MXPA99004308A - Method of preparing amino carboxylic acids - Google Patents

Abstract

Process for the preparation of an N-acyl amino carboxylic acid by means of a carboxymethylation reaction. In this reaction, a reaction mixture is formed which contains a base pair, carbon monoxide, hydrogen and an aldehyde with the base pair conprising 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.

Description

METHOD FOR PREPARING AMINOCARBOXYLIC ACIDS BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates, in general, to the preparation of aminocarboxylic acids, salts and esters thereof and, in a preferred embodiment, to the preparation of N- (phosphonomethyl) glycine, its salts and its esters, wherein the method of Preparation comprises a step of carboxymethylation.

DESCRIPTION OF THE RELATED TECHNIQUE The aminocarboxylic acids are useful in various applications. For example, glycine is widely used as an additive in processed foods, beverages and other processed food materials. It is also widely used 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 to combat the presence of a large variety of undesirable vegetation, including agricultural weeds. Between 1988 and 1991 approximately 5,252 to 8.08 million hectares per year were treated, worldwide, with glyphosate, which makes it one of the most important herbicides in the world. Therefore, convenient and economical methods for preparing glyphosate and other aminocarboxylic acids are of utmost importance. Franz and co-authors, in Glyphosate: A Unique Blogal Herbicide (ACS Monograph 189, 1997), on pages 233-257, identify numerous routes by which glyphosate can be prepared. According to one of them, the disodium salt of iminodiacetic acid (DSIDA) is treated with formaldehyde and phosphorous acid or phosphorus trichloride to produce N- (phosphonomethyl) -iminodiacetic acid and sodium chloride. A carboxymethyl group is then oxidatively divided into N- (phosphonomethyl) iminodiacetic acid, in the presence of a carbon catalyst, to produce the glyphosate acid. An important disadvantage in 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 amounts of trapped organic material. Such trapped organic material prevents the use of sodium chloride for many purposes, for example, in food or in food. The subsequent recrystallization of sodium chloride increases the cost, which makes recycling economically impossible. Other alternative methods of disposing of sodium chloride without detriment to the environment are expensive and difficult.

Franz and coauthors (at 242-243) describe another method by which phosphonomethylane N-isopropylglycine to produce N-isopropyl-N- (phosphonomethyl) glycine. In this method, N-isopropyl-N- (phosphonomethyl) glycine is heated at 300 ° C with 50% sodium hydroxide and then treated with hydrochloric acid to produce the glyphosate. The severe and expensive conditions, necessary to separate the N-isopropyl group, represent a major disadvantage in that method. In addition, this method also produces a significant stream of waste sodium chloride. In U.S. Patent No. 4,400,330, Wong writes a method for the preparation of glyphosate, in which 2,5-diketopiperazine is reacted with paraformaldehyde and a phosphorus trihalide in a carboxylic acid solvent, to produce N, N'- (di (phosphonomethyl) -2,5-diketo-piperazine.) The product is then saponified to form a sodium salt of glyphosate.Wong's method is limited by the fact that diketopiperazine is a relatively expensive starting material. , the conversion of the sodium salt of glyphosate to the acid form or to other salts, produces an undesirable stream of waste sodium chloride.

BRIEF DESCRIPTION OF THE INVENTION Among the objectives of the present invention, therefore, is to provide a low-cost, well-defined process for the production of aminocarboxylic acids, in general, and N- (phosphonomethyl) glycine, in particular; and provide said procedure in which no sodium chloride is generated as a by-product. In the process of the present invention, an N-acyl-aminocarboxylic acid is formed by a carboxymethylation reaction. In that reaction, a reaction mixture containing a base pair, carbon monoxide and an aldehyde is formed, the base pair being derived from a carbamoyl compound and a carboxymethylation catalyst precursor. In a preferred embodiment, the carbamoyl compound and the aldehyde are selected to produce an N-acylamino-carboxylic acid, which is readily converted to N- (phosphonomethyl) -glycine, or a salt or ester thereof, which It has the following structure: wherein R7, R8 and Rg, independently, are hydrogen, hydrocarbyl, substituted hydrocarbyl or an agronomically acceptable cation. In general, carbamoyl compounds that are selected to produce N- (phosphonomethyl) glycine correspond to structure (II): wherein: R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, -NR3R4, -OR5 or -SR6; 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, that (1) at least one of R2 and R2a is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing a N-H linkage; or (2) R1 is -NR3R4 and at least one of R3 and R4 is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing an N-H linkage. In one embodiment of the process of the present invention, therefore, an aminocarboxylic acid or a salt or 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 is combined with the carboxymethylation catalyst precursor, and the components of the reaction mixture are reacted to generate a product mixture containing a reaction product of N-acyl-aminocarboxylic acid and a catalyst reaction product. In another embodiment of the process of the present invention, a reaction mixture is formed which contains the carbamoyl compound, carbon monoxide, hydrogen, an aldehyde and a carboxymethylation catalyst precursor, cobalt derivative. The components of the reaction mixture are reacted to generate a product mixture containing a reaction product of N-acyl-aminocarboxylic acid 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 still another 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, a reaction product of N-acylamino acid is prepared by carboxymethylation of a carbamoyl compound in a reaction mixture formed by combining the compound carbamoyl, formaldehyde, carbon monoxide, hydrogen and a carboxymethylation catalyst precursor, cobalt derivative. The reaction product of N-acylamino acid is converted to N- (phosphonomethyl) glycine or a salt or ester thereof, where the conversion comprises deacylating the reaction product of N-acylamino acid to generate a carboxylic acid and an amino acid. The carboxylic acid is reacted with the amine to generate the carbamoyl compound or a compound from which the carbamoyl compound can be derived. In still another embodiment, N- (phosphonomethyl) -glycine or a salt or ester thereof, of N-acetyliminodiacetic acid, is derived. The N-acetyliminodi-acetic acid is prepared in a reaction mixture formed by combining acetamide, acetic acid, water, formaldehyde, carbon monoxide, hydrogen and a carboxymethylation catalyst precursor, cobalt derivative. The N-acetyliminodiacetic acid is converted to N- (phosphonomethyl) glycine or a salt or ester thereof, where the conversion comprises deacylating N-acetyliminodiacetic acid. In another embodiment N- (phosphonomethyl) glycine or a salt or ester thereof is derived from the reaction product of N-acylamino acid and carboxylic acid, which is prepared from a reaction mixture containing a carbamoyl compound selected from the ureas and the N-alkyl substituted amides, a carboxymethylation catalyst precursor, formaldehyde and carbon monoxide. The reaction product of N-acylaminocarboxylic acid 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) comprises (n): oxidatively dealkylating the reaction product of N-acyl-aminocarboxylic acid, in the presence of oxygen, using a noble metal catalyst. The present invention is further directed to the certain key starting materials used and to the intermediates prepared in the process of the present invention. Other fields of application of the present invention will be apparent from the detailed description that follows. However, it should be understood that the following detailed description and examples, while indicating preferred embodiments of the invention, are given by way of illustration only, as various changes and modifications will become apparent to those skilled in the art within the scope of the invention. spirit and scope of the invention, from that detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a graph of the molar ratio of acetic acid to cobalt, against the yield of N-acetyliminodiacetic acid (XVI), under the conditions described in example 4. Figure 2 is a graph of the molar ratio of acetic acid to cobalt, against the yield of N-acetyliminodiacetic acid (XVI), under the conditions described in Example 5. Figure 3 is a graph of the time required to regenerate a cobalt (II) salt under five separate series of reaction conditions , in which the partial pressure ratio of carbon monoxide to hydrogen is decreased, and the concentrations of acetamide (AcNH2) and acetic acid (HOAc) are varied, under the conditions described in example 13.

DETAILED DESCRIPTION OF THE INVENTION The process of the present invention is broadly directed to the carboxymethylation of carbamoyl compounds, in which strong acid cocatalysts or anhydrous conditions are not necessary. Schematically illustrated in reaction scheme 1, a preferred embodiment of this method, in which hydridocobaltotetracarbonyl is identified for convenience of discussion, such as the carboxymethylation catalyst precursor.

REACTION SCHEME 1 Compound + hydridocobalt - CO pair / aldehyde product of + Product of Carbamoyl tetracarbonyl bases 5 acid reaction - reaction of N-acylamino Cobalt Reproduction of cobalt Salt of Co (ll) Co2 (C As illustrated, a carbamoyl compound is reacted with hydridocobaltotetracarbonyl to produce a base pair of the present invention. The base pair, when present in a reaction mixture, together with carbon monoxide and an aldehyde (or an aldehyde source), reacts to produce a reaction product N-acylamino-carboxylic acid and a cobalt reaction product . The reaction product can then be deacylated to N-acylamino-carboxylic acid, for example, by hydrolysis, or it can be reacted in another manner, as described elsewhere herein. Hydrodocobaltotetracarbonyl which is reacted to form the base pair in any of the following ways can be obtained. In one embodiment of the present invention, it is generated in situ, in a reaction mixture prepared by combining the carbamoyl compound and dicobaltoctaccarbonyl by recycling and regenerating a cobalt (II) salt which is recovered from a previous carboxymethylation step. The recovery of a cobalt (II) salt is described to convert it to the cobalt-octacarbonyl dimer, in 'Weisenfeld, Ind. Eng. Chem. Res., Volume 31, No. 2, pages 636-638 (1992). In a second embodiment of the present invention, the cobalt (II) salt is regenerated using carbon monoxide and hydrogen by conventional techniques to produce hydridocobaltotetracarbonyl, which is combined with the carbamoyl compound in a reaction mixture. In a third embodiment of the present invention, the hydridocobaltotetracarbonyl is converted using carbon monoxide and hydrogen in the presence of the compound which produces a reaction mixture containing the base pair; Aldehyde is then introduced into the reaction mixture to produce the reaction product N-acyl-aminocarboxylic acid.

A.- PREPARATION OF THE PAR OF BASES The base pair is formed by the reaction of a carbamoyl compound and a carboxymethylation catalyst precursor. In general, the carbamoyl compound is an amide, a urea or a carbamate, preferably an amide or a urea. More preferably, the carbamoyl compound is a compound having the structure (II): wherein R1, R2 and R2a are as previously defined. In one embodiment of the present invention, R1 is hydrocarbyl or substituted hydrocarbyl, typically a hydrocarbyl or substituted hydrocarbyl of 1 to about 20 carbon atoms. In this embodiment R1 preferably is from 1 to about 10 carbon atoms, more preferably, about 1 to 6 carbon atoms, still more preferable, 1 carbon atom. In another embodiment of the present invention R1 is -NH3R4. In that embodiment, R3 and R4 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl. In general, if any of R3 or R4 is hydrocarbyl, it is a hydrocarbyl of 1 to about 20 carbon atoms, preferably 1 to about 10 carbon atoms, more preferably, 1 to about 6 carbon atoms, and even more preferable, methyl or isopropyl. If R3 or R4 is substituted hydrocarbyl, it is typically hydrocarbyl substituted from 1 to about 20 carbon atoms, preferably from 1 to about 10 carbon atoms, more preferably, 1 to about 6 carbon atoms, and still more preferable is phosphonomethyl (-CH2PO3H2), hydroxymethyl (-CH2OH), amidomethyl (-CH2N (R ') C (O) R "), carboxymethyl (-CH2CO2H), or an ester or a carboxymethyl or phosphonomethyl salt. R2a are each hydrocarbyl or substituted hydrocarbyl, it is preferred that at least one of R3 and R4 is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing an NH linkage. , the preferred amidomethyl substituents correspond to the structure: wherein R11 and R12 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxymethyl, carboxymethyl, phosphonomethyl, or an ester or a carboxymethyl or phosphonomethyl salt. Preferably at least one of R 2 and R 2a is hydrogen, hydroxymethyl or amidomethyl, More preferably, at least one of R 2 and R 2a is hydrogen. However, if R2 or R2a is hydrocarbyl, it is typically a hydrocarbyl of 1 to about 20 carbon atoms, preferably 1 to about 10 carbon atoms, more preferably 1 to about 6 carbon atoms and, still, more preferable, methyl or isopropyl. If R2 or R2a is substituted hydrocarbyl, it is typically a hydrocarbyl substituted from 1 to about 20 carbon atoms, preferably from 1 to about 10 carbon atoms and, more preferably, from 1 to about 6 carbon atoms. The substituted hydrocarbyl may be, for example, phosphonomethyl, hydroxymethyl, amidomethyl, carboxymethyl, an ester or a carboxymethyl or phosphonomethyl salt, or (N'-alkyl-amido) methyl, preferably phosphonomethyl, carboximyl, amidomethyl or an ester or a carboxymethyl or phosphonomethyl salt. It is possible that R2 and R2a are non-identical. For example, R2 may be hydrocarbyl and R2a may be substituted hydrocarbyl. In one embodiment, R2 can be an alkyl, such as methyl, while R2a can be, for example, a (N'-alkylamido) methyl group, such as (N'-methylamido) methyl or hydroxymethyl. The carboxymethylation catalyst precursor that is reacted with the carbamoyl compound to form the base pair can be any composition known to be useful in carboxymethylation reactions which generally contain a metal of group VIII of the Periodic Table (CAS version). ). These compositions are referred to as the carboxymethylation catalyst precursors herein, since the precise form of the catalyst participating in the reaction has not been precisely determined. Without being bound by any particular theory, however, it is currently believed that the base pair itself that is produced by the interaction of the carboxymethylation catalyst precursor and the carbamoyl compound in the presence of carbon monoxide and hydrogen, serves as a catalyst for the carboxymethylation reaction. In any case, the cobalt or palladium carboxymethylation catalyst precursor is preferably derived, preferably from cobalt, and, even more preferably, the metal cobalt carboxy, cobalt oxide, organic and inorganic salts carboxymethylation catalyst precursor is derived. for example, halides such as cobalt chloride and cobalt bromide, aromatic and aliphatic carboxylates, such as cobalt acetate, cobalt propionate, cobalt octanoate, cobalt stearate, cobalt benzoate and cobalt naphthenate, and complex compounds containing one or more ligands such as carbonyls, nitriles and phosphines. Preferred cobalt-containing carboxymethylation catalyst precursors are: dicobalto-octacarbonyl (Co2 (CO) 8), hydridocobalt-tetracarbonyl (HCo (CO) 4), cobalt-tetracarbonyl anion ([Co (CO) 4] ~ 1) or a salt of cobalt (II). Depending on the nature of the carbamoyl compound, the bass pair can be formed in the presence of the aldehyde (or an aldehyde source that can contain water) and carbon monoxide, or it is first formed and then combined with the aldehyde source . When the carbamoyl compound is an amide, such as acetamide, the reaction mixture can be formed by introducing the amide, the aldehyde source, the carbon monoxide and the carboxymethylation catalyst precursor into the mixture, without pre-mixing the amide and the amide. carboxymethylation catalyst precursor to form the base pair; as a result, the base pair is formed in the presence of the aldehyde source. To obtain significant yields of reaction product of N-acylamino-carboxylic acid, when urea or a substituted urea is used as bis-phosphonomethylurea, as the carbamoyl compound, however, the base pair is preferably formed in the essential absence of water and aldehyde sources that contain water; under these conditions, the base pair is obtained in good yield. The resulting base pair is then mixed with the source of aldehyde and carbon monoxide. Without attempting to adhere to any particular theory, and based on experimental evidence obtained so far, it appears that the formation of the desired base pair is related to the basicity of the carbamoyl compound; that is, carbamoyl compounds, such as acetamide, appear to be sufficiently basic to produce the desired base pair in the presence of water and aldehyde sources containing water, while ureas that are less basic than acetamide are not. In other words, the experimental evidence obtained to date suggests: (1) the carboxymethylation catalyst precursor is deprotonated under the conditions of the carboxymethylation reaction, and forms a base pair with various species present in the reaction mixture; (2) only those base pairs formed with the carbamoyl compound are productive (ie, they will lead to the formation of the N-acylaminocarboxylic acid reaction product) and (3) the amides, such as acetamide, will form a sufficiently basic pair with the hydridocobaltotetracarbonyl anion, in the presence of an aldehyde source containing water, while the urea and the comparable bases do not.

B.- THE REACTION OF CARBOXIMETILACIÓN In the process of the present invention, the base pair that is formed is reacted with carbon monoxide and an aldehyde (or an aldehyde source) in a carboxymethylation reaction to produce a reaction product of N-acylaminocarboxylic acid. The pressure at which the carboxymethylation reaction is carried out can be about 1, 400 kPa to 28,000 kPa. Preferably the pressure is about 7,000 kPa to 26,000 kPa and, more preferably, about 9,000 kPa to 24,000 kPa. In the carboxymethylation reaction, hydrogen or other diluent gases, such as nitrogen or helium, can be introduced with the carbon monoxide. Preferably the atmosphere contains a significant partial pressure of hydrogen. Typically, the partial pressure ratio of carbon monoxide to hydrogen will be at least 1: 1, preferably around 70:30 to about 99: 1 and, more preferably, about 85:15 to 97: 3. In general, the carboxymethylation reaction can be operated at any temperature at which reagents and equipment can be conveniently handled. Typically the reaction temperature will be within the range of about 50 ° C to 170 ° C, preferably about 65 ° C to 140 ° C, more preferably about 80 ° C to 130 ° C and, even more preferable, around 95 ° C to 115 ° C.

