Carboxylic Arndt—Eistert

Arndt-Eistert synthesis A procedure for converting a carboxylic acid to its next higher homologue, or to a derivative of a homologous acid, e.g. ester or amide. 

ARNDT EISTERT Homoiogation Homologalion of carboxylic acids or ketones... 

The Arndt-Eistert synthesis allows for the conversion of carboxylic acids 1 into the next higher homolog 4. This reaction sequence is considered to be the best method for the extension of a carbon chain by one carbon atom in cases where a carboxylic acid is available. 

The Kolbe synthesis of nitriles is an important method for the elongation of an alkyl chain by one carbon center (see also the Arndt-Eistert synthesis). The nitrile 2 can for example easily be converted to the corresponding carboxylic acid by hydrolysis. 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

In the Arndt-Eistert synthesis an acyl halide is converted to a carboxylic acid with... 

The reaction between acyl halides and diazomethane is of wide scope and is the best way to prepare diazo ketones.1714 Diazomethane must be present in excess or the HX produced will react with the diazo ketone (0-71). This reaction is the first step of the Arndt-Eistert synthesis (8-8). Diazo ketones can also be prepared directly from a carboxylic acid and diazomethane or diazoethane in the presence of dicyclohexylcarbodiimide.1715 OS III, 119 VI, 386, 613 69, 180. 

Aminomethyl)biphenyl-2-carboxylic acid (70) and -acetic acid (69) have been prepared from dibenzo-substituted oxepin-2-one 66 by potassium phthalimide ring opening. Further Arndt-Eistert homologation of 67 provided 68.[104]... 

Esters, amides, and primary alcohols are obtained from benzo[6]-thiophene carboxylic acids by standard procedures.337 481,585 692 093,695 Acid chlorides undergo the Arndt-Eistert reaction,337,568,689 react with diethyl ethoxymagnesium malonate to give the corresponding methyl ketone,144 557 and are reduced to the aldehyde with 1 ithium tri-ferf-butoxy aluminohydride.33 7... 

The Arndt-Eistert Synthesis allows the formation of homologated carboxylic acids or their derivatives by reaction of the activated carboxylic acids with diazomethane and subsequent Wolff-Rearrangement of the intermediate diazoketones in the presence of nucleophiles such as water, alcohols, or amines. 

Cleavage of the silyl protecting groups under acidic conditions, followed by exposure to MeS03H. results in ketalization of 26 to the pyran-lactol 27 (Figure 8) [20]. To complete the synthesis of the CP compounds, the primary alcohol has to be oxidized to the carboxylic acid and the carboxylic acid side chain has to be elongated by means of an Arndt-Eistert reaction. 

The Wolff and Amdt-Eistert rearrangements are probably among the earliest known reactions promoted by silver ions.2,3 Discovered at the turn of the nineteenth/ twentieth century, the Wolff rearrangement allows the transformation of a-diazo-ketones to carboxylic acids,4 while the Arndt-Eistert rearrangement is a similar sequence also leading to carboxylic acids, but including the preparation of a-dia-zoketones from a shorter acid chloride (Scheme 3.1).5... 

Fig. 8.13. Arndt-Eistert homologation of carboxylic acids—addition of H20 to a ketene in part 2 of the third reaction of this three-step reaction sequence.

The homologation of carboxylic acids is a reaction frequently needed in synthetic chemistry. The Arndt-Eistert reaction though aesthetically pleasing, is not preferred today, owing to the use of diazomethane and silver reagents. We provided47 a solution to this problem by the addition of carbon radicals to... 

The Wolff rearrangement is the third step of the Arndt-Eistert homologation of carboxylic acids. Figure 11.25 picks up an example that was discussed in Section 7.2, that is, the homologation of trifluoroacetic acid to trifluoropropionic acid. The first step of the Arndt-Eistert synthesis consists of the activation of the carboxylic acid via the acid chloride. The Q elongation to an a-diazoketone occurs in the second step. 

In the first step of the reaction sequence a methyl ester is formed via a Wolff rearrangement. The Wolff rearrangem ent provides acids, esters or amides from a-diazo ketones and is often used in a ring contractive way to form strained ring systems, which are not accessible by other sequences.It also occurs as the key step in the Arndt-Eistert homologation of carboxylic acids. ... 

Arndt-Eistert homologation One-carbon homologation of carboxylic acids. 18... 

A carbon chain may be extended by one unit by using the Arndt-Eistert synthesis. In the first step, an acyl halide is treated with diazomethane to form the a-diazo ketone. This is then treated with water and silver oxide. The resultant product is the free acid. If an alcohol is used instead of water, then the related ester is formed. This is the best way of extending a chain by one unit if the carboxylic acid is available. The process of extension in this manner is called homologation. 

Arndt-Eistert reaction The conversion of an acid chloride to the carboxylic acid that is its... 

Wolff rearrangement The rearrangement of a diazo ketone, RCOCHN2, via the keto carbene, RCOCH, to the ketene, RCHCO, which may then be hydrated to a carboxylic acid, RCH2C02H, as in the Arndt-Eistert synthesis. 

The well-known Arndt-Eistert homologation" of an acyl halide to a carboxylic acid also involves the migration of an R group (with its electron pair) to an electron-deficient acyl carbene (presumably through a hypercarbon species) [Eq. (6.132)]. This rearrangement is also known as the Wolff rearrangement. 

Apart from the well-known Arndt-Eistert homologization of carboxylic acids and the many and varied intermolecular reactions of the ketenes formed... 

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