Graebe

P. Hedden andj. E. Graebe,/ Plant Growth Regul 4, 111 (1985). 

Anthraquinone chemistry began in 1868 with the elucidation of the stmcture of the naturally occurring compound alizarin (1) (1,2-dihydroxyanthraquinone) [72-48-0] by C. Graebe and C. Liebermann. 

GOMBERG - BACHMANN - GRAEBE - ULLMANN Arylatwn Atykaryl bond formation via diazonium salts Carbazole synthesis by intramolecular aryl-aryl bond formation. 

The lead dioxide-alkali method has also been applied successfully by Graebe and Kraft to the three cresols, the three toluic acids, and 2,4-dimethylphenol. For the preparation of 2-hydroxyisophthalic acid, it is the only one-step method that starts from readily obtainable materials. 

The nature of the nucleus in chelidonine and sanguinarine was established by Spath and Kuffner,i who showed that both alkaloids on distillation with zinc dust yielded a-naphthaphenanthridine (V), first prepared by Graebe, and on that basis formula (IV) was suggested for sanguinarine. 

Graebe, Lleberniann, Annalcn, 1871,160, 131 . A. G. I erkiu. Piivate conmiunication. 

The thermal decomposition of triazole 1 to form carbazole 2 is regarded as the Graebe-Ullmann carbazole synthesis. 

In 1896, Graebe and Ullman reported the formation of carbazole (5) by reacting 2-aminodiphenylamine (3) with nitrous acid, followed by the thermolysis of the benzotriazole 4 which resulted. ... 

The Graebe-Ullman carbazole synthesis is normally carried out in sealed tubes and at high temperature. The carbazoles/substituted carbazoles are obtained in general in poor to moderate yields. ... 

The Graebe-Ullman carbazole synthesis has been enmloyed in the preparation of substituted carbolines, as well as indolo[2,3-i] quinolines, which are often difficult to synthesize via other approaches, for example, the Fischer indole process. 

Hagan et al. utilized the Graebe-Ullmann process to synthesize polycyclic acridines 14 which exhibit anti-tumor activity. ... 

The extension of the method to the synthesis of y-carboline from 1-y-pyridylbenztriazole (199) and of a 3,4-benz-y-carboline from a l-(4-quinolyl)benztriazole proceeded smoothly. In an alternative approach excellent yields of y-carboline were obtained by heating l-phenylpyrido[3,4-d] -triazole (200) at 320-350°. The synthesis of halogeno-substituted j8- and y-carbolines via the Graebe-Ullmann reaction has been reported. ... 

Shortly before this work by Pschorr, similar ring closures had been described for other compounds in which two benzene rings are already linked. Thus Graebe and Ullmann (1894) found that 2-diazobenzophenone can be converted into fluorenone in the analogous manner (Scheme 10-74). Similarly, when Staedel (1894) added nitrous acid to 2,2 -diaminobenzophenone he obtained some 1-hydroxyfluorenone. The ring closure of 2-benzylbenzenediazonium ion to give fluorene (Scheme 10-75) was described by Fischer and Schmidt (1894). 

Hie reactions of 4-chloropyridines and quinolines 17 with benzotriazoles 18 in a modified Graebe-Ullman synthesis give excellent yields of Y arbolines and their benzo-fused derivatives 20. Excellent yields for preparation of the penultimate benzotriazole precursors 19 are reported as well. In the optimized one-pot conditions, the combined neat substrates are heated with microwave irradiation (MW) for short (7-10 min) durations. The crude 19 is treated with H4P2O7 and irradiated futher (4-6 min). The resultant y-carbolines 20 were methylated to form the quaternary salts. These were tested and found to lack DNA intercalation properties <96JOC5587>. 

This serendipitous discovery marked the beginning of the synthetic dyestuffs industry, based on coal tar as its main raw material, which is, incidentally, a waste product from another industry, steel manufacture. The development of mauveine was followed by efficient syntheses of natural dyes such as alizarin in 1869 (Graebe and Liebermann, 1869), and indigo in 1878 (Bayer, 1878 Heumann, 1890). The synthetic production of these dyes marked the demise of the agricultural production of these materials and the advent of a science-based, predominantly German chemical industry. The present-day fine chemicals and specialties, e.g. pharmaceuticals, industries developed largely as spin-offs of this coal tar-based dyestuffs industry. 

The only practical methods of preparing o-chlorobenzoic acid consist in the oxidation of o-chlorotoluene and the replacement of the amino group in anthranilic acid by a chlorine atom. Both of these methods have been fully discussed by Graebe,1 who recommends the former for the preparation of relatively large quantities. The oxidation of o-chlorotoluene by permanganate was originally described by Emmerling.2... 

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