Quinazolino-quinazolines

One should be aware that, in the literature, some members of the quinazolino-quinazolines are described by either one of two fusion locants as a result of numbering either of the quinazoline moieties. 

Amidation of N-(2-carboxyphenyl)anthranilic acid (532) gave the 2,2 -dicarbamoyldiphenylamines (533), which were then cyclized with chloro-acetyl chloride to the quinazolino[l,2-a]quinazolines (534) (81JOC1571). 

Katritzky et al. [76CC48 77JCS(P1)1162] synthesized the quina-zolin[l,2-a]-quinazoline (536) by the reaction of 2,2 -bis(chloroformyl) diphenylamine (535) with N,N-diphenylbenzamidine. 

Examples of this ring system (539) were prepared by cyclization of 2-(2-carboxyphenyl)aminoquinazolin-4-one (537) (59JCS1512 83AP702) or 2-amino-3-(2-carboxyphenyl)quinazolin-4-one (538) (59JCS1512). Alternatively, cyclodehydration of 3-(2-benzamido)quinazoline-2,4(l//,3//)- 

It has already been mentioned that the reaction of 2,4-dithioxo-l,3-benzothiazine (544) with anthranilamide gave a complex mixture of products from which benzoisothiazolo[2,3-a]quinazolin-5-one (221) was isolated (see Section VI. A). The quinazolino[3,2-a]quinazoline (545) has also been isolated from this mixture (75JHC1077). 

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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.

Oxidation of 3-amino-2-(2,5-dihydroxybenzyl)quinazolin-(3i/)-one (494) with acidic ferric chloride or aqueous sodium hydroxide gave a quinone that spontaneously cyclized to the quinazolino[3,2-fc]cinnoline-2,7(13//)-dione (495) [66JCS(C)2190]. 

The reported examples of this ring system were obtained by the reaction of 2-ureidobenzonitrile (89JPR537) or 2-alky 1-4H--3, l-benzoxazin-4-one (84CPB2160) with anthranilic acid nitrile to give 6-aIkyI-13//-quinazolino[3,4-a]quinazolin-13-ones (546). 

Isocyanatobenzoyl chloride reacted with isatoic anhydride (76JOC2728) or nitromethane in benzene [83IJC(B)485] to yield 5H,12H-quinazolino[3,2-a]3,1 -benzoxazine-5,12-dione (540) (76JOC2728). Cyclodehydration of 3-(2-carboxyphenyl)quinazoline-2,4(l//,3/f)-dione (575) (66ACH77 67MI1) also afforded the same compound (540). 

Quinazolino[3,2-c]l,2,3-benzotriazin-8(7//)-imine (611) was prepared from 4-amino-2-(2-aminophenyl)quinazoline (609) by diazotization, followed by basilication of the resulting diazonium salt (610). The isomeric... 

An efficient microwave-assisted multi-step synthesis of8//-quinazolino [4,3-b] quina-zolin-8-one has been investigated by Besson and co-workers77. The synthesis involved two Niementowski condensations starting from substituted anthranilic acids (Scheme 3.49). Both homogeneous and heterogeneous conditions were studied in an effort to develop a convenient synthesis of the desired compounds. The solventless procedure allowed easier access to the quinazolino[4,3-fi]quinazolin-8-ones and gave better yields than the method performed in the presence of solvents. However, the procedure with solvents would offer the possibility of investigating the microwave-assisted solid-phase synthesis of these quinazolinones, which would faciltate purification of the final products. 

Alexandre, F.R., Berecibar, A., Wrigglesworth, R. and Besson, T., Novel series of of 8H-quinazolino [4,3-fr]quinazolin-8-ones via two Niementowski condensation, Tetrahedron, 2003,59, 1413-1419. 

When 8-[(4-Cyanophenyl)imino]-87f-quinazolino[3,2-c][l,2,3]benzotriazine (13) is subjected to decomposition in ethanol, acetic acid, mineral acids, or acetic acid containing iodide, bromide, or azide ions, and 2-naphthol, 4-(4-cyanoanilino)-2-[2-(substituted)phenyl]quinazolines 14 are obtained. ... 

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