Process for preparing cyanoacetates
This invention relates to a process for producing cyanoacetates using aspartic acid as a precursor.
1. A process for the preparation of a cyanoacetate, steps of which comprise:
(a) contacting aspartic acid with an alcohol, in the presence of an acetyl halide, under appropriate conditions and for a time sufficient to yield a beta-ester of the aspartic acid;
(b) optionally, separating therefrom the so formed beta-ester of the aspartic acid;
(c) contacting the beta-ester of the aspartic acid with a halogenating agent under appropriate conditions and for a time sufficient to yield a cyanoacetate; and
(d) optionally, separating therefrom the so formed cyanoacetate.
2. The process of claim 1 , wherein the cyanoacetate is a C 1-20 alkyl cyanoacetate, a C 6-20 aryl cyanoacetate, a C 7-20 alkaryl cyanoacetate or a C 7-20 aralkyl cyanoacetate, any of which may be substituted by one or more hydroxyl groups or C 1-20 alkyl ether groups.
3. The process of claim 1 , wherein the cyanoacetate is a C 1-20 alkyl cyanoacetate, wherein the C 1-20 alkyl may contain one or more points of unsaturation and may be substituted and/or interrupted by one or more heteroatoms or heteroatom-containing groups, or substituted by halogens or substituted or interrupted by halogen-containing groups.
4. The process of claim 1 , wherein the cyanoacetate is a C 1-20 alkyl cyanoacetate selected from methyl cyanoacetate, ethyl cyanoacetate, propyl cyanoacetates, butyl cyanoacetates, pentyl cyanoacetates, octyl cyanoacetates, alkoxy ether alkyl cyanoacetates, allyl cyanoacetates, and combinations thereof.
5. The process of claim 1 , wherein the cyanoacetate is a C 6-20 aryl cyanoacetate selected from phenyl cyanoacetate.
6. The process of claim 1 , wherein the cyanoacetate is a C 7-20 aralkyl cyanoacetate selected from phenethyl cyanoacetate, benzyl cyanoacetate, or toluyl cyanoacetate.
7. The process of claim 1 , wherein the alcohol is an alkyl alcohol, an aryl alcohol, an alkaryl alcohol or an aralkyl alcohol.
8. The process of claim 1 , wherein the alcohol is selected from methanol, ethanol, propanols, proparganols, butanols, pentanols, hexanols, octanols, nonanols, oxononanols, decanols, dodecanols, allanol, cyclohexanol, tetrahydrofurfurol, chloroethanol, 2,2,2-trifluoroethanol, hexafluoroisopropanol, alkoxy ether alkanols, dialkyl siloxanols, or trialkylsilylalkanols.
9. The process of claim 1 , wherein the alcohol is an aromatic alcohol.
10. The process of claim 1 , wherein the alcohol is selected from phenol, benzyl alcohol or derivatives thereof.
11. The process of claim 1 , wherein the acetyl halide is selected from acetyl bromide or acetyl chloride.
12. The process of claim 1 , wherein the beta-ester of the aspartic acid is a beta-alkyl ester.
13. The process of claim 1 , wherein the beta-ester of the aspartic acid is selected from beta-methyl ester of aspartic acid, beta-ethyl ester of aspartic acid, a beta-propyl ester of aspartic acid, a beta-butyl ester of aspartic acid, a beta-pentyl ester of aspartic acid, a beta-octyl ester of aspartic acid, a beta-alkoxy ether ester of aspartic acid, a beta-allyl ester of aspartic acid, a beta-phenyl ester of aspartic acid or a beta-phenethyl ester of aspartic acid.
14. The process of claim 1 , wherein the halogenating agent is selected from trihaloisocyanuric acid, N-halosuccinimide, hypochlorites and N-halo-p-toluenesulfonamide salts.
15. The process of claim 1 , wherein the halogenating agent is selected from tribromoisocyanuric acid or trichloroisocyanuric acid.
16. The process of claim 1 , wherein the halogenating agent is selected from N-chlorosuccinimide or N-bromosuccinimide.
17. The process of claim 1 , wherein the halogenating agent is selected from sodium hypochlorite or calcium hypochlorite.
18. The process of claim 1 , wherein the halogenating agent is selected from N-chloro-p-toluenesulfonamide sodium salt.
19. The process of claim 1 , wherein the beta-ester of the aspartic acid is formed preferentially to an alpha-ester of the aspartic acid.
20. The process of claim 1 , wherein the beta-ester of the aspartic acid is formed in an amount of greater than about 80%.
21. The process of claim 1 , wherein the beta-ester of the aspartic acid is formed in an amount of greater than about 90%.
22. The process of claim 1 , wherein for each equivalent of the beta-ester of the aspartic acid between about 2 to about 3 equivalents of acetyl halide and between about 12 and about 17 equivalents of alcohol are used in step (a).
23. The process of claim 1 , wherein step (b) is substantially free from the aspartic acid and/or the acetyl halide, and/or halogenating agent, and by-products.
24. The process of claim 1 , wherein step (d) is substantially free from the aspartic acid, the acetyl halide, and/or halogenating agent, and by-products.