Auwers

Figure 22 represents the main consequences on pyrazole reactivity when a positive charge is present at the 2-position of the nucleus. A similar situation occurs in the indazolium salts, which thermally decompose into an alkylindazole and an alkyl halide, a reaction sequence described by von Auwers. 

The addition of diazomethane to unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers who showed that the primary addition product is a A -pyrazoline (2) which rearranges spontaneously to the conjugated A -pyrazoline (3). 

The Auwers flavone synthesis consists of treatment of dibromo-coumarones 1 with alcoholic alkali to give the flavonols 2. It can also be described as the three-step sequence of 3 — 6. 

In 1908, while working at University of Heidelberg, Auwers and Muller described the transformation of 4-methyl-2-cumaranone (3) to flavanol 6. Thus aldol condensation of 3 with benzaldehyde gave benzylidene derivative 4, which was brominated to give dibromide 5. Subsequent treatment of 5 with alcoholic KOH then furnished 2-methylflavonol 6. In the following years, Auwers published more extensively on the scope and limitations of this reaction. ... 

There is no published mechanistic study on the Auwers flavone synthesis. The mechanism may involve the nucleophilic addition of oxonium 7, derived from 1, with hydroxide to give 8. Base-promoted ring opening of 8 could provide the putative intermediate 9, which then could undergo an intramolecular Michael addition to form 10. Expulsion of bromide ion from 10 would then give flavonol 2. 

Auwers and others soon discovered that the transformation 3 —> 6 did not consistently give flavonols such as 2. For example, alcoholic alkali treatment of dibromide 11 produced 2-benzoyl-benzofuran-3-one 12 instead of the corresponding flavonol. The same observation was made by Robert Robinson in a failed attempt to make datiscetin in 19257 It has reported that when there is a meta (to the coumarone ring oxygen) substituent such as methyl or methoxy, flavonol formation is hindered, whereas methyl, methoxy, and chlorine substituents at the ortho and para positions are conducive to flavonol formation. ... 

Adopting Auwers original method, Milton and Stephen prepared 2-chloroflavonol 16 from 4-chlorocoumaran-2-one 13 in 3 steps in 70% overall yield. 4-Chloroflavonol was synthesized via the same sequence. The same group also carried out the bromination of 2-benzylidenedihydro-b-naphthafurano-l-one (17) and subsequently treated the dibromide with aqueous potassium hydroxide to give 5,6-benzflavonol 18. However,... 

In summary, the Auwers flavone synthesis has seen only very limited utility in organic synthesis. 

Molar refractivity is an additive property, and the predominant tautomer can be found by comparing the experimentally determined value with that calculated for the alternative forms. For example, Auwers used this method to demonstrate that pyrid-2-one exists as such and not as 2-hydroxypyridine. 

Early work on the exaltation of the molecular refractivity of in-dazole and its 1- and 2-alkyl derivatives by Auwers and Diiesberg was considered to indicate that structure 18 represented the predomi-... 

Auwers has paid considerable attention to the terpinene question, and especially in regard to the tact that the molecular refraction of the terpinenes shows considerable variation according to the method of preparation, and often appears to indicate that the terpinenes are exceptions to Briihl s laws of refraction. He came to the conclusion that the terpinenes are usually mixtures of more than one modification, together with a certain amount of a hydrocarbon of the formula —... 

The above procedure is a modification 1 of the method of von Auwers and Moller.2... 

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