Diazoketones are typically generated as described here, but other methods such as diazo-group transfer can also apply. The consequence of the 1,2-rearrangement is that the methylene group alpha to the carboxyl group in the product is the methylene group from the diazomethane reagant. Ardnt-Eistert Homologation The Ardnt-Eistert synthesis is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic homologue. In other words, the homologation process is used to add an additional carbon atom onto a carboxylic acid while generating an acid chloride. In the homologation process, first a carboxylic acid is activated, then, homologated with diazomethane, finally followed by the Wolff-Rearrangement of the intermediate diazoketones in the presence of nucleophiles. The second step of an Arndt-Eistert Homologation: Homologation with diazomethane.
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Variations The Arndt—Eistert synthesis is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic acid homologue i. Acid chlorides react with diazomethane to give diazoketones. In the presence of a nucleophile water and a metal catalyst Ag2O , diazoketones will form the desired acid homologue. While the classic Arndt—Eistert synthesis uses thionyl chloride to convert the starting acid to an acid chloride, any procedure can be used that will generate an acid chloride.
Diazoketones are typically generated as described here, but other methods such as diazo-group transfer can also apply. Since diazomethane is toxic and violently explosive, many safer alternatives have been developed, such as the usage of ynolates Kowalski ester homologation or diazo trimethylsilyl methane. Reaction mechanism The key step in the Arndt—Eistert synthesis is the metal-catalyzed Wolff rearrangement of the diazoketone to form a ketene.
In the insertion homologation of t-BOC protected S -phenylalanine 2-aminophenylpropanoic acid , t-BOC protected S aminophenylbutanoic acid is formed. The consequence of the 1,2-rearrangement is that the methylene group alpha to the carboxyl group in the product is the methylene group from the diazomethane reagant.
Heat, light, platinum, silver, and copper salts will also catalyze the Wolff rearrangement to produce the desired acid homologue.
Conditions[ edit ] Aside from the acid chloride substrate, three reagents are required: diazomethane, water, and a metal catalyst. Each has been well investigated. The diazomethane is required in excess so as to react with the HCl formed previously. Mild conditions allow this reaction to take place while not affecting complex or reducible groups in the reactant-acid.