The molar ratio of the metal atoms of the carboxymethylation catalyst to the carbamoyl compound can vary on a scale from about 0.1 to about 30. Preferably, it is about 0.5 to 15, more preferable, about 2 to 13. The aldehydes useful in the process of the present invention may be present in pure form, in polymeric form, in aqueous solution or as acetal. A wide scale of aldehydes can be used; the aldehyde may contain more than one formyl group and, in addition to the oxygen atom (s) of the formyl group (s), the aldehyde may contain other oxygen atoms or other heteroatoms, such as in the fufruryl acetaldehyde, 4-acetoxyphenylacetaldehyde and 3-methyl-thiopropionaldehyde. More suitably, the aldehyde has the general formula R-CHO, wherein R is hydrogen, hydrocarbyl or substituted hydrocarbyl. In general, R contains up to 20 carbon atoms, more suitably, up to 10 carbon atoms. Examples of said aldehydes are phenylacetaldehyde, formylcyclohexane and 4-methylbenzaldehyde. Preferably R is hydrogen, a linear or branched alkyl group containing up to 6 carbon atoms, or an arylalkyl group in which the aryl contains from 6 to 12 carbon atoms and the alkyl contains up to 6 carbon atoms. It is more preferred that the aldehyde be formaldehyde, acetaldehyde, 3-methylthiopropionaldehyde or isobutyraidehyde and, in a particularly preferred embodiment, the aldehyde is formaldehyde, the formaldehyde source being formalin.

In one embodiment of the present invention, an acid cocatalyst is included in the reaction mixture. For some carbamoyl compounds, such as acetamide (and its acetamide equivalents), the acid cocatalyst is preferably an organic acid, such as a carboxylic acid having a pKa greater than about 3. The organic acid cocatalyst may be, for example : formic acid, acetic acid or propionic acid, preferably formic acid or acetic acid and, very preferably, acetic acid. In general, when the carbamoyl compound is an amide, it is preferred that the organic acid cocatalyst be the carboxylic acid corresponding to the amide (ie, the carboxylic acid of which the amide is a derivative). The carboxymethylation reaction can be carried out in the presence of a solvent that is physically and chemically comble with the reaction mixture. Preferably the solvent is a weaker base than the carbamoyl compound. The solvent may be, for example, an ether, a ketone, an ester, a nitrile, a carboxylic acid, a formamide, such as dimethylformamide, or a mixture thereof. Preferably the solvent is an ether, a ketone or a nitrile; more preferably, the solvent may be ethylene glycol, dimethoxyethane (DME), tetrahydrofuran (THF), acetone, 2-butanone, acetonitrile, acetic acid or tert-butyl methyl ether. In a preferred embodiment, the carboxymethylation reaction is carried out in the presence of water. In this embodiment, the molar ratio of water to the carbamoyl compound in the carboxymethylation reaction mixture is generally less than about 10: 1, preferably between about 2: 1 and about 5: 1 and, more preferably, between about of 3: 1 and around 4: 1. The charge is measured as the mass of carbamoyl compound divided by the mass of the reaction solvent. Whoever is skilled in the art will recognize that the useful load scales will depend, in part, on the physical state of the carbamoyl compound used as starting material, under the reaction conditions employed, and its compatibility with the solvents used. Typically, the charge will vary throughout the approximate scale of 0.001 g of carbamoyl compound per gram of solvent (g > gs) in the reaction mixture, up to about 1 g_ gs- Preferably, it is about 0.01 gc / gs, more preferable, at least about 0.1 gc / s »still more preferable, between about 0.12 gc / gs and about 0.35 gc / gs, and in a particularly preferred embodiment, between about 0.15 gc / gs and about 0.3 gc / gs. The reaction can be carried out intermittently or continuously. When carried out continuously, the residence time in the reaction zone can vary widely, depending on the specific reagents and the conditions employed. Typically, the residence time may vary on a scale of about 1 minute to 500 minutes, preferably about 10 minutes to 250 minutes, more preferably, about 30 minutes to 100 minutes. When operating in an intermittent mode, the reaction time typically ranges from approximately 10 seconds to 12 hours, preferably, from about 2 minutes to 6 hours, more preferably, about 10 minutes to 3 hours.

C- RECOVERY OF THE CARBOXIMETERATION CATALYST After the carboxymethylation reaction, the catalyst is preferably recovered to be used again in a subsequent carboxymethylation reaction. The nature of the recovery step will vary depending on the catalyst, and any catalyst recovery method that is compatible with the carboxymethylation reaction mixture and with the products, Weisenfeld may be used (US Patent No. 4,954,466) reported a method for recovering cobalt catalyst values of carboxymethylation reaction mixtures, in which a cobalt-N-acetyliminodiacetic complex was dissolved in an aqueous solution with a strong acid, and then extracted with a hydrocarbon solvent containing a trialkylamine, to transfer the cobalt of the aqueous solution to the hydrocarbon solvent. Then the cobalt was separated from the hydrocarbon solvent, with water, and precipitated with a strong base. Another method for recovering cobalt catalyst values from carboxymethylation reaction mixtures is described in European Patent Application Publication No. EP 0 779 102 A1. In that method cobalt is recovered from the carboxymethylation reaction mixtures, such as those producing N-acyl sarcosines, by treatment of the final reaction mixture with aqueous hydrogen peroxide or with aqueous hydrogen peroxide and sulfuric acid, thereby converting the cobalt catalyst to water-soluble cobalt (II) salts The aqueous phase containing the water-soluble cobalt (II) salts is then separated from the non-aqueous phase. The excess hydrogen peroxide is then removed from the aqueous phase, for example, by heating. An alkali metal hydroxide is then added to the aqueous phase, which causes precipitation of the cobalt hydroxide (II). The cobalt hydroxide (II) is then collected and washed in preparation for its regeneration into a cobalt catalyst. Alternatively, and in accordance with one aspect of the present invention, the completed carboxymethylation reaction mass is oxidized to a soluble cobalt (II) species. The oxidation step is carried out by exposing the reaction mixture of caboxymethylation, when complete, to a gas containing molecular oxygen, for a suitable time. Oxygen exposure can be achieved by any convenient means, for example, by bubbling the oxygen-containing gas through the reaction mixture, or by maintaining an atmosphere of an oxygen-containing gas over the reaction mixture. The progress of the reaction can be monitored by color changes, in which the final oxidized system has an intense red color or a purple-red color, which does not undergo additional changes. Alternatively, the progress of the reaction can be monitored by infrared spectroscopy, or by cyclic voltammetry. The concentration of molecular oxygen in the oxygen-containing gas used in the cobalt recovery step of the present invention may vary depending on the reaction conditions. The oxygen concentration is typically about 0.1% by weight to 100% by weight. The higher oxygen concentrations in the oxygen-containing gas will typically cause faster rates of the oxidation reaction. However, relatively low oxygen concentrations in the oxygen-containing gas are favored when volatile organic solvents are present in the reaction mixture, which thus presents a safety risk. It is preferred that the oxygen concentration in the oxygen-containing gas be an allergen of 5% by weight to about 80% by weight, more preferably, about 10% by weight to 30% by weight. The gas containing oxygen may also contain a diluent gas. It is preferred that the diluent be inert under the conditions of the reaction. Typical diluent gases are: nitrogen, helium, neon and argon, preferably nitrogen. Air can conveniently be used as an oxygen-containing gas. Oxidation can be carried out under atmospheric pressure, at atmospheric pressure or at superatmospheric pressure. It is preferred to carry it out at pressures ranging from about 70 to about 700 kPa, more preferably, from about 200 to about 400 kPa.

The oxidized cobalt (II) species can be converted, in situ, to an insoluble cobalt (II) salt complex, with the product of the N-acylamino-carboxylic acid reaction, allowing the reaction mixture to stand for a period of time. appropriate time. For example, it is convenient to allow the reaction mixture to stand overnight to achieve the precipitation of the insoluble cobalt (II) salt complex. As the insoluble cobalt (II) salt complex forms, it precipitates out of the solution. The formation and precipitation of the cobalt (II) salt complex can be accelerated, elevating the temperature of the system. The temperature of the reaction mixture during the oxidation step and during the complexing step of the present invention typically ranges from about room temperature to about 150 ° C, preferably about 60 to 110 ° C, more preferable, around 70 ° C to 100 ° C. Alternatively, the formation and precipitation of oxidized cobalt (II) salts is facilitated by the presence of a composition such as an organic acid (eg, formic, acetic, oxalic or propionic acids), which is present in the step of carboxymethylation. Alternatively, the composition can be introduced when the step of the carboxymethylation reaction is completed. The insoluble cobalt (II) salt complex can be separated from the reaction mass by any convenient means, for example, by filtration. or centrifugation, and can subsequently be recycled to fresh cobalt catalyst for use in an additional carboxymethylation reaction. The oxidation to the cobalt (II) species and the conversion of the cobalt (II) species to an insoluble cobalt (II) salt complex can optionally be carried out as two discrete steps or can be combined in a single step, in which is carried out oxidation and salt formation almost simultaneously. As a further alternative, the formation and precipitation of the oxidized cobalt (II) salts can also be accelerated by the addition of a solvent. Typical solvents include: dimethyl ether ("DME"), acetone or any suitable solvent in the carboxymethylation step. In general, the amount of excess solvent is at least 50% of the volume of the reaction mass, more preferably, about 75% to about 150% of the reaction mass and, most preferably, between about 90% and about 110% of the reaction mass. Instead of introducing molecular oxygen into the carboxymethylation reaction mixture, the cobalt (II) species can be formed under anaerobic conditions. In this approach the reaction mixture is simply heated, refluxed or distilled at a temperature of about 60 ° C to 100 ° C, to effect the precipitation of an insoluble salt of cobalt (II). See, for example, example 27. Additionally, the formation and precipitation of the oxidized cobalt (II) salts can also be accelerated by the presence of an organic acid or by the addition of a solvent, as previously described in the case in which molecular oxygen is introduced into the system.

P.- CATALYST REGENERATION Various methods for regenerating a cobalt catalyst have been reported in the literature, which can be used in accordance with one aspect of the present invention. For example, in US Pat. No. 4,954,466a, by Weisenfeld, it is suggested to convert a precipitate of cobalt (II) to dicobaltoctaccarbonyl, by reacting the precipitate with carbon monoxide and hydrogen, at a temperature of 150 to 180 ° C, with a pressure of 10,345 to 41, 380 kPa. Another method for the regeneration of a cobalt catalyst for carboxymethylation is described in European Patent Application Publication No. EP 0 779 102 A1. In this method, the cobalt hydroxide is recovered from a carboxymethylation reaction and introduced into the molten bath of an N-acylamino acid derivative., such as an N-acilsarcosine. The mixture is then added to a polar aprotic solvent and reacted with carbon monoxide or with a mixture of carbon monoxide and hydrogen to form a catalytic mixture of carboxymethylation. Surprisingly, it has been found that the rate of regeneration of the cobalt (II) salt can be dramatically increased if it is reacted with a carbamoyl compound of the present invention, together with carbon monoxide and hydrogen. Advantageously, the product of this reaction is the base pair that participates in the carboxymethylation step. When the carbamoyl compound is an amide, therefore, productivity is significantly increased by the regeneration of the cobalt (II) salt, in the presence of the amide. Additionally, when the carbamoyl compound is a urea, the resulting base pair will react with carbon monoxide and an aldehyde to produce a reaction product of N-acyl-aminocarboxylic acid, in relatively good yields; a product that is not believed to have been previously reported to have been obtained by a carboxymethylation reaction. According to the present invention, therefore, when the carbamoyl compound is an amide, the cobalt (II) salt can be regenerated in the presence of the amide, an aldehyde, the amide and the aldehyde, or neither the amide nor the aldehyde. When the carbamoyl compound is urea (or another compound which is a less competent base than the amides), however, the cobalt (II) salt is preferably regenerated in the presence of the carbamoyl compound and in the essential absence of water and aldehyde sources that contain water. If the active catalyst mixture is regenerated in the absence of the carbamoyl compound, therefore, it is further advantageous to add the carbamoyl compound to the reaction mixture before the addition of the aldehyde source. For example, when the carbamoyl compound is a urea (structure (II), wherein R1 is -NR3R4), it is advantageous to treat the cobalt (II) salt with carbon monoxide, hydrogen and urea, before adding the source of aldehyde to the reaction mixture. During regeneration, the reaction pressure generally varies between about 1, 400 and about 28,000 kPa, preferably between about 5,600 and about 26,000 kPa; and more preferably, between about 10,500 and about 24,000 kPa. In general, the partial pressure ratio of carbon monoxide at hydrogen partial pressure during regeneration ranges from about 99: 1 to about 1: 99, preferably from about 30: 709 to about 90:10 and, more preferable, around 50:50 to around 75:25. The progress of the regeneration reaction can be monitored by monitoring gas absorption, for example, by monitoring the column pressure. During the regeneration step it is often advantageous to heat the reaction mixture. Typically, the temperatures of the reaction mixture range from about 70 ° C to about 170 ° C, preferably around 90 ° C to 150 ° C, and more preferably, about 100 ° C to 140 ° C. The reaction times for the regeneration step can vary from about 5 minutes to about 2 hours and, more preferably, from about 10 minutes to about 1 hour. If desired, the regeneration step can be carried out in the presence of the organic acid cocatalyst used in the carboxymethylation step. If desired, the regenerated complex of active catalyst can be used directly in a carboxymethylation reaction, after regeneration. The anionic portion of the cobalt salt is not critical to the regeneration step. For example, the cobalt (II) may be in the form of a salt of the conjugate base of the carboxymethylation reaction product from which the cobalt (II) was recovered. Alternatively, the cobalt (II) may be in any other convenient form, such as cobalt acetate tetrahydrate, cobalt stearate, cobalt acetonate or cobalt oxalate.

E.- THE DEVELOPMENT In many embodiments of the present invention it is convenient to deacylate the reaction product of N-acyl-aminocarboxylic acid, which is the result of the carboxymethylation step. In general, deacylation can be achieved by hydrolysis or by the formation of a diketopiperazine species. In general, the reaction product of N-acylaminocarboxylic acid is hydrolyzed in the presence of a hydrolysis catalyst, for example, an acid or a base, preferably a mineral acid. Suitable mineral acids, useful for this purpose, include: hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid or phosphorous acid. The product of the N-acyl reaction can be hydrolyzed in the absence of a mineral acid to form an amino acid by heating the reaction product of N-acyl-aminocarboxylic acid in the presence of water. Instead of hydrolyzing, the reaction product of N-acylaminocarbonylic acid can be deacylated, and cyclized in a single step to form 2,5-diketopiperazines, as illustrated in reaction scheme 2: REACTION SCHEME 2 wherein R2 and R2a are independently hydrogen, alkyl or carboxymethyl, or their salts or esters. Examples of such reactions include the preparation of 1,4-di (carboxymethyl) -2,5-diketopiperazine (XVII) from N-acetyliminodiacetic acid (XVI) (see reaction scheme 7), the preparation of 2, 5-diketopiperazine (XXX) from N-acetylglycine (XVIII) (see reaction scheme 9a) and the preparation of 1,4-dimethyl-2,5-diketopipeazine (XXXI) from N-acetyl-N- methylglycine (XX) (see reaction schemes 11 and 15). Typically, the reaction temperatures for the formation of the diketopiperazines range from about 100 ° C to about 250 ° C, preferably between about 150 and about 220 ° C, more preferably, about 185 ° C to 200 ° C. C. The reaction is relatively rapid and the reaction time typically ranges from about 1 minute to about 10 hours, preferably about 5 minutes to about 5 hours; even more preferable, about 10 minutes to about 3 hours. The amount of water added, measured as a percentage of the starting material, generally ranges up to about 85% by weight, preferably about 5% by weight to 70% by weight and, more preferably, about 9 { % by weight a % by weight. If desired, a catalyst can be added to the reaction mixture. It is preferred that it be an organic acid and, even more, it is preferred that it be a carboxylic acid of about 1 to 3 carbon atoms. What is most preferred is that the acid catalyst is acetic acid. The solvents may optionally be present in the reaction mixture.

For example, ethers, ketones or nitriles can be added. The formation of the 2,5-diketopiperazines from the reaction products of N-acylamino acid is advantageous for numerous reasons. As a general rule, they are less soluble in many solvents and in water, that the corresponding amino acid. As a result, diketopiperazine can be more easily precipitated from the reaction mixture, separated and handled. Additionally, since the deacylation reaction does not require strong mineral acids, it is less corrosive to the processing equipment than a hydrolysis reaction in which strong mineral acids are employed. The deacylation and hydrolysis reactions of the N-acylamino acid reaction products can occur simultaneously, which results in a mixture of products. That mixture of deacylation and hydrolysis products can be used subsequently as it is produced, that is, without separation or purification, or it can be separated to its component products. The ratio of the hydrolysis and deacylation products, obtained in the final reaction mixture, depends on the conditions selected for the reaction. For example, in reaction scheme 3, N-acetyliminodiacetic acid (XVI) is heated in water to form iminodiacetic acid (XIV), 1,4-di (carboxymethyl) -2,5-diketopiperazine (XVII) or mixtures thereof.

REACTION SCHEME 3 (XVII) The ratio of (XIV) to (XVII) can be controlled as a function of the various conditions under which the reaction is carried out. For example, Table 1 shows the effect on the ratio of (XIV) to (XVII), as a consequence of heating N-acetyliminodiacetic acid (XVI) (45 grams) under varying conditions of temperature, time, added water and added acetic acid . (See example 28 for a more complete description).

TABLE 1 If desired, the reaction conditions that maximize the amount of compound (XVII) formed relative to the amount of compound (XIV) formed can be selected. By way of illustration, examples 28.1 and 28.2 and examples 28.7, 28.8 and 28.9 show that longer reaction times tend to increase the ratio of (XVII) to (XIV). Similarly, examples 28.4 and 28.8 show that higher temperatures tend to increase the ratio of (XVII) to (XIV). In contrast, examples 28.2 and 28.4 show that increasing the amount of water added decreases the ratio of (XVII) to (XIV). Examples 28.6 and 28.7 show that increasing the amount of added carboxylic acid, in this case acetic acid, decreases the ratio of (XVII) to (XIV). At temperatures below 100 ° C, the reaction may take several hours. By increasing the pressure to the reaction system, temperatures well above 100 ° C can be achieved and, under these conditions, hydrolysis and deacylation can be obtained in much shorter periods of time, for example, in minutes. In general, a wide variety of N-acylaminocarboxylic acid reaction products, useful in the present invention, can be hydrolyzed or deacylated using the conditions described herein. Examples of reaction products of N-acylaminocarboxylic acid that can be hydrolyzed or deacylated, and the products of the reactions that are described herein, are given in Table 2.

