Anilinomethylenemalonates

In 1939, Gould and Jacobs reported the condensation of aniline with acetyl malonic ester (AME) and ethoxymethylenemalonate (EMME), respectively, followed by cyclization of anilinomethylenemalonic ester 13 and 14 in mineral oil to afford the esters 15 and 16. Saponification of the esters gave the known acids 17 and 18, respectively. 

Although there is versatility in the synthetic methodologies of each individual quinolone antibacterial, two different methods are utilized to synthesize the basic skeleton of l,4-dihydro-4-oxoquinoline-3-carboxylic acid. The first method is based on the Gould-Jacobs reaction [9] using appropriately substituted aniline derivatives and diethyl ethoxymalonate, which results in the formation of the intermediate anilinomethylenemalonate. Further thermal cyclization of this intermediate followed by hydrolysis gives rise to the targeted l,4-dihydro-4-oxoquinoline-3-carboxylic acid, according to Scheme 1. 

Synthesis of 4-hydroxyquinolines from anilines and diethyl ethoxymalonate via cyclization of the intermediate anilinomethylenemalonate followed by hydrolysis and decarboxylation ... 

Anilinomethylenemalonates, anilinofumarates and anilinomaleates 16 are similarly cyclized in the presence of chlorosulfonic acid or oleum to yield quinolinecarboxylic acids and their derivatives 17 (Equation The... 

Ethyl anilinomethylenemalonate in dry ether added to a soln. of LiAlH4 in dry ether at a rate such as to produce gentle reflux, and stirring continued for 3.5 hrs. 3-anilinoallyl alcohol. Y 80-90%. F. e. s. R. L. Shivalkar and S. V. 

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