Wohl-Aue

Wohl-Aue synthesis Wohlwill process Wolff-Chaikoff effect... 

Many substituted quinolines are intermediates for antimalarials. The 2,4-di-substituted quinolines are produced from aniline and 1,3-diketones by the Combes quinoline synthesis (28). The reaction of aniline with nitrobenzene in the presence of dry sodium hydroxide at 140°C leads to formation of phenazine [92-82-0] and by-products (Wohl-Aue synthesis) (29). 

Wittig reaction, 2 64-65, 19 65 Wobbe Number, 12 378-379 Wohl-Aue synthesis, 2 787 Wohlwill refining process, 22 647 Wolff-Chaikoff effect, 14 373 Wolff-Kichner reduction, 13 569-570,... 

Anilines undergo oxidative cyclization with substituted nitrobenzenes (Wohl-Aue method) in alkaline media in refluxing toluene or benzene to afford phenazine iV-oxides 1, as well as other side products such as azo and azoxy derivatives at higher temperatures (140°C), the parent phenazines 2 are formed in low yield. - -... 

WOHL - AUE Phenazinesynthesis Synthesis of phenazine N-oxide from amtmes and nitrobenzene... 

This two-step process is analogous to, but much more efficient than, the classic Wohl-Aue synthesis of phenazines [233]. The versatility of this approach has been demonstrated by the synthesis of 1-methoxyphenazine that can be obtained from two different pairs nitroarene-aniline , namely, nitrobenzene-wta-anisidine or weta-nitroanisole-aniline (Scheme 98) [84]. 

Bahnmiiller et al. have applied the Wohl—Aue procedure for the synthesis of ketal-protected natural product saphenic acid. Heating anthranilic acid and ethylene ketal-protected 3-nitroacetophenon in the presence of KOH and sand to 200 °G afforded saphenic acid (27) in very low yield (less than 5%). ... 

Scheme 4. Wohl-Aue Reaction Heating to 200 °C in Sand or Strong Base (KOH)...

Accordingly, both the Wohl—Aue and Bamberger-Ham procedures have received limited attention in the literature due to poor yields, harsh conditions. 

In 1901, one of the first methods for preparation of phenazines was reported by Wohl and Aue. They discovered that anilines and nitrobenzenes form phenazines or phenazine-A/ xides upon heating to 200 °C in the presence of a strong base (Scheme 4). The starting materials were generally readily available however, yields were modest and significant amounts of byproducts, primarily consisting of aza-compounds, were formed under the harsh reaction conditions. 

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