Dehalogenative decarboxylation

When heated at I20°C in concentrated aqueous alkaline solution./3-chloro-cw-cinnamic acid is converted into phenylacetylene. A dehydrohalogenation followed by a decarboxylation would explain this sequence, but more probably a direct dehalogenative decarboxylation occurs as such reactions are observed in the absence of vinylic hydrogen, e.g. 

Electron-withdrawing substituents in the phenyl group promote the stereospecific route and electron-releasing substituents favour the carbonium ion mechanism (see Section 8.1 

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The work of Jones and Lu has embraced a wide range of reactions including hydrogenations, borohydride reductions, aromatic dehalogenations, decarboxylations and hydrogen isotope exchange processes, (Scheme 9.3, Eqs. 1-3). In addition to the accelerated rates of reaction, new environmentally friendly routes have been developed, particularly solventless reactions that minimise waste production and facilitate containment107-110. 

In weakly alkaline solution, dehalogenative decarboxylation of /3-halo-carboxylic acids occurs readily . In the case of //-arts-cinnamic acid dibromides, the stereochemical fate of the /3-bromostyrene is determined by the solvent and substituents in the benzene ring (274) . ... 

The intermediacy of a lactone (276) would seem reasonable, but the predominance of the tra/is-alkene is not explicable in this case. As long as the acid was completely ionised, the rate of dehalogenative decarboxylation was independent of pH (in aqueous solution). However, in more strongly alkaline solution (pH > II), the E2 dehydrohalogenation becomes competitive, but the rate coefficient for the dehalogenative decarboxylation also increases . An initial attack of hydroxide on the acid, giving (277) and a second-order term in the rate law, has been suggested. 

Degradation Decarboxylation, deamination, dehalogenation, dehydroxylation, ring fission, demethoxylation, deacetylation... 

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.)... 

Phenylthioacetylene has been prepared by elimination of thiophenol and dehydrobromination of cis-1,2-bis(phenylthio)ethylene5 and cis-1-bromo-2-phenylthioethylene,2 7 respectively. The latter was obtained by addition of thiophenol to propiolic acid in ethanol and subsequent one-pot bromine addition, decarboxylative dehalogenation, and careful distillation to remove the trans isomer.2.7 on the other hand, cis-1,2-bis(phenylthio)ethylene was prepared by double addition of thiophenol to cis-1,2-dichloroethylene.5a d Although these procedures can provide useful amounts of phenylthioacetylene, they were found to be somewhat less satisfactory in our hands as far as operation and/or overall yields are concerned. Furthermore, we have encountered problems with regard to the reproducibility of one-pot dehydrobrominations of phenylthio-1,2-dibromoethane.6 However, the stepwise execution of the double dehydrobromination, as described in the modified procedure reported here, provides preparatively useful quantities of phenylthioacetylene in a practical manner. 

There are examples of ipso attack during the nitration of pyrroles, furans and thiophenes and in the corresponding benzo-fused systems. Reactions resulting in nitro-dealkylation, nitrodeacylation, nitro-decarboxylation and nitro-dehalogenation are to be found in the monograph reactivity chapters of CHEC. Treatment of the 3-azophenylindole (64) with nitric acid in acetic acid at room temperature gives 80% of the 3-nitroindole (65) (81JCS(P2)628). 

The halo-furans and -benzo[f>]furans are particularly important as precursors of the lithio derivatives (Section 3.11.3.9). Direct halogenation of furan (Section 3.11.2.2.5) is unsatisfactory, and halofurans are prepared by decarboxylation of halofurancarboxylic acids, from chloromercurio compounds, by decarboxylative halogenation of furancarboxylic acids or by partial dehalogenation of polyhalofurans. 

Bromo-,344 495 5-bromo-,318 and several polyfluorobenzo[6]thio-phenes100,110 have been prepared by decarboxylation of the corresponding 2-carboxylic acid with copper and quinoline. Good yields of fluoro compounds are obtained by this method, but those of the bromo compounds are rather low, probably owing to some simultaneous dehalogenation. 

Various 3-halopyruvate derivatives have been reported to be decarboxylated and simultaneously dehalogenated, yielding acetate, carbon dioxide and a halogenide ion as the only reaction products [133,158], A similar reaction may occur upon enzymatic decarboxylation of 3-hydroxypyruvate, which is an alternative substrate and a strong competitive inhibitor of PDC [159],... 

Dealkylation of tertiary amines with dibenzoyl peroxide, 44, 74 Decarboxylation, intermolecular, of isocyanates to carbodiimides, 43,32 Decker synthesis of amines, 44, 7t, 75 Dehalogenation of l,l,2-trichloro-2,3,3-trifluorocydobutane, 42,45 Dehydration, of formamides with phosphorus oxychloride to isocy-anides, 41, 13, 101 of 4- 2-hydroxyethyl)piperidine to quinuclidine, 44, 90 Dehydrohalogenation of 2-chloroallyl-amines to propargylamines, 44,55 Delepine reaction, to prepare 2-bromo-allylamine, 43, 6 Deoxyanisoin, 40,16 Deoxybenzoin, 40, IT Deoxypiperoin, 40, IT Deaylamine, 41, 8T... 

Decarboxylation of benzoates in the presence of an aryl halide (20, 33, 211) affords the biphenyl substitution products in yields of up to 50% if the medium is an iV-heteroaromatic solvent. The solvent must be dry to avoid reductive dehalogenation (54). If the solvent is dry diglyme or xylene, an ester can be isolated in high yield (54). 

Figure 9-10. Examples of photoinduced reactions in drug molecules. (I) Photoinduced isomerization (Ib), cyclization and enol-keto isomerization (Ic) of stilboestrol (la). (II) Photoinduced reactions of ketoprofen (Ila) and its degradation product (Ilb) decarboxylation (Ilb), reduction (lie), and dimerization (IIc) products of the drug. (Ill) A -dealkylation of methotrexate followed by oxidation. (IV) Dehalogenation (IVb) and photohydrolysis (IVc) of frusemide (IVa) [44].

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