Condensed isoquinolines 29. Oxidation reactions of 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium salts

Abstract

The first representatives of the isoquino[2,3-a]quinazoline system were obtained quite recently [2, 3] and they included 5-aryl-substituted derivatives [2,4]. However, by contrast to 5-oxoisoquino[2,3-a]quinazolines, the properties of the latter were not studied. The already existing data for the biological activity of isoquinoquinazolines [5, 6] and 4-arylquinazolines condensed along the a edge [7-9] points to the potential of such an investigation.We have previously proposed [4] a method for the synthesis of the 5-aryl-7,12-dihydroisoquino-[2,3-a]quinazolinium salts 1a-c consisting of reaction of o-(bromomethyl)phenylacetonitrile with o-aminobenzophenones 2a-c and subsequent cyclization of the initially formed 2-aryl-3-imino-1,4-dihydroisoquinoline hydrobromides 3a-c in the presence of perchloric acid. In this work the reaction was subjected to closer study with the aim of optimizing the method of synthesizing the isoquinoquinazolinium salts 1 and to study the spectroscopic and chemical properties of the products.We have found that the outcome of the reaction of o-(bromomethyl)phenylacetonitrile with benzophenones 2 depends markedly on both the reaction conditions and on the nature of the substituent in reagent 2. Hence heating in acetonitrile, in some examples (2b,c) gave a mixture of the isoquinolineimine bromides 3 together with an unknown product. Addition of catalytic amounts of acetic acid to the reaction mixture virtually suppresses the formation of the side product. When the reaction is carried out in 2-propanol the unknown material is the sole product. And in the case of the benzophenone 2d gives the unknown material _______ * For Communication 28 see [1].

Condensed isoquinolines 31. Reaction of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents

“…In addition, for an evaluation of the steric proximity of the individual protons NOESY-1D and NOESY spectra were used. For various spectra of compound 5b a whole series of analogies was found with the corresponding spectra of compounds 4a,b and the 3-chloro-5-phenylisoquino [2,3-a]quinazolin-13-ium perchlorate [4]. Hence in the proton spectrum a singlet with an unusually low field chemical shift of 11.73 ppm was found.…”

“…The formation of alkylation products of the isoquinoquinazolines 1a,b with phenacyl bromides upon heating a mixture of the reagents in acetonitrile was unexpectedly successful. It should be noted that an oxidation and not alkylation frequently occurs in this reaction in the case of condensed isoquinolines [6,9]. Oxidation also occurs in the reaction with 5-arylisoquino[2,3-a]quinazolines but gives the 5-aryl-7-(2-aryl-2-oxoethyl)-3-haloisoquino[2,3-a]quinazolin-13-ium bromides 5a-c.…”

“…Spectroscopic data identified the reaction product as the 7-acetyl derivatives. The 1 H NMR spectrum of compound 3 showed a three-proton singlet for the introduced acetyl group (2.55 ppm), the absence of a signal for the methine H-7 proton, and the aromatic proton signals shifted to low field of those in the unsubstituted isoquinoquinazoline 1a [4] (see Table 1, mean ∆δ ~ 0.2 ppm). The greatest low field shift was observed for the H-8 proton at 8.07 ppm (∆δ = 1.0 ppm) which falls in the deshielding region of the 7-acetyl substituent carbonyl group.…”

“…Oxidation also occurs in the reaction with 5-arylisoquino[2,3-a]quinazolines but gives the 5-aryl-7-(2-aryl-2-oxoethyl)-3-haloisoquino[2,3-a]quinazolin-13-ium bromides 5a-c. The structure of the alkylation products which is rather complex and not only possible was established by a comparison of their spectroscopic data with the data of the more simple 3-chloroisoquino-5-phenyl- [2,3-c]quinazolin-13-ium perchlorate [4] and dimer salts 4a,b [4]. The IR spectra of the compounds 5a-c showed carbonyl group stretching vibrations in the range 1670-1685 cm -1 , characteristic of an Ar-C=O system which points to the presence of an acetophenone fragment in the molecule.…”

“…the C-7 atom (the β-carbon of the enamine fragment C(7)=C(6a)-N(13) and the N-6 atom (of the C(5)=N(6) imino group). We have previously [4] found a number of similarities in the behavior of 5-arylisoquinoquinazolines 1a,b and their protonated 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium perchlorate salts with the behavior of other condensed isoquinolines [5][6][7][8] in oxidation reactions, i.e. a tendency for dehydrogenation at the benzyl position (7 and 12) to form aromatic derivatives including those with a dimeric structure.…”