Martius

V-Alkylaniline and /V,/V-di alkyl aniline hydrochlorides can be rearranged to C-alkyl anilines by heating the salts to 200—300°C. In this reaction, known as the Hofmann-Martius rearrangement, the alkyl group preferentially migrates to the para position. If this position is occupied, the ortho position is alkylated. 

Another important piece of the puzzle came from the work of Carl Martius and Franz Knoop, who showed that citric acid could be converted to isocitrate and then to a-ketoglutarate. This finding was significant because it was already known that a-ketoglutarate could be enzymatically oxidized to succinate. At this juncture, the pathway from citrate to oxaloacetate seemed to be as shown in Figure 20.3. Whereas the pathway made sense, the catalytic effect of succinate and the other dicarboxylic acids from Szent-Gyorgyi s studies remained a puzzle. 

FIGURE 20.3 Martius and Knoop s observation that citrate could be converted to isocitrate aud then a-ketoglutarate provided a complete pathway from citrate to oxaloacetate. 

Aromatic diazonium compounds became industrially very important after Griess (1866a) discovered in 1861/62 the azo coupling reaction, by which the first azo dye was made by C. A. Martius in 1865 (see review by Smith, 1907). This is still the most important industrial reaction of diazo compounds. Hantzsch and Traumann (1888) discovered that a heteroaromatic amine, namely 2-aminothiazole, can also be diazotized. Heteroaromatic diazonium compounds were, however, only used for azo dyes much later, to a small extent in the 1930 s, but intensively since the 1950 s (see Zollinger, 1991, Ch. 7). 

When HCl salts of arylalkylamines are heated at 200-300°C, migration occurs. This is called the Hofmann-Martius reaction. It is an intermolecular reaction, since crossing is found. For example, methylanilinium bromide gave not only the normal products o- and p-toluidine but also aniline and di- and trimethylanilines." As would be expected for an intermolecular process, there is isomerization when R is primary. 

This interpretation offered by Ogston was confirmed by further isotope experiments (Potter and Heidelberger, 1949 Martius and Schorre, 1950). Ochoa and his colleagues also demonstrated that in pigeon-liver preparations which had been freed from aconitase, thus preventing isomerization between citrate and isocitrate, citrate was the product of the condensation of oxaloacetate and acetate. 

Aconitase was first described 50 years ago by Martius (1,2) and soon there after named by Breusch (3). The enzyme demonstrated the then surprizing ability to distinguish between the chemicadly identical acetyl arms of citrate (4). The stereo-specificity of enzyme catalyzed reactions was not fully understood until the late 1940 s when Ogston point out that as long as a substrate attaches to an asymmetric enzyme at three points, the enzyme can differentiate between two identical amis of a symmetrical molecule (5). 

Dinitro-l-naphthol (Martius Yellow) [605-69-6] M 234.2, m 81-82°. Crystd from benzene or aqueous EtOH. 

Similar to Hoffmann-Martius Rearrangement except that it uses Lewis acids and the amine rather than protic acid and the amine salt. 

See M. B. Smith, J. March in March s Advanced Organic Chemistry, 5lh ed., John Wiley and Sons, Inc., New York, 2001, pp. 728-730 for the Fischer-Hepp Rearrangement as well as the Orton and Hofmann-Martius Rearrangements. 

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