Radical reactions Hunsdiecker reaction

Generation and stereospecific reaction of fluorocyclopropyl radicals provided experimental evidence for the nonplanarity of the fluoroalkyl radical [23]. Hunsdiecker reaction... 

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. 

The Hunsdiecker reaction is a free-radical reaction for the synthesis of an alkyl halide. The starting material comes from the reaction of a silver carboxylate with a solution of a halogen in a solvent such as carbon tetrachloride (see Figure 12-44). The overall free-radical mechanism is shown in Figure 12-45. 

Hunsdiecker Reaction A free-radical reaction for the synthesis of an alkyl halide. 

Problem 16.20 Suggest a typical free-radical mechanism for the Hunsdiecker reaction which requires the initial formation of an acyl hypobromite. RC—OBr, from the Ag salt and Br,. ... 

The first step is not a free-radical process, and its actual mechanism is not known.451 25 is an acyl hypohalite and is presumed to be an intermediate, though it has never been isolated from the reaction mixture. Among the evidence for the mechanism is that optical activity at R is lost (except when a neighboring bromine atom is present, see p. 682) if R is neopentyl, there is no rearrangement, which would certainly happen with a carbocation and the side products, notably RR, are consistent with a free-radical mechanism. There is evidence that the Simonini reaction involves the same mechanism as the Hunsdiecker reaction but that the alkyl halide formed then reacts with excess RCOOAg (0-24) to give the ester.452 See also 9-13. 

Hunsdiecker reactions of salts of perfluoroalkanoic acids are known primarily as perhaps the best way of making perfluoroalkyl halides [58,306,307], but there have been other synthetic uses found for the perfluoroalkyl radicals which are formed by this decarboxylative process [308]. 

Hunsdiecker reaction does not work so well in aromatic carboxylic acids [75, 76]. The rate constants for decarbonylation of acyl radicals are lowered as shown in Table 1.18. 

The most useful reaction in the literature for this is the pyrolysis of a suitable per-ester in the presence of a hydrogen atom transfer reagent, but the yields are often unsatisfactory.2 8 Conversion of an acid to the corresponding aldehyde and subsequent rhodium-based decarbonylation involves two steps, but is more reliable.4 The Borodin-Hunsdiecker reaction converts the acid to a nor-halide, which can be reduced by radical methods. However, this works well only with primary acids, is incompatible with many sensitive functions,5 and is expensive since the Ag salt of the acid is usually used. 

The following reaction, known as the Hunsdiecker reaction, proceeds by a radical chain mechanism. Show the steps in this mechanism. (Hint The weakest bond in the compound, the oxygen-bromine bond, is broken in the initiation step.)... 

Surprisingly, the Hunsdiecker reaction using the silver salts of exo- and endo-7-chlorobicyclo[4.1.0]heptanecarboxylic acids and bromine at 0°C did not result in the same ratio of products but instead showed a high retention to inversion ratio of 88 12 for the exo acid and 88 12 for the endo acid". This anomalous result may be a reflection of the bromine radical s ability to trap the cyclopropyl radical but this is unlikely. Altman and Baldwin as well as Ando and coworkers found that the reduction of each of the isomers of 7-bromo-7-chlorobicyclo[4.1.0]heptane, 30 and 31, respectively, by the excellent radical scavenger triphenyltin hydride resulted in an identical mixture (21 79) of exo-(32) and en io-7-chlorobicyclo[4.1.0]heptane (33). This ratio of products is, within experimental error, identical with that found in the thermal decomposition of exo- and endo-t-buiy 7-chlorobicyclo[4.1.0]heptane-7-percarboxylate in cumene. 

