Niementowski quinoline synthesis

Niementowski quinoline synthesis. Formation of y-hydroxyquinoline derivatives from anthranilic acids and carbonyl compounds. 

Niementowski Quinoline Synthesis Richard A. Hartz 7.4.1 Description... 

The Niementowski quinoline synthesis is the reaetion of an anthranilic acid (1) with an aldehyde or ketone containing an a methylene group that can undergo deprotonation (2) followed hy cyclodehydration to produce a 4-hydroxyquinoline (3). The reaction occurs under thermal conditions at temperatures generally ranging from 120-250 °C, depending on the nature of the substrates. 

The mechanism for the Niementowski quinoline synthesis is presumably similar to that of the closely related Friedlander reaetion. The mechanism for the Friedlander reaction has been studied extensively" and two possible mechanistic pathways exist, as illustrated below. There is support for both pathways. Most of the evidence, however, tends to favor initial formation of the SchifTs base intermediate (13) followed by cyclization to give quinoline 15 however, the reaction conditions and structures of the reactants may influence the pathway by which the reaetion proeeeds. ... 

Since the Niementowski quinoline synthesis involves the condensation of an aldehyde or ketone (2) with an anthranilic acid (1), it is... 

In another variant of the Niementowski reaction, it was found that this transformation can be carried out under relatively mild, base-catalyzed conditions. Since a variety of substituted anthranilamides (29) can be prepared by a regiospecific ortho metalation-amination sequence, this method appears to be a very versatile modification of the Niementowski quinoline synthesis. Lithiation of 28 with 5-butyllithium was followed by treatment with tosyl azide. Reduction of the azide with sodium borohydride under phase transfer conditions furnished 29. After conversion of 29 into the corresponding imine 30, treatment of 30 with LDA afforded 31 in good yield. 

A modification of the Niementowski quinoline synthesis for the preparation of 4-hydroxyquinolines bearing an arylketone at the 3-position was reported by Wang et al Reaction of 36 with 37 afforded 4-hydroxyquinoline 38. This 4-hydroxy quinoline with a 2-thiomethyl... 

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