Intramolecular cyclisation of 2-aminobenzophenones; a new 9-acridone synthesis

Abstract

Cyclisation of 2-amino-or 2-acetamido-2'-methoxybenzophenones occurred in the presence of sodium hydride to give 9-acridones. This is a method of wide applicability for the synthesis of substituted acridones. A mechanism Department of Chemistry, University of Aberdeen AB9 2U E, Scotland for the cyclisation is discussed.IN connection with studies on the synthesis of natural products under biomimetic conditions we became interested in the synthesis of naturally occurring 9-acridones, a group of alkaloids found only in the plant family Rutaceae.2 The similarity in ring number, ring size, and substituent pattern of the acridone alkaloids to xanthones 3 suggested that oxidative coupling of 2-aminobenzophenones might give the 9-acridone system in an analogous manner to that reported for the conversion of 2-hydroxybenzophenones into ~a n t h o n e s . ~ The poor yields which were obtained for this type of cyclisation 5 led us to investigate alternative methods for the ring closure of 2-aminobenzophenones. In our earlier oxidative experiments 2'-amino-2,3,4-trimethoxybenzophenone (1) cyclised to 3,4-dimethoxy-9-acridone (2) in 7% yield, whereas reduction of 2,4,6-trihydroxy-2'nitrobenzophenone (3) gave 1,3-dihydroxy-9-acridone (6; R = H , R 1 = R 2 = OH), quantitatively, presumably via the amine Our interpretation of these cyclisations involved intramolecular displacement of the adjacent ortho-methoxy-group by nucleophilic nitrogen, or, in the case of the amine (4), a Schiff-base-type condensation with the keto-form of the phloroglucinol ring (5). To establish the utility of this type of cyclisation a

Anti-Herpes Simplex Virus Activity of Substituted 1-Hydroxyacridones

“…The synthesis of 1,3-dihydroxyacridones has been accomplished through a one-step procedure involving the coupling of substituted anthranilic acids or their esters with phloroglucinol in the presence of a mild Lewis acid. , Originally, the synthesis of 1 was performed in this way with 3-chloroanthranilic acid and phloroglucinol in the presence of zinc chloride at reflux in n -butyl alcohol. This reaction is believed to go through a Friedel−Crafts-like mechanism for the initial electrophilic aromatic substitution and subsequently form the acridone system through hydrolytic cyclization occurring between the primary amine and the hydroxyl adjacent to the substitution . The reaction gave only minimal yield after refluxing for 48 h and was not repeatable.…”

Synthesis of Heterocyclic Compounds via Nucleophilic Aroylation Catalyzed by Imidazolidenyl Carbene

“…There are several routes to synthesize acridones 37) -intramolecular nucleophilic substitution of 2Ј-O-substituted 2-aminobenzophenones, 38) acid catalyzed cyclization of N-phenylanthranilic acid, 39) and pyrolysis or photolysis of 3-arylanthranils. 40) Analogous to xanthone synthesis, our acridone synthesis is based on the cyclization of 2,2Ј-difluorobenzophenones by the substitution of two o-florines with one N-nucleophile.…”

Structure–activity relationship studies of acridones as potential antipsoriatic agents. 1. Synthesis and antiproliferative activity of simple N-unsubstituted 10H-acridin-9-ones against human keratinocyte growth

“…This conversion can be rationalized in a straightforward manner as a process involving regioselective ketal cleavage at C-9 followed by a BaeyereVilliger type rearrangement of an intermediate peroxide [32]. Methylation of phenolic 9 with dimethyl sulfate to 10, hydrolysis to the carboxylic acid 11, and Curtius reaction [34] using diphenylphosphoryl azide (DPPA) afforded the carbamate 12, which was directly cyclized to the acridone 5 by sodium hydride in dimethyl sulfoxide according to a literature method [35]. Ether cleavage with hydrobromic acid provided the desired aza-anthralin (4).…”