Acyl bromides 2-bromination

In the following the reaction is outlined for an a-bromination. The reaction mechanism involves formation of the corresponding acyl bromide 3 by reaction of carboxylic acid 1 with phosphorus tribromide PBr3. The acyl bromide 3 is in equilibrium with the enol derivative 4, which further reacts with bromine to give the a -bromoacyl bromide 5 ... 

The a -brotnoacyl bromide 5 converts unreacted carboxylic acid 1 by an exchange reaction into the more reactive acyl bromide 3, which subsequently becomes a-brominated as formulated above ... 

Carboxylic acids can be converted to acyl chlorides and bromides by a combination of triphenylphosphine and a halogen source. Triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.100 Similarly, carboxylic acids react with the triphenyl phosphine-bromine adduct to give acyl bromides.101 Triphenviphosphine-iV-hromosuccinimide also generates acyl bromide in situ.102 All these reactions involve acyloxyphosphonium ions and are mechanistically analogous to the alcohol-to-halide conversions that are discussed in Section 3.1.2. 

Formation of the acyl bromide speeds up the reaction because acid-catalyzed enolization of the acyl bromide occurs much more readily than enolization of the parent acid. Bromine probably reacts with the enol of the acyl bromide in the same way as it reacts with the enols of ketones (Section 17-2 A). 

The final step is the formation of the a-bromo acid by bromine exchange between the a-bromoacyl bromide and the parent acid the acyl bromide, which is necessary for continued reaction, is thus regenerated ... 

Phosphorus reacts with bromine to give phosphorus tribromide, and in the first step this converts the carboxylic acid into an acyl bromide. 

An acyl bromide can readily exist in the end form, and this tautomer is rapidly brominated at the a-carbon. The monobrominated compound is much less nucleophilic, so the reaction stops at this stage. This acyl intermediate compound can undergo bromide exchange with unreacted carboxylic acid via the anhydride, which allows the catalytic cycle to continue until the conversion is complete. 

In contrast to eq. 2.29, eq. 2.30 shows the oxidative conversion of aldehydes (62) to amides (63) via acyl bromides with NBS/AIBN/R2NH under refluxing conditions in CC14 [74]. The reaction comprises of the abstraction of the formyl hydrogen atom by the succinimidyl radical, bromine atom abstraction from NBS by the acyl radical, and lastly,... 

The bromine is introduced onto the a-carbon by treating the carboxylic acid with Br2 and a catalytic amount of PBr, in a process known as the Hell-Volhard-Zelinsky reaction. This reaction proceeds through an enol intermediate. Because carboxylic acids form enols only with difficulty, a catalytic amount of PBr3 is added to form a small amount of the acyl bromide, which enolizes more readily than the acid. Addition of bromine to the enol produces an a-bromoacyl bromide (see Section 20.2). This reacts with a molecule of the carboxylic acid in a process that exchanges the Br and OH groups to form the... 

Next the acyl bromide is brominated at the a-carbon. This acid catalyzed halo-genation, described in Section 20.2, proceeds through an enol. 

Q Loss of a proton produces the a-brominated acyl bromide. 

The acyl bromide can reenter the mechanism at step 2 and undergo enolization and bromination, Therefore, only a catalytic amount of PBr3 is necessary. 

The Br of the acyl bromide exchanges with the OH of another molecule of the carboxylic acid to produce the o-brominated acid and an acyl bromide. This exchange reaction proceeds through an anhydride intermediate. 

The Hell-Volhard-Zelinsky (HVZ) reaction replaces a hydrogen atom with a bromine atom on the a carbon of a carboxylic acid. The carboxylic acid is treated with bromine and phosphorus tribromide, followed by water to hydrolyze the intermediate a-bromo acyl bromide. 

Bromination of acid derivatives is usually carried out not on the acid itself but by converting it to an acyl bromide or chloride, which is not isolated but gives the a-bromoacyl halide via the enol. This used to be done in one step with red phosphorus and bromine, but a two-step process is usually preferred now, and the bromoester is usually made directly without isolating any of the intermediates. We can summarize the overall process like this. 

The first mole equivalent of bromine reacts with the phosphorus tribromide to form the solid pentabromide which, in turn, is rapidly consumed in the formation of the acyl bromide. 

This second mechanism is less satisfactory because cyclization of the carboxy radical 5-40 is unlikely. Alkyl carboxy radicals are highly unstable and they decarboxylate so rapidly that fragmentation would be expected to occur faster than cyclization. The previous mechanism has at least two other advantages. First, it proceeds through the radical 5-41, which is stabilized by resonance with two phenyl substituents, so that hydrogen abstraction to form 5-41 should compete effectively with homolytic scission of the acyl bromide to form 5-40. Second, it will occur rapidly because it is a radical chain process the bromine radical formed in the cyclization of 5-41 regenerates 5-41 from the acyl hypobromite. 

S-tert-buty thioates can be deprotected by indirect electrochemical oxidation using bromide/bromine as mediator the reaction probably goes through a bromosulfonium intermediate. By direct anodic oxidation, 4-methoxyphenylthiomethyl esters are readily converted to carboxylic acids. The initially formed radical cation cleaves on reaction with water to the acylated hemiacetal and further to the acid [144,145]. 

A convenient one-pot procedure for the preparation of a-bromo thioesters from carboxylic acids based on the HVZ reaction was developed by H.-J. Liu and co-workers.The neat carboxylic acid was mixed with 0.4 equivalents of PBrs, the resulting mixture was heated to 100-120 °C in an oil bath and 1.2 equivalents of liquid bromine was added in 1.5h. In the same flask, now containing the a-bromo acyl bromide, the solution of the thiol in dichloromethane was added to give the desired a-bromo thioesters in high yield. 

A very different, but similarly effective, auxiliary is the chiral carbonyl(t/5-cyclopentadienyl)(tri-phenylphosphine)iron moiety. When the z./i-unsaturated acyl-iron complex ( -)-(/ )-11 is treated by a modified Simmons Smith reagent, a 91 9 mixture of cyclopropane diastereomers is isolated in good yield73. Precomplexation of the starting iron complex by the Lewis acid zinc(II) chloride seems to be necessary to obtain good selectivity. The chiral iron moiety can then be removed oxidatively by bromine treatment, and the intermediate acyl bromides converted into amides by reaction with (/ )- -phenylethylamine. 

Acyl bromides. Heating aldehydes with Br3COOEt and (PhCOO)2 in toluene accomplishes radical bromination. ... 

USE Brominating agent for converting organic acids to acyl bromides. 

In the first step of the HVZ reaction, PBr3 converts the carboxylic acid into an acyl bromide by a mechanism similar to the one by which PBr3 converts an alcohol into an alkyl bromide (Section 12.3). (Notice that in both reactions PBr3 replaces an OH with a Br.) The acyl bromide is in equilibrium with its enol. Bromination of the end forms the a-brominated acyl bromide, which is hydrolyzed to the a-brominated carboxylic acid. 

As the introduction of a halogen into an acyl halide takes place more rapidly than into the acid itself, the substitution-products of the fatty acids are more conveniently prepared by the action of chlorine or bromine on these compounds. It is not necessary to isolate the latter the acid to be bromin-ated, for example, is mixed with red phosphorus, heated at about 80°, and bromine is slowly added. The phosphorus bromide first formed interacts with the acid to form the acyl bromide, which is converted by the free bromine present into a bromoacyl bromide. The latter yields with water the halogen substitution-product of the acid —... 

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