Synthetic Application of HVZ Reaction

Figure 1(above): Synthetic Application of the Hell-Volhard-Zelinsky reaction.¹



Figure2: Reaction Mechanism of the HVZ reaction.¹



The preparation of a-bromo thioesters from carboxylic acids based on the Hell-Volhard-Zelinsky reaction was developed by H.J. Liu.¹ The procedure for the reaction in Figure 1 can be found at the website referenced below. The mechanism found in Figure 2 shows the movement of electrons to form the a-halo acyl halide. In this mechanism the a-halo acyl halide undergoes one further step, hydrolysis. However, in Figure 1, the a-bromo thioester is produced before the hydrolysis step.

The Hell-Volhard-Zelinsky halogenation reaction halogenates carboxylic acids at the a carbon. PBr₃ replaces the carboxylic OH with a bromide, resulting in a carboxylic acid bromide. The acyl bromide can then tautomerize to an enol, which will readily react with the Br₂ to brominate a second time at the α position.²

More information about the Hell-Volhard-Zelinsky reaction can be found at the following website:

http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation

References:

1.       Kurti, L; Czako, B; Strategic Applications of Named Reactions in Organic Synthesis; Elsevier’s Inc.; [online-Google Books]; Page 200-201;  http://books.google.com/books?id=mjpJmiZ9OZ8C&pg=PA200&lpg=PA200&dq=hell+volhard+zelinsky+reaction+procedure&source=bl&ots=8lgjm8WLP0&sig=ZgZWbtmXu3xww_OaUUE9bgfCuzY&hl=en&ei=yU6uTc3qJoiU0QH87cG6Cw&sa=X&oi=book_result&ct=result&resnum=3&ved=0CCAQ6AEwAg#v=onepage&q=hell%20volhard%20zelinsky%20reaction%20procedure&f=false; Accessed April 19, 2011

2.       Hell-Volhard-Zelinsky halogenation; [online] http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation; Accessed April 19, 2011