Bromo acyl bromide

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. 

If a derivative of the a-bromoacid is desired, the a-bromo acyl bromide serves as an activated intermediate (similar to an acid chloride) for the synthesis of an ester, amide, or other derivative. If the a-bromoacid itself is needed, a water hydrolysis completes the synthesis. 

HVZ reaction) Reaction of a carboxylic acid with Br2 and PBr3 to give an a-bromo acyl bromide, often hydrolyzed to an a-bromo acid. (p. 1059)... 

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. 

Hell-Volhard-Zelinsky (HVZ) reaction Reaction of a carboxylic acid with Br2 and PBr3 to give an a-bromo acyl bromide, often hydrolyzed to an a-bromo acid. (p. 1051) malonic ester synthesis Alkylation or acylation of malonic ester (diethyl malonate), followed by hydrolysis and decarboxylation, to give substituted acetic acids, (p. 1076)... 

Reaction of the enol tautomer with bromine gives an a-bromo acyl bromide. An exchange reaction between the a-bromo acyl bromide and the unreacted carboxylic acid then occurs giving an a-bromo carboxyhc acid. The second product, an acyl bromide, then reacts with bromine to form additional a-bromo acyl bromide. That is why only a catalytic amount of PBt3 is required to convert all the carboxyhc acid to an a-bromo derivative. 

Hell—Volhard—Zelinsky reaction Reaction of a carboxylic acid with bromine and PBr to give an a-bromo acyl bromide. 

An ester of alanine with an arylaliphatic alcohol has shown promise as a non-tricyclic antidepressant. It may be speculated that the hindered milieu of the ester linkage protects the compound from hydrolysis by endogenous esterases. The preparation starts by reaction of pheny-lacctate 83 with methyl magnesium iodide to give tertiary carbinol 84. Acylation with 2-bromo-]>ropionyl bromide leads to ester 85 displacement of halogen with ammonia leads to alaproclate ( 6) [211. 

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins with reaction of the carboxylic acid with PBr3 to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with Br2 in an cr-substitution reaction to give an cv-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the a-bromo carboxylic acid product. 

The intermediate o-bromo acid bromide undergoes a nucleophilic acyl substitution reaction with methanol to give an a-bromo ester. 

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 ... 

K. Bock, C. Pedersen, and P. Rasmussen, Reaction of acylated pentoses with acyl bromide. Preparation of some bromo-deoxy-pentoses, Acta Chem. Scand., B29 (1975) 389-393. 

The reaction is likely to proceed by a radical-chain mechanism, involving intermediate formation of carboxyl radicals, as in the related Kolbe electrolytic synthesis. Initially the bromine reacts with the silver carboxylate 1 to give an acyl hypobromite species 3 together with insoluble silver bromide, which precipitates from the reaction mixture. The unstable acyl hypobromite decomposes by homolytic cleavage of the O-Br bond, to give a bromo radical and the carboxyl radical 4. The latter decomposes further to carbon dioxide and the alkyl radical 5, which subsequently reacts with hypobromite 3 to yield the alkyl bromide 2 and the new carboxyl radical 4Z... 

The initial series of major tranquilizers consists of alkylated derivatives of 4-aryl-4-hydroxypiperidines. Construction of this ring system is accomplished by a set of rather unusual reactions. Condensation of methylstyrenes with formaldehyde and ammonium chloride afford the corresponding hexahydro-1,3-oxazines (119). Heating these oxazines in the presence of acid leads to rearrangement with loss of water to the tetrahydropyridines. Scheme 1 shows a possible reaction pathway for these transformations. Addition of hydrogen bromide affords the expected 4-bromo compound (121). This last is easily displaced by water to lead to the desired alcohol (122) The side chain (123) is obtained by Friedel-Crafts acylation of p-fluorobenzene with 4-chloro-butyryl chloride. Alkylation of the appropriate arylpiperidinol with 123 affords the desired butyrophenone derivative. Thus,... 

When 1-methyl-, 1,2- and 1,3-dimethyl-indoles were oxidized on a platinum electrode in methanolic ammonium bromide solution, in addition to the oxidation products, products of nuclear bromination at the 3-and 5-positions were observed. 1,2- Dimethylindole (20) gave 3-bromo-1,2-dimethylindole (81CCC3278) [bromine in chloroform gave the same product (85CHE786)]. In acidic conditions the amidinium cation formed from 20 was brominated in the 5-position (Scheme 14). Acylated 2-aminoindoles reacted similarly in neutral media to give 3-bromo derivatives and when protonated to give 5-bromo products. Bromine in chloroform transformed l-methyl-2-dimethylaminoindole (21) into the 3-bromo derivative (85CHE782) (Scheme 15). 

The cyclization of IV-allyl-o-haloanilines was adapted to the solid phase for both indoles [332, 333] and oxindoles [334]. For example, as illustrated below, a library of l-acyl-3-aIkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [332], Zhang and Maryanoff used the Rink amide resin to prepare Af-benzylindole-3-acetamides and related indoles via Heck cyclization [333], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-N-acryloylanilines [334], This latter cyclization route to oxindoles is presented later in this section. 

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