TABLE 2 EXAMPLES OF HYDROLYSIS OR DESACILATION PRODUCTS F.- PHOSPHONOMETRY In certain embodiments of the present invention it is preferred that the product of the N-acyl reaction is phosphonomethylated. Phosphono-methylation reactions of amines and amino acids have been reported. For example, Moedritzer and co-authors (J. Org. Chem., 1966, 31, 1603-1607) reported the reaction of primary and secondary amino acids with phosphorous acid and formaldehyde to form, respectively, di- and monophosphonomethylated amino acids. Moedritzer also reported (U.S. Patent No. 3,288,846) the reaction of iminodiacetic acid (XIV) with phosphorous acid and formaldehyde to prepare N- (phosphonomethyl) -iminodiacetic acid (XV). Miller and co-inventors (US Patent No. 4,657,705) describe a process in which phosphonomethylareas, amides and carbamates are made to produce N-substituted aminomethylphosphonic acid, which can be converted to glyphosate; in the process described, (1) the urea, the amide or the carbamate is mixed with an aqueous acid medium comprising phosphorous acid and an acid selected from the sulfuric, hydrochloric and hydrobromic acids; and (2) is heated to a temperature between about 70 and about 120 ° C. Phosphonomethylation reactions can also be carried out using phosphorus trichloride in place of phosphorous acid (for example, U.S. Patent 4,400,330). Typically, the reaction product is N-acylaminocarboxylic acid which is phosphonomethylated with a source of phosphorous acid and a source of formaldehyde. Preferably another mineral acid is added, such as sulfuric acid or hydrochloric acid. The reaction temperatures generally range from about 80 ° C to about 150 ° C, preferably around 100 ° C to about 140 ° C, more preferably, around 120 ° C to 140 ° C. Reaction times generally vary between about 10 minutes and about 5 hours, preferably about 20 minutes to about 3 hours, more preferable, around 30 minutes to around 2 hours. Any source of phosphorous acid or phosphorous acid equivalent can be used in the phosphonomethylation reaction. For example, phosphorous acid, phosphorus trichloride, phosphorus tribromide, phosphorous acid esters, chlorophosphonic acid and chlorophosphonic acid esters can be used. Phosphorous acid and phosphorus trichloride are preferred. Formaldehyde can be derived from any source, for example, paraformaldehyde or formalin. In one embodiment of the present invention, the phosphonomethylation reaction results in the replacement of the N-acyl substituent of the N-acylaminocarboxylic acid reaction product with an N-phosphonomethyl group to produce an N- (phosphonomethyl) amino acid. This reaction is shown generically in Scheme 4, where R1 and R2 are as previously defined.

REACTION SCHEME 4 (XXV) (XXVI) Examples of this type of reaction include the conversion of N-acylsarcosine to N-methyl-N- (phosphonomethyl) -glycine, N-acyliminodiacetic acid to N- (phosphonomethyl) iminodiacetic acid, and N-acylglycine to glyphosate. In another embodiment of the present invention, 2,5-diketopiperazines are phosphonomethylated with phosphorus trichloride, phosphorous acid or a source of phosphorous acid in the presence of a source of formaldehyde to form N-substituted-N- (phosphonomethyl) glycine , as shown in the reaction scheme 4a.

REACTION SCHEME 4A where R2 and R2a are independently hydrogen, alkyl or carboxymethyl, or their salts or esters thereof. In another embodiment of the present invention, an N-acylglycine is phosphonomethylated to form N- (phosphonomethyl) glycine (I). For example, the reaction of N-acetylglycine (XVIII), phosphorous acid or phosphorus trichloride and a formaldehyde source produces N- (phosphonomethyl) glycine (I) (see reaction scheme 9). In still another aspect of the present invention, the N-acyl-N-alkylglycine compounds can be phosphonomethylated to produce N-alkyl-N- (phosphonomethyl) glycine compounds. For example, N-acetyl-N-methylglycine (XX) can be reacted with a source of formaldehyde and with phosphorous acid or phosphorus trichloride to produce N-methyl-N- (phosphonomethyl) glycine (XXI). (See reaction schemes 12 and 16).

G.- OXIDIZING DESALQUILATION In one modality of the present invention converts the carboxymethylation reaction product to N-alkyl-N- (phosphonomethyl) glycine ("N-substituted glyphosate"), which is dealkylated in an oxidizing manner to generate N- (phosphonomethyl) -glycine. Preferably, oxidation is carried out by combining the N-substituted glyphosate with water and feeding the combination to a reactor, together with a gas containing oxygen or a liquid containing dissolved oxygen. In the presence of a noble metal catalyst, the N-substituted glyphosate reagent and various by-products are converted oxidatively. 02, H20 Noble Crystal Metal? + b: products where R7, R8 and R9 are as previously defined, and R21 and R22 are independently hydrogen, halogen, -PO3H2, -SO3H2, -NO2, hydrocarbyl or unsubstituted hydrocarbyl, other than -CO2H. In a preferred embodiment, the catalyst is subsequently separated by filtration and the glyphosate is isolated by precipitation, for example by evaporation of a portion of the water and cooling. The amount of N-substituted glyphosate reagent in the aqueous medium is typically about 1 to 80% by weight ([mass of N-substituted glyphosate reagent + total reaction mass] x 100%). It is more preferred that the amount of N-substituted glyphosate reagent be about 5 to 50% by weight and, most preferably, about 20 to 40% by weight. Preferably, the reaction is carried out at a temperature of approximately 50 ° C to 200 ° C. It is preferred that the reaction be carried out at a temperature of about 70 ° C to 150 ° C and, most preferably, about 125 ° C to 150 ° C. The pressure in the reactor during oxidation depends in general on the temperature used. It is preferred that the pressure be sufficient to prevent the reaction mixture from boiling. If a gas containing oxygen is used as the source of oxygen the pressure is also adequate to cause the oxygen in the reaction mixture to dissolve, at a rate sufficient to maintain the desired reaction rate. Preferably, the pressure is at least equal to atmospheric pressure. Preferably the pressure is about 210.9 kPa gauge at 1,406 kPa gauge. It is more preferred that the temperature be in the highly preferred range of about 125 to 150 ° C, and then the pressure will be about 281.2 to 703 kPa gauge. The oxygen source for the oxidation reaction can be any gas containing oxygen or a liquid containing dissolved oxygen. Preferably the oxygen source is a gas containing oxygen. How it is used here, an "oxygen containing gas" is any gaseous mixture containing oxygen that optionally may contain one or more diluents that are not reactive with oxygen or with the reagent or product under the reaction conditions. Examples of these gases are: air, pure molecular oxygen or molecular oxygen diluted with helium, argon, neon, nitrogen or other gases that contain non-molecular oxygen. Preferably at least about 20% by volume of the oxygen-containing gas is molecular oxygen and, more preferably, at least about 20% by volume. 50% of the gas containing oxygen is molecular oxygen. Oxygen can be introduced by conventional means into the reaction medium, in a manner that maintains the concentration of dissolved oxygen in the reaction mixture, at the desired level. If an oxygen-containing gas is used, it is preferably introduced into the reaction medium in a manner that maximizes the contact of the gas with the reaction solution. Such contacting can be achieved, for example, by dispersing the gas through a diffuser, such as a frit of porous glass or by concretion, shaking or other methods known to those skilled in the art. Preferably the oxygen is fed into the reaction mixture at a rate that is sufficient to maintain the concentration of dissolved oxygen at a finite level. It is more preferred to feed the oxygen at a rate sufficient to maintain the concentration of dissolved oxygen at a value no greater than about 2 ppm, while maintaining the desired reaction rate. It should be noted that the partial pressure of the oxygen in the reactor affects the rate at which the oxygen is supplied to the reaction mixture and, preferably, is about 0.5 to 10 atmospheres.

The catalyst comprises a noble metal, preferably platinum (Pt), palladium (Pd), rhodium (Rh), iridium (Ir), osmium (Os) or gold (Au). In general, platinum and palladium are more preferred, and platinum is very preferred. Because platinum is currently the most preferred, much of the following discussion will be directed to the use of platinum. However, it must be understood that the same discussion is generally applicable to other noble metals and their combinations. The noble metal catalyst may not be supported, for example, platinum black, commercially available from various sources, such as Aldrich Chemical Co., Inc., Milwaukee, Wl; Engelhard Corp., Iselin, NJ; Y Degussa Corp., Ridgefield Park, NJ. Alternatively, the noble metal catalyst can be deposited on the surface of a support, such as carbon, alumina (AI2O3), silica (SIO2), titanium oxide (TiO), zirconium oxide (ZrO2), siloxane or barium sulfate ( BaSO4), preferably silica, titanium oxide or barium sulfate. Supported metals are common in the art and can be obtained commercially from various sources, for example, 5% platinum on activated carbon, Catalog No. Aldrich 29,593-1; platinum or alumina powder, Catalog No. Aldrich 31, 132-4; palladium on barium sulfate (reduced) Catalog No. Aldrich 27,799-1; and palladium on activated charcoal, 5%, Catalog No. Aldrich 20,568-9. As for the carbon supports, graffiti supports are generally preferred, because said supports tend to have greater selectivity to glyphosate.

The concentration of the noble metal catalyst on a support surface can vary within wide limits. Preferably it is in the approximate range of 0.5 to 20% by weight ([noble metal mass + total catalyst mass] x 100%), more preferable, about 2.5 to 10% by weight and, most preferably, about 3 at 7.5% by weight. At concentrations greater than about 20% by weight, noble metal layers and lumps tend to form. Thus, there are fewer noble metal surface atoms per total amount of noble metal used. This tends to reduce the activity of the catalyst and is not an economical use of the noble, expensive metal. The weight ratio of the noble metal to the N-substituted glyphosate reagent present in the reaction mixture is preferably about 1: 500 to about 1: 5. More preferably, the ratio is about 1: 200 to about 1: 10 and, most preferably, about 1:50 to 1: 10. In a preferred embodiment, a molecular electroactive molecule (ie, a molecular species that can be reversibly oxidized or reduced by electron transfer) is adsorbed to the noble metal catalyst. It has been discovered, in accordance with this invention, that the selectivity and / or conversion of the noble metal catalyst can be improved by the presence of said electroactive molecular species, in particular when the catalyst is being used to effect the oxidation of NMG to form glyphosate. In that case, the electroactive adsorb is preferably hydrophobic and has an oxidation potential (E1 / 2) of at least about 0.3 volts against SCE (saturated calomel electrode). A compilation of the oxidation potential and the investment capacity for a large number of electroactive species can be found in Encyclopedia of Electrochemistry of the Elements, (A.

Bard and H. Lund, eds., Marcel Dekker, New York). Other references that identify oxidation for specific electroactive species include: for triphenylmethane, J. Perichon, M. Herlem, F. Bobilliart and A. Thiebault Encyclopedia of Electrochemistry of the Elements, volume 11, page 163 (A.

Bard and H. Lund, eds., Marcel Dekker, New York, NY, 1978); for N-hydroxyphthalimide, Masui, M, Ueshima, T. Ozaki, S. J. Chem. Soc. Chem. Commun., 479-80 (1983); for tris- (4-bromophenyl-amine, Dapperheid, S., Steckhan, E., Brinkhaus, K., Chem. Ber., 124, 2557-67 (1991); for N-oxide 2,2,6,6-tetramethylpiperidine ("TEMPO"), Semmelhack, M., Chou, C. and Cortés, D., J. Am. Chem. Soc, 105, 4492-4 (1983); for 5,10,15-20-tetracis (pentafluorophenyl) -21H, 23H-porphine-iron (lll) chloride ("Fe (lll) TPFPP"), Dolphin, D., Traylor, T., and Xie , L. Acc. Chem. Res., 30, 251-9 (1997); and for various porphyrins: J. H. Fuhrhop, Porphyrins and Metalloporphirins, 593 (K. Smith, ed., Elsevier, New York, 1975). The electroactive molecular species are also useful in the context of the oxidation of N-isopropyl-glyphosate to form glyphosate. In this context, an electroactive molecular species is adsorbed, preferably in a noble metal catalyst, on a graphitic carbon support. It has been found that in the presence of the graphitic carbon support the electroactive molecular species increases the glyphosate selectivity of the noble metal catalyst. Examples of generally suitable electroactive molecular species include: triphenylmethane, N-hydroxyphthalimide, Fe (III) TPFPP chloride, 2,4,7-trichlorofluorene, 2,2-6,6- tris (4-bromophenyl) amine N-oxide. tetramethylpiperidine (sometimes referred to as ("TEMPO"); 5,10,15,20-tetraphenyl-21 H, 23H-porphine-iron (lll) chloride (sometimes referred to as "Fe (lll) TPP" chloride), , 10,15,20-tetraphenyl-21 H, 23H-porphine-nickel (ll) (sometimes referred to as (Ni (II) TPP "), 4,4'-difluorobenzophenone and phenothiazine.When the metal catalyst is being used noble to catalyze the oxidation of NMG to glyphosate, the highly preferred electroactive species includes N-hydroxyphthalimide, tris (4-bromophenyl) -amine, TEMPO, Fe (lll) TPP chloride and Ni (ll) TPP. electroactive molecules in the noble metal catalyst using various methods generally known in the art.The electroactive molecular species can be directly added to the reaction mixture of oxidation, separately from the noble metal catalyst. For example, 2,2,6,6-tetramethylpiperidine N-oxide ("TEMPO") can be added to the reaction mixture without first adsorbing it on the noble metal catalyst. Using this method, the electroactive molecule is adsorbed on the noble metal catalyst while it is in the reaction mixture. Alternatively, the electroactive molecular species is adsorbed on the noble metal catalyst before being added to the oxidation reaction mixture. In general, the electroactive molecular species can be adsorbed to the catalyst using, for example, liquid phase deposition or gas phase deposition. Preferably the oxidation reaction is used in an intermittent reactor, so that the reaction can be contained until the conversion to glyphosate is complete. However, other types of reactors can also be used, such as continuous stirred tank reactors, which can also be used, although, preferably (1) there must be sufficient contact between oxygen, the N-substituted glyphosate reagent and the catalyst; and (2) there must be an adequate retention time for the substantial conversion of the glyphosate N-substituted glyphosate reagent. The oxidative separation may be carried out, if desired, in the presence of a solvent, for example, a solvent containing water. It can also be carried out in the presence of other chemical species, such as N-methyl-glyphosate, aminomethylphosphonic acid ("AMPA") and N-methyl-aminomethyl-phosphonic acid ("MAMPA"), which may arise in connection with the preparation of glyphosate. .

H.- PREPARATION OF THE GLYPHOSATE In a preferred embodiment of the present invention the reaction product of N-acyl, of the carboxymethylation reaction, is converted to glyphosate, or to one of its salts or one of its esters, which have the structure (I): wherein R7, R8 and R9 independently comprise hydrogen, hydrocarbyl, substituted hydrocarbyl or an agronomically acceptable cation. When R7, R8 and R9 of the structure (I) are each hydrogen, the structure (I) is glyphosate. In general, the reaction product of N-acyl can be converted to glyphosate when the formaldehyde (or a source of formaldehyde) is selected as the aldehyde and the carbamoyl compound is selected from those compounds having the structure (II): O (II) R1- ^ NR2R2a wherein R1 is hydrocarbyl, substituted hydrocarbyl or -NR3R4, R2 and R2a are independently hydrogen, hydrocarbyl or substituted hydrocarbyl, provided that -NR2R2a can be carboxylated. Preferably formalin is selected as the source of formaldehyde; R1 is alkyl or -NR3R4; R2 and R3 are independently hydrogen, alkyl, hydroxymethyl, amidomethyl, phosphonomethyl, carboxymethyl, or an ester or a carboxymethyl or phosphonomethyl salt; and R 2a and R 4 are independently hydrogen, hydroxymethyl or another substituent that is hydrolysable under the carboxymethylation reaction conditions. More preferably, R1 is methyl, ethyl, isopropyl or -NR3R4; R2 and R3 are independently hydrogen, methyl, ethyl, isopropyl, hydroxymethyl, carboxymethyl, phosphonomethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R2a and R4 are independently hydrogen or hydroxymethyl. It is highly preferable that R1 is methyl or -NR3R4; R2 and R3 are independently hydrogen, methyl, hydroxymethyl, carboxymethyl, phosphonomethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R2a and R4 are independently hydrogen or hydroxymethyl. Thus, examples of carbamoyl compounds include: acetamide, urea, acetamides substituted with N-alkyl, N-phosphonomethyl, and N-carboxymethyl; the esters and salts of acetamides substituted with N-phosphonomethyl and N-carboxymethyl; ureas substituted with N, N'-dialkyl, N, N'-diphosphonomethyl and N, N'-dicarboxymethyl; the esters and salts of ureas substituted with N, N'-diphosphonomethyl and N, N'-dicarboxymethyl; and the amide equivalent compounds, selected from the group consisting of: wherein R > 13 and, R r 14 are independently hydrogen, hydroxymethyl, alkyl, carboxymethyl, phosphonomethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R15, R16 and R17 are independently alkyl or -NR3R4. Preferred alkyl substituents for any of R13, R14, R15, R16 and R17 are methyl, ethyl and isopropyl. The sequence used to convert the reaction product from N-acyl to glyphosate depends on the starting carbamoyl compound. However, in general, the N-acyl group is hydrolyzed or otherwise removed from the N-acyl reaction product and, if the carbamoyl compound does not contain an N-phosphonomethyl substituent, the reaction product is phosphonomethylated, either simultaneously with, or after deacylation to remove the N-acyl substituent. Additional steps that can be employed include oxidizing separation and recirculation of the carboxymethylation catalyst, as described elsewhere herein.

GLYPHOSATE PREPARATION FROM ACETAMIDE The preparation of glyphosate using acetamide as a carbamoyl compound is illustrated in the reaction scheme 6.

