Substituted Phenoxypropionic Acids

The preparation of IVF involved the condensation of substimted phenox)tpro-pionyl chlorides M20 and 2-(l-hydroxyethyl)-5,5-dimethyl-l,3,2-dioxaphosph-inane-2-one IVB-11 in the presence of triethylamine as a base. The substituted phenoxypropionyl chlorides M20 could be easily obtained by the reaction of substituted phenoxypropionic acids M19 and thionyl chloride in high yields. Substituted phenoxypropionic acids M19 could be synthesized starting from... 

Substituted phenoxypropionic acids M19 could be synthesized starting from substituted phenols and 2-bromopropionic acid ester (Scheme 9.24). 

General procedure To a three-necked boiling flask, an appropriate substituted phenol (0.04 mol), ethyl 2-bromopropionate (0.042 mol), and potassium carbonate (5.8 g) were added by order, then DMSO (100 mL) was added as solvent. The mixture was stirred and kept at 70-80 °C for 5 h, then was treated with ice water immediately. After yellow solid was filtered off, and dissolved in acetone (20 mL), 2 mol/L NaOH were added, then stirred for another 2 h at room temperature. Then added 2 mol/L HCI, and the corresponding substituted phenoxypropionic acid M19 was formed. The solid could be recrystallized as a white crystal. Several M19 could be obtained by this procedure in 75-95 % yields. 

The structures, physicochemical data, and yields of substituted phenoxypropionic acids M19 are listed in Table 9.35. 

Table 9.35 Stmcture and physicochemical data of substituted phenoxypropionic acids M19...

Substituted phenoxypropionyl chlorides M20 could be obtained by the reaction of substituted phenoxypropionic acids M19 and thionyl chloride (Scheme 9.25). 

An appropriate substituted phenoxypropionic acid (0.1 mol) and thionyl chloride (50 mL) were refluxed for 2- h at 70 °C and then the unreacted thionyl chloride was removed under reduced pressure (50-52 °C/1.5 h/11.3 kPa) to give the corresponding substituted phenoxypropionyl chloride M20 as a yellow liquid. Several M20 were obtained by this procedure in 85-96 % yields, which could be used for the next reaction without purification. 

The phenoxypropionic acid herbicides (Chapter 31) rely on an SN2 reaction to convert the S-2-chloropropionic acid (1) to the ff-2-aryloxy derivative 2.3 These compounds are also available from lactic acid by substitution reactions -lactic acid (3) requires two inversions, whereas S-lactate (4) only requires one (Schemes 22.2 and 22.3).4... 

The fragmentation pathways for the methyl esters are strongly dependent on the type of acid, i.e. whether a derivative of phenoxyacetic acid, phen-oxypropionic acid, or phenoxybutyric acid, and on the nature of the substitution of the aromatic ring. The methyl esters of chlorinated phenoxyacetic and phenoxypropionic acids show reasonably abundant molecular ions (about 20% relative to the base peak) which, together with the chlorine isotope patterns, permit easy identification of these compounds. In contrast, the spectra of the methyl esters of chlorinated phenoxybutyric acids are dominated by the fragment ion at m/z 101, with only low abundance of molecular ions. However, the spectra also show... 

The range of action of a-phenoxypropionic acids differs from that of phenoxyacetic acids, as was established by Luckwill and Lloyd-Jones (1960). They assumed that decarboxylation causing the detoxication of the molecule is inhibited in certain plant species because of the a-methyl substitution, and that this kills the weeds resistant to phenoxyacetic acids (Fawcett et al., 1953 Lush and Leafe, 1956). Leafe (1962) found that Galium aparine (cleavers), resistant to MCPA, is killed by... 

An ortho substituted methoxy group reduces auxin activity, but does not cancel it in compounds of otherwise strong activity. The meta methoxy group strengthens the auxin action in phenoxyacetic acids, but causes decreased activity in otherwise strongly active compounds. The para methoxy group enhances activity in phenoxyacetic acids, but reduces it in phenoxypropionic acids. 

The oxidation of phenols to catechols or hydroquinones by tyrosinase enzymes has been developed for biocatalysis. For example, the ortho-hydroxylation of L-tyrosine 162 (and also substituted variants) to give l-DOPA 163 has been extensively studied due to the importance of l-DOPA in the treatment of Parkinson s disease [92, 93]. An arene hydroxy lating enzyme having a broad substrate scope is 2-hydroxybiphenyl 3-monooxygenase from Pseudomonas azelaica, which is able to oxidize many ortho-substituted phenols 68 to the corresponding catechols 127 [94], as shown in Scheme 32.19. A notable example of an industrial biocatalytic arene hydroxylation that has been employed on very large scale (lOOm fermentation) is the pora-hydroxylation of R)-2-phenoxypropionic acid 164 by whole cells of Beauveria bassiana Lu 700 to give (R)-2-(4-hydroxyphenoxy)propionic acid 165, an important intermediate in herbicide manufacture [95]. 

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