Hunsdiecker reactions bromine

Oxidative decarboxylation of optically active l-methyl-2,2-diphenylcyclopropanecarboxylic acid (10) with lead tetraacetate in the presence of iodine leads to racemized 1-iodo-l-methy 1-2,2-diphenylcyclopropane (11) in 45% yield. Subjecting 10 to the Cristol-Firth modification of the Hunsdiecker reaction (bromine and mercuric oxide in carbon tetrachloride) leads to racemic 1-bromo-l-methyl-2,2-diphenylcyclopropane (12) however, the yield is poor (5 /o). ... 

Silver carboxylates 1 can be decarboxylated by treatment with bromine, to yield alkyl bromides 2 in the so-called Hunsdiecker reaction. ... 

Suitable substrates for the Hunsdiecker reaction are first of all aliphatic carboxylates. Aromatic carboxylates do not react uniformly. Silver benzoates with electron-withdrawing substituents react to the corresponding bromobenzenes, while electron-donating substituents can give rise to formation of products where an aromatic hydrogen is replaced by bromine. For example the silver /)-methoxybenzoate 6 is converted to 3-bromo-4-methoxybenzoic acid 7 in good yield ... 

In a modified procedure the free carboxylic acid is treated with a mixture of mercuric oxide and bromine in carbon tetrachloride the otherwise necessary purification of the silver salt is thereby avoided. This procedure has been used in the first synthesis of [1.1.1 ]propellane 10. Bicyclo[l.l.l]pentane-l,3-dicarboxylic acid 8 has been converted to the dibromide 9 by the modified Hunsdiecker reaction. Treatment of 9 with t-butyllithium then resulted in a debromination and formation of the central carbon-carbon bond thus generating the propellane 10." ... 

The Hunsdiecker reaction is the treatment of the dry silver salt of a carboxylic acid with bromine in carbon tetrachloride. Decarboxylation occurs, and the product isolated is the corresponding organic bromide 16). Since dry silver salts are tedious to prepare, a modification of the reaction discovered by Cristol and Firth (77) is now... 

Bromotrithiatriazepine 8 can also be obtained from the carboxylic acid 6 in 52 % yield by a modified Hunsdiecker reaction involving irradiation of a mixture of the acid, bromine, mer-cury(II) oxide and carbon tetrachloride. The iodo derivative is formed when iodine is employed418... 

Bromocyclopropane has been prepared by the Hunsdiecker reaction by adding silver cyclopropanecarboxylate to bromine in dichlorodifluoromethane at —29° (53% yield) or in tetrachloro-ethane at —20° to —25° (15-20% yield).3 Decomposition of the peroxide of cyclopropanecarboxylic acid in the presence of carbon tetrabromide gave bromocyclopropane in 43% yield.4 An attempt to prepare the bromide via the von Braun reaction was unsuccessful.3... 

A related method for conversion of carboxylic acids to bromides with decarboxylation is the Hunsdiecker reaction.276 The usual method for carrying out this transformation involves heating the carboxylic acid with mercuric oxide and bromine. 

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 procedure described here allows for a convenient and efficient preparation in very high yields of large quantities of bromides from carboxylic acids containing an olefinic functionality. The Hunsdiecker reaction is traditionally accomplished by treating anhydrous silver carboxylates with bromine or iodine.2 Heavy metal salts such as mercury,3 lead,4 and thallium5 have also been used successfully as well as tert-butyl hypoiodite.6 The major disadvantages associated with the above methods, such as use of heavy metal salts and non-tolerance towards olefins, has led to the development of a more versatile method using O-acyl thiohydroxamates.7 8 The O-... 

Mercury(II) oxide together with a halogen is an early development of the classic Hunsdiecker reaction (bromodecarboxylation of a carboxylic acid silver salt, see below) which is still in use.20 22 A double Hunsdiecker reaction of cyclobutane-1,1-dicarboxylic acid with red mer-cury(ll) oxide in the presence of bromine gave 1,1-dibromocyclobutane (2) in 46% yield.21 However, a similar reaction performed on spiro[3.3]heptane-2-carboxylic acid afforded 2-bro-mospiro[3.3]heptane (3) in only 16% yield.22... 

