Halogenated Phenylacetates

Component B is a monomeric reductase with a molecular weight of 35,000 and contains per mol of enzyme, 1 mol of FMN, 2.1 mol of Fe, and 1.7 mol of labile sulfur. After reduction with NADH, the ESR spectrum showed signals that were attributed to a [2Fe-2S] structure and a flavo-semiquinone radical (Schweizer et al. 1987). The molecular and kinetic properties of the enzyme are broadly similar to the Class IB reductases of benzoate 1,2-dioxygenase and 4-methoxybenzoate monooxygenase-O-demethylase. 

Substrate Specificity of 4-Chlorophenylacetate 3,4-Dioxygenase in Component A of Pseudomonas sp. Strain CBS (Markus et al. 1986) 

FIGURE 9.18 Transformation of 3,5-diacetamido-2,4,6-triiodobenzoate by Trametes versicolor. (From Neilson, A.H. and Allard, A.-S., The Handbook of Environmental Chemistry, Vol. 3R, Springer Verlag, 2002, pp. 1-74. With permission.) 

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The halogens in o-bromo- or o-iodo-veratric acids are replaced by ketone enolates to give primary products which on lactonization or lactamization lead to benzazepines or benzoxepines respectively.126 There would appear to be no reason why this reaction could not be extended to reactions of o-halo-phenylacetic acids in general. 

In analogy to the reduction of aliphatic halogen compounds, the reduction of sulfonates can be used for the alkylation of phenylacetic acids 435) ... 

Auxins are defined as organic substances that promote cell elongation when applied in low concentrations to plant tissue segments in a bioassay. By this definition, there are several other native auxins that have been reported to occur in plants in addition to the most often studied auxin, IAA. These include the halogen-substituted 4-C1-IAA,23 as well as phenylacetic acid and indole-3-butyric acid.24 All native auxins are found in planta as both free acids and conjugated forms through ester or amide linkages. IAA, the auxin most extensively studied, will be the focus of this chapter. 

Prior structure-activity studies with diclofenac analogs indicate that methyl or chlorine substituents on the lower aniline ring of the inhibitor in the ortho position are required for potent inhibition of COX (44). Analogs with halogen substitutions (fluorine or chlorine) at the 5 position of the phenylacetic acid ring demonstrate an even higher potency for COX inhibition (44). 

Halogenated aromatic compounds can be condensed with alkyl or aryl halides by using copper to remove the halogen Zincke350 prepared ethyl phenylacetate in this way from bromobenzene and ethyl chloroacetate and Ullmann and his co-workers351 prepared biaryls from 2 moles of aryl halide and copper (for a review see Fanta352). 

This type of oxidative addition involving the carbon-halogen bond cleavage may be involved in other catalytic processes using alcohols in the presence of hydrogen halide. For example, in the carbonylation of benzyl alcohol in the presence of HI, phenylacetic acid can be catalyfically produced in the presence of aPd(O) complex (Eq. 1.5) [25]. 

Cobaltcarbonyls are used for the carbonylation of benzyl halides or aromatic halides [74-76]. For example, as shown in eq. (17.31), benzylcarboxylic acid is prepared by the reaction of benzyl halide with carbon monoxide. The reaction mechanism is thought to be as follows at first the halogen atom of the halide is substituted by a cobalt atom and the Co-C bond formed is inserted into by a carbonyl. The phenylacetic acid is industrially produced by using this cobalt catalyst [77]. On aromatic halides, not only monocarbonylation but also double carbonylation is liable to proceed [74,75]. 

Carboxylations of halogen compounds include the technically useful conversion of chloroacetate to malonate (eq 15), and several patent reports of quantitative conversion of Benzyl Chloride to phenylacetic acid. The incorporation of two molecules of carbon monoxide to give a-keto-acids, as exemplified by the reaction of benzyl chloride (eq 16), is remarkably solvent-dependent and almost certainly involves reaction of the halide with Co(CO)4 . 

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