Halogenation decarboxylative

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

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. 

Dauben et al. found that the CCI3 radical produced by sonolysis of carbon tetrachloride can be used in a decarboxylation-halogenation sequence (Scheme 3.5) [43]. Sonication of a thiohydroxamic ester at 33 °C for 10 - 50 min in carbon tetrachloride leads to the corresponding chloride in high yield. In the presence of bromotrichloromethane or iodoform, bromides and iodides are formed in yields > 80 %. This reaction can be successfully applied to primary, secondary, or tertiary esters and offers an interesting variant to the usual Hunsdiecker procedure. 

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. 

One great advantage of the decarboxylative halogenation with O-acyl esters of A-hydroxy-2-thiopyridone is that the reaction does not require any heavy metal such as Ag or Hg, unlike the Hunsdiecker reaction [24, 25]. Moreover, decarboxylative bromination of p-methoxybenzoic acid can be also carried out in good yield, while it does not proceed with the Hunsdiecker reaction instead, electrophilic bromination on the aromatic ring occurs. 

Acyl hypohalites are usually prepared in situ by reaction of a metal salt of die carboxylic acid widi a halogen (equation 3). Classically the silver salt is used, but problems associated widi die preparation of dry silver carboxylates, as well as the more obvious economic factor, have led to the development of methods using mercury and thallium salts. Evidently, those functional groups which react readily widi halogens are not compatible with this approach. A major limitation of the acyl hypohalites is the readiness with which they transfer halogen atoms to alkyl radicals this property essend ly limits their use to decarboxylative halogenation reactions. 

The use of stable, crystallizable thallium(l) carboxylates with bromine in tetrachloromediane at reflux has also been demonstrated to be effective in bringing about overall decarboxylative halogenation, provided the correct stoichiometry (equation 26) is adhered to. 

It is also possible to decarboxylate the carboxylic acids with other reagents, leading to useful functionalized products such as sulfide, selenide and bromo derivatives. For example, decarboxylative halogenation of A on treatment with CCI4, BrCCls or CH2I2 gives the corresponding alkyl halide. ... 

Radiotracer experiments were used to elucidate the biosynthetic precursors to eudistomin H (7) and I (8) in Floridian collections of Eudistoma olivaceum. Both radiolabeled tryptophan and proline were incorporated by E. olivaceum into eudistomins H and I and tryptamine was incorporated into eudistomin I, to the exclusion of eudistomin H. Bromotryptamine and bromotryptophan are incorporated into eudistomin H (Scheme 30). These results suggest eudistomin biosynthesis proceeds from the amino acids via decarboxylation, halogenation, then condensation with proline. 

---