Arndt–Eistert reaction
The Arndt- Eistert homologation or Arndt Eistert synthesis is a reaction from the field of organic chemistry. In this case, a carboxylic acid is increased in three stages to a methylene group ( homologated ). The third stage is also referred to as a Wolff rearrangement.
The reaction is complete after their discoverers, chemists Fritz Arndt (1885-1969) and Bernd Eistert (1902-1978), named.
Survey
In the first stage the carboxylic acid is converted to the corresponding acid chloride. After the addition of the methyl group, which is provided by the diazomethane is carried out. The result is an α -diazo methyl ketone. The third stage, the Wolff rearrangement, leads with example Silver oxide as a catalyst and water to form the homologous carboxylic acid. Through the exchange of water with other compounds, however, other derivatives can arise ( see below).
In practice, the reaction with an additional equivalent of diazomethane is carried out, since the splitting off of HCl is added to the molecule and capable of giving a diazoketone α -halo ketone. Additional equivalent of diazomethane transferred HCl in chloromethane, which is not reactive enough.
Mechanism
From carboxylic acid 1, the acid chloride 2 is first formed. Thereafter, at the terminal carbon atom is carried out, the nucleophilic addition of the methyl group of diazomethane. This results in a transition state, a Diazoniumbetain 3, which merges with the elimination of HCl in the resonance-stabilized diazo ketone 4 (addition - elimination mechanism ).
Diazoketones may cleave with silver and copper catalysts taking along the bonding electrons of molecular nitrogen at elevated temperature. The intermediate product is a classic carbene 5 In the next step, a Wolff rearrangement takes place, so that the ketene 6 forms. This reacts with water in a nucleophilic addition to the carboxylic acid 7
6, the ketene can be reacted with other H-acidic, nucleophilic compounds in a nucleophilic addition:
If one uses instead of water an alcohol, we obtain the corresponding ester 8 by addition of ammonia or amines can be obtained 9 or 10 amides.