REACTION SCHEME 6 (Co (ll) Salt n? «*. CO * 2 CHO "SSolveir" te * ". W 1V X, * * Brf« K * r CC_H Vil XVI xrv Frostrcrnetilation XV As illustrated, an acetamide equivalent is reacted VII with two equivalents of each of carbon monoxide and formaldehyde, in the presence of a carboxymethylation catalyst and solvent precursor; under these conditions, the acetamide is protonated and forms a base pair (designated BH + [Co (CO) 4] ") with the carboxymethylation catalyst precursor.The reaction produces N-acetyliminodiacetic acid XVI and a reaction product of the carboxymethylation (BH + [Co (CO) 4] ", where" B "is acetamide).

In the presence of water and an acid, such as hydrochloric acid, N-acetyliminodiacetic acid XVI is hydrolyzed to form iminodiacetic acid XIV and acetic acid. The iminodiacetic acid is reacted separately XIV with formaldehyde and H3PO3, PCI3 or another source of H3PO3, to produce N- (phosphonomethyl) iminodiacetic acid XV, which is oxidized in the presence of a carbon or platinum on carbon catalyst, to produce glyphosate i.

The cobalt used in the reaction carboxymethylation step can be recovered, such as a cobalt (II) salt described previously in section C. In addition, regenerating the cobalt (II) salt in the presence of acetamide (: B), monoxide of carbon and hydrogen, results in the formation of the base pair that is recycled to the carboxymethylation reaction mixture.

Similarly, the acetic acid that is generated by the hydrolysis of N-acetyliminodiacetic acid XVI to iminodiacetic acid XIV can be reacted with ammonia to form acetamide and recycled for use as a starting material in the carboxymethylation reaction. As a result, high atomic efficiency is obtained by converting ammonia, carbon monoxide and formaldehyde to iminodiacetic acid.

In a preferred embodiment, wherein the amide is acetamide or an acetamide equivalent (ie, a composition that can be hydrolysed to acetamide under the carboxymethylation reaction conditions), the reaction mixture for the carboxymethylation reaction contains acetic acid as an organic acid cocatalyst. When used as a cocatalyst, it has been found that acetic acid provides the following significantly beneficial results: 1) certain ratios of cobalt to acetic acid in the carboxymethylation reaction mixture increase the yield of the reaction product N-acylaminocarboxylic acid; 2) the preferred ratio of cobalt to acetic acid exhibits dependence on pressure; 3) the presence of acetic acid results in an unexpected ability to increase the yield of the N-acylaminocarboxylic acid reaction product, increasing the pressure (typically increases in pressure will lead to increased reaction rates, but not increased yield); and 4) the increase in yields, which can be achieved by increases in pressure, allows an increase in load. As a result, high yields of N-acetyliminodiacetic acid (XVI) can be obtained at relatively high loads. According to the present invention, the molar ratio of acetic acid to cobalt is generally in the approximate range of 2 to 60, preferably, about 7 to 55 and, more preferably still, about 10 to 50. At relatively lower pressures , for example, at pressures below 12,500 kPa), the molar ratio of acetic acid to cobalt is generally in the approximate range of 2 to 20, preferably around 7 to 15, and still more preferable, about 11 to 13. At intermediate pressures, for example, pressures within the range of about 12,500 to 17,250 kPa, the molar ratio of acetic acid to cobalt is generally in the approximate range of 2 to 45, preferably about 8 to 30 and, more preferably still, about 10 to 20. At relatively high pressures, for example, at pressures of at least about 17.2550 kPa, the molar ratio of acetic acid to cobalt in general is on the approximate scale of 4 to 60, preferably around 8 a 55 and, more preferably still, around 10 to 50. The surprising effect of using acetic acid, on the carboxymethylation of acetamide (VII), is illustrated in example 22 and the table associated with it, showing the percentage yield of N-acetyliminodiacetic acid (XVI) based on the initial amount of acetamide (VII) under different reaction conditions, pressure, filler, solvent, added water, amount of catalyst precursor of C 2 (CO) s, and additional acetic acid cocatalyst. The experimental data obtained so far suggest further that the yield is surprisingly improved when acetic acid is used as a cocatalyst in the carboxymethylation of acetamide (VII) when water is present in the reaction mixture. This effect is illustrated in the table that appears in association with example 23, which shows the percentage yield of N-acetyliminodiacetic acid (XVI), based on the starting amount of acetamide (Vil) when the HOAc / Co ratio is varied against the moles of H2O. The reaction conditions included: 10.545 kPa of CO: H2 (95: 5), 90 ml of DME solvent, 11.8 g of acetamide, 13.6 g of 95% paraformaldehyde and 4.1 g of Co2 (CO) 8. Typically, the molar ratio of water to acetamide starting material is about 1 to 5, preferably about 2 to 4 and, more preferably, about 3.2 to 3.8. As illustrated in Example 24, the yield of N-acetyliminodiacetic acid increases surprisingly as the pressure increases. Conventionally, the reaction velocities do not increase when the pressure increases. Consequently, if less catalyst loading, or higher reaction payload, is desired for the reaction mixture, it is preferred that the carboxymethylation reaction of the acetamide be carried out at a pressure of at least about 3,500 kPa, better still, at less around 10,500 kPa and, most preferably, around 21,000 to 24,000 kPa. Example 25 further illustrates that an increase in pressure allows an increase in payload. For a given catalyst load, increasing the pressure allows an increase in the payload, while maintaining high commercially or unacceptably high yields of N-acetyliminodiacetic acid. Thus, for example, pressure increases from 10,340 kPa to 22,000 kPa allow the payload to be doubled, without loss of performance, while a doubling of the payload to 10,340 kPa results in a significant loss in the payload. performance. An alternative route for the preparation of glyphosate I from acetamide VII is illustrated in reaction scheme 7.

REACTION SCHEME 7 Fosfrareulac n In general, the sequence of reactions in reaction scheme 7 is the same as in reaction scheme 6, except that N-acetyliminodiacetic acid XVI is deacylated to form 1,4-di (carboxymethyl) -2,5- diketopiperazine XVII which is then phosphonomethylated directly in the same manner as iminodiacetic acid XIV is phosphonomethylated in the reaction scheme 6. A third alternative reaction scheme for the preparation of glyphosate I from acetamide VII is illustrated in reaction scheme 8 : REACTION SCHEME 8 HOHO In general, the sequence of reactions in reaction scheme 8 is the same as that of reaction scheme 7, except that 1,4-di (carboxymethyl) -2,5-diketopiperazine XVII is hydrolyzed, using water and an acid, as hydrochloric acid, to iminodiacetic acid XIV, which is then phosphonomethylated as written in the reaction scheme 6.

A fourth alternative reaction scheme for the preparation of glyphosate I from acetamide VII is illustrated in reaction scheme 9: REACTION SCHEME 9 As illustrated in the step 9 scheme, one equivalent of acetamide VII is reacted with one equivalent of each of carbon monoxide and formaldehyde, in the presence of a carboxymethylation catalyst and solvent precursor, to give N-acetylglycine XVIII. In this reaction sequence, the formation of the base pair and the recycling and regeneration of the cobalt (II) salt are as described in relation to the reaction scheme 6. In contrast to the reaction scheme 6, however, N-acetylglycine XVIII is reacted with formaldehyde and H3PO3, PCI3 or another source of H3PO3, to produce N- (phosphonomethyl) -N-acetylglycine XIX, which is hydrolyzed using water and an acid, such as hydrochloric acid, to produce glyphosate I and acetic acid. The acetic acid that is produced in the hydrolysis step can be reacted with ammonia to generate acetamide for the carboxymethylation step. A fifth alternative reaction scheme for the preparation of glyphosate I from acetamide VII is illustrated in reaction scheme 9a: DIAGRAM OF REACTION 9a.

The sequence of reactions in reaction scheme 9a is comparable to that reported in reaction scheme 9, except that N-acetylglycine XVIII is deacylated to form 2,5-diketopiperazine XXX. The 2,5-diketopiperazine XXX is then reacted with formaldehyde and H3PO3, PCI3 or another source of H3PO3 to produce N- (phosphonomethyl) glycine I and acetic acid. The acetic acid that is produced in the hydrolysis step can be reacted with ammonia to generate acetamide for the carboxymethylation step.

Instead of starting with the acetamide in the preceding reaction scheme, one equivalent of acetamide can be used. As used herein, an acetamide equivalent is a composition that, by hydrolysis, produces acetamide or hydroxymethylacetamide. Examples of acetamide equivalents include the following compositions: SAW Thus, for example, acetamide can be replaced by these compounds, in any of the reaction schemes 6, 7, 8, 9 and 9a.

PREPARATION OF GLYPHOSATE FROM N-METHYLACETAMIDE The preparation of N- (phosphonomethyl) glycine, using N-methylacetamide as the carbamoyl compound is illustrated in reaction scheme 10: REACTION SCHEME 10 PM reaction H203P- N '"C02H Pt / O, H2 ° 3P N C02H I H CH3 XXI As illustrated, one equivalent of N-methylacetamide IX is reacted with one equivalent of each of carbon monoxide and formaldehyde in the presence of a carboxymethylation catalyst and solvent precursor, to give N-acetyl sarcosine XX. In the presence of water and an acid such as hydrochloric acid, N-acetyl sarcosine XX is hydrolyzed to sarcosine XXIII and acetic acid. Sarcosine XXIII is reacted with formaldehyde and H3PO, PCI or another source of HPO, which is oxidized in the presence of a platinum and oxygen catalyst, to glyphosate I.

Similar to the preparation of glyphosate from acetamide, which is described with respect to reaction scheme 6, the reaction product of the carboxymethylation catalyst (BH + [Co (CO) 4] ", where" B "is N- methylacetamide), it is recycled and then regenerated in the presence of N-methylacetamide Also the acetic acid that is generated by the hydrolysis of N-acetyl sarcosine XX to sarcosine XXIII is reacted with methylamine to form N-methylacetamide and recycled for use as starting material in the carboxymethylation reaction An alternative route for the preparation of glyphosate I from N-methylacetamide IX is illustrated in reaction scheme 11: REACTION SCHEME 11 _ In general, the sequence of reactions in reaction scheme 11 is the same as in reaction scheme 10, except that N-acetyl sarcosine XX is deacylated to form 1,4-dimethyl-2,5-diketopyperazine XXV. Then, 1,3-dimethyl-2,5-diketopiperazine XXV phosphonomethylane is phosphonomethylated in the same manner as sarcosine XXIII is phosphonomethylated in reaction scheme 10. Alternatively, 1,4-dimethyl-2,5-diketopiperazine XXV is hydrolyzed. to sarcosine XXIII and phosphonomethyla as described with respect to reaction scheme 10.

A third alternative reaction scheme for the preparation of glyphosate I from N-methylacetamide IX is illustrated in reaction scheme 12: REACTION SCHEME 12 Pt O H203P '"N O, H I 2 H As illustrated, the carboxymethylation step of reaction scheme 12 is equal to the carboxymethylation step of reaction schemes 10 and 11. However, in reaction scheme 12 N-acetyl sarcosine XX is reacted with formaldehyde and H3PO3, PCI3 or another source of H3PO3 to produce N- (phosphonomethyl) -N-methylglycine XXI, which is oxidized in the presence of a platinum and oxygen catalyst, to glyphosate I and acetic acid. The acetic acid is then reacted with methylamine to give the starting material N-methylacetamide.

PREPARATION OF GLYPHOSATE FROM N-ACETYLGLYCIN XVIII The preparation of N- (phosphonomethyl) -glycine from N-acetylglycine XVIII in the reaction schemes 13 and 14 is illustrated. In this reaction scheme, N-acetylglycine XVIII is carboxymethylated to produce N-acetyliminodiacetic acid XVI which is then converted to glyphosate I, as described in reaction schemes 6, 7 and 8. Acetic acid is produced as a hydrolysis product in each of the reaction schemes 13 and 14. The acetic acid is reacted with ammonia to generate acetamide V1, which can then be carboxymethylated to form compound XVIII.

REACTION SCHEME 13 PM reaction REACTION SCHEME 14 GLYPHOSATE PREPARATION FROM AN EQUIVALENT OF N-METILACET AMIDA The preparation of N- (phosphonomethyl) -glycine is illustrated using VIII, which is an equivalent of N-methylacetamide, in reaction schemes 15 and 16. Thus, carboxymethyl VIII is formed to form N-methyl-N-acetylglycine XX, which it is converted to glyphosate I, as described in reaction schemes 10, 11 and 12. REACTION SCHEME 15 REACTION SCHEME 16 Salt H + fCoíCOy Pf / O, H2Q3P ^ N ^ 02H GLYPHOSATE PREPARATION FROM UREA The preparation of N- (phosphonomethyl) glycine, from urea, is illustrated in reaction scheme 17.

REACTION SCHEME 17 XIII HCl PM reaction Oxidation H2 ° 3P N C02H i H As illustrated, one equivalent of urea V is reacted with four equivalents of each of carbon monoxide and formaldehyde, in the presence of a carboxymethylation catalyst precursor and solvent. In contrast to the reaction scheme 6, in this reaction scheme, urea V is reacted with the carboxymethylation catalyst precursor in the absence of formalin to form the base pair (BH + [Co (CO) 4] ", where B is urea).

The products of the carboxymethylation reaction are tetrahydric Xlll and the reaction product of the carboxymethylation catalyst (BH + [Co (CO) 4] ", where" B "is urea.) Tetra-acid Xlll is hydrolyzed to two equivalents of iminodiacetic acid XIV and carbon dioxide and iminodiacetic acid XIV is converted to glyphosate I as described in relation to reaction schemes 6 and 8.

PREPARATION OF GLIFOSATE FROM N.N-DIMETILUREA The preparation of N- (phosphonomethyl) glycine from N, N-dimethylurea is illustrated in reaction scheme 18: REACTION SCHEME 18 C02 + 2 NH '"C02H XXIII PM reaction As illustrated, one equivalent of N, N-dimethylurea X is reacted with two equivalents of each of carbon monoxide and formaldehyde in the presence of a carboxymethylation catalyst precursor and solvent. In a manner similar to reaction scheme 18, in this reaction scheme N, N-dimethylurea X is reacted with the carboxymethylation catalyst precursor, in the absence of formalin to form the base pair (BH + [Co (CO) 4] "), where BH + is the protonated N, N'-dimethylurea X.

The products of the carboxymethylation reaction are the diacid XXII and the reaction product of the carboxymethylation catalyst (BH + [Co (CO) 4] ", where B is N, N'-dimethylurea.) Diacid XXII is hydrolysed to two equivalents of sarcosine XXIII and the carbon dioxide and sarcosine XXIII is converted to glyphosate I, as described with respect to reaction schemes 10 and 15. An alternative method for the preparation of N- (phosphonomethyl) glycine I from N, N'-dimethylurea X is illustrated in reaction scheme 19: REACTION SCHEME 19 PM reaction C02 + 2 H203P N "" C02H XXI CH: Pt O H2 ° 3P N C02H As illustrated, the carboxymethylation reaction is carried out as described with respect to reaction scheme 18, to produce the diacid XXII and the reaction product of the carboxymethylation catalyst (BH + [Co (CO) 4] "where" B "is N, N'-dimethylurea.) However, in this reaction scheme the diacid XXII is reacted with formaldehyde and H3PO3, PCI3 or another source of H3PO3 to produce N- (phosphonomethyl) -N-methylglycine XXI which is oxidized in the presence of a platinum and oxygen catalyst, to glyphosate I.

PREPARATION OF GLYPHOSATE FROM BIS-PHOSPHONOMETILUREA The preparation of N- (phosphonomethyl) glycine from bis-phosphonomethylurea XII is illustrated in reaction scheme 20: REACTION SCHEME 20 X »Hydrolysis 2 H203P / ^ N ^^ C02H H I As illustrated, one equivalent of bis-phosphonomethylurea is reacted with two equivalents of each of carbon monoxide and formaldehyde, in the presence of a carboxymethylation catalyst precursor and solvent. In this reaction scheme, bis-phosphonomethylurea XII is reacted with the caboxymethylation catalyst precursor, in the absence of formalin, to form the base pair (BH + [Co (CO) 4] "), where BH + is bis-phosphonomethylurea protonade XII The products of the carboxymethylation reaction are XXIV and the product of the reaction of the carboxymethylation catalyst (BH + [Co (CO) 4] ", where" B "is bisphosphonomethylurea). XXIV is hydrolysed in the presence of a hydrolysis catalyst (preferably an acid or a base, and, more preferably, a mineral acid, to form N- (phosphonomethyl) glycine I.

PREPARATION OF GLYPHOSATE FROM N-ACETYL-N-PHOSPHONO-METHYLAMINE In the reaction scheme 21 the preparation of N- (phosphonomethyl) glycine I from N-acetyl-N-phosphonomethylamine XI is illustrated: REACTION SCHEME 21 XI Hydrolysis H203P- "N ^^ 0O2H H As illustrated, an equivalent of N-acetyl-N-phosphonomethylamine XI is reacted with one equivalent of each of carbon monoxide and formaldehyde, in the presence of a carboxymethylation catalyst precursor and solvent. In this reaction scheme N-acetyl-N-phosphonomethylamine is reacted with the carboxymethylation catalyst precursor, in the absence of formalin to form the base pair (BH + [Co (CO) 4] "), where BH + is protonated N-acetyl-N-phosphonomethylglycine XI The products of the carboxymethylation reaction are XIX and the reaction product of the carboxymethylation catalyst (BH + [Co ( CO) 4] ", where" B "is N-acetyl-N-phosphonomethylamine). XIX is hydrolyzed in the presence of a hydrolysis catalyst (preferably an acid or a base and, more preferably, a mineral acid) to form N- (phosphonomethyl) glycine I.

