Cyclic amidines. Part XX. Polyaza- and oxapolyaza-benzonaphthanthracenes

Abstract

Polyaza-and oxapolyaza-benzonaphthanthracenes, isosteric with tricycloquinazoline, have been synthesised.Various eliminations from appropriately substituted arylpolyazabenzanthracenes readily gave these hexacyclic compounds. The oxadiaza analogue is intensely carcinogenic. Correlation of their activities with previously described isomers and isosteres shows the critical significance of certain symmetry factors for activity. THE carcinogen, tricycloquinazoline (I) has a unique trigonal symmetry; loss of symmetry by replacement of the 5 , 10, or 15 nitrogen by methine or reorganisation of the structure into the tetra-azanaphthonaphthacene N 0 N (11) or its isostere (111) abolishes activity. To obtain further evidence on this symmetry factor, isomeric and isosteric analogues of tricycloquinazoline with modifications at positions 4a, 5, and 14c have been synthesised. N-Phenyl-o-nitrobenzimidoyl chloride condensed with diethyl sodiomalonate to yield diethyl N-phenylo-nitrobenzimidoylmalonate, which with phosphoryl chloride furnished the chloroquinoline (IV; R1 = CO,Et, R2 = C1, R3 = NO,). The production of the last compound from the hydroxyquinoline (IV; R1 = CO,Et, R2 = OH, R3 = NO,), readily formed by thermal cyclisation of the benzimidoylmalonate, was less efficient. The chloroquinoline (IV; R 1 = CO,Et, R 2 = C1, R3 = NO,) reacted preferentially with amines at chlorine rather than at the ester; thus when heated with aniline, it gave the anilino-ester (IV; R1 = CO,Et, R2 = 1 Part XIX, M. W. Partridge, S. A. Slorach, and H.

Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

“…In the course of their investigations on tricycloquinazoline and its carcinogenic properties, published mostly in the 1960s, Partridge and co-workers synthesized a number of related cyclic amidine derivatives, including isomers of 139.1 ( 140.7 , 140.9 , and 140.15 ), triaza systems ( 140.12 , 140.13 , 140.17 , 140.19 ), and diazaoxa systems 140.3 , and 140.22 , (Scheme ). The synthetic strategies mostly relied on classical dehydrative condensations and nucleophilic substitutions, and were generally concise and high-yielding.…”

“… a Reagents and conditions: (a) AcOH, 180–190 °C, 90 min; (b) (1) acetone, 30 min, (2) NH 3 /EtOH; (c) neat, 210 °C, 1 h; (d) (1) NaCl, AlCl 3 , 100–320 °C, 1 h, (2) NaNO 3 , HNO 3 (76% as nitrate), (3) NEt 3 ; (e) (1) POCl 3 , PCl 5 , 120–140 °C, 3 h, (2) 2-aminopyridine; (f) NaCl, AlCl 3 , 320 °C, 1 h; (g) neat, 320 °C, 15 min; (h) N 2 H 4 , Raney Ni, EtOH, 70 °C; (i) aniline, reflux, 30 min; (j) DMF, aq NaOH, reflux, 15 min; (k) H 2 , Pd/C, EtOH. …”

Synthetic methods involving neighboring group interaction in o-substituted nitrobenzene derivatives

“…The formation of phenoxathiins (e.g., 295, 297) by the reaction of o-chloronitroarenes (293) with o-mercaptophenol (294) and its derivatives (296) was first reported by Mauth-nersi9,320 an(j later by Poliak and Riesz.321•322 However, no attempt was made to establish the orientation of the phenoxathiin products. The problem of orientation was clarified by Stevenson and Smiles323 who demonstrated that the intramolecular displacement of the nitro group implicit in these reactions is effected by the hydroxy rather than the thiol group (cf.…”

Cyclic amidines. Part 26. The reported syntheses of 7-anilino-6-aryl-5,12-diazabenz[a]anthracenes are reinvestigated and their correct structures identified

“…The same triazaphenalene had previously been reported by Moszew by oxidation of alleged 7-anilino-6-phenyl-5,12-diazabenz[a]anthracene (5). However the compound (2) prepared by the unequivocal method of Partridge ' melted at 317 "C whereas Moszew reported a melting point of 245 "C and, more importantly, antitumour properties.' In the light of this atypical activity in a series of compounds noted for their frequent and often intense mutagenic and carcinogenic properties6 it was decided to reinvestigate the reaction and establish the structure of Moszew's product.…”