Oxidations Kuhn-Roth method

Martin B. Neuworth The Kuhn-Roth method has a number of limitations. These were discussed by Brandenberger et al. (Anal. Chem. 33, 453 (1961)). The normal method for estimating C-methyl groups is based on a determination of total acidity calculated as acetic acid. Brandenberger has shown that other acids can be produced during the oxidation—e.g., benzoic acid, and these acids steam distil with the acetic acid. Therefore, when the classical Kuhn-Roth procedure is applied to a substance like coal, it would lead to methyl group values of questionable significance. 

Kuhn-Roth method for C-methyl determination. Oxidation of organic compounds with chromic and sulfuric acids in such a manner that the C-methyl groups are converted to acetic acid which can be assayed volumetrically. The method has been modified and extended (1) to saturated fatty acids and alcohols containing up to about 20 carbon atoms, and (2) to aliphatic long-chain compounds of very high molecular weight. 

This reaction was first reported by Kuhn and Roth in 1933. It is a method for quantifying the number of methyl groups attached to the carbon atom in an organic molecule, which involves the oxidation of such an organic compound with chromic acid in the presence of sulfuric acid, followed by steam distillation to collect the generated acetic acid and quantification of the acetic acid via acid/base titration. In addition, the collected acetic acid can be further analyzed by conversion of acetic acid into lithium acetate, pyrolysis of lithium acetate to acetone, and transformation of acetone into iodoform by hypoiodite. Therefore, this reaction is generally known as the Kuhn-Roth C-methyl determination, Kuhn-Roth chromic acid oxidation, Kuhn-Roth degradation, Kuhn-Roth determination, or Kuhn-Roth oxidation. " ... 

In 1947, Kinney (15) drew attention to a direct relationship between the amount of acetic acid formed on oxidizing coal with nitric acid and potassium dichromate and the yields of methane obtained by low temperature carbonization. The oxidation method leading to acetic acid is a variation of the standard Kuhn-Roth procedure, and hence what Kinney indicated as the methane yielding structure is obviously the methyl groups in coal. However, the relationship he pointed out can only be qualitative since true C-methyl content (as shown in the present work) cannot be obtained by any... 

The first report of the incorporation of radioactively labelled mevalonic acid into dendrobine (82) was by Yamazaki et al. (224). Sodium [2— CJmevalonate [( )-463 ] was administered to stems of D. nobile by the cotton-wick method. After 12 days, the plants were extracted and radioactive dendrobine (82) was isolated by column chromatography. The total incorporation was 0.012%. Subsequent Kuhn-Roth oxidation led to acetic acid that showed the expected activity assuming the biosynthesis pathway a leading to the picrotoxanes via a cadalene as precursor (Scheme 55, pathway c). 

Clearly the most elegant chemical synthesis of chiral acetate is the route reported by Townsend et al. (33). The method, outlined in Scheme 2, has the advantage that tritium is introduced at a late stage in the synthesis, and both of the remaining steps, pyrolysis and Kuhn-Roth oxidation, proceed in high... 

The seco Compounds. The structures of these compounds were rapidly elucidated once systematic studies were undertaken (Chart 5.5). Of great value was the use of the Kuhn-Roth oxidation as a simple method to monitor the presence or absence of a C-methyl group. The properties of ring C and its 3a proton parallel those of the same moiety in yohimbine, and as might be expected selenium dehydrogenation furnished the tetrabyrine analogue, alstyrine. 

Hydrolysis of the labeled compound with 2 N sulfuric acid furnished 3-amino-4-methyl-2-hexanone which, on treatment with iodine in the presence of sodium hydroxide, furnished isoleucine and iodoform. The iodoform was oxidized to carbon dioxide, while treatment of isoleucine with ninhydrin furnished 2-methylbutanal, isolated as its 2,4-dinitrophenylhydrazone. Kuhn-Roth oxidation of the aldehyde gave acetic acid which was degraded by the Schmidt procedure to carbon dioxide and methylamine. The 2-methylbutanal was also degraded stepwise by the method of Strassman. Determination of the radioactivity of the various degradation products showed that 94% of the activity was equally shared between the lactam C(2) and side-chain C(10) carbonyl atoms. The remaining activity was shared between C(4) of the lactam ring and the a> carbon atom of the ec-butyl side chain. The results are consistent with derivation of tenuazonic acid from isoleucine and two molecules of acetic acid. However, the direct incorporation of isoleucine into tenuazonic acid was not investigated. 

Haworth/ These methods remained unchanged for many years, until certain aprotic solvents became commercially available. The first major advance was the use by Kuhn and his associates of N,W-dimethylforma-mide or methyl sulfoxide (MczSO) as solvents in conjunction with methyl iodide or methyl sulfate, and silver oxide or strontium oxide, and, at about the same time, Roth and Kgman used methyl sulfoxide for the methylation of amino sugars. 

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