Camps quinoline synthesis

Camps quinoline synthesis entails the base-catalyzed intramolecular condensation of a 2-acetamido acetophenone to substituted quinolines. Usually, 2-acetamido compounds are elaborated by the reaction of substituted benzoxazinones with the appropriate carbon nucleophiles. 

The reaction mechanism is based on the deprotonation of the amide under the basic reaction conditions and its condensation on the ketone to afford substituted 2-quinolones. In the case of 4-hydroxy-substituted products, the reaction pathway follows deprotonation of the ketone, followed by its reaction on the amide. 

An interesting modification of Camps reaction was presented recently. It was based on the use of isatoic anhydride or benzoxazinones as active components for the in situ formation of intermediate amides, which were readily cyclized to the desired products. Thus, reaction of isatoic anhydride or benzoxazinones with malonates and/or ketoesters afforded libraries of quinoline compounds in high yields even at multikilogram scale.  

The described method was expanded to provide an easy access to quinoline alkaloid analogues by using one-step reaction between benzoxazinones and ketene silyl-acetals in the presence of titatium tetrachloride.  

Knorr showed that aniline could be condensed with ethylacetoacetate when heated to provide the acetoanilide (6). Conrad and Limpach established that further heating 

Little work has been done to confirm the mechanism of the Camps reaction. The presumed mechanism is shown. Deprotonation a to the ketone portion 1 (11) followed 

A general method for malting Camps precursors has been developed/ Treatment of an anthranilic acid 15 with an acid anhydride or chloride in the usual way results in the corresponding benzoxazinone (16). Subsequent treatment with the dianion of an N-substituted acetamide furnishes P-keto amide 17. The reactions were run with crude 16, yields typically 50-80% overall. The effect of substituents on the reaction has not been extensively investigated. 

As one might expect, most of the reported cases of Camps quinoline syntheses involve reactions in which only one of the carbonyl groups is enolizable, thus eliminating the regioselectivity problem. 

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An interesting use of the Camps quinoline synthesis is in the ring contraction of macrocycles. Treatment of 9 member ring 24 with sodium hydroxide in water furnished quinolin-4-ol 25, while 26 furnishes exclusively quinolin-2-ol 27 under the same reaction conditions (no yield was given for either reaction). The reaction does not work with smaller macrocycles. The authors rationalize the difference in reactivity based upon ground state conformation differences, but do not elaborate. 

The last two decades of the 19th century proved to be an important era for the development of quinoline chemistry. It was during this time period that various methods for synthesizing quinolines, such as the Friedlander quinoline synthesis, Pfitzinger quinoline synthesis, Doebner-Miller quinoline synthesis, Conrad-Limpach quinoline synthesis, Combes quinoline synthesis, and Camps quinoline synthesis were first reported. In 1882, Friedlander showed that the condensation of 2-aminobenzaldehyde (4) with acetaldehyde (5) provided quinoline (6). ... 

Camps Quinoline Synthesis Cannizzaro Reaction Carbylamine Reaction Carroll Rearrangement Castro Reaction Castro-Stephens Coupling CBS... 

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