Phenylpyruvic acid methyl ester

By analogy with the rearrangement of styrene oxide compounds, more complicated substances, e. g. phenylpyruvic acid methyl ester derivatives, can be synthesized from readily available glycidic acid esters, as shown in Figure 3. These esters can be used as intermediates for herbicides (e. g. the triazinones) and for the synthesis of L-amino acids. 

In gas-phase reactions zeolites are superior to non-zeolitic molecular sieves, metal phosphates, and metal oxides. Over the mildly acidic [B]-MFI (Si/B = 24) the synthesis of phenylpyruvic acid methyl ester yields up to 94 % at 200 °C and WHSV = 3 h 95 % product yield could be achieved with the cesium-doped material (0.6 % w w) [8]. With these concepts a-ketocarboxylic acid esters can be prepared from readily available feedstocks whereas conventional methods require the use of costly and environmentally problematical Grignard reactions. 

Increasing the temperature to 350 °C results in decarbonylation of the phenylpyruvic acid methyl ester derivatives and the phenyl acetic ester is formed with a ratio of 65 % a-ketoester to 35 % acetic acid ester. Until now the industrial process for the synthesis of phenylacetic acid ester has started from benzyl chloride, which is converted to benzyl cyanide by KCN, followed by hydrolysis. Every step of this reaction must be performed in a separate reactor and special measures must be taken for handling large amounts of toxic KCN. The new route is certainly an environmentally benign alternative [8,27]. 

A second commercial synthesis of papaverine was performed by Wahl (62) in 1947 but not published until three years later. 3,4-Dimethoxy-phenylpyruvic acid (XXXVIII), prepared from veratraldehyde and hip-puric acid, was treated with ammonium hydroxide at 100° under pressure, and the resultant diamide (XXXIX) was hydrolyzed to the corresponding 3- (3,4- dimethoxyphenyl)- a- (3,4- dimethoxyphenylacetamido) propionic acid. The methyl ester of this compound was cyclized readily with phosphorus oxychloride, and the resulting ester was saponified to 3,4-dihydro-papa verine-3-carboxylic acid (XL). The latter was decarboxylated at 140° in tetralin solution to 3,4-dihydropapaverine, and addition of palladium-on-carbon catalyst to the reaction mixture furnished papaverine, four parts of vanillin leading to one part of the alkaloid in over-all yield. 

The cyclic dipeptide cyclopenin (12) has been neatly synthesised by condensation of a modified anthranilic acid moiety with phenylpyruvic acid. The reaction strategy (Scheme 2) was patterned on biogenetic considerations. 2-Nitrobenz-amide (13) condensed with phenylpyruvic acid to give the hippuric acid (14) the ester (15), upon iV-methylation, reduction, and cyclisation, gave the 3,10-dehydro-derivative (18), which had been converted previously into cyclopenin. 

Perhaps the most successful and widely used artificial sweetener is aspartame, the methyl ester of a dipeptide formed from phenylalanine and aspartic acid. Aspartame is roughly 100 times as sweet as sucrose. It undergoes slow hydrolysis in solution, however, which limits its shelf life in products such as soft drinks. It also cannot be used for baking because it decomposes with heat. Furthermore, people with a genetic condition known as phenylketonuria cannot use aspartame because their metabolism causes a buildup of phenylpyruvic acid derived from aspartame. Accumulation of phenylpyruvic acid is harmful, especially to infants. Alitame, on the other hand, is a compound related to aspartame, but with improved properties. It is more... 

Fig. 5.18 shows the spectrum of 2-oxoisovaleric acid as its TMS-oxime derivative. The TMS groups give rise to the silyl ions at mjz 73, 75, 147, as already described, which together with M, M —15, M—43 and M-117 are also present in the spectrum of derivatized phenylpyruvic acid (Fig. 5.18). The aromatic ring helps to stabilize the molecular ion, while at the same time directing fragmentation of the benzyl bond to give mjz 91 (CeHgCH. The ion at mjz 189 is formed by the sequential loss of the ester and a methyl radical from the oxime silyl group (-CH3-CO2TMS).

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