DEFINITIONS The following definitions are provided in order to help the reader understand the detailed description of the present invention: "Glyphosate" means N- (phosphonomethyl) glycine in the form of an acid or in any of its salt or ester forms. "Hydrocarbyl" means a group composed of carbon and hydrogen. This definition includes alkyl, alkenyl and alkynyl groups, which are each straight chain or branched chain, - or cyclic hydrocarbons of one to about 20 carbon atoms. Also included in this definition are the aryl groups, consisting of carbon and hydrogen. Thus, the hydrocarbyl includes, for example: methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopentyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, ethyne, propyne, butyne, pentino , hexane, phenyl, naphthyl, anthracenyl, benzyl and their isomers. "Substituted hydrocarbyl" means a hydrocarbyl group in which one or more hydrogens have been substituted with a group containing a heteroatom. Such substituent groups include, for example, halogen, oxo, heterocycle, alkoxy, hydroxy, aryloxy, -NO2, amino, alkylamino or amido. When the substituent group is oxo, the substituted hydrocarbyl can be, for example, an acyl group. "Heteroatom" means an atom of any element other than carbon or hydrogen, which is capable of forming chemical bonds.

"Heterocycle" means a single-ring, multi-ring, saturated or unsaturated carbocycle, where one or more carbon atoms are replaced by N, S, P or O. This includes, for example, the following structures: where Z, Z ', Z "or Z'" is C, S, P, O or N, provided that one of Z, Z ', Z "or Z'" is different from carbon, but not be O or S, when it is fixed to another atom Z, by a double bond or when it is fixed to another atom of O or S. Additionally, it is understood that the optional substituents are fixed to Z, Z ', Z "or Z "'only when each is C. The binding point to the molecule of interest may be in the heteroatom or at some other point within the ring. "Halogen" or "halo" means a fluorine, chlorine, bromine or iodine group, "carbamoyl" means a group containing a fully saturated nitrogen atom, fixed by a simple ligation to a carbonyl moiety. "Carboxymethyl" means a group containing a carboxylate moiety attached by the carbon atom of the carboxylate, to a saturated carbon atom which, in turn, is attached to the molecule of interest.

"Carboxymethylation catalyst" means a catalyst that is useful in carbonylation reactions and, in particular, in carboxymethylation reactions. "Carboxymethylation" means the introduction of a substituted or unsubstituted carboxymethyl group, into the molecule of interest. "Load" or "payload" means the mass of starting material divided by the mass of the reaction solvent. "PM" means phosphonomethylation. "GC" means gas chromatography. "HPLC" means high pressure liquid chromatography. "Cl" means ion chromatography. "NMR" means nuclear magnetic resonance spectroscopy. "EM" means mass spectrometry. The following examples will illustrate the invention.

EXAMPLES In the following representative examples of carboxymethylation, a stainless steel autoclave of 300 or 2,000 ml was used, equipped with magnetic stirrer and heating system. All compound numbers are Roman numerals and reflect the structures that appear in reaction schemes 1-21. The progress of the reaction was monitored following gas consumption. At the end of each heating period, the reaction mixture was cooled to room temperature, before analysis. The N-acetyliminodiacetic acid (XVI) was quantified by HPLC analysis, using an ion exclusion column Interaction Ion 310, at 30 ° C and detection of UV absorption at 210 nm. The mobile phase of H2SO4 0.04N was pumped at 0.5 ml / minute, which gave retention times of 4.6 to 4.8 minutes for (XVI). All yields are based on charged moles of acetamide.

EXAMPLE 1 Examples 1 and 2 illustrate that increasing the reaction pressure has no effect on the yield of (XVI) when HCl is used as cocatalyst. A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 1.8 g (0.018 mol) of 37% HCl, 90 ml of DME and 4.1 g (0.012 mol) of Co2 (CO) 8, and pressurized to 10.345 kPa of CO at 25 ° C. This mixture was heated at 110 ° C for 30 minutes. HPLC analysis of this stream gave an 87% yield of (XVI) 0.5% iminodiacetic acid (XIV) and 4.0% N-acetylglycine (XVIII).

EXAMPLE 2 A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 1.8 g (0.018 mol) of HCl at 37%, 90 ml of DME and 4.1 g (0.012 mol) of Co2 (CO) 8, and pressurized to 27,580 kPa of CO at 25 ° C. This mixture was encouraged at 110 ° C for 30 minutes. HPLC analysis of this stream gave a yield of 87% of (XVI), 0.5% of (XIV) and 4.0% of (XVIII).

EXAMPLE 3 This example illustrates a typical reaction in the absence of added acetic acid. A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 90 ml of DME and 4.1 g (0.012). mol) of Co2 (CO) 8, and pressurized to 10.345 kPa of CO: H2 (95: 5) at 25 ° C for 30 minutes. HPLC analysis of this stream gave a yield of 89% of (XVI), 1% of (XIV) and 8% of (XVIII).

EXAMPLE 4 This example illustrates an unexpected increase in the yield of (XVI) observed when maintaining a specific molar ratio of acetic acid to cobalt catalyst at 10.345 kPa. A typical reaction is described below. The results of the reactions carried out under identical conditions, as described below, but with varying amounts of added acetic acid are summarized in Table 1 and Figure 1. An autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 5.4 g (0.09 mol) of acetic acid, 90 ml of dimethoxyethane (DME) and 4.1 g (0.012 mol) of Co2 (CO) 8 and put under pressure at 10.345 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes. The reaction was allowed to cool to room temperature. HPLC analysis of the reaction gave a yield of 92% of (XVI), 1% of (XIV) and 7% of (XVIII).

TABLE 3 PERFORMANCE AGAINST ACETIC ACID ADDED TO 10,345 kPa a of Example 3b expressed as the number of moles of cobalt atoms. Cobalt was supplied as C? 2 (CO) 8.

EXAMPLE 5 This example illustrates that the optimum molar ratio of acetic acid to cobalt, necessary to obtain high yields of (XVI) varies with the reaction pressure. A typical reaction is described below, where the reaction was carried out at 22,069 kPa. The results of the reactions carried out under conditions identical to those described below, but with varying amounts of added acetic acid are summarized in Table 4 and Figure 2. An autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 4.2 g (0.07 mol) of acetic acid, 90 ml of tetrahydrofuran (THF) and 1 g (0.03 mol) of Co2 (CO) 8, and put under pressure at 22.069 kPa of CH: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes. The reaction was allowed to cool to room temperature. HPLC analysis of the reaction gave 97% yield of (XVI).

TABLE 4 PERFORMANCE AGAINST ACETIC ACID ADDED TO 22,069 kPa a of Example 3b expressed as the number of moles of cobalt atoms. Cobalt was supplied as C? 2 (CO) 8.

EXAMPLE 6 This example illustrates that the optimum acetic acid: cobalt molar ratio varies with the reaction pressure. A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.42 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 21.2 g (0.33 mol) of acetic acid , (0.24 g / ml DME), 90 ml of DME and 4.1 g of Co2 (CO) 8 (0.012 mol) and put under pressure of 15.170 kPa) of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes. HPLC analysis of this stream gave a yield of 95% of (XVI), 1% of (XIV) and 3% of (XVIII).

EXAMPLE 7 This example illustrates the production of extremely high yields of (XVI), using the process of this invention. A 300 ml autoclave was charged with 5.9 g (0.1 mol) of acetamide, 6.8 g (0.22 mol) of 95% paraformamide, 6.45 g (0.36 mol) of water, 10.6 g (0.18 mol) of acetic acid (0.12 g). / ml of DME), 90 ml of DME and 2.0 g (0.0058 mol of Co2 (CO) 8, and pressurized to 10.345 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated to 125 ° C for 30 minutes The HPLC analysis of the reaction gave a yield of 99% of (XVI) and 1% of (XVIII).

EXAMPLE 8 This example illustrates the preparation of (XVI) in the presence of reduced levels of cobalt catalyst. An autoclave was charged with 11.8 g (0.2 mol) of acetamide (VII), 13. 6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (072 mol) of water, 16.8 g (0.28 mol) of acetic acid (0.19 g / ml DME), 90 ml of DME and 2.1 g (0.006 mol) of Co2 (CO) 8 and put under pressure 17,240 kPa of CO: H2 (95: 5) at 25 ° C.

This mixture was heated at 125 ° C for 30 minutes. HPLC analysis of this stream gave a yield of 97% of (XVI), 1% of (XIV) and 0.5% of (XVIII).

EXAMPLE 9 This example illustrates a way in which a cobalt salt (II) can be converted to recycle it from the carboxymethylation reaction mixture. A distillation apparatus was charged with a reaction stream of (XVI), represented by example 2. Once the background temperature of 90 ° C was maintained, a distillate with a steam temperature of 85 ° C was collected, in a receiving flask. At that time anhydrous DME was added to the distillation vessel, at a rate similar to the distillation removal at 85 ° C. After removing 115 g of distillate at 85 ° C and the addition of 120 g of DME, a pink precipitate of Co (N-acetyliminodiacetic acid) 2 was present in the distillation vessel. This solid was isolated by filtration. The analysis of the filtrate revealed that it contained 13 ppm of cobalt, which implies that 99.8% of the cobalt was removed from the reaction stream.

EXAMPLE 10 This example illustrates how a catalyst precursor can be regenerated from a cobalt (II) salt and used in the reaction step to give high yields of (XVI). An autoclave was charged with 26.85 g (0.108 mol) of cobalt acetate tetrahydrate and 106 g (1.77 mol) of acetic acid, and pressurized .170 kPa of CO: H2 (90:10) at 25 ° C. This mixture was heated at 130 ° C for 5 hours. Gas absorption indicated that approximately 55% of the cobalt (II) salt had been converted to catalyst precursor. The regenerated catalyst precursor was transferred, under pressure of CO: H2, to the autoclave containing CO: H2 (95: 5) at 5517 kPa, 29.5 g (0.5 mol) of acetamide (Vil), 34.0 g (1.08 mol) of 95% paraformaldehyde, 32.2 g (1.79 mol) of water and 650 ml of DME. An atmosphere of CO: H2 (95: 5) at 10.345 kPa was immediately established. This mixture was heated to 100 ° C. The reaction was heated to 125 ° C and maintained at that temperature for one hour. HPLC analysis of that stream gave a yield of 95% of (XVI), 2% of (XIV), 2.5% of (XVIII) and 0.5% of N-methyliminodiacetic acid.

EXAMPLE 11 This example illustrates how a cobalt salt (II) can be regenerated and used in the reaction step to give (XVI). An autoclave was charged with 40.0 g (0.158 mol) of cobalt acetate tetrahydrate, 4.1 g (0.012 mol) of Co2 (CO) 8 and 102 g (1.70 mol) of acetic acid and pressurized to 15,170 kPa of CO. : H2 (90:10) at 25 ° C. This mixture was heated at 130 ° C for one hour. The gas absorption indicated that approximately 55% of the cobalt (II) salt had been converted to the catalyst precursor. The regenerated catalyst precursor was transferred, under pressure of CO: H2, to the autoclave at 95 ° C, containing CO: H2 (95: 5) at 6.210 kPa, 59.0 g (1.0 mol) of acetamide (Vil), 68.0 g (2.16 mol) of paraformaldehyde at 95%, 64.5 g (3.60 mol) of water and 750 ml of DME. An atmosphere of CO: H2 (95: 5) at 10.345 kPa was immediately established. This mixture was heated to 125 ° C and maintained at that temperature for one hour. HPLC analysis of this stream gave a yield of 77% (XVI), 4% (XIV), 7.0% (XVIII) and 0.1% N-methyliminodiacetic acid.

EXAMPLE 12 This example illustrates how a cobalt (II) salt can be regenerated and used in the reaction step, to give high yields of (XVI). An autoclave was charged with 40.0 g (0.158 mol) of cobalt acetate tetrahydrate, 4.1 g (0.012 mol) of Co2 (CO) 8 and 100 g (1.69 mol) of acetic acid, and pressurized to 15,170 kPa of CO: H2 (90:10), at 25 ° C. This mixture was heated at 130 ° C for one hour. Gas absorption indicated that approximately 51% of the cobalt (II) salt had been converted to the catalyst precursor. The regenerated catalyst precursor was transferred, under CO: H2 pressure, to the autoclave at 95 ° C, which contained CO: H2 (95: 5) at 6.210 kPa, 59.0 g (1.0 mol) of acetamide (VII), 68.0 g (2.16 mol) of 95% paraformaldehyde, 64.5 g (3.60 mol) of water and 600 ml of DME. An atmosphere of CO: H2 (95: 5) at 15,170 kPa was immediately established. This mixture was heated to 1250 ° C and maintained at that temperature for one hour. HPLC analysis of this stream gave a yield of 95% of (XVI), 4% of (XIV), 7.0% of (XVIII) and 0.1% of N-methyliminodiacetic acid.

EXAMPLE 13 This example illustrates the advantage of carrying out the regeneration of a Co (II) salt to an active carboxymethylation catalyst, in the presence of an amide.

A 2 liter autoclave was charged with 128.5 g (2.2 mol) of acetamide (Vil), 33 g (0.13 mol) of Co (OAc) 2.4H20, 750 ml of THF and 250 ml of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established, at 25 ° C, with agitation at 2,000 r.p.m. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 10 minutes a rapid absorption of gas was observed, indicating the regeneration of the cobalt (II) salt.

For comparative purposes this procedure was repeated, except that it was used four times (but in one a partial pressure of CO: H2 (90:10) was used in the absence of acetimide and in 1 000 ml of acetic acid (without THF for give (upper bar) 960 ml of THF and 40 ml of acetic acid (second bar down), in third, without THF or acetimide, and in the fourth bar down, without THF The advantage of having added amide during regeneration it is further illustrated in Figure 3, which shows the tremendous increase in the regeneration regime that is achieved in the presence of additional amide, as compared to the examples in which amide is not added.

EXAMPLE 14 This example illustrates the conversion of a variety of different cobalt (II) salts to a mixture of active carboxymethylation catalyst, in the presence of additional amide. A.- A 2-liter autoclave was charged with 128.5 g (2.2 moles) of acetamide (VII), 83 g (0.13 moles) of Co (II) stearate and 1 liter of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa of CO: H 2 (70:30) was established at 25 ° C, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 10 minutes, a rapid absorption of gas was observed. B.- A 2-liter autoclave was charged with 128.5 g (2.2 moles) of acetamide (VII), 34 g (0.13 mol) of cobalt acetylacetonate (II) and 1 liter of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa, of CO: H2 (70:30) at 25 ° C was established, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 17 minutes a rapid absorption of gas was observed.

C- A 2-liter autoclave was charged with 128.5 g (2.2 mol) of acetamide (VII), 48.4 g (0.12 mol) of cobalt (II) bis-N-acetyliminodiacetate and 1 liter of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 20 minutes a rapid absorption of gas was observed.

EXAMPLE 15 These examples illustrate how different amides can be used in the process of this invention. A.- A 2-liter autoclave was cured with 60 g (1.0 mol) of urea (V), 66 g (0.26 mol) of Co (OAc) 2.4H2O and 1 liter of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about one hour a rapid absorption of gas was observed. The reaction mass was cooled to 85 ° C and the feed gas was changed to a composition of CO: H2 (90:10). Under a constant pressure of 22,069 kPa, 320 ml (5.28 moles) of 47% by weight formalin was supplied at 16 ml / minute. The reaction was stirred at 85 ° C for 90 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and concentrated to an oil, under reduced pressure. The oil was treated with 2 liters of 10% HCl at 100 ° C for two hours. This resulted in a yield of 13% (XIV) and 5% glycine. B.- A 2-liter autoclave was chopped with 130 g (1.0 mol) of methylenebisacetamide (VI), 49 g (0.20 mol) of Co (OAc) 2.4H20 and 1 liter of THF. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After approximately 0.5 hour a rapid absorption of gas was obstructed. Under a constant of 22,069 kPa, 300 ml (4.95 mol) of 47% by weight formalin was supplied at 10 ml / minute. The reaction was stirred at 130 ° C for 60 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and analyzed. A 62% yield of (XVI) was observed. C- A 1 liter autoclave was charged with 160 g (2.2 moles) of N-methylacetamide (IX), 33 g (0.13 mol) of Co (OAc) 2.4H20 and 1 liter of acetic acid. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 0.5 hour a rapid absorption of gas was observed. The reaction mass was cooled to 85 ° C. Under a constant pressure of 22,069 kPa, 180 ml (2.97 moles) of 47% by weight formalin was supplied at 6 ml / minute. The reaction was stirred at 85 ° C for 30 minutes, after the addition of formalin was complete. The reaction was then cooled to 25 ° C, separated from the autoclave and analyzed for N-acetyl-sarcosine. This resulted in a yield of 92% of (XX). D.- A 1 liter autoclave was charged with 90 g (1.23 mol) of N-methylacetamide (IX), 16.5 g (0.13 mol) of Co (OAc) 2.4H20 and 500 ml of tetrahydrofuran. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about one hour a rapid absorption of gas was observed. The reaction mass was cooled to 65 ° C and the pressure was slowly reduced to 10.345 kPa. At that point carbon monoxide was established as the feed gas for carboxymethylation. Under a constant pressure of 10.345 kPa, 180 ml (2.97 moles) of 47% by weight formalin was supplied at 6 ml / minute. The reaction was stirred at 65 ° C for 30 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and analyzed for N-acetyl sarcosine (XX). This resulted in a yield of 85% of (XX). E.- A 2-liter autoclave was charged with 96.9 g (1.1 mol) of 1,3-dimethylurea (X), 33 g (0.13 mol) of Co (OAc) 2.4H2O and 500 ml of acetic acid. After sealing the autoclave a pressure of 15 was established, 172 kPa CO: H (70:30) at 25 ° C, with stirring at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H (70:30) was established. After about one hour, rapid absorption of gas was observed. The reaction mass was cooled to 85 ° C. Under a constant pressure of 22,069 kPa, 201 ml (3.31 moles) of 47% formalin was supplied at 6 ml / minute. The reaction was stirred at 85 ° C for 60 minutes, after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and concentrated to an oil, under reduced pressure. The oil was treated with 2 liters of 10% HCl, at 100 ° C, for two hours. This resulted in a 5% yield of (XXIII). F.- A 1 liter autoclave was charged with 12.3 g (0.05 mol) of bis (phosphonomethyl) urea (XII), 2.4 g (0.01 mol) of Co (OAc) 2.4H2O and 300 ml of acetic acid. After sealing the autoclave a pressure of ,172 kPa of CO: H2 (70:30), at 25 ° C, with stirring, at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 1.5 hours, a rapid absorption of gas was observed. The reaction mass was cooled to 95 ° C. Under a constant pressure of 22,069 kPa, 10 ml (0.17 mol) of 47% by weight formalin was supplied at 0.5 ml / minute. The reaction was stirred at 95 ° C for 60 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and concentrated to an oil, under reduced pressure. The oil was treated with 500 ml of 10% HCl, at 100 ° C, for 2 hours. This resulted in a 5% yield of glyphosate (I). G.- A 300 ml autoclave was shied with 23.4 g (0.20 mol) of N-acetylglycine (XVIII), 6.8 g (0.22 mol) of 95% paraformaldehyde, 6.5 g (0.36 mol) of water, 16.8 g (0.28 g) mol) of acetic acid, 90 ml of DME and 2.01 g (0.006 mol) of Co2 (CO) 8, and was pressurized to 10.345 kPa of CO: H2 (95: 5), at 25 ° C. This mixture was heated at 110 ° C for 30 minutes. The analysis of HPLC of that stream gave a yield of 87% of (XVI), 1.0% of (XIV) and 10% of (XVIII) unreacted. H.- A 2-liter autoclave was charged with 130 g of a solid with a composition of 85% methylenebisacetamide (VI) / 10% of [CH3C (O) N (H) CH] 2NC (O) CH3 / 5% of acetamide (Vil), 49 g (0.20 mol) of Co (OAc) 2.4H2O and 1 liter of THF. After sealing the autoclave, a pressure of 15,172 kPa of CO: H2 (70:30) was established at 25 ° C, with agitation at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 0.5 hour, rapid absorption of gas was observed. Under a constant pressure of 22,069 kPa, 300 ml (4.95 mol) of 47% by weight formalin was supplied at 10 ml / minute. The reaction was stirred at 130 ° C for 60 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C and removed from the autoclave. HPLC analysis of the reaction indicated a 58% yield of (XVI). I.- A 2-liter autoclave was charged with 128.5 (2.2 mole) of acetamide (Vil), 33 g (0.13 mole) of Co (OAc) 2.4H20, 960 ml of THF and 40 ml of acetic acid. After sealing the autoclave a pressure of ,172 kPa of CO: H 2 (70:30), at 25 ° C, with stirring at 2,000 rpm. The contents of the autoclave were heated to 130 ° C and a pressure of 22,069 kPa of CO: H2 (70:30) was established. After about 75 minutes a rapid absorption of gas was observed. The autoclae contents were cooled to 85 ° C and a pressure of 22,069 kPa was established with CO: H2 feed (90:10).

