N-acetylglycine is an important chemical building block for many chemical products, such as glycine, aspartame and other amino acids. More specifically, N-acetylglycine can be the intermediate for phenylalanine synthesis via reactions with benzaldehyde, followed by hydrolysis and selective hydrogenation of an acetaminocinnamic acid intermediate (Chemical Marketing Reporter, May 14, 1984).
The synthesis of N-acetyl-.alpha.-amino acid from aldehyde and carbon monoxide was first reported by Wakamatsu, in Chemical Communication, 1540, (1970) and U.S. Pat. No. 3,766,266. This patent teaches the use of paraformaldehyde, acetaldehyde, propionaldehyde, i-butyraldehyde, phenylacetaldehyde, .beta.-cyanopropionaldehyde etc. as reactants. The amide included in a formyl group and a carbamoyl group having at least one active hydrogen atom. Where paraformaldehyde was reacted with acetamide, N-acetylglycine was produced at only about 46% yield. Here there is the problem of the cobalt catalyst complexing with solid N-acetylglycine product and causing the loss of cobalt from reacting solvent medium. This disadvantage has prevented this synthesis from being commercialized. An improvement of this catalyst system would be desirable.
In amidocarbonylation, the aldehyde can be generated in situ from allyl alcohol, alkyl halide, oxiranes, alcohols and olefins followed by the reaction with amide and carbon monoxide to produce N-acyl- .alpha.-amino acid. Disclosures of such reactions can be found in Tetrahedron Letters, Vol. 23, No. 24, pp. 2491-2494, 1982; U.S. Pat. No, 3,996,288; German Offen. DE 3,242,374 and U.S. Pat. No. 4,264,515, respectively. In these references the synthesis of N-acetylglycine was not addressed. The problem of catalyst deposition on N-acetylglycine was not encountered by other amidoacid analogs.
N-acetylglycine (the smallest molecule in the amido acid family) has a melting point of 207.degree. C. to about 209.degree. C., which makes the distillation techniques for isolating the product impractical. This highly polar product has also strong tendency to chelate cobalt metal. Comparative Example 2 in this specification indicated &gt;90% cobalt was deposited on the N-acetylglycine product. Therefore an improved catalyst system allowing for high-yield and exhibiting good cobalt recovery would be desirable in order to achieve commercial feasibility.
Many ligands or promoters have been used to improve the performance of cobalt catalysts.
In U. S. Pat. Nos. 4,209,467 and 3,996,164, amine ligands including pyridine, 2-hydroxypyridine and cycloaliphatic amines were employed with dicobalt octacarbonyl for hydroformylation or carbonylation of olefins. The function of the ligands was to stabilize the catalyst and increase the product selectivity.
In. U.S. Pat. No. 3,931,332, the importance of the cobalt and diamine promoter ratio was demonstrated. Increasing the added amount of added diamine-stabilizer markedly reduced the reaction rate of hydroformylation. A smaller amount of ligand to cobalt is preferred with respect to reaction rate.
In U.S. Pat. No. 4,612,403, an organic nitrile promoter was used to improve the process of hydroformylation. In U.S. Pat. No. 4,476,326, a sulfoxide promoter was used to improve the cobalt catalyst for methanol homologation to ethanol by reactions with a CO-H.sub.2 mixture.
These products are aldehydes, alcohols, esters or carboxylic acids, which are distillable and less polar than N-acetylglycine. The use of these specific promotors would not be relevant to N-acetylglycine synthesis.
The amidocarbonylation of an aldehyde, amide and carbon monoxide to form an amidoacid involves the cobalt catalyzed carbonylation of an aldehyde-acetamide adduct under unusually mild reaction temperatures (ca 120.degree. C.) compared with cobalt-catalyzed hydroformylation carbonylation or methanol homologation. The examples in the instant invention demonstrate the importance of certain ligands for this reaction. The nature of the solid product which acts as a strong chelating agent required experimentation to find the most suitable ligands.
For comparison, succinonitrile and sulfoxide ligands aided the cobalt recovery and the product selectivity; diamine and acetonitrile (large amount used as solvent) adversely affected the reaction. Although these effects are not well understood, we believe that the suitability of ligands is dependent on the strength of the ligand to cobalt complex and on the amount of ligands used. In the process of the instant invention ligands have been relied upon which complexed with cobalt stronger than the amido acid product did and which had no deactivating ability.
Our experimental results reveal that promoters which work for oxo, carbonylation or other CO reactions could not be simply applied to amidocarbonylation. For example, amine ligands are not suitable for N-acetylglycine synthesis. Furthermore, our invention particularly deals with paraformaldehyde to N-acetylglycine synthesis. Comparative example (3) illustrates that the synthesis of N-acetylalanine from acetaldehyde, acetamide and carbon monoxide did not have the problem of cobalt deposition because it exhibits less polarity.
USPTO Backgrounds
USPTO Backgrounds