Von Richter reaction

B (11— 12— 14). Examination of a more recent study suggests the von Richter reaction probably involves simultaneous attack of the triple bond on the diazo group accompanied by attack by a halide ion but not by a water molecule. The halocinnoline 13 is then hydrolyzed under the von Richter reaction conditions to furnish the 4-hydroxycinnoline derivative 14 (11 - 12- 13 14, pathway A). 

Obviously any mechanism proposed for a reaction must account for all the products obtained and for their relative proportions, including products formed by side reactions. Incorrect mechanisms for the von Richter reaction (13-21) were accepted for many years because it was not realized that nitrogen was a major product. A proposed mechanism cannot be correct if it fails to predict the products in approximately the observed proportions. For example, any mechanism for the reaction... 

Addition of a suspected intermediate. If a certain intermediate is suspected, and if it can be obtained by other means, then under the same reaction conditions it should give the same products. This kind of experiment can provide conclusive negative evidence if the correct products are not obtained, the suspected compound is not an intermediate. However, if the correct products are obtained, this is not conclusive since they may arise by coincidence. The von Richter reaction (3-25) provides us with a good example here too. For many years it had been assumed that an aryl cyanide was an intermediate, since cyanides are easily hydrolyzed to carboxylic acids (6-5). In fact, in 1954, p-chlorobenzonitrile was shown to give p-chlorobenzoic acid under normal von Richter conditions.29 However, when the experiment was repeated with 1-cyanonaphthalene, no 1-naphthoic acid was obtained, although... 

Summarize the types of labeling experiments that could be used to study the proposed mechanism for the von Richter reaction (Figure 8.54). 

There has been a review of the von Richter reaction, which involves cyanide attack on nitroarenes to give cmc-substituted carboxylic acid derivatives, such as... 

The von Richter reaction is the nucleophilic aromatic substitution of a nitroarene (1) with potassium cyanide to give the cme-substituted benzoic acid (2). The reaction is characterized by the observed regiochemistry of the product where the carboxyl group occupies a position ortho to the nitro group that is lost. 

The von Richter reaction, also known as the von Richter rearrangement, was first disclosed in 1871 and the results were revised in 1875 to reflect the correct regiochemistry of the benzoic acid products. The reaction was largely ignored until the mid-20 century "when it was further examined in a series of critical experiments that lead to a fuller understanding of the scope and ultimate elucidation of the mechanism. The reaction has been of limited synthetic value due to the low isolated yield of the products. 

The scope of the von Richter reaction has been examined with respect to substituent effects where the sum of the arene field effects plays an important role in determining optimal conversion to the product. Bunnett reported in 1956 that appreciable conversion was observed only with substituents having summed sigma values, excluding the nitro group, between -0.2 and 0.6 where optimal conversion occurs with sigma values between 0.2 and 0.5. The reaction is inhibited by substituents ortho- to the nitro group which prevent efficient orbital overlap of the pi-system due to steric interactions. 

Many examples of the von Richter reaction have been conducted in sealed reaction vessels, however, a more convenient method involves refluxing the reaction mixture, a modification that has been shown to give comparable yields. The reaction proceeds optimally in aqueous alcohol... 

The synthetic utility of the von Richter reaction has been limited due to the low isolated yields of the benzoic acid products. The reported yields starting from nitroarenes range from 0.5-50%, though in some cases unreacted starting material can also be recovered. The low overall conversion is believed to be due, at least in part, to competing hydrolysis of the cyanide reagent in the reaction medium and often improved conversion is observed with greater excess of cyanide salts. ... 

Published examples of the von Richter reaction have been limited to nitrobenzene and nitronapthalene derivatives. In the case of 2-nitronapthalene, treatment with potassium cyanide in refluxing 48% ethanol for 4 h provides a 13% yield of 1-carboxynapthalene. ... 

Recently, a variation of the von Richter reaction was disclosed involving A -arylnitrones as surrogate nitroarenes that also are proposed to undergo a c/ e-substitution reaction with potassium cyanide. The reaction with potassium cyanide in refluxing 33% ethanol for 2 h provides a 52% yield of benzoic acid and is one of the highest yielding examples of a von Richter reaction. 

The second possibility requires an alternative to the elimination-addition mechanism to account for the formation of the cine-substitution product. Several such reactions are known, the von Richter reaction [equation (16)] being the oldest and most thoroughly studied. Since the accepted mechanism of this reaction specifically requires the presence of a nitro group, it has been suggested that if nitro groups are absent cine-substitution may be taken as good evidence of an aryne mechanism. While this statement may be valid for simple benzenoid compounds it does not necessarily hold for highly substituted or heterocyclic aromatics. 

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