Niementowski 4-quinazoline

Niementowski quinazoline synthesis. Formation of 4-oxo-3,4-dihydroquinazolines by cycli-zation of the reaction products of anthranilic acid and amides. 

The striking improvement in the Niementowski quinazoline synthesis [156, 157] has been fulfilled using microwave irradiation by Besson et al. [158,159] (Scheme 7). Using microwave irradiation and/or Appel s salt, new efficient routes to various substituted and fused quinazolines have been developed by Besson et al. [158,159] and also by others [ 160,161]. 

Scheme Microwave-assisted Niementowski quinazoline synthesis [158,159]...

Niementowski Quinazoline Synthesis Richard A. Hartz 8.4.1 Description... 

The Niementowski quinazoline synthesis is the condensation of an anthranilic acid (1) with an amide (2) to produce a 4-keto-3,4-dihydro-quinazoline product (3). The reaction occurs under thermal conditions, and reaction temperatures > 100 °C are generally required. This reaction is also often referred to as the Niementowski reaction, and occasionally as the Niementowski 4-quinazolone synthesis or von Niementowski synthesis. ... 

Another multistep protocol that initially involves the formation of fused pyrimidines (quinazolines) has been described by Besson and coworkers in the context of synthesizing 8f-/-quinazolino[4,3-b]quinazolin-8-ones via double Niementowski condensation reactions (Scheme 6.250) [437]. In the first step of the sequence, an anthranilic acid was condensed with formamide (5.0 equivalents) under open-vessel microwave conditions (Niementowski condensation). Subsequent chlorination with excess POCl3, again under open-vessel conditions, produced the anticipated 4-chloro-quinazoline derivatives, which were subsequently condensed with anthranilic acids in acetic acid to produce the tetracyclic 8H-quinazolino[4,3-b]quinazolin-8-one target structures. The final condensation reactions were completed within 20 min under open-vessel reflux conditions (ca. 105 °C), but not surprisingly could also be performed within 10 min by sealed-vessel heating at 130 °C. 

Scheme 6.250 Formation of 8H-quinazolino[4,3-b]quinazolin-8-ones through double Niementowski condensation.

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