1. Field of the Invention
The present invention relates, in general, to the preparation of amino carboxylic acids, salts, and esters, and, in a preferred embodiment, to the preparation of N-(phosphonomethyl)glycine, its salts, and its esters, wherein the method of preparation comprises a carboxymethylation step.
2. Description of Related Art
Amino carboxylic acids are useful in various applications. Glycine, for example, is widely used as an additive in processed meat, beverages, and in other processed food stuffs. It is also used widely as a raw material for pharmaceuticals, agricultural chemicals, and pesticides. N-(phosphonomethyl)glycine, also known by its common name glyphosate, is a highly effective and commercially important herbicide useful for combating the presence of a wide variety of unwanted vegetation, including agricultural weeds. Between 1988 and 1991, approximately 13 to 20 million acres per year worldwide were treated with glyphosate, making it one of the most important herbicides in the world. Convenient and economical methods of preparing glyphosate and other amino carboxylic acids are, therefore, of great importance.
Franz, et al. in Glyphosate: A Unique Global Herbicide (ACS Monograph 189, 1997) at p. 233-257 identify a number of routes by which glyphosate can be prepared. According to one of these, iminodiacetic acid disodium salt (DSIDA) is treated with formaldehyde and phosphorous acid or phosphorous trichloride to produce N-(phosphonomethyl)-iminodiacetic acid and sodium chloride. A carboxymethyl group on the N-(phosphonomethyl) iminodiacetic acid is then oxidatively cleaved in the presence of a carbon catalyst to produce glyphosate acid. A significant drawback of this method is that it produces as a side product three equivalents of sodium chloride per equivalent of glyphosate. Sodium chloride streams of this nature are difficult to recycle because typically after precipitation the salt contains significant quantities of entrapped organic matter. Such entrapped organic matter prevents the sodium chloride from being used for many purposes, for example in foods or feed. Further recrystallization of the sodium chloride adds cost which makes recycle economically unfeasible. Alternate methods of disposing of sodium chloride without detriment to the environment are expensive and difficult.
Franz et al. (at 242-243) describe another method in which N-isopropylglycine is phosphonomethylated to produce N-isopropyl-N-(phosphonomethyl)glycine. In this method, the N-isopropyl-N-(phosphonomethyl)glycine is heated to 300xc2x0 C. with 50% sodium hydroxide and then treated with hydrochloric acid to produce glyphosate. The severe and costly conditions necessary to cleave the N-isopropyl group represents a significant disadvantage of that method. In addition, this method also produces a significant sodium chloride waste stream.
In U.S. Pat. No. 4,400,330, Wong discloses a method for the preparation of glyphosate in which 2,5-diketopiperazine is reacted with paraformaldehyde and a phosphorous trihalide in a carboxylic acid solvent to produce N,Nxe2x80x2-di(phosphonomethyl)-2,5-diketopiperazine. The product is then saponified to form a glyphosate sodium salt. The Wong method is limited by the fact diketopiperazine is a relatively expensive starting material. Furthermore, the conversion of glyphosate sodium salt to the acid form or to other salts produces an undesired sodium chloride waste stream.
Among the objects of the present invention, therefore, is the provision of a well-defined, low-cost process for the production of amino carboxylic acids, in general, and N-(phosphonomethyl)glycine, in particular, and the provision of such a process in which sodium chloride is not generated as a by-product.
In the process of the present invention, an N-acyl amino carboxylic acid is formed via a carboxymethylation reaction. In this reaction, a reaction mixture is formed which contains a base pair, carbon monoxide and an aldehyde with the base pair being derived from a carbamoyl compound and a carboxymethylation catalyst precursor. In a preferred embodiment, the carbamoyl compound and aldehyde are selected to yield an N-acyl amino carboxylic acid which is readily converted to N-(phosphonomethyl)glycine, or a salt or ester thereof having the following structure: 
wherein R7, R8, and R9 independently are hydrogen, hydrocarbyl, substituted hydrocarbyl, or an agronomically acceptable cation. In general, carbamoyl compounds which are selected to produce N-(phosphonomethyl)glycine correspond to structure (II): 
wherein R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, xe2x80x94NR3R4, xe2x80x94OR5, or xe2x80x94SR6;
R2 and R2a are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl;
R3 and R4 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl; and
R5 and R6 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, or a salt-forming cation;
provided, however, (1) at least one of R2 and R2a is hydrogen, hydroxymethyl, amidomethyl, or another substituent which, under the carboxymethylation reaction conditions, is capable of producing an Nxe2x80x94H bond, or (2) R1 is xe2x80x94NR3R4 and at least one of R3 and R4 is hydrogen, hydroxymethyl, amidomethyl, or another substituent which, under the carboxymethylation reaction conditions, is capable of producing an Nxe2x80x94H bond.
