Halogenative decarboxylation

If only the monocarboxybc acid is required, the ester after hydrolysis with potash may be strongly acidified with sulphuric acid and the mixture heated under reflux the mineral acid promotes decarboxylation at a temperature just above 100°. The net result is the replacement of the halogen atom of the alkyl halide by —CH COOH thus in the above example ... 

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

Claisen condensation, 6, 156 reactions, S, 92 IsothiazoIe-3-carboxyIic acids decarboxylation, 6, 156 Isothiazole-4-carboxylic acids decarboxylation, 6, 156 Isothiazole-5-carboxylic acids decarboxylation, S, 92 6, 156 IR spectroscopy, 6, 142 Isothiazole-3-diazonium borofluoride decomposition, 6, 158 IsothiazoIe-4-diazonium chloride, 3-methyl-reactions with thiourea, 6, 158 Isothiazole-5-diazonium chloride, 4-bromo-3-methyl-halogen exchange, 6, 163 Isothiazole-5-diazonium chloride, 3-methyl-reactions... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

The anticonvulsant activity of some 1,3-benzisoxazoles was discovered in routine testing. One of the more interesting of the subsequent analogues prepared was zonisamide (39). One of its syntheses starts with l,2-benzisoxazole-3-acetic acid (36) which is brominated and subsequently decarboxylated to give 37. Displacement of halogen in 37 with sodium bisulfite interestingly... 

Reaction between diazonium salts and CuCl or CuBr (Sandmeyer) Decarboxylative halogenation (Hunsdiecker)... 

Burkholderia cepacia strain 2CBS is able to degrade ort/jo-halogenated benzoates by dioxygenation to catechol with the elimination of halide and decarboxylation. The enzyme contains a ferredoxin-and a Rieske-type [2Fe-2S] center. These could be distinguished on the basis of their EPR spectra, and the results were compared with those for other [2Fe-2S] clusters (Riedel et al. 1995). 

Dioxygenation with decarboxylation bnt withont loss of halogen to prodnce chlorocatechols that may be degraded by several ring-fission pathways (3- and 4-chlorobenzoates) Dioxygenation with loss of only halogen to prodnce a dihydroxybenzoate (2-chlorobenzoate)... 

FIGURE 9.29 Transformation of 2-halogenated benzoates to catechol by concomitant decarboxylation and dehalogenation. (From Neilson, A.H. and Allard, A.-S., The Handbook of Environmental Chemistry, Vol. 3R, Springer Verlag, 2002, pp. 1-74. With permission.)... 

A contrasting pathway was found for the metabolism of 2-fluoro-4-nitrobenzoate by Nocardia erythropolis that does not involve loss of fluorine concomitant with decarboxylation (Cain et al. 1968). The pathway (Figure 9.30) therefore differs from what has subsequently emerged as the principal pathway for metabolism of nonhydroxylated 2-halogenated benzoates. 

When X—Y is R3Sn—H the net reaction is decarboxylation and reduction of the original acyloxy group. Halogen atom donors can also participate in such reactions. 

Successful thermal decarboxylation of metal arenoates other than poly-halogenoarenoates are restricted to mercury compounds and fall into three categories, namely (i) those where electron-withdrawing substituents other than halogens are present in the organic groups, (ii) those where substituents and/or conditions are used which favor a different mechanism, e.g., classic electrophilic aromatic substitution, or (iii) those where the conditions are sufficiently forcing for both mercuration and decarboxylation to occur. 

Decarboxylativehalogenation (12,417). The Hunsdiecker reaction is not useful for aromatic acids, but decarboxylative halogenation of these acids can be effected in useful yield by radical bromination or iodination of the thiohydroxamic esters, as reported earlier for aliphatic acids.1 Thus when the esters 2 are heated at 100° in the presence of AIBN, carbon dioxide is evolved and the resulting radical is trapped by BrCCl3 to provide bromoarenes (3). Decarboxylative iodination is effected with iodoform or methylene iodide as the iodine donor. 

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