Alkyl radical, Hunsdiecker reaction

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. 

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. 

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... 

The first step of the Hunsdiecker reaction is quite straightforward. The reaction between silver carboxylate 1 and bromine gives rise to insoluble silver bromide along with acyl hypobromite 3. The unstable acyl hypobromite 3 undergoes a homolytic cleavage of the O-Br bond to provide carboxyl radical 4. Carboxyl radical 4 then decomposes via radical decarboxylation to release carbon dioxide and alkyl radical 5, which subsequently reacts with another molecule of acyl hypobromite 3 to deliver alkyl bromide 2, along with regeneration of carboxyl radical 4. Because of the radical pathway, chirality is often lost for the chiral carbon atom immediately adjacent to the carboxylic acid. 

The last, but certainly not the least, is the Barton modification to the Hunsdiecker reaction.24-26 It involves decomposition of thiohydroxamate esters in halogen donor solvents such as CCU, BrCCh, CHI3, or CH2I2 promoted by a source of radical initiation, which could be radical initiator (e.g., 18—>20),24 thermal (e.g., 21—>22),25 or photolytic26 conditions. The Barton modification is highly compatible with most functional groups. For example, under photolytic conditions, acid 23 was converted to acid chloride 24, which, without isolation, was treated with the sodium salt of Z/-hydroxypyridine-2-thione (19) with bromotrichloromethane as solvent to give alkyl bromide 25 in 90% yield.26... 

In the Hunsdiecker reaction, the silver salt of a carboxylic acid (RC02Ag) is treated with Br2 to give an alkyl bromide RBr with one fewer C atoms. The reaction does not work well with aromatic acids, suggesting that a free-radical mechanism is involved. The carboxylate and bromine react to give an acyl hy-pobromite, which decomposes by a free-radical chain mechanism. 

One particular radical decarboxylation reaction, which is used in the synthesis of alkyl or aryl bromide (Hunsdiecker reaction), involves reaction of the silver salt of a carboxylic acid with bromine, and results overall in loss of CO2 to form the corresponding alkyl or aryl bromide (Scheme 4.47). When silver carboxylate is treated with I2 ester formation occurs (Simonini reaction). 

This fast, easily performed variant to the Hunsdiecker procedure, applies successfully to primary, secondary, or tertiary esters, even unsaturated ones (p. 353). From citronellic acid, despite the presence of a double bond in a position permitting cyclization, the latter reaction was not detected. Mechanistically, the sonochemical reaction differs from the photochemical analogue, during which the initiation occurs from the cleavage of the thiohydroxamic ester itself. The initiation probably takes place in the bubble then the halogen atom couples with the alkyl radical in the solution, possibly by a chain mechanism. 

In a similar vein, the silver (Ag+) salts of carboxylic adds undergo decarboxylation in the presence of bromine (Br2) to produce silver bromide and bromoalkane (the Hunsdiecker reaction). The Hunsdiecker reaction also appears to involve radicals as shown in Scheme 9.101, where,in the first step,silver bromide precipitates from the reaction mixture with formation of an acyl hypobromite (RC(D2Br). Then, homolysis of the oxygen-bromine bond generates bromine atoms and the carboxyl radical, seen here as the same radical generated in Scheme 9.100. Following loss of carbon dioxide (CO2), it is held that the alkyl radical is captured by the bromine atom (Br ) to produce alkylbromide (1-bromoethane [CH3CH2Br]). 

FIGURE 17.58 The decarboxylation of the carboxylate radical is also involved in the Hunsdiecker reaction, a synthesis of alkyl bromides from carboxylic acids. The recycling, chain-propogating carboxyl radical is highlighted. 

The Hunsdiecker Reaction. The classical Hunsdiecker reaction is somewhat restricted due to the relatively harsh conditions required. In the Barton version, alkyl radicals generated from O-acyl thiohydroxamates, under either thermal or photolytic conditions, are efficiently trapped either by CI3C-X (X=C1 or Br CbC is the chain carrier) or by IodoformThe method is applicable to sensitive substrates for which the classical methods are unsuitable. thus allowing the preparation of a wide range of alkyl chlorides, bromides, and iodides by the one-carbon degradation of a carboxylic acid. Similar reactions of aromatic acid derivatives tend to require an additional radical initiator (e.g. Azo-bisisobutyronitrile), if high yields (55-85%) are to be obtained. ... 

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