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 the silver salts of carboxylic acids in the presence of bromine or chlorine, the Hunsdiecker reaction, often is useful for the synthesis of alkyl halides ... 

In a Hunsdiecker reaction, the silver salt of an aromatic carboxylic acid is converted by bromine treatment to an acyl halide. 

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. 

Needless to say, this was readily proven to be the case and a variety of chlorides, bromides and iodides have been prepared from the corresponding acids in good to excellent yields, by this method.14,15,26 31 In terms of mildness of conditions, generality and yields, this method is far superior to the classical Borodin-Hunsdiecker reaction and its variants.1011,26"31 As a demonstration of the mildness of the conditions, decarboxyl-ative bromination of the heavily functionalized acid 19 was carried out by Professor Ikegami to afford 20 (75 % yield), and... 

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.)... 

Of lesser relevance to this discussion are halogenation methods involving the modification of the carbon skeleton (synthesis and degradation). The Hunsdiecker reaction, as applied to certain heterocyclic acids, has had limited application for the synthesis of halogen derivatives. The preparation of 3-bromo-4,6-dimethyl-2-pyridone from the silver salt of the respective 3-carboxylic acid by treatment with bromine in carbon tetrachloride is a rare example of success.13 The interaction of carbenes with heterocycles also has been employed infrequently, but recent advances in carbene generation may reactivate this approach.14 The Ciamician-Dennstedt ring expansion of pyrrole to / -halopyridines is a case in point18 [Eq. (4)] ... 

The classical Hunsdiecker reaction (equation 18), involving the reaction of silver caiboxylates widi halogens, and the various associated side reactions, has been reviewed several tunes. Optimum yields are obtain widi bromine, followed by chlorine. Iodine gives acceptable yields provid diat the correct stoichiometry of 1 1 is used. The reaction is most frequently carried out in tetrachloromediane at reflux. From a practical pmnt of view, one drawback is the difficulty encountered in the preparation of dry silver caiboxylates the reaction of silver oxide on the acyl chloride in tetrachloromediane at reflux has been employed to circumvent diis problem. Evidendy the use of molecular bromine limits die range of functional groups compatible widi die reaction the different reaction pathways followed by the silver salts of electron poor (equation 19) and electron rich (equation 20) aryl carboxyl s illustrate this point well. 

Fragmentation with loss of CO2 also occurs in the Hunsdiecker reaction, in which a silver salt of a carboxylic acid reacts with bromine to produce an alkyl halide. The reaction results in shortening of the carbon chain by one carbon. The overall reaction is as follows ... 

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) . 

During the final stages of the asymmetric total synthesis of antimitotic agents (+)- and (-)-spirotryprostatin B, the C8-C9 double bond had to be installed, and at the same time the carboxylic acid moiety removed from C8. R.M. Williams et al. found that the Kochi- and Suarez modified Hunsdiecker reaction using LTA or PIDA failed and eventually the Barton modification proved to be the only way to achieve this goal. After the introduction of the bromine substituent at C8, the C8-C9 double bond was formed by exposing the compound to sodium methoxide in methanol. This step not only accomplished the expected elimination but also epimerized the C12 position to afford the desired natural product as a 2 1 mixture of diastereomers at C12. The two diastereomers were easily separated by column chromatography. 

This is a good method of synthesising symmetrical alkanes. The Kolbe reaction is usually performed using the potassium or sodium salt of the carboxylic acid. If the silver salt is reacted with bromine, then decarboxylation occurs again, but this time the alkyl bromide is formed. This reaction is called the Hunsdiecker reaction. The first step involves the formation of an acyl hypohalite, RC02X. 

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