Under a constant pressure of 22.069 kPa (90: 1 O / CO feed: H2), 320 ml (5.28 moles) of 47% formalin was supplied at 9 ml / minute. The reaction was stirred at 85 ° C for 60 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and analyzed for N-acetyliminodiacetic acid. This resulted in a yield of 85% of (XVI) and 3% yield of (XVIII).

EXAMPLE 16 This example illustrates a preferred mode of conducting the carboxymethylation reaction, where formaldehyde is introduced in a controlled manner. A 2 liter autoclave was charged with 129.8 g (2.2 moles) of acetamide (VII), 1 liter of THF and 45 g of acetic acid, and purged with argon for 10 minutes. 20.9 g (0.06 mol) of C? 2 (CO) 8 was added under purge with argon. After sealing the autoclave, a pressure of 1.034 kPa of CO: H2 (95: 5) was established at 25 ° C, and the pressure was slowly relieved. Then a pressure of 15,172 kPa of CO: H2 (95: 5) was established at 25 ° C with agitation at 2,000 rpm. The contents of the autoclave were heated to 100 ° C and a pressure of 22,069 kPa of CO: H2 (95: 5) was established. Under a constant pressure of 22,069 kPa, 320 ml (5.28 moles) of 47% by weight formalin were supplied, 40 ml / minute. The reaction was stirred at 100 ° C for 52 minutes after the addition of formalin was complete. The reaction was then cooled to 25 ° C, removed from the autoclave and analyzed for N-acetyliminodiacetic acid. This resulted in a 95% yield of (XVI) and 1% glycine.

EXAMPLES 17-19 Examples 17-19 illustrate the profound effect that the amount of water present in the reaction has on the yield of (XVI). Example 17 does not contain water; Example 18 contains 0.36 mole% of water; Example 19 contains 0.60 mole% water.

EXAMPLE 17 A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 10.6 g (0.18 mol) of acetic acid (0.12 g / ml DME), 90 ml of DME and 4.1 g (0.012 mol) of Co2 (CO) 8, and pressurized to 10.345 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes HPLC analysis of this stream indicated a 30% yield of (XVI), and a 47% yield of (XVIII).

EXAMPLE 18 A 300 ml autoclave was charged with 11.8 g (0.2 mol) of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 6.5 g (0.36 mol) of water, 16.8 g (0.28 mol) of acetic acid (0.19 g / ml of DME), 90 ml of DME and 4.1 g (0.012 mol) of Co2 (CO) 8 and put under pressure at 10.345 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes. HPLC analysis of this stream gave a yield of 93% of (XVI), 1% of (XIV) and 4% of (XVIII).

EXAMPLE 19 A 300 ml autoclave was charged with 11.8 g (0.2 mol) = of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 10.8 g (0.60 mol) of water, 16.8 g (0.28 mol) of acid acetic acid (0.19 g / ml DME), 90 ml DME and 4.1 g (0.012 mol) of Co2 (CO) 8 and put under pressure at 10.345 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 125 ° C for 30 minutes. HPLC analysis of this stream indicated a yield of 91% of (XVI), 1% of (XIV) and 3% of (XVIII).

EXAMPLE 20 This example illustrates the use of acetonitrile as a solvent. A 300 ml autoclave was charged with 11.8 g (0.2 mol) = of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 16.8 g (0.28 mol) of acid acetic acid, 90 ml of acetonitrile and 4.1 g (0.012 mol) of Co2 (CO) 8 and pressurized to 22.069 kPa of CO: H2 (95: 5) a ° C. This mixture was heated at 110 ° C for 30 minutes. The analysis of HPLC of this stream indicated a 96% yield of (XVI), 1% of (XIV) and 3% of (XVIII).

EXAMPLE 21 This example illustrates the use of acetone as a solvent. A 300 ml autoclave was charged with 11.8 g (0.2 mol) = of acetamide (Vil), 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 2.1 g (0.035 mol) of acid acetic acid, 90 ml of acetone and 2.1 g (0.006 mol) of Co2 (CO) 8 and pressurized to 22.069 kPa of CO: H2 (95: 5) at 25 ° C. This mixture was heated at 110 ° C for 30 minutes. HPLC analysis of this stream indicated a 95% yield of (XVI), 0.5% of (XIV) and 4.5% of (XVIII).

EXAMPLE 22 This example illustrates the utility of various reaction conditions for the carboxymethylation of acetamide (VII). The reactions were carried out in a manner similar to that of example 1. Table 5 summarizes the reaction conditions used and the results of those reactions. A 300 ml autoclave was charged with 95% paraformaldehyde, such that the molar ratio of paraformaldehyde to acetamide was 2.15, 90 ml of solvent and the indicated amounts of acetamide, water, Co2 (CO) 8 and acetic acid. The autoclave was pressurized at the indicated pressure with CO: H2 (95: 5), at 25 ° C. Each mixture was heated at 125 ° C for 30 minutes. The analyzes were by HPLC. In the table, "DME" is dimethoxyethane; "THF" is tetrahydrofuran and "HOAc" is acetic acid.

TABLE 5 PERCENTAGE OF PERFORMANCE OF (XVI) BASED ON THE STARTING AMOUNT OF ACET AMIDA (HIV) UNDER DIFFERENT CONDITIONS OF REACTION EXAMPLE 23 The pictures contained in this example illustrate how certain combinations of the reaction conditions result in extremely high yields of (XVI).

TABLE 6 PERCENTAGE YIELD OF (XVI) BASED ON THE AMOUNT OF ACETAMID DEPARTURE (VID WHEN THE HOAc / Co REASON VERSUS THE MOLES DE H? Q.

The reaction conditions included 10.345 kPa of CO: H2 (95: 5), 90 ml of DME solvent, 11.8 g of acetamide, 13.6 g of 95% paraformaldehyde and 4.1 g of C? 2 (CO) 8. The values in parentheses represent the sample numbers in Table 5.

• Calculated using the number of moles of Co atoms (supplied in the reaction as Co2 (CO) 8) TABLE 7 PERCENTAGE PERFORMANCE OF (XVI) BASED ON THE AMOUNT INITIAL OF ACET AMIDA (VID WHEN THE MMOLES OF ACETIC ACID (HOAc) AGAINST THE MMOLES OF Co? (CO) «.

Reaction conditions include 10.345 kPa of CO: H2 (95: 5), 90 ml of DME solvent, 12.9 g of water, 13.6 g of 95% paraformaldehyde and 11.8 g of acetamide. The values in parentheses represent sample numbers from Table 5.

TABLE 8 PERCENTAGE PERFORMANCE OF (XVI) BASED ON ACETAMID (VID WHEN ACETIC ACID (HOAc) VERSUS COATED (CO) "; The reaction conditions include 22.069 kPa of CO: H2 (95: 5), 90 ml of THF solvent, 12.9 g of water, 13.6 g of 95% paraformaldehyde and 11.8 g of acetamide. The values in parentheses represent sample numbers from Table 5.

EXAMPLE 24 This example illustrates the effect of pressure on the yields of (XVI) in the presence of acetic acid.

TABLE 9 The reaction conditions included CO: H2 (95: 5), 90 ml of DME solvent, 12.9 g of water, ratio of acetic acid to cobalt, about 15: 1 (based on cobalt atoms), 13.6 g of 95% paraformaldehyde and 11.8 g of acetamide. The sample numbers refer to the examples in table 5.

EXAMPLE 25 This example illustrates how the increase in pressure in the carboxymethylation reactions allows a dramatic increase in performance at higher reaction payloads.

TABLE 10 Effect of pressure on the percentage yield of (XVI) at various concentrations of acetamide load. Reaction conditions included 13,545 to 28,896 kPa of CO: H 2 (95: 5), 90 ml of DME solvent, 3.6 molar ratio of water to acetamide, about 15, .0 of molar ratio of acetic acid to cobalt atoms and 13.6 g of 95% paraformaldehyde. The numbers in the examples refer to examples in table 5.

EXAMPLE 26 This example illustrates the effect that several solvents have on the yield of (XVI).

TABLE 11 Reaction conditions included CO: H2 (95: 5), 90 ml of solvent, 0.2 mol of acetamide, 12.9 g of water and 13.6 g of 95% paraformaldehyde. The sample numbers refer to the examples in table 5.

Example 27 This example illustrates how cobalt (II) bis-N-acetyliminodiacetate can be recovered from a typical carboxymethylation reaction mixture. A.- An amount of 144.07 g of final carboxymethylation reaction mass was generated, in a procedure similar to that described in example 1. An autoclave was charged with 11.8 g (0.2 mol) of acetamide, 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 33.0 g (0.55 mol) of acetic acid, 70 g of acetone and 2.55 g (0.007 mol) of Co2 (CO) 8. After sealing the autoclave, a pressure of 1.034 kPa of CO: H2 (95: 5) was established ° C and let it escape slowly. Then a pressure of ,172 kPa of CO: H2 (95: 5) at 25 ° C, with stirring, at 2,000 rpm. The contents of the autoclave were heated to 100 ° C and a pressure of 22,069 kPa of CO: H2 (95: 5) was established. This mixture was heated at 100 ° C for 30 minutes.

From this reaction mass, 141.3 g was transferred to a round bottom flask.

Air was bubbled through the stirred reaction mass at room temperature for 130 minutes, until the solution turned deep purple, with slight turbidity. The air supply was disconnected and the reaction mixture was heated to reflux for 80 minutes. A pink precipitate began to appear after 30 minutes of heating and continued during the warm-up period. The system was cooled to 30 ° C and the pink solid filtered, washed with acetone and dried to give 5.89 g of solid. The analysis showed that the solid contained 13.7% cobalt and 79.87% N-acetyliminodiacetic acid. The analysis of the liquid filtrate showed 242 ppm of cobalt and 22.64% of N-acetyliminodiacetic acid. Of the cobalt 96.7% was in the pink solid and 3.3% was in the filtrate. B.- An amount of 149.00 g of a final carboxymethylation reaction mass was generated, in a procedure similar to that described in example 1. An autoclave was charged with 11.8 g (0.2 mol) of acetamide, 13.6 g (0.43 mol) of 95% paraformaldehyde, 12.9 g (0.72 mol) of water, 33.0 g ( 0.55 mol) of acetic acid, 70.1 g of acetone and 3.03 g (0.009 mol) of Co2 (CO) 8. After sealing the autoclave, a pressure of 1035 kPa of CO: H2 (95: 5) was established at 25 ° C and allowed to escape slowly. After a pressure of ,172 kPa of CO: H2 (95: 5) at 25 ° C, with stirring, at 2,000 rpm. The contents of the autoclave were heated to 100 ° C and a pressure of 22,069 kPa of CO: H2 (95: 5) was established. This mixture was heated at 100 ° C for 30 minutes. From that reaction mass 143.9 g was transferred to a round bottom flask.

Air was bubbled through the stirred reaction mass, while being brought to 61.5 ° C. It remained there for 120 minutes, while the air continued to bubble. The solution was clear and intense red to purple, after 40 minutes and the pink precipitate first appeared after 60 minutes. The system was cooled to 30 ° C and the pink solid was filtered off, washed with acetone and dried to give 6.59 g of solid. Analysis of the solid showed 13.4% cobalt and 78.97% N-acetyliminodiacetic acid. The analysis of the liquid filtrate showed 215 ppm of cobalt and 20.63% of N-acetyliminodiacetic acid. Of the cobalt, 97.2% was in the pink solid and 2.8-% was in the filtrate. C- In a typical carboxymethylation reaction, a 300 ml autoclave was charged with a mixture of 12.9 g of water, 33.0 g of glacial acetic acid, 90 ml of acetone, 13.6 g of paraformaldehyde powder of greater than 95%, 11.8 g of acetamide and 4,109 g of C? 2 (CO) 8, equivalent to about 1416 mg of cobalt. A mixture of CO: H2 gas (95: 5) was charged to an initial pressure of 22.069 kPa, the reactor was heated at 110 ° C for 30 minutes, with stirring and then cooled to below 20 ° C. The pressure was allowed to slowly escape, the system was purged with nitrogen (N2) and the reactor was sealed. The contents were heated with stirring (closed system) at 90 ° C, stirred at 90 ° C for 3 hours and then cooled to 20 ° C. The pressure in the reactor, after cooling, was 1103 kPa. The pressure was relieved, the reactor was opened and the contents were filtered to obtain 8.44 g of a pink powder containing 11.8% cobalt (996 mg, 70% of the cobalt used). It was found that the mother liquors contained 203 mg of cobalt. Some solids adhered to the reactor. They were removed by dissolving them in water and found to contain 267 mg of cobalt. D.- In a typical carboxymethylation reaction, a 300 ml autoclave was charged with a mixture of 12.9 g of water, 33.0 g of glacial acetic acid, 90 ml of tetrahydrofuran, 13.6 g of paraformaldehyde as a 95 +% powder, 11.8 g of acetamide and 2,078 g of Co2 (CO) 8, equivalent to about 716 mg of cobalt. A gaseous mixture of CO: H2 (95: 5) was charged at an initial pressure of 22.069 kPa; the reactor was heated at 110 ° C for 30 minutes, with stirring, and then cooled to below 20 ° C. The pressure was slowly allowed to escape, the system was purged with N2 and the reactor was opened under an inert atmosphere and its contents were transferred to a 250 ml glass, three-necked round bottom flask equipped with an inlet tube. gas, thermometer with thermocouple and a distillation head. The vessel was heated under N2 atmosphere and the contents were distilled (vessel temperature: 70-80 ° C, distillation head temperature: 64 ° C) until 60 ml of distillate was collected. A pink precipitate formed on the bottom during the distillation. After cooling, the bottom was filtered to obtain 4.96 g of pink powder containing 12.0% cobalt (596 mg, 83% of the cobalt used). It was found that the mother liquors contained 13 mg of cobalt. Some solids adhered to the distillation flask. They were removed by dissolving in water and found to contain 37 mg of cobalt.

EXAMPLE 28 This example illustrates the conversion of (XVI) to a mixture of (XVII) under various reaction conditions. 175 g of N-acetyliminodiacetic acid monohydrate (XVI) and varying amounts of water and acetic acid were heated at 175 ° C or 195 ° C for various periods of time. After cooling to ambient temperature the mixture was filtered. It was washed with 10 ml of water and dried to give 1,4-di (carboxymethyl) -2,5-diketopipeazine. The following table shows solid yields under various conditions.

TABLE 12 EXAMPLE 29 This example illustrates that the amount of (XVII) or of (XIV) obtained from (XVI) may vary, depending on the conditions of the reaction. 10 g of N-acetyliminodiacetic acid monohydrate (XVI), 5 g of acetic acid and 35 g of water were heated at 150 ° C in an autoclave. Table 13 shows the relative quantities of products, based on 1H NMR analysis, at various times: TABLE 13 EXAMPLE 30 This example illustrates the conversion of N-acetyliminodiacetic acid (XVI) to minodiacetic acid (XIV) in the presence of a mineral acid. A.- 8.45 g of N-acetyliminodiacetic acid monohydrate (XVI) and 11 g of 9N HCl were heated at reflux for 30 minutes. Analysis of the mixture showed 99% conversion to minodiacetic acid hydrochloride. After cooling, the mixture was filtered and the solid was dried to give iminodiacetic acid hydrochloride. B. A mixture of 30% of H2SO4, 30% of H2O and 40% of NAIDA XVI (by weight) was heated in an oil bath at 110 ° C for 20 minutes. Analysis of the mixture showed that the hyrolysis to minodiacetic acid (XIV) was complete.

