Nierenstein reaction

Nierenstein reaction. Formation of omega-chloroacetophenones by reaction of diazomethane in dry ether with aroyl chlorides. Coumaranones are obtained if an ortho-hydroxy group is present. 

This reaction is similar to the Wolff Rearrangement and Nierenstein Reaction. 

This reaction was first reported by Staudinger in 1914, subsequently by Clibbens and Nierenstein in 1915, and extensively studied by Nierenstein. It is the synthesis of a -chloromethyl ketone by treatment of an aliphatic or aromatic acyl chloride with diazomethane. Therefore, it is generally known as the Nierenstein reaction." Occasionally, it is also referred to as the Clibbens-Nierenstein reaction or Nierenstein chloromethylation. ... 

Other references related to the Nierenstein reaction are cited in the literature. ... 

This reaction has been extended to directly convert aldehydes into -keto esters by reacting with ethyl diazoacetate in the presence of a catalytic amount of SnCl2. In addition, the reaction between diazoalkanes and acyl halides to form a-halomethyl ketones, known as the Nierenstein Reaction, should be considered as another extension of the Schlotterbeck reaction. 

This reaction is closely related to the 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. 

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. 

An interesting application of the Nierenstein reaction in the synthesis of heterocycles came from Miyahara at Kyushu University in Japan. Using the Nierenstein reaction to prepare chloromethyl ketones 17, Miyahara reported a methodology for a facile synthesis of 2,5-diacylthiophenes 20 bearing a variety of substitutents from readily available nonthiophenic... 

The Nierenstein reaction has been applied in the synthesis of 4-(P-chloromethyl)-2-aminothiazole by Carroll and Smith in 1933. The a, P-dichloromethylethyl ketone 22 was prepared via the Nierenstein reaction of the corresponding chloropropionyl chloride 21. Reaction with thiourea yielded the cyclized product 23. The authors additionally prepared the same ketone using an alternative approach involving the addition of ethylene to chloroacetyl chloride with aluminium chloride as a condensing agent. 

Synthesis of a, P-Dichloromethylethyl Ketone (1,4-dichioro-butanone-2) through the Nierenstein Reaction ... 

Obtained from 3-methoxy-4-methylbenzoyl chlo-COCH2CI jjy Nierenstein reaction [6051]. 

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