Acid chloride Nierenstein reaction

Nierenstein reaction is the reaction of an acid chloride 1 with diazomethane at room temperature to yield a a-chloroketone 2. It differs from the Arndt-Eistert reaction in that the latter specifically forms diazoketone, which is used to form the higher homolog of the substrate acid chloride. 

In 1915, Maximilian Nierenstein and Douglas Arthur Clibbens at the University of Bristol reported that when an ethereal solution of 1 equivalent of freshly diazomethane is added to an acid chloride at laboratory temperature and the mixture is stirred, the corresponding chloromethylketone 2 is obtained. The sequence of addition and the temperature appeared to be rather specific. Nierenstein proposed that this tendency of acid chlorides to form the chloroketones was analogous to the reaction of aldehydes with diazomethane to yield ketones 3 reported by Schlotterbeck. ... 

It is interesting that the conditions used by Robinson and coworkers were different from the ones described by Nierenstein, and they involved the addition of acid chloride to excess diazomethane rather than stoichiometric in the reverse order, with the reaction mixture cooled with ice and the ethereal solution of acid chloride being added to diazomethane rather than the reverse Thus, unlike Nierenstein, Robinson and co-workers had added the acid chloride to the diazomethane solution whereby the tendency for the nonformation of the chloroketone might be dominant. 

Nierenstein reaction takes place when 1 equivalent of diazomethane is added to the acid chloride solution at 35 °C. Nierenstein reaction is now accepted to take place through the in situ generation of HCl during the formation of diazoketone 4, which reacts with it further to form the chloromethyl ketone 2. Thus diazoketone is an intermediate in the reaction. 

One vital observation made by Nierenstein was that there was a considerable reluctance of acyl bromides to form the corresponding bromomethyl ketones. Acid bromides on reaction with diazomethane were also found to form substituted 1,4-dioxanes or specifically 3,6-dibromo-3,6-diphenyl-1,4-dioxane 8, resulting from the dimerization of adducts. The dimerization according to him could be attributed to the poor mobility of the bromide compared to the chloride group. 

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See also in sourсe #XX -- [ ]

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