EXAMPLE 31 This example illustrates the preparation of N- (phosphonomethyl) iminodiacetic acid, from the N-acetyliminodiacetic acid monohydrate (XVI). N-acetyliminodiacetic acid monohydrate (XVI), sulfuric acid, water and phosphorous acid were heated at 110 ° C and 6.5 ml (0.10 mol) of 42% formalin was added over a period of one hour. After another 1.75 hours at 110 ° C, the mixture was cooled and filtered. The solid was washed and dried to give N- (phosphonomethyl) iminodiacetic acid (PMIDA). All reagents / solvents appear in the table below, along with the amount of PMIDA (XV) produced. Unless stated otherwise, the amount of H3PO3 is 11.39 g (0.14 mol).

TABLE 14 PHOSPHONOMETHODS OF (XVI) EXAMPLE 32 This example illustrates the preparation (XV) from 1,4-di (carboxymethyl) -2,5-diketopiperazine (XVII). A.- 0.8059 g of 1,4-di (carboxymethyl9-2,5-diketopiperazine (XVII), 0.51 g of water, 4.25 g of 12 N HCl and 0.5342 g of 47.4% formalin in a sealed tube in a bath were heated. of oil at 105 ° C with stirring for one hour, then heated at 105 ° C for one hour to yield 55% of (XV) B.- 11.9 g of 1,4-di (carboxymethyl) was heated at 120 ° C. ) -2,5-diketopiperazine, 26 g of phosphorus trichloride hydrolyzate (43.8% of H3PO3, 16. 8% HCl) and 26 g of 20% HCl, and 8.4 g (47.42%) of formalin was added, over a period of 30 minutes. The solution was maintained at 120 ° C during 1. 75 hours to produce 88.2% of (XV).

EXAMPLE 33 This example illustrates the direct preparation of (I) from (XVIII). A one liter flask was charged with 117.0 g (1.0 mol) of N-acetylglycine (XVIII), 100 ml of acetic acid and 18 g (1.0 mol) of water. 137 g (1.0 mol) of phosphorus trichloride was slowly added at 25 ° C, with rapid stirring. The temperature of the reaction mass was rapidly heated to 50 ° C during that time. Then 60 ml (1.03 mol) of 47% by weight formalin was added at 45 ° C for 0.5 hour. The solution to 75 ° C for 19 hours after the addition of formalin. Analysis of the reaction at that time indicated a 15% yield of glyphosate (I).

EXAMPLE 34 This example illustrates the conversion of (XVII) to (XIV) in the presence of mineral acid, under various conditions. 1 g of 1,4-di (carboxymethyl) -2,5-diketopiperazine (XVII) was refluxed under reflux in 1N, 3N, 6N, 9N and 12N aqueous HCl. The following table shows the percentage of (XVII) remaining at various times. It was shown by NMR that the hydrolysis product was mainly (XIV).

TABLE 15 PERCENTAGE OF (XVII) REMNANT EXAMPLE 35 These examples illustrate the conversion of (XX) to (XXI). A.- 20.0 g (152.5 mmol) of N-acetyl sarcosine (XX), 12.5 g (152.4 mmol) of phosphorous acid and 37.6 g of concentrated HCl were mixed and left to reflux in an oil bath at 120 ° C. 13.6 g (167.6 mmol) 37% formalin was added dropwise over 20 minutes and the reaction was continued for a further 19 hours. HPLC analysis indicated a 99% yield of N-methylglifosate (XXI), based on the moles of (XX) charged.

B.- 20.0 g (137.8 mmol) of N-propionyl-sarcosine was converted, according to the conditions described in (A), to N-methylglifosate, using 11. 3 g (137.8 mmol) of phosphorous acid, 10.0 g of concentrated hydrochloric acid and 12.3 g (152.1 mmol) d 37% formalin. HPLC analysis indicated a 96.6% yield of N-methyl glyphosate (XXI) based on the moles of charged N-propionylsarcosine. C- 2.06 g (14.50 mmoles) of sarcosine anhydride (XXV) was converted, following the conditions described in (A), to N-methyl glyphosate (XXI), using 2.38 g (29.02 mmol) of phosphorous acid, 5.7 g of acid concentrated hydrochloric acid and 2.6 g (32.0 mmol) of 37% formalin. HPLC analysis indicated a 97.2% yield of (XXI), based on the mmoles of (XXV) loaded. D.- 2.0 g (15.3 mmol) of N-acetyl sarcosine (XX), 1.25 g (15.3 mmol) of phosphorous acid, were mixed with 3.1 g of concentrated sulfuric acid and 1.7 g of water; then it was left to reflux in an oil bath at 120 ° C. 1.4 g of 37% formalin (16.7 mmol) was added dropwise over 20 minutes, and the reaction was continued for a further 18 hours. The 31P NMR analysis indicated a 98% yield of (XXI) based on the mmoles of (XX) loaded.

EXAMPLE 36 This example illustrates the conversion of sarcosine (XXIII) to (XXI). 89.09 g (1.00 mol) of sarcosine (XXIII), 82.0 g (1.0 mol) of phosphorous acid and 110 g of concentrated hydrochloric acid were mixed and left to reflux in an oil bath at 130 ° C. Droplet 89.3 g (1.1 mole) of 37% formalin was added dropwise during 20 minutes, and the reaction was continued for others 85 minutes At this point, 31 P NMR indicated the following product distribution (on a molar basis): 89.9% N-methyl glyphosate, 2.1% phosphorous acid, 1.9% phosphoric acid, 0.4% hydroxymethyphosphorous acid, and 5.7% of a unknown product. NMR: triple band, 8.59 ppm). After cooling to room temperature, 40 g (1 mole) of sodium hydroxide was added, followed by 250 g of water, which leads to the formation of a white precipitate which was recovered by filtration and analyzed by HPLC. The total recovered yield of N-methylglifosate was 70.5% based on the amount of sarcosine and phosphorous acid used.

EXAMPLE 37 This example illustrates the conversion of an N-methyl glyphosate (XXI) to glyphosate (I) using a platinum and oxygen catalyst. A.- 10.0 g of N-methyl glyphosate (XXI), 140 g of water and 1 g of platinum black (Aldrich Chemical) were combined in a round-bottomed flask equipped with a water-cooled reflux condenser, immersed in water. an oil bath at 150 ° C. Oxygen was bubbled through the reaction mixture for four hours, while stirring the solution. At the end of that period, the HPLC analysis revealed the following product distributions (on a molar basis): 6.4% glyphosate (I), 8.7% N-methyl glyphosate (XXI), 2.2% aminomethylphosphonic acid and 2.7% of phosphoric acid. Glyphosate (I) precipitated from the solution after cooling to room temperature. B.- It was stirred for two hours with 40 minutes, a mixture of 10.0 g of N-methylglifosate (XXI), 2.0 g of platinum black and enough water to bring the total volume of the mixture to 200 ml, stirred for two hours. hours plus 40 minutes, at a temperature of 80 ° C, while oxygen was bubbled at a pressure of one atmosphere, through the reaction mixture. The analysis of the reaction mixture indicated the following distribution of products (on a molar basis: N-methyl glyphosate (XXI), not detected, glyphosate (I) (85.4%), phosphoric acid (8.1%). reaction mixture were not identified.

EXAMPLE 38 This example illustrates the conversion of N-isopropylglyphosate to glyphosate (I) using a platinum (Pt) catalyst and oxygen. 1.0 g of N-isopropylglifosate, 10 g of water and 0.3 g of platinum black (Aldrich) were combined in a round-bottomed flask equipped with a water-cooled reflux condenser and immersed in an oil bath at 80 ° C. . An oxygen stream was introduced into the reaction surface for 18 hours, as the solution was stirred. At the end of this period, MRI with 31P indicated the following distribution of product (on a molar basis): glyphosate (I), 91%; aminophosphonic acid, 1%; 6% phosphoric acid, and an unknown product (2%, 15.0 ppm). Glyphosate (I) precipitated from the solution after cooling to room temperature.

EXAMPLE 39 COBALT PRECIPITATION THROUGH THE OXIDATION METHOD ANAERÓBICA - REFLUJO In a typical carboxymethylation reaction, a 300 ml autoclave was charged with a mixture of 12.9 g of distilled and deionized water, 33.0 g of glacial acetic acid, 90 ml of tetrahydrofuran, 13.6 g of paraformaldehyde, as a powder of more than 95% , 11.8 g of acetamide and 2,105 g of the cobalt-tetracarbonyl dimer (equivalent to approximately 26 mg of Co). A 95: 5 gaseous mixture of CO: H2 was charged to an initial pressure of 22,496 kPa, the reactor was heated at 110 ° C for 30 minutes with stirring, and then cooled to below 20 ° C. The pressure was slowly relieved, the system was flushed with nitrogen and the reactor was opened under an inert atmosphere, and the contents were transferred to a 250 ml glass, three-necked round bottom flask equipped with an inlet tube for gas, thermometer with thermocouple and a distillation head. The vessel was heated to reflux under nitrogen atmosphere for three hours. A pink precipitate formed during heating. After cooling, the mixture was filtered to obtain 5.62 g of pink powder containing 12.6% cobalt (708 mg, 98% of the cobalt used). It was found that mother liquors contained 13 mg of cobalt (2% cobalt used).

EXAMPLE 40 This example illustrates the improved selectivities that can be achieved in the oxidative dealkylation of an N-alkylamino acid reaction product, when the electroactive molecular species is adsorbed to a noble metal catalyst. All the electroactive molecular species adsorbed in platinum black, in this example, undergo oxidation and reduction by electron transfer. Thus, the treatment of platinum-containing catalysts by electroactive molecular species as well as their oxidation precursors is exemplified herein. This experiment was carried out by refluxing a mixture containing 1 g of N- (phosphonomethyl) -N-methyl-glycine XXI ("NMG"), 20 ml of water and 50 mg of metallic platinum, in a bottom flask round magnetically stirred, equipped with reflux condenser. Oxygen was bubbled for 5 hours using a needle. The catalyst was then filtered off and the filtrate was analyzed by HPLC. To prepare the catalysts treated with organic compounds, 0.5 g of platinum black (Aldrich Chemical Co., Inc., Milwaukee, WI, USA) was added to a solution of 25 mg of the poison (ie, the electroactive molecular species) in 50 ml of anhydrous acetonitrile. The mixture seat was capped in an Erlenmeyer flask for four days, except that the 4,4'-difluorobenzophenone catalyst was exposed only one day to the solution. The catalyst was subsequently recovered by filtration, rinsed with acetonitrile and diethyl ether, and air-dried overnight. The 2,4,7-trichlorofluorene catalyst was prepared using 0.3 g of Pt black and 30 ml of a solution consisting of 834.5 ppm of 2,4,7-trichlorofluorene in acetonitrile / 1% solution of methylene chloride ( used to facilitate the dissolution of the electroactive molecular species), which was allowed to evaporate at room temperature. Subsequently the catalyst was washed with ethanol and air dried. The catalysts treated with the inorganic compound were prepared by combining 050 g of Pt black, 50 ml of tetrahydrofuran and 25 or 100 mg of the inorganic electroactive molecular species and stirring overnight at room temperature in a sealed Erlenmeyer flask, 125 ml. The catalyst was recovered by filtration, washed with diethyl ether and air dried.

The inorganic species used, all of which were obtained from Aldrich Chemical (Milwaukee, WI, USA), were: 1. 5,10,15,20-tetracycline (pentafluorophenyl) -21H, 23H-porphine-iron chloride (lll) (abbreviated "Fe (lll) TPFPP chloride" in Table 16). Approximately 25 mg was used to prepare the catalyst. 2. Chloride of 5, 10,15,20-tetraphenyl-21 H, 23H-porphine-iron (III) (abbreviated "Fe (III) TPP chloride" in Table 16). Approximately 25 mg was used to prepare the catalyst. 3. 5,10,15-20-tetraphenyl-21 H, 23H-porphine (II) (abbreviated "Ni (ll) TPP" in Table 16). Approximately 25 mg was used to prepare the catalyst. 4. Ruthenium-tris dichloride (2,2'-bipyridine) (abbreviated "[Ru (bpy) 3] CI2" in Table 16. Approximately 100 mg was used to prepare the catalyst 5. Ferrocene Approximately 100 was used mg to prepare the catalyst When available, the literature data on the oxidation potential (E? / 2) of the electroactive molecular species is reported in table 16. This example illustrates that the electroactive molecular species that are relatively soluble in water (for example, ferrocene and [Ru (bpy) 3] Cl2) are less effective in increasing glyphosate selectivity This example also demonstrates that hydrophobic electroactive molecular species increase the selectivity of the catalyst.

The electroactive molecular species that have oxidation potentials more negative than around +0.3 V against SCE, generally decrease the conversion. Thus, the preferred electroactive molecular species for increasing selectivity and conversion of NMG oxidation may be organic or inorganic, but must be hydrophobic and have oxidation potentials more positive than about 0.3 volts against SCE.

TABLE 16 Use of electroactive molecular species on the oxidation of NMG EXAMPLE 41 This example illustrates the effect of the electroactive molecular species on the platinum catalyzed oxidation of N-isopropylglyphosate, using the commercially available catalyst 20% Pt on carbon Vulcan XC-72R (manufactured by Johnson-Matthey and obtainable from Alfa / Aesar (Ward Hill, MA, USA) The commercial catalyst was tested together with a catalyst that had been impregnated with two electroactive molecular species: N-hydroxyphthalimide and triphenylmethane.These catalysts were used to oxidize N-isopropylglyphosate by the method described in previous example: N- (phosphonomethyl) -N-methylglycine XXI was replaced by approximately 1 g of N-isopropylglyphosate The results shown in Table 17 demonstrate that electroactive molecular species improve the selectivity of platinum catalysts on carbon, for This reaction Modifiers with less positive oxidation potentials, such as triphenylmethane, appear to be more effective than those with more positive oxidation potentials, such as N-hydroxyphthalimide. This example also demonstrates that the use of graphitic supports for platinum is less effective in suppressing undesirable side reactions in oxidations of N-isopropylglyphosate, as is the case for N- (phosphonomethyl) -N-methyl-glycine (XXI).

TABLE 17 USE OF ELECTROACTIVE MOLECULAR SPECIES DURING THE OXIDATION OF N-ISOPROPYL-GLYPHOSATE EXAMPLE 42 This example demonstrates the selectivities that can be obtained when N-alkyl glyphosates are oxidized at low oxygen delivery rates and moderate conversion, if an electroactive molecular species, such as TEMPO (ie N-2-oxide), is added to the reaction mixture. , 2,6,6-tetramethyl piperidine). No pretreatment of the catalyst is necessary. This example further demonstrates that the conversion improves with respect to the first few cycles, when the electroactive molecular species is added to the mixture. Finally, this example demonstrates that the electroactive molecular species reduces the amount of noble metal loss.

A 300 ml glass pressure bottle was fitted with a thermocouple and two fritted filters. One of the filters was placed approximately 1. 27 cm above the center of the bottom of the bottle, and was used for gas dispersion. The second filter, located around 2.54 cm from the bottom and not centered, was used for the extraction of liquids. A gas outlet line was also provided which leads to a pressure regulator, regulated to maintain the pressure at 351.5 kPa gauge. About 60 g of N- (phosphonomethyl) -N-methylglycine XXI, 180 ml of water, 3 g of platinum black (Aldrich Chemical, Milwaukee, Wl, USA) and 40 mg of TEMPO were dissolved in the pressure reactor. in 1 ml of acetonitrile. The mixture was heated to 125 ° C while stirring under a nitrogen atmosphere at 351.5 kPa gauge, which formed a homogeneous mixture. A nitrogen / oxygen mixture (75% nitrogen, 25% oxygen by volume) was bubbled through the mixture for 90 minutes, at a flow rate of 1 liter per minute at normal temperature and pressure, while maintaining the pressure at 351.5 kPa gauge. The reaction mixture was then extracted through a fritted filter, leaving behind the catalyst. Another 60 g of N- (phosphonomethyl) -N-methyl-glycine XXI, 180 ml of water and 40 mg of TEMPO in 1 ml of acetonitrile were added to the flask., and the cycle was repeated. In total, four cycles were carried out. In all cases the concentrations of (M) AMPA were below quantifiable limits, although traces were detected. The only quantifiable by-product detected was phosphoric acid. The conversions and selectivities at the end of each of the four cycles are shown in Table 18. The concentration of dissolved platinum was determined at the end of each operation, by mass spectrometry, by inductively coupled plasma. This concentration of dissolved platinum was less than 0.1 ppm in cycles 2, 3 and 4. This is less than the platinum concentration that was observed (ie, 0.3 to 1.1 ppm) when platinum black was used without the presence of a electroactive molecular spice, under similar reaction conditions, for 7 cycles. While there was a larger amount of platinum leached to the solution during the first cycle (ie, the platinum dissite was 8.3 ppm), it is believed that the majority of the platinum lost was primarily unreduced platinum that was on the surface of the black of platinum. In fact, the same phenomenon occurred when platinum black was used without an electroactive species; in that case, the concentration of dissolved platinum was 4.2 ppm.

TABLE 18 OXIDATION OF NMG XXI IN THE PRESENCE OF TEMPO AT 125 ° C FOR 90 MINUTES In view of the above, it will be seen that the various objects of the invention are achieved and other advantageous results are obtained. Since several changes can be made to the above methods, without departing from the scope of the invention, it is intended that all material contained in the preceding description, or shown in the accompanying drawings, be construed as illustrative and not in a limiting sense.

