General preparative route to benzo[g]quinolines (1‐azaanthracenes)

Abstract

A convenient synthetic pathway to benzo[g]quinolines (1‐azaanthracenes) has been developed. The nickel catalyzed coupling of methyl 2‐chloronicotinate (3a) with benzylic organo zinc reagents 2a‐e led to the methyl 2‐benzylic substituted nicotinates 4a‐e. Treatment of methyl 2‐chloro‐6‐methylnicotinate (3b)with 2a in a similar manner led to methyl 2‐benzyl‐6‐methyInicotinate (4f). The coupling of 2‐chloro‐3‐acetylpyridine (5) with benzyl zinc bromide (2a) led to 2‐benzyl‐3‐acetylpyridine (4g). The coupling of the 2,5‐dichlorobenzylic organic zinc reagent (2f) with methyl 2‐choronicotinate (3a) was unselective but readily coupled with methyl 2‐bromonicotinate (6) to yield methyl 2‐(2,5‐dichlorobenzyl)nicotinate (4h). The esters 4a‐f,h on reduction with lithium aluminum hydride led to the corresponding alcohols 7a‐f,h which were subsequently oxidized with manganese dioxide to the respective 2‐benzylic substituted pyridine‐3‐carboxaldehydes 8a‐f,h. In one case the coupling of benzy] zinc bromide (2a) with 2‐chloropyridine‐3‐carboxaldehyde (9) led directly to 2‐benzylpyridine‐3‐carboxaldehyde (8a), but in poor yield. Cyclizations of the aldehydes 8a‐d,f,h or the ketone 4g with polyphosphoric acid afforded the benzo[g]quinolines 10a‐d,f‐h in high yields. Aldehyde 8e was cyclized to 10e using a solution of sulfuric acid in methanol. Several of the benzo[g]quinolines 10c,d could be readly converted into the benzo[q]quinoline‐5,10‐diones 11c,d on treatment with ammonium ceric nitrate.

Unusual Product Distribution from Friedländer Reaction of Di- and Triacetylbenzenes with 3-Aminonaphthalene-2-carbaldehyde and Properties of New Benzo[g]quinoline-Derived Aza-aromatics

“…2 afforded the monocondensed 1-(benzo[ g ]quinolin-2-yl)-4-acetylbenzene ( 5 ) in 45% yield, which also led to formation of 3d and 4 in a similar ratio by subsequent Friedländer reaction with additional 2 . The structure of 4 was confirmed by physical properties and comparison to the spectral data in the literature [27]. 1 H-NMR showed two characteristic resonances for H 2 and H 3 of BQ moiety as a doublet of doublets at δ 8.97 ( J 2,3 = 4.3, J 2,3 = 1.2 Hz) for H 2 and δ 7.35 ( J 3,4 = 8.5, J 2,3 = 4.3 Hz) for H 3 , respectively.…”

Synthesis of Ethano-Bridged Diazapolycenes as Potential Precursors for Diazapolycenes and Their Properties

“…1 H-NMR spectral data of selected protons are summarized in Table 1. All the proton resonances were assigned by comparison with previously reported data for related compounds such as quinoline [32], benzo[ g ]quinoline [33], and 5-azapentacene [17] and by double quantum H-H COSY experiments. The resonances of H4 and the proton at the peri -position in the most of the polypyridines and polyquinolines, are characteristic and have been used as a diagnostic probe for understanding the structural information.…”

“… (a) Ref. [32]; (b) Taken from 250 MHz 1 H-NMR in CDCl 3 ; (c) Ref [33]; (d) Taken from the ChemDraw ® computer program from CambridgeSoft; (e) Ref [17]. …”

Synthetic routes to Cleistopholine and methylated analogues

“…Addition of 9a-c to a mixture of the methyl ester 10, 13 bis(triphenylphosphine)nickel (II) chloride and THF yielded 11a-c, respectively, in high yields. 14,15 Treatment of 11a-c with lithium aluminum hydride afforded the corresponding alcohols 12a-c in nearly quantitative yields. Oxidations of the alcohols 12a-c with pyridinium chlorochromate (PCC) gave the aldehydes 13a-c in good yields.…”

“…15,16 Finally, ceric ammonium nitrate (CAN) oxidations 17 of 14a-c afforded cleistopholine (1, 52%), 2 (33%) and 3 (40%).…”