Carboxylic acids Hunsdiecker reactions, bromine

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 ... 

The Hunsdiecker reaction, a bromodecarboxylation classically involving treatment of the silver salt of a carboxylic acid with molecular bromine, results in the transient generation of an acyl hypobromite, followed by O-Br homolysis. It works with protected silver aldonates, as shown in Scheme 7.5. 

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... 

Reaction of a silver salt of a carboxylic acid with bromine is called the Hunsdiecker... 

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. 

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... 

Reaction of a silver salt of a carboxylic acid with bromine is called the Hunsdiecker reaction438 and is a way of decreasing the length of a carbon chain by one unit.439 The reaction is of... 

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. 

Perhaloalkanes serve as bromination or iodination agents in the radical decarbox-ylative halogenation of carboxylic acids. In an interesting modification of the Hunsdiecker-Bodin reaction Barton and coworkers have applied iV-hydroxypyridine-2-thione esters as nonelectrophilic intermediates for the decarboxylative bromination and iodination of primary, secondary and tertiary aliphatic and alicyclic592, as well as aroma-... 

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)] ... 

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. 

The disodium salt of l-hydroxybenzimidazole-2-carboxylic acid can be decarboxylated merely by heating in acid <88JCS(P1)681>. In a Borodin-Hunsdiecker-type reaction alkaline bromination of 4-... 

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. 

Decarboxylation of an aliphatic acid to the hydrocarbon is best effected by the so-called salt degradation method. That method is to treat the silver or mercury salt of, preferably, an aliphatic or alicyclic carboxylic acid with bromine in an inert solvent a halogenated hydrocarbon is then formed, together with carbon dioxide and the metal bromide, usually in an exothermic reaction, and the bromine can then usually be readily removed either cata-lytically or by means of a Grignard reagent (the Hunsdiecker reaction) ... 

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. 

There are other functional group transformations that lead to alkyl halides. A classical transformation converts carboxylates to allyl bromides (C—CO2 C—Br). This transformation is called the Hunsdiecker reaction (jt jjag also been called the Borodin reaction) 3 and it is most useful for the preparation of econdary halides. The silver salt of a carboxylic acid is heated with bromine to give the bromide via decarboxylation. An example is conversion of the silver salt of cyclohexane carboxylic acid (163) to bromo-cyclohexane.1 4 Phosphorus and bromine also react with acids in the Hell-Volhard-Zelinsky reaction. 

In the Hunsdiecker reaction, the silver salt of a carboxylic acid, prepared by treating the acid with silver oxide, is treated with a halogen. Bromine is the usual reagent, but iodine may also be used. Carbon dioxide is evolved and the corresponding alkyl halide is obtained, usually in fair to good yield. 

In a useful modification of the Hunsdiecker reaction, the carboxylic acid is treated with mercuric oxide and bromine. 

To prepare 4-iodooxazoles, Vedejs protocol with DMPU cosolvent allows for efficient synthesis. When DMF is used as the solvent, 2,4-unsubstituted oxazoles can be regioselectively brominated at the 4-position widi NBS on kilogram scale. Hunsdiecker reaction of a C4-carboxylic acid also provides the C4 bromide. With a substituted C2 position, Nicolaou and co-workers achieved chlorination of the C4 position using NCS to prepare an intermediate in the partial synthesis of diazonamide Similar to C2 trifloyloxazole synthesis, trapping of 4-oxazolones with triflic anhydride yields 4-trifloyloxazoles. These triflates, in contrast to 2- or 5-trifloyloxazoles are stable and can generally be utilized in cross-coupling reactions. 

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). 

Carboxylic acids (RCOOH) can be converted to norhalides (RBr or RI) by the Hunsdiecker reaction (silver salt and bromine) or by some modification of this (mercuric oxide and bromine, lead tetra-acetate and iodine, or thallium salt and bromine). 

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