In one embodiment of the process of the present invention, therefore, an amino carboxylic acid or a salt or an ester thereof is prepared by carboxymethylation of a carbamoyl compound. In this process, a reaction mixture is formed by combining the carbamoyl compound and a carboxymethylation catalyst precursor in the presence of carbon monoxide and hydrogen. Water and an aldehyde are introduced into the reaction mixture after the carbamoyl compound and the carboxymethylation catalyst precursor are combined and the components of the reaction mixture are reacted to generate a product mixture containing an N-acyl amino carboxylic acid reaction product and a catalyst reaction product.
In another embodiment of the process of the present invention, a reaction mixture containing the carbamoyl compound, carbon monoxide, hydrogen, an aldehyde, and a carboxymethylation catalyst precursor derived from cobalt is formed. The components of the reaction mixture are reacted to generate a product mixture containing an N-acyl amino carboxylic acid reaction product and a catalyst reaction product. The catalyst reaction product is recovered from the product mixture and the catalyst reaction product is regenerated in the presence of the carbamoyl compound.
In a further embodiment, the process of the present invention is directed to the preparation of N-(phosphonomethyl)glycine or a salt or ester thereof. In this process, an N-acyl amino acid reaction product is prepared by carboxymethylating a carbamoyl compound in a reaction mixture formed by combining the carbamoyl compound, formaldehyde, carbon monoxide, hydrogen and a carboxymethylation catalyst precursor derived from cobalt. The N-acyl amino acid reaction product is converted to N-(phosphonomethyl)glycine or a salt or ester thereof wherein said conversion comprises deacylating the N-acyl amino acid reaction product to generate a carboxylic acid and an amino acid. The carboxylic acid is reacted with an amine to generate the carbamoyl compound or a compound from which the carbamoyl compound may be derived.
In a further embodiment, N-(phosphonomethyl)glycine or a salt or ester thereof is derived from N-acetyliminodiacetic acid. The N-acetyliminodiacetic acid is prepared by carboxymethylating acetamide in a reaction mixture formed by combining acetamide, acetic acid, water, formaldehyde, carbon monoxide, hydrogen, and a carboxymethylation catalyst precursor derived from cobalt. The N-acetyliminodiacetic acid is converted to N-(phosphonomethyl)glycine or a salt or ester thereof wherein said conversion comprises deacylating N-acetyliminodiacetic acid.
In a further embodiment, N-(phosphonomethyl)glycine or a salt or ester thereof is derived from an N-acyl amino acid carboxylic acid reaction product which is prepared from a reaction mixture containing a carbamoyl compound selected from among ureas and N-alkyl substituted amides, a carboxymethylation catalyst precursor, formaldehyde, and carbon monoxide. The N-acyl amino carboxylic acid reaction product is then converted to N-(phosphonomethyl)glycine or a salt or ester thereof. If the carbamoyl compound is an N-alkyl substituted amide, the conversion step(s) comprise oxidatively dealkylating the N-acyl amino carboxylic acid reaction product in the presence of oxygen using a noble metal catalyst.
The present invention is additionally directed to the certain key starting materials used and intermediates prepared in the process of the present invention.
For example, in one embodiment, the present invention is directed to a compound having the formula: 
In another embodiment, the present invention is directed to a compound having the formula: 
In yet another embodiment, the present invention is directed to an acetamide equivalent compound selected from the group consisting of compounds having the formula: 
wherein R13 and R14 are independently hydrogen, hydroxymethyl, alkyl, carboxymethyl, phosphonomethyl, or an ester or salt of carboxymethyl or phosphonomethyl; R15, R16 and R17 are independently alkyl or xe2x80x94NR3R4; and R3 and R4 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl.
In still a further embodiment, the present invention is directed to a compound having the formula: 
wherein R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, xe2x80x94NR3R4, or SR6; R3 and R4 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl; and R6 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a salt-forming cation.
Further scope of the applicability of the present invention will become apparent from the detailed description provided below. It should be understood, however, that the following detailed description and examples, while indicating preferred embodiments of the invention, are given by way of illustration only since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.