Claims (93)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A process for the preparation of an aminocarboxylic acid or a salt or ester thereof, by carboxymethylation of a carbamoyl compound; characterized in said process because it comprises: forming a reaction mixture containing the carbamoyl compound, a carboxymethylation catalyst precursor, carbon monoxide, hydrogen, water and an aldehyde; where the reaction mixture is formed by combining the carbamoyl compound and the carboxymethylation catalyst precursor in the presence of carbon monoxide and hydrogen, and introducing the water and the aldehyde into the reaction mixture after combining the carbamoyl compound and the precursor of carboxymethylation catalyst; and reacting the components of the reaction mixture to generate a product mixture containing an N-acylaminocarboxylic acid reaction product and a catalyst reaction product.
2. 2. The process according to claim 1, further characterized in that the carbamoyl compound has the formula: wherein R 1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, -NR 3 R 4, -OR 5 O-SR 6; 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 sai-forming cation; provided, however, that (1) at least one of R2 and R2a is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing a N-H linkage; or (2) R1 is -NR3R4 and at least one of R3 and R4 is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing an N-H linkage.
3. 3. The process according to claim 2, further characterized in that the carboxymethylation catalyst precursor is cobalt derivative.
4. 4. The process according to claim 3, further characterized in that the reaction is carried out at a pressure of at least about 7,000 kPa. 5. - The process according to claim 3, further characterized in that R is alkyl or -NR3R4; R2 and R3 are independently hydrogen, alkyl, hydroxymethyl, amidomethyl, phosphonomethyl, carboxymethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R2a and R4 are independently hydrogen, hydroxymethyl or another substituent that is hydrolysable under the carboxymethylation reaction conditions. 6. The process according to claim 3, further characterized in that R1 is methyl or -NR3R4; R2 and R3 are independently hydrogen, methyl, isopropyl, hydroxymethyl, carboxymethyl, phosphonomethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R2a and R4 are independently hydrogen or hydroxymethyl. 7. The process according to claim 1, further characterized in that the carbamoyl compound comprises an N-phosphonomethyl substituent. 8. The process according to claim 3, further characterized in that R1 is -NR3R4, one of R2 and R2a is alkyl and one of R3 and R4 is alkyl. 9. The process according to claim 1, further characterized in that the carbamoyl compound is a urea. 10. The process according to claim 1, further characterized in that the carbamoyl compound is bis-phosphonomethylurea. 11. The process according to claim 3, further characterized in that the molar ratio of cobalt atoms of the carboxymethylation catalyst to carbamoyl compound is about 0.5 to 15. 12. The process according to claim 3, further characterized in that the molar ratio of water to carbamoyl compound in the carboxymethylation reaction mixture is between about 2: 1 and about 5: 1. 13. The procedure according to claim 1, further characterized in that the reaction product of N-acylaminocarboxylic acid contains an N-alkyl substituent and the process comprises oxidatively dealkylating the reaction product of N-acylaminocarboxylic acid in the presence of oxygen, using a noble metal catalyst. 14. The process according to claim 1, further characterized in that the method comprises the step of converting the reaction product of N-acylaminocarboxylic acid to 2,5-diketopiperazine, which has the formula: wherein R2 and R2a are hydrogen, alkyl, carboxymethyl or a salt or ester thereof. 15. The process according to claim 14, further characterized in that diketopiperazine is precipitated from the product mixture. 16. The process according to claim 14, further characterized in that the process further comprises the passage of phosphonomethylar 2,5-diketopiperazine. 17. The process according to claim 1, further characterized in that the aldehyde is provided in pure form, in polymeric form, in aqueous solution, or as an acetal. 18. The process according to claim 1, further characterized in that the aldehyde is formaldehyde, acetaldehyde, 3-methylthiopropionaldehyde or isobutyraldehyde. 19. The process according to claim 1, further characterized in that the aldehyde is formaldehyde, the formaldehyde source being formaldehyde. 20. The process according to claim 3, further characterized in that the reaction mixture contains at least about 0.1 g of carbamoyl compound per gram of solvent. 21. The process according to claim 3, further characterized in that the reaction mixture contains at least about 0.15 g of carbamoyl compound per gram of solvent. 22. The process according to claim 3, further characterized in that the process further comprises the step of regenerating the catalyst reaction product in the presence of the carbamoyl compound. 23. The process according to claim 3, further characterized in that the catalyst reaction product is recovered by exposing the product mixture to a gas containing molecular oxygen, forming a solid containing a cobalt salt (II) and filtering the solid of the mixture. 24. The process according to claim 23, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the product mixture; adding excess solvent to the product mixture or distilling the solvent from the product mixture. 25. The process according to claim 3, further characterized by recovering the catalyst reaction product from the product mixture forming a solid containing a cobalt (II) salt under anaerobic conditions, and filtering the solid from mix. 26. The process according to claim 25, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the product mixture, by adding excess solvent to the product mixture, or by distilling the solvent from the product mixture. reaction mixture. 27. - The process according to claim 24, further characterized in that the molar ratio of carbon monoxide to hydrogen is about 70:30 to about 99: 1. 28. A process for the preparation of an aminocarboxylic acid or a salt or ester thereof, by carboxymethylation of a carbamoyl compound; characterized in said process because it comprises: forming a reaction mixture containing the carbamoyl compound, carbon monoxide, hydrogen, an aldehyde and a carboxymethylation catalyst precursor, cobalt derivative; reacting the components of the reaction mixture to generate a product mixture containing a reaction product of N-acylaminocarboxylic acid and a catalyst reaction product; recover the catalyst reaction product, from the product mixture; and regenerating the catalyst reaction product in the presence of the carbamoyl compound. 29. The process according to claim 28, further characterized in that the carbamoyl compound has the formula: wherein: R 1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, -NR 3 R 4, -OR 5 O-SR 6; 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, that (1) at least one of R2 and R2a is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing a N-H linkage; or (2) R1 is -NR3R4 and at least one of R3 and R4 is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing an N-H linkage. 30. The process according to claim 29, further characterized in that the reaction is carried out at a pressure of at least about 9,000 kPa. 31. The process according to claim 29, further characterized in that R1 is methyl or -NR3R4; R2 and R3 are independently hydrogen, methyl, isopropyl, hydroxymethyl, carboxymethyl, phosphonomethyl or an ester or a carboxymethyl or phosphonomethyl salt; and R2a and R4 are independently hydrogen or hydroxymethyl. 32. The process according to claim 29, further characterized in that R1 is -NR3R4, one of R2 and R2a is alkyl and one of R3 and R4 is alkyl. 33. The process according to claim 28, further characterized in that the carbamoyl compound comprises an N-phosphonomethyl substituent. 34. The process according to claim 28, further characterized in that the carbamoyl compound is selected from the group consisting of urea, N-alkylurea, N, N'-dialkylurea, acetamide, N-alkylacetamide and bisphosphonomethylurea. 35. The process according to claim 28, further characterized in that the molar ratio of carbon monoxide to hydrogen is about 70:30 to about 99: 1. 36.- The process according to claim 28, further characterized in that the molar ratio of cobalt atoms of the carboxymethylation catalyst to carbamoyl compound is about 2 to 13. 37.- The process according to the claim 28, further characterized in that the reaction product N-acylaminocarboxylic acid contains an N-alkyl substituent and the process comprises oxidatively dealkylating the reaction product N-acylaminocarboxylic acid in the presence of oxygen, using a noble metal catalyst. 38.- The process according to claim 28, further characterized in that the aldehyde is formaldehyde, the formaldehyde source being formaldehyde. 39.- A process for the preparation of N- (phosphonomethyl) glycine or a salt or ester thereof, characterized in that said method comprises: preparing a reaction product of N-acylamino acid by carboxymethylation of a carbamoyl compound in a mixture of reaction formed by combining the compound carbamoyl, formaldehyde, carbon monoxide, hydrogen and a carboxymethylation catalyst precursor, cobalt derivative; convert the reaction product of N-acylamino acid to N- (phosphonomethyl) glycine or a salt or ester thereof; wherein the conversion comprises deacylating the reaction product of N-acylamino acid to generate a carboxylic acid and an amino acid; reacting the carboxylic acid with an amine to generate the carbamoyl compound or a compound from which the carbamoyl compound can be derived. 40. The process according to claim 39, further characterized in that the carbamoyl compound comprises an N-phosphonomethyl substituent. 41. The process according to claim 39, further characterized in that the carbamoyl compound is selected from the group consisting of acetamide and N-alkylacetamide. The method according to claim 39, further characterized in that the reaction product N-acylaminocarboxylic acid contains an N-alkyl substituent and the process comprises: oxidatively dealkylating the reaction product N-acylaminocarboxylic acid in the presence of of oxygen, using a noble metal catalyst. 43.- The method according to claim 39, further characterized in that the method comprises the step of converting the reaction product N-acylaminocarboxylic acid to a 2,5-diketopiperazine having the formula: wherein R2 and R2a are hydrogen, alkyl, carboxymethyl; or a salt or an ester thereof. 44. The process according to claim 43, further characterized in that diketopiperazine is precipitated from the product mixture. 45.- The process according to claim 39, further characterized in that the catalyst reaction product is recovered by exposing the product mixture to a gas containing molecular oxygen, forming a solid containing a cobalt salt (11) and filtering the solid of the mixture. 46. The process according to claim 45, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the product mixture; adding excess solvent to the product mixture; or distilling solvent from the product mixture. 47. The process according to claim 39, further characterized in that the catalyst reaction product is recovered by forming a solid containing a cobalt (II) salt under anaerobic conditions; and filtering the solid of the product mixture. 48. The process according to claim 47, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the product mixture; adding excess solvent to the product mixture; or distilling solvent from the product mixture. 49.- The process according to claim 45, further characterized in that the cobalt (II) salt is regenerated in the presence of the carbamoyl compound. 50.- The process according to claim 45, further characterized in that the cobalt (II) salt is regenerated using carbon monoxide and hydrogen to produce hydridocobalt-tetracarbonyl and combining the hydridocobalt-tetracarbonyl with the carbamoyl compound. 51. The process according to claim 50, further characterized in that the hydridocobalt-tetracarbonyl is combined with the carbamoyl compound by absorbing the hydridocobalt-tetracarbonyl in a volume of the carbamoyl compound. 52. A process for the preparation of N- (phosphonomethyl) glycine or a salt or ester thereof, characterized in that said process comprises: preparing N-acetyliminodiacetic acid carboxymethylating acetamide in a reaction mixture formed by combining acetamide, acetic acid, water, formaldehyde, carbon monoxide, hydrogen and a cobalt-derived carboxymethylation catalyst precursor; and converting N-acetyliminodiacetic acid to N- (phosphonomethyl) glycine or a salt or ester thereof, wherein the conversion comprises deacylating N-acetylimino-diacetic acid. 53.- The procedure according to claim 52, further characterized in that the reaction is carried out at a pressure of at least about 7,000 kPa. 54.- The process according to claim 52, further characterized in that the reaction is carried out at a pressure of at least about 9,000 kPa. 55.- The process according to claim 52, further characterized in that the molar ratio of acetic acid to cobalt is between about 2 and about 60. The process according to claim 52, characterized also because the molar ratio of acetic acid to cobalt is between about 10 and about 50. The process according to claim 52, further characterized in that the pressure is less than about 12,500 kPa, and the molar of acetic acid to cobalt is between about 2 and about 20. 58. The process according to claim 52, further characterized in that the pressure is less than about 12,500 kPa and the molar ratio of acetic acid to Cobalt is between around 7 and around 15. 59. - The process according to claim 52, further characterized in that the pressure is between about 12,500 kPa and about 17,500 kPa and the molar ratio of acetic acid to cobalt is about 8 to about 30. 60.- The The process according to claim 52, further characterized in that the pressure is between about 12,500 kPa and about 17,500 kPa and the molar ratio of acetic acid to cobalt is about 10 to about 20. 61.- The process of according to claim 52, further characterized in that the pressure is greater than 17,500 kPa and the molar ratio of acetic acid to cobalt is about 10 to about 50. 62. The process according to claim 52, further characterized in that the molar ratio of carbon monoxide to hydrogen is about 85:15 to about 97: 3. 63.- The process according to claim 52, further characterized in that the molar ratio of cobalt atoms of the carboxymethylation catalyst to carbamoyl compound is about 0.5 to 15. 64.- The process according to the claim 52, further characterized in that the molar ratio of cobalt atoms of the carboxymethylation catalyst to carbamoyl compound is about 2 to 13. 65. The process according to claim 52, further characterized in that the molar ratio of water to acetamide in the carboxymethylation reaction mixture is between about 2: 1 and about 5: 1. 66. The process according to claim 52, further characterized in that the molar ratio of water to acetamide in the carboxymethylation reaction mixture is between about 3: 1 and about 4: 1. 67.- The process according to claim 52, further characterized in that the process further comprises reacting the acetic acid with ammonia to convert it to acetamide. 68.- The method according to claim 52, further characterized in that the method comprises the step of converting the reaction product N-acylaminocarboxylic acid to a 2,5-diketopiperazine having the formula: wherein R) 2, and, R D2 ^ a3 are carboxymethyl or a salt or ester thereof. 69. The process according to claim 68, further characterized in that diketopiperazine is precipitated from the reaction mixture. 70.- The process according to claim 69, further characterized in that the catalyst reaction product is recovered from the reaction mixture, refluxing the reaction mixture under anaerobic conditions, to form a solid containing a salt of cobalt (II), and filtering the solid of the mixture. 71.- The process according to claim 69, further characterized in that the catalyst reaction product is recovered from the reaction mixture, exposing the reaction mixture to a gas containing molecular oxygen, forming a solid containing a salt of cobalt (II) and filtering the solid of the mixture. 72. The process according to claim 71, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the reaction mixture; the addition of excess solvent to the reaction mixture, or the distillation of the solvent from the reaction mixture. 73.- The process according to claim 69, further characterized in that the catalyst reaction product is recovered from the reaction mixture by forming a solid containing a cobalt (II) salt under anaerobic conditions, and filtering the solid mix. 74. - The process according to claim 73, further characterized in that the formation of the solid is accelerated by the addition of an organic acid to the reaction mixture; adding excess solvent to the reaction mixture, or distilling solvent from the reaction mixture. 75.- The procedure according to claim 69, further characterized in that the cobalt (II) salt is regenerated using carbon monoxide and hydrogen to produce hydridocobalt-tetracarbonyl and combining the hydrodocobalt-tetracarbonyl with the carbamoyl compound. The process according to claim 75, further characterized in that the hydridocobalt-tetracarbonyl is combined with the carbamoyl compound by absorbing the hydridocobalt-tetracarbonyl in a volume of the carbamoyl compound. 77.- The process according to claim 70, further characterized in that the cobalt (II) salt is regenerated in the presence of acetamide. 78.- A process for the preparation of N- (phosphonomethyl) glycine or a salt or ester thereof, characterized in that said method comprises: forming a reaction mixture containing a carbamoyl compound, a carboxymethylation catalyst precursor, formaldehyde and carbon monoxide; reacting the components of the reaction mixture to generate a product mixture containing an N-acylaminocarboxylic acid reaction product and a catalyst reaction product; and converting the reaction product N-acylaminocarboxylic acid to N- (phosphonomethyl) -glycine or a salt or ester thereof; where the carbamoyl compound has the formula: R1 is -NR3R4; R2 and R2a are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; R3 and R4 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; provided that at least one of R2, R2a, R3 and R4 is hydrogen, hydroxymethyl, amidomethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing a N-H linkage. 79. The process according to claim 78, further characterized in that the carbamoyl compound is urea, bisphosphonomethylurea, N-alkylurea and N, N'-dialkylurea. 80.- The process according to claim 78, further characterized in that the carbonylation catalyst precursor is a composition containing cobalt. 81. The process according to claim 78, further characterized in that the reaction mixture is formed by combining the carbamoyl compound and the carboxymethylation catalyst precursor in the presence of carbon monoxide and hydrogen; and introducing water and the aldehyde into the reaction mixture, after combining the carbamoyl compound and the carboxymethylation catalyst precursor. 82.- The process according to claim 78, further characterized in that the catalyst reaction product is regenerated in the presence of the carbamoyl compound. 83.- A process for the preparation of N- (phosphonomethyl) glycine or a salt or ester thereof, characterized in that said method comprises: forming a reaction mixture containing a carbamoyl compound, a carboxymethylation catalyst precursor, formaldehyde and carbon monoxide; reacting the components of the reaction mixture to generate a product mixture containing a reaction product N-acyl-N-alkylaminocarboxylic acid, and a catalyst reaction product; and oxidatively dealkylating the reaction product N-acyl-N-alkylaminocarboxylic acid in the presence of oxygen, using a noble metal catalyst; where the carbamoyl compound has the formula: R1 is alkyl; R2 is hydrocarbyl or substituted hydrocarbyl; and R2a is hydrogen, hydroxymethyl or another substituent which, under the conditions of the carboxymethylation reaction, is capable of producing a N-H linkage. 84. - The process according to claim 83, further characterized in that R 2 is methyl or isopropyl. 85.- The process according to claim 83, further characterized in that the noble metal catalyst comprises platinum. 86.- The process according to claim 83, further characterized in that R2 is methyl or isopropyl and the noble metal catalyst has an electroactive, hydrophobic molecular species, adsorbed therein. 87. The method according to claim 86, further characterized in that the electroactive molecular species has an oxidation potential of at least about 0.3 volts against SCE. 88. The process according to claim 87, further characterized in that R2 is methyl or isopropyl and the noble metal catalyst comprises platinum. 89.- A compound characterized because it has the structure: 90. - A compound characterized because it has the structure: 91. - An acetamide equivalent compound, characterized in that it is 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 a carboxymethyl or phosphonomethyl salt; R15, R16 and R17 are independently alkyl or -NR3R4; and R3 and R4 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl. 92. The composition according to claim 91, further characterized in that R13, R14, R15, R16 and R17 are independently methyl, ethyl and isopropyl. 93. - A compound characterized in that it has the formula: wherein R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, -NR3R4, or -SR6; R3 and R4 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; and R6 is hydrogen, hydrocarbyl, substituted hydrocarbyl or a salt-forming cation.