Since the early 1980s this process has been scaled-up to a production level of hundreds of tons per year. Fig. 6 shows the Degussa process for manufacturing l-methionine, l-6 [9 a]. The biocatalyst is produced in bulk quantities and its operational stability is high hence this continuous EMR-acylase process demonstrates high efficiency, especially on a large-scale [9]. 

Degussa manufactures methionine by a process, in which practically no salts accumulate as waste, and aU the side-products are recyclable cf. Chapter 4). 

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