Glyphosate production

These results contrasted sharply with those obtained with a HHT that was relatively unstable to the reaction conditions. For example, the commercially available HHT of glycinonitrile 28 gave a very poor yield (6%) of coupled glyphosate product with diethyl phosphite because the reaction must be run with acid-catalysis at much lower temperatures (27,38). Somewhat higher yields were observed when 28 was used directly under the modified, acidic Mannich conditions to provide iV-phosphonomethylglycinonitrile 29, which was hydrolyzed direedy to GLYNa3 (39). 

Activated carbon is thus being applied in the last step of the glyphosate production the oxidative decarboxylation of PMIDA toward glyphosate uses oxygen gas as the oxidant, forming carbon dioxide and formaldehyde as side products (Scheme 17.1). 

Scheme 17.2 Possible side reactions during the glyphosate production.

Extensive research, performed at Cabot Norit Activated Carbon, has been done to determine the most optimal conditions for the glyphosate process as well as to study the influence of various properties of the activated carbon catalyst on the glyphosate production. The impact of these quantitative and qualitative parameters on the glyphosate reaction is discussed later. These studies were carried out in a 400 ml aqueous 2-3 wt% PMIDA solution containing 1-5 wt% activated carbon at 60-95 C applying a constant oxygen flow of 0-500ml/min. 

Figure 17J Activity (a) and selectivity (b) profiles for glyphosate production by four Norit SXRO activated carbon samples with different pore size distributions ranging from 2 to 8a.u.

At the time of its discovery in 1970, few chemical methods were known for the laboratory syntheses of such molecules. Fewer still were appropriate for their industrial scale production. Unlike many other amino acid derivatives, gl rphosate is stable in strong acid or base, even at elevated temperatures. It can also tolerate strong reductants and some oxidants (1,2). This stability accounts for the diversity of synthetic methods that have been explored and developed to prepare glyphosate and its heterocyclic derivatives over the last 25+ years. 

The HHT of ethyl glycinate 25 also reacted quantitatively with aliphatic phosphites under comparable conditions to give the corresponding aliphatic glyphosate triester 26, which was identical in all respects to the corresponding Mannich product (31). The product mixture from diethyl thiophosphite was much mote complex and led to dramatically lower yields (27). 

An interesting variation of this reaction that made use of a three-component, one-pot solventless procedure with the corresponding trialkyl phosphites gave dramatically improved yields of many heterosubstituted glyphosate phosphonate diesters (37). When exactly one equivalent of water, 25, and tris-p-chloroethyl phosphite were mixed and heated under neat conditions for a few hours, nearly quantitative yields of displaced p-chloroethanol and the desired triester product 27 were obtained. If desired, the displaced alcohol was first removed by vacuum distillation, or the mixture could be hydrolyzed directly to GLYH3. Various oxygen, sulfur, nitrogen, cyano, and carboxylate functionalities were similarly accommodated in the trialkyl phosphite. 

Considerably higher product yields resulted under much milder conditions when diaryl phosphites were condensed with ffilTs. Whereas vigorous neat conditions and temperatures exceeding 100 °C were usually necessary with aliphatic phosphites, often quantitative conversions to the desired glyphosate derivatives were obtained in common organic solvents using aromatic or benzylic phosphites (40). 

Certain 1,3,4-oxadiazole and 1,2,4-triazole glyphosate derivatives have been conveniently prepared in a faster, more efficient manner by heating the thionoester intermediates 73 with the appropriate acid hydrazide (61). These versatile thionoesters 73 have been synthesized in nearly quantitative yield from the readily available nitrile 31a, described previously, through the intermediate imidate ester 72. The oxadiazole products such as 70 obtained using this procedure were identical to those obtained from the HHT approach. 

The parent tetrazole derivative of glyphosate 78 has been reported as a product of the 1,3-dipolar cycloaddition of n-Bu3SnN3 across the nitrile linkage in 76 and subsequent hydrolysis of the resulting diester 77 (62). 

The effects of glyphosate on phenolic compound production are two-fold 1) accumulation of phenolic compounds that are derivatives of aromatic amino acids is reduced and 2) pools of phenolic compounds derived from constituents of the shikimate pathway prior to 5-enolpyruvylshikimate-3-phosphate become larger. Assays that do not distinguish between effects on these two groups, such as that for hydroxyphenolics of Singleton and Rossi (18), can lead to equivocal and difficult to interpret results (e.g. 3-5). 

Many herbicides and other chemicals have been reported to influence levels of various phenolic compounds in higher plants by unknown mechanisms. It is unlikely that more than a few of these compounds have a primary influence on secondary phenolic compound synthesis. For instance, in our survey of the effects of 17 herbicides on anthocyanin accumulation, only glyphosate appeared to directly influence accumulation (31). The effects of several compounds on secondary phenolic compound production for which the mechanism of influence is unknown are summarized in Table II. A much longer list could be derived from the literature. Unfortunately, many of these compounds are phytotoxic or are known to have effects other than on secondary aromatic compound production. In most cases the effects on these compounds correlate well with extractable PAL activity (31, 71, 72, 73, 74) (Figure 5), even though they do not directly affect the enzyme. 

Several compounds with excellent potential for manipulation of phenolic allelochemic production have been discussed. These include glyphosate, AOPP, chlorsulfuron, and acifluorfen. 

Little information has been published on pesticide degradation products, produced in coffee, that may have significant physiological effects. Some information has been published, however, for glyphosate,191 aldicarb,194 and carbofuran,187 although there is some controversy surrounding the carbofuran data.188... 

Because the enzyme targeted by glyphosate is not present in humans or other animals, the product is advertised as entirely safe by the industry. The EPA rates glyphosate as toxicity class II—practically nontoxic even by direct ingestion. Industry advocates celebrate glyphosate as an international ecological success. ... 

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