Synthesis of 10‐Aryl‐ and 10‐(Arylmethyl)acridin‐9(10H)‐ones via the Reaction of (2‐Fluorophenyl)(2‐halophenyl)methanones with Benzenamines and Arylmethanamines

Abstract

The reaction of 1-fluoro-2-lithiobenzenes, generated from 1-bromo-2-fluorobenzenes 1 and BuLi, with 2-halobenzaldehydes and subsequent oxidation of the resulting alcohols 2 afforded (2-fluorophenyl)(2-halophenyl)methanones 3, which, on treatment with benzenamines or arylmethanamines, followed by NaH, gave rise efficiently to 10-aryl-or 10-(arylmethyl)acridin-9(10H)-ones (5 or 7), respectively.Introduction. -Acridin-9(10H)-one derivatives have attracted much attention of not only medicinal but also synthetic chemists, because a number of molecules with this heterocyclic skeleton have been reported to exhibit a variety of biological activities [1] [2], and some have been isolated from nature [3]. The acridin-9(10H)-one structure has been constructed by intramolecular FriedelÀCrafts acylation of 2-(arylamino)benzoic acids with appropriate acid catalysts under harsh conditions [2] [4], while several direct methods for the synthesis of 10-substituted acridin-9(10H)-ones have recently reported by several groups [5]. In this article, we describe a new method for the preparation of 10-substituted acridin-9(10H)-ones starting with 1-bromo-2-fluorobenzenes 1 and 2-halobenzaldehydes. We found that 10-aryl-and 10-(arylmethyl)acridin-9(10H)-ones, 5 and 7, respectively, which are rather difficult to prepare by previously described methods [2] [4] [5], can be obtained by the substitution reaction of (2fluorophenyl)(2-halophenyl)methanones 3, derived by an easy two-step sequence from these starting materials, with benzenamines and arylmethanamines, followed by cyclization of the resulting intermediates 4 and 6, respectively, by treatment with NaH. After completion of this work, a similar approach, which allows the synthesis of fluorinated acridin-9(10H)-ones by the reaction of highly fluorinated benzophenones with primary amines under heating, has been reported as a special case [5d].Results and Discussion. -The key precursors, (2-fluorophenyl)(2-halophenyl)methanones 3, were prepared as outlined in Scheme 1. 1-Bromo-2-fluorobenzenes 1 were treated with BuLi in Et 2 O at À 788 to generate 1-fluoro-2-lithiobenzenes, which were allowed to react with 2-halobenzaldehydes to give (2-fluorophenyl)(2-halophenyl)methanols 2. These were oxidized with pyridinium chlorochomates (PCC) in CH 2 Cl 2 at room temperature to give 3 in satisfactory yields.

A Convenient Synthesis of 9H-Thioxanthen-9-ones and Their Aza-Analogues

“…4 When these compounds (1) were treated with Na 2 S·9H 2 O in DMF at 60 °C, substitution of the two halogens with the sulfur atom proceeded smoothly and cleanly to afford, after addition of water followed by recrystallization of the precipitated crude products, the corresponding 9H-thioxanthen-9-ones (2) in good to excellent yields, as shown in Scheme 1. 4 When these compounds (1) were treated with Na 2 S·9H 2 O in DMF at 60 °C, substitution of the two halogens with the sulfur atom proceeded smoothly and cleanly to afford, after addition of water followed by recrystallization of the precipitated crude products, the corresponding 9H-thioxanthen-9-ones (2) in good to excellent yields, as shown in Scheme 1.…”

“…under the conditions reported for the preparation of 1a-1d 4. Typical Procedure for the Preparation of 9H-Thioxanthen-9-ones (2).…”

Synthesis of 10-Substituted Pyrido[2,3-b][1,8]naphthyridin-5(10H)-ones (Anthyridin-5(10H)-ones) Based on the Reaction of Bis(2-chloropyridin-3-yl)methanones with Primary Amines

“…This method was also successfully applied to the synthesis of 10-substituted pyrido[2,3-b] [1,8]naphthyridin-5(10H)-ones (6) starting with (2-chloropyridin-3-yl)(3-chloropyridin-4yl)methanone (4). This is the first report on the construction of this ring system.…”

“…3 Therefore, we became interested in developing a convenient method for the general preparation of this type of heterocycles. In conjunction with our previously achieved syntheses of 10-substituted acridin-9(10H)-ones 4 and benzo[b] [1,8]naphthyridin-5(10H)-ones, 5 we envisioned the synthesis of 10-substituted pyrido[2,3-b] [1,8]naphthyridin-5(10H)-ones (3) based on the reaction of bis(2-chloropyridin-3-yl)methanone (1) with primary amines. In this paper, we wish to report the results of our study, which provide a facile method for the preparation of this type of pyridonaphthyridinones.…”

Regioselective Synthesis of Thieno[3,2‐b]quinolones by Acylation/Two‐Fold Buchwald–Hartwig Reactions

“…The quinolone substructure, contained in thienoquinolones, shows many of the attributes of an ideal antibiotic, combining high potency, a broad spectrum of activity, good bioavailability and a potentially low incidence of side‐effects . Furthermore, acridones, benzoannulated 4‐quinolones, have attracted attention of both medicinal and synthetic chemists, due to their biological activities . Acridone derivatives have been reported to be significant antifungal and antiviral agents, , , and can also be employed as chemosensors and fluorescent labels in biodiagnostics, or find application as opto‐electronic materials such as OLEDs .…”