Hunsdiecker reaction of the silver salts of both cis-(56) and trans-2-methylcyclopropanecarboxylic acid (57) yielded the same mixture of cis- (58) and trans-1-bromo-2-methylcyclopropane (59), thus demonstrating that the 2-methylcyclopropyl radical was incapable of maintaining its configuration . Brominative decarboxylation of the silver salts of exo- (60) and em/o-norcarane-7-carboxylic acid (61) produced the same mixture (16 84) of exo- (62) and entio-7-bromonorcarane (63)". Similarly, cis- and trans-silver 1,2-cyclopropanedicarboxylate gave rise to the same isomer ratio (24 76) of cis- and fraws-1,2-dibromocyclopropane. Consistent with these results is the report that the Hunsdiecker reaction with the silver salt of trans-2,2,3-d3-cyclopropanecarboxylic acid (64) gives an equimolar mixture of cis- (65) and rrans-2,2,3-d3-cyclopropane (66) . 

Recently, Paquette and coworkers reported on the stereochemical consequences of having a trimethylsilyl substituent at the radical site. The Hunsdiecker reaction, as well as the Cristol-Firth modification thereof, on ( —)-(R)-l-trimethylsilyl-2,2-diphenyl-cyclopropanecarboxylic acid (71) resulted in racemic ( )-l-bromo-l-trimethylsilyl-2,2-diphenylcyclopropane (72). The trimethylsilyl group, bulky as it is, could not slow down the inversion frequency of the cyclopropyl a radical sufficiently to prevent complete racemization. More to the point, recentESR studies have demonstrated that the radical intermediate is planar, or nearly so. 

Only unrearranged cyclopropyl products were reported for photochemical chlori-nation and vapor phase nitration of cyclopropane. The Hunsdiecker reaction of silver cyclopropanecarboxylate and the thermal decomposition of cyclopropanoyl peroxide also gave exclusively unrearranged product as did the di-t-butyl peroxide initiated decarbonylation of 1-methyl and 1-phenylcyclopropanecarboxaldehyde. In general one can predict that when a good radical scavenger, solvent or substrate, is present in the reaction, unrearranged product will result (i.e. see Tables 11 and 13). 

The preparation of chlorides by decarboxylation of carboxylic acids with lead tetraacetate and N-chlorosuccinimide as the chlorine donor in a 5 1 mixture of DM F and glacial acetic acid has been reported [71 a]. The reaction has been applied particularly often to the preparation of secondary and tertiary chlorides when the classic Hunsdiecker reaction gives low yields (Scheme 13.50) [71b]. This reaction proceeds by a radical pafhway. 

Radicals from Carboxylic Acids. Carboxy radicals appear to be involved in three venerable reactions in preparative carbohydrate chemistry, the Ruff degradation, the Hunsdiecker reaction and the Kolbe electrolysis. 

The Hunsdiecker reaction, in which the silver salt of a benzoic acid is thermally decarboxylated in the presence of bromine, gives moderate yields of aryl bromides. The mechanism is uncertain, but may involve the generation of aryl radicals (Scheme 9.5). 

A somewhat different approach to a polymer-supported radical source was described by Giacomelli and coworkers, who used an N-hydroxythiazole 2(3)-thione anchored to a Wang resin [95]. The reagent was prepared in solution and equipped with a pendant COOH group to facilitate attachment to the resin. The applicability of the reagent in radical-mediated reactions was then investigated via a Hunsdiecker reaction (Scheme 6.24). Treatment of the reagent with an acyl... 

Decarboxylation of silver carboxylates is a well known thermal process and is involved in the Hunsdiecker76 or Kolbe77 reactions. The Hunsdiecker reaction is the thermal decarboxylation of silver salts of acids and is used for the formation of bromoalkanes and related compounds, while the Kolbe process involves electrolysis of carboxylates as a route to decarboxylated radicals that can dimerize. Silver carboxylates are also photochemically reactive and the irradiation has been described as a facile process for the formation of alkyl radicals, as illustrated in equation 678. Later experimentation has shown that the irradiation of silver trifluoroacetate can serve as a route to trifluoromethyl radicals. This development uses irradiation of silver trifluoroacetate in the presence of titanium dioxide as a photocatalyst. The reaction follows the usual path with the formation of metallic silver and the formation of radicals. However, in this instance the